1,464 results on '"Aminopyrine"'
Search Results
2. Non-alcoholic fatty liver disease causes dissociated changes in metabolic liver functions
- Author
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Stephen Hamilton-Dutoit, Hendrik Vilstrup, Peter Lykke Eriksen, Karen Louise Thomsen, Michael Sørensen, and Henning Grønbæk
- Subjects
Adult ,Male ,medicine.medical_specialty ,Population ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Liver function tests ,Medicine ,Humans ,Urea cycle ,education ,Aminopyrine ,Non-alcoholic steatohepatitis ,Breath test ,education.field_of_study ,Hepatology ,medicine.diagnostic_test ,business.industry ,Fatty liver ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,digestive system diseases ,Indocyanine green ,Hepatic elimination ,medicine.anatomical_structure ,Cross-Sectional Studies ,Liver ,030220 oncology & carcinogenesis ,Hepatocyte ,Hepatocytes ,030211 gastroenterology & hepatology ,Female ,Liver function ,Steatohepatitis ,business - Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is a major health concern affecting 25% of the world's population. It is generally held that a fatty liver does not influence liver function, but quantitative measurements of metabolic liver functions have not been systematically performed. We aimed to study selected hepatocellular metabolic functions in patients with different stages of NAFLD. Methods: Twenty-five non-diabetic, biopsy-proven NAFLD patients [12 with simple steatosis; 13 with non-alcoholic steatohepatitis (NASH)] and ten healthy controls were included in a cross-sectional study. Hepatocyte cytosolic function was assessed by the galactose elimination capacity (GEC), mitochondrial-cytosolic metabolic capacity by the functional hepatic nitrogen clearance (FHNC), microsomal function by the aminopyrine breath test, and excretory liver function by indocyanine green (ICG) elimination. Results: GEC was 20% higher in NAFLD than in controls [3.15 mmol/min (2.9–3.41) vs. 2.62 (2.32–2.93); P = 0.02]. FHNC was 30% lower in NAFLD [23.3 L/h (18.7–28.9) vs. 33.1 (28.9–37.9); P = 0.04], more so in simple steatosis [19.1 L/h (13.9–26.2); P = 0.003] and non-significantly in NASH [27.9 L/h (20.6–37.8); P = 0.19]. Aminopyrine metabolism was 25% lower in simple steatosis [8.9% (7.0–10.7)] and 50% lower in NASH [6.0% (4.5–7.5)] than in controls [11.9% (9.3–12.8)] (P < 0.001). ICG elimination was intact. Conclusions: The hepatocellular metabolic functions were altered in a manner that was dissociated both by different effects on different liver functions and by different effects of different stages of NAFLD. Thus, NAFLD has widespread consequences for metabolic liver function, even in simple steatosis.
- Published
- 2019
3. Liver Function Breath Tests for Differentiation of Steatohepatitis From Simple Fatty Liver in Patients With Nonalcoholic Fatty Liver Disease
- Author
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George Tribonias, Dimitrios Pectasides, Dina Tiniakos, Ekaterini Margariti, and George V. Papatheodoridis
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Severity of Illness Index ,digestive system ,Gastroenterology ,Liver Function Tests ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,medicine ,Humans ,Aminopyrine ,Aged ,Breath test ,Carbon Isotopes ,medicine.diagnostic_test ,Receiver operating characteristic ,Cumulative dose ,business.industry ,Fatty liver ,Galactose ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,digestive system diseases ,Fatty Liver ,Cross-Sectional Studies ,Breath Tests ,ROC Curve ,Liver biopsy ,Female ,Liver function ,Steatohepatitis ,business - Abstract
GOALS We investigated the utility of liver function breath tests [C-Aminopyrine Breath Test (C-ABT), C-Galactose Breath Test (C-GBT)], for the diagnosis of nonalcoholic steatohepatitis (NASH) among nonalcoholic fatty liver disease (NAFLD) patients. BACKGROUND Liver biopsy is currently the gold standard for the differentiation between simple fatty liver (NAFL) and NASH in NAFLD patients. MATERIALS AND METHODS Thirty-six patients with histologically proven NAFLD (NAFL:16, NASH:20) underwent C-ABT and C-GBT. The results were expressed as the percentage of administered C dose recovered per hour (%dose/h) and as cumulative percentage of administered C dose recovered over time (%cumulative dose). Histologic lesions were scored according to Brunt and Kleiner's classifications. RESULTS C-ABT results correlated inversely with activity grade (r=-0.650, P=0.001), NAFLD activity score (r=-0.473, P=0.026), and fibrosis stage (r=-0.719, P=0.001). Compared with NAFL, NASH patients had significantly lower %dose/h and %cumulative dose at 60, 90, and 120 minutes (always P
- Published
- 2014
4. 13C-aminopyrine demethylation is decreased in cirrhotic patients with normal biochemical markers
- Author
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Mark Wright, Steve A. Wootton, Alan Jackson, and Paul R. Afolabi
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Bilirubin ,Methylation ,Gastroenterology ,Inorganic Chemistry ,Young Adult ,chemistry.chemical_compound ,Liver disease ,Liver Function Tests ,Internal medicine ,medicine ,Humans ,Environmental Chemistry ,Young adult ,Aminopyrine ,Finland ,General Environmental Science ,Demethylation ,Breath test ,Carbon Isotopes ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Breath Tests ,chemistry ,Alkaline phosphatase ,Female ,business ,Liver function tests ,Biomarkers - Abstract
This study determined the rates of (13)C-aminopyrine metabolism in patients with varying degrees of liver cirrhosis as defined by clinical scores. Twenty-five cirrhotic patients and 18 healthy subjects underwent a (13)C-aminopyrine breath test. The cumulative per cent dose recovery (cPDR) of (13)C on breath expressed as a percentage of the administered dose at 2 h was significantly lower in cirrhotic patients than in healthy subjects (median: 1.7% versus 9.0%; p
- Published
- 2013
5. Relationship Between 13C-Aminopyrine Breath Test and the MELD Score and Its Long-Term Prognostic Use in Patients with Cirrhosis
- Author
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Vincenzo Savarino and Edoardo G. Giannini
- Subjects
Liver Cirrhosis ,Male ,medicine.medical_specialty ,Cirrhosis ,Physiology ,Kaplan-Meier Estimate ,Gastroenterology ,Cohort Studies ,End Stage Liver Disease ,Liver disease ,Transplant surgery ,Liver Function Tests ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,In patient ,Prospective Studies ,Aminopyrine ,Breath test ,Carbon Isotopes ,medicine.diagnostic_test ,business.industry ,Middle Aged ,Hepatology ,Prognosis ,medicine.disease ,Liver Transplantation ,Survival Rate ,Breath Tests ,ROC Curve ,Female ,Liver function ,Liver function tests ,business ,Follow-Up Studies - Abstract
(13)C-Aminopyrine breath test ((13)C-ABT) is a non-invasive, dynamic, quantitative liver function test, and the model for end-stage liver disease (MELD) is a recognised biochemical score used to predict survival in patients with cirrhosis.The purpose of this study was to evaluate the relationship between the (13)C-ABT and MELD score in a cohort of cirrhotic patients and, moreover, to assess the prognostic value of (13)C-ABT results in the same group of patients.Forty-six patients with cirrhosis and without hepatocellular carcinoma who underwent (13)C-ABT and who had at least 1-year follow-up were prospectively included in this study. MELD score was calculated at entry into the study in all patients. End-points of the study were 1-year liver-related death or liver transplantation.(13)C-ABT %dose/h at 30 min (%dose/h30) results showed significant, inverse correlation with MELD scores (r = -0.414, P = 0.004). During 1-year follow-up nine patients died (19.6 %) and two were transplanted (4.3 %). Median (13)C-ABT %dose/h30 results (3.2 vs. 1.8) were significantly higher in patients who survived as compared to those who died or underwent transplantation (P = 0.04). Receiver operating characteristics curves showed that a (13)C-ABT %dose/h30 cut-off of 2.0 had the best accuracy (c-index = 0.717) in assessing 1-year prognosis.We observed a correlation between a flow-independent quantitative liver function test and the MELD score, and found that the (13)C-ABT may accurately provide long-term prognostic information in cirrhotic patients.
- Published
- 2013
6. In vitro effect of glucagon-like peptide-1 (7-36)amide, oxyntomodulin, vasoactive intestinal peptide and somatostatin on gastric acid and pepsinogen secretion
- Author
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W. K. Man, J. Spencer, A. A. Houssein, and A. Ben-Hamida
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Male ,medicine.medical_specialty ,Immunology ,Vasoactive intestinal peptide ,Glucagon-Like Peptides ,Peptide ,Gastric Acid ,chemistry.chemical_compound ,Pepsin ,Glucagon-Like Peptide 1 ,Internal medicine ,medicine ,Animals ,Secretion ,Rats, Wistar ,Aminopyrine ,Pharmacology ,chemistry.chemical_classification ,biology ,Pepsinogens ,Glucagon-like peptide-1 ,Rats ,Oxyntomodulin ,Somatostatin ,Endocrinology ,chemistry ,Histamine H2 Antagonists ,Gastric Mucosa ,biology.protein ,Gastric acid ,Cimetidine ,Peptides ,Histamine ,Vasoactive Intestinal Peptide - Published
- 2016
7. Pyrazolones metabolites are relevant for identifying selective anaphylaxis to metamizole
- Author
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Maria Salas, José A. G. Agúndez, Maria I. Montañez, James R. Perkins, María José Torres, Elena García-Martín, Inmaculada Andreu, Adriana Ariza, Miguel Blanca, Cristobalina Mayorga, and Natalia Blanca-López
- Subjects
0301 basic medicine ,Drug ,Adult ,Male ,media_common.quotation_subject ,Primary Cell Culture ,Dipyrone ,Basophil Degranulation Test ,Pilot Projects ,Pharmacology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,Medicine ,Humans ,Aminopyrine ,Anaphylaxis ,Biotransformation ,media_common ,Aged ,Multidisciplinary ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Ampyrone ,Middle Aged ,medicine.disease ,Metamizole ,In vitro ,Basophils ,Basophil activation ,030104 developmental biology ,030228 respiratory system ,chemistry ,Case-Control Studies ,Immunology ,Pyrazolones ,Female ,business ,medicine.drug - Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of hypersensitivity reactions, with pyrazolones the most frequent drugs inducing selective reactions. Immediate selective hypersensitivity to pyrazolones is thought to be mediated by specific-IgE. Sensitivity of in vitro diagnostic tests is low and this may be due to the incomplete characterization of the structures involved. Here we investigated whether main metabolites of metamizole (dipyrone) in human could be involved in the immune response using the basophil activation test (BAT). We studied subjects with confirmed selective immediate hypersensitivity to metamizole and performed BAT with metamizole and its metabolites: 4-methylamino-antipyrine (MAA), 4-aminoantipyrine (AA), 4-acetylamino-antipyrine (AAA) and 4-formylamino-antipyrine (FAA). BAT results showed an increase of positive results from 37.5% to 62.5% using metamizole plus metabolites as compared with the BAT carried out only with the parent drug, demonstrating that metamizole metabolites have a role in the reaction and can induce specific basophil activation in patients with immediate hypersensitivity to this drug. Our findings indicate that pyrazolone metabolites are useful for improving the in vitro diagnosis of allergic reactions to metamizole.
- Published
- 2016
8. Effect of Nicorandil upon Different Guinea-pig and Rat Isolated Organ Preparations in vitro
- Author
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Cecilio Alamo, Alfonso Velasco, Alberto Barcenilla, Alfonso Carvajal, and Javier García-Pozo
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Male ,Serotonin ,medicine.medical_specialty ,Potassium Channels ,Vasodilator Agents ,Potassium ,Guinea Pigs ,chemistry.chemical_element ,In Vitro Techniques ,Biology ,Guinea pig ,chemistry.chemical_compound ,Vas Deferens ,Internal medicine ,Drug Discovery ,medicine ,Animals ,Rats, Wistar ,Aminopyrine ,Nicorandil ,Nicotinamide ,Anti-Inflammatory Agents, Non-Steroidal ,Uterus ,Vas deferens ,Acetylcholine ,Potassium channel ,Rats ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Barium ,Organ Specificity ,Female ,Histamine ,medicine.drug - Abstract
A study of the effect of nicorandil (N-2-(hydroxyethyl)nicotinamide nitrate, CAS 65141-46-0), a potassium channel and guanylatecyclase activator, upon preparations of rat was deferens and uterus, and guinea pig ileum was performed. Nicorandil does not modify rat isolated was deferens responses to noradrenaline (norepinephrine) and potassium. The drug exerts a non-competitive antagonist effect upon rat isolated uterus response to serotonin, histamine, oxytocin, and, at high concentrations, inhibits guinea-pig isolated ileum responses to acetylcholine, histamine, 4-aminopyridine and potassium.
- Published
- 2011
9. Effects of IY-81149, a Newly Developed Proton Pump Inhibitor, on Gastric Acid Secretion in vitro and in vivo
- Author
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Seung Mok Lee, Dow Kwon, Eun Ju Kim, Chan Wong Park, Yong Sik Kim, Joo Byung Chae, Kil Do Cho, In Hoi Huh, and Dong Yeun Kim
- Subjects
Male ,Antiulcer drug ,medicine.drug_class ,Proton-pump inhibitor ,In Vitro Techniques ,Pharmacology ,2-Pyridinylmethylsulfinylbenzimidazoles ,Gastric Acid ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Oral administration ,Drug Discovery ,medicine ,Animals ,Enzyme Inhibitors ,Aminopyrine ,Omeprazole ,Parietal cell ,Stomach ,Proton Pump Inhibitors ,Anti-Ulcer Agents ,Rats ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Gastric Mucosa ,Sulfoxides ,Gastric acid ,Benzimidazoles ,Pentagastrin ,Rabbits ,Histamine ,medicine.drug - Abstract
The inhibitory effects of IY-81149 (2-[[(4-methoxy-3-methyl)-2- pyridinyl]methyl-sulfinyl]-5-(1H-pyrol-1-yl)-1H-benzimidazole, CAS 172152-36-2), a newly developed proton pump inhibitor (PPI) on gastric acid secretion were investigated in vitro and in vivo. In rabbit parietal cell preparation, IY-81149 irreversibly inhibited H+/K(+)-ATPase in dose-dependent manner with an IC50 of pump inhibitory activity of 6.0 x 10(-6) mol/l and that of omeprazole (CAS 73590-58-6) was 1 x 10(-4) mol/l at pH 7.4. On cumulation of 14C-aminopyrine in histamine stimulated parietal cells, the IC50 of IY-81149 was 9.0 x 10(-9) mol/l and that of omeprazole was 1.9 x 10(-8) mol/l. The inhibition rates of IY-81149 and omeprazole at a concentration of 1 x 10(-9) mol/l in human parietal cells were 137% and 64%, respectively. In pylorus-ligated rats, IY-81149 showed a 2-3 times stronger inhibitory activity than omeprazole against gastric acid secretion. The ED50 of IY-81149 and omeprazole administered intraduodenally was 1.6 mg/kg and 3.8 mg/kg. In the case of oral administration, the ED50 of IY-81149 and omeprazole was 1.94 mg/kg and 5.64 mg/kg, respectively. But after 24 h administration, the anti-secretory activity of IY-81149 was lower than that of omeprazole at all doses tested. In anesthetized rats, IY-81149 dose-dependently increased gastric pH which was lowered by histamine infusion. In the case of i.v. injection, the ED50 of IY-81149 and omeprazole was 1.2 and 1.4 mg/kg and in the case of i.d. administration, the ED50 of IY-81149 and omeprazole was 3.9 and 4.1 mg/kg, respectively. IY-81149 also significantly inhibited pentagastrin-stimulated gastric secretion. Its ED50 was 2.1 mg/kg and that of omeprazole was 3.5 mg/kg with i.d. administration. In the case of i.v. injection, IY-81149 was equipotent to omeprazole. IY-81149 also inhibited gastric acid secretion strongly in fistular rats. The ED50 of IY-81149 administered intraduodenally was 0.43 mg/kg and that of omeprazole was 0.68 mg/kg. In Heidenhain pouch dogs, the acid output was completely blocked at 0.3 mg/kg, 135 min after i.v. administration. Omeprazole showed a similar effect as IY-81149. The histamine induced increase of acid output in the Heidenhain pouch dog was blocked by 71% 150 min after oral administration of enteric-coated IY-81149 at a dose of 3 mg/kg, and omeprazole showed similar effects. In conclusion, IY-81149 revealed the characteristics as a strong proton pump inhibitor, and its potency against gastric acid secretion was superior to that of the reference drug, omeprazole.
- Published
- 2011
10. Antisecretory actions of Baccharis trimera (Less.) DC aqueous extract and isolated compounds: Analysis of underlying mechanisms
- Author
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Thais Maíra A. Biondo, A. J. Lapa, Caden Souccar, Eliana Della Coletta, Maria Teresa R. Lima-Landman, and M.M. Tanae
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Male ,Cyclohexanecarboxylic Acids ,Acid secretion ,medicine.medical_treatment ,Mice, Inbred Strains ,Asteraceae ,Pharmacology ,Diterpenes, Clerodane ,Gastric Acid ,Mice ,chemistry.chemical_compound ,Baccharis trimera ,Stress, Physiological ,Antacid ,Gastric glands ,Drug Discovery ,H+, K+-ATPase ,medicine ,Gastric mucosa ,Clerodane diterpene ,Animals ,Antiulcer ,Stomach Ulcer ,Aminopyrine ,Flavonoids ,Rabbit gastric glands ,biology ,Plant Extracts ,Chemistry ,Baccharis ,Stomach ,Plant Components, Aerial ,biology.organism_classification ,Disease Models, Animal ,medicine.anatomical_structure ,Biochemistry ,Gastric Mucosa ,Gastric acid ,Antacids ,Rabbits ,Kidney disorder ,Chlorogenic Acid ,Diterpenes ,Histamine ,Phytotherapy - Abstract
Ethnopharmacological relevance Baccharis trimera (Less.) DC. (Asteraceae) is a species native to South America used in Brazilian folk medicine to treat gastrointestinal and liver diseases, kidney disorders and diabetes. Previous studies from this laboratory confirmed the antacid and antiulcer activities of the plant aqueous extract (AE) in rat and mouse models. Aim of the study To investigate the mechanisms involved in the antacid action of AE and isolated compounds from Baccharis trimera. Materials and methods AE was assayed in vivo in cold-restraint stress gastric ulcers and in pylorus-ligated mice. Nine fractions (F2–F10) previously isolated from AE were assayed in vitro on acid secretion measured as [ 14 C]-aminopyrine ([ 14 C]-AP) accumulation in rabbit gastric glands, and on gastric microsomal H + , K + -ATPase preparations. Chlorogenic acids (F2, F3, F6, F7), flavonoids (F9), an ent -clerodane diterpene (F8) and a dilactonic neo -clerodane diterpene (F10) have been identified in these fractions. Results Intraduodenal injection of AE (1.0 and 2.0 g/kg) in 4 h pylorus-ligated mice decreased the volume (20 and 50%) and total acidity (34 and 50%) of acid secretion compared to control values. Administered orally at the same doses AE protected against gastric mucosal lesions induced in mice by restraint at 4 °C. Exposure of isolated rabbit gastric glands to fractions F8 (10–100 μM) and F9 (10–300 μg/ml) decreased the basal [ 14 C]-AP uptake by 50 and 60% of control (Ratio = 6.2 ± 1.1), whereas the remaining fractions were inactive. In the presence of the secretagogues F2 and F4 (30–300 μg/ml) decreased the [ 14 C]-AP uptake induced by histamine (His) with a 100-fold lower potency than that of ranitidine. F5 and F6 reduced the [ 14 C]-AP uptake stimulated by carbachol (CCh), but they were 10 to 20-fold less potent than atropine. F8 (diterpene 2 ) and F9 (flavonoids) decreased both the His- and CCh-induced [ 14 C]-AP uptake, whereas F10 (diterpene 1 ) was inactive against the [ 14 C]-AP uptake stimulated by secretagogues. Diterpene 2 was the most active of all tested compounds being 7-fold less potent than ranitidine and equipotent to atropine in reducing acid secretion in vitro . This compound also reduced the gastric H + , K + -ATPase activity by 20% of control, while the remaining fractions were inactive on the proton pump in vitro . Conclusions The results indicate that Baccharis trimera presents constituents that inhibit gastric acid secretion by acting mainly on the cholinergic regulatory pathway. The plant extract also contains compounds that exert moderate inhibition of the histaminergic regulatory pathway of acid secretion and the gastric proton pump. Altogether these active constituents appear to provide effective inhibition of acid secretion in vivo , which may explain the reputed antiulcer activity of the plant extract.
- Published
- 2011
11. TUMOUR INDUCTION IN SYRIAN HAMSTERS FED A COMBINATION OF AMINOPYRINE AND NITRIT
- Author
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Frank Bergman and T. Wahlin
- Subjects
Male ,medicine.medical_specialty ,Lung Neoplasms ,Sodium ,Intrahepatic bile ducts ,chemistry.chemical_element ,Chenodeoxycholic Acid ,chemistry.chemical_compound ,Adenoma, Bile Duct ,Cricetinae ,Internal medicine ,Chenodeoxycholic acid ,medicine ,Animals ,Aminopyrine ,Nitrites ,Syrian hamsters ,Carcinogen ,Mesocricetus ,Sodium Nitrite ,Tumour induction ,General Medicine ,Bile Ducts, Intrahepatic ,Endocrinology ,Bile Duct Neoplasms ,chemistry ,Female - Abstract
Hamsters fed a aminopyrine/sodium nitrit mixture in drinking water showed a high incidence of intrahepatic bile duct tumours. Chenodeoxycholic acid was not found to have any promoting effect on the liver carcinogenicity induced by this combination of aminopyrine and sodium nitrit in hamsters.
- Published
- 2009
12. In Vitro Medullary Granulocytic Progenitor (CFUC) Cultures from 6 Cases of Granulocytopenias
- Author
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Gil Tchernia, Morardet N, E. Subtil, L. Diakhate, and Claude Parmentier
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Medullary cavity ,Cellular differentiation ,Bone Marrow Cells ,Granulocyte ,Biology ,Colony-Forming Units Assay ,Andrology ,Leukocyte Count ,Bone Marrow ,Cephalothin ,medicine ,Humans ,Aminopyrine ,Mitosis ,Cells, Cultured ,Aged ,Progenitor ,Thiamphenicol ,Granulocytopenias ,Hematology ,Middle Aged ,Hematopoietic Stem Cells ,In vitro ,medicine.anatomical_structure ,Female ,Stem cell ,Agranulocytosis - Abstract
Medullary granulocyte progenitor (CFUc) cultures were grown in vitro from samples taken from 6 patients with toxic granulocytopenia caused by either thiamphenicol cephalothin or amidopyrine and who are now apparently cured. A decreased in the medullary concentration of CFUc has been observed and a calculated estimate shows that there was a decrease in their absolute number. A decrease in the number of CFUc per 10(5) metamyelocytes suggests a possible compensation by mitotic amplification between the stem cell and the differentiated cells. Two successive cultures have shown that the course of such medullary cultures is variable. The existence of medullary anomalies before drug toxicity as well as the practical consequences of the contrast between the apparent cure and the decrease in CFUc are discussed.
- Published
- 2009
13. CYCLO-OXYGENASE-1 INHIBITION INCREASES ACID SECRETION BY MODULATING H+,K+-ATPase EXPRESSION AND ACTIVATION IN RABBIT PARIETAL CELLS
- Author
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Jyotirmoy Nandi, Robert A. Levine, J. Michael Zinkievich, Pratap K Das, and Juan Diego Baltodano
- Subjects
Male ,medicine.medical_specialty ,Physiology ,ATPase ,Prostaglandin ,H(+)-K(+)-Exchanging ATPase ,Dinoprostone ,Gastric Acid ,Inhibitory Concentration 50 ,chemistry.chemical_compound ,Parietal Cells, Gastric ,Physiology (medical) ,Internal medicine ,Gastric glands ,medicine ,Animals ,Cyclooxygenase Inhibitors ,Secretion ,Aminopyrine ,Cells, Cultured ,Parietal cell ,Pharmacology ,biology ,Chemistry ,Endocrinology ,medicine.anatomical_structure ,Cyclooxygenase 2 ,Cyclooxygenase 1 ,biology.protein ,Gastric acid ,Rabbits ,Histamine - Abstract
1. In the present study, we evaluated the role of cyclo-oxygenase (COX)-1 and COX-2 on gastric acid secretion in rabbit isolated parietal cells and gastric glands by examining [(14)C]-aminopyrine uptake, prostaglandin (PG) E(2) synthesis and COX-1, COX-2 and proton pump expression at baseline and after treatment with various concentrations of specific COX-1 (SC-560), COX-2 (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methyl-sulphonyl)phenyl-2 (5H)-furanone; DFU) and non-specific COX (indomethacin) inhibitors. 2. In parietal cells, SC-560 and indomethacin, over the concentration range 10(-8) to 10(-4) mol/L, dose-dependently increased basal and 10(-4) mol/L histamine-stimulated aminopyrine uptake and inhibited PGE(2) synthesis, whereas DFU (10(-8) to 10(-5) mol/L) had no effect. However, at 10(-4) mol/L, DFU augmented histamine-stimulated aminopyrine uptake by 135% and inhibited PGE(2) synthesis by 39%, indicating an inhibition of COX-1 at this higher concentration. 3. The SC-560-, DFU- and indomethacin-induced augmentation of histamine-stimulated aminopyrine uptake was reduced to basal levels after 10(-5) mol/L lansoprazole treatment in parietal cells and gastric glands, whereas 10(-4) mol/L ranitidine only partially inhibited such augmentation. 4. Only COX-1 was detected in parietal cells. However, both COX-1 and COX-2 were expressed in gastric glands, with relative protein density of COX-1 being sixfold higher than that of COX-2. Protein levels of COX-1 in parietal cells and those of COX-1 and COX-2 in gastric glands remained unchanged, regardless of inhibitor treatment, either alone or with histamine. 5. Parietal cell proton pump expression was significantly enhanced by 10(-5) mol/L SC-560 and 10(-4) mol/L indomethacin (by 29 and 31%, respectively) and pump activity was enhanced by 61 and 65%, respectively. In contrast, 10(-5) mol/L DFU had no effect. 6. In conclusion, the data indicate that inhibition of COX-1- but not COX-2-derived PGE(2) synthesis is involved in augmentation of non-steroidal anti-inflammatory drug-induced gastric acid secretion in parietal cells by enhancing expression and activation of the proton pump.
- Published
- 2009
14. Inhibition of the gastric H+,K+-ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews
- Author
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Myllene P. Bossolani, Antonio José Lapa, Caden Souccar, Maria Teresa R. Lima-Landman, Carla Schultz, and Luce Maria Brandão Torres
- Subjects
Male ,Plectranthus ,Chemical Fractionation ,In Vitro Techniques ,Muscarinic Agonists ,Pharmacognosy ,Pharmacology ,H(+)-K(+)-Exchanging ATPase ,Gastric Acid ,Mice ,chemistry.chemical_compound ,Gastric glands ,Drug Discovery ,Plectranthus barbatus ,medicine ,Animals ,Enzyme Inhibitors ,Aminopyrine ,Lamiaceae ,Dose-Response Relationship, Drug ,biology ,Stomach ,Proton Pump Inhibitors ,Gastric Acidity Determination ,Bethanechol ,Anti-Ulcer Agents ,biology.organism_classification ,Plant Leaves ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Gastric Mucosa ,Abietanes ,Gastric acid ,Rabbits ,Brazil ,Histamine - Abstract
This work assessed the mechanism underlying the antisecretory gastric acid effect of Plectranthus barbatus Andrews (Lamiaceae) and active constituents. Popularly known as "false-boldo", this plant is used in Brazilian folk medicine to treat gastrointestinal and hepatic ailments. The plant aqueous extract (AE) and isolated compounds were assayed in vivo in pylorus-ligated mice, and in vitro on acid secretion measured as [(14)C]-aminopyrine ([(14)C]-AP) accumulation in rabbit gastric glands and gastric H(+),K(+)-ATPase preparations. Injected into the duodenal lumen, the AE of the plant leaves (0.5 and 1.0 g/kg) decreased the volume (62 and 76%) and total acidity (23 and 50%) of gastric acid secretion in pylorus-ligated mice. Bioguided purification of the AE yielded an active fraction (IC(50)=24 microg/ml) that inhibited acid secretion in rabbit gastric glands with a potency 10 to 18 times greater than that of the originating extract, on both the basal and stimulated acid secretion by histamine (His) (1 microM) or bethanechol (100 microM). At the same concentrations the gastric H(+),K(+)-ATPase activity was also inhibited. The active constituent was chemically identified as the abietanoid dienedione plectrinone A which reduced the H(+),K(+)-ATPase activity with IC(50)=171 microM. The results indicate that inhibition of the gastric proton pump by this diterpenoid may account for the antisecretory acid effect and reputed anti ulcer activity of Plectranthus barbatus.
- Published
- 2007
15. Cytochrome P450 activity mirrors nitric oxide levels in postoperative sepsis: Predictive indicators of lethal outcome
- Author
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Bernhard Holzmann, Heike Weighardt, Stefan Maier, Markus Schwaiger, Alexander Novotny, Holger Bartels, Claus-Dieter Heidecke, J. Stadler, Alexandra Westerholt, Klaus Emmanuel, and J. R. Siewert
- Subjects
Male ,medicine.medical_specialty ,Pathology ,Nitric Oxide ,Systemic inflammation ,Severity of Illness Index ,Gastroenterology ,Nitric oxide ,Sepsis ,chemistry.chemical_compound ,Postoperative Complications ,Cytochrome P-450 Enzyme System ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,Carbon Radioisotopes ,Aminopyrine ,Aged ,Breath test ,medicine.diagnostic_test ,Tumor Necrosis Factor-alpha ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Breath Tests ,Liver ,chemistry ,Bacteremia ,Female ,Surgery ,Tumor necrosis factor alpha ,Liver function ,medicine.symptom ,business ,Biomarkers ,Liver Failure ,Abdominal surgery - Abstract
Background The development of liver failure significantly influences prognosis during the course of major septic complications. Although the underlying cause for septic liver failure is still unclear, research using animal models has demonstrated that an increased nitric oxide (NO) synthesis compromises detoxification processes in the liver. Methods In the present study, serum NO levels were measured by high-performance liquid chromatography (HPLC) and aminopyrine breath test (ABT) scores, reflecting the in vivo activity of cytochrome P450-dependent liver enzymes, were investigated in 42 patients (23 who survived sepsis [survivors]/19 patients who ultimately died of sepsis [nonsurvivors]) suffering from major septic complications after abdominal surgery. Additionally, TNF-α serum levels, serving as indicators for major systemic inflammation, were monitored using enzyme-linked immunosorbent assay (ELISA). Results The increased serum NO levels that were found during sepsis correlated with the severity of the septic course. Compared with preoperative values of 42.77 ± 5.84 mM, nitrite/nitrate levels reached 72.88 ± 10.16 mM in early sepsis. An increased NO synthesis also was accompanied by a rise in serum TNF-α levels. Monitoring of liver function by ABT allowed an early differentiation between transient sepsis and sepsis with a lethal outcome (P = .006). In contrast, cytochrome P450 activity as measured by the ABT was significantly diminished in septic patients (0.45 ± 0.02 [% dose × kgBW per (mmol CO2)−1] before sepsis onset/0.16 ± 0.01 [% dose × kgBW per (mmol CO2)−1] in sepsis). Like the NO and TNF-α levels, ABT scores showed a difference between transient sepsis and sepsis with a lethal outcome. Serum NO levels were inversely correlated with ABT scores (P = .022) and positively correlated with TNF-α levels (P = 0.015) in the late phase of sepsis. Serum TNF-α levels and ABT scores were inversely correlated in the early (P = .027), as well as in the late (P = .015) phases of sepsis. Conclusions This study supports the hypothesis that septic liver failure is linked to the induction of NO synthesis in major systemic inflammation. Therefore, the ABT provides a clinically useful tool for predicting the outcome in the early stages of sepsis. This may aid in the decision-making process when early surgical intervention is considered.
- Published
- 2007
16. Assessment and monitoring of liver function by ¹³C-aminopyrine breath test after selective transarterial chemoembolisation of hepatocellular carcinoma
- Author
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K, Schütte, R, Seidensticker, O, Milbradt, J, Bornschein, A, Kandulski, M, Pech, S, Kropf, J, Ricke, and P, Malfertheiner
- Subjects
Male ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Reproducibility of Results ,Prognosis ,Sensitivity and Specificity ,Treatment Outcome ,Breath Tests ,Cytochrome P-450 Enzyme System ,Liver Function Tests ,Humans ,Female ,Carbon Radioisotopes ,Chemoembolization, Therapeutic ,Drug Monitoring ,Aminopyrine ,Aged ,Neoplasm Staging - Abstract
Liver function and tumor staging are essential parameters for selection of treatment modalities in patients with hepatocellular carcinoma (HCC). Transarterial chemoembolization (TACE) is associated with a risk of deterioration of liver function. In clinical routine hepatic function in patients with liver cirrhosis is assessed by the Child-Pugh-classification. Dynamic breath tests allow the assessment of the hepatic functional mass and have the potential to give more accurate information on hepatic function periinterventionally.A prospective clinical study was performed in 13 patients receiving a total of 18 TACE sessions. (13)C-aminopyrine breath test was performed the day before TACE, 2 days and 30 days after TACE and correlated with standard laboratory work-up of the patients.Fourteen TACE sessions were performed in Child A liver cirrhosis, 4 in Child B cirrhosis. All patients presented with impaired aminopyrine metabolism at baseline. No significant changes in the (13)C aminopyrine breath test following TACE were observed. Two patients treated in Child A cirrhosis decompensated to Child B, one of them recovered. No further decompensation was observed in patients treated in Child B cirrhosis.Liver function assessment with (13)C-aminopyrine breath test and Child-Pugh-classification following TACE was discordant in a large proportion of patients. Whether a quantification of mitochondrial liver function in patients planned to undergo locoregional treatment of HCC in liver cirrhosis is helpful in the prediction of postprocedural liver decompensation needs to be addressed in larger prospective clinical trials.
- Published
- 2015
17. Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis
- Author
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Vreni Schneider, M. Ledermann, H. Saegesser, Juerg Reichen, and Markus Neef
- Subjects
Male ,medicine.medical_specialty ,Cirrhosis ,Blotting, Western ,Administration, Oral ,Gene Expression ,Biology ,Liver Cirrhosis, Experimental ,Collagen Type I ,Transforming Growth Factor beta1 ,Transforming Growth Factor beta2 ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Aminopyrine ,PI3K/AKT/mTOR pathway ,Antibacterial agent ,Sirolimus ,Dose-Response Relationship, Drug ,Hepatology ,Reverse Transcriptase Polymerase Chain Reaction ,medicine.disease ,digestive system diseases ,Extracellular Matrix ,Rats ,Collagen Type I, alpha 1 Chain ,Survival Rate ,Disease Models, Animal ,Treatment Outcome ,Endocrinology ,Breath Tests ,chemistry ,Biliary tract ,Hepatic stellate cell ,Matrix Metalloproteinase 2 ,Liver function ,Thioacetamide ,Immunosuppressive Agents ,medicine.drug - Abstract
Background/Aims Mammalian target of rapamycin (mTOR) signalling is central in the activation of hepatic stellate cells (HSCs), the key source of extracellular matrix (ECM) in fibrotic liver. We tested the therapeutic potential of the mTOR inhibitor rapamycin in advanced cirrhosis. Methods Cirrhosis was induced by bile duct-ligation (BDL) or thioacetamide injections (TAA). Rats received oral rapamycin (0.5mg/kg/day) for either 14 or 28 days. Untreated BDL and TAA-rats served as controls. Liver function was quantified by aminopyrine breath test. ECM and ECM-producing cells were quantified by morphometry. MMP-2 activity was measured by zymography. mRNA expression of procollagen-α1, transforming growth factor-β1 (TGF-β1) and β2 was quantified by RT-PCR. Results Fourteen days of rapamycin improved liver function. Accumulation of ECM was decreased together with numbers of activated HSCs and MMP-2 activity in both animal models. TGF-β1 mRNA was downregulated in TAA, TGF-β2 mRNA was downregulated in BDL. 28 days of rapamycin treatment entailed a survival advantage of long-term treated BDL-rats. Conclusions Low-dose rapamycin treatment is effectively antifibrotic and attenuates disease progression in advanced fibrosis. Our results warrant the clinical evaluation of rapamycin as an antifibrotic drug.
- Published
- 2006
18. Noninvasive ratio indexes to evaluate fibrosis staging in chronic hepatitis C: role of platelet count/spleen diameter ratio index
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Luis Isola, S. Milazzo, Emanuela Testa, Roberto Testa, Paolo Borro, Domenico Risso, Edoardo G. Giannini, P. B. Lantieri, and P. Ceppa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pathology ,Concordance ,Gastroenterology ,Statistics, Nonparametric ,Liver Function Tests ,Fibrosis ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Platelet ,Aminopyrine ,Ultrasonography ,Breath test ,medicine.diagnostic_test ,Platelet Count ,business.industry ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Breath Tests ,Liver ,ROC Curve ,Female ,Liver function ,business ,Hepatic fibrosis ,Liver function tests ,Body mass index ,Biomarkers ,Spleen - Abstract
Objectives. Noninvasive evaluation of fibrosis is an on-going effort in the management of chronic hepatitis C. This study was planned to noninvasively evaluate fibrosis staging. Design. We evaluated the biochemical, functional [aminopyrine breath test (ABT)] and ultrasonographic variables of 75 chronic hepatitis C patients. Results. Clinical [body mass index (BMI)], biochemical [aspartate aminotransferase (AST), alanine aminotransferase (ALT) and platelets (PLT)] and ratio indexes, together with the ABT, showed a higher relationship with fibrosis: initial (score ≤ 2) versus evident (score > 2) fibrosis: BMI (24 ± 2 vs. 26 ± 2, P = 0.0007), AST (56 ± 36 vs. 88 ± 65, P = 0.0159), ALT (92 ± 54 vs. 139 ± 108, P = 0.0290), PLT (220 ± 64 vs. 173 ± 61, P = 0.0007), PLT/spleen diameter ratio (PLT/SPD) (2133 ± 786 vs. 1540 ± 681, P = 0.0003), AST/platelet count ratio index (APRI) (0.80 ± 0.87 vs. 1.51 ± 1.47, P = 0.0010), ABT%d/h30 min (10.8 ± 4.5 vs. 7.6 ± 3.8, P = 0.0007), ABT%d/cum120 min (8.9 ± 3.3 vs. 6.5 ± 3.1, P = 0.0007). Considering the differences between fibrosis score 2 and 3 patients, BMI, ABT and PLT/SPD ratio proved to be statistically significant. Multivariate stepwise analysis (with and without BMI) identified two models for distinguishing between initial and evident fibrosis: Model 1: −0.569 +(BMI × 0.107) + (APRI × 0.169)−(PLT/SPD × 0.304), and Model 2: 2.376 + (APRI × 0.152)−(ABTd/h30 × 0.043)−(PLT/SPD × 0.249). These models showed concordance in identifying or ruling out evident fibrosis in 76% and 78.7% of the patients respectively. The PLT/SPD ratio also showed 78.7% concordance with the histological score. Conclusion. These results suggest that noninvasive evaluation of fibrosis in chronic hepatitis C may be considered an effective tool thanks to the use of an inexpensive, reproducible ratio index.
- Published
- 2006
19. Comparison of various doses of carbon 13-labeled aminopyrine for a carbon 13-labeled aminopyrine demethylation blood test in healthy dogs
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Jörg M. Steiner, David A. Williams, Mark Alan Tetrick, John Burr, and E. Michael Moeller
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Male ,Evacuated tube ,Coefficient of variation ,Hydrochloric acid ,Methylation ,chemistry.chemical_compound ,Dogs ,Liver Function Tests ,medicine ,Animals ,Blood test ,Dog Diseases ,Aminopyrine ,Demethylation ,Carbon Isotopes ,Cross-Over Studies ,Chromatography ,Dose-Response Relationship, Drug ,General Veterinary ,medicine.diagnostic_test ,Chemistry ,Liver Diseases ,Carbon-13 ,Heparin sodium ,General Medicine ,Health ,Female - Abstract
Objective—To determine an optimal dose of carbon 13 (13C)-labeled aminopyrine for use in a 13C-aminopyrine demethylation blood test in healthy dogs. Animals—9 adult dogs. Procedures—Food was withheld from each dog for 12 hours. A 2-mL baseline blood sample was obtained from each dog and placed into an evacuated tube containing sodium heparin. Carbon 13-labeled aminopyrine was administered IV at doses of 1, 2, 5, or 10 mg/kg. Additional blood samples (2 mL) were obtained and placed into evacuated tubes containing sodium heparin 30, 45, 60, and 75 minutes after 13C-aminopyrine administration. Hydrochloric acid was used to extract CO2 from blood samples. The extracted gas was analyzed by fractional mass spectrometry to determine the percentage dose of 13C administered as 13C-aminopyrine and recovered in extracted gas (PCD). Results—Gross evidence of clinical adverse effects was not detected in any dog after administration of 13C-aminopyrine. The mean coefficient of variation (CV) for PCD was significantly lower than the mean CV for the summation of PCD values up to a given sampling time (CUMPCD). Mean PCD values among the 4 doses for each sample time were not significantly different. Administration of 13C-aminopyrine at a dose of 2 mg/kg resulted in the lowest interindividual variability. Conclusions and Clinical Relevance—The PCD is superior to CUMPCD for the quantification of aminopyrine demethylation. Administration of 13C-13C-aminopyrine at a dose of 2 mg/kg is appropriate for use in the 13C-aminopyrine demethylation blood test in healthy dogs.
- Published
- 2006
20. Hyaluronic acid and aspartate aminotransferase levels normalized by liver function can reflect sinusoidal impairment in chronic liver disease
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Cinzia Cordiviola, Domenico Risso, Edoardo G. Giannini, Sara Milazzo, Tiziana Cotellessa, Federica Malfatti, Elisa Marabotto, Emanuela Testa, Mario Mamone, Paola Ceppa, and Roberto Testa
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Biopsy ,Chronic liver disease ,Gastroenterology ,chemistry.chemical_compound ,Model for End-Stage Liver Disease ,Fibrosis ,Internal medicine ,Hyaluronic acid ,medicine ,Humans ,Aspartate Aminotransferases ,Endothelium ,Liver damage ,Hyaluronic Acid ,Aminopyrine ,Breath test ,Hepatology ,medicine.diagnostic_test ,business.industry ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Breath Tests ,Liver ,chemistry ,Disease Progression ,Female ,Liver function ,business ,Biomarkers - Abstract
Background/Aim: To evaluate the relationship between hyaluronic acid/aminopyrine breath test (HA/ABT) ratio and fibrosis score in chronic hepatitis, and between HA/ABT and clinical staging (child-turcotte-pugh'score, CTP; and model for end stage liver disease, MELD) in cirrhosis, as well as to evaluate the aspartate aminotransferase (AST)/ABT in relation to the HA/ABT. Methods: We studied 48 patients with histologically proven chronic hepatitis C (CHC) and 35 patients with compensated cirrhosis (CIR). Results: HA/ABT and AST/ABT showed a more significant correlation with the fibrosis score than HA or ABT or AST alone in the 48 CHC patients: r=0.568 (P
- Published
- 2006
21. Influence of 1-Week Helicobacter pylori Eradication Therapy with Rabeprazole, Clarithromycin, and Metronidazole on 13C-Aminopyrine Breath Test
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Federica Malfatti, Edoardo G. Giannini, Emanuela Testa, Federica Botta, Mario Mamone, Simone Polegato, Roberto Testa, Alessandra Fumagalli, and Vincenzo Savarino
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Population ,Rabeprazole ,Pharmacology ,Gastroenterology ,2-Pyridinylmethylsulfinylbenzimidazoles ,Helicobacter Infections ,Anti-Infective Agents ,Cytochrome P-450 Enzyme System ,Liver Function Tests ,Clarithromycin ,Metronidazole ,Internal medicine ,medicine ,Humans ,Drug Interactions ,Enzyme Inhibitors ,Aminopyrine ,education ,Aged ,Antibacterial agent ,Breath test ,Carbon Isotopes ,education.field_of_study ,Helicobacter pylori ,medicine.diagnostic_test ,biology ,Chemistry ,Middle Aged ,biology.organism_classification ,Anti-Bacterial Agents ,Breath Tests ,Liver ,Benzimidazoles ,Drug Therapy, Combination ,Female ,Liver function ,Omeprazole ,medicine.drug - Abstract
Helicobacter pylori eradication therapy is commonly prescribed in the general population. Treatment consists of drugs that are mainly metabolized by the liver cytochrome P-450 (CYP) enzymatic pool. Most H. pylori-infected patients often take drugs for comorbid illnesses, therefore increasing the potential for drug-drug interactions. We aimed to evaluate the interactions of rabeprazole, clarithromycin, and metronidazole 1-week H. pylori eradication therapy with CYP-dependent liver metabolic function in clinical practice. Ten patients referred to our unit for H. pylori infection underwent 1-week eradication therapy with rabeprazole (20 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and metronidazole (500 mg, b.i.d.). We chose the 13C-aminopyrine breath test (13C-ABT) to evaluate CYP-dependent liver function since it is noninvasive and nonharmful. All patients underwent 13C-ABT at three time points: before therapy (to), at the end of therapy (t8), and after 1 month of follow-up (t38). Mean 13C-ABT dose/hr (t0 = 14.0 +/- 5.4, t8 = 13.5 +/- 4.0, t38 = 16.1 +/- 5.6) as well as 13C-ABT cumulative dose (t0 = 2.4 +/- 1.1, t8 = 2.4 +/- 0.8, t38 = 2.6 +/- 1.0) were not statistically different at the three time points of the study. These results did not seem to be influenced by drugs being administered concomitantly. In everyday clinical practice rabeprazole-based H. pylori eradication therapy does not seem to display any significant interactions with CYP-dependent liver function, even in patients on multiple drugs.
- Published
- 2005
22. Biochemical background of toxic interaction between tiamulin and monensin
- Author
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Gyula Szucs, Katalin Monostory, Viola Tamasi, and Péter Laczay
- Subjects
Male ,CYP3A ,Metabolite ,Administration, Oral ,Tiamulin ,Toxicology ,Dexamethasone ,Troleandomycin ,chemistry.chemical_compound ,Cytochrome P-450 CYP3A ,Animals ,Ethylmorphine ,Drug Interactions ,Monensin ,Enzyme inducer ,Aminopyrine ,Dose-Response Relationship, Drug ,Ionophores ,biology ,Cytochrome P450 ,Oxidoreductases, N-Demethylating ,General Medicine ,Metabolic intermediate ,Anti-Bacterial Agents ,Rats ,chemistry ,Biochemistry ,Enzyme Induction ,Phenobarbital ,Microsomes, Liver ,biology.protein ,Female ,Aryl Hydrocarbon Hydroxylases ,Diterpenes - Abstract
Tiamulin, a diterpene antibiotic, is used for treatment of pulmonary and gastrointestinal infections in swine and poultry. Combined administration of tiamulin and ionophores (e.g. monensin) to farm animals may lead to intoxication manifested in severe clinical symptoms. Tiamulin metabolite complex with cytochrome P450 has been suggested to be the basis of drug-interactions. However, the formation of metabolic intermediate complex is questionable. The effect of tiamulin-treatment on cytochrome P450 activities was investigated in rats. Ethylmorphine and aminopyrine N-demethylation activities as well as monensin metabolism (O-demethylation) increased in liver microsomes of tiamulin-treated (200 mg/kg) animals. CYP3A1 induction caused by tiamulin was confirmed by the results of Western blot analysis. To test metabolic intermediate complex formation as a result of tiamulin treatment, cytochrome P450 activities were also determined in the presence of potassium ferricyanide. The findings together with those of in vitro complex formation suggested that formation of metabolic intermediate complexes of tiamulin with cytochrome P450 could be excluded. On the other hand, the results of inhibition studies showed significant decrease of ethylmorphine or aminopyrine as well as monensin demethylation in the presence of tiamulin. Our results proved that tiamulin has dual effect on cytochromes P450. It is able to induce and directly inhibit CYP3A enzymes, which are predominantly responsible for monensin O-demethylation. The direct effect of tiamulin as an inhibitor might play a more important role in toxicity than its putative effect as a chemical inducer of CYP3A enzymes.
- Published
- 2004
23. Quantitative evaluation of liver function by the methionine and aminopyrine breath tests in the early stages of liver transplantation
- Author
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Mauro Bernardi, Angelo Santoliquido, Marcello Candelli, Cristiana Di Campli, Antonino Cavallari, Bruno Nardo, Maria Assunta Zocco, Giuseppina Angelini, Alessandro Armuzzi, and Antonio Gasbarrini
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Liver transplantation ,Gastroenterology ,chemistry.chemical_compound ,Methionine ,Liver Function Tests ,Internal medicine ,medicine ,Humans ,Postoperative Period ,Aminopyrine ,Aged ,Breath test ,Postoperative Care ,Analysis of Variance ,Carbon Isotopes ,medicine.diagnostic_test ,Hepatology ,business.industry ,Middle Aged ,Surgery ,Liver Transplantation ,Transplantation ,Treatment Outcome ,chemistry ,Breath Tests ,Aminophenazone ,Female ,Liver function ,Analysis of variance ,business ,Liver function tests - Abstract
Objective The early phase after liver transplant is considered the period of greatest risk for graft failure. In recent years breath tests have been proposed as a noninvasive method to assess liver function. In particular, the aminopyrine breath test is useful for evaluating the liver viable mass, and the methionine breath test could be used to evaluate oxidative capacity of liver mitochondria. We aimed to perform these tests in the early phase following liver transplant in order to correlate the time course of these tests to the outcome of transplantation. Methods Twenty-three patients undergoing liver transplant were enrolled. The methionine and aminopyrine breath tests were performed on the days 1, 3 and 5, and 2, 4 and 6, respectively, after transplant. Results were expressed as the percentage of administered 13C recovered per hour and as the cumulative percentage of the 13C dose recovered over the test period. Results All but two transplants were successful in the short term and the cumulative percentage of the dose of 13C progressively increased after transplantation, reaching values not significantly different from controls (methionine at day 5). In two patients, primary non-function occurred: in these patients the cumulative percentage of the 13C dose did not increase after orthotopic liver transplant and the results of both breath tests indicated that it always remained significantly lower compared to that of other patients. Conclusions A combination of breath tests, exploring both mitochondrial and microsomal function, could be useful in the early phase after liver transplant in order to evaluate the graft outcome. Eur J Gastroenterol Hepatol 15: 727-732 © 2003 Lippincott Williams & Wilkins
- Published
- 2003
24. Effects of Antioxidant 1-O-Hexyl-2,3,5-trimethylhydroquinone or Ascorbic Acid on Carcinogenesis Induced by Administration of Aminopyrine and Sodium Nitrite in a Rat Multi-organ Carcinogenesis Model
- Author
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Satoru Takahashi, Mitsuru Futakuchi, Seiko Tamano, Tomoyuki Shirai, Hideaki Yada, Masao Hirose, Maasashi Sano, Mayumi Kawabe, and Tokutaro Miki
- Subjects
Male ,Vitamin ,Cancer Research ,Antioxidant ,Carcinogenesis ,medicine.medical_treatment ,Ascorbic Acid ,Pharmacology ,medicine.disease_cause ,Article ,Antioxidants ,chemistry.chemical_compound ,medicine ,Animals ,Aminopyrine ,Sodium nitrite ,Anticarcinogen ,Carcinogen ,Glutathione Transferase ,Sodium Nitrite ,Chemistry ,Body Weight ,Neoplasms, Experimental ,Organ Size ,Ascorbic acid ,Rats, Inbred F344 ,Hydroquinones ,Rats ,Oncology ,Biochemistry ,Nitrosamine ,Rat - Abstract
The effect of antioxidant, 0.25% 1‐O‐hexyl‐2,3,5‐trimethylhydroquinone (HTHQ) or 0.25% ascorbic acid (AsA), on Carcinogenesis induced by administration of 0.05% aminopyrine (AP) and 0.05% sodium nitrite (NaNO2), was examined using a rat multi‐organ carcinogenesis model. Groups of twenty F344 male rats were treated sequentially with an initiation regimen of N‐diethylnitrosamine, N‐methyl‐N‐nitrosourea, N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine, N, N′‐dimethylhydrazine and 2,2′‐dihydroxy‐di‐n‐propylnitrosamine during the first 4 weeks, followed by AP+NaNO2, AP+NaNO2+HTHQ, AP+NaNO2+AsA, NaNO2+HTHQ, NaNO2+AsA, each of the individual chemicals alone or basal diet and tap water as a control. All surviving animals were killed at week 28, and major organs were examined histopathologically for development of preneoplastic and neoplastic lesions. In the AP+NaNO2 group, the incidences of hepatocelluar adenomas and hemangiosarcomas were 95% and 35%, respectively. When HTHQ or AsA was simultaneously administered, the incidences decreased to 58% and 11%, or to 80% and 15%, respectively. On the other hand, in the AP+NaNO2 group and the NaNO2‐alone group, when HTHQ, but not AsA, was simultaneously administered, the incidence of carcinomas in the forestomach significantly increased. The results suggest that HTHQ can prevent tumor production induced by AP and NaNO2 more effectively than AsA. On the other hand, an enhancing or possible carcinogenic effect of simultaneous administration of HTHQ and NaNO2 only on the forestomach is suggested, while simultaneous treatment with the same dose of AsA and NaNO2 may not be carcinogenic to the fore‐stomach or other organs.
- Published
- 2002
25. Serum thrombopoietin levels are linked to liver function in untreated patients with hepatitis C virus-related chronic hepatitis
- Author
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Paola Romagnoli, Emanuela Testa, Edoardo G. Giannini, Paolo Borro, Mario Mamone, Roberto Testa, Simone Polegato, Federica Botta, Alessandra Fumagalli, Federica Malfatti, Bruno Chiarbonello, and Elena Podestà
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Hepatitis C virus ,medicine.disease_cause ,Gastroenterology ,Pathogenesis ,Necrosis ,Fibrosis ,Internal medicine ,Humans ,Medicine ,Aminopyrine ,Thrombopoietin ,Breath test ,Carbon Isotopes ,Hepatology ,medicine.diagnostic_test ,Platelet Count ,business.industry ,Hepatitis C ,Hepatitis C, Chronic ,Middle Aged ,medicine.disease ,Thrombocytopenia ,Breath Tests ,Liver ,Liver biopsy ,Immunology ,Female ,Liver function ,business ,Spleen - Abstract
Thrombocytopenia can be found in patients with chronic hepatitis related to hepatitis C virus (HCV). Both hypersplenism and decreased liver production of thrombopoietin (TPO) have been hypothesized as mechanisms responsible for thrombocytopenia.To assess the presence of relationships among platelet count, spleen size, TPO serum levels, liver histology, and liver function in a group of patients with HCV-related chronic hepatitis.Platelet count, TPO serum levels, and spleen size were assessed in 25 untreated HCV positive chronic hepatitis patients undergoing liver biopsy. These parameters were correlated to liver histology and liver function as evaluated by means of [(13)C]aminopyrine breath test (ABT).Both platelet counts (146 +/- 48 vs. 202 +/- 56 x 10(9)/1, P0.03) and TPO serum levels (103 +/- 24 vs. 158 +/- 7 1 pg/ml, P0.02) were lower among patients with high fibrosis scores as compared to patients with low fibrosis scores. Patients with thrombocytopenia as well as patients with high fibrosis scores had lower ABT results as compared to patients with normal platelet counts and patients with no or mild fibrosis, respectively. TPO serum levels were correlated to platelet count (r(s) = 0.493, P = 0.016), and negatively correlated to fibrosis stage (r(s) = -0.545, P = 0.008). Lastly, low TPO serum levels were associated to a decrease in liver function.Our study showed that in patients with chronic hepatitis related to HCV infection serum TPO levels are correlated to liver functional impairment and to the degree of liver fibrosis.
- Published
- 2002
26. CaMKII is activated and translocated to the secretory apical membrane during cholinergically conveyed gastric acid secretion
- Author
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Ursula Seidler, Michael Fährmann, and Alexander Heinzmann
- Subjects
Male ,medicine.medical_specialty ,Carbachol ,Cholinergic Agonists ,Biology ,environment and public health ,Gastric Acid ,H(+)-K(+)-Exchanging ATPase ,Parietal Cells, Gastric ,1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ,Ca2+/calmodulin-dependent protein kinase ,Internal medicine ,medicine ,Animals ,Secretion ,Rats, Wistar ,Aminopyrine ,Protein kinase A ,Cells, Cultured ,Protein kinase C ,Dose-Response Relationship, Drug ,Secretory Vesicles ,musculoskeletal, neural, and ocular physiology ,Cell Membrane ,Cell Polarity ,Colocalization ,Cell Biology ,Apical membrane ,Rats ,Cell biology ,Enzyme Activation ,Protein Transport ,Endocrinology ,nervous system ,Calcium-Calmodulin-Dependent Protein Kinases ,cardiovascular system ,Rabbits ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,tissues ,Intracellular ,medicine.drug - Abstract
The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is thought to be activated during the cholinergic stimulation of gastric acid secretion. The carbachol-induced acid production of cultured rabbit parietal cells was dose-dependently inhibited by the CaMKII inhibitor KN-62 as measured by accumulation of the weak base [(14)C]aminopyrine ([(14)C]-AP). Inhibition by KN-62 was most efficient at concentrations of carbachol10(-6) M. After carbachol stimulation, we observed an activation of CaMKII activity, and its translocation to the apical membrane of gastric mucosal cells. We found a doubling of the abundance of CaMKII to the stimulus-associated apical membrane (SA vesicles) compared to the apical membrane from the resting state after carbachol induction. This was shown by both an anti-CaMKII serum and the 1.8-fold increase of the CaMKII phosphotransferase activity in vitro. The SA vesicles exhibited a strong increase of autoactivated CaMKII probed with an anti-autoactivated CaMKII antibody. Additionally, we observed a colocalization of both CaMKII and the H(+)-K(+)-ATPase of SA vesicles similar to the colocalization of both enzymes to the tubulovesicles suggesting them as at least one pool for the SA vesicular CaMKII. Our data indicate that the activation of CaMKII and the carbachol-dependent redistribution of CaMKII to the SA vesicles are distinct processes that occur in parallel to regulate the activity and localization of CaMKII. These findings contribute to the model implicating an involvement for CaMKII in the intracellular dynamics of the acid secretion.
- Published
- 2002
27. [The comparative study of the of clinical effectiveness of the Candibiotic, Otipax, and Anauran ear drops for the treatment of acute external and middle ear otitis]
- Author
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A B, Kiselev and V A, Chaukina
- Subjects
Adult ,Male ,Adolescent ,Administration, Topical ,Lidocaine ,Middle Aged ,Otitis Externa ,Anti-Bacterial Agents ,Drug Combinations ,Otitis Media ,Young Adult ,Treatment Outcome ,Acute Disease ,Humans ,Drug Therapy, Combination ,Female ,Aminopyrine ,Child ,Aged - Abstract
The objective of the present work was to study in vitro antimicrobial activity of the Candibiotic, ear drops used for the combined treatment of acute external ear otitis and acute otitis media Their anesthetic and anti-inflammatory action was compared with the effects of Otipax, and Anauran ear drops. The results of the study give a reason to recommend the application of Candibiotic ear drops as the highly effective medication for the endo-aural treatment of acute external ear otitis and acute otitis media.
- Published
- 2014
28. Non-invasive methods for the assessment of hepatic fibrosis: transient elastography, hyaluronic acid, 13C-aminopyrine breath test and cytokeratin 18 fragment
- Author
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Antonina Smedile, Rinaldo Pellicano, Maria Lorena Abate, Gian Paolo Caviglia, Giovanni Antonio Touscoz, Alessia Ciancio, Mario Rizzetto, Antonella Olivero, and Chiara Rosso
- Subjects
Adult ,Liver Cirrhosis ,Male ,medicine.medical_specialty ,Pathology ,Cirrhosis ,Liver fibrosis ,Specialties of internal medicine ,Serum Hyaluronic Acid ,Chronic hepatitis C ,Gastroenterology ,Cohort Studies ,non-invasve fibrosis markers ,Internal medicine ,medicine ,Humans ,Hyaluronic Acid ,Aminopyrine ,Aged ,Breath test ,Carbon Isotopes ,Non-invasive fibrosis markers ,Keratin-18 ,Hepatology ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,General Medicine ,Hepatitis C, Chronic ,Middle Aged ,Liver biopsy ,medicine.disease ,Fibroscan ,Breath Tests ,Liver ,ROC Curve ,RC581-951 ,Elasticity Imaging Techniques ,Female ,Elastography ,Hepatic fibrosis ,Transient elastography ,business - Abstract
Background. In the management of chronic hepatitis C (CHC) patients, liver biopsy is the gold standard for liver fibrosis assessment despite some technical limits and risks. Non-invasive approaches have been proposed as alternative methods to evaluate structural liver damage. Aim. To investigate the diagnostic accuracy of transient elastography, 13C-aminopyrine breath test ( 13 C-ABT), serum hyaluronic acid (HA) and cytokeratin 18 Asp396 fragment (CK-18) as non-invasive methods of liver fibrosis assessment ad their correlation to METAVIR score. Material and methods. In a cohort of 57 CHC patients, liver stiffness, cumulative percentage of administered dose of 13C-aminopyrine at 120 min, serum HA and serum CK-18 concentration were determined. Diagnostic accuracy in detecting significant fibrosis (F ≥ 2), severe fibrosis (F ≥ 3) and cirrhosis (F = 4) was assessed by the area under the receiver operating characteristic curve. Results. Liver fibrosis score showed a strong correlation with liver stiffness (r = 0.667; p < 0.0001) and a significant inverse correlation with 13C-ABT results (r = -0.418; p = 0.0012). A weaker correlation was found with CK18 (r = 0.329; p = 0.0126) and no correlation with HA. Areas under the curve of elastography, 13C-ABT, HA and CK18 were: 0.98, 0.75, 0.69, 0.64, respectively, for F ≥ 2; 0.97, 0.69, 0.80, 0.66, respectively, for F ≥ 3; 0.95, 0.64, 0.70, 0.56, respectively, for F = 4. Conclusion. Elastography has the best diagnostic accuracy for the assessment of the degree of liver fibrosis in CHC patients. Its application can provide an alternative useful tool for monitoring the disease evolution.
- Published
- 2014
29. Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis-B virus does not occur in rapid acetylators
- Author
-
Yoseph Caraco, Micha Levy, Rifaat Safadi, Ester Zylber-Katz, and L. Granit
- Subjects
Adult ,Male ,Hepatitis B virus ,medicine.medical_specialty ,Metabolic Clearance Rate ,Dipyrone ,Biology ,medicine.disease_cause ,Models, Biological ,Asymptomatic ,Pharmacokinetics ,Elimination rate constant ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Pyrazolones ,Aminopyrine ,Pharmacology ,Hepatitis ,Anti-Inflammatory Agents, Non-Steroidal ,Acetylation ,General Medicine ,medicine.disease ,Ampyrone ,Endocrinology ,Area Under Curve ,Carrier State ,Immunology ,Female ,medicine.symptom ,Asymptomatic carrier ,Algorithms ,Drug metabolism ,Pharmacogenetics ,Half-Life - Abstract
Objective: We previously found that, compared with healthy subjects, asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the formation of 4-acetylaminoantipyrine (AAA) was unchanged. The present study was designed to examine the effect of the asymptomatic HBV carrier state on the metabolism of dipyrone, as a model drug, in rapid acetylators. Methods: The plasma and urine concentrations of the metabolites of dipyrone were measured in eight asymptomatic HBV carriers and eight healthy subjects who had normal liver function tests, all displaying the rapid acetylation phenotype and genotype, after the administration of a 1.0-g oral dose of dipyrone. Results: The following pharmacokinetic parameters were evaluated: peak plasma concentration, time to peak plasma concentration, elimination rate constant, area under the plasma concentration–time curve (0→∞), amount excreted (0→∞), renal and non-renal clearances for MAA and the clearances of formation for AA, FAA and AAA. No significant differences were found between the two subject groups. Conclusion: The effect of hepatic viral carrier state on drug metabolism may vary according to metabolic pathways and genetic polymorphism.
- Published
- 2001
30. Pituitary adenylate cyclase-activating polypeptide induces hyperthermia in the rat
- Author
-
Miklós Jászberényi, Ágnes Adamik, Mónika Mácsai, Gyula Telegdy, and Imre Pataki
- Subjects
Male ,Hyperthermia ,endocrine system ,medicine.medical_specialty ,Pituitary gland ,Fever ,Colon ,Adenylate kinase ,Cyclase ,Body Temperature ,Cellular and Molecular Neuroscience ,Internal medicine ,medicine ,Animals ,Cyclooxygenase Inhibitors ,Rats, Wistar ,Aminopyrine ,Injections, Intraventricular ,Pharmacology ,Antiserum ,Dose-Response Relationship, Drug ,biology ,Neuropeptides ,Thermoregulation ,medicine.disease ,Rats ,Endocrinology ,medicine.anatomical_structure ,Mechanism of action ,biology.protein ,Pituitary Adenylate Cyclase-Activating Polypeptide ,Cyclooxygenase ,medicine.symptom ,hormones, hormone substitutes, and hormone antagonists - Abstract
The effects of centrally administered pituitary adenylate cyclase-activating polypeptide (PACAP-38) on body temperature were investigated in rats. Intracerebroventricular (i.c.v.) administration of PACAP-38 in doses of 500 and 1000 ng induced a dose-related elevation in colon temperature 2, 3, 4, 5 and 6 h after injection. The i.c.v. pretreatment of the animals with different dilutions of PACAP-38 antiserum prevented the development of hyperthermia in PACAP-38-treated animals, whereas PACAP-38 antiserum alone did not modify the colon temperature. An intramuscular injection of noraminophenazone (a cyclooxygenase inhibitor) abolished the PACAP-38-induced hyperthermia. Our data indicate that PACAP may induce hyperthermia via the central nervous system, and this hyperthermic effect may be mediated via a cyclooxygenase-involved pathway.
- Published
- 2000
31. Early acute cellular rejection: no effect on late hepatic allograft function in man
- Author
-
Christian Seiler, D. Didonna, Jürg Reichen, Eberhard L. Renner, A Czerniak, and Markus W. Büchler
- Subjects
Adult ,Graft Rejection ,Male ,Nephrology ,medicine.medical_specialty ,Pathology ,medicine.medical_treatment ,Liver transplantation ,Gastroenterology ,Liver Function Tests ,Internal medicine ,Biopsy ,Humans ,Medicine ,Prospective Studies ,Aminopyrine ,Aged ,Kidney ,Transplantation ,medicine.diagnostic_test ,business.industry ,Liver cell ,Galactose ,Bilirubin ,Middle Aged ,Liver Transplantation ,medicine.anatomical_structure ,Breath Tests ,Acute Disease ,Female ,Liver function ,business ,Liver function tests - Abstract
Whereas early acute cellular rejection, even if successfully treated, seems to have an impact on late function and survival of kidney and heart transplants, little quantitative data are available on its effect(s) on liver transplants. Routine liver function tests, the functioning liver cell mass (galactose elimination capacity) and microsomal metabolic capacity (aminopyrine breath test) were determined prospectively in 37 consecutive patients 1 year after liver transplantation. Of these, 19 (7 females and 12 males, 32-69 years of age) had previously required treatment for at least one biopsy proven acute cellular rejection episode occuring a median 7 days after grafting, while 18 (6 females and 12 males, 30-67 years of age) had not. The functioning liver cell mass and microsomal metabolic capacity were both within normal limits for the majority of patients and did not differ significantly between patients with and without previous acute cellular rejection episodes. In contrast to other solid organ transplants, early acute cellular rejection episodes do not affect late function of liver allografts in man.
- Published
- 1999
32. Microsomal Cytochrome P-450 Monooxygenase System and Its Drug-metabolizing Activity after Partial Portal Vein Ligation in the Rat
- Author
-
Yasutaka Kokudo, Kunihiko Izuishi, Hajime Maeta, Takashi Maeba, Hisao Wakabayashi, and Munemasa Ryu
- Subjects
Male ,medicine.medical_specialty ,Cytochrome ,medicine.medical_treatment ,Blotting, Western ,Rats, Sprague-Dawley ,Cytochrome P-450 Enzyme System ,Internal medicine ,medicine ,Animals ,Aminopyrine ,Ligation ,Chromatography, High Pressure Liquid ,Analysis of Variance ,biology ,Portal Vein ,business.industry ,Lidocaine ,Cytochrome P450 ,Monooxygenase ,Embolization, Therapeutic ,Rats ,Endocrinology ,Microsomes, Liver ,biology.protein ,Microsome ,Surgery ,Liver function ,Hepatectomy ,business ,Drug metabolism - Abstract
Percutaneous transhepatic portal vein embolization (PTPE) has been used to decrease the risk of hepatic failure after hepatectomy in patients with poor liver function. The effect of PTPE on hepatic drug-metabolizing activities is not clear. Therefore we examined the effect of portal vein branch ligation, a model of PTPE, on hepatic drug-metabolizing activities in Sprague-Dawley rats. Ligated and nonligated lobes were harvested separately. Drug-metabolizing activities and concentrations of components of the microsomal cytochrome P-450 monooxygenase system were examined. In ligated lobes, drug-metabolizing activities (lidocaine and aminopyrine) and enzymatic concentrations of the microsomal cytochrome P-450 monooxygenase system gradually decreased over 10 days. In nonligated lobes these functions were depressed rapidly to 60% of those before PBL but then recovered 10 days after PBL. From the viewpoint of drug metabolism, hepatic dysfunction occurred in both ligated and nonligated lobes.
- Published
- 1999
33. Modulation of peroxisomal and microsomal fatty acid oxidation by acetone. A comparative study between liver and kidney
- Author
-
Myriam Orellana, Ramón Rodrigo, Elena Valdés, Paula Jimenez, and Lilian Thielemann
- Subjects
Male ,Physiology ,Mitochondria, Liver ,Biology ,Kidney ,Microbodies ,Biochemistry ,Acetone ,Hydroxylation ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Animals ,Glucuronosyltransferase ,Rats, Wistar ,Aminopyrine ,Molecular Biology ,Beta oxidation ,chemistry.chemical_classification ,Catabolism ,Fatty Acids ,Lauric Acids ,Kidney metabolism ,Cytochrome P450 ,Fatty acid ,Peroxisome ,Catalase ,Lauric acid ,Mitochondria ,Rats ,Liver ,chemistry ,Organ Specificity ,biology.protein ,Oxidation-Reduction - Abstract
The effect of acetone consumption on some microsomal and peroxisomal activities was studied in rat kidney and these results were compared with data from former investigations in liver. Acetone increased the microsomal lauric acid hydroxylation, the aminopyrine N-demethylation catalyzed by cytochrome P450 and the microsomal UDP-glucuronyltransferase activity. Also, acetone increased the peroxisomal beta-oxidation of palmitoyl CoA and catalase activities in kidney. These studies suggest that acetone is a common inducer of the microsomal and peroxisomal fatty acid oxidation, as previously shown in both starved and ethanol treated rats. Our results support the hypothesis that microsomal fatty acid omega-hydroxylation results in the generation of substrates being supplied for peroxisomal beta-oxidation. We propose that the final purpose of these linked fatty acid oxidations could be the catabolism of fatty acids or the generation of a substrate for the synthesis of glucose from fatty acids. This pathway would be triggered by acetone treatment in a similar way in liver and kidney.
- Published
- 1998
34. Mucosal interleukin-1beta production and acid secretion in enlarged fold gastritis
- Author
-
Shuji Kanayama, Yasuhisa Shinomura, Yoko Murayama, Yoshiji Miyazaki, Yuichi Yasunaga, Michihiro Yabu, H. Nishibayashi, Yoshifumi Higashimoto, Shinji Kitamura, and Yuji Matsuzawa
- Subjects
Adult ,Male ,medicine.medical_specialty ,Spirillaceae ,Helicobacter Infections ,Gastric Acid ,Gastric glands ,Internal medicine ,Gastrins ,Biopsy ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Secretion ,Aminopyrine ,Gastritis, Hypertrophic ,Aged ,Antibacterial agent ,Helicobacter pylori ,Hepatology ,medicine.diagnostic_test ,biology ,business.industry ,Stomach ,Gastroenterology ,Middle Aged ,biology.organism_classification ,medicine.anatomical_structure ,Endocrinology ,Gastric Mucosa ,Immunology ,Female ,Rabbits ,Gastritis ,medicine.symptom ,business ,Interleukin-1 - Abstract
Background: We have previously shown that eradication of Helicobacter pylori increases acid secretion in H. pylori-associated enlarged fold gastritis. Aim: To investigate whether locally produced interleukin-1β is possibly involved in the inhibition of acid secretion in H. pylori gastritis. Methods: IL-1β release from the gastric body mucosa was determined by short-term culture of biopsy specimens in 13 patients with enlarged fold gastritis (all H. pylori-positive), five H. pylori-positive and 10 H. pylori-negative patients without enlarged folds. The acid-inhibitory effect of locally produced IL-1β was examined by []> 14C]-aminopyrine uptake assay using isolated rabbit gastric glands. Results: IL-1β release was significantly greater in patients with enlarged fold gastritis, significantly correlated with both basal and tetragastrin-stimulated acid outputs in the H. pylori-positive patients (r = −0.591 and r = −0.641, respectively; P
- Published
- 1997
35. Functional capacity of the liver after two-thirds partial hepatectomy in the rat
- Author
-
Masaji Hashimoto and Kensho Sanjo
- Subjects
Indocyanine Green ,Male ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,chemistry.chemical_compound ,Parenchyma ,medicine ,Animals ,Hepatectomy ,Rats, Wistar ,Aminopyrine ,biology ,DNA synthesis ,business.industry ,Liver cell ,DNA ,Liver regeneration ,Liver Regeneration ,Rats ,Proliferating cell nuclear antigen ,Clamp ,chemistry ,biology.protein ,Surgery ,business ,Indocyanine green ,Antipyrine - Abstract
Background. Liver cell proliferation after partial hepatectomy in rats has been thoroughly investigated. Although DNA synthesis and morphologic restoration have been studied in this rat model, the functional capacity of the remnant liver during regeneration has not been elucidated. Methods. We measured the indocyanine green disappearance rate (ICG-k) and serum aminopyrine (CLamp) in rats at various intervals after two-thirds hepatectomy. Morphologic restoration of the liver after hepatectomy was evaluated on the basis of remnant liver weight, proliferating cell nuclear antigen labeling index, and the DNA content of the regenerating liver. Serial changes in ICG-k and CLamp after two-thirds hepatectomy were compared with the degree of morphologic restoration. Results. ICG-k and CLamp were reduced by one third in rats after two-thirds hepatectomy. Although the rate of restoration of remnant liver weight was steady after hepatectomy, ICG-k and CLamp were lowest about 36 hours after hepatectomy. The restoration of ICG-k was comparable to that of liver weight, but the restoration of CLamp was delayed. Conclusions. Functional liver capacity was minimal during parenchymal cell mitosis in the regenerating liver. Functional restoration after two-thirds hepatectomy was delayed in comparison with morphologic restoration in rat.
- Published
- 1997
36. Microsomal and peroxisomal fatty acid oxidation in bile duct ligated rats: A comparative study between liver and kidney
- Author
-
Montserrat Abarca, Elena Valdés, Nicolas Avalos, and Myriam Orellana
- Subjects
Male ,medicine.medical_specialty ,Biology ,Kidney ,Microbodies ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Cholestasis ,Microsomes ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Aminopyrine ,Ligation ,Beta oxidation ,Pharmacology ,chemistry.chemical_classification ,Unspecific monooxygenase ,Fatty Acids ,Lauric Acids ,Fatty acid ,Cytochrome P450 ,Peroxisome ,Catalase ,medicine.disease ,Lauric acid ,Rats ,medicine.anatomical_structure ,Endocrinology ,Liver ,chemistry ,Biochemistry ,biology.protein ,Bile Ducts - Abstract
1. 1. Microsomal cytochrome P-450 and peroxisomal fatty acid oxidation was studied in the kidney of rats 7 days after bile duct ligation (BDL) and a comparative study between kidney and liver was done. 2. 2. Only in the liver did cholestasis decrease the cytocrome P-450 content and the peroxisomal fatty acid (3-oxidation, the catalase activity, and the microsomal metabolism of lauric acid and aminopyrine. 3. 3. In contrast, cholestasis did not influence these activities in the kidney. The microsomal and peroxisomal activities studied responded in a coordinate way to cholestasis. 4. 4. These results could suggest the possibility of a cause-and-effect relationship between microsomal cytochrome P-450 and peroxisomal activity.
- Published
- 1997
37. Effects of Central Nervous Stimulants on Spino-Bulbo-Spinal Reflex Potentials in Cats
- Author
-
Hiroshi Kondo, Ahmmed Ally, Yukio Hara, and Haruaki Nakaya
- Subjects
Enoxacin ,Male ,Action Potentials ,Withdrawal reflex ,Synaptic Transmission ,chemistry.chemical_compound ,Anti-Infective Agents ,Reflex ,Animals ,Picrotoxin ,Medicine ,Neurons, Afferent ,Aminopyrine ,Motor Neurons ,CATS ,General Veterinary ,Vagovagal reflex ,business.industry ,Anti-Inflammatory Agents, Non-Steroidal ,Spinal reflex ,Strychnine ,Phenylbutyrates ,Electrophysiology ,chemistry ,Anesthesia ,Cats ,Central Nervous System Stimulants ,Female ,Spinal Nerve Roots ,business - Abstract
Effects of central nervous stimulants on the spino-bulbo-spinal reflex potential were evaluated in anesthetized intact cats, and compared with those on segmental spinal reflex potentials in anesthetized spinal cats. In spinal cats, strychnine augmented polysynaptic reflex potential, picrotoxin inhibited dorsal root reflex potential, aminopyrine potentiated mono- and poly-synaptic reflex potentials but inhibited dorsal root reflex potential, and 4-aminopyridine potentiated all the three types of segmental reflex potentials. A combination of fenbufen, a non-steroidal antiinflammatory agent, and enoxacin, a new quinolone antimicrobial, inhibited all the three types of segmental reflex potentials. In contrast, all these drugs consistently produced an augmentation of the spino-bulbo-spinal reflex potential in anesthetized intact cats. From these findings, we suggest that the spino-bulbo-spinal reflex potential may be used as an electrophysiological parameter for the evaluation of central nervous stimulants.
- Published
- 1997
38. GSSG/GSH ratios in cryopreserved rat and human hepatocytes as a biomarker for drug induced oxidative stress
- Author
-
Oriol Morales-Ibanez, Miriam Zanuy, Joan Albertí, and Sonia Sentellas
- Subjects
Male ,Iodoacetic acid ,Toxicology ,medicine.disease_cause ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,In vivo ,medicine ,Animals ,Humans ,Tolmetin ,Cytotoxicity ,Aminopyrine ,Cells, Cultured ,chemistry.chemical_classification ,Cryopreservation ,Reactive oxygen species ,Glutathione Disulfide ,General Medicine ,Glutathione ,Flutamide ,Oxidative Stress ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Apoptosis ,Hepatocyte ,Cyclosporine ,Hepatocytes ,Oxidative stress ,Biomarkers - Abstract
The formation of reactive oxygen species (ROS) could cause cellular damage and eventually lead to apoptosis and necrosis. The ratio between oxidized glutathione and reduced glutathione (GSSG-to-GSH ratio) has been used as an important in vitro and in vivo biomarker of the redox balance in the cell and consequently of cellular oxidative stress. This paper optimizes a LC-MS/MS method for the simultaneous determination of GSH and GSSG. The proposed method is based on the derivatization of reduced GSH using iodoacetic acid (IAA) in order to prevent its rapid oxidation to GSSG during sample preparation. The optimized analytical method was applied to evaluate the effect of different pharmaceutical agents on GSSG-to-GSH ratio in cryopreserved rat and human hepatocytes in culture. Hepatocyte viabilities were also determined at the same time by using the WST-1 assay as a direct measurement of cell mitochondrial respiration. The results obtained demonstrate that cryopreserved rat and human hepatocytes in culture are reliable in vitro models for the evaluation of cellular oxidative stress. In addition, the GSSG-to-GSH ratio measurements could be a biomarker of hepatotoxicity providing similar results to those of cytotoxicity assay.
- Published
- 2013
39. Reply to: 'Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: the impact of validation'
- Author
-
ALBA ROCCO, Gerardo Nardone, Debora Compare, Rocco, Alba, Compare, Debora, and Nardone, GERARDO ANTONIO PIO
- Subjects
Male ,Breath Tests ,Hepatology ,Humans ,Female ,Hepatitis C, Chronic ,Aminopyrine ,Antiviral Agents - Published
- 2013
40. Albumin but not fibrinogen synthesis correlates with galactose elimination capacity in patients with cirrhosis of the liver
- Author
-
A B Sterchi, Jürg Reichen, P.E. Ballmer, M A McNurlan, P J Garlick, and Susan Elizabeth Anderson
- Subjects
Adult ,Liver Cirrhosis ,Male ,Radioisotope Dilution Technique ,medicine.medical_specialty ,Cirrhosis ,Phenylalanine ,Fibrinogen ,Gas Chromatography-Mass Spectrometry ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Aminopyrine ,Serum Albumin ,Aged ,Breath test ,Galactose Elimination Capacity ,Blood Volume ,Hepatology ,medicine.diagnostic_test ,Chemistry ,Albumin ,Galactose ,Middle Aged ,Deuterium ,Hepatitis B ,medicine.disease ,Hepatitis C ,Kinetics ,Endocrinology ,Biochemistry ,medicine.drug - Abstract
Albumin and fibrinogen synthesis rates were measured in 15 subjects with different clinical stages of postviral cirrhosis and compared with galactose elimination capacity and aminopyrin breath test. Forty-three mg per kg body weight [ 2 H 5 ring]phenylalanine with an isotopic enrichment of 10 atom% were intravenously injected. [ 2 H 5 ring]phenylalanine enrichments in the plasma-free phenylalanine and the albumin and fibrinogen isolates were measured by gas chromatography-mass spectrometry. Fractional synthesis rates of albumin were normal in Child A cirrhosis (7.6 ± 2.2%d), but were lower in both Child B (3.5 ± 0.8%d) and C (4.5 ± 2.8%d). Absolute rates of albumin synthesis were (103 ± 30 mg/kg/d) in the child A group and substantially lower in the Child B (50 ± 3 mg/kg/d) and C (36 ± 20 mg/kg/d) group. The average fractional synthesis rate of fibrinogen was 16.7 ± 7.5%d and the absolute synthesis rate 11.6 ± 6.4 mg/kg/d. The values of the galactose elimination capacity and the aminopyrin breath test were below the normal range in all patients, gradually decreasing with an increase in the severity of the clinical stage of cirrhosis. Albumin synthesis rates significantly correlated with the Child scores, the galactose elimination capacity, and the aminopyrin breath test, whereas fibrinogen synthesis rates showed no such correlations. (Hepatology 1996 Jul;24(1):53-9)
- Published
- 1996
41. Involvement of CYP2E in 8-Hydroxylation of Theophylline in Mouse Hepatic Microsomes-Difference from Its N-Demethylations
- Author
-
Akira Yamaji, Kunihiko Morita, and Hiroki Konishi
- Subjects
Male ,Pregnenolone Carbonitrile ,Population ,Pharmaceutical Science ,Mice, Inbred Strains ,Hydroxylation ,Acetone ,Nitrophenols ,Mice ,chemistry.chemical_compound ,Cytochrome P-450 Enzyme System ,Theophylline ,Oxazines ,medicine ,Aminoacetonitrile ,Animals ,Enzyme Inhibitors ,Aminopyrine ,education ,Fomepizole ,Pharmacology ,chemistry.chemical_classification ,education.field_of_study ,biology ,Cytochrome P450 ,Cytochrome P-450 CYP2E1 ,General Medicine ,Metabolic pathway ,Enzyme ,chemistry ,Biochemistry ,Phenobarbital ,Microsomes, Liver ,biology.protein ,Microsome ,Pyrazoles ,medicine.drug - Abstract
We examined which cytochrome P-450 (P-450) species other than CYP1A participates in the oxidative metabolism of theophylline (TP) in mouse hepatic microsomes. Among the three metabolic pathways of TP, only 8-hydroxylation was selectively enhanced by acetone, a potent inducer of CYP2E. We assumed that two P-450 populations with different metabolic ability were involved in this metabolic process, and kinetic analyses revealed that the enhancement was due to the induction of a high-capacity P-450 population. The 8-hydroxylation at a substrate concentration, where most of the total activity was attributed to the catalysis of the high-capacity phase, was markedly impaired by CYP2E inhibitors such as 4-methylpyrazole and aminoacetonitrile, whereas the N-demethylations were little affected by these agents. The activity of TP 8-hydroxylation was significantly correlated with that of p-nitrophenol hydroxylation, a probe for CYP2E, in untreated microsomes. The activities of these oxidative reactions were modified to a similar degree by known enzyme inhibitors with a range of inhibitory potencies and affinity for P-450 isoforms. On the other hand, a relationship between TP N-demethylations and p-nitrophenol hydroxylation was not apparent, but there was a behavioral similarity between the two types of N-demethylations. The results indicated that TP 8-hydroxylation, which accounts for a large portion of TP oxidations, involves CYP2E, and that its N-demethylations are mediated by a common or closely similar P-450 species distinct from CYP2E.
- Published
- 1996
42. Dietary fish oil and cytochrome P-450 monooxygenase activity in rat liver and kidney
- Author
-
Nicolas Avalos, Myriam Orellana, Eleva Valdes, and Patricio Vega
- Subjects
Male ,medicine.medical_specialty ,Docosahexaenoic Acids ,Kidney ,Biochemistry ,chemistry.chemical_compound ,Fish Oils ,Cytochrome P-450 Enzyme System ,Dietary Fats, Unsaturated ,Microsomes ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Aminopyrine ,chemistry.chemical_classification ,Organic Chemistry ,Lauric Acids ,Fatty acid ,Cell Biology ,Metabolism ,Fish oil ,Lauric acid ,Eicosapentaenoic acid ,Rats ,Endocrinology ,medicine.anatomical_structure ,Eicosapentaenoic Acid ,chemistry ,Docosahexaenoic acid ,Microsomes, Liver ,Oxygenases ,Microsome - Abstract
Lauric acid hydroxylation and aminopyrine N-demethylation were studied in kidney and liver microsomes from rats treated with fish oil. Different doses of fish oil containing 20% eicosapentaenoic acid and 10% docosahexaenoic acid were provided daily to the rats for seven days. In all the groups studied, the lauric acid metabolism was higher in kidney microsomes and the aminopyrine metabolism in the liver microsomes. Although no effect on the renal cytochrome P-450 concentration was detectable, all four fish oil doses increased the hepatic concentration of cytochrome P-450 by a mean 27%. The higher fish oil doses used increased the renal and hepatic microsomal metabolism of aminopyrine. The lauric acid metabolism was increased by fish oil only in the liver. Fish oil, a known inducer of fatty acid peroxisomal beta-oxidation, also induced microsomal activity. These results show that liver and kidney respond in different ways to dietary factors such as fish oil. In addition, our study would suggest that fish oil increased the activity of two different families of liver cytochrome P-450. The activity of kidney lauric acid 11- and 12-hydroxylation, however, was not modulated by fish oil.
- Published
- 1995
43. Inhibitory Effect of Leminoprazole on Acid Secretion in Parietal Cells Isolated from Guinea Pig Gastric Mucosa
- Author
-
Eiichi Saito and Yutaka Matsuo
- Subjects
Male ,medicine.medical_specialty ,Carbachol ,Guinea Pigs ,Stimulation ,In Vitro Techniques ,Biology ,Gastric Acid ,Guinea pig ,chemistry.chemical_compound ,Parietal Cells, Gastric ,Internal medicine ,Gastrins ,medicine ,Gastric mucosa ,Animals ,Aminopyrine ,Parietal cell ,Gastrin ,Pharmacology ,Anti-Ulcer Agents ,Endocrinology ,medicine.anatomical_structure ,Bucladesine ,chemistry ,Gastric acid ,Benzimidazoles ,Histamine ,medicine.drug - Abstract
Isolated guinea pig parietal cells, the function of which is similar to that of human parietal cells, were used in this study. The accumulation of 14C-aminopyrine (14C-AP) was measured to study the inhibitory mechanism of leminoprazole in cells. Stimulation by 10 microM histamine, 0.1 mM carbachol, 1 microM gastrin or 1 mM db-cAMP brought about satisfactory incorporation of 14C-AP, and leminoprazole concentration-dependently inhibited acid secretion induced by these stimulants. At 10(-5) M, almost 100% inhibition was observed. The IC50 values of leminoprazole obtained from its inhibitory action on histamine, carbachol, gastrin and db-cAMP-stimulated acid secretion were 4.0 x 10(-7) M, 3.5 x 10(-7) M, 2.5 x 10(-7) M and 5.6 x 10(-7) M, respectively. Thus the extent of inhibition was the same for the responses to all the secretagogues. These results indicate that the site of action of leminoprazole is intracellular and distal from cAMP (intracellular second messenger), but not at the receptor sites. The results also strongly suggest that the inhibitory action of leminoprazole on H+,K(+)-ATPase may contribute to the inhibitory effect of this drug on gastric acid secretion.
- Published
- 1995
44. Low selenium status in alcoholic cirrhosis is correlated with aminopyrine breath test
- Author
-
A. Van Gossum and Jean Neve
- Subjects
Adult ,Male ,medicine.medical_specialty ,Alcoholic liver disease ,Cirrhosis ,Thiobarbituric acid ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,chemistry.chemical_element ,Thiobarbituric Acid Reactive Substances ,Biochemistry ,Inorganic Chemistry ,Lipid peroxidation ,Selenium ,chemistry.chemical_compound ,Liver Function Tests ,Liver Cirrhosis, Alcoholic ,Reference Values ,Malondialdehyde ,Internal medicine ,medicine ,Humans ,Aspartate Aminotransferases ,Carbon Radioisotopes ,Aminopyrine ,Breath test ,medicine.diagnostic_test ,Biochemistry (medical) ,General Medicine ,Middle Aged ,medicine.disease ,Zinc ,Endocrinology ,chemistry ,Prothrombin Time ,Female ,Lipid Peroxidation ,Liver function - Abstract
The relationship among impaired selenium status, lipid peroxidation, and liver function was examined in 19 hospitalized patients with severe alcoholic cirrhosis. Plasma selenium was found to be significantly lower (mean +/- SD: 54 +/- 13 micrograms/L) than in healthy controls (83 +/- 11 micrograms/L) and plasma malondialdehyde, assessed as thiobarbituric acid reactants, which reflects lipid peroxidation, was increased (2.0 +/- 1.2 mumol/L vs < 1.2 mumol/L in controls). The mean 14C aminopyrine breath test, an indicator of liver function, was lower than normal (2.7 +/- 1.9 vs 6.3 +/- 0.9% in controls) and found to be significantly correlated with plasma selenium (r = 0.59, p < 0.05). A prospective, randomized selenium supplementation trial was conducted in a group of 16 patients who received either daily 100 micrograms selenium as enriched yeast during 4 mo or a placebo. Among the 10 patients who completed the study, plasma selenium significantly increased in the supplemented group (n = 4; before: 58 +/- 10 micrograms/L, and after 101 +/- 12 micrograms/L, p < 0.01) contrary to the placebo group (n = 6, before: 47 +/- 10 micrograms/L, after: 57 +/- 9 micrograms/L, n.s.). 14C aminopyrine breath test improved in three out of four selenium-supplemented patients and in three out of six placebo patients, but the small number of patients did not allow statistical evaluation. These results demonstrate that low selenium status in alcoholic cirrhosis is correlated to liver function and could be improved by supplementation.
- Published
- 1995
45. A phase II study of sunitinib in advanced hepatocellular carcinoma
- Author
-
Maurizio Pompili, Michele Basso, Marco Biolato, Alessandro Iaculli, Vittoria Rufini, Carlo Barone, Maria Sole Basso, Antonio Grieco, Paola Castaldi, Lucia Leccisotti, Laura Riccardi, Anna Maria De Gaetano, and Luca Miele
- Subjects
Sorafenib ,Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Indoles ,Nausea ,Settore MED/12 - GASTROENTEROLOGIA ,Phases of clinical research ,Administration, Oral ,Antineoplastic Agents ,Gastroenterology ,Risk Assessment ,Risk Factors ,Internal medicine ,Sunitinib ,Medicine ,Humans ,Neoplasm Invasiveness ,Pyrroles ,Adverse effect ,Aminopyrine ,Aged ,Neoplasm Staging ,Methacetin ,Aged, 80 and over ,Settore MED/06 - ONCOLOGIA MEDICA ,Hepatology ,Performance status ,business.industry ,Settore MED/09 - MEDICINA INTERNA ,Liver Neoplasms ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,PET ,Treatment Outcome ,Hepatocellular carcinoma ,Alpha-fetoprotein ,Disease Progression ,Female ,Upper gastrointestinal bleeding ,medicine.symptom ,business ,medicine.drug - Abstract
Background In 2007, sorafenib was the first drug able to improve overall survival in patients with advanced hepatocellular carcinoma. Aim In 2005 we designed a phase II study to assess safety and efficacy of sunitinib. Methods This is a single arm, open-label, single-centre phase II trial. Eligibility criteria were advanced hepatocellular carcinoma; no prior chemotherapy, performance status 0–1; and Child ≤ B8. The treatment schedule was 50 mg each day orally, 4 weeks on, 2 weeks off. Results Between 10/2007 and 10/2010, 34 patients were enrolled. A significant worsening of liver functional reserve after sunitinib was observed. Grade 3/4 adverse effects occurred in 80% of patients and included fatigue (47%), nausea (15%), liver failure (15%), encephalopathy (12%) and upper gastrointestinal bleeding (12%). Six patients (18%) died within 60 days of enrolment. A partial response was observed in 4 patients (12%). Median time to tumour progression was 2.8 months and median overall survival was 5.8 months. Conclusion A dose of 50 mg/d induces a high rate of severe adverse events. Toxicity remains a key concern also at the dose of 37.5 mg/d. However, sunitinib is able to induce a prolonged response in some patients. Positron Emission Tomography/Computed Tomography scans may select good responders.
- Published
- 2012
46. [Clinical trial on the effect of buphenine, aminophenazone and diphenylpyraline hydrochloride in treating the common cold in children of 6 to 24 months of age]
- Author
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Ericka, Montijo-Barrios, Francisco, Cadena, Jaime A, Ramírez-Mayans, and Pedro, Gutiérrez-Castrellón
- Subjects
Male ,Nylidrin ,Common Cold ,Infant ,Sneezing ,Nasal Mucosa ,Double-Blind Method ,Piperidines ,Child, Preschool ,Humans ,Drug Therapy, Combination ,Female ,Aminopyrine ,Acetaminophen - Abstract
Acute respiratory infections are the second leading cause of morbidity in children under 18 years. Several drugs have been used with variable efficacy and safety, trying to reduce the associated symptoms and improve quality of life.To evaluate the efficacy and safety of buphenine, aminophenazone and diphenylpyraline hydrochloride when compared with placebo for the control of symptoms associated with common cold in children 6-24 months of age.Randomized clinical trial, double blind, placebo controlled, in 100 children24 months of any gender, with symptoms associated to common cold. They received the drug under study vs. placebo for seven days. Both groups received acetaminophen. The change on common cold related symptoms were evaluated. Statistic analysis was made with STATA 11.0 for Mac.Fifty-three children were randomized to study drug and forty-seven to placebo. Age of children in each group was similar (12.2 +/- 5.8 months vs. 12.7 +/- 5.8 months, p NS). There were significant differences between groups in relation to rhinorrea and sneezing resolution, with better results in Flumil group and no adverse events observed.The results in this study indicates that Flumil is a safe and effective drug for control of symptoms present in the common cold in children aged 6-24 months.
- Published
- 2012
47. High-performance liquid chromatographic assay for metamizol metabolites in rat plasma: application to pharmacokinetic studies
- Author
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Alma Rosa Cortés-Arroyo, Patricia Carrillo Calzadilla, Martín Gómez-Hernández, Marcela Hurtado y de la Peña, Adriana Miriam Domínguez-Ramírez, José Raúl Medina López, and Francisco Javier López-Muñoz
- Subjects
Male ,Clinical Biochemistry ,Dipyrone ,Pharmaceutical Science ,High-performance liquid chromatography ,Lower limit ,Analytical Chemistry ,Pharmacokinetics ,Drug Discovery ,medicine ,Animals ,Drug Interactions ,Rats, Wistar ,Hplc method ,Aminopyrine ,Spectroscopy ,Chromatography, High Pressure Liquid ,Chromatography, Reverse-Phase ,Chromatography ,Plasma samples ,Morphine ,Chemistry ,Solid Phase Extraction ,Rats ,Ampyrone ,Calibration ,Extraction methods ,medicine.drug - Abstract
In order to evaluate the pharmacokinetics of metamizol in the presence of morphine in arthritic rats, after subcutaneous administration of the drugs, an easy, rapid, sensitive and selective analytical method was proposed and validated. The four main metamizol metabolites (4-methylaminoantipyrine, 4-aminoantipyrine, 4-acetylaminoantipyrine and 4-formylaminoantipyrine) were extracted from plasma samples (50–100 μl) by a single solid-phase extraction method prior to reverse-phase high performance liquid chromatography with diode-array detection. Standard calibration graphs for all metabolites were linear within a range of 1–100 μg/ml ( r 2 ≥ 0.99). The intra-day coefficients of variation (CV) were in the range of 1.3–8.4% and the inter-day CV ranged from 1.5 to 8.4%. The intra-day assay accuracy was in the range of 0.6–9.6% and the inter-day assay accuracy ranged from 0.9 to 7.5% of relative error. The lower limit of quantification was 1 μg/ml for all metabolites using a plasma sample of 100 μl. Plasma samples were stable at least for 4 weeks at −20 °C. This method was found to be suitable for studying metamizol metabolites pharmacokinetics in arthritic rats, after simultaneous administration of metamizol and morphine, in single dose.
- Published
- 2012
48. Liver involvement in hereditary hemorrhagic telangiectasia: can breath test unmask impaired hepatic first-pass effect?
- Author
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Gian Ludovico Rapaccini, Gennaro M. Lenato, Antonio Gasbarrini, Giulia Bosco, Marcello Candelli, Carlo Sabbà, Maurizio Pompili, Arnaldo Scardapane, and Patrizia Suppressa
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pathology ,liver ,Gastroenterology ,Arteriovenous Malformations ,Young Adult ,First pass effect ,Internal medicine ,otorhinolaryngologic diseases ,Internal Medicine ,medicine ,Humans ,Clinical significance ,telangiectasia ,Aminopyrine ,Telangiectasia ,Aged ,Breath test ,medicine.diagnostic_test ,Hepatic first pass effect ,business.industry ,Significant difference ,Settore MED/09 - MEDICINA INTERNA ,Middle Aged ,Breath Tests ,Case-Control Studies ,Inactivation, Metabolic ,Emergency Medicine ,Female ,Telangiectasia, Hereditary Hemorrhagic ,medicine.symptom ,business ,Perfusion ,Drug metabolism - Abstract
Hepatic arteriovenous malformations (HAVMs) in hereditary hemorrhagic telangiectasia (HHT) have long been considered to have scarce clinical significance in most cases. Nevertheless, data are lacking regarding the influence of HAVMs on the liver first-pass effect on drugs in HHT patients. To gain insight into the effect of HAVMs on hepatic drug clearance by means of two specific (13)C-labeled probes, namely the (13)C-methacetin and (13)C-aminopyrine, 46 HHT patients and 44-matched healthy controls were enrolled. The liver first-pass effect was studied by the (13)C-based breath test using methacetin and aminopyrine. The methacetin breath test showed statistically significant reduced metabolism rates (p0.0001) in HHT when compared with controls, both in patients with and without CT-detectable HAVMs, and when expressed both as cumulative (13)C-percentage dose per hour and as (13)C-percentage peak after 15 min. In contrast, no significant difference was found between HHT and controls regarding aminopyrin metabolism rates. In HHT, (13)C%-methacetin breath test values are significantly lower than those found in normal subjects, probably due to the effect of hepatic shunts. A reduced perfusion and an impaired hepatic metabolism might affect hepatic drug clearance in HHT. Therefore, an appropriate dosage adjustments should be considered when high-hepatic-metabolism drugs are administered to HHT patients.
- Published
- 2012
49. EVALUATION OF INDOCYANINE GREEN RETENTION AND AMINOPYRINE BREATH TESTS IN PATIENTS WITH MALIGNANT BILIARY OBSTRUCTION
- Author
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K. W. Tam Yu, Chung Mao Lo, Edward C. S. Lai, Q. S. Wang, ST Fan, and Jason W. H. Wong
- Subjects
Indocyanine Green ,Male ,medicine.medical_specialty ,Malignancy ,Gastroenterology ,chemistry.chemical_compound ,Liver Function Tests ,Internal medicine ,medicine ,Humans ,Postoperative outcome ,In patient ,Postoperative Period ,Aminopyrine ,Aged ,Aged, 80 and over ,Breath test ,Prothrombin time ,Cholestasis ,medicine.diagnostic_test ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,Breath Tests ,chemistry ,Female ,Obstructive jaundice ,High incidence ,business ,Indocyanine green - Abstract
Impaired hepatic function is a major contributory factor to the high incidence of postoperative morbidity and mortality in patients with malignant biliary obstruction. Dynamic hepatic function tests such as indocyanine green (ICG) retention and aminopyrine breath tests were evaluated in such patients to define whether they were clinically useful for prediction of postoperative morbidity and mortality. Forty-four patients with malignant biliary obstruction undergoing surgery for relief of obstructive jaundice were recruited into the study. Indocyanine green retention and aminopyrine breath tests were carried out in all patients pre-operatively and repeated in 36 patients postoperatively. The ICG retention was abnormal in all patients before surgery and there was significant improvement 2 weeks after surgery (32.8 +/- 2.5% vs 18.3 +/- 2.8%, P = 0.001). The change in ICG retention levels correlated with the serum bilirubin levels but the pre-operative ICG retention value could not predict postoperative morbidity and mortality. The aminopyrine breath test was abnormal in all but one patient. It correlated with pre-operative prothrombin time of the patients before surgery but it did not improve significantly after surgery and was not predictive of postoperative outcome. It is concluded that both ICG retention and aminopyrine breath tests have limited clinical value in the pre-operative evaluation of patients with malignant biliary obstruction.
- Published
- 1994
50. Stimulus-Secretion Coupling in Rat Parietal-Cells Is Affected by Extracellular Magnesium
- Author
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Frank C. Mooren, W. Beil, Wolfram Domschke, E. Spyrou, and R. Stoll
- Subjects
Male ,medicine.medical_specialty ,Biophysics ,chemistry.chemical_element ,Calcium ,Biochemistry ,Gastric Acid ,Basal (phylogenetics) ,Parietal Cells, Gastric ,Internal medicine ,Extracellular ,medicine ,Animals ,Magnesium ,Secretion ,Rats, Wistar ,Aminopyrine ,Molecular Biology ,Incubation ,Cells, Cultured ,Cell Biology ,Rats ,Coupling (electronics) ,Endocrinology ,chemistry ,Carbachol ,Stimulus secretion coupling - Abstract
We investigated the effects of extracellular magnesium on stimulus-secretion coupling in isolated rat parietal cells. A high concentration of extracellular magnesium (10mM) decreased basal and carbachol-stimulated calcium levels, whereas low magnesium levels (0.2mM) had the opposite effect. The calcium-triggered acid secretion was influenced in the same manner. Basal and carbachol-stimulated acid secretion could be enhanced by incubation in a buffer of low magnesium concentration, whereas a high magnesium concentration totally suppressed the carbachol-induced acid secretion. These results demonstrate that magnesium plays a modulative role in calcium-dependent stimulus-secretion coupling in rat parietal cells.
- Published
- 1994
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