Equilibrium-dialysis studies of the interaction between cholic acid and 100000g-supernatant preparations from the rat liver

1. The binding of cholic acid to 100000g supernatants from rat livers was investigated by equilibrium dialysis and gel-exculsion chromatography. 2. Supernatants were found to contain at least two classes of binding site for cholic acid. 3. These recptor molecules are probably proteins since incubation with proteolytic enzymes resulted in complete loss of cholic acid binding. 4. Supernatants were added to columns of Sephadex G-75, and two groups of fractions were shown to bind cholic acid. One of these contained low-affinity binding sites and the other contained both low- and high-affinity binding sites. 5. Feeding cholestyramine had no effect on cholic acid binding. 6. Increased cholic acid binding occurred after injection of phenobarbitone. There was an increase in the amount of the low-affinity component but no change in the high-affinity component. 7. The dissociation constants of the binding of cholic acid suggest that the binding proteins may be involved in bile acid transport.     

Adenoid squamous carcinoma of the conjunctiva--a clinicopathological study of 14 cases

Idiopathic or congenital coronary artery ectasias and aneurysms are uncommon forms of coronary artery disease. The prognosis and optimal management of such patients remains unknown. The authors describe the case of an otherwise healthy 30-year-old man with concomitant severe right coronary artery ectasia and left main coronary artery aneurysm who sustained a mild anterior myocardial infarction. There was no obstructive coronary artery disease, and no cause for the lesions could be identified. Chronic anticoagulation and antiplatelet therapy were initiated with resolution of symptoms.     

Cisapride reduces neonatal postoperative ileus: randomised placebo controlled trial

AIM: To assess the efficacy of cisapride in reducing ileus persisting to the tenth postoperative day after neonatal abdominal surgery. METHODS: A prospective, randomised, double blind trial comparing rectal cisapride (1.4-2.3 mg/kg/day) with placebo over seven days was undertaken in 33 neonates. RESULTS: Seven of 12 (58%) patients receiving placebo and eight of 11 (73%) receiving cisapride achieved a first sustained feed during treatment. Of those receiving cisapride, the first sustained feed occurred at 2.3 days (SEM 0.6) compared with 4.7 days (SEM 0.8) with placebo. By the seventh day the mean daily net enteral balance was 69 (SEM 18) ml/kg in the cisapride subgroup and 17 (SEM 8) ml/kg for those receiving placebo. Stool was passed on 6.3 (SEM 0.4) treatment days in the cisapride subgroup compared with 4.1 (SEM 1.0) treatment days in the placebo subgroup. CONCLUSION: Cisapride is effective in neonates with a prolonged ileus after abdominal surgery.     

A pilot study of lithium carbonate plus divalproex sodium for the continuation and maintenance treatment of patients with bipolar I disorder

PURPOSE OF STUDY: To assess whether selected periapical radiographs, taken according to High Yield Criteria, can reveal as much intra-osseous pathology as universal panoramic screening. POPULATION STUDIED: The records of 1101 RAF recruits enlisted in 1988-89, average age 19 years (range 16-26). METHODS: The clinical records and bitewing radiographs of the recruits were examined and the requirement for periapical radiographs determined according to high yield criteria. A template, cut out to simulate the area covered by a periapical bitewing radiograph, was placed over the suspect region on the panoramic film and any findings found within the template recorded. The entire dental panoramic tomograph was then examined on a masked screen under 2X magnification and any further findings recorded. FINDINGS: There was a considerable number of findings reported, including three large isolated radiolucent areas, 75 periradicular radiolucent areas, four probable cysts and 1187 unerupted mandibular third molars. However, when the clinical significance of these 'lesions' was assessed only those related to dental causes appeared to have significant clinical implications and the results indicated that these could have been detected by selective radiology. CONCLUSION: This study showed that the only pathology which occurs frequently enough to justify radiographic screening of the jaws in young adults is related to teeth. It seems probable that this type of pathology can be at least as well detected by selective periapical screening, using high yield criteria, as is possible by universal panoramic screening.     

Glutathione and catalase provide overlapping defenses for protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae

Glutathione (GSH) is an abundant and ubiquitous low-molecular-weight thiol which has proposed roles in many cellular processes including protection against the deleterious effects of reactive oxygen species. Our experiments have addressed the role of GSH in protection against hydrogen peroxide in the yeast Saccharomyces cerevisiae, and have shown that GSH and catalase provide overlapping defense systems. GSH appears to be the primary antioxidant for protection against hydrogen peroxide since mutants lacking GSH (gsh1) or glutathione reductase (glr1) are sensitive, whereas, strains lacking catalase A (cta1) or catalase T (ctt1) are unaffected in resistance to this oxidant. Furthermore, following treatment with hydrogen peroxide, the levels of oxidized, protein-bound and extracellular GSH were all increased at the expense of intracellular GSH. However, there are two lines of evidence that indicate catalases are required in the absence of GSH; firstly, strains that lack both catalase A and T accumulate increased levels of oxidized glutathione following treatment with hydrogen peroxide; and secondly, deletion of catalase genes exacerbates the hydrogen peroxide sensitivity of glr1 and gsh1 mutants.     

The synthesis and in vitro characterization of the mucoadhesion and swelling of poly(acrylic acid) hydrogels

Depression is a significant problem in epilepsy. Suicides occur in epileptic patients five times more often than in general population. Material included 34 epileptics with 76 suicidal attempts and 24 patients with no history of suicide. Psychical state was studied with Beck Depression Inventory and Hamilton Depression Rating Scale. In the group with suicidal attempts 65% of patients had depression (54.5% of them had major depression) and in group without suicide attempts depression was noted in 54% (23% with major depression). Patients with depression were divided into two groups: group I with suicidal attempts and group II without history of suicide. In group I more patients were alcohol abusers (50% vs 31%), more were treated because of epilepsy longer than 10 years (59% vs 46%) and more had tonic-clonic seizures (82% vs 46%). In group I, 54% of patients were on polytherapy (more than half of them with fenobarbital). In group II, 31% of epileptics were on polytherapy (no one with fenobarbital). Major depression was significantly more frequent in epileptics with suicidal attempts. The severity of depression may influence the risk of suicide. Major depression may be associated with late age of onset of epilepsy, longer treatment duration, tonic-clonic seizures, polytherapy (mainly with fenobarbital) and alcohol abuse.     

Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position

As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.