The effect of the synthetic neuroprotective dipeptide noopept on glutamate release from rat brain cortex slices

The level of spontaneous and K⁺-stimulated release of endogenous glutamate was studied in experiments on slices of brain cortex of Wistar rats. Pronounced spontaneous release of the neuromediator and its increase under conditions of stimulation were registered by high-performance liquid chromatography with electrochemical detection. The effect of the nootropic and neuroprotective dipeptide Noopept (GVS-111) on release of glutamate was investigated. The peptide in concentrations of 10^?5 and 10^?6 M caused a statistically significant decrease in spontaneous and K⁺-stimulated glutamate release. This effect could be the basis of the neuroprotective action of the peptide, suggesting that further studies of Noopept as neuroprotector are very promising.     

Dynamics of HIV replication in lymphocytes and the efficacy of protease inhibitors

Using a system that allows transfection of resting peripheral blood lymphocytes (PBLs) two questions were addressed: the kinetics of HIV replication from the state of proviral latency, and the impact of different parameters on the efficacy of protease inhibitors to control HIV replication. PBLs were transfected with an infectious full length HIV-DNA harboring a luciferase reporter gene and activated thereafter. Ritonavir was added at different times at doses ranging from to 0.06 to 1 microM. Viral expression was assessed by quantifying luciferase activity in cell extracts and levels of p24 HIV antigen in culture supernatants. After transfection and cell activation, intracellular expression of HIV proteins, as assessed by luciferase detection, occurred within 2 hr. HIV-gag p24 antigen was detected in culture supernatants between 6 and 8 hr post-activation. Ritonavir was effective in blocking viral replication when given within 4 hr following HIV reactivation, but a delay in ritonavir administration or breaches in ritonavir levels after 6 hr from transfection resulted in viral escape. HIV reactivation from proviral latency in PBLs is an extremely rapid process, faster than estimated from previous models. These data stress the need for maintaining effective antiretroviral concentrations to block completely viral replication.     

Animal model of bile duct dilatation created with minimally invasive surgery

RATIONALE AND OBJECTIVES: The purpose of the study was to evaluate a method of producing obstruction of the common bile duct and concomitant biliary duct dilatation in an animal model. MATERIALS AND METHODS: Laparoscopic placement of a double-balloon occlusion device was used to produce common bile duct obstruction and bile duct dilatation in pigs. RESULTS: One week after the procedure, common bile duct obstruction and dilatation of the biliary tree were demonstrated with either percutaneous transhepatic cholangiography or percutaneous cholecystography. CONCLUSION: The use of this method is technically feasible and provides a useful subacute and chronic animal model of common bile duct obstruction and dilatation of the biliary tree for percutaneous interventional training and research purposes.     

A Chryseobacterium meningosepticum outbreak observed in 3 clusters involving both neonatal and non-neonatal pediatric patients

Three clusters of Chryseobacterium meningosepticum infections in a tertiary health center in July 2006 and January 2007 involving 8 newborns and 5 older children were investigated. The index patient was from the neonatal intensive care unit, and the older patients were from other pediatric wards. Cultures were obtained from the environment and from health care workers' hands as part of an outbreak investigation. C meningosepticum was isolated from hand cultures obtained from a senior resident and from environmental cultures obtained from powdered infant formula, an electrical button, a computer keyboard, phone, a doorknob, and an Ambu bag. Antibiogram typing and enterobacterial repetitive intergenic consensus sequence polymerase chain reaction indicated that all of the isolates were epidemiologically related. Nine patients improved on antimicrobial treatment, and 4 premature infants died after the infection. C meningosepticum is a well-known etiologic agent for nosocomial infections involving newborns and immunocompromised patients. Wet and dry environmental surfaces and equipment may act as a source or play a role in disseminating the microorganism. Outbreaks may be controlled with strong emphasis on infection control measures.     

Anti-GM2 antibody positive Guillain-Barré syndrome presenting with ataxia in a pediatric patient: An atypical manifestation

Guillain-Barré syndrome (GBS) is the most prevalent cause of acquired paralytic neuropathy in children, however, ataxia as the initial presenting sign in children is very rare. Antiganglioside antibodies are presumed to have an important role in the pathophysiology and some phenotypic correlations have been reported. Anti-GM2 antibody, unlike other antibodies, is far less detected in GBS. Here, we report a 7.5-year-old female, initially presenting with ataxia, an atypical presenting symptom in a child, is promptly diagnosed and treated successfully as GBS. Atypical history of urinary infection in our patient is an interesting aspect. The presence of isolated anti-GM2 IgM antibody and ataxia in a pediatric patient is rare. In this case report, we aim to describe an atypical initial presentation, with positive anti-GM2 antibodies, as well as review literature on isolated anti-GM2 positive pediatric GBS patients.     

Hepatitis C Virus Capsid Protein and Intracellular Lipids Interplay and its Association With Hepatic Steatosis

Background:

Hepatitis C Virus (HCV) is a major causative agent for chronic liver disease worldwide. Hepatic steatosis is a frequent histological feature in patients with chronic HCV. Both host and viral factors are involved in steatosis development. It results from uncontrolled growth of cytoplasmic lipid droplets (LDs) in hepatocytes. LDs are intracellular organelles playing key role in the HCV life cycle. HCV core protein localizes at the LD surface and this localization is crucial for virion production.

Objectives:

We explored in vitro interplay of core and LDs to investigate the role of core in steatosis.

Materials and Methods:

Core expression vectors were transfected in Huh-7 cells. The effect of core protein on LDs content and distribution in the cells was monitored by confocal microscopy. Cells were treated with oleic acid to analyze the effect of increased intracellular LDs on core expression. Core protein expression was monitored by western blot analysis.

Results:

Core expression altered the intracellular lipid metabolism, which resulted in a change in LDs morphology. Core LDs interaction was required for this effect since the mutation of two prolines (P138A, P143A), which impair LDs localization, had no impact on LDs morphology. Conversely, oleic acid induced intracellular LD content resulted in increased core expression.

Conclusions:

Core-LDs interaction may be an underlying molecular mechanism to induce liver steatosis in patients with HCV infection. This interaction is also crucial for efficient viral replication and persistence in infected cells. Steatosis can also interfere with efficient standard interferon therapy treatment. Management of steatosis should be considered along with standard care for achieving higher sustained virological response (SVR) in patients receiving interferon regimen.