Influence of food and antacid administration on fluoride bioavailability from enteric-coated sodium fluoride tablets.

The relative bioavailability of enteric-coated sodium fluoride (NaF) tablets (10 mg F-) has been assessed following administration with a standard calcium-rich breakfast or calcium-poor lunch, and 2 h before or simultaneously with antacid administration (2.4 g aluminum-magnesium hydroxide), versus intake on an empty stomach. Twelve volunteers were studied 3 times according to an open, three-way crossover design over a 24 h period at weekly intervals. Meals were found to decrease the peak serum concentration of NaF from 122 micrograms/L during fasting (after baseline subtraction) to 71 and 88 micrograms/L with breakfast and lunch respectively, and to slow its absorption rate with Tmax increasing from 3.3 to 7.3 and 11.2 hours, without altering its bioavailability. Antacid impaired the bioavailability of NaF by 80% when administered simultaneously, with AUC decreasing from 987 to 155 micrograms.h/L, but had no significant effect when taken 2 h before NaF. In conclusion, the enteric-coated NaF tablets used in this study can be administered with food or after a 2-hour delay following antacid administration, but should not be taken simultaneously with antacid.

Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials.

OBJECTIVE: This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated. BACKGROUND: Prolonged treatment with oral NAC has been investigated in a number of studies of patients with CB. NAC prevented acute exacerbations and symptoms of CB in some but not all trials. METHODS: The trials included in this analysis were selected from a MEDLINE search of the period from January 1, 1980, through June 30, 1995; references in the articles retrieved in the initial search; and consultation with 2 experts. Selection was based on the following criteria: published, double-blind, placebo-controlled, chronic bronchopulmonary disease, duration of therapy > or =2 months, and data sufficient to calculate an outcome variable permitting direct comparison of studies (effect size) for both NAC and placebo groups. The primary end point was the incidence of acute exacerbations in 7 of 8 trials and clinical assessment in the other. In 7 studies, inclusion criteria were based on Medical Research Council criteria for CB, with an additional criterion in some trials. For the meta-analysis, the end points of individual trials were transformed into an effect size as a common outcome. RESULTS: Of 21 trials initially identified, 8 qualified for inclusion. References from the 8 papers and consultation with the experts produced 8 additional publications, 1 of which qualified for inclusion. NAC was administered orally at a daily dose of 400 mg (1 study), 600 mg (5 studies), or 1200 mg (1 study). One other trial used a dose of 600 mg 3 times per week. The duration of treatment was 3 months (1 study), > or =5 months (2 studies), or 6 months (7 studies). The results of this meta-analysis showed a statistically significant effect size for NAC compared with placebo. The overall value of effect size was -1.37 (95% CI, -1.5 to -1.25). Sensitivity analyses did not significantly alter these results. In a subset analysis of trials with the number of acute exacerbations as a clinical end point, a mean difference of -0.32 clinical event (95% CI, -0.50 to -0.18) was found (ie, a 23% decrease in the number of acute exacerbations compared with placebo). CONCLUSION: These findings suggest that a prolonged course of oral NAC prevents acute exacerbations of CB, thus possibly decreasing morbidity and health care costs.

In-vitro versus in-vivo activities of new 5-lipoxygenase inhibitors with antiinflammatory activity.

The possible relationship between in-vitro inhibition of lipoxygenase (LO)/cyclooxygenase (CO) and in-vivo antiinflammatory effects of compounds such as isoflavanes (Zy 16369, Zy 16372, Zy 16681) was investigated. The latter were all shown to be potent 5-LO inhibitors when tested in vitro on human peritoneal macrophages (IC50 = 1-7 mumol/l). Zy 16372 and Zy 16681 also inhibited the 12- and 15-LO and, to a minor extent, the CO. In order to evaluate the antiinflammatory and antiproliferative effects of these compounds in vivo they were applied topically to mice. No definite correlation could be made between the inhibition of the ear oedema induced by arachidonic acid (AA), the inhibition of the epidermal ornithine-decarboxylase (ODC) activity induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), and the in-vitro activities of the compounds. Zy 16372 appeared to inhibit the oedema dose-dependently (ED50 = 5 mumol/ear) and seemed to be the most potent among the 3 compounds tested and slightly more potent than the reference compound nordihydroguaiaretic acid. As inhibitors of TPA-induced ODC, all 3 compounds exhibited comparable activity. These results suggest that the in-vivo effects of the compounds might be mediated by components other than AA metabolites, and/or be related to their specific kinetic patterns.

[Effect of the lipid-lowering agent, procetofen, on the makeup of human biliary lipids]. / Influence de l'hypolipémiant procétofène sur la composition des lipides biliaires chez l'homme.

The effect of lipid-lowering treatment with procetofen (3 x 100 mg/day for 4-6 weeks) on the cholesterol saturation index (S.I.) of bile has been studied in 6 patients with type IIa or IIb pattern hyperlipoproteinemia. Compared with a control period with placebo, the S.I. was increased by more than 20% during active treatment in 2 patients. Oversaturation was reached in one case. In the other 4 patients, the changes did not exceed 20% of the control value. Thus, increased lithogenicity of bile does not appear to be a frequent effect of procetofen. A larger number of patients should therefore be studied to establish its true incidence.

[Acute atropinic syndrome caused by abuse of anti-asthmatic cigarettes (Datura stramonium)]. / Syndrome atropinique aigu par abusif de cigarettes anti-asthmatiques (datura stramonium).

Over a 3-month period four patients (3 males and 1 female) aged 17 to 23 were admitted to an emergency unit with an acute anticholinergic syndrome. All of them had ingested aniasthmatic cigarettes containing Datura stramonium leaves for psychedelic purposes. The clinical features were characterized by striking peripheral signs of anticholinergic inhibition associated with central nervous system manifestations such with central state, hallucinations and abnormal behaviour. One patient had to be treated with physostigmine salicylate. The other three received supportive care only. The central and peripheral symptomatology subsided gradually over 12-48 hours. All four patients had more or less extensive amnesia regarding the acute toxic phase. Based on these observations, the possible causes, differential diagnosis and treatment of acute atropinic intoxication are reviewed. The discussion also considers the problem of abuse of "over-the-counter" atropine containing preparations.

[Bile acid concentration in serum after a test meal in hepatobiliary diseases. A comparison with quantitative liver function tests]. / Die Gallensäurenkonzentration im Serum nach einer Testmahlzeit bei hepatobiliären Erkrankungen. Ein Vergleich mit quantitativen Tests der Leberfunktion.

The concentration of bile acids in serum was measured by an enzymatic-fluorometric method under fasting conditions and 2 hours after a standardized meal in 26 patients with chronic liver disease (chronic hepatitis, liver cirrhosis, primary biliary cirrhosis) and compared with other tests of liver function. Postprandial bile acids and transaminases were false negative in only 12% and are thus the most sensitive tests after the BSP-retention test (3% false negative results). In comparison, fasting bile acids proved to be a relatively insensitive screening test for liver disease (38% false negative results). Postprandial bile acids were more closely correlated with BSP retention and BSP disappearance rate constant (Ki) than fasting bile acids. In view of these findings postprandial serum bile acid concentrations should be preferred to fasting bile acid concentrations in screening for liver disease and monitoring liver function.

[Myoclonic encephalopathy due to bismuth salts. Negative search for an associated toxic element]. / L'encéphalopathie myoclonique associée aux sels de bismuth recherche négative d'un élément toxique associé

Five cases of bismuth associated encephalopathy have been observed in the area of Geneva (Switzerland). Thy typical clinical picture is described and the blood and urinary bismuth levels are analyzed in comparison with a group of patients on bismuth treatment but without encephalopathy. A link is established between these observations and previously reported cases of bismuth toxicity, and also with other toxic encephalopathies. With regard to pathogenesis, two hypotheses are discussed: alkylation of bismuth in vivo, and association with another neurotoxic element. With this in view, the urinary excretion of arsenic, lead and mercury was measured. The results were within normal limits.

[Procetophen--an alternative in the treatment of hypercholsterinemia?]. / Procetophen--eine Alternative in der Behandlung der Hypercholesterinämie?

18 patients with primary hyperlipoproteinemia of type IIa and type IIb, on regularly controlled dietary treatment for 6 months and a 4 weeks placebo period, were given 300 mg procetofene per day for 12 weeks. The subjective tolerance of the drug was good. The serum triglyceride levels were lowered by about 35%, total cholesterol by 15%, LDL-cholesterol by 12% and Apo B by 20%. The HDL-cholesterol values remained unchanged. A slight increase in SGPT values indicates that liver function should be regularly checked in patients undergoing procetofene therapy.

Hepatic handling of a gamma-emitting bile salt derivative, 123I-cholylglycylhistamine, in the dog.

The hepatic handling of the bile salt derivative 123I-cholylglycylhistamine has been compared with that of the physiologic bile salt taurocholate in boxer dogs equipped with a Thomas duodenal cannula. After intravenous injection of trace amounts, 123I-cholylglycylhistamine and 14C-taurocholate disappeared from plasma with nearly identical disappearance rate constants. Excellent scintiscans of the liver were obtained with the Anger camera after injection of 3 mCi of 123I-cholylglycylhistamine. Monitoring of radioactivity over a hepatic region of interest revealed rapid uptake of 123I-cholylglycylhistamine by the liver, which reached a maximum 5.7 +/- 0.4 min after injection. The biliary excretion rates of the compounds closely paralleled each other, reaching their maximum within 15 min after injection. Cumulative biliary excretion within 45 min was 58.5 +/- 2.9% and 61.4 +/- 5.0% of the dose for 123I-cholylglycylhistamine and 14C-taurocholate, respectively. Modification of the side chain and gamma-labelling of bile salts may provide scintigraphic agents for the study of the biliary system, which in the behaviour closely resemble the physiologic parent compounds.

[Biliary excretion kinetics of the biliary contrast media ioglycamide, iodoxamate and iotroxamate in the dog]. / Die Kinetik der biliären Ausscheidung der Gallekontrastmittel Ioglycamid, Iodoxamat und Iotroxamat beim Hund.

The biliary excretion of meglumine iotroxamate (ITX) and meglumine iodoxamate (IDX), two new intravenous cholangiographic contrast materials, was compared with that of meglumine ioglycamide (IGL) in bile-fistula dogs following intravenous infusion in a steady state. With any equimolar infusion rate or plasma concentration, more ITX and IDX were secreted in the bile than IGL. The maximum rate of biliary excretion (Emax.) of either ITX (2.23 +/- SD 0.28 mumol/min/kg) or IDX (2.91 +/- SD 0.39 mumol/min/kg) was significantly greater than that of IGL (1.22 +/- SD 0.19 mumol/min/kg); the biliary concentration was always greater for ITX and IDX than for IGL.

[Comparison of the biliary excretion of the radiographic contrast media Iotroxamate and Ioglycamide in the dog]. / Vergleich der biliären Ausscheidung der Röntgenkontrastmittel Iotroxamat und Ioglycamid beim Hund.

Biliary excretion of iotroxamat (ITX) and ioglycamide (IGL) in cholecystectomized dogs fitted with a Thomas duodenal cannula is compatible with saturation kinetics exhibiting maximal excretory velocities of 2.23 +/- SD 0.18 and 1.22 +/- 0.19 mumol/min/kg, respectively. While biliary excretion of ITX obeyed classical Michaelis Menten kinetics, the data obtained with IGL suggested a more complex process. The choleretic effects of both contrast agents (23.6 +/- SD 2.29 and 25.8 +/- 2.21 microliter of excreted substance) were comparable. On the basis of these results and in view of the similar toxicity of the two contrast agents in animals, it may be expected that ITX will have advantages over IGL for intravenous cholangiography.

Cost-effectiveness analysis of oral N-acetylcysteine as a preventive treatment in chronic bronchitis.

UNLABELLED: Chronic bronchitis has a prevalence of approximately 11% in the population aged over 35 years and its frequent acute exacerbations (AECBs) are an important cause of morbidity and costs in health-care resources. Oral N -acetylcysteine (NAC) is administered during the winter months as a way of reducing AECBs. This cost-effectiveness analysis was done from the payers' point of view in the Swiss health-care system, based on a retrospective analysis of published placebo-controlled studies. The pooled data show that continuous administration of 400 mg day(-1)per os of NAC leads to a significant reduction in the number of AECBs (NAC: 16.2 vs 25.2% AECBs per month); a significantly smaller percentage of days of sick leave (NAC: 3.6 vs 5.3%) and a lower rate of hospitalizations (NAC: 1.5 vs 3.5% over a period of 6 months). Taking into account the poor compliance of these patients, calculations assumed a compliance of 80%. Direct costs were those of an NAC treatment, the management of an AECB (biological tests in 59%, X-rays in 65% and pulmonary function tests in 45%; antibiotics 70%, bronchodilators in 89%, corticosteroids in 24% and 'others' in 25% of the patients), and of hospitalizations (estimated at 10 days per case). Based on these figures, the mean direct costs of an untreated patient were CHF 869 vs CHF 700 in the NAC-treated patient. Univariate sensitivity analysis indicated that cost neutrality is reached with 0.6 (<0.25-1. 94, 95% CI) AECBs per 6 months. Indirect costs (based on sick leave) were also significantly different; the mean in untreated patients was CHF 1324 vs CHF 779 in the NAC-treated patients. CONCLUSION: Treating chronic bronchitis patients with NAC during the winter months is cost-effective both from the payer's and a social point of view.

A pneumotoxin, O,O,S-trimethyl phosphorothioate, induces hemorheological alteration in rats.

O,O,S-trimethyl phosphorothioate (OOS-TMP), an impurity present in widely used organophosphorus insecticides, has been shown to induce lung injury after oral administration. To date, very little is known about the hemorheological changes which may occur during the inflammation of lung caused by OOS-TMP. The present study has demonstrated that oral administration of OOS-TMP (10 mg/kg, 20 mg/kg) to rats produced an increase in whole blood apparent viscosity at 24, 48 and 72 h following the treatment in rats. Concomitantly, the plasma fibrinogen level and red blood cell (RBC) aggregation were increased at 24 and 48 h. There was no change in RBC filterability. Thus, OOS-TMP, a pneumotoxin, was capable of causing a systemic hemorheological alteration, probably via increase in fibrinogen content, an acute-phase protein, in rats.