Relationship between HLA-DRB1*0101, DRB1*0301 alleles and interleukin-12 in haemophilic patients and hepatitis C virus positive hepatocellular carcinoma patients

The immune system can effectively eliminate hepatitis C virus (HCV) in 15 % of acute hepatitis cases. It is assumed that certain HLA-DR alleles present HCV epitopes more effectively to CD4 helper T cells than do others resulting in vigorous proliferative response to these epitopes and probably HCV recovery. So, we aimed at investigating the frequency of HLA-DRB1*0101 and DRB1*0301 alleles in child and adult haemophilics and in HCV positive hepatocellular carcinoma (HCC) patients in a trial to predict patients who require early therapeutic intervention. We also evaluated interleukin (IL)-12 levels in these patients since IL-12 induces interferon (IFN)-gamma production. This study was conducted on 50 antiHIV negative male patients subdivided into: 25 HCV negative haemophilics (group I), 10 HCV positive haemophilics (group II) and 15 HCV positive HCC (group III). Fifteen healthy persons of matched age and free of HCV and HIV infections were chosen as controls (group IV). All patients and controls were subjected to thorough history taking and clinical examination, routine and diagnostic investigations, viral markers, DRB1*0101 and DRB1*0301 amplification by polymerase chain reaction and plasma IL-12 quantitation by enzyme linked immunosorbent assay (ELISA). The frequencies of DRB1*0101 and DRB1*0301 were 20% and 30% respectively in HCV positive haemophilics and 13.3% and 40%, respectively in HCC. IL-12 levels were significantly lower in HCC cases than in HCV positive haemophilics. Among the haemophilics, IL-12 levels were non-significantly higher in children than in adults and were associated with the given number of blood product bags. DRB1*0101 and DRB1*0301 may have a role in HCV clearance and persistence in Egyptian patients with haemophilia and HCC. Low IL-12 levels encountered in HCV positive haemophilics suggest its relation to immunopathogenesis and outcome of HCV infection.     

Safety and effi cacy of hepatitis A vaccine in children with chronic liver disease

INTRODUCTION Hepatitis A virus (HAV) infection is common. In general, hepatitis A is a self-limited illness with a recovery time measured in months[1]. Young children are often asymptomatic, whereas adults are more likely to be symptomatic and may present…     

In Acute Myocardial Infarction Liver Parameters Are Associated With Stenosis Diameter

Detection of high-risk subjects in acute myocardial infarction (AMI) by noninvasive means would reduce the need for intracardiac catheterization and associated complications. Liver enzymes are associated with cardiovascular disease risk. A potential predictive value for liver serum markers for the severity of stenosis in AMI was analyzed.Patients with AMI undergoing percutaneous coronary intervention (PCI; n = 437) were retrospectively evaluated. Minimal lumen diameter (MLD) and percent stenosis diameter (SD) were determined from quantitative coronary angiography. Patients were classified according to the severity of stenosis (SD ≥ 50%, n = 357; SD < 50%, n = 80). Routine heart and liver parameters were associated with SD using random forests (RF). A prediction model (M10) was developed based on parameter importance analysis in RF.Age, alkaline phosphatase (AP), aspartate aminotransferase (AST), and MLD differed significantly between SD ≥ 50 and SD < 50. Age, AST, alanine aminotransferase (ALT), and troponin correlated significantly with SD, whereas MLD correlated inversely with SD. M10 (age, BMI, AP, AST, ALT, gamma-glutamyltransferase, creatinine, troponin) reached an AUC of 69.7% (CI 63.8–75.5%, P < 0.0001).Routine liver parameters are associated with SD in AMI. A small set of noninvasively determined parameters can identify SD in AMI, and might avoid unnecessary coronary angiography in patients with low risk. The model can be accessed via http://stenosis.heiderlab.de.     

Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles

Background

Nanoparticles (NPs) play an important role in anticancer delivery systems. Surface modified NPs with hydrophilic polymers such as human serum albumin (HSA) have long half-life in the blood circulation system.

Methods

The method of modified nanoprecipitation was utilized for encapsulation of paclitaxel (PTX) in poly (lactic-co-glycolic acid) (PLGA). Para-maleimide benzoic hydrazide was conjugated to PLGA for the surface modifications of PLGA NPs, and then HSA was attached on the surface of prepared NPs by maleimide attachment to thiol groups (cysteines) of albumin. The application of HSA provides for the longer blood circulation of stealth NPs due to their escape from reticuloendothelial system (RES). Then the physicochemical properties of NPs like surface morphology, size, zeta potential, and in-vitro drug release were analyzed.

Results

The particle size of NPs ranged from 170 to 190 nm and increased about 20–30 nm after HSA conjugation. The zeta potential was about -6 mV and it decreased further after HSA conjugation. The HSA conjugation in prepared NPs was proved by Fourier transform infrared (FT-IR) spectroscopy, faster degradation of HSA in Differential scanning calorimetry (DSC) characterization, and other evidences such as the increasing in size and the decreasing in zeta potential. The PTX released in a biphasic mode for all colloidal suspensions. A sustained release profile for approximately 33 days was detected after a burst effect of the loaded drug. The in vitro cytotoxicity evaluation also indicated that the HSA NPs are more cytotoxic than plain NPs.

Conclusions

HSA decoration of PLGA NPs may be a suitable method for longer blood circulation of NPs.     

Daily mood and sleep: reciprocal relations and links with adjustment problems

Children's sleep problems are common and associated with increased risk for adjustment problems. We examined daily links between children's sleep and mood, using a daily diary method and actigraphy. We also tested children's daily mood as a mediator of relations among sleep and children's broader internalizing and externalizing symptoms. A community sample of 142 children (mean age = 10.69 years; 57% girls; 69% European American, 31% African American) and their parents participated. For 1 week, children wore actigraphs and parents completed a daily telephone interview about their child's mood. Following the week of actigraphy, mothers and fathers reported on their child's adjustment. Multi‐level models indicated within‐person relations between children's mood and subsequent sleep fragmentation (indicated by increased activity) and sleep latency, and between‐person relations between sleep latency and subsequent mood on the next day. Significant indirect effects were found such that a more negative daily mood (aggregated across diary days) mediated relations between poor sleep efficiency and longer sleep latency and parent‐reported internalizing and externalizing symptoms. Findings extend previous research by highlighting disruptions to children's daily mood as a potential mechanism linking sleep problems to children's mental health.     

Inhibition of dipeptidyl peptidase-4 reduces glycemia, sustains insulin levels, and reduces glucagon levels in type 2 diabetes

The stimulation of insulin vs. inhibition of glucagon secretion in relation to the antidiabetic action of glucagon-like peptide-1 (GLP-1) is not established. Here, the influence of a 4-wk increase in circulating GLP-1 by inhibition of dipeptidyl peptidase-4 (DPP-4) on 24-h glucose and insulin and glucagon responses to breakfast was studied in subjects with dietary controlled diabetes [age: 65 +/- 8 yr (SD), body mass index: 27.3 +/- 3.3 kg/m(2), fasting plasma glucose: 9.0 +/- 1.3 mmol/liter]. Compared with placebo (n = 19), a specific DPP-4 inhibitor [(1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine) (LAF237); 100 mg daily, n = 18] reduced fasting glucose by 0.70 mmol/liter (P = 0.037), 4-h prandial glucose excursion by 1.45 mmol/liter (P < 0.001), and mean 24-h glucose by 0.93 mmol/liter (P < 0.001). Baseline and postprandial active GLP-1 were increased by LAF237. The glucagon response to breakfast was reduced by LAF237 (glucagon levels at 60 min were 88 +/- 8 pg/ml before treatment vs. 77 +/- 5 pg/ml after; P = 0.001). In contrast, the overall insulin levels were not altered. The 4-wk reduction in glucagon correlated with the reduction in 2-h glucose (r = 0.61; P = 0.008). No such association was observed for insulin. Thus, improved metabolic control by DPP-4 inhibition in type 2 diabetes is seen in association with reduced glucagon levels and, despite the lower glycemia, unaltered insulin levels.     

Dosing Accuracy of Two Disposable Insulin Pens According to New ISO 11608-1: 2012 Requirements

Objective:

The aim was to compare 2 disposable insulin pens, FlexTouch® (Novo Nordisk, insulin aspart) and SoloSTAR® (Sanofi, insulin glulisine), according to new ISO 11608-1:2012 requirements for dosing accuracy.

Methods:

Sixty pens of each type were tested at 1, 40, and 80 U doses. Following the new ISO requirements, each dose was delivered from the front, middle, and rear one-third of the pen. Statistical analysis was performed using Student’s t test.

Results:

Both pens delivered all doses within ISO limits. The difference between the average measured dose and the target dose was significantly smaller for SoloSTAR than FlexTouch at 40 U (P = .009) and 80 U (P = .008), but not at 1 U (P = .417).

Conclusion:

Both insulin pens fulfilled the dosing accuracy requirements defined by ISO 11608-1:2012 at all 3 dosage levels.     

Enhanced thromboxane synthesis during chronic reductions in uterine perfusion pressure in pregnant rats

BACKGROUND: The purpose of this study was to determine the role of thromboxane A2 (TXA2) in a conscious, chronically instrumented rat model of pregnancy-induced hypertension (PIH) produced by chronic reductions in uterine perfusion pressure (RUPP). METHODS: Mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and 24-h urinary excretion of TXB2 (metabolite of TXA2) were determined in normal pregnant rats and RUPP pregnant rats. RESULTS: At day 20 of pregnancy, RUPP rats showed a significantly (P < .05) higher MAP (125 +/- 3 mm Hg v 100 +/- 2 mm Hg) as compared with normal pregnant controls. The elevation in arterial pressure in RUPP group was associated with a marked increase (P < .05) in the urinary concentration of TXB2 compared with normal pregnant group (3663 +/- 488 v 2646 +/- 257 pg/24 h). Baseline GFR (1.74 +/- 0.13 v 2.40 +/- 0.20 mL/min, respectively, P < .05) and ERPF (5.13 +/- 0.44 v 6.44 +/- 0.58 mL/min, respectively) were decreased in RUPP rats relative to pregnant controls. Infusion of a TX receptor antagonist, SQ 29,548 (2 mg/kg bolus plus 2 mg/kg per h infusion) had no significant effect on increased MAP in RUPP pregnant rats. Similarly, ERPF and GFR did not change during acute blockade of TXA2 receptors in this group. CONCLUSION: These findings suggest that enhanced production of TXA2 does not play a major role in mediating the hypertension and renal vasoconstriction produced by chronic RUPP in pregnant rats.