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Carbonic anhydrases (CAs, EC 4.2.1.1) are enzymes involved in a multitude of diseases, and their inhibitors are in clinical use as drugs for the management of glaucoma, epilepsy, obesity, and tumours. In the last decade, multitargeting approaches have been proposed by hybridisation of CA inhibitors (CAIs) of sulphonamide, coumarin, and sulphocoumarin types with NO donors, CO donors, prostaglandin analogs, β-adrenergic blockers, non-steroidal anti-inflammatory drugs, and a variety of anticancer agents (cytotoxic drugs, kinase/telomerase inhibitors, P-gp and thioredoxin inhibitors). Many of the obtained hybrids showed enhanced efficacy compared to the parent drugs, making multitargeting an effective and innovative approach for various pharmacological applications. [ABSTRACT FROM AUTHOR]

Etodolac is a nonsteroidal anti-inflammatory drug with selective cyclooxygenase-2 inhibition to treat pain and inflammation associated with osteoarthritis in humans and dogs. The aim of the study was to investigate the pharmacokinetics of etodolac following single oral administration of 200 mg to 10 healthy beagle dogs. The plasma concentrations of etodolac were detected using liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was conducted using the noncompartmental method and modeling approaches. Etodolac was rapidly absorbed (Tmax = 0.85 h, Ka = 1.49 h−1) and slowly eliminated (T1/2 = 39.55 h) following oral administration to the dogs. A two-compartment pharmacokinetic model with first-order absorption and elimination rate constants was successfully explained for the pharmacokinetic aspects of etodolac in dogs. From a Monte Carlo simulation (1000 repetitions), the accumulation index and AUCτ at steady state were predicted as 1.60 [90% confidence intervals (CI), 1.24–2.81] and 408.18 ng·hr/mL [90% CI, 271.26–590.58 ng·hr/mL], respectively. This study will help to enact a more accurate optimal dosing regimen of etodolac in dogs with osteoarthritis, and may be useful in developing a novel formulation of etodolac for human in the future. [ABSTRACT FROM AUTHOR]

Hosta plantaginea was a traditional Chinese medicinal plants used to treat inflammatory and painful diseases with partial scientific validation. Solvent extractions followed by repeated chromatographic purification of the H. plantaginea flowers led to the isolation of one new flavonoid glycoside, hostaflavone A (1), together with one related known compound, kaempferol-3-O-sophoroside-7-O-glucoside (2), and their structures were elucidated on the basis of chemical and spectral evidence, as well as by comparison with literature data. Compounds 1 and 2 were evaluated for the anti-inflammatory activites against cyclooxygenases (COX-1 and COX-2) and DPPH free radical-scavenging activities in vitro. The results revealed that 1 and 2 exhibited significant COX-1 inhibition and moderate COX-2 inhibition compared to the reference celecoxib. Additionally, 1 and 2 displayed insignificant antioxidant activities compared to the positive control L-ascorbic acid. [ABSTRACT FROM AUTHOR]

Introduction: Osteoarthritis constitutes one of the leading causes of pain and disability worldwide with a significant impact on health-care costs. Patients with osteoarthritis are often affected by a number of cardiovascular comorbidities, including hypertension, which is present in about 40% of cases. Just recently, a single tablet combination of amlodipine besylate, a calcium channel blocker, and celecoxib, a nonsteroidal anti-inflammatory drug, indicated for patients for whom treatment with amlodipine for hypertension and celecoxib for osteoarthritis are appropriate, has been recently approved. Areas covered: We reviewed data from clinical studies that investigated safety and efficacy of the combination of amlodipine and celecoxib in hypertensive patients with osteoarthritis published before 31 August 2018. The literature search was conducted using research Methodology Filters. Expert commentary: The advantages of this single formulation over sequential administration include increased compliance, possibly reduced cost, and less likelihood of dosage-related issues. Moreover, this single tablet formulation combines the anti-inflammatory activity of the celecoxib with the systemic vasodilatation induced by the amlodipine. It is a promising treatment for patients with osteoarthritis and hypertension. Nevertheless, celecoxib may cause a variable degree of blood pressure increase and only a small clinical trial has been conducted before approval to assess interactions related to blood pressure effect between these two molecules. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the echocardiographic parameters that can predict the presence of patent ductus arteriosus (PDA) and haemodynamically significant ductus arteriosus (HSDA) at different time points.Methods: Echocardiogram was performed on postnatal days 3 and 7(D3-Echo and D7-Echo, respectively) in 71 very low birthweight infants with a median gestational age of 28.0 weeks. We first assessed the correlation between D3-Echo findings among infants with ductal patency and persistent ductal patency on D7-Echo. We subsequently assessed the correlation between D7-Echo findings and ultimate need for PDA treatment.Results: Forty-nine (69.0%) infants had ductal patency on D3-Echo, and 32(65.3%) of these had persistent PDA on D7-Echo. Twenty of the latter (62.5%) underwent PDA treatment at a median chronological age of 19 days. PDA treatment was significantly correlated with DA size and DA peak-systolic-to-end-diastolic velocity(S/D) ratio on D3- and D7-Echo. Receiver operating characteristic curve analysis revealed that DA size ≥2.040 mm and S/D ratio ≥2.016 had fair sensitivity, specificity, and predictive values for PDA treatment.Conclusion: The significance of different echocardiographic parameters associated with future ductal patency or HSDA depends on the time of assessment. DA size and S/D ratio on day 7 are two reliable indicators of the need for future PDA treatment. [ABSTRACT FROM AUTHOR]

Myrica rubraSieb. et Zucc. is a valuable fruit tree that is used in Chinese, Japanese and Taiwanese traditional medicine. We investigated the anti-inflammatory activity ofM. rubraleaves extracted with four different solvents. Total phenolics were determined using the Folin–Ciocalteu method. Extracts were investigated for their inhibitory activity toward the pro-inflammatory enzymes cyclooxygenase-1 and -2 (COX-1, COX-2) and 5-lipoxygenase (5-LOX). The ethanol extract ofM. rubraleaves demonstrated a strong inhibition of prostaglandin E2(PGE2) biosynthesis catalyzed by both COX-1 (93.42%) and COX-2 (75.71%) and leukotriene B4(LTB4) formation catalyzed by 5-LOX (82.72%). Further we identified selective COX-1 inhibition by then-butanol and aqueous fractions of the ethanol extract (with an IC50for COX-1 inhibition of 1.07 and 0.71 µg mL−1,respectively) and dual 5-LOX/COX inhibition by the ethyl acetate fraction (with an IC50of 3.29 for COX-1, 2.54 for COX-2 and 8.30 µg mL−1for 5-LOX). [ABSTRACT FROM AUTHOR]

The analgesic and physical properties of acetaminophen powder suitable as an inhaled drug produced by spray freeze-drying (SFD) were compared with those of raw acetaminophen. A laser particle size analyzer and scanning electron microscopy (SEM) were applied to estimate physical structure and properties of the particles. A cyclooxygenase (COX) inhibitor screening assay was used to compare the antipyretic and analgesic activity of raw and SFD acetaminophen. According to SEM, SFD acetaminophen particles had various shapes and sizes with porous structures. The optimized conditions for solvent, annealing temperature, and annealing time were water/ethanol mixture (60% water and 40% ethanol), −40°C, and 7 h, respectively. The diameter of optimized acetaminophen powder was 7.33 µm, and the aerodynamic particle size was 3.38 µm. The antipyretic and analgesic activities of acetaminophen after SFD were from 84.3 to 97.1% for COX-1 and from 91.6 to 102.9% for COX-2 compared to those of raw acetaminophen, respectively. [ABSTRACT FROM PUBLISHER]

1. We examined the effect of lipopolysaccharide (LPS), a component of Gram-negative bacteria, on food passage in the digestive tract of chickens (Gallus gallus) in order to clarify whether bacterial infection affects food passage in birds. 2. Food passage in the crop was significantly reduced by intraperitoneal (IP) injection of LPS while it did not affect the number of defecations, suggesting that LPS may affect food passage only in the upper digestive tract. 3. Similar to LPS, prostaglandin E2 (PGE2), one of the mediators of LPS, also reduced crop-emptying rate in chickens while it had no effect on the number of defecations. 4. Pretreatment with indomethacin, which is an inhibitor of cyclooxygenase (COX), a prostaglandin synthase, had no effect on LPS-induced inhibition of crop emptying. 5. IP injection of LPS did not affect the mRNA expression of COX2 in the upper digestive tract of chickens. 6. It is therefore likely that LPS and PGE2 reduced food passage rate in the crop by a prostaglandin-independent pathway in chickens. [ABSTRACT FROM AUTHOR]

A series of 2-(4-substitutedmethylphenyl)propionic acid derivatives(6a–6m)were synthesized, characterized and evaluated for cyclooxygenase (COX) enzyme inhibitory and antimicrobial activity. Test compounds that exhibited good COX inhibition and antibacterial activity were further screened for their cytotoxicity and genotoxicity. Compounds6hand6lshowed better COX-1 and COX-2 inhibition when compared to ibuprofen. Inhibition potency of these compounds against COX-2 was very close to that of nimesulide. The compounds6d, 6h, 6land6mdisplayed promising antibacterial property when compared to chloramphenicol. However, the compound6lwas emerged as the best dual COX inhibitory-antibacterial agent in this study. The ADME prediction of the compounds revealed that they may have a good pharmacokinetic profile. Docking results of the compounds6hand6lwith COX-1 (PDB ID: 1EQG) also exhibited a strong binding profile. [ABSTRACT FROM PUBLISHER]

A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives13a–pwere synthesizedviaaldol condensation of 3/4-nitroacetophenones with appropriately substituted aldehydes followed by cyclization of the formed chalcones with 4-methanesulfonylphenylhydrazine hydrochloride. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All compounds were more potent inhibitors for COX-2 than COX-1. While most compounds showed good anti-inflammatory activity, compounds13d,13f,13kand13owere the most potent derivatives (ED50 = 66.5, 73.4, 79.8 and 70.5 μmol/kg, respectively) in comparison with celecoxib (ED50 = 68.1 μmol/kg). Compounds13d,13f,13kand13o(ulcer index = 3.89, 4.86, 4.96 and 3.92, respectively) were 4–6 folds less ulcerogenic than aspirin (ulcer index = 22.75) and showed approximately ulceration effect similar to celecoxib (ulcer index = 3.35). In addition, molecular docking studies were performed for compounds13d,13f,13kand13oinside COX-2 active site which showed acceptable binding interactions (affinity in kcal/mol −2.1774, −6.9498) in comparison with celecoxib (affinity in kcal/mol −6.5330). [ABSTRACT FROM PUBLISHER]

Dietary phenolics have remarkable attention as potential anti-inflammatory agents. This study investigated cyclooxygenase inhibitory activity of nutraceuticals isolated from hydroalcohol extract ofCorchorus olitorius L. (Co) andVitis viniferaL. (Vv). Molecular docking calculations using AutoDock Vina was used to evaluate the binding mode of these nutraceuticals and its major derivatives in the active site of both cyclooxygenase enzymes.In vitrostudies showed that quercetin derivatives exhibit a recognizable selective inhibition of cyclooxygenase-II (60%) compared to cyclooxygenase-I (37%). Results showed quercetin ability to explore extra hydrophobic pocket present in the structure of cyclooxygenase-II enzyme, thus explaining its potential selectivity toward cyclooxygenase-II. [ABSTRACT FROM PUBLISHER]

A new group of 1-phenylpyrazolo[3,4-d]pyrimidine derivatives14a–d–21were synthesized from 2-(6-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)acetohydrazide (12). All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity and ulcerogenic liability. All the target compounds were more potential in inhibiting COX-2 than COX-1. Compounds having pyrazolyl moiety in a hybrid structure with pyrazolo[3,4-d]pyrimidine scaffold (14a–d,16and17) showed higher edema inhibition percentage activities (34–68%) and the 5-aminopyrazole derivative (14c, ED50 = 87.9 μmol/kg) was the most potent one > celecoxib (ED50 = 91.9 μmol/kg). While, thein vivopotent compounds (14a–d,16,17and21) caused variable ulceration effect (ulcer index = 0.33–4.0) comparable to that of celecoxib (ulcer index = 0.33), the pyrazol-3-one derivative (16)and the acetohydrazide (21) were the least ulcerogenic derivatives showing the same ulcerogenic potential of celecoxib. [ABSTRACT FROM AUTHOR]

Environmental pollution by pharmaceuticals has become a major problem in many countries worldwide. However, little is known about the concentrations of pharmaceuticals in water sources in Japan. The objective of this study was to clarify variations in the concentrations of seven nonsteroidal anti-inflammatory drugs (NSAIDs) and in cyclooxygenase(COX)-inhibiting activities in river water and domestic wastewater collected from the Tone Canal and the Edo River Basin in Japan. Total NSAID concentrations were higher in the Tone Canal than in the Edo River, and the highest concentration was observed at the domestic wastewater inflow point located in the Tone Canal (concentration averages of salicylic acid, ibuprofen, felbinac, naproxen, mefenamic acid, diclofenac, and ketoprofen in wastewater samples were 55.3, 162.9, 39.7, 11.8, 30.8, 259.7, and 48.3 ng L−1, respectively). Gas chromatography-tandem mass spectrometry showed that wastewater samples collected during cooler seasons contained higher levels of COX-inhibiting activity. COX-inhibiting activities were highly correlated with NSAID concentrations (particularly for ketoprofen and diclofenac); however, other COX inhibitors, such as NSAIDs that were not examined in this study and/or other chemicals with COX-inhibiting activity, could exist in the water samples because the concentrations of NSAIDs obtained from the water samples did not account for the total COX-inhibiting activities observed. Therefore, COX inhibition assays may be helpful for evaluating the aquatic toxicity of COX inhibitors. In this study, we demonstrated that COX inhibitors in surface water may influence aquatic organisms more than was expected based on NSAID concentrations. Thus, further studies examining other COX inhibitors in the aquatic environment are necessary. [ABSTRACT FROM AUTHOR]

Purpose: Inhibition of cyclooxygenase (COX) and nitric oxide synthesis (NOS) has previously been shown to modify hypoxia-induced relaxation of retinal arterioles in vitro. The purpose of the present study was to investigate whether these findings can be reproduced in vivo. Methods: Twenty healthy persons aged 20-55 years were examined. Using the dynamic vessels analyzer (DVA), the resting diameter and diameter changes during isometric exercise and flicker stimulation were studied before and during breathing of a hypoxic gas mixture. The examinations were carried out before and during intravenous infusion of the NOS-inhibitor l-NMMA, and were repeated on a second study day after topical administration of the COX-inhibitor diclofenac. Results: The resting diameter of retinal arterioles increased significantly during hypoxia and decreased significantly during l-NMMA infusion ( p < 0.0001) which compensated for changes in the blood pressure. During hypoxia and l-NMMA infusion together contraction of retinal arterioles could not compensate for the increased blood pressure as assessed by a gain factor significantly lower than one ( p = 0.002). The arteriolar contraction induced by isometric exercise was significantly reduced by diclofenac and flicker-induced dilatation of retinal arterioles was increased during l-NMMA infusion ( p < 0.0001). Conclusion: Diameter changes of retinal vessels during acute hypoxia in vivo are modified by inhibiting NO and prostaglandin synthesis. The evidence points to possible new targets of intervention on the diameter regulation of retinal arterioles in diseases where retinal hypoxia is part of the disease pathogenesis. [ABSTRACT FROM AUTHOR]

3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions. [ABSTRACT FROM AUTHOR]

Context: Prangos ferulacea (L.) Lindl. (Apiaceae) is a perennial plant found in the Middle-East, where it is commonly used as an antispasmodic and anti-inflammatory agent. It is a rich source of coumarins. Objective: To purify several coumarins from P. ferulacea and to screen their cytotoxicity and anti-herpes activity. Materials and methods: Acetone extract of roots of P. ferulacea was subjected to several chromatographic separations to render pure coumarins ( 1-8). Anti-herpes virus effects of 1- 7 were evaluated at concentration 2.5, 5, and 10 µgmL−1, on a confluent monolayer of Vero cells infected with 25 PFU of HSV1. Cytotoxic effects of 1 and 2 were evaluated on an A2780S cell line using the MTT assay. The cells were exposed to a series of concentrations of coumarins (0.01-2.5 mM, 37°C, 72 h). Results: Compounds 1- 8 were identified as osthole, isoimperatorin, oxypeucedanin, psoralen, oxypeucedanin hydrate, gosferol, oxypeucedanin methnolate, and pranferol. This is the first report of occurrence of 4 and 7 in this plant. Compound 1 showed a viability of 9.41% ± 2.4 at 2.5 mM on A2780S cells (IC50 = 0.38 mM). The cell survival of 2 at 2.5 mM was 46.86% ± 5.5 with IC50 equal to 1.1 mM. Discussion and conclusion: Compound 1 shows cytotoxic effects on the A2780S cell line. Compound 2 is a cyclooxygenase-2 inhibitor and the A2780S cell line does not express COX-2 which may interpret the non-toxic effect of the compound on this cell line. None of the tested compounds showed an anti-HSV effect at non-toxic concentrations. [ABSTRACT FROM AUTHOR]

While it is known that non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 (COX-2) inhibitors influence BP, the exact relationship and underlying mechanisms are still unclear. We investigated the effect of etoricoxib, a selective COX-2 inhibitor on the antihypertensive efficacy of atenolol; beta-blocker, ramipril; angiotensin converting enzyme inhibitor and telmisartan; angiotensin receptor blocker in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a mineralocorticoid volume expansion model. Etoricoxib attenuated the antihypertensive-induced reduction of systolic (atenolol; P < .001, ramipril; P = .011, telmisartan; P = .003) and mean arterial pressure (atenolol; P < .001, ramipril; P = .032, telmisartan; P = .023). These results demonstrate that COX-2 dependent mechanisms play a significant role in blood pressure regulation, and etoricoxib-induced COX-2 inhibition blunts the therapeutic effect of different classes of antihypertensives in this mineralocorticoid volume expansion model of hypertension. [ABSTRACT FROM AUTHOR]

Ginger extract (GE), a potential natural anticancer agent, has compromised therapeutic utilization due to poor bioavailability and physicochemical properties. Present study aimed at assigning GE with a pharmaceutical couture so as to improve its biopharmaceutical performance by monitoring its localized (though prolonged) delivery in the distal parts of gastrointestinal tract for the treatment of colon cancer. Alginate beads entrapping 85.9 ± 1.78% GE were subjected to Eudragit S100 coating. Latter is insoluble at acidic and near neutral (6.8) pH of stomach and upper part of small intestine and it led to 50% retardation (upto 12 h) in release of GE. However, it was solubilised at pH > 7.0 resulting in colon targeted system. Developed beads were free flowing, showed a particle size of 0.9 ± 0.006 mm and super class-II release controlled by swelling and polymer relaxation. Preclinical evaluation using 1,2-dimethylhydrazine-induced colon cancer, in male Wistar rats, in terms of histopathology, oxidative stress, mitochondrial complex activity, β-glucuronidase and ammonia concentration determinations indicated GE loaded beads (50 mg/kg) to be significantly better ( p < 0.05) than free GE. Highlight of the study was that GE loaded coated alginate beads were administered after the induction of colon cancer and significant recession of the cancers was observed after 4 weeks of treatment. [ABSTRACT FROM AUTHOR]

ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor, exists as a crystalline form. According to an Oak Ridge thermal ellipsoid plot drawing, carbonyl oxygen O (5) makes an intermolecular hydrogen bond with the hydrogen bonded to N (3) in the crystal structure. The FTIR and the solid-state 13C NMR spectra suggest that the network is spread out in the amorphous state and the hydrogen bonding gets weaker than that in the crystalline phase, because the carbonyl signals significantly shift in both spectra. When amorphous ER-34122 was heated, crystallization occurred at around 140°C. Similar crystallization happened in the solid dispersion; however, the degree of crystallization was much lower than that observed in the pure amorphous material. Also, the DSC thermogram of the solid dispersion did not show any exothermic peaks implying crystallization. The heat of fusion (Δ Hf) determined in the pure amorphous material was nearly equal to that for the crystalline form, whereas the Δ Hf value obtained in the solid dispersion was less than a third of them. These data prove that crystallization of the amorphous form is dramatically restrained in the solid dispersion system. The carbonyl wavenumber shifts in the FTIR spectra indicate that the average hydrogen bond in the solid dispersion is lower than that in the pure amorphous material. Therefore, HPMC will suppress formation of the intermolecular network observed in ER-34122 crystal and preserve the amorphous state, which is thermodynamically less stable, in the solid dispersed system. [ABSTRACT FROM AUTHOR]

Cyclooxygenase-2 (COX-2) expression and prostaglandin production are suggested to play important, complex roles in the pathogenesis of various liver diseases. Studies on the effects of COX-2 inhibitors on the progression of liver fibrosis present controversial results, and the proposed therapeutic potential of these agents in chronic liver disease is predicated largely on their effectiveness in modulating hepatic stellate cell activation in vitro. This study investigated the modulatory effect of celecoxib, a selective COX-2 inhibitor, in CCl4-mediated hepatotoxicity in rats. Thirty Wistar albino rats, weighing 120-180 g, were assigned into five groups of 6 rats/group. Groups 1 and 2 received saline (10 mL/kg) and CCl4 (80 mg/kg), respectively. Group 3 was given celecoxib (5.7 mg/kg), whereas groups 4 and 5 were pretreated with 2.9 and 5.7 mg/kg/day of celecoxib, respectively, 1 hour before CCl4 treatment. Plasma aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activities increased significantly by 118.5, 150.0, and 51.3%, respectively, with an accompanying decrease ( P < 0.05) in total protein and albumin after CCl4 treatment. Hepatotoxicity was associated with a significant increase in plasma cholesterol, hepatic lipid peroxidation (LPO), and severe hepatic necrosis with marked fatty and cellular (i.e., mononuclear cells) infiltration. Although celecoxib neither reduced CCl4-induced increases in marker enzymes of hepatotoxicity nor significantly attenuated hepatic necrosis, it, however, was effective in reducing elevated cholesterol by 16.5 and 20.8% and LPO by 12.9 and 35.5% at 2.9 and 5.7 mg/kg, respectively. Data suggest that COX-2 inhibitors may be effective in controlling hypercholesterolemia and peroxidative changes associated with liver injury. [ABSTRACT FROM AUTHOR]

Context: Doxorubicin (DX) is a highly effective chemotherapeutic agent used widely in the treatment of solid tumors; however, its optimal use was associated with cardiotoxicity and nephrotoxicity. The exact mechanism of DX-induced cardiotoxicity and nephrotoxicity is not fully explored. Induction of cyclooxygenase-2 (COX-2) activity in either cardiac or renal tissue by DX has been previously reported, indicating a possible role of COX-2 in DX-induced tissue injury. However, the nature of this role in either tissue injury is an issue of controversy. Objective: This study was the first that simultaneously evaluated the effects of a selective COX-2 inhibitor, nimesulide, and a non-selective COX-inhibitor, indomethacin, on DX-induced cardiotoxicity and nephrotoxicity in male Wistar rats. Materials and methods: Rats were allocated into four groups. Control group, DX group (received 15 mg/kg, ip), DX + nimesulide (10 mg/kg/day, po) group, and DX + indomethacin (2 mg/kg/day, po) group. Nimesulide and indomethacin were started at the same day of DX injection and continued for 5 days. Results: The results of the present study showed that inhibition of COX-2 either by selective or non-selective COX-2 inhibitor ameliorated DX-induced cardiotoxicity but aggravated DX-induced nephrotoxicity in rats, as evidenced biochemically and histopathologically. Discussion and conclusion: Our study indicates that production of COX-2 is organ specific; consequently, the differential effect of COX-inhibitors should be considered in DX-treated patients. However, a wide scale experiment is needed for further confirmation and testing other members of COX-inhibitors (e.g. celecoxib and diclofenac). [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients. [ABSTRACT FROM AUTHOR]

Background. Among dialysis patients, acute mesenteric ischemia is mostly caused by non-occlusive mesenteric ischemia (NOMI). There is a very high mortality rate associated with this complication, but prognostic factors associated with NOMI are not well-known. Method. In this study, we retrospectively reviewed the records of dialysis patients to identify prognostic factors associated with mortality from NOMI. Overall, there were 541 patients on hemodialysis (HD) and 158 patients on peritoneal dialysis (PD) in our hospital from January 2007 to December 2008. Among these 699 patients, we diagnosed NOMI by surgical and/or radiological criteria. A total of 12 dialysis patients (9 on HD and 3 on PD) developed NOMI during the study period. Result. The incidence of NOMI was 1.04% per patient-year for all dialysis patients (0.95% for HD and 1.35% for PD patients). Most of the 12 patients had chronic hypotension (83.3%, 10/12). Four patients expired following development of NOMI. Our results showed that mortality was significantly higher in patients who were administered a cyclooxygenase ( COX) inhibitor prior to ischemia. Hypobicarbonemia during NOMI, which might indicate the severity of hypoperfusion, is also associated with higher mortality. Conclusion. NOMI is rare in dialysis patients. COX inhibitor administration should be given with caution in long-term hypotensive dialysis patients. [ABSTRACT FROM AUTHOR]