Testosterone supplementation improves spatial and verbal memory in healthy older men.

OBJECTIVE: To determine the relationship between exogenous testosterone administration and cognitive abilities in a population of healthy older men. BACKGROUND: Serum levels of total and bioavailable testosterone gradually decrease with age in men and are associated with reductions in muscle mass, osteoporosis, decreased sexual activity, and changes in cognition. METHODS: Twenty-five healthy, community-dwelling volunteers, aged 50 to 80 years, completed a randomized, double-blind, placebo-controlled study. Participants received weekly intramuscular injections of either 100 mg testosterone enanthate or placebo (saline) for 6 weeks. Cognitive evaluations were conducted at baseline, week 3, and week 6 of treatment by use of a battery of neuropsychologic tests. RESULTS: Circulating total testosterone was raised an average of 130% from baseline at week 3 and 116% at week 6 in the treatment group. Because of aromatization of testosterone, estradiol increased an average of 77% at week 3 and 73% at week 6 in the treatment group. Significant improvements in cognition were observed for spatial memory (recall of a walking route), spatial ability (block construction), and verbal memory (recall of a short story) in older men treated with testosterone compared with baseline and the placebo group, although improvements were not evident for all measures. CONCLUSIONS: The results suggest that short-term testosterone administration enhances cognitive function in healthy older men. However, it remains unclear whether these improvements in cognition are attributable to increased testosterone or estradiol levels, or both. The potential role of testosterone vs its metabolites on cognition requires further research.     

The effects of inducing a follicular phase gonadotropin secretory pattern in normal women during the luteal phase

It has been hypothesized that the slowing of the luteinizing hormone (LH) pulse frequency in the luteal phase may be necessary for the demise of the corpus luteum, the intercycle rise in baseline follicle-stimulating hormone (FSH), or ovarian follicular development in the subsequent cycle. For assessment of the physiologic role of the luteal phase LH pulse pattern, this pattern was converted to a follicular pattern in six normal women who used exogenous gonadotropin-releasing hormone administered with a portable pump (dose 50 to 100 ng/kg subcutaneously every 90 minutes beginning in the early luteal [n = 3] and midluteal [n = 3] cycle phases). There was no significant difference between the treated and the subsequent cycle for luteal progesterone production [186.3 versus 159.0 (ng/ml) day], preovulatory follicular size (23.1 versus 22.5 mm), estradiol levels, luteal phase length (15.6 versus 14.3 days), and daily gonadotropin concentrations including the intercycle FSH rise (160.5 versus 139.1 ng/ml). A follicular phase gonadotropin pulse pattern (increased frequency, decreased amplitude) in the luteal phase had no discernible effects on the corpus luteum or on follicular development in the subsequent cycle.     

Gonadotropin-releasing hormone-induced changes in testosterone secretion in normal women

This study investigated the pattern of testosterone (T) secretion in spontaneous (n = 14) and gonadotropin-releasing hormone (GnRH)-treated (n = 6) menstrual cycles in normal women. In spontaneous cycles, T was found to increase progressively over the follicular phase (P less than or equal to 0.001), with the peak T value occurring on cycle day 0 (luteinizing hormone [LH] surge). The mean (+/- standard error of the mean [SEM]) T values on cycle day -14 and cycle day 0 were 35 +/- 4 and 51 +/- 4 ng/dl, respectively. GnRH was administered intravenously to six women at 1.3 to 1.7 micrograms per dose every 30 minutes in a study that assessed the ovarian effects of a rapid gonadotropin pulse frequency. In three of the women, the T levels followed a normal follicular phase pattern, whereas in the remaining three GnRH-treated women, there were marked increases in T with peak levels of 97, 123, and 81 ng/dl on day 0. The GnRH-treated subgroup with increased T levels had significantly increased follicular levels of LH, follicle-stimulating hormone (FSH), LH-bio and number of preovulatory ovarian follicles. This study demonstrated that increased levels of LH, FSH, and LH/FSH are capable of acutely increasing the secretion of ovarian androgens.     

Randomized controlled trial of dexamethasone treatment in very-low-birth-weight infants with ventilator-dependent chronic lung disease

This randomized controlled trial was designed to answer the question: does administration of dexamethasone to neonates with bronchopulmonary dysplasia decrease the need for assisted ventilation? Twenty-five infants with a birth weight < 1501 g, requiring mechanical ventilation and FiO₂ of ± 0.30 at 21-35 days of age, were randomized to treatment with iv dexamethasone or to sham injections for 12 days. The primary outcome criterion was extubation within seven days after study entry. Treatment (n= 12) and control (n= 13) groups were well matched at entry. Dexamethasone facilitated weaning from assisted ventilation (p= 0.0154). There was no increased incidence of infection. Dexamethasone treatment resulted in a significant increase in glucosuria (p= 0.0002) and in systolic blood pressure (p= 0.0034). There was a significant decrease in heart rate (p= 0.0001) and a significant weight loss (p= 0.0002) following dexamethasone treatment. Dexamethasone treatment facilitated weaning from assisted ventilation but several systemic effects were noted that deserve further evaluation before dexamethasone becomes routine treatment.     

HIV-1tat induced apoptosis of T-cells is not mediated by TGF-β

Recent reports have demonstrated that the HIV-1 transactivator protein,tat, induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood mononuclear cells, and stimulates a cascade of events resulting in up-regulation of the potent immunosuppressive cytokine, transforming growth factor-β (TGF-β). In this study we evaluated the ability of TGF-β to mediatetat induced apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF-β1 or a combination of tat and pan-specific TGF-β neutralizing antibodies showed little change in the amount of apoptosis. When treated with pan-specific TGF-β neutralizing antibodies, Jurkat cells that stably expresstat protein (Jurkat-tat) showed only a modest decrease in apoptosis, while CEM-TART cells (CEM T-cells expressing both HIV-1tat andrev) demonstrated little change in the amount of apoptosis. In conclusion, we have demonstrated that TGF-β does not play a significant role in mediatingtat induced T-cell apoptosis.     

Hetisine-type diterpenoid alkaloids from the Bhutanese medicinal plant Aconitum orochryseum

Investigation of Aconitum orochryseum, a Bhutanese traditional medicine ("gSo-ba Rig-pa") plant locally known as "Bong-kar", resulted in the isolation of three new hetisine-type diterpenoid alkaloids, named orochrine (1), 2-O-acetylorochrine (2), and 2-O-acetyl-7alpha-hydroxyorochrine (3), together with the previously reported alkaloids atisinium chloride (4) and virescenine (5). The structures of the new alkaloids were elucidated by spectroscopic data analysis.     

Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis

BACKGROUND: Studies in animals showed that the hippocampus, a brain area involved in learning and memory, is sensitive to stress. Although several MRI studies showed smaller hippocampal volume in adults with chronic PTSD, others did not show significant differences from controls. These studies are typified by small sample sizes which may limit the ability to show significant differences. We therefore performed a meta-analytic study of all of these studies to clarify the role of hippocampal structural changes in subjects with PTSD. METHODS: Nine studies with a total of 133 adult subjects with chronic PTSD, 148 healthy controls, and 53 traumatized controls were included in the meta-analysis. RESULTS: There was significantly smaller volume in both right and left hippocampi in adult subjects with chronic PTSD in comparison with both healthy controls and traumatized controls. CONCLUSION: These findings are consistent with smaller hippocampal volume in adult subjects with chronic PTSD.     

Lung cancer and cyclooxygenase-2

Lung cancer is by far the leading cause of cancer-related death. Overall survival is poor and has not improved substantially over the last half century. It is clear that new approaches are needed and these should include prevention, screening for early detection, and novel treatments based on our understanding of the molecular biology of this disease. Recently attention has been drawn to the role of the cyclooxygenase (COX) enzyme and its involvement in tumorigenesis. Investigations have documented two isoforms, COX-1 and COX-2, encoded by different genes. COX-1 is constitutively expressed in most tissues and appears to be responsible for the production of prostaglandins mediating normal physiologic functions, such as the maintenance of gastric mucosa and regulation of renal blood flow. In contrast, COX-2 is normally undetectable in most tissues, and is induced by cytokines, growth factors, oncogenes, and tumor promoters. A growing body of evidence indicates COX-2 plays a key role in lung cancer, and can serve as a potential marker of prognosis in this disease. Furthermore, the recent availability of COX-2 inhibitor medications offers a unique opportunity to interfere with the development of lung cancer and the progression of metastasis. Because COX-2 inhibitors have been demonstrated to interfere with tumorigenesis, the COX-2 enzyme may be an attractive target for therapeutic and chemoprotective strategies in lung cancer patients.     

Complications after sub-Tenon's eye block

IMPLICATIONS: The use of blunt instead of sharp needles for ophthalmic local anesthesia techniques has reduced the incidence of injury to intra-orbital structures. This case review of complications from blunt needle sub-Tenon's block suggests that sight-threatening or even life-threatening complications can still occur.