Serum zinc as a factor predicting response to interferon-alpha2b therapy in children with chronic hepatitis B

Although it has been unclear why more than 50% of children with chronic hepatitis B virus infection do not respond to interferon therapy, in some instances resistance to interferon probably is caused by an inability to stimulate appropriately cellular immune responses to hepatitis B virus. It is known that immune integrity is tightly linked to zinc status. We examined the relationship between serum zinc levels and response to interferon (INF)-α therapy in children with chronic hepatitis B. Twenty-five children with chronic hepatitis B infection were injected with 5 × 10⁶ units/m² recombinant IFN-α 2b subcutaneously three times weekly for 9 mo. Children were followed for at least 9 mo after the end of therapy. Sustained response was obtained in eight (32%) patients. Although initial serum zinc and alanine aminotransferase levels were significantly higher; initial hepatitis B Virus (HBV)-DNA values, hepatic activity index, periportal necrosis, and fibrosis scores were significantly lower in sustained responders than in nonresponders. Mean baseline serum zinc, alanine aminotransferase and HBV-DNA values, histologic activity index, periportal necrosis, and fibrosis scores were predictive of response to IFN-α 2b therapy. These findings suggest that serum zinc levels might be used as a factor predicting response to interferon-α 2b therapy, and so may help in identifying those children with a better chance of response.     

The effect of hyperbaric oxygen on neuroregeneration following acute thoracic spinal cord injury

AimsAlthough hyperbaric oxygen (HBO) treatment following spinal cord injury (SCI) have been studied in terms of neurological function and tissue histology, there is a limited number studies on spinal cord tissue enzyme levels.Main methodsThe effect of HBO treatment in SCI was investigated by measuring superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), nitric oxide synthase (NOS) and nitric oxide (NO) activity in the injured tissue. SCI was induced by applying an aneurysm clip extradurally at the level of T9-T11 vertebrae. Preoperative HBO (preopHBO) treatment was applied for 5 days and postoperative HBO (postopHBO) for 7 days.Key findingsIn the preopHBO group, a significant decrease was observed in NOS and NO compared to the SCI group. There was a decrease in SOD, NOS and NO in the postopHBO group when compared to the SCI group. In the pre–postHBO group SOD, GPx, NOS and NO decreased significantly. There was a decrease in SOD in postopHBO compared to preopHBO. In the prepostopHBO, SOD decreased significantly compared to that in the preopHBO group. The prepostopHBO presented a significant decrease in GPx compared to postopHBO (p < 0.05 for all parameters). No significant difference was observed for catalase for all groups. Significant improvement was found in BBB scores for both postopHBO and prepostHBO groups when compared to the SCI group (p < 0.05).SignificanceHBO treatment was found to be beneficial following SCI in terms of biochemical parameters and functional recovery in the postoperative period.     

Sequence-defined glycopolymer segments presenting mannose: synthesis and lectin binding affinity

We present for the first time the synthesis of sequence-defined monodisperse glycopolymer segments via solid-phase polymer synthesis. Functional building blocks displaying alkyne moieties and hydrophilic ethylenedioxy units were assembled stepwise on solid phase. The resulting polymer segments were conjugated with mannose sugars via 1,3-dipolar cycloaddition. The obtained mono-, di-, and trivalent mannose structures were then subject to Con A lectin binding. Surface plasmon resonance studies showed a nonlinear increase in binding regarding the number and spacing of sugar ligands. The results of Con A lectin binding assays indicate that the chemical composition of the polymeric scaffold strongly contributes to the binding activities as well as the spacing between the ligands and the number of presented mannose units. Our approach now allows for the synthesis of highly defined glycooligomers and glycopolymers with a diversity of properties to investigate systematically multivalent effects of polymeric ligands.     

Rosiglitazone treatment reduces hippocampal neuronal damage possibly through alleviating oxidative stress in chronic cerebral hypoperfusion

Oxygen free radicals and lipid peroxidation may play significant roles in the progress of injury induced by chronic cerebral hypoperfusion of the central nervous system. Rosiglitazone, a well known activator of PPARγ, has neuroprotective properties in various animal models of acute central nervous system damage. In the present study, we evaluate the possible impact of rosiglitazone on chronic cerebral hypoperfused-rats in regard to the levels of oxidative stress, reduced glutathione, and hippocampal neuronal damage. Chronic cerebral hypoperfusion was generated by permanent ligation of both common carotid arteries of Wistar rats for one month. Animals in treatment group were given rosiglitazone orally at doses of 1.5, 3, or 6mg/kg per day of the 1month duration. The treatment significantly lowered the levels of both malondialdehyde and neuronal damage, while elevated the reduced glutathione level markedly. These findings suggest that the beneficial effect of rosiglitazone on hypoperfusion-induced hippocampal neuronal damage might be the result of inhibition of oxidative insult.     

Evaluation of biological effects induced by diagnostic ultrasound in the rat foetal tissues

In recent years, there has been growing interest in estimating the degree of heating caused by the diagnostic ultrasound in clinical practice. Both theoretical and experimental methods have been suggested for estimating the heating potential, or thermal hazard, of diagnostic ultrasound. Aim of this study was to evaluate in vivo effects of ultrasound exposure of variable duration (from 10 up to 20 min) with commercially available imaging systems commonly used for diagnostic imaging. Numerical results related to the thermal effect are obtained by simulation program based on B-mode (scanning) and Doppler (non-scanning). To investigate the biological effects of the ultrasound exposure to the brain and liver tissues, the antioxidant enzyme activity and thiobarbituric acid reactive substances (TBARS) of the tissues were evaluated. In liver tissue, as a lipid peroxidation index, TBARS levels very significantly increase in Doppler group compared to control. However, in B-mode, TBARS levels are the same with the control group. Use of B-mode in foetal tissue is more reliable than Doppler mode because temperature rise is very small compared to the Doppler mode. On the other hand, the antioxidant enzyme activities tend to increase in B-mode and Doppler groups compared to the control group as a defensive mechanism. In the brain tissue, lipid peroxidation is increased slightly in B-mode compared to the control group. This situation is related to the molecular structure of the brain tissue because of its high lipid concentration. In brain tissue, the antioxidant enzyme activities and lipid peroxidation were significantly increased, such as liver tissue in Doppler groups. Doppler ultrasound may produce harmful effects in rat foetus liver and brain tissues as a result of the high temperature rises.     

A novel mutation for TAP deficiency and its possible association with Toxoplasmosis

We describe two siblings (a male patient and his older sister) with a novel mutation in the peptide transporter associated to antigen processing (TAP). The index case presented with not only granulomatous skin lesions and recurrent sino-pulmonary infections, often associated with this deficiency, but also a severe pulmonary toxoplasmosis. His toxoplasmosis and skin lesions were successfully treated.     

Repulsive separation of the cytoplasmic ends of transmembrane helices 3 and 6 is linked to receptor activation in a novel thyrotropin receptor mutant (M626I)

Ligand-dependent activation of G protein-coupled receptors (GPCRs) involves repositioning of the juxtacytoplasmic ends of transmembrane helices TM3 and TM6. This concept, inferred from site-directed spin labeling studies, is supported by chemical cross-linking of the cytoplasmic ends of TM3 and TM6 blocking GPCR activation. Here we report a novel constitutive active mutation (M626I) in TM6 of the TSH receptor (TSHR), identified in affected members of a family with nonautoimmune hyperthyroidism. The specific constitutive activity of M626I, measured by its basal cAMP generation corrected for cell surface expression, was 13-fold higher than that of wild-type TSHR. Homology modeling of the TSHR serpentine domain based on the rhodopsin crystal structure suggests that M626 faces the side chain of I515 of TM3 near the membrane-cytoplasmic junction. Steric hindrance of the introduced isoleucine by I515 is consistent with the fact that shorter or more flexible side chains at position 626 did not increase constitutivity. Furthermore, a reciprocal mutation at position 515 (I515M), when introduced into the M626I background, acts as revertant mutation by allowing accommodation of the isoleucine sidechain at position 626 and fully restoring the constitutive activity to the level of wild-type TSHR. Thus, repulsive separation of the juxtacytoplasmic TM6 and TM3 in the M626I model conclusively demonstrates a direct link between the opening of this cytoplasmic face of the receptor structure and G protein coupling.     

Changes in the Expression of Selenoproteins in Mesial Temporal Lobe Epilepsy Patients

Selenoproteins are enzymes containing selenium in their structure and are involved in cellular processes such as defense against oxidative stress and cell survival. The aim of this study is to investigate the expression of four selenoproteins (GPX1, TRXR1, SELP and SELW) in the hippocampus of intractable mesial temporal lobe epilepsy (MTLE) patients who underwent curative surgery. The selenoproteins is investigated at the mRNA level via RT-PCR and in situ hybridization and by immunostaining at the protein level. The expression of SELW exhibited a relative induction of more than tenfold, and immunostaining findings provided evidence that this upregulation is confined to neurons. GPX1 was also upregulated 2.3-fold, and TRXR1 was downregulated between 70 and 20% in MTLE patients. The profound induction of SELW has been accompanied by GPX1 and displayed a strong correlation with BCL2 expression, suggesting a protective role for these selenoproteins, and may be an indicator of a defense mechanism in surviving neurons.