Enhanced Antitumor Efficacy of Vasculostatin (Vstat120) Expressing Oncolytic HSV-1

Oncolytic viral (OV) therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific receptor. To date, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested the therapeutic efficacy of combining Vstat120 gene delivery in conjunction with OV therapy. We constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter. Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO-produced Vstat120 efficiently inhibited endothelial cell migration and tube formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited angiogenesis (P = 0.007) in vivo. There was a significant suppression of intracranial and subcutaneous glioma growth in mice treated with RAMBO compared to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically significant reduction in tumor vascular volume fraction (VVF) and microvessel density (MVD) was observed in tumors treated with RAMBO. This is the first study to report the antitumor effects of Vstat120 delivery into established tumors and supports the further development of RAMBO as a possible cancer therapy.     

Interaction of the hepatitis C virus (HCV) core with cellular genes in the development of HCV-induced steatosis

Hepatitis C virus (HCV) has chronically infected a large number of patients, leading to the development of steatosis, cirrhosis and, ultimately, hepatocellular carcinoma. The pathogenesis of HCV has not been fully explained, although steatosis is considered to contribute greatly to liver fibrosis progression, modulating host-cell lipid metabolism. Suspected underlying molecular mechanisms include interactions between HCV proteins and intracellular lipid metabolic pathways. Recent studies have suggested that the nucleocapsid of HCV (core) acts as a pathogenic factor involved in lipid droplet accumulation, changes in lipogenic gene expression and/or the activity of lipogenic proteins in a genotype-specific manner. In this review, we have tried to summarize the current knowledge regarding HCV-induced steatosis and the regulation of expression of host genes and receptors that aid in the viral life cycle and promote liver diseases.     

Persistent protein losing enteropathy in post measles diarrhoea.

Faecal alpha 1 antitrypsin was measured in two groups of children with diarrhoea aged 6 months to 6 years during the acute and recovery stages of the illness. Group 1 comprised 19 children with a history of measles in the two weeks preceding admission to hospital. In this group there were six cases of Shigella species, six enterotoxigenic Escherichia coli, and five rotavirus, and two did not yield an aetiologic agent. Group 2 comprised 15 children with diarrhoea only. In this group there were five cases of Shigella species, five enterotoxigenic Escherichia coli, and five rotavirus. Children with rotavirus diarrhoea belonging to both groups showed a transient high faecal clearance of alpha 1 antitrypsin during the acute stage. Post measles cases of diarrhoea showed significantly higher faecal clearance of alpha 1 antitrypsin than group 2 subjects in both the acute and recovery stages. The faecal clearance of alpha 1 antitrypsin in both groups was significantly higher during the acute stage compared with the recovery stage. Highest faecal clearances of alpha 1 antitrypsin were observed in children with post measles shigellosis in the acute stage and they also had persistently raised concentrations, thus suggesting prolonged protein losing enteropathy.     

Influence of maternal diabetes on serum leptinemic and insulinemic status of the offspring: A case study of selected patients in a tertiary care hospital in Bangladesh

IntroductionLeptin is now known to be an important hormone affecting intrauterine fetal growth. Since growth of fetus is also affected by the glycemic status of the mother. Serum leptin of infant is influenced by the maternal diabetic state. Investigation of cord blood leptin in babies of DM (Diabetes Mellitus) and GDM (Gestational Diabetes Mellitus) mothers (controlled blood glucose levels) may provide some indication about involvement of genetic factor in the development of leptin abnormalities in fetus.AimThe study was taken to investigate whether cord blood insulin, c-peptide and leptin levels correlate with birth weight in offspring of DM mother.MethodsBlood was drawn from umbilical cord of 30 babies from GDM mothers (GDM-babies), 45 babies from Type 2 DM Mothers (DM-babies), and 30 babies from ND (Nondiabetic) mothers (ND-babies) of term pregnancy. Weight, blood glucose, placenta, serum leptin and c-peptide of the babies were measured.ResultsBirth weight of GDM and DM babies were significantly higher compared to ND-babies. Glucose level in GDM babies was significantly higher than ND and DM babies. Leptin levels in GDM babies were significantly higher than that of ND and DM babies. Serum c-peptide in GDM babies was significantly higher than DM and ND babies. However, there was no significant difference in leptin–glucose ratio among the three groups. Irrespective of degree of hyperglycemia leptin is a major determinant of fetal growth.ConclusionsDM mother produces different insulinemic and leptinemic responses in the fetus indicating a possible genetic involvement.     

Randomized trial of Telemonitoring to Improve Heart Failure Outcomes (Tele-HF): study design

BackgroundTelemonitoring, the use of communication technology to monitor clinical status, is gaining attention as a strategy to improve the care of patients with heart failure. A system of frequent monitoring could alert clinicians to early heart failure decompensation, providing the opportunity for intervention before patients become severely ill and require hospitalization. Moreover, patients' participation in a daily monitoring program could have a favorable effect on their health behaviors. The literature on telemonitoring for heart failure, however, is quite limited.Methods and MaterialsTelemonitoring to Improve Heart Failure Outcomes (Tele-HF) is a randomized, controlled, trial designed to compare an automated, daily symptom, and self-reported weight monitoring intervention with usual care in reducing (all-cause) hospital readmissions and mortality among patients recently hospitalized with decompensated heart failure. The intervention will be implemented and all outcomes will be assessed over a 6-month period. The purpose of the intervention is to collect information about symptoms, clinical status and weight and to engage participants in their own self-care. Participants are recruited from general cardiology, heart failure specialty, and primary care practices across the United States.ConclusionsThe results of this study may inform future policy decisions regarding implementation of telemonitoring in treatment of heart failure.     

Educational disadvantage impairs functional recovery after hospitalization in older persons

PURPOSE: To determine whether low educational level is associated with poor functional recovery after hospitalization in older adults. METHODS: We followed 862 patients (374 with low education, defined as 相似文献   

Erratum to: Bicarbonate therapy in the treatment of septic shock: a second look

The use of supplemental sodium bicarbonate for the treatment of patients with septic shock and elevated blood lactate levels remains a controversial therapy. We conducted a retrospective study between March 2004 and February 2009 of 36 consecutive patients diagnosed with septic shock who received continuous infusion of bicarbonate therapy. A control group was matched 1:1 for age, site of infection, and predicted mortality by APACHE II. All patients were managed according to standard protocols. The median time until reversal of shock did not achieve statistical significance between the bicarbonate group (44.5 h [95% confidence interval [CI] 34–54] and the control group (55.0 h [95% CI 39–60] (p = 0.09). The median time to liberation of mechanical ventilation was significantly reduced in the bicarbonate group (10 days [95% CI 5.0–13.0] compared to the control group (14 days [95% CI 9.0–19.0], p = 0.02). The length of intensive care unit (ICU) stay was also shorter in the surviving patients who received bicarbonate compared to controls (median 11.5 days (95% CI 6.0–16.0) vs. 16.0 days (95% CI 13.5–19.0), respectively; p = 0.01). However, there was no difference in 28-day mortality between the two study groups (28%; 95% CI 14–45% vs. 33%; 95% CI 19–51%, respectively; p = 0.79). Infusion of sodium bicarbonate in septic patients with arterial hyperlactatemia may facilitate weaning from mechanical ventilation and reduce length of ICU stay.     

Gender differences in serum leptin concentrations from umbilical cord blood of newborn infants born to nondiabetic, gestational diabetic and type-2 diabetic mothers

To investigate gender differences, if any, in leptin concentrations from umbilical cord blood of new born infants of mothers with type 2 diabetes mellitus (DM), gestational diabetes mellitus (GDM), and Non diabetic (ND) at delivery. Serum leptin concentrations were measured in 105 newborns (53 males and 52 females in the three groups). Blood was taken from the umbilical cord of the babies at delivery. Maternal anthropometric measurements were recorded within 48 hours after delivery. Pearson correlation coefficient was used to explore the relationship between serum leptin concentrations and anthropometric measures of the fetus and their mother. Both Serum leptin level and serum C-peptide was measured by chemiluminescence based ELISA. The median range of leptin concentration in cord blood was ND group: Male [13.91 (3.22 – 47.63)], Female [16.88 (2 – 43.65)]; GDM group: Male [32 (7 – 76.00)], Female [36.73 (4.80 – 81.20)]; DM group: Male [20.90 (2 –76.00)], Female [32 {2.58 – 80.67)]. Cord serum leptin levels correlated with birth weight(r=0.587, p=0.0001), ponderal index (PI) (r=.319, p=0.024)of the babies and body mass index (BMI) (r=−0.299, p=0.035) of their mothers but did not correlate with gestational age, cord serum C-peptide concentration or placental weight at delivery. Leptin concentrations were higher in the female fetus in comparison to the male fetus. Birth weight of the female fetuses were also higher than that of male fetus. We found that there are very strong associations between cord leptin concentrations at delivery and birth weight, ponderal index of the baby, body mass index of the mothers with Type 2 DM. We also found that high leptin levels could represent an important feedback modulator of substrate supply and subsequently for adipose tissue status during late gestation or adipose tissue is the major determinant of circulating leptin levels.     

Effect of Solanum trilobatum on hepatic drug metabolising enzymes during diethylnitrosamine-induced hepatocarcinogenesis promoted by Phenobarbital in rat

The present study was aimed to investigate the chemopreventive effects of Solanum trilobatum (ST) extract against diethylnitrosamine (DEN)-induced hepatocarcinogenesis promoted by Phenobarbital (PB) in Wistar rats. Hepatocarcinogenesis was initiated by a single intraperitoneal injection of DEN (200 mg/kg b.w.) and promoted with PB (0.05%) in basal diet. The experimental study extended for periods of 13 and 26 weeks. Alcoholic extract of ST was orally administered for the entire experimental period after initiation along with commencement of promotion. The chemopreventive effect of ST was assessed from the incidence of nodules, drug metabolizing phase I components such as contents of cytochrome P450, cytochrome b(5), activities of NADPH cytochrome c reductase, NADH - cytochrome b(5) reductase and phase II components such as levels of glutathione, activities of UDP-glucuronyl transferase, glutathione S-transferase and gamma-glutamyl transpeptidase in the liver. Lipid peroxidation at basal and prooxidants-induced (NADPH + ADP + Fe and Ascorbate + Fe) states was assessed in the microsomes. Animals administered with ST extract evidenced significant inhibition of tumor nodular incidence in DEN + PB + ST animals compared to DEN + PB animals, with favorable alterations in the hepatic drug-metabolizing phase I and phase II components. Administration of ST inhibited basal and pro-oxidant-induced lipid peroxidation. The present result suggests the probable mediation of chemoprevention by ST against DEN-induced carcinogenesis by the modulation of drug metabolizing components in the liver of treated animals.