Circadian and cAMP-dependent modulation of retinal cone cGMP-gated channels does not require protein synthesis or calcium influx through L-type channels

Circadian oscillators of chicken retinal cone photoreceptors modulate the gating properties of cGMP-gated channels (CNGCs) such that they have a higher apparent affinity for cGMP during the subjective night. This effect is driven in part by cAMP, which acts through Erk MAP kinase to initiate a cascade leading to modulation of CGNCs. Here, we show that cAMP effects on the gating properties CNGCs persist when protein synthesis is blocked. The effects is cAMP also persist when calcium influx through L-type channels is blocked by nitrendipine. The mechanisms whereby cAMP modulates CNGCs therefore differ from those previously reported to underline regulation of melatonin synthesis and secretion.     

Esophagorespiratory fistula: long-term results of palliative treatment with covered expandable metallic stents in 61 patients

PURPOSE: To evaluate long-term clinical results of palliative treatment of esophagorespiratory fistulas (ERFs) with covered expandable metallic stents. MATERIALS AND METHODS: Sixty patients with ERFs due to esophageal or bronchogenic carcinoma and one patient with ERF due to pressure necrosis caused by initial esophageal stent placement for esophageal carcinoma were treated with covered expandable esophageal or tracheobronchial metallic stents. Information about technical success of stent placement, initial clinical success and failure, fistula reopening, and complications was obtained. Survival curves for both patient groups with initial clinical success and failure were obtained and compared with Kaplan-Meier methods and log-rank test. RESULTS: Stent placement was technically successful in all patients, with no immediate procedural complications. The stent completely sealed off the fistula in 49 (80%) of 61 patients so that they had no further aspiration symptoms (initial clinical success). Twelve (20%) of 61 patients had persistent aspiration symptoms due to incomplete ERF closure (initial clinical failure). During follow-up, the fistula reopened in 17 (35%) of 49 patients with initial clinical success: In eight patients, the reopened ERF was sealed off successfully with stent placement or balloon dilation. In two patients with reopened ERF caused by food impaction, the reopened fistula resolved spontaneously. Seven patients did not undergo further treatment. All patients died during follow-up, and mean survival was 13.4 weeks (range, 1-56 weeks) after stent placement. Mean survival in patients with initial clinical success was significantly longer than that in patients with initial clinical failure (15.1 vs 6.2 weeks, P <.05). CONCLUSION: Covered expandable metallic stents were placed in 61 patients with ERFs, but the initial clinical success rate was poor and the rate of reopening was high; however, interventional treatment was effective for sealing off reopened ERFs. Copyright RSNA, 2004     

Effects of ginsenosides Rg<Subscript>3</Subscript> and Rh<Subscript>2</Subscript> on the proliferation of prostate cancer cells

Ginseng has an anti-cancer effect in several cancer models. This study was to characterize active constituents of ginseng and their effects on proliferation of prostate cancer cell lines, LNCaP and PC3. Cell proliferation was measured by [3H]thymidine incorporation, the intracellular calcium concentration by a dual-wavelength spectrophotometer system, effects on mitogen-activated protein (MAP) kinases by Western blotting, and cell attachment and morphologic changes were observed under a microscope. Among 11 ginsenosides tested, ginsenosides Rg3 and Rh2 inhibited the proliferation of prostate cancer cells. EC50s of Rg3 and Rh2 on PC3 cells were 8.4 microM and 5.5 microM, respectively, and 14.1 microM and 4.4 microM on LNCaP cells, respectively. Both ginsenosides induced cell detachment and modulated three modules of MAP kinases activities differently in LNCaP and PC3 cells. These results suggest that ginsenosides Rg3 and Rh2-induced cell detachment and inhibition of the proliferation of prostate cancer cells may be associated with modulation of three modules of MAP kinases.     

Reduced high serum hepatocyte growth factor levels after successful cardioversion in patients with atrial fibrillation

1. Serum hepatocyte growth factor (HGF) is considered to be a potent marker of vascular endothelial injury. The present study was designed to examine serum HGF levels in atrial fibrillation and after successful direct current (DC) cardioversion. 2. We measured serum HGF levels before and 7 days and 1 month after DC cardioversion in 39 patients with atrial fibrillation in whom sinus rhythm was maintained for at least 7 days after DC cardioversion and in 30 age- and sex-matched normal control subjects with sinus rhythm. We also measured acetylcholine-induced changes in forearm blood flow (FBF) using venous occlusive plethysmography in 10 patients. 3. Serum HGF levels were significantly higher in the atrial fibrillation patients (both lone atrial fibrillation and with underlying heart disease) than in the controls (0.16 +/- 0.07 vs 0.10 +/- 0.04 ng/mL; P < 0.001). Seven days after successful DC cardioversion, the patients' serum HGF levels had decreased significantly (0.16 +/- 0.07 vs 0.12 +/- 0.06 ng/mL; P < 0.05) and in the 24 patients maintaining sinus rhythm 1 month after DC cardioversion, serum HGF levels decreased to control values (0.10 +/- 0.08 ng/mL at 1 month). Serum HGF levels of the 15 patients who had relapsed into atrial fibrillation 1 month after DC cardioversion tended to decrease 7 days after DC cardioversion, but increased again 1 month after DC cardioversion. Percentage changes in FBF between baseline and the highest dose of acetylcholine before and after DC cardioversion were 180 +/- 98 and 323 +/- 196%, respectively (P = 0.0051). The rate of increase in FBF at the highest dose of acetylcholine between before and after DC cardioversion correlated negatively with the rate of decrease in serum HGF levels between before and after DC cardioversion (r = -0.837; P = 0.0025). 4. This study is the first to demonstrate that serum HGF levels increase in atrial fibrillation and decrease after successful DC cardioversion. This may reflect the fact that atrial fibrillation induces vascular endothelial injury.     

Polymorphic metabolic susceptibility genes and longevity: a study in octogonarians

In order to investigate possible associations of genetic variants in genes of xenobiotic metabolism with longevity, we compared allele frequencies and genotype distributions of polymorphic genes between 205 octogenarians and a non-cancer reference group of 294 persons aged less than 80 years. We analyzed common sequence variations in the cytochrome P-450 genes CYP1A1 T461N, 3801 T > C and CYP1B1 V432L, and in the glutathione S-transferase genes GSTM1 (deletion), GSTT1 (deletion), and GSTP1 (I105V). In octogenarians, the CYP1B1 432L allele was less prevalent than in the reference group (allele frequency 0.49 versus 0.60; odds ratio, OR, 0.63, 95% confidence limits (CI) 0.40-1.00). Octogenarians turned out to have marginally significant more GSTM1 negatives (frequency 0.56 versus 0.48; OR 1.41, 95% CI 0.97-2.05), but less GSTT1 deficient genotypes (frequency 0.14 versus 0.21; OR 0.64; 95% CI 0.38-1.06). In octogenarians without cancer, GSTT1 negative carriers were less prevalent than in the aged with cancer (frequency 0.12 versus 0.27; OR 2.81; 95% CI 1.00-7.38). Polymorphic metabolic susceptibility genes could become relevant for processes of aging when toxic defense mechanisms decline.     

Hydatidosis of the Orbit in Turkey: Results from Review of the Literature 1963–2001

Hydatidosis can involve almost every organ or tissue in the body via the systemic circulation, but hydatid infestation of the orbit comprises far less than 1% of the total incidence. This study investigated the data on all patients of orbital hydatid disease reported in Turkey since 1963. In this meta-analysis, a total of 25 patients were included and slowly progressive unilateral proptosis, with or without pain, was the most frequent clinical manifestation (80%). The other presenting symptoms were visual loss (48%), periorbital pain (24%), chemosis (16%), and headache (12%). The presumptive diagnosis of hydatid cyst was made on the images obtained from ultrasonography (US), computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations. These diagnostic studies demonstrated a well-circumscribed cystic mass in almost all patients. Total surgical removal without rupture remains the best mode of therapy for orbital hydatid disease. The study indicates that in Turkey hydatidosis remains a serious problem, causing blindness. Orbital hydatid cyst should be included in the differential diagnosis of unilateral proptosis and visual handicap in patients from countries where hydatidosis is endemic. This material was used in part for a poster presentation at the XXth International Congress of Hydatidology, 4–8 June 2001 in Kutadası, Turkey.     

Flumazenil-induced ballism

Flumazenil, an imidazobenzodiazepine, is the first benzodiazepine antagonist and is being used to reverse the adverse pharmacological effects of benzodiazepine. There have been a few reports on the central nevous system side effects with its use. We report a patient with generalized ballism following administration of flumazenil. The mechanism through which flumazenil induced this symptom is unknown. It is conceivable that flumazenil may antagonize the GABA-benzodiazepine receptor complex and induce dopamine hypersensitivity, thus induce dyskinesic symptoms.     

Roles of glial cells in the formation, function, and maintenance of the neuromuscular junction

Like other vertebrate synapses, the neuromuscular junction (NMJ) has glial cells that are closely associated with the pre- and post-synaptic components. These "perisynaptic Schwann cells" (PSCs) cover nerve terminals and are in close proximity to the synapse, yet their role at the NMJ has remained mysterious for decades. In this review we explore historical perspectives on PSCs and highlight key developments in recent years that have provided novel insight into PSC functions at the NMJ. First among these developments is the generation of specific antibody probes for PSCs. Using one such antibody and the principle of complement-mediated cell lysis, we have developed a novel technique to selectively ablate PSCs en masse from frog NMJs in vivo. Applying this approach, we have shown that PSCs are essential for the long-term maintenance of synaptic structure and function. In addition, PSCs are essential for the growth and maintenance of NMJs during development. Probes for PSCs also allow us to observe in vivo that processes extended by PSCs guide nerve terminals during synapse development, remodeling, and regeneration. PSCs may therefore dictate the pattern of innervation at the NMJ. Finally, PSCs may also induce postsynaptic acetylcholine receptor expression and aggregation. This wealth of recent findings about PSCs suggests that these synapse-associated glial cells are a more integral and essential component of the NMJ than previously appreciated. New approaches currently being applied at the NMJ may further support the emerging view that glial cells help make bigger, stronger, and more stable synapses.     

Alcohol consumption and the risk of borderline and invasive ovarian cancer

OBJECTIVE: To examine the hypothesis that alcohol consumption is associated with the risk of ovarian cancer by conducting a population-based, case-control study in Hawaii and Los Angeles, California. METHODS: In-person interviews were obtained from 558 women with ovarian cancer and 607 population controls regarding lifetime alcohol consumption and other factors that may be related to the development of ovarian cancer. RESULTS: We found no overall association of alcohol drinking with the odds ratios (OR) for ovarian cancer. However, current alcohol drinkers, but not former drinkers, had a significantly lower OR for ovarian cancer compared with never drinkers (OR 0.69, 95% confidence interval [CI] 0.50, 0.96). Odds ratios for ovarian cancer associated with the current consumption of beer, wine, and spirits were also reduced, but were only significant for wine drinkers. Among current wine drinkers, women who drank red wine had a significantly reduced OR for ovarian cancer compared with never drinkers (OR 0.61, 95% CI 0.39, 0.94). The inverse association of current alcohol drinking with the OR for ovarian cancer was restricted to invasive tumors, especially the endometrioid cell type. The number of glasses of alcohol consumed on a weekly basis was inversely related to the OR for invasive ovarian cancer (P =.009): Current drinkers consuming 14 or more drinks per week had an OR of 0.36 (95% CI 0.19, 0.70) compared with never drinkers. A significantly increased risk of borderline serous tumors was associated with the use of spirits (OR 2.66, 95% CI 1.46, 4.85). The risk for borderline mucinous tumors was also significantly elevated for former wine drinkers.CONCLUSIONS: These findings suggest that the association of alcohol consumption with the OR for ovarian cancer may vary by alcohol type, tumor invasiveness, and histology.