Search

Although nucleoside analogs as a group inhibit mtDNA replication, individually they target specific organs for toxicity. For example, dideoxyinosine(ddI) is most closely associated with clinical pancreatitis and dideoxycytosine (ddC) with peripheral neuropathy. Comparison of the differential effects of these analogs on mitochondrial function in relevant human cell lines could provide general clues as to the mechanisms of their differential toxicity. We compared the effects of ddI [and its intracellular metabolite dideoxyadenosine (ddA)], with other nucleoside analogs ddC, Azidothymidine (AZT) and didehydrodeoxythymidine(d4T) on mtDNA elongation, cytotoxicity, oxidative phosphorylation, and cellular ATP concentration in a human pancreatic cell line, Capan-1 cells. AZT, like all the other analogs tested, altered mtDNA elongation, but had no other effect on these cells. Both ddC and d4T, but not ddI (20 μm and 50 μM), reduced total dish protein (a measure of cell numbers) in cells grown to confluence. The effect of ddA was intermediate. All (except AZT) increased lactate concentration in the cell culture medium. Dideoxycytosine (ddC) and d4T did not significantly affect cell oxygen consumption, expressed as a fraction of total dish protein. By contrast, ddI and ddA reduced basal and/or FCCP-stimulated oxygen consumption. %Dideoxycytosine (ddC) but not ddI or ddA (50 μM) was cytotoxic to cells after six days of growth. Nevertheless, the ATP content (expressed as a fraction of surviving cells) for ddC-, ddI-, and ddA-treated cells was similar to control cells. Cytotoxicity was apparent for ddI, ddA, as well as ddC after seven days. Paradoxically, cell ATP content was now significantly higher than control cells. Electron microscopy of cells treated with ddI confirmed significant ultrastructural changes affecting the inner mitochondria membrane and cristae. In conclusion, these data suggest that nucleoside analogs uniformly induce damage to mtDNA. However, the mitochondrial phenotypic damage induced by ddI and ddA appear to result in less Capan-1 cytotoxicity than ddC and d4T. The link between these differential effects and ddI pancreatitis is unclear. [ABSTRACT FROM AUTHOR]

Our objective was to identify factors that might correlate with human immunodeficiency virus (HIV) disease stage in intravenous drug abusers (IVDA). Particular attention was given to alcohol abuse. We accordingly explored in a cross-sectional study the relation between stage of HIV disease and age, sex, needle sharing, ethnicity, self-reported history of alcohol consumption and CAGE scores. IVDA from a single municipal hospital were subdivided into three groups according to HIV disease status. Group 1 comprised 42 individuals with AIDS; group 2 comprised 114 who were HIV positive but without AIDS; and group 3 comprised 52 who were HIV negative. Information on alcohol consumption and CAGE responses were obtained by questionnaire and interview. Discriminant analysis indicated that alcohol abuse, assessed either by self-reported consumption or by CAGE scores, was significantly more common in the AIDS group than in either the HIV positive or the HIV negative groups, when controlled for age, sex, and needle sharing status. The relative risk of AIDS was 3.8 times higher in the heavy drinkers than in moderate drinkers. Needle sharing was also more common in the AIDS group than in the HIV positive or HIV negative groups when the other factors were controlled for. AIDS was more common in black than white IVDA, and this increased frequency did not appear related to alcohol consumption since the distribution of heavy drinkers within each category of HIV disease did not differ within the ethnic groups. These data indicate that a history of heavy alcohol consumption is more common in IVDA with AIDS than in IVDA at earlier stages of HIV disease. [ABSTRACT FROM AUTHOR]

The changes in serum trypsin concentration have been measured in 47 subjects for up to 2 hours after a Lundh meal. In 18 healthy controls, mean fasting trypsin concentration was 285 +/- 125 ng/ml (mean +/- 2 SD). The maximum increase after the Lundh meal (the trypsin response ratio) was 6.7 +/- 7.5%. Six patients with chronic renal failure had elevated fasting serum trypsin concentrations (range 460-1100 ng/ml) but trypsin response ratios fell within the control range. Of five patients with relapsing pancreatitis, two had raised and three normal or low fasting trypsins. After stimulation two had elevated trypsin response ratios; one of the two had evidence of main duct obstruction. Eleven out of 12 patients with chronic pancreatitis (with or without insufficiency) had low fasting trypsin concentrations (range 0-120 ng/ml) Seven of the 12 also had raised trypsin response ratios. In six patients with cancer of the pancreas, fasting trypsin was low in three, normal in two, and raised in one. Both patients with a normal fasting level had a raised trypsin response ratio. The combination of a single estimation of fasting serum trypsin concentration followed by serial measurements after a Lundh meal provides a useful screening test for chronic pancreatic disease. [ABSTRACT FROM PUBLISHER]

125I-labelled human trypsin metabolism has been investigated in man. Three subjects received 125I-trypsin and 131I-albumin intravenously. Against a background secretin infusion (1 U/kg/h), trypsin decayed biexponentially from the serum with half-lives of 17.5, 21, and 24 minutes for the rapid disappearance phase and 520, 540, and 560 minutes for the slow phase. Between 13% and 38% of the 125I injected was recovered from duodenal juice aspirated continously over 300 minutes. In contrast, less than 1% of the 131I-albumin injected was recovered. When bile and pure pancreatic juice were collected at endoscopic retrograde cholangiopancreatography after intravenous 125I-trypsin in a fourth subject 125I radioactivity was found to be secreted via both these routes. After 125I-trypsin infusion into the duodenum 11% of the total dose was found to be present in the circulation after 75 minutes. These results support the concept that recirculation of trypsin exists in man. [ABSTRACT FROM PUBLISHER]

Trypsin in duodenal aspirate and pure pancreatic juice samples has been measured by both radioimmunoassay and enzymatic mathods. The radioimmunossay has been shown to be specific and to detect trypsin in the presence of aprotinin (Trasylol). In duodenal juice samples from control subjects and from patients with primary biliary cirrhosis a good correlation was obtained between both immunoreactive trypsin concentration and trypsin activity. The immunoreactive trypsinogen concentration in pure pancreatic juice also correlated well with activated trypsin activity. The mean immunoreactive trypsin concentration and the concentration of enzymatically inert immunoreactive trypsin in duodenal juice samples from patients with primary biliary cirrhosis were significantly lower than controls, suggesting pancreatic hyposecretion in this disease. After five duodenal juice samples had been stored for three months at -70 degrees C, immunoreactive trypsin concentration in samples stored without Trasylol were reduced by 12 . 0 +/- 4 . 2 (mean +/- SD) times the concentration of samples stored in Trasylol. Trypsin autodegradation continues even at -70 degrees C; Trasylol protects against this. Radioimmunoassay is a reliable method of trypsin estimation in duodenal juice and has advantages over conventional enzymatic analysis. [ABSTRACT FROM PUBLISHER]

Pancreatic function was studied in 29 patients with extrahepatic portal venous obstruction, and 30 age-matched controls. The aetiology of the portal venous obstruction was known in 20 out of 29 patients. No patient had a history of pancreatitis. Serum trypsin, both fasting and for 120 minutes after a Lundh meal, was significantly lower in the patients than in controls (P less than 0.005). 5/28 (18%) patients had reduced fasting serum trypsin levels and in 5/14 trypsin was abnormal after a Lundh meal. Mean fasting serum glucose (3.8 +/- ).49 mmol/l was significantly higher than in control subjects (mean 3.4 +/- 0.42 mmol/l) (P less than 0.05). After 100 g glucose orally, mean serum glucose at 180 minutes (5.26 +/- 1.58 mmol/l) was higher than the control value (3.96 +/- 1.45 mmol/l) (P less than 0.05), and 30 and 60 minutes serum C-peptide values were significantly lower (P less than 0.005). Pancreatic hypofunction found in these patients probably results from an abnormal portal circulation in association with mild pancreatic damage secondary to chronic venous congestion. [ABSTRACT FROM PUBLISHER]

Presents information on a study that examined the gastric secretory function of the frequency of gastrointestinal infections and diarrhea in patients with the acquired immunodeficiency syndrome (AIDS). Methodology of the study; Results and discussion on the study.

Study Objective: To correlate oral ketoconazole absorption with gastric acid secretion in patients with the acquired immunodeficiency syndrome (AIDS).Design: Prospective measurement of maximal acid output and oral ketoconazole absorption with and without 0.1-N hydrochloric acid.Setting: Hospital in-patients in university medical center.Patients: Ten consecutive male patients with AIDS.Intervention: Maximal acid output was determined after pentagastrin stimulation in all patients. Serum ketoconazole levels were measured the day after ingestion of a 200-mg ketoconazole tablet in the fasted state. On the final day, ketoconazole was ingested with 200 mL of 0.1-N hydrochloric acid.Measurements and Main Results: Maximal acid output was below 15 mEq/h in 7 of 10 patients. In all 7, the area under the serum ketoconazole concentration-time curve was below normal (1.4 +/- 0.9 mg/h.L; mean +/- SE), and absorption was normalized by hydrochloric acid (9.9 +/- mg/h.L). Two of three patients with maximal acid outputs above 15 mEq/h had normal ketoconazole absorption (15.1 +/- 6.7 mg/h.L).Conclusions: The bioavailability of oral ketoconazole is reduced in patients with AIDS, largely as a result of gastric hypochlorhydria. Ketoconazole tablets should therefore be given with acid in these patients. [ABSTRACT FROM AUTHOR]

Ketamine-induced sclerosing cholangitis has been described with chronic intranasal and intravenous use. Our case follows chronic topical use for peripheral neuropathy. It is also uniquely associated with early inflammatory bowel disease, a known complication of primary sclerosing cholangitis., (© 2024 Published by Elsevier Inc. on behalf of the AGA Institute.)