Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells

The effect of Aroclor 1254 and the ameliorative effect of Vitamin C and E on Sertoli cell function were studied in adult male rats. The rats were administered Aroclor 1254 at a dose of 2 mg/kg bw/day intraperitoneally for 30 days. One group of rats received Vitamin C (100 mg/kg bw/day) while the other group received Vitamin E (50 mg/kg bw/day) orally simultaneously with Aroclor 1254 for 30 days. Necropsy was performed at 24 h after the last injection. Sertoli cells were isolated for the estimation of enzymatic antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GST), and gamma-glutamyl transpeptidase (gamma-GT). Lipid peroxidation (LPO), hydrogen peroxide and hydroxyl radical were estimated. Sertoli cellular androgen binding protein (ABP) and lactate were also quantified. Whereas body weight, testis weight, relative weight of testis, ABP, lactate and specific activities of SOD, CAT, GPx, GR, GST, gamma-GT were all decreased, the levels of hydrogen peroxide, hydroxyl radical and LPO were significantly increased in the Sertoli cells of Aroclor 1254 treated rats. Simultaneous administration of Vitamin C or E restored these parameters to a normal range. Thus, the present study suggests that Aroclor 1254 exposure induces oxidative stress in rat Sertoli cells and furthermore that simultaneous administration of Vitamin C or E ameliorated these effects.     

Studies on dengue in rural areas of Kurnool District, Andhra Pradesh, India

A dengue case was reported for the 1st time in a rural area of Kurnool District, Andhra Pradesh, India. Entomological and serological investigations were carried out to determine the prevalence of dengue vectors and dengue virus. Aedes aegypti was recorded for the 1st time in rural areas of Andhra Pradesh. Breeding of Ae. aegypti was observed only in containers with nonpotable water. Cement cisterns and tanks, stone tubs, and clay pots were the major breeding habitats of Ae. aegypti. Larval indices for Ae. aegypti ranged as follows: house index 28-40%, container index 13-37%, and Breteau index 32-60. A serological survey indicated that humans in Kurnool District have been exposed to dengue virus infections. The potential threat of an outbreak of dengue fever in rural areas because of the prevalence of the vector (Ae. aegypti) and dengue virus is discussed.     

Expression of connective tissue growth factor after glaucoma filtration surgery in a rabbit model

PURPOSE: Connective tissue growth factor (CTGF) appears to play a significant role in mediating fibrosis in several tissues. To gain further understanding of the role of CTGF in the scar formation that occurs after glaucoma filtering surgery (GFS), experiments were performed in a rabbit model. METHODS:. Three experiments were performed: (1) CTGF and transforming growth factor (TGF)-beta expression were measured quantitatively after GFS, using ELISA. (2) After GFS conjunctival bleb tissues were immunostained for the presence of CTGF and TGF-beta. (3) Exogenous CTGF was injected into mitomycin-C (MMC)-treated filtering blebs and the scaring response compared to TGF-beta and physiological saline-injected blebs. RESULTS: CTGF and TGF-beta were expressed maximally by day 5 after surgery and were both shown to be present in the bleb tissues after GFS. The addition of exogenous CTGF and TGF-beta increased the rate of failure of GFS blebs. CONCLUSIONS: These data support the hypothesis that CTGF plays an important role in scarring and wound contracture after GFS. Inhibition of CTGF synthesis or its action may help prevent bleb failure and improve long-term GFS outcomes.     

Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction  

Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study.     

Focal complex formation in adult cardiomyocytes is accompanied by the activation of beta3 integrin and c-Src

In pressure-overloaded myocardium, our recent study demonstrated cytoskeletal assembly of c-Src and other signaling proteins which was partially mimicked in vitro using adult feline cardiomyocytes embedded in three-dimensional (3D) collagen matrix and stimulated with an integrin-binding Arg-Gly-Asp (RGD) peptide. In the present study, we improved this model further to activate c-Src and obtain a full assembly of the focal adhesion complex (FAC), and characterized c-Src localization and integrin subtype(s) involved. RGD dose response experiments revealed that c-Src activation occurs subsequent to its cytoskeletal recruitment and is accompanied by p130Cas cytoskeletal binding and focal adhesion kinase (FAK) Tyr925 phosphorylation. When cardiomyocytes expressing hexahistidine-tagged c-Src via adenoviral gene delivery were used for RGD stimulation, the expressed c-Src exhibited relocation: (i) biochemical analysis revealed c-Src movement from the detergent-soluble to the -insoluble cytoskeletal fraction and (ii) confocal microscopic analysis showed c-Src movement from a nuclear/perinuclear to a sarcolemmal region. RGD treatment also caused sarcolemmal co-localization of FAK and vinculin. Characterization of integrin subtypes revealed that beta3, but not beta1, integrin plays a predominant role: (i) expression of cytoplasmic domain of beta1A integrin did not affect the RGD-stimulated FAC formation and (ii) both pressure-overloaded myocardium and RGD-stimulated cardiomyocytes exhibited phosphorylation of beta3 integrin at Tyr773/785 sites but not beta1 integrin at Thr788/789 sites. Together these data indicate that RGD treatment in cardiomyocytes causes beta3 integrin activation and c-Src sarcolemmal localization, that subsequent c-Src activation is accompanied by p130Cas binding and FAK Tyr925 phosphorylation, and that these events might be crucial for growth and remodeling of hypertrophying adult cardiomyocytes.     

Oral glutamine attenuates surgical manipulation-induced alterations in the intestinal brush border membrane

BACKGROUND: Our earlier work has shown that surgical manipulation of the intestine results in oxidative stress and mucosal damage along with alterations in the brush border membrane (BBM). Glutamine feeding is known to offer protection against damage to mucosa under various conditions and this study looked at the effect of oral supplementation of glutamine or glutamic acid in the intestinal BBM alterations after surgical manipulation. MATERIALS AND METHODS: Control and rats pretreated for 7 days with 2% glutamine or glutamic acid or isonitrogenous amino acids, glycine, or alanine were subjected to surgical manipulation of the intestine. BBMs were isolated from the intestine and functional and structural alterations to these membranes were assessed and compared. RESULTS: Surgical manipulation resulted in oxidative stress in the enterocyte BBM and these changes included a decrease in alkaline phosphatase activity and alpha-tocopherol content along with an increase in lipid peroxidation parameters. A decrease in glucose transport by the isolated BBM vesicles suggested functional impairment. Surgical manipulation also resulted in phospholipid degradation possibly mediated by PLA(2) and membrane protease activation. Glutamine or glutamic acid supplementation prevented these changes but not by glycine or alanine. CONCLUSION: This study suggests that oral glutamine or glutamic acid supplementation prior to surgery can offer protection to the intestine and this might prevent postsurgical complications.     

Telomerase activity in Indian patients with carcinomas of the aerodigestive tract.

The activation of telomerase, a ribonucleoprotein maintaining telomeric length, might represent an additional required event in the multigenetic process of tumorigenesis in human cancer. To investigate whether telomerase activity is a prerequisite or a useful indicator of malignant potential, we assayed the enzyme in squamous cell carcinomas and tried to observe any correlation with clinical staging and histopathological grading. We have studied telomerase activity in 23 samples of squamous cell carcinomas of the aerodigestive tract and in 22 corresponding samples of adjoining tissues using the telomerase repeat amplification assay. Telomerase activity was detected in 100% of the tumor samples studied. The telomerase activity increased with tumor grading, but was not statistically significant. Low levels of enzyme activity were also detected in 60.86% of the adjoining normal tissue samples. Reactivation of telomerase may play an important role in the carcinogenesis of aerodigestive tract tumors. Detection of enzyme activity in the adjoining normal tissue is suggestive of microinvasion of tumor cells and/or early activation of telomerase in the progression towards cancer, before possible pathological identification.     

Aplasia cutis congenita,terminal limb defects and periventricular leukomalacia in one sibling with minor findings in the other-probable autosomal recessive Adams-Oliver Syndrome

We report on siblings with probable Adams-Oliver syndrome. The older brother had symmetric intra-uterine growth retardation, plagiocephaly, a cardiac defect and periventricular calcification. The younger sister was born with abdominal and scalp skin defects and small fingers and toes. Prenatal cranial imaging in the younger sibling suggested possible bilateral closed lip schizencephaly and neuronal migrational defect.These siblings are thought to have Adams-Oliver syndrome with the older sibling's features at the milder end of the spectrum while the younger sibling is more severely affected.Several case reports have been published discussing the clinical variability and the possibility of autosomal recessive inheritance. Recently reports suggest an increased frequency of seizures and central nervous system involvement in autosomal recessive Adams-Oliver syndrome. We report affected siblings born to healthy non-consanguineous parents and review previously published similar sibships and case reports in relation to the clinical features.     

Expert clinical assessment of thorax stiffness of infants and children during chest compressions

BackgroundHigh-fidelity manikins have been shown to be useful in teaching appropriate cardiopulmonary resuscitation (CPR) techniques. Similarity of manikin chest compression characteristics to real children is desirable. Little data exists on thorax stiffness in infants and children to guide manikin construction.ObjectiveTo determine a ‘consensus clinical-expert assessment’ of the pediatric chest stiffness for two specific age groups—infants and 5-year-olds.MethodsFour manikins in each of two sizes (5-year child, 6-month infant) were identically constructed, except for thorax downstroke spring stiffness. Health care providers with pediatric CPR experience provided chest compressions to each manikin in random order, masked to thoracic stiffness. Each health care provider was instructed to identify the manikin with downstroke thoracic stiffness most similar to children on whom they have performed chest compressions. Duplicate assessment of a randomly selected, previously assessed manikin was performed to assess health care provider consistency using the kappa statistic. Subject inter-rater agreement on which manikin best approximated a child of that age was assessed by calculating the percentage of subjects who identified that manikin as the best approximation of an actual child.ResultsA convenience sample of 63 international experts was obtained: 52 from Critical Care, 3 from Emergency Medicine, 4 from Pediatrics, and 4 from other specialties. There were 6 and 8 experts whose assessments were inconsistent for the infant manikins and child manikins, respectively. Approximately half of the subjects agreed on a single manikin as the best approximation of the human for both the infant (46%) and child manikins (43%). Excluding assessments of stiffness “out of range”, the percentage of experts who agreed on a single manikin as the best approximation for the human increased to approximately 90% for each manikin size.ConclusionExperienced health care providers consistently identified and agreed on the manikin thorax stiffness which they felt best approximated downstroke chest compression stiffness of children and infants. Expert opinion can be used to create manikins with realistic spring stiffness for CPR training. Further study is needed to evaluate whether enhanced manikin biofidelity will improve CPR performance.     

Posterior reversible encephalopathy syndrome in a patient with hepatitis B induced type 1 membranoproliferative glomerulonephritis

Posterior reversible encephalopathy syndrome (PRES) is a rare complication of nephrotic syndrome and corticosteroid therapy. Here, we discuss an 18 year old man with type 1 membranoproliferative glomerulonephritis (MPGN) secondary to hepatitis B infection who developed posterior leukoencephalopathy while on therapy with lamivudine and prednisone. He developed seizures and vision loss. He also had hypertension, but no sudden elevation was recorded at any time. Magnetic resonance imaging revealed patchy areas of altered signal intensity involving cortical gray and subcortical white matter in the bilateral frontoparietal regions, occipital cortices, temporal cortices and cerebellar hemispheres, and hyperintensity on T2W and FLAIR sequences. Tapering of prednisone and controlling hypertension resulted in clinical improvement within a few days, and in a month MRI was normal. Diagnosing PRES requires a high index of suspicion when treating similarly susceptible patients. PRES as a complication during the treatment of MPGN secondary to hepatitis B has, to our knowledge, never been reported previously in the literature.