Melatonin reduces nitric oxide synthase activity in rat hypothalamus

Abstract: In this report, rat hypothalamic nitric oxide synthase (NOS) activity is shown to be partially inhibited by physiological concentrations of the pineal hormone melatonin. In vitro studies demonstrate that 1 nM melatonin, which approximates the physiological concentration of the hormone at night, significantly inhibited NOS activity. In vivo studies show that administering melatonin or collecting the hypothalamus from animals at night, when endogenous melatonin levels are elevated, results in a significant decrease of NOS activity. Results also show that calmodulin may be involved in this process since its presence in the incubation medium prevents the inhibitory effect of melatonin on NOS activity.     

Endoscopic stapling diverticulotomy: an audit of difficulties, outcome, and patient satisfaction.

OBJECTIVE: To evaluate the procedure in terms of technical difficulties, patient satisfaction, symptom relief, recurrence, and further management. STUDY DESIGN: Retrospective study including 41 patients who underwent endoscopic stapling diverticulotomy. Clinical notes were reviewed, and patients were sent a patient satisfaction questionnaire. Statistical analysis was done using the chi(2) square test. SETTING: Teaching hospital. RESULTS: Larger pouches had the best results; 81.578% were satisfied with the surgery, and 86.84% had improved swallowing. Complications presented in 6 patients (15%), including a perforated pouch and an esophageal perforation. Complications were more frequent in small pouches. CONCLUSIONS AND SIGNIFICANCE: Endoscopic stapling diverticulotomy offers rapid recovery in most patients, with early oral intake and short hospital stay. There is a high degree of symptoms relief, and the patient's satisfaction rate is high. The assessment of the pharyngeal pouch size is an important factor when deciding the best management for a patient with a pharyngeal pouch.     

Ontogenetic Development of 5-HT1D Receptors in Human Brain: An Autoradiographic Study

The pattern of pre- and postnatal appearance of 5-HT_1D receptors throughout the different areas of the human brain was studied by quantitative in vitro autoradiography, using [¹²⁵I]GTI (serotonin O -carboxymethyl-glycyl-[¹²⁵I]tyrosinamide) as a ligand. The anatomical distribution of 5-HT_1D receptors in neonatal, infant and children's brain was in good agreement with that observed in the adult, the basal ganglia and substantia nigra being the most intensely labelled areas. The development of these receptors throughout the human brain was mainly postnatal: low densities of [¹²⁵I]GTI binding sites were observed at the fetal/neonatal stage in most regions analyzed, in contrast with the high levels of labelling found in infant and children's brains. Indeed, in a number of regions, including the globus pallidus, substantia nigra and visual cortex, a peak of overexpression of 5-HT_1D receptors was observed in the first decade of life. Such overexpression could support a regulatory role for 5-HT_1D receptors in advanced periods of the CNS developmental process. Our results also indicate that the administration of drugs acting on 5-HT_1D receptors during the early postnatal period of life could result in modifications of their properties, as these receptors are already functional in this period.     

Activity of the hypothalamic-pituitary-adrenal axis in mice selected for left- or right-handedness

Asymmetry in brain modulation of the immune system has been previously described. In mice, paw preference has been shown to be associated with immune reactivity but the mechanisms involved in such an association are not yet known. The autonomic nervous system and the neuroendocrine system are considered as major candidates for neural influences on the immune system. In the present study, the activity of the hypothalamic-pituitary-adrenal (HPA) axis of adult female mice selected for paw preference (left-handers vs. right-handers) was assessed by measuring both adrenocorticotropic hormone (ACTH) and corticosterone plasma levels, as well as the in vitro responses of hypothalamus and adrenocortical cells to various hormone releasing stimuli. The results reported here showed no difference in the activity of the HPA axis between left- and right-handed mice, suggesting that this neuroendocrine axis is not implicated in the association between functional brain asymmetry and immune reactivity. However, our results do not exclude the possibility that the HPA axis could play a role in such an association under other circumstances, such as during development or stressful situations.     

Human tonsil,blood and bone marrow in vivo-induced B cells capable of spontaneous and high-rate immunoglobulin secretion in vitro: Differences in the requirements for factors and for adherent and bone marrow stromal cells,as well as distinctive adhesion molecule expression

Human B cells capable of spontaneous IgG secretion are commonly found in circulation and in lymphoid tissues such as tonsil and bone marrow (BM). The present study compares the mechanisms that regulate tonsil, blood and BM B cells capable of spontaneous IgG secretion. The BM cell subset produced IgG during a markedly longer period of time (14 days) than did tonsil and blood cell subsets (2–3 days). Blood and BM, but not tonsil, B cell IgG secretion depended on the presence of adherent cells, as demonstrated by adherent cell depletion and re-addition experiments. Stromal BM cells supported linear IgG secretion by non-adherent BM cells for 2 weeks, but were unable to prolong the short-term IgG secretion by tonsil and blood cells. Different factors induced IgG secretion in each of the three B cell populations as optimal IgG secretion by tonsil, blood or BM cell subsets required either tumor necrosis factor-α, interleukin-6 or fibronectin + interleukin-6, respectively. Finally, these populations also showed differences in the expression of adhesion molecules; the tonsilar cell subset was PNA^+/? CD44⁺ CD49d⁺ CD49e^? Leu-8^+/?, the blood cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8⁺ and the BM cell subset was PNA^? CD44^+/? CD49d⁺ CD49e^? Leu-8^?. These results suggest that the mechanisms controlling the final differentiation and the expression of adhesion molecules in these B lymphocytes exhibit territorial specificity.     

Cholesterol-lowering drugs and advanced prostate cancer incidence in a large U.S. cohort.

BACKGROUND: 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors, commonly known as statins, account for the great majority of cholesterol-lowering drug use in the United States. Long-duration statin use was associated with substantially reduced risk of advanced prostate cancer in a recent large prospective study. METHODS: We examined the association between use of cholesterol-lowering drugs and prostate cancer incidence by disease stage and grade among 55,454 men in the Cancer Prevention Study II Nutrition Cohort. Proportional hazards modeling was used to calculate RRs. RESULTS: During follow-up from 1997 to 2003, we identified 3,413 cases of incident prostate cancer, including 317 cases of advanced prostate cancer. After adjustment for age, history of prostate-specific antigen testing, and other potential prostate cancer risk factors, current use of cholesterol-lowering drugs for 5 or more years was not associated with overall prostate cancer incidence (multivariate adjusted rate ratio, 1.06; 95% confidence interval, 0.93-1.20), but was associated with a marginally statistically significant reduction in risk of advanced prostate cancer (rate ratio, 0.60; 95% confidence interval, 0.36-1.00). CONCLUSION: These results provide some support for the hypothesis that long-term statin use is associated with reduced risk of advanced prostate cancer.     

Degradation of extracellular matrix proteins (fibronectin, vitronectin and laminin) by serine-proteinases isolated from Lonomia achelous caterpillar hemolymph.

Lonomia achelous is a caterpillar distributed in southern Venezuela and in northern Brazil that causes an acute hemorrhagic syndrome in people who have contact with its bristles. The effect of the crude hemolymph and its chromatographic fractions (FDII, Lonomin V and Lonomin V-2) on extracellular matrix proteins was studied. The chromatographic fractions show activities similar to plasmin and urokinase. In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, both lonomins appear as a protein band of 25 kDa under reduced conditions. By exclusion chromatography, the molecular weights of Lonomin V and Lonomin V-2 were 26.5 and 24.5 kDa, respectively. Fibronectin, laminin and vitronectin were degraded by all venom components. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, under reduced conditions, shows that lonomins degrade fibronectin in four main fragments of 116, 60, 50 and 30 kDa. Molecular exclusion chromatography in native conditions shows that the molecular masses of these fragments are > or = 300, 62 and 27 kDa. The proteolytic effect of lonomins was abolished by benzamidine/HCl, iodoacetic acid and aprotinin. The extracellular matrix protein degradation together with the fibrino(geno)lytic activity of hemolymph and its fractions could explain, in part, the hemorrhagic syndrome, and the wound dehiscence in persons who have had contact with the L. achelous caterpillar.     

Experience with hemoperfusion for organophosphate poisoning.

OBJECTIVE: To evaluate the usefulness of extracorporeal clearance techniques in the treatment of organophosphate poisoning, particularly hemoperfusion. DESIGN: Retrospective study. SETTING: An ICU of a general hospital. PATIENTS: Ten patients with organophosphate poisoning initially received classic treatment with gastric lavage and washing of the whole skin surface, as well as the administration of cathartics, activated charcoal, atropine, and obidoxime or pralidoxime. All patients underwent one to three hemoperfusions. MEASUREMENTS AND MAIN RESULTS: Plasma insecticide concentrations and cholinesterase activity were determined daily. Two to three biopsies of fat tissue were carried out at 1- to 2-wk intervals. The amount of the insecticide removed during hemoperfusions was also determined. Five patients presented with a prolonged nicotinic syndrome. Two of these patients showed sequelae of delayed neurotoxicity. Another two of the five patients died and the remaining patient recovered without sequelae. In none of the patients could > 0.1% of the total absorbed poison be removed by hemoperfusion. No changes in symptoms were observed after these procedures. Fat tissue concentrations of the insecticide were 20 to 50 times higher than the concentrations in plasma. Atropine decreased the intestinal transit time, and 10 days after poisoning, a powerful cathartic treatment indicated the persistence of gut content, which probably caused prolonged absorption of the toxin. CONCLUSIONS: Extracorporeal cleansing mechanisms did not remove any clinically important amount of insecticide from our patients due to the high lipid solubility of these agents and no changes in symptoms were observed after these methods. The use of atropine decreases bowel peristalsis. Early use of powerful cathartics could avoid protracted absorption of the poison stored in the gut, although the potential benefits of this therapy require confirmation by the performance of prospective, controlled investigations.     

Cognitive profiles of individual patients with Parkinson's disease and dementia: comparison with dementia with lewy bodies and Alzheimer's disease.

We describe the pattern of cognitive profiles within a community-based sample of patients with Parkinson's disease (PD) and dementia (PDD) using cluster analyses, and compare the results with data from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Fifty patients with PDD and 39 with AD from Stavanger, Norway, and 62 patients with DLB from San Diego, CA, USA were diagnosed by either standardized clinical procedures or criteria (all PDD and all AD cases) or necropsy (all DLB cases). Four subgroups were identified: two subgroups with a subcortical cognitive profile (one with mild and one with moderate dementia severity), one subgroup with global impairment and severe dementia, and one subgroup with a cortical cognitive profile and moderate dementia. Of the patients with PDD and with DLB, 56% and 55%, respectively, had a subcortical cognitive profile, compared with only 33% of the AD patients. Conversely, 30% of the patients with PDD and 26% of those with DLB had a cortical cognitive profile, compared with 67% of the patients with AD. These findings suggest that in some patients with PDD, frontosubcortical changes are the main contributing factor to dementia, whereas in other patients, cortical and hippocampal changes are more important.