Reduced Lrp6 Expression And Increase In The Interaction Of Gsk3β With P53 Contribute To Podocyte Apoptosis In Diabetes Mellitus And Are Prevented By Green Tea.

In diabetes mellitus (DM), podocyte apoptosis leads to albuminuria and nephropathy progression. Low-density lipoprotein receptor-related protein 6 (LRP6) is WNT pathway receptor that is involved in podocyte death, adhesion and motility. Glycogen synthase kinase 3 (GSK3) interaction with p53 (GSK3-p53) promotes apoptosis in carcinoma cells. It is unknown if GSK3-p53 contributes to podocyte apoptosis in DM. In experimental DM, green tea (GT) reduces albuminuria by an unknown mechanism. In the present study, we assessed the role of the GSK3β-p53 in podocyte apoptosis and the effects of GT on these abnormalities. In diabetic spontaneously hypertensive rats (SHRs), GT prevents podocyte's p-LRP6 expression reduction, increased GSK3β-p53 and high p53 levels. In diabetic SHR rats, GT reduces podocyte apoptosis, foot process effacement and albuminuria. In immortalized mouse podocytes (iMPs), high glucose (HG), silencing RNA (siRNA) or blocking LRP6 (DKK-1) reduced p-LRP6 expression, leading to high GSK3β-p53, p53 expression, apoptosis and increased albumin influx. GSK3β blockade by BIO reduced GSK3β-p53 and podocyte apoptosis. In iMPs under HG, GT reduced apoptosis and the albumin influx by blocking GSK3β-p53 following the rise in p-LRP6 expression. These effects of GT were prevented by LRP6 siRNA or DKK-1. In conclusion, in DM, WNT inhibition, via LRP6, increases GSK3β-p53 and podocyte apoptosis. Maneuvers that inactivate GSK3β-p53, such as GT, may be renoprotective in DM.

Theobromine Increases Nad⁺/sirt-1 Activity And Protects The Kidney Under Diabetic Conditions.

Reduction in sirtuin 1 (Sirt-1) is associated with extracellular matrix (ECM) accumulation in the diabetic kidney. Theobromine may reduce kidney ECM accumulation in diabetic rats. In the current study, we aimed to unravel, under diabetic conditions, the mechanism of kidney ECM accumulation induced by a reduction in Sirt-1 and the effect of theobromine in these events. In vitro, we used immortalized human mesangial cells (iHMCs) exposed to high glucose (HG; 30 mM), with or without small interfering RNA for NOX4 and Sirt-1. In vivo, spontaneously hypertensive rats (SHR) were rendered diabetic by means of streptozotocin and studied after 12 wk. The effects of treatment with theobromine were investigated under both conditions. HG leads to a decrease in Sirt-1 activity and NAD(+) levels in iHMCs. Sirt-1 activity could be reestablished by treatment with NAD(+), silencing NOX4, and poly (ADP-ribose) polymerase-1 (PARP-1) blockade, or with theobromine. HG also leads to a low AMP/ATP ratio, acetylation of SMAD3, and increased collagen IV, which is prevented by theobromine. Sirt-1 or AMPK blockade abolished these effects of theobromine. In diabetic SHR, theobromine prevented increases in albuminuria and kidney collagen IV, reduced AMPK, elevated NADPH oxidase activity and PARP-1, and reduced NAD(+) levels and Sirt-1 activity. These results suggest that in diabetes mellitus, Sirt-1 activity is reduced by PARP-1 activation and NAD(+) depletion due to low AMPK, which increases NOX4 expression, leading to ECM accumulation mediated by transforming growth factor (TGF)-β1 signaling. It is suggested that Sirt-1 activation by theobromine may have therapeutic potential for diabetic nephropathy.

Polyphenol-enriched Cocoa Protects The Diabetic Retina From Glial Reaction Through The Sirtuin Pathway.

Cocoa is rich in flavonoids, which are potent antioxidants with established benefits for cardiovascular health but unproven effects on neurodegeneration. Sirtuins (SIRTs), which make up a family of deacetylases, are thought to be sensitive to oxidation. In this study, the possible protective effects of cocoa in the diabetic retina were assessed. Rat Müller cells (rMCs) exposed to normal or high glucose (HG) or H2O2 were submitted to cocoa treatment in the presence or absence of SIRT-1 inhibitor and small interfering RNA The experimental animal study was conducted in streptozotocin-induced diabetic rats randomized to receive low-, intermediate-, or high-polyphenol cocoa treatments via daily gavage for 16 weeks (i.e., 0.12, 2.9 or 22.9 mg/kg/day of polyphenols). The rMCs exposed to HG or H2O2 exhibited increased glial fibrillary acidic protein (GFAP) and acetyl-RelA/p65 and decreased SIRT1 activity/expression. These effects were cancelled out by cocoa, which decreased reactive oxygen species production and PARP-1 activity, augmented the intracellular pool of NAD(+), and improved SIRT1 activity. The rat diabetic retinas displayed the early markers of retinopathy accompanied by markedly impaired electroretinogram. The presence of diabetes activated PARP-1 and lowered NAD(+) levels, resulting in SIRT1 impairment. This augmented acetyl RelA/p65 had the effect of up-regulated GFAP. Oral administration of polyphenol cocoa restored the above alterations in a dose-dependent manner. This study reveals that cocoa enriched with polyphenol improves the retinal SIRT-1 pathway, thereby protecting the retina from diabetic milieu insult.

Aspectos técnicos da monitorização da pressão intracraniana pelo método subaracnóideo no traumatismo craniencefálico grave

Two hundred and six patients with severe head injury (Glasgow Coma Scale of 8 points or less after nonsurgical resuscitation on admission), managed at Intensive Care Unit-Hospital das Clínicas - Universidade Estadual de Campinas were prospectively analysed. All patients were assessed by CT scan and 72 required neurosurgical intervention. All patients were continuously monitored to evaluate intracranial pressure (ICP) levels by a subarachnoid device (11 with subarachnoid metallic bolts and 195 with subarachnoid polyvinyl catheters). The ICP levels were continuously observed in the bedside pressure monitor display and their end-hour values were recorded in a standard chart. The patients were managed according to a standard protocol guided by the ICP levels. There were no intracranial haemorrhagic complications or hematomas due the monitoring method. Sixty six patients were punctured by lateral C1-C2 technique to assess infectious complications and 2 had positive cerebrospinal fluid samples for Acinetobacter sp. The final results measured at hospital discharge showed 75 deaths (36,40%) and 131 (63,60%) survivors. ICP levels had significantly influenced the final results (p<0,001). The subarachnoid method to continuously assess the ICP levels was considered aplicable, safe, simple, low cost and useful to advise the management of the patients. The ICP record methodology was practical and useful. Despite the current technical advances the subarachnoid method was considered viable to assess the ICP levels in severe head injury.

Quantificação de fluxos de mercúrio gasoso na interface solo/atmosfera utilizando câmara de fluxo dinâmica: aplicação na bacia do Rio Negro

Gaseous mercury sampling conditions were optimized and a dynamic flux chamber was used to measure the air/surface exchange of mercury in some areas of the Negro river basin with different vegetal coverings. At the two forest sites (flooding and non-flooding), low mercury fluxes were observed: maximum of 3 pmol m-2 h-1 - day and minimum of -1 pmol m-2 h-1 - night. At the deforested site, the mercury fluxes were higher and always positive: maximum of 26 pmol m-2 h-1 - day and 17 pmol m-2 h-1 - night. Our results showed that deforestation could be responsible for significantly increasing soil Hg emissions, mainly because of the high soil temperatures reached at deforested sites.

Variabilidade espacial e sazonal da concentração de elementos-traço em sedimentos do sistema estuarino de Santos-Cubatão (SP)

Multi-element analyses of sediment samples from the Santos-Cubatão Estuarine System were carried out to investigate the spatial and seasonal variability of trace-element concentrations. The study area contains a rich mangrove ecosystem that is a habitat for tens of thousands of resident and migratory birds, some of them endangered globally. Enrichments of metals in fine-grained surface sediments are, in decreasing order, Hg, Mn, La, Ca, Sr, Cd, Zn, Pb, Ba, Cu, Cr, Fe, Nb, Y, Ni and Ga, relative to pre-industrial background levels. The maximum enrichment ranged from 49 (Hg) to 3.1 (Ga). Mercury concentrations were greater in the Cubatão river than in other sites, while the other elements showed greater concentrations in the Morrão river. Concentrations of Mn were significantly greater in winter and autumn than in summer and spring. However, other elements (e.g. Cd and Pb) showed the opposite, with greater concentrations in summer and spring. This study suggests that seasonal changes in physical and chemical conditions may affect the degree of sediment enrichment and therefore make the assessment of contamination difficult. Consequently, these processes need to be considered when assessing water quality and the potential contamination of biota.

Qualidade de vida e avaliação fisica em intoxicados por mercurio : estudo observacional transversal descritivo

Universidade Estadual de Campinas . Faculdade de Educação Física

Aerobic and anaerobic metabolism for the zebrafish, Danio rerio, reared under normoxic and hypoxic conditions and exposed to acute hypoxia during development

In order to verify the influence of chronic and acute ambient oxygen levels from egg to adult stage of the zebrafish, in vivo oxygen consumption (MO2), critical tensions of oxygen (Pcrit), heart rate (fH) and total body lactate concentration (Lc) were determined for Danio rerio (Hamilton, 1822) raised at 28 °C under normoxic (7.5 mgO2.L-1 or 80 mm.Hg-1) and hypoxic conditions (4.3 mgO2.L-1) and exposed to acute hypoxia during different developmental stages. Our findings confirmed that very early stages do not respond effectively to ambient acute hypoxia. However, after the stage corresponding to the age of 30 days, D. rerio was able to respond to acute hypoxia through effective physiological mechanisms involving aerobic and anaerobic metabolism. Such responses were more efficient for the fishes reared under hypoxia which showed that D. rerio survival capability increased during acclimation to mild hypoxia. Measurements of body mass and length showed that moderate hypoxia did not affect growth significantly until the fish reached the stage of 60 days. Moreover, a growth delay was verified for the hypoxic-reared animals. Also, the D. rerio eggs-to-larvae survival varied from 87.7 to 62.4% in animals reared under normoxia and mild hypoxia, respectively. However, the surviving animals raised under moderated hypoxia showed a better aptitude to regulate aerobic and anaerobic capacities when exposed to acute hypoxia.

Heavy metal concentrations in soils from a remote oceanic island, Fernando de Noronha, Brazil

This paper examines the role of parent rock, pedogenetic processes and airborne pollution in heavy metal accumulation in soils from a remote oceanic island, Fernando de Noronha, Brazil. We studied five soil profiles developed from different volcanic rocks. Mineralogical composition and total concentrations of major and trace elements were determined in 43 samples. The obtained concentrations range for heavy metals were: Co: 26-261 ppm; Cu: 35-97 ppm; Cr: 350-1446 ppm; Ni: 114-691 ppm; Zn: 101-374 ppm; Hg: 2-150 ppb. The composition of soils is strongly affected by the geochemical character of the parent rock. Pedogenesis appears to be responsible for the accumulation of Zn, Co, and, to a lesser extent, of Ni and Cu, in the upper, Mn- and organic carbon-enriched horizons of the soil profiles. Pedogenic influence may also explain the relationship observed between Cr and the Fe. Hg is likely to have been added to the soil profile by long-range atmospheric transport. Its accumulation in the topsoil was further favoured by the formation of stable complexes with organic matter. Clay minerals do not appear to play an important role in the fixation of heavy metals.

Avaliação da contaminação por elementos metálicos dos sedimentos do Estuário Santos - São Vicente

Three approaches were applied to evaluate metal contamination in 41 sediment samples from the Santos - São Vicente Estuarine System: normalization to Al, statistical analysis and sediment quality guidelines (SQGs). The results showed increases in the concentrations of Zn, Ni, Pb, Cd, Cr and Hg, which seemed to be associated with human activities. The levels of Al, Fe and Co probably were associated with crustal material or natural weathering processes. About 45% of the samples presented concentrations exceeding TEL-ERL, levels occasionally associated with adverse biological effects. Four of these samples presented concentrations above PEL-ERM, levels frequently associated with adverse biological effects.

Mercúrio total em cabelo de crianças de uma população costeira, Cananéia, São Paulo, Brasil

Os níveis de mercúrio (Hg) total em cabelos estão diretamente relacionados à alimentação, particularmente ao consumo de peixes por populações costeiras com grande representação caiçara. No presente estudo foram avaliados os níveis de mercúrio total em cabelos de crianças com idade entre 4 e 12 anos, pertencente a três escolas públicas da cidade de Cananéia, São Paulo, Brasil. Os resultados obtidos (mediana e intervalo) para mercúrio total foram de: 0,04mg.kg-1 (0,01-0,77mg.kg-1), 0,39mg.kg-1 (< 0,01-3,33mg.kg-1) e 0,39mg.kg-1 (< 0,01-2,81mg.kg-1) considerando as escolas ES1, ES2 e ES3, respectivamente. Em geral, os valores encontrados estiveram bem abaixo do valor preconizado pela Organização Mundial da Saúde para uma população adulta não exposta ao mercúrio (2,0mg.kg-1). Os baixos valores observados e a inexistência de valores de referência para mercúrio total em cabelos de crianças brasileiras possibilitam a consideração desses valores como possível referência nacional em cabelos de populações costeiras, uma vez que foram obtidos em região de baixo impacto ambiental.

Observations on Haemagogus janthinomys Dyar (Diptera: Culicidae) and other mosquito populations within tree holes in a gallery forest in the northwestern region of Sao Paulo state, Brazil

In 2000, an outbreak of sylvatic yellow fever possibly occurred in gallery forests of the Grande river in the Paraná basin in the northwestern region of São Paulo state. The aim of this study was to obtain information on the bionomics of Haemagogus and other mosquitoes inside tree holes in that area. Eighteen open tree holes were sampled for immature specimens. Adults were collected twice a month in the forest in Santa Albertina county from July 2000 to June 2001. The seasonal frequency of fourth instars was obtained by the Williams geometric mean (Mw), while the adult frequency was estimated either by hourly arithmetic or the Williams' means. Cole's index was applied to evaluate larval inter-specific associations. Among the ten mosquito species identified, the most abundant was Aedes terrens Walker followed by Sabethes tridentatus Cerqueira and Haemagogus janthinomys Dyar. Larval and adult abundance of these species was higher in summer than in winter. Although larval abundance of Hg. janthinomys peaked in the rainy season, correlation with rainfall was not significant. Six groups of larval associations were distinguished, one of which the most positively stable. The Hg. janthinomys and Ae. terrens association was significant, and Limatus durhamii Theobald was the species with most negative associations.

Ecologia de Haemagogus e Sabethes (Diptera: Culicidae) em áreas epizoóticas do vírus da febre amarela, Rio Grande do Sul, Brasil

Objetivou-se com este estudo investigar característica ecológica e o hábito alimentar de Haemagogus e Sabethes em área epizoótica da febre amarela silvestre em duas localidades do Rio Grande do Sul, capturados com aspirador, armadilha de Shannon e puçá. Para identificação do sangue ingerido pelas fêmeas foi utilizada a técnica imunoenzimática ELISA de captura. Obteve-se maior atividade de Hg. leucocelaenus na primavera e outono, entre 12 e 17 horas, enquanto Sabethes albiprivus e Sa. quasycianus durante todo o ano. Para fêmeas de Hg. leucocelaenus em Santo Antônio das Missões, houve predomínio de sangue humano e para as demais espécies destaca-se a atratividade para bovinos nos dois municípios. A capacidade vetorial do Hg. leucocelaenus fundamenta vigilância entomológica em seu papel de estratificar áreas problemas ou a sustentabilidade do programa de imunização da população

Disponibilidade de metais pesados em Latossolo com aplicação superficial de escória, lama cal, lodos de esgoto e calcário

O objetivo deste trabalho foi avaliar alguns atributos químicos do solo e a disponibilidade de cádmio (Cd), cromo (Cr), níquel (Ni), mercúrio (Hg), chumbo (Pb) e arsênio (As), por meio da extração pelo DTPA,em conseqüência da aplicação superficial de escória de aciaria, lama cal e lodos de esgoto centrifugados e de biodigestores, nas doses 0 (testemunha), 2, 4 e 8 Mg ha-1 e um tratamento adicional composto pela calagem superficial na dose 2 Mg ha-1. O experimento foi conduzido em delineamento de blocos ao acaso, em condições de campo, em área sob sistema plantio direto, durante 2003 e 2004. A aplicação superficial de escória de aciaria,lama cal, lodo de esgoto centrifugado e de biodigestor, até a dose 8 Mg ha-1, assim como o calcário na dose 2 Mg ha-1, não trazem problemas de disponibilidade ao ambiente, com relação aos metais pesados Cd, Cr, Hg, Pb, Ni e As, quando aplicados sobre a superfície em Latossolo Vermelho distrófico, no sistema plantio direto. A fitodisponibilidade de metais pesados às culturas da soja e aveia-preta foi nula, quando foram aplicadas doses de até 8 Mg ha-1 de lodo de esgoto, escória e lama cal sobre a superfície do solo, no sistema plantio direto

Selenium and Mercury in the Brazilian Amazon: Opposing Influences on Age-Related Cataracts

BACKGROUND: Age-related cataracts (ARCs) are an important cause of blindness in developing countries. Although antioxidants may be part of the body's defense to prevent ARC, environmental contaminants may contribute to cataractogenesis. In fish-eating populations of the lower Tapajos region, elevated exposure to mercury (Hg) has been reported, and blood levels of selenium (Se) range from normal to very high (> 1,000 mu g/L). OBJECTIVES: We examined ARCs in relation to these elements among adults (>= 40 years of age) from 12 riverside communities. METHODS: Participants (n = 211) provided blood samples and underwent an extensive ocular examination. Inductively coupled plasma mass spectrometry was used to assess Hg and Se in blood and plasma. RESULTS: One-third (n = 69; 32.7%) of the participants had ARC. Lower plasma Se (P-Se; < 25th percentile, 110 mu g/L) and higher blood Hg (B-Hg; >= 25th percentile, 25 mu g/L) were associated with a higher prevalence odds ratio (POR) of ARC [adjusted POR (95% confidence interval), 2.69 (1.11-6.56) and 4.45 (1.43-13.83), respectively]. Among participants with high P-Se, we observed a positive but nonsignificant association with high B-Hg exposure, whereas among those with low B-Hg, we observed no association for P-Se. However, compared with the optimum situation (high P-Se, low B-Hg), the POR for those with low P-Se and high B-Hg was 16.4 (3.0-87.9). This finding suggests a synergistic effect. CONCLUSION: Our results suggest that persons in this population with elevated Hg, the cataractogenic effects of Hg may be offset by Se. Because of the relatively small sample size and possible confounding by other dietary nutrients, additional studies with sufficient power to assess multiple nutrient and toxic interactions are required to confirm these findings.