A comparison of body and organ weights, physiologic parameters, and pathologic changes in target organs of rats given combinations of exercise, anabolic hormone, and protein supplementation

This study was engineered to closely mimic the training protocol of a competitive athlete using repetitive exercise sessions, dietary protein supplementation, and anabolic steroids. The length of the study was 37 days. Thirty-four Sprague Dawley male rats Crl:CD(SD)BR in the weight range of 150 to 175 grams were used. These were randomly divided into four exercise groups, varying protein consumption and anabolic hormone administration. Eight nonexercised control rats were kept separate from the study to act as a comparison for organ weight, hematology, and serology. Exercise consisted of a 30 minute swim three times a week. Parameters recorded were total body weight and percent gain, wet and dry muscle weight of the isolated anterior tibialis, weights of designated organs, hematologic profiles, and serum chemistries including triglycerides, high density and low density lipids. Histopathology of known "target organs" was performed and bone marrow aspirates were taken. Body weights of rats given anabolic steroid, protein supplement, and exercise were the lowest of all groups. Testicular weight was significantly decreased in the anabolic groups. Anabolic groups had the lowest hematocrits of the exercised groups. All serology values were within normal ranges and no pathologic changes were seen in any of the tissues taken from specific "target organs."     

Effect of phenotypic variation on kin selection

An expression for the equilibrium of the mean phenotypic value of a quantitative character is derived for a model in which the fitness of an individual depends on its own phenotype and the mean phenotypic value of a group of related individuals. When selection is weak the equilibrium mean is well predicted by Hamilton's k > 1/r rule (k is the ratio of mean fitness gained by recipient of altruistic behavior to mean fitness lost by donor; r is mean coefficient of relationship between donor and recipient). When selection is strong, however, the equilibrium mean depends on the heritability of the character. Low heritability can lead to substantially more “altruism” than predicted by the k > 1/r rule.     

Loss of bone mineral density in Chinese pre-menopausal women with systemic lupus erythematosus treated with corticosteroids

The adverse effect of disease and chronic corticosteroid therapy on bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE) has been reported in several studies of Caucasian populations. As the factors controlling bone homeostasis may be different in Asian populations, we measured BMD in 52 pre-menopausal Chinese women (mean age 34.1 +/- 8.0 yr) with SLE (mean disease duration 6.4 +/- 4.5 yr) treated with prednisone (mean daily dose 11.4 +/- 10.8 mg/day). Lumbar spine, hip (total and subregions) and total body BMDs were measured in the SLE patients using dual-energy X-ray absorptiometry (DEXA), and compared with those from healthy controls matched for age, sex and body mass index. Compared to controls, SLE patients were found to have lower BMD (g/cm2) at several sites: the lumbar spine (0.98 vs 0.90, P = 0.001), Ward's triangle (0.72 vs 0.67, P = 0.03), total body (1.04 vs 1.01, P = 0.04) and total hip (0.87 vs 0.82, P = 0.05). There was no correlation between BMD at any region and duration of disease, activity of disease or prednisone therapy (mean daily dose, cumulative dose or treatment duration). When BMDs were compared between controls and SLE patients, subgrouped according to those not on calcium and those arbitrarily receiving calcium supplements (1 g/day), significantly lower BMDs were found in those not on calcium compared to both controls and SLE patients on calcium. BMDs in SLE patients on calcium were not different from those in controls. The low prevalence of osteoporosis in our SLE patients (4-6%) suggests significant loss of BMD in Chinese SLE patients on corticosteroid therapy is less than that reported in Caucasians (12-18%).      

Effect of exercise on the reproductive outcome and fetal development of diabetic rats

The aim of this study was to evaluate the effect of exercise on pregnancy outcome in streptozotocin-induced diabetic Wistar rats (n = 11 animals/group). These animals were randomly assigned to sedentary (G1) and exercised groups, beginning from day 0 (G2) or 7 (G3) to day 20 of pregnancy. The moderate exercise was a swimming programme. At day 21 of pregnancy, all rats were anaesthetized and killed to obtain pregnancy outcome data. All rats presented glycaemia higher than 300 mg/dl, regardless of the exercise training. The G3 group showed higher live fetus number per implantation site and lower resorption number per implantation site compared with the G1 group. The fetal and placental mean weights per litter and the total number of ossification sites were significantly lower in the exercised groups (P < 0.05). Placental index was lower in the G2 and G3 groups compared with the G1 group. The occurrence of skeletal anomalies indicated that exercise increased the number of altered fetuses. Thus, moderate exercise achieved better outcomes by increasing the number of live births and decreasing resorption. However, exercise increased skeletal anomalies and decreased fetal and placental weights.     

Vigabatrin induces tonic inhibition via GABA transporter reversal without increasing vesicular GABA release

Two forms of GABAergic inhibition coexist: fast synaptic neurotransmission and tonic activation of GABA receptors due to ambient GABA. The mechanisms regulating ambient GABA have not been well defined. Here we examined the role of the GABA transporter in the increase in ambient [GABA] induced by the anticonvulsant vigabatrin. Pretreatment of cultured rat hippocampal neurons with vigabatrin (100 microM) for 2-5 days led to a large increase in ambient [GABA] that was measured as the change in holding current induced by bicuculline during patch-clamp recordings. In contrast, there was a decrease in the frequency of spontaneous miniature inhibitory postsynaptic currents mIPSCs with no change in their amplitude distribution, and a decrease in the magnitude of IPSCs evoked by presynaptic stimulation during paired recordings. The increase in ambient [GABA] was not prevented by blockade of vesicular GABA release with tetanus toxin or removal of extracellular calcium. During perforated patch recordings, the increase in ambient [GABA] was prevented by blocking the GABA transporter, indicating that the GABA transporter was continuously operating in reverse and releasing GABA. In contrast, blocking the GABA transporter increased ambient [GABA] during whole cell patch-clamp recordings unless GABA and Na(+) were added to the recording electrode solution, indicating that whole cell recordings can lead to erroneous conclusions about the role of the GABA transporter in control of ambient GABA. We conclude that the equilibrium for the GABA transporter is a major determinant of ambient [GABA] and tonic GABAergic inhibition. We propose that fast GABAergic neurotransmission and tonic inhibition can be independently modified and play complementary roles in control of neuronal excitability.     

Chemosensitive serotonergic neurons are closely associated with large medullary arteries

We have previously shown that serotonergic neurons of the medulla are strongly stimulated by an increase in CO(2), suggesting that they are central respiratory chemoreceptors. Here we used confocal imaging and electron microscopy to show that neurons immunoreactive for tryptophan hydroxylase (TpOH) are tightly apposed to large arteries in the rat medulla. We used patch-clamp recordings from brain slices to confirm that neurons with this anatomical specialization are chemosensitive. Serotonergic neurons are ideally situated for sensing arterial blood CO(2), and may help maintain pH homeostasis via wide-ranging effects on brain function. The results reported here support a recent proposal that sudden infant death syndrome (SIDS) results from a developmental abnormality of medullary serotonergic neurons.     

Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation in coronary artery bypass surgery.

The cost-effectiveness of amiodarone prophylaxis of atrial fibrillation (AF) in patients undergoing coronary artery bypass grafting (CABG) was determined. A decision analysis using current hospital data and values from the literature was conducted. Under the base-case scenario, CABG patients received usual care (no prophylaxis) or 2 g of oral amiodarone hydrochloride over one to three days before surgery and 400 mg daily for seven days after surgery. Costs of hospitalization in the intensive care unit (ICU) and the cardiac step-down unit (SDU), cardioversion costs, electrocardiogram costs, drug costs, nursing administration charges, and pharmacy i.v. admixture charges were included. A sensitivity analysis using a Monte Carlo simulation and a one-way sensitivity analysis were performed. The mean cost per AF event avoided was lower in the amiodarone group ($15,750, 95% confidence interval [CI]: $15,591-$15,999) than the control group ($17,426,95% CI: $17,252-$17,600). A majority of the cost difference was due to the cost of hospitalization for patients without AF, the frequency of AF, and the cost of hospitalization in the SDU for patients with AF. For patients treated with amiodarone who did not develop AF, the cost difference was sensitive to changes in the cost of hospitalization and the efficacy of amiodarone. For patients who did develop AF, the cost difference was robust. Prophylaxis of AF with amiodarone in CABG patients was more cost-effective than usual care in the short term from a hospital perspective; the results were sensitive to changes in the cost of hospitalization of patients who did not develop AF and the efficacy of amiodarone.     

(-)-Epigallocatechin-3-gallate inhibition of ultraviolet B-induced AP-1 activity

Green tea polyphenols have been shown to inhibit cancer in a variety of tumor models, including ultraviolet B (UVB)-induced non-melanoma skin cancer. In green tea extracts, the major dry mass constituent is the family of catechins, of which (-)-epigallocatechin-(3)-gallate (EGCG) is considered to be important for the chemopreventive activity. EGCG has been shown to have antioxidant properties, but there has been little progress toward identifying the specific targets and mechanisms of its action. Using cultured human keratinocytes, we show that UVB- induced AP-1 activity is inhibited by EGCG in a dose range of 5.45 nM to 54.5 microM. EGCG is effective at inhibiting AP-1 activity when applied before, after or both before and after UVB irradiation. EGCG also inhibits AP-1 activity in the epidermis of a transgenic mouse model. This work begins to define a mechanism by which EGCG could be acting to inhibit UVB-induced tumor formation.