Endothelial and neuronal nitric oxide synthase inhibitors influences angiotensin II pressor effect in central nervous system

The present study investigated the central role of angiotensin II and nitric oxide on arterial blood pressure (MAP) in rats. Losartan and PD123349 AT 1 and AT 2 (selective no peptides antagonists angiotensin receptors), as well as FK 409 (a nitric oxide donor), N W-nitro-L-arginine methyl ester (L-NAME) a constituve nitric oxide synthase inhibitor endothelial (eNOSI) and 7-nitroindazol (7NI) a specific neuronal nitric oxide synthase inhibitor (nNOSI) were used. Holtzman strain, (Rattus norvergicus) weighting 200-250 g were anesthetized with zoletil 50 mg kg -1 (tiletamine chloridrate 125 mg and zolazepan chloridrate 125 mg) into quadriceps muscle anda stainless steel cannula was stereotaxically implanted into their Lateral Ventricle (LV). Controls were injected with a 0.5 μl volume of 0.15 M NaCl. Angiotensin II injected into LV increased MAP (19±3 vs. control 3±1 mm Hg), which is potentiated by prior injection of L-NAME in the same site 26±2 mm Hg. 7NI injected prior to ANG II into LV also potentiated the pressor effect of ANG II but with a higher intensity than L-NAME 32±3 mm Hg. FK 409 inhibited the pressor effect of ANG II (6±1 mm Hg). Losartan injected into LV before ANG II influences the pressor effect of ANG II (8±1 mm Hg). The PD 123319 decreased the pressor effects of ANG II (16±1 mm Hg). Losartan injected simultaneously with FK 409 blocked the pressor effect of ANG II (3±1 mm Hg). L-NAME produced an increase in the pressor effect of ANG II, may be due to local vasoconstriction and all at once by neuronal NOS inhibition but the main effect is of the 7-NIT an specific nNOS inhibitor. The AT 1 antagonist receptors improve basal nitric oxide (NO) production and release. These data suggest the involvement of constitutive and neuronal NOS in the control of arterial blood pressure induced by ANG II centrally, evolving AT 1 receptor-mediated vasoconstriction and AT 2 receptor-mediated vasodilatation. These results were confirmed by the experiment using FK 409. © 2006 Asian Network for Scientific Information.

Effects of nitric oxide and arginine vasopressin on sodium intake induced by central angiotensin II. Part 2

We study the effects of angiotensin receptors antagonists, arginine vasopressin receptor antagonist, L-arginine and L-NAME, injected into supraoptic nucleus of the hypothalamus (SON) on sodium intake induced by the injection of angiotensin II (ANGII). Holtzman rats weighing 200-250 g with canulae implanted into the SON were used. The drugs were injected in 0.5 μL over 30-60 sec. Sodium intake after injection of saline SAL+SAL 0.15 M NaCl was 0.10±00.1 mL 2 h -1; SAL+ANGII injected into SON increased sodium intake. Losartan injected prior to ANGII into SON decreased sodium intake induced by ANGII. PD123319 injected prior to ANGII produced no changes in sodium intake induced by ANGII. AVPA receptor V 1 antagonist injected prior to ANGII reduced sodium intake with a less intensity than losartan. L-arginine injected prior to ANGII decreases sodium intake at a same intensity than losartan. L-NAME injected prior to ANGII potentiated sodium intake induced by ANGII. Losartan injected simultaneously with L-arginine prior to ANGII blocked the natriorexigenic effect of ANGII. These results confirm the importance of SON in the control of sodium intake. Also suggest that both AT 1 and arginine vasopressin V 1 receptors interact with nitrergic pathways within the SON influencing the sodium metabolism by changing sodium appetite induced by ANGII. © 2007 Asian Network for Scientific Information.

Goppa codes through polynomials of B[X;(1/2^2)Z_0] and its decoding principle

In this paper, we present a decoding principle for Goppa codes constructed by generalized polynomials, which is based on modified Berlekamp-Massey algorithm. This algorithm corrects all errors up to the Hamming weight $t\leq 2r$, i.e., whose minimum Hamming distance is $2^{2}r+1$.

Physical inactivity of adults and 1-year health care expenditures in Brazil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Endectocide activity of a pour-on formulation containing 1.5 per cent ivermectin +0.5 per cent abamectin in cattle

The present work aimed to evaluate, through ten different studies, the therapeutic efficacy of a new pour-on formulation, containing 1.5 per cent ivermectin +0.5 per cent abamectin, against parasites of cattle. Results obtained on trials against Rhipicephalus (Boophilus) microplus showed that the pour-on combination of 1.5 per cent ivermectin +0.5 per cent abamectin obtained superior efficacy indexes against this ectoparasite, when compared with formulations containing 0.5 per cent ivermectin, 1 per cent ivermectin and the combination of 1 per cent abamectin +20 per cent levamisole. The results of efficacy of the ivermectin+abamectin and the 0.5 per cent ivermectin against Haematobia irritans were similar. Against Cochliomyia hominivorax larvae, all pour-on formulations tested (1.5 per cent ivermectin +0.5 per cent abamectin, 0.5 per cent ivermectin and 0.5 per cent abamectin), as well as 1 per cent doramectin administered subcutaneously, were considered ineffective. Cattle medicated with 1.5 per cent ivermectin +0.5 per cent abamectin, pour-on, remained free from parasitism by Dermatobia hominis larvae during 42 days (96 per cent efficacy), while values superior to 90 per cent were obtained by 0.5 per cent ivermectin (92 per cent) and 0.5 per cent abamectin (93 per cent) until the 42nd and 35th days post treatment, respectively. Against Haemonchus placei and Oesophagostomum radiatum, the pour-on of ivermectin+abamectin showed better efficacy than the 0.5 per cent ivermectin and 0.5 per cent abamectin. As to Cooperia punctata, there was no difference regarding efficacy results obtained by the avermectins combination and abamectin. The pour-on combination of 1.5 per cent ivermectin +0.5 per cent abamectin obtained high efficacy against R. (B.) microplus, D. hominis and some species of cattle gastrointestinal helminths when compared with formulations of 0.5 per cent ivermectin and 0.5 per cent abamectin administered through the same route.

A label-free impedimetric immunosensor for direct determination of the textile dye Disperse Orange 1

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análises celulares e moleculares dos efeitos do peptídeo vasoativo angiotensina-(1-7) no processo tumoral pulmonar e a atuação do microrna 21-5P

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group

Background To determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated. Methods This was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years). Results Overall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001). Conclusions A majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.

ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H+-ATPase subcellular vesicle trafficking

The effect of angiotensin II (ANG II) or arginine vasopressin (AVP) alone or plus atrial natriuretic peptide (ANP) on H+-ATPase subcellular vesicle trafficking was investigated in MDCK cells following intracellular pH (pHi) acidification by exposure to20 mMNH4Cl for 2 min in a Na+-free solution containing Schering 28080, conditions under which H+-AT-Pase is the only cell mechanism for pHi recovery. Using the acridine orange fluorescent probe (5mM) and confocal microscopy, the vesicle movement was quantified by determining, for each experimental group, the mean slope of the line indicating the changes in apical/basolateral fluorescence density ratio over time during the first 5.30 min of the pHi recovery period. Under the control conditions, the mean slope was 0.079 ± 0.0033 min-1 (14) and it increased significantly with ANG II [10-12 and 10-7 M, respectively to 0.322 ± 0.038 min-1 (13) and 0.578 ± 0.061 min-1 (12)] or AVP [10-12 and 10-6 M, respectively to 0.301 ± 0.018 min-1 (12) and 0.687 ± 0.049 min-1 (11)]. However, in presence of ANP (10-6 M, decreases cytosolic free calcium), dimethyl-BAPTA/AM (5 × 10-5 M, chelates intracellular calcium) or colchicine (10-5 M, 2-h preincubation; inhibits microtubule-dependent vesicular trafficking) alone or plus ANG II or AVP the mean slopes were similar to the control values, indicating that such agents blocked the stimulatory effect of ANG II or AVP on vesicle trafficking. The results suggest that the pathway responsible for the increase in cytosolic free calcium and the microtu-bule-dependent vesicular trafficking are involved in this hormonal stimulating effect. Whether cytosolic free calcium reduction represents an important direct mechanism for ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H+-ATPase subcellular vesicle trafficking, or is a side effect of other signaling pathways which will require additional studies.

Lifestyle factors and colorectal cancer risk (1): systematic review and meta-analysis of associations with body mass index

OBJECTIVE: Excess body weight, defined by body mass index (BMI), may increase the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we undertook a systematic review and meta-analysis of prospective observational studies to quantify colorectal cancer risk associated with increased BMI and explore for differences by gender, sub-site and study characteristics. METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. Random-effects meta-analyses and meta-regressions of study-specific incremental estimates were performed to determine the risk ratio (RR) and 95% confidence intervals (CIs) associated with a 5 kg/m(2) increase in BMI. RESULTS: We analysed 29 datasets from 28 articles, including 67,361 incident cases. Higher BMI was associated with colon (RR 1.24, 95% CIs: 1.20-1.28) and rectal (1.09, 1.05-1.14) cancers in men, and with colon cancer (1.09, 1.04-1.12) in women. Associations were stronger in men than in women for colon (P < 0.001) and rectal (P = 0.005) cancers. Associations were generally consistent across geographic populations. Study characteristics and adjustments accounted for only moderate variations of associations. CONCLUSION: Increasing BMI is associated with a modest increased risk of developing colon and rectal cancers, but this modest risk may translate to large attributable proportions in high-prevalence obese populations. Inter-gender differences point to potentially important mechanistic differences, which merit further research.

Virological outcome and management of persistent low-level viraemia in HIV-1-infected patients: 11 years of the Swiss HIV Cohort Study

BACKGROUND Management of persistent low-level viraemia (pLLV) in patients on combined antiretroviral therapy (cART) with previously undetectable HIV viral loads (VLs) is challenging. We examined virological outcome and management among patients enrolled in the Swiss HIV Cohort Study (SHCS). METHODS In this retrospective study (2000-2011), pLLV was defined as a VL of 21-400 copies/mL on ≥3 consecutive plasma samples with ≥8 weeks between first and last analyses, in patients undetectable for ≥24 weeks on cART. Control patients had ≥3 consecutive undetectable VLs over ≥32 weeks. Virological failure (VF), analysed in the pLLV patient group, was defined as a VL>400 copies/mL. RESULTS Among 9972 patients, 179 had pLLV and 5389 were controls. Compared to controls, pLLV patients were more often on unboosted PI-based (adjusted odds ratio, aOR, [95%CI] 3.2 [1.8-5.9]) and NRTI-only combinations (aOR 2.1 [1.1-4.2]) than on NNRTI and boosted PI-based regimens. At 48 weeks, 102/155 pLLV patients (66%) still had pLLV, 19/155 (12%) developed VF, and 34/155 (22%) had undetectable VLs. Predictors of VF were previous VF (aOR 35 [3.8-315]), unboosted PI-based (aOR 12.8 [1.7-96]) or NRTI-only combinations (aOR 115 [6.8-1952]), and VLs>200 during pLLV (aOR 3.7 [1.1-12]). No VF occurred in patients with persistent very LLV (pVLLV, 21-49 copies/mL; N=26). At 48 weeks, 29/39 patients (74%) who changed cART had undetectable VLs, compared to 19/74 (26%) without change (P<0.001). CONCLUSIONS Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL ≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV >200 copies/ml.

Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case-control study using centralized ultrasensitive 454 pyrosequencing.

OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

Na 1 Nachlass Max Horkheimer, 568 - Korrespondenzen u.a. mit Margot von Mendelssohn (p. VI 28, 232-393)

133 Briefe zwischen Max Horkheimer und Margot von Mendelssohn; 2 Briefe zwischen Margot von Mendelssohn und Western Defense Command and Fourth Army (San Francisco), 1942; 1 Briefe an die Wartime Civil Control (San Francisco) von Margot von Mendelssohn, 1.12.1942; 1 Brief von Max Horkheimer an die Wartime Civil Control (San Francisco), [1942]; 3 Briefe an das Police Department (West Los Angeles) von Max Horkheimer, 1942; 1 Brief von Margot von Mendelssohn an L. M. Newberry, 03.09.1942; 1 Brief an L. M. Newberry von Max Horkheimer, 31.08.1942; 1 Brief von Max Horkheimer an U. S. Attorney (Los Angeles), 16.06.1942; 1 Brief von der Hebrew Sheltering and Immigrant Aid Society (New York) an Max Horkheimer, 29.10.1941; 1 Brief an das Department of State (Washington D. C.) von F. Pollock, 30.07.1941; 1 Brief von Leo Löwenthal an das Department of State (Washington D. C.), 28.07.1941;

Chemical analysis with regard to global and local climatic forcing measured on sediment core GeoB3711-1, GeoB3711-3 and GeoB4917-8

Global and local climatic forcing, e.g. concentration of atmospheric CO2 or insolation, influence the distribution of C3 and C4 plants in southwest Africa. C4 plants dominate in more arid and warmer areas and are favoured by lower pCO2 levels. Several studies have assessed past and present continental vegetation by the analysis of terrestrial n-alkanes in near-coastal deep sea sediments using single samples or a small number of samples from a given climatic stage. The objectives of this study were to evaluate vegetation changes in southwest Africa with regard to climatic changes during the Late Pleistocene and the Holocene and to elucidate the potential of single sample simplifications. We analysed two sediment cores at high resolution, altogether ca. 240 samples, from the Southeast Atlantic Ocean (20°S and 12°S) covering the time spans of 18 to 1 ka and 56 to 2 ka, respectively. Our results for 20°S showed marginally decreasing C4 plant domination (of ca. 5%) during deglaciation based on average chain length (ACL27-33 values) and carbon isotopic composition of the C31 and C33 n-alkanes. Values for single samples from 18 ka and the Holocene overlap and, thus, are not significantly representative of the climatic stages they derive from. In contrast, at 12°S the n-alkane parameters show a clear difference of plant type for the Late Pleistocene (C4 plant domination, 66% C4 on average) and the Holocene (C3 plant domination, 40% C4 on average). During deglaciation vegetation change highly correlates with the increase in pCO2 (r² = 0.91). Short-term climatic events such as Heinrich Stadials or Antarctic warming periods are not reflected by vegetation changes in the catchment area. Instead, smaller vegetation fluctuations during the Late Pleistocene occur in accordance with local variations of insolation.

Long chain 1,13- and 1,15-diols in surface sediments ans SST reconstruction for sediment core GeoB6518-1

Although commonly reported in marine and freshwater environments, little is known about the biological sources of long chain alkyl 1,13- and 1,15-diols, and factors controlling their distributions. Here we analyzed the occurrence and distribution of these lipids in a comprehensive set of marine surface sediments and compare their distributions with environmental conditions like sea surface temperature (SST), salinity and nutrient concentrations. Fractional abundances of the C28 1,13-, C30 1,13- and C30 1,15-diols show a strong correlation with SST and based on these results, we propose the Long chain Diol Index (LDI), which expresses the C30 1,15-diol abundance relative to those of C28 1,13-, C30 1,13- and C30 1,15-diols. The LDI shows a strong linear correlation with SST (LDI = 0.033 × SST + 0.095; R2 = 0.969, n = 162) over a temperature range of -3 to 27 °C. Long chain diol distributions in sediments from the South Atlantic close to the Congo River outflow (West Africa) provided a 43 kyr LDI SST record. This record reflects several known climatic events and shows similarities with an alkenone-derived SST record obtained using the same suite of sediments, both in trend and in terms of absolute SST. This confirms the potential of the LDI as a proxy for palaeo-SST reconstruction.