Constraint of the Nuclear Dissipation Coefficient in Fission of Hypernuclei.

Experimental studies of nuclear fission induced by fusion, transfer, spallation, fragmentation, and electromagnetic reactions in combination with state-of-the-art calculations are successful to investigate the nuclear dissipation mechanism in normal nuclear matter, containing only nucleons. The dissipation mechanism has been widely studied by the use of many different fission observables and nowadays the dissipation coefficients involved in transport theories are well constrained. However, the existence of hypernuclei and the possible presence of hyperons in neutron stars make it necessary to extend the investigation of the nuclear dissipation coefficient to the strangeness sector. In this Letter, we use fission reactions of hypernuclei to constrain for the first time the dissipation coefficient in hypernuclear matter, observing that this coefficient increases a factor of 6 in the presence of a single Λ hyperon with respect to normal nuclear matter.

Bioindicators of severe ocean acidification are absent from the end-Permian mass extinction.

The role of ocean acidification in the end-Permian mass extinction is highly controversial with conflicting hypotheses relating to its timing and extent. Observations and experiments on living molluscs demonstrate that those inhabiting acidic settings exhibit characteristic morphological deformities and disordered shell ultrastructures. These deformities should be recognisable in the fossil record, and provide a robust palaeo-proxy for severe ocean acidification. Here, we use fossils of originally aragonitic invertebrates to test whether ocean acidification occurred during the Permian-Triassic transition. Our results show that we can reject a hypothesised worldwide basal Triassic ocean acidification event owing to the absence of deformities and repair marks on bivalves and gastropods from the Triassic Hindeodus parvus Conodont Zone. We could not, however, utilise this proxy to test the role of a hypothesised acidification event just prior to and/or during the mass extinction event. If ocean acidification did develop during the mass extinction event, then it most likely only occurred in the latest Permian, and was not severe enough to impact calcification.

Gastric and intestinal absorption of oxprenolol in humans.

The gastrointestinal absorption of the beta blocker oxprenolol was investigated in four healthy subjects by an intubation technique. Oxprenolol was introduced into the stomach, dissolved in a homogenized meal containing the marker 14C-polyethylene glycol (PEG) 4000. Unlabeled PEG 4000 was perfused during the whole experiment into the duodenum at the ampulla of Vater. Samples of luminal contents were collected at regular intervals over four hours in the stomach, at the angle of Treitz, and 30 cm below this point. Blood was also collected. Oxprenolol was not absorbed in the stomach. About 80% of the drug emptied from the stomach was absorbed in the duodenum, and 80% of that released from the duodenum was absorbed in a 30-cm segment of the jejunum. The amounts absorbed in these two intestinal segments were directly proportional to the amounts delivered. The areas under the plasma concentration-time curves were not related to the amounts absorbed. A single dose of oxprenolol taken with an homogenized meal did not modify the gastric emptying and secretory response.

[Vidarabine treatment of chronic active hepatitis associated with hepatitis B virus multiplication. A randomized multicenter study]. / Traitement par la vidarabine de l'hépatite chronique active associée à la multiplication du virus de l'hépatite B. Etude multicentrique randomisée.

A randomized controlled study of one course of vidarabin was carried out in 30 patients with HBs Ag, HBe Ag, DNAp, positive chronic active hepatitis: 15 patients were treated with vidarabin given intravenously (15 mg/kg/day for 7 days then 7.5 mg/kg/day for 14 days); the other 15 patients received a placebo for 21 days. During treatment, DNA polymerase activity fell dramatically in 13 treated patients and in no controls (p less than 0.001). Six months after inclusion, ALT normalization was observed in 40 p. 100 of the treated patients and 6 p. 100 of the controls (p less than 0.05), a decrease in inflammatory activity on liver biopsies was observed in 70 p. 100 of the treated patients and 20 p. 100 of the controls (p less than 0.05), a permanent lost of DNA polymerase and of HBe Ag occurred in 33 p. 100 and 13 p. 100 of the treated patients and 20 p. 100 and 7 p. 100 of the controls, respectively. In addition, a second course of vidarabin was administered to the 12 patients who were still HBe Ag positive 6 months after the first course. During the next 6 months, 8 patients lost DNA polymerase and 4 lost HBe Ag. Altogether, the final score of durable inhibition of HBV replication was 11/15 (73 p. 100) within one year. The above results demonstrate that one course of vidarabin can significantly improve ALT and liver inflammatory activity but the effect upon HBV replication is only transient. A second course does however increase efficacy on HBV replication without additional side effects.

[Comparative elimination of pirprofen from the plasma and synovial fluid of the knee. 26 cases]. / Elimination comparée du pirprofène à partir du plasma et du liquide synovial du genou. 26 observations.

Twenty-six patients with various inflammatory diseases of the knee were treated with a 400 mg dose of pirprofen orally twice a day for 2 days. On the third day, samples of blood and synovial fluid were taken 3 h and 10 h approximately after a fifth 400 mg dose of the drug. Pirprofen concentrations, as determined by gas-liquid chromatography, were higher in plasma than in synovial fluid during the 2-5 h period post-dosing. They decreased with an elimination half-life of 6 h in plasma as against 41 hours in synovial fluid. This study demonstrates that pirprofen diffuses into the synovial fluid where it remains significantly longer than in plasma.

The gastrointestinal absorption of drugs in man: a review of current concepts and methods of investigation.

The various mechanisms which have been advanced to explain drug absorption are critically reviewed and the limitations of current theories are discussed. Various techniques for investigating drug absorption and transit through the gut are presented, and the results obtained with metoprolol are briefly considered to illustrate the potential of some of these methods.

Importance of analytical methods in pharmacokinetic and drug metabolism studies.

Pharmacokinetic and drug metabolism studies first request that good analytical data are available. The various methods that permit unchanged drugs and their metabolites to be separated, identified and quantitatively assayed are briefly reviewed. The present importance of gas chromatography/mass spectrometry is emphasized, as well as the limits of immunological assays. The sensitivity of the analytical assay has a direct impact on the validity of the pharmacokinetic model which is built up from plasma concentration data. The precision and accuracy of the assay is also critical, and it is not always easily estimated. A new significant parameter is the speed of analysis, and the resulting massive production of analytical data. New drugs coming from biotechnology, and new dosage forms, like targeted drugs, will create new analytical problems in the future. They will probably call for the development of new biological or pharmacological assay procedures, in addition to the physicochemical means of analysis.

[Interest of tiaprid in chronic ethylism and psychic disorders (author's transl)]. / Intérêt du tiapride dans l'éthylisme chronique et les troubles du caractère.

Tiapride was applied to 25 mostly alcoholic patients affected by tremor, agitation and psychic disorders, with favourable results in more than half cases. By oral or parenteral way, efficacy is the same and the minimal active dose may be fixed at 300-400 mg/24 h. The treatment is well tolerated.

[The effect of ethanol and antabus-antabus-alcohol-reaction on histamin and mast cell. Contents of the lung (author's transl)]. / Die Wirkung von Athanol und Antabus-Alkohol-Reaktion auf den Histamin- und Mastzell gehalt der Lunge

Alcohol--orally given in concentrations from 1 to 4 g/kg body-weight--leads to a reduction of mast cells in the guinea pig lung. At the same time a minor decrease of histamine concentration was observed. The incompatibility reaction with alcohol after disulfiram intake (DAR) shows an additional degranulation oft mast cells of the lungs and decrease of histamine-content. So far, there seems little difference between the influence of disulfiram alone and the DAR. Besides thrombocytes and basophile leucocytes, the mast cells of the lung are responsible for the release of histamine and serotonine during higher alcohol concentrations and alcohol-disulfiram-reactions. We think that the intolerance phenomena of humans after alcohol--f.e. in form of flush-reaction--is at least partly related to the concomitant influence oft mast cell-substances.

Pharmacokinetic comparison of cefroxadin (CGP 9000) and cephalexin by simultaneous administration to humans.

The pharmacokinetic parameters of cefroxadin and cephalexin were compared after simultaneous oral administration of the two cephalosporins to 21 subjects. The influence of the dose, the formulation, and food intake on these parameters was investigated. Both drugs were equally well absorbed from all of the tested formulations; identical percentages of the dose were recovered in the urine in all cases. The elimination half-life of cefroxadin and, consequently, the area under the plasma concentration-time curve were about 10% less than those of cephalexin. Plasma concentrations and cumulative excretion curves of the two drugs were almost superimposable. Food intake had the same effect on both drugs; absorption was slowed, but the amounts absorbed were almost the same as those in fasted subjects.

Investigation of drug absorption from the gastrointestinal tract of man. II. Metoprolol in the jejunum and ileum.

Absorption of metoprolol in jejunum and ileum was investigated in eight healthy subjects using an intestinal perfusion technique below an occlusive balloon. An isotonic saline solution, with or without metoprolol, was perfused at a flow rate of 10 ml/min, either at the angle of Treitz or in the middle part of the ileum. The absorption in a 30 cm intestinal segment was evaluated at metoprolol concentrations of 20, 40 and 60 mg/l. Metoprolol did not affect gut motility. Metoprolol was similarly absorbed in the jejunum and ileum. The absorption rates appeared to be linearly related to the perfusion rates and to the mean concentration in the segment, indicating a first-order kinetic process. The absorption rate of metoprolol perfused in the jejunum in a saline solution appeared to be lower than that observed after gastric administration of the drug incorporated in a meal. The findings in this and other studies in this series indicate that metoprolol is similarly absorbed throughout the small intestine.

Investigation of drug absorption from the gastrointestinal tract of man. III. Metoprolol in the colon.

The colonic absorption of metoprolol was indirectly evaluated by measuring drug appearance in plasma following intravenous, jejunal or colonic infusion in six healthy volunteers. Plasma concentrations of alpha-hydroxymetoprolol and urinary excretion of the main metabolites were also measured. Plasma profiles of metoprolol after colonic and jejunal perfusion were similar, and the relative bioavailabilities of the drug from these two regions of the gut were not significantly different. The concentrations of alpha-hydroxymetoprolol, the major metabolite in plasma, were similar after jejunal and colonic perfusion, but higher than those observed after intravenous administration. The percentage of the dose recovered in urine over 24 h as two metabolites was not significantly influenced by the route of administration.

Investigation of drug absorption from the gastrointestinal tract of man. IV. Influence of food and digestive secretions on metoprolol jejunal absorption.

The influence of nutrients and digestive secretions on the intestinal absorption and bioavailability of the beta-adrenoceptor antagonist, metoprolol, was investigated in an isolated segment of jejunum using an intestinal perfusion technique. Two solutions containing metoprolol, one with, and one without nutrients, were perfused into the jejunum with an occluding balloon inflated or deflated. Jejunal fluid, blood and urine samples were then collected for drug or metabolite estimation. In the segment studied, metoprolol absorption from the nutrient solution was four times that observed during perfusion of the saline solution. Bile salts did not enhance drug absorption. Both in the presence and absence of nutrients, a linear relationship was observed between the computed cumulative amount of drug absorbed from the gastrointestinal tract and the resulting plasma concentration at each sampling time, indicating that first-pass loss was not saturated. This result was also reflected in the similarity of the AUC:dose ratios, and in the lack of effect of nutrients on the metabolism of the drug.