Enhancement of performance by methyl β-carboline-3-carboxylate, in learning and memory tasks

Benzodiazepines are known to induce a profound anterograde amnesia in man. In this report, it is shown that methyl β-carboline-3-carboxylate (β-CCM), an inverse agonist of the benzodiazepine receptor, has the opposite effect; it enhances performance in learning and memory tasks. Three different learning models were used: habituation to a new environment and passive avoidance in mice and imprinting in chicks. The opposite effects of both β-CCM and the benzodiazepine diazepam were blocked by administration of the benzodiazepine receptor antagonist Ro 15-1788, provicling evidence that the benzodiazepine receptor is involved in these effects.     

Ascorbic acid, HDL, and total plasma cholesterol in the elderly

The relationships between ascorbic acid (plasma and dietary) and plasma HDL cholesterol (HDL-C), total plasma cholesterol (T-C) and T-C:HDL-C ratio were examined in a population of 235 males and 445 females, age 60-98 years. Many known or suspected determinants of HDL-C and T-C, including age, sex, triceps skinfold thickness, fasting blood glucose, alcohol intake, and others, were considered as covariates due to their potential confounding or modifying effects on the relationships under study. The results show that plasma ascorbic acid is significantly (p less than 0.05) correlated with HDL-C (r = 0.09), T-C:HDL-C (r = 0.10), but not with T-C (r = 0.03). There is a strong age interaction with the largest effect of ascorbic acid in the youngest age group studied (60-69 years). The effects of dietary ascorbic acid are similar but slightly reduced in magnitude.     

Lhermitte-Duclos disease

Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum) is a rare pseudo-neoplastic disorder of the cerebellum with typical MRI findings. A 25-year-old man presenting with progressive neck pain, dizziness, and impaired vision is reported. CT and MRI revealed a left cerebellar haemispheric mass and obstructive hydrocephalus. Lhermitte-Duclos disease was histologically confirmed after surgical removal of the lesion. The typical MRI appearance of a nonenhancing haemispheric cerebellar mass with preservation and exaggeration of the normal gyral pattern allows pre-operative diagnosis of this condition. The literature is reviewed and clinical presentation, radiology and histopathology are discussed.     

In Vitro Growth of Thymic Tumor Cell Lines from Xenopus

A spontaneous lymphoid thymus tumor was discovered in a male Xenopus of the MHC ff genotype. The tumor cell can be transplanted in histocompatible larval ff hosts, but not in ff adults unless irradiated (3000 rad). The tumor is rejected by allogeneic hosts. The tumor cells express neither markers of the B-cell lineage nor MHC encoded molecules; they express only markers of the T-cell lineage. Its lymphoid population is clonal as revealed by the existence of a stable rearrangement pattern of the immunoglobulin genes. Cell lines growing continuously in vitro have been derived from the tumor.     

A three step supercritical process to improve the dissolution rate of eflucimibe.

The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.     

Pre-adaptation, adaptation and de-adaptation to high altitude in humans: hormonal and biochemical changes at sea level

High altitude residence is known to modify body biochemistry and hormone status. However, the effects of such a sojourn on these status observed at sea level both immediately and later after return are not as well established as are the effects of an intermittent acclimation. The aim of this study was therefore to investigate these changes. To achieve our objectives, nine subjects received intermittent acclimation at low pressure in a barometric chamber (8?h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m) before an expedition to the Himalayas. Hormonal and biochemical changes were studied using samples of venous blood taken at sea level before and after acclimation, after return from the expedition and 1 and 2 months after descent. Concentrations of thyroid hormones, adrenaline, noradrenaline (NA), hormones of hydromineral metabolism (aldosterone, renin, arginine vasopressin, atrial natriuretic peptide) as well as prolactin, cortisol, insulin and endothelin 1 were measured. Biochemical measurements made were plasma osmolality, and concentrations of glucose, total cholesterol, total proteins, pre-albumin, transferrin, complement 3C, apolipoproteins A₁ and B and serum iron. Acclimation induced no alteration in hormone (except for NA with increases of about 1.5, fold P<0.05) and biochemistry data. After the expedition, hormone responses were characterized by a higher total triidothyronine concentration (+18%, P<0.05) while other hormones did not vary. A linear relationship was found between thyroid-stimulating-hormone and body mass changes after the expedition (r=0.67, P<0.05). The observed increased concentrations of plasma proteins and total cholesterol (P<0.05) could be related to the restoration of lean body mass. At 1 and 2 months after return, no changes in hormones were observed but a significant decrease in transferrin concentration was noticed. The higher serum iron concentration reported after 1 month (P<0.05) could have been the result of a physiological haemolysis. It was concluded that both acclimation and the expedition in the Himalayas affected hormone status and body biochemistry status even though the observed changes were slight and rapidly reversed.     

Ginkgo biloba Extract (EGb 761) Pretreatment Limits Free Radical Oxidative Stress in Patients Undergoing Coronary Bypass Surgery

A growing body of evidence supports the trigger role of free radicals in the delayed functional and metabolic myocardial recovery following cardiopulmonary bypass (CPB) in humans, thus opening the field to specific therapies. This clinical study was designed to evaluate, in 15 patients undergoing aortic valve replacement, whether the extent of CPB- and reperfusion-induced lipid peroxidation, ascorbate depletion, tissue necrosis, and cardiac dysfunction is reduced by orally administered EGb 761, a Ginkgo biloba extract withpotent in vitro antiradical properties. Patients received either EGb 761 (Tanakan, 320 mg/day, n = 8) or a matching placebo (n = 7) for 5 days before surgical intervention. Plasma samples were obtained from the peripheral circulation and the coronary sinus at crucial stages of the operation (i.e., before incision, during ischemia, and within the first 30 minutes post-unclamping), and up to 8 days postoperatively. Upon aortic unclamping, EGb 761 inhibited the transcardiac release of thiobarbituric acid species (p ` 0.05), as assessed by high-performance liquid chromatography, and attenuated the early (5–10 minute) decrease in dimethylsulfoxide/ascorbyl free radical levels, an electron spin resonance index of the plasma ascorbate pool (p ` 0.05). EGb 761 also significantly reduced the more delayed leakage of myoglobin (p = 0.007) and had an almost significant effect on ventricular myosin leakage (p = 0.053, 6 days postoperatively). The clinical outcome of recovery of treated patients was improved, but not significantly, compared with untreated patients. Our results demonstrate the usefulness of adjuvant EGb 761 therapy in limiting oxidative stress in cardiovascular surgery and suggest the possible role of highly bioavailable terpene constituents of the drug.     

Differential Effect of Diarrhea on FK506 Versus Cyclosporine A Trough Levels and Resultant Prevention of Allograft Rejection in Renal Transplant Recipients

Diarrhea is the most frequently reported adverse event in patients treated with mycophenolate mofetil. Twenty-six renal transplant patients on a mycophenolate mofetil-based immunosuppressive regime with persistent afebrile diarrhea were examined. Diarrhea caused a significant rise in FK-506 trough levels despite intake of stable doses, necessitating FK-506 dose reductions of 30% to obtain pre-diarrhea trough levels. In contrast, trough levels of cyclosporine A remained stable without dose adjustments. This suggests that absorption and/or metabolism is differentially altered for FK506 compared with cyclosporine A in patients with diarrhea. In nine patients mycophenolate mofetil was reduced or stopped because of persistent diarrhea without identifiable cause. This resulted in end-stage renal disease because of chronic rejection in two patients, and in acute rejection in two patients, all taking FK506 and steroids. Therefore, dose adjustments of FK506 in patients with diarrhea must be carefully monitored, especially when doses of mycophenolate mofetil are also reduced.