Rhabdomeric phototransduction initiated by the vertebrate photopigment melanopsin

Melanopsin is the photopigment that confers light sensitivity on intrinsically photosensitive retinal ganglion cells. Mammalian intrinsically photosensitive retinal ganglion cells are involved in the photic synchronization of circadian rhythms to the day-night cycle. Here, we report molecular components of melanopsin signaling using the cultured Xenopus dermal melanophore system. Photo-activated melanopsin is shown to initiate a phosphoinositide signaling pathway similar to that found in invertebrate photo-transduction. In melanophores, light increases the intracellular level of inositol trisphosphate and causes the dispersion of melanosomes. Inhibition of phospholipase C and protein kinase C and chelation of intracellular calcium block the effect of light on melanophores. At least four proteins, 43, 74, 90, and 134 kDa, are phosphorylated by protein kinase C upon light stimulation. This provides evidence of an invertebrate-like light-activated signaling cascade within vertebrate cells.     

Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA)

OBJECTIVE: To undertake a multicentre epidemiological study reflecting acromegaly in Spain. DESIGN: Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. METHODS: Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. RESULTS: Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). CONCLUSIONS: This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.     

Does washing medical devices before and after use decrease bacterial contamination?: An in vitro study

Surface treatment of medical devices may be a way of avoiding the need for replacement of these devices and the comorbidities associated with infection. The aim of this study was to evaluate whether pre- and postcontamination washing of 2 prostheses with different textures can decrease bacterial contamination.The following microorganisms were evaluated: Staphylococcus aureus, Staphylococcus epidermidis, Proteus mirabilis and Enterococcus faecalis. Silicone and expanded polytetrafluoroethylene vascular prostheses were used and divided into 3 groups: prostheses contaminated; prostheses contaminated and treated before contamination; and prostheses contaminated and treated after contamination. Treatments were performed with antibiotic solution, chlorhexidine and lidocaine. After one week of incubation, the prostheses were sown in culture medium, which was incubated for 48 hours. The area of colony formation was evaluated by fractal dimension, an image analysis tool.The antibiotic solution inhibited the growth of S epidermidis and chlorhexidine decrease in 53% the colonization density for S aureus in for both prostheses in the pre-washing. In postcontamination washing, the antibiotic solution inhibited the growth of all bacteria evaluated; there was a 60% decrease in the colonization density of S aureus and absence of colonization for E faecalis with chlorhexidine; and lidocaine inhibited the growth of S aureus in both prostheses.Antibiotic solution showed the highest efficiency in inhibiting bacterial growth, especially for S epidermidis, in both washings. Lidocaine was able to reduce colonization by S aureus in post-contamination washing, showing that it can be used as an alternative adjuvant treatment in these cases.     

A Decreased Response to Resistin in Mononuclear Leukocytes Contributes to Oxidative Stress in Nonalcoholic Fatty Liver Disease

Digestive Diseases and Sciences - Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of...     

Nitrogen‐containing bisphosphonate therapy: assessment of the alveolar bone structure in rats – a blind randomized controlled trial

This study aimed to assess the effect of zoledronic acid exposure on structures of the alveolar bone of rats. The sample was composed of 42 male Wistar rats. Animals in the T1 and T2 groups received weekly doses of 0.2 mg/kg intraperitoneal zoledronic acid for 3 weeks, while animals in the T3 group received the same treatment for 8 weeks. The control groups C1, C2 and C3 received equivalent doses of saline. The first upper molars of Wistar rats in the C2, T2, C3 and T3 groups were extracted. Cone‐beam computerized tomography scans were performed, and the image density was analysed by grey levels. The presence and type of inflammatory infiltrate, vascularization and bone necrosis were assigned by histological qualitative scores. Histomorphometric analysis of bone density was performed in the groups without extraction. No significant differences were found in the bone grey density estimated by grey‐level value and histomorphometric analysis between the C1 and T1 groups (P > 0.05). The grey levels in the T3 group were lower (P < 0.05) than in the C3 group, corresponding to the bone defect. Histological assessments showed the presence of bone necrosis in the T3 group and lower levels of bone remodelling in the test groups (T2 and T3) compared to the control groups (C2 and C3). The results of qualitative analyses did not differ significantly between the groups (P > 0.05). Zoledronic acid‐exposed animals showed maxillary changes including reduced grey levels, the presence of bone necrosis and a higher prevalence of inflammatory signs.     

Effects of cyclosporin A on water-immersion stress-induced gastric lesion and gastric secretion in rats

Cyclosporin A is an immunosuppressive agent which is well known as a specific inhibitor of calcineurin (protein phosphatase 2B). In this study, we investigated the effects of cyclosporin A on water-immersion stress-induced gastric ulcer formation and gastric acid secretion in rats. We also examined the localization of calcineurin immunohistochemically. Calcineurin was specifically expressed in gastric parietal cells and chief cells of the gastric mucosa. The intraperitoneal administration of cyclosporin A dose-dependently suppressed the development of gastric mucosal lesions induced by water-immersion stress and inhibited gastric acid secretion, as assessed by pylorus ligation. These results indicated that calcineurin may play an important role in gastric acid secretion. Received: October 14, 1999 / Accepted: January 28, 2000     

Results of treatment of acute myocardial infarction with thrombolytic therapy. Experiences in 437 patients in the coronary care unit of the National Institute of Cardiology "Ignacio Chavez"]

OBJECTIVE: To review the results and complications of thrombolysis in patients with acute myocardial infarction (AMI) and its complications. METHODS: Since june 1989 to august 1994 we studied patients with AMI, who underwent thrombolysis. Clinical characteristics, complications and angiographic results are described. RESULTS: Of the total population 86.3% patients received Streptokinase (SK) and 13.7% recombinant tissue plasminogen activator (rt-PA). In 20 patients the age was under 40 years, 373 between 40-70 years, and 80 patients over 70 years. 84% were men and 16% women. 72% had smoking habit; 21% diabetes mellitus, 43% hypertension, 54% had previous angina and previous AMI in 22%. The location of AMI was anterior in 234 patients and 239 inferior. In 63% enzyme washout was observed, and rapid electrocardiographic evolution in 81%. Postthrombolisis arrhythmias was observed in 64.7%. Major bleeding in 11.8% and central nervous system hemorrhage in 0.4% only with rt-PA. Postinfarction angina in 22%, and re-infarction in 4%. Cardiac rupture in 1.4%, with shock and death. Mitral insufficiency in 2.1% demonstrated by echocardiogram. Coronary angiography was done in 373 patients (80%), of which 50.7% was made in the first 5 days. The culprit artery was anterior descending in 273 patients and right coronary in 95. Left ventricular dysfunction was seen in 23% in patients with anterior AMI, and 5% with inferior AMI. Cardiogenic shock was seen in 7%. Coronary artery bypass grafting was undertaken in 106 patients and coronary angioplasty in 67. The ten days mortality was 8.8%, principally due to cardiogenic shock, ventricular arrhythmias and ventricular rupture. CONCLUSIONS: The usefull permeability in the culprit artery was obtained in 40%, who had coronary angiography done 145 hours posthrombolysis. Mortality was under 10% in this study.