Correlation between Oxidative Stress and Thyroid Function in Patients with Nephrotic Syndrome

Background. The present study is to look for a correlation between oxidative stress and thyroid function in patients with the nephrotic syndrome in the remission phase as well as in a persistent proteinuric state. Introduction. Nephrotic syndrome is a form of chronic kidney disease due to which blood loses protein through the urine. We wanted to know if there was an increased loss of thyroid hormones in urine affecting thyroid function. Methods. 60 patients with nephrotic syndrome and 20 healthy non-proteinuric individuals as control subjects were enrolled in the study. We measured their serum tri-iodothyronine, thyroxine and thyroid-stimulating hormone. Estimation of lipid peroxidation (LPx) catalase, superoxide dismutase (SOD), and Glutathione peroxidase (GPx) were carried out by standard methods. Results. TSH was elevated in the nephrotic patients compared to controls, while TT4 and TT3 were significantly lower in the patients than in controls. Lipid Peroxidation and GPx were significantly higher in the nephrotic syndrome patients than in the controls, while SOD and catalase were significantly lower than in patients than in the control subjects. Conclusion. Nephrotic patients can lose significant amounts of thyroid hormones along with protein in urine, which can affect thyroid status, but this is reversible on remission

Paclobutrazol effects on cacao seedlings

O efeito do paclobutrazol (2RS, 3RS)-1-(4-Clorofenil) - 4,4-dimefil - 2 - (1H, 2,4 - triazol -1-it) - pentan-3-ol), ICI PP333 nas características morfológicas de plântulas de cacau (Theobroma cacao L.) foi avaliado sob condições de casa de vegetação. O delineamento experimental utilizado foi o inteiramente casualizado com cinco tratamentos e dez repetições. O experimento consistiu na aplicação de 0, 5, 15,45, e 90 ppm de PP333 em plântulas de cacau "Catongo" de 5 meses de idade crescendo em sacos de polietileno com 5 kg de solo. A altura da planta foi o parâmetro mais afetado pela ação do PP333. As maiores dosagens reduziram a altura em 32% em relação ao tratamento testemunha. A dosagem de 15 ppm reduziu o crescimento em 17% e a de 5 ppm não diferiu estatisticamente do controle. A exceção de 90 ppm, que reduziu significativamente o diâmetro do caule em 15%, não se verificaram diferenças significativas nos outros tratamentos em relação a testemunha. A área de cada folha, nas duas maiores dosagens, foi significativamente menor em relação aos tratamentos 0, 5 e 15 ppm. As dosagens maiores decresceram, aproximadamente, 25% a área das folhas. A dosagem de 90 ppm diminuiu o peso da matéria seca total em 21% em relação ao controle. Os pesos da matéria seca da raiz, caule e folhas a 90 ppm foram 32%, 27% e 22% menores, respectivamente, em relação às mesmas partes das plântulas testemunha. A dosagem maior do produto modificou a partição dinâmica de assimilados, decrescendo a razão peso seco da matéria seca da raiz/peso seco da malária seca parte aérea, que foi significativamente menor em relação aos outros tratamentos.The effects of paclobutrazol (2RS, 3RS) -1-(4-Chlorophenyl) - 4,4-dimethyl-2-(1H, 2, 4-triazol- 1 -yl)-pentan-3-ol), ICI PP333 on the morphological characteristics of cacao (Theobroma cacao L.) seedlings were evaluated under greenhouse conditions. The experimental design was a complete randomized design with five treatments and 10 replications. Applications of 5, 15, 45, and 90 ppm of PP333 were made directly to the soil in which 5-months old 'Catongo' cacao seedlings were grown in 5,0 kg poliethylene bags. Plant height was the parameter more affected by the action of PP333. The height reduction by the highest rates was 32% with respect to control plants. The 15 ppm application reduced height by 17% and the 5 ppm did not statistically differ from the control. With the exception of the 90 ppm treatment which significantly reduced stem diameter, the other treatments were not statistically different from the control. Individual leaf area, in the two higher doses, was significantly lower than the control, 0,5, and 15 ppm treatments, by approximately 28%. Total dry weight of plants al the highest rate of PP333 were 21% lower than the control seedlings. Root, stem, and leaf dry weight for the 90 ppm seedlings were 32, 17 and 22% lower than control plants, respectively. The highest dose changed the partitioning of photosynthates, decreasing the root/shoot ratio which was significantly lower

High glucose-mediated oxidative stress impairs cell migration

Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we evaluate the hypothesis that high glucose concentrations inhibit cell migration. Using CHO.K1 cells, NIH-3T3 fibroblasts, mouse embryonic fibroblasts and primary skin fibroblasts from control and diabetic rats cultured in 5 mM Dglucose (low glucose, LG), 25 mM D-glucose (high glucose, HG) or 25 mM L-glucose medium (osmotic control - OC), we analyzed the migration speed, protrusion stability, cell polarity, adhesion maturation and the activity of the small Rho GTPase Rac1. We also analyzed the effects of reactive oxygen species by incubating cells with the antioxidant N-AcetylCysteine (NAC). We observed that HG conditions inhibited cell migration when compared to LG or OC. This inhibition resulted from impaired cell polarity, protrusion destabilization and inhibition of adhesion maturation. Conversely, Rac1 activity, which promotes protrusion and blocks adhesion maturation, was increased in HG conditions, thus providing a mechanistic basis for the HG phenotype. Most of the HG effects were partially or completely rescued by treatment with NAC. These findings demonstrate that HG impairs cell migration due to an increase in oxidative stress that causes polarity loss, deficient adhesion and protrusion. These alterations arise, in large part, from increased Rac1 activity and may contribute to the poor wound healing observed in diabetic patients

Pair production of the heavy leptons in future high energy linear e^{+}e^{-} colliders

The littlest Higgs model with T-parity predicts the existence of the T-odd particles, which can only be produced in pair. We consider pair production of the T-odd leptons in future high energy linear $e^{+}e^{-}$ collider ($ILC$). Our numerical results show that, as long as the T-odd leptons are not too heavy, they can be copiously produced and their possible signals might be detected via the processes $e^{+}e^{-}\to \bar{L}_{i}L_{j}$ in future $ILC$ experiments.Comment: Discussions added, typos and references correcte

Telethonin protein expression in neuromuscular disorders

Telethonin is a 19-kDa sarcomeric protein, localized to the Z-disc of skeletal and cardiac muscles. Mutations in the telethonin gene cause limb-girdle muscular dystrophy type 2G (LGMD2G). We investigated the sarcomeric integrity of muscle fibers in LGMD2G patients, through double immunofluorescence analysis for telethonin with three sarcomeric proteins: titin, alpha-actinin-2, and myotilin and observed the typical cross striation pattern, suggesting that the Z-line of the sarcomere is apparently preserved, despite the absence of telethonin. Ultrastructural analysis confirmed the integrity of the sarcomeric architecture. the possible interaction of telethonin with other proteins responsible for several forms of neuromuscular disorders was also analyzed. Telethonin was clearly present in the rods in nemaline myopathy (NM) muscle fibers, confirming its localization to the Z-line of the sarcomere. Muscle from patients with absent telethonin showed normal expression for the proteins dystrophin, sarcoglycans, dysferlin, and calpain-3. Additionally, telethonin showed normal localization in muscle biopsies from patients with LGMD2A, LGMD2B, sarcoglycanopathies, and Duchenne muscular dystrophy (DMD). Therefore, the primary deficiency of calpain-3, dysferlin, sarcoglycans, and dystrophin do not seem to alter telethonin expression. (C) 2002 Elsevier Science B.V. All rights reserved.Univ São Paulo, Ctr Study Human Genome, Dept Biol, IBUSP, BR-05508900 São Paulo, BrazilInt Ctr Genet Engn & Biotechnol, Tieste, ItalyUniv Padua, CRIBI Biotechnol Ctr, I-35121 Padua, ItalyHarvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USAUniv Helsinki, Helsinki, FinlandUNIFESP, Dept Neurol, São Paulo, BrazilFMUSP, Dept Neurol, São Paulo, BrazilFMUSP, Dept Pathol, São Paulo, BrazilUNIFESP, Dept Neurol, São Paulo, BrazilWeb of Scienc

Mutation in the MICOS subunit gene APOO (MIC26) associated with an X-linked recessive mitochondrial myopathy, lactic acidosis, cognitive impairment and autistic features.

BACKGROUND: Mitochondria provide ATP through the process of oxidative phosphorylation, physically located in the inner mitochondrial membrane (IMM). The mitochondrial contact site and organising system (MICOS) complex is known as the 'mitoskeleton' due to its role in maintaining IMM architecture. APOO encodes MIC26, a component of MICOS, whose exact function in its maintenance or assembly has still not been completely elucidated. METHODS: We have studied a family in which the most affected subject presented progressive developmental delay, lactic acidosis, muscle weakness, hypotonia, weight loss, gastrointestinal and body temperature dysautonomia, repetitive infections, cognitive impairment and autistic behaviour. Other family members showed variable phenotype presentation. Whole exome sequencing was used to screen for pathological variants. Patient-derived skin fibroblasts were used to confirm the pathogenicity of the variant found in APOO. Knockout models in Drosophila melanogaster and Saccharomyces cerevisiae were employed to validate MIC26 involvement in MICOS assembly and mitochondrial function. RESULTS: A likely pathogenic c.350T>C transition was found in APOO predicting an I117T substitution in MIC26. The mutation caused impaired processing of the protein during import and faulty insertion into the IMM. This was associated with altered MICOS assembly and cristae junction disruption. The corresponding mutation in MIC26 or complete loss was associated with mitochondrial structural and functional deficiencies in yeast and D. melanogaster models. CONCLUSION: This is the first case of pathogenic mutation in APOO, causing altered MICOS assembly and neuromuscular impairment. MIC26 is involved in the assembly or stability of MICOS in humans, yeast and flies

Burden and predictors of hypertension in India: results of SEEK (Screening and Early Evaluation of Kidney Disease) study

Background: Hypertension (HTN) is one of the major causes of cardiovascular morbidity and mortality. The objective of the study was to investigate the burden and predictors of HTN in India. Methods: 6120 subjects participated in the Screening and Early Evaluation of Kidney disease (SEEK), a community-based screening program in 53 camps in 13 representative geographic locations in India. Of these, 5929 had recorded blood pressure (BP) measurements. Potential predictors of HTN were collected using a structured questionnaire for SEEK study. Results: HTN was observed in 43.5% of our cohort. After adjusting for center variation (p < 0.0001), predictors of a higher prevalence of HTN were older age ≥40 years (p < 0.0001), BMI of ≥ 23 Kg/M2 (p < 0.0004), larger waist circumference (p < 0.0001), working in sedentary occupation (p < 0.0001), having diabetes mellitus (p < 0.0001), having proteinuria (p < 0.0016), and increased serum creatinine (p < 0.0001). High school/some college education (p = 0.0016), versus less than 9th grade education, was related with lower prevalence of HTN. Of note, proteinuria and CKD were observed in 19% and 23.5% of HTN subjects. About half (54%) of the hypertensive subjects were aware of their hypertension status. Conclusions: HTN was common in this cohort from India. Older age, BMI ≥ 23 Kg/M2, waist circumference, sedentary occupation, education less, diabetes mellitus, presence of proteinuria, and raised serum creatinine were significant predictors of hypertension. Our data suggest that HTN is a major public health problem in India with low awareness, and requires aggressive community-based screening and education to improve health

Regularity Properties and Pathologies of Position-Space Renormalization-Group Transformations

We reconsider the conceptual foundations of the renormalization-group (RG) formalism, and prove some rigorous theorems on the regularity properties and possible pathologies of the RG map. Regarding regularity, we show that the RG map, defined on a suitable space of interactions (= formal Hamiltonians), is always single-valued and Lipschitz continuous on its domain of definition. This rules out a recently proposed scenario for the RG description of first-order phase transitions. On the pathological side, we make rigorous some arguments of Griffiths, Pearce and Israel, and prove in several cases that the renormalized measure is not a Gibbs measure for any reasonable interaction. This means that the RG map is ill-defined, and that the conventional RG description of first-order phase transitions is not universally valid. For decimation or Kadanoff transformations applied to the Ising model in dimension $d \ge 3$, these pathologies occur in a full neighborhood $\{ \beta > \beta_0 ,\, |h| < \epsilon(\beta) \}$ of the low-temperature part of the first-order phase-transition surface. For block-averaging transformations applied to the Ising model in dimension $d \ge 2$, the pathologies occur at low temperatures for arbitrary magnetic-field strength. Pathologies may also occur in the critical region for Ising models in dimension $d \ge 4$. We discuss in detail the distinction between Gibbsian and non-Gibbsian measures, and give a rather complete catalogue of the known examples. Finally, we discuss the heuristic and numerical evidence on RG pathologies in the light of our rigorous theorems.Comment: 273 pages including 14 figures, Postscript, See also ftp.scri.fsu.edu:hep-lat/papers/9210/9210032.ps.