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- Heat Shock Proteins in the Brain: Role of Hsp70, Hsp 27, and HO-1 (Hsp32) and Their Therapeutic Potential. [Journal Article]
- Transl Stroke Res 2013 Dec; 4(6):685-92.
Heat shock proteins (Hsps) are induced by heat shock via heat shock factor proteins binding to heat shock elements in their promoters. Hsp70 is massively induced in response to misfolded proteins following cerebral ischemia in all cell types but is induced mainly in neurons in the ischemic penumbra. Overexpression of Hsp70 via transgenes and viruses or systemic administration of Hsp70 fusion proteins that allow it to cross the blood brain barrier protects the brain against ischemia in most reported studies. Hsp27 can exist as unphosphorylated large oligomers that prevent misfolded protein aggregates and improve cell survival. P-Hsp27 small oligomers bind specific protein targets to improve survival. In the brain, protein kinase D phosphorylates Hsp27 following ischemia which then binds apoptosis signal-regulating kinase 1 to prevent MKK4/7, c-Jun NH(2)-terminal kinase, and Jun-induced apoptosis, and decrease infarct volumes following focal cerebral ischemia. Heme oxygenase-1 (HO-1) metabolizes heme to carbon monoxide, ferrous ion, and biliverdin. CO activates cGMP to promote vasodilation, and biliverdin is converted to bilirubin which can serve as an anti-oxidant, both of which may contribute to the reported protective role of HO-1 in cerebral ischemia and subarachnoid hemorrhage. However, ferrous ion can react with hydrogen peroxide to produce pro-oxidant hydroxyl radicals which may explain the harmful role of HO-1 in intracerebral hemorrhage. Heat shock proteins as a class have great potential as treatments for cerebrovascular disease and have yet to be tested in the clinic.
- Serum bile acid fractions in neonates on total parenteral nutrition is lithocholic acid responsible for the occurrence of cholestasis? [Journal Article]
- Asia Pac J Clin Nutr 1992 Jun; 1(2):67-72.
In order to determine whether lithocholic acid (LCA) contributes to the occurrence of total parenteral nutrition (TPN) associated intrahepatic cholestasis (IHC) in neonates, we investigated the serum bile acid fractions of neonates on TPN. Twenty-five surgical neonates, receiving TPN for more than 2 weeks were studied. TPN associated IHC was defined as serum defect bilirubin greater than 2.0 mg/dL. Serum bile acid fractions were examined by HPLC using 3α -hydroxy steroid dehydrogenase. Eight patients (32%; IHC group) developed TPN associated IHC. Serum direct bilirubin concentrations in the non IHC and IHC groups were 0.99 and 3.31 mg/dL respectively. Serum total bile acid levels in both groups were 14.4 and 71.6 nmol/ml respectively. Glycine and taurine conjugated cholic and chenodeoxycholic acids could be detected, and unconjugated and secondary (deoxycholic and lithocholic) bile acid were detected in trace levels in both the IHC and non-IHC groups. In conclusion, LCA is unlikely to be a causative factor in TPN associated IHC in neonates.
- Factors Associated with Aggravation of Esophageal Varices after B-RTO for Gastric Varices. [JOURNAL ARTICLE]
- Cardiovasc Intervent Radiol 2013 Dec 10.
To retrospectively evaluate risk factors for aggravation of esophageal varices (EV) within 1 year after balloon-occluded retrograde transvenous obliteration (B-RTO) of gastric varices (GV) and to clarify suitable timing for upper endoscopy to detect EV aggravation after B-RTO.Participants included 67 patients who underwent B-RTO for GV between January 2006 and December 2010. Whether EV aggravation occurred within 1 year was evaluated, and the time interval from B-RTO to aggravation was calculated. Factors potentially associated with EV aggravation were analyzed.B-RTO was successfully performed in all patients. EV aggravation at 1 year after B-RTO was found in 38 patients (56.7 %). Multivariate logistic regression analysis showed that total bilirubin (T-bil) (P = 0.032) and hepatic venous pressure gradient (HVPG) (P = 0.011) were significant independent risk factors for EV aggravation after B-RTO. Cutoff values of T-bil and HVPG yielding maximal combined sensitivity and specificity for EV aggravation were 1.6 mg/dL and 13 mmHg, respectively. The patients with T-bil ≥ 1.6 mg/dL or HVPG ≥ 13 mmHg had a median aggravation time of 5.1 months. All five patients with ruptured EV belonged to this group. In contrast, patients with T-bil < 1.6 mg/dL and HVPG < 13 mmHg had a median aggravation time of 21 months.T-bil and HVPG were significant independent risk factors for EV aggravation after B-RTO. The patients with T-bil ≥ 1.6 mg/dL or HVPG ≥ 13 mmHg require careful follow-up evaluation, including endoscopy.
- Influence of Plasmodium vivax malaria on the relations between the osmotic stability of human erythrocyte membrane and hematological and biochemical variables. [JOURNAL ARTICLE]
- Parasitol Res 2013 Dec 10.
This study evaluated the influence of infection by Plasmodium vivax on the relations between hematological and biochemical variables and the osmotic stability of the erythrocyte membrane in a Brazilian Amazon population. A total of 72 patients with P. vivax malaria were included in the study and invited to return after 14 days, post-treatment with chloroquine and primaquine, for clinical and laboratorial reevaluations. The osmotic stability of the erythrocyte membrane was analyzed by nonlinear regression of the dependency of the absorbance of hemoglobin, released with hemolysis, as a function of the salt concentration, and it was represented by the inverse of the salt concentration at the midpoint of the curve (1/H 50) and by the variation of salt concentration, which promotes lysis (dX). Bivariate and multivariate methods were used in the analysis of the results. Prior to treatment of the disease, the erythrocytes showed greater stability, probably due to the natural selection of young and also more stable erythrocytes. The bivariate analysis showed that 1/H 50 was positively correlated with red cell distribution width (RDW), urea, triglycerides, and very low-density lipoprotein (VLDL)-cholesterol, but negatively associated with albumin, HDL-cholesterol, and indirect bilirubin, while dX was negatively associated with the mean corpuscular hemoglobin concentration. These associations were confirmed by canonical correlation analysis. Stepwise multiple linear regression showed that albumin, urea, triglycerides, and VLDL-cholesterol are the variables with the highest abilities of predicting erythrocyte stability. The bivariate analysis also showed that the hematological index RDW was related to elevated levels of bilirubin and decreased levels of albumin and urea, associated with liver damage resulting from malaria.
- [Compound nutrients promote liver rehabilitation and regeneration in rats with CCl4;-induced liver cirrhosis]. [English Abstract, Journal Article]
- Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2013 Dec; 29(12):1237-41.
Objective To explore the effects of compound nutrients on liver rehabilitation and regeneration in rats with CCl4;-induced liver cirrhosis. Methods The rat cirrhotic models were prepared by injecting intraperitoneally the mixture of CCl4; (40%) and oil (60%) by 2 mL/kg body weight twice a week for 12 weeks. The nutrition treatment group was treated with compound nutrients and the spontaneous recovery group was not treated with nutrients after stopping CCl4; injection. Then liver tissues and blood samples were harvested to detect the expressions of augmenter of liver regeneration (ALR) and proliferating cell nuclear antigen (PCNA) by immunohistochemistry, the level of hepatocyte growth factor (HGF) by ELISA, the levels of albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TBIL), glucose, triglyceride (TG) and cholesterol (CHOL) by automatic biochemical analyzer, and the levels of amino acids in blood plasma by mass spectrometry. Results The expressions of ALR and PCNA were higher in nutrition treatment group than in spontaneous recovery group. The level of HGF in serum was higher in nutrition treatment group than in spontaneous recovery group (98.92±2.42 vs 60.99±27.63, t=3.349, P=0.020). The levels of ALT (60.18±6.39 vs 84.6±17.91, t=3.146, P=0.019) and TBIL (2.08±0.46 vs 6.97±2.58, t=4.56, P=0.001) were lower in nutrition treatment group than in spontaneous recovery group. The level of ALB was higher in nutrition treatment group than in spontaneous recovery group (33.15±1.36 vs 24.62±2.48, t=7.39, P=0.000). The level of branched chain amino acids (BCAA) in blood plasma was higher in nutrition treatment group than in spontaneous recovery group (381.53±35.86 vs 283.05±79.14, t=2.78, P=0.02). Conclusion Compound nutrients can be good for liver rehabilitation and regeneration in CCl4;-induced cirrhotic rat model, and the liver regeneration may relate to high BCAA level in blood plasma.
- Validity of establishing pediatric reference intervals based on hospital patient data: A comparison of the modified Hoffmann approach to CALIPER reference intervals obtained in healthy children. [JOURNAL ARTICLE]
- Clin Biochem 2013 Dec 4.
To compare pediatric reference intervals calculated using hospital-based patient data with those calculated using samples collected from healthy children in the community as part of the CALIPER study.Hospital-based data for 13 analytes (calcium, phosphate, iron, ALP, cholesterol, triglycerides, creatinine, direct bilirubin, total bilirubin, ALT, AST, albumin and magnesium), measured on the Vitros 5600, collected between 2007 and 2011 were obtained. The data for each analyte were partitioned by age and gender as previously defined by the CALIPER study. Outliers in each partition were removed using the Tukey method. The cumulative distribution function (cdf) was then determined for each analyte value following which, the inverse cdf values of a standard Gaussian distribution were calculated. The analyte values were plotted against the inverse cdf of the standard Gaussian distribution. Piece-wise regression determined the linear portion of the resulting graph using the statistical software R. Linear regression determined an equation for the linear portion in each partition and reference intervals were calculated by extrapolating to identify the 2.5th and 97.5th centiles in each partition based on the inverse cdf values (which would correspond to the values -1.96 and 1.96 of the Gaussian distribution). Using the 90% confidence intervals for the reference intervals defined by CALIPER and the Reference Change Value (RCV) as the criteria, these calculated reference intervals were compared to those reported previously by CALIPER. Reference samples were also measured on the Vitros 5600 analyzer in an attempt to validate the calculated reference intervals.In general, the reference intervals calculated from hospital-based data were generally wider than those calculated by CALIPER. None of the reference intervals calculated using the Hoffmann approach fell completely within the 90% confidence intervals calculated by CALIPER.These results suggest that calculating pediatric reference intervals from hospital-based data may be useful, as a guide, in some cases but will likely not replace the need to establish reference intervals in healthy pediatric populations.
- Short-term administration of an aqueous extract of kalanchoe integra var. crenata (andr.) cuf leaves produces no major organ damage in sprague-dawley rats. [JOURNAL ARTICLE]
- J Ethnopharmacol 2013 Dec 3.
Kalanchoe intergra (Ki) leaf extract is an orally administered multipurpose plant medicine in Ghana and other parts of the world for the treatment of ulcers, pain and adenoma of the prostate gland. There is paucity of information concerning its short-term usage. The present study is aimed at conducting histopathological and biochemical studies in a 14-day sub acute toxicity studies using female sprague-dawley rats.Crude extract of Ki leaves was prepared and freeze-dried. . A 14-day sub- acute toxicity studies was conducted using 2 week old nulliparous and non-pregnant female Sprague-Dawley rats (120g-150g). Reconstituted Ki was administered at a dosage of 900 mgkg(-1) (high dose), 300 mgkg(-1) with a control group receiving an equivalent volume of distilled water (as vehicle) by gastric lavage. Histopathological studies of major organs and blood chemistry analysis were performed on blood obtained via cardiac puncture into EDTA tubes after euthanisation.There was a significant decrease in urea (p<0.016) and creatinine levels (p<0.001) in both the high and low dose group. There was an increase in ALP levels (P=0.01) in both the high and low dose group. ALT and AST rather decreased significantly in both the high and low dose groups (p<0.0001). Histopathological results did not show any abnormalities in all the H&E stained paraffin sections. Thus the photo micrographs of the liver, kidney and heart were within histopathological limits.Ki leaf extract is non-toxic when administered by the oral route over a time period of 14 days at the above doses.
- A Nonhuman Primate Model of Human Radiation-Induced Venocclusive Liver Disease and Hepatocyte Injury. [JOURNAL ARTICLE]
- Int J Radiat Oncol Biol Phys 2013 Dec 5.
Human liver has an unusual sensitivity to radiation that limits its use in cancer therapy or in preconditioning for hepatocyte transplantation. Because the characteristic veno-occlusive lesions of radiation-induced liver disease do not occur in rodents, there has been no experimental model to investigate the limits of safe radiation therapy or explore the pathogenesis of hepatic veno-occlusive disease.We performed a dose-escalation study in a primate, the cynomolgus monkey, using hypofractionated stereotactic body radiotherapy in 13 animals.At doses ≥40 Gy, animals developed a systemic syndrome resembling human radiation-induced liver disease, consisting of decreased albumin, elevated alkaline phosphatase, loss of appetite, ascites, and normal bilirubin. Higher radiation doses were lethal, causing severe disease that required euthanasia approximately 10 weeks after radiation. Even at lower doses in which radiation-induced liver disease was mild or nonexistent, latent and significant injury to hepatocytes was demonstrated by asialoglycoprotein-mediated functional imaging. These monkeys developed hepatic failure with encephalopathy when they received parenteral nutrition containing high concentrations of glucose. Histologically, livers showed central obstruction via an unusual intimal swelling that progressed to central fibrosis.The cynomolgus monkey, as the first animal model of human veno-occlusive radiation-induced liver disease, provides a resource for characterizing the early changes and pathogenesis of ven occlusion, for establishing nonlethal therapeutic dosages, and for examining experimental therapies to minimize radiation injury.
- [Time of cord clamping and neonatal complications, a prospective study.] [JOURNAL ARTICLE]
- An Pediatr (Barc) 2013 Dec 3.
To assess the effects of early or late clamping of the umbilical cord in term newborns, assessing the levels of hemoglobin, hematocrit, and ferritin, and their correlation with some of the complications.A prospective study of healthy newborns at term or born by dystotic or eutocic delivery in our hospital between May 2009 until May 2010. Patients were assigned according to the time of clamping, group 1 (<60seconds), group 2 (1 to<2minutes), and group 3 (2 to 3minutes). Laboratory tests were performed at birth and at 48hours of life, assessing the levels of hemoglobin, hematocrit, ferritin, and bilirubin. The risk of polycythemia, respiratory distress syndrome, neonatal phototherapy or admission to the Intensive Care Unit and the hospital stay, were evaluated.A total of 242 patients were included: group 1 (g1=80), group 2 (g2=31) y group 3 (g3=131). The background maternal and neonatal characteristics were similar in all sets. The first test showed significant differences in ferritin levels in those infants with delayed clamping (g1: 111 mg/dl, g2: 125 mg/dl, g3: 173 mg/dl; p<0.01). In the second analysis the values of hemoglobin (g1: 17.3 g/dl, g2: 18.9 g/dl, g3: 19.2 g/dl; p<0.01), hematocrit (g1: 53.4%, g2: 58%, g3: 59%; p<0.01) and ferritin (g1: 254 mg/dl, g2: 254.7 mg/dl, g3: 313 mg/dl; p = 0.008) were statistically higher in this group. As regards complications, a significant increase was observed in the number of cases of polycythemia symptoms in group 3.The late cord clamping is associated with an increase in hematocrit, hemoglobin and ferritin at 48hours of life, as well as an increased risk of polycythemia present with symptoms.