Hepatitis C virus quasispecies in chronically infected children subjected to interferon–ribavirin therapy

Accumulating evidence suggests that certain features of hepatitis C virus (HCV), especially its high genetic variability, might be responsible for the low efficiency of anti-HCV treatment. Here, we present a bioinformatic analysis of HCV-1a populations isolated from 23 children with chronic hepatitis C (CHC) subjected to interferon–ribavirin therapy. The structures of the viral quasispecies were established based on a 132-amino-acid sequence derived from E1/E2 protein, including hypervariable region 1 (HVR1). Two types of HCV populations were identified. The first type, found in non-responders, contained a small number of closely related variants. The second type, characteristic for sustained responders, was composed of a large number of distantly associated equal-rank variants. Comparison of 445 HVR1 sequences showed that a significant number of variants present in non-responding patients are closely related, suggesting that certain, still unidentified properties of the pathogen may be key factors determining the result of CHC treatment.     

Microencapsulation of probiotics by efficient vibration technology

The target site of action of probiotics is the intestine. They must be surviving the stomach acidic condition before reaching the target site. Three probiotic bacteria were microencapsulated in sodium alginate beads using a sophisticated microencapsulation technology provided by BÜCHI B-390. This study reports the tolerance of the different microencapsulated Lactobacillus at low pH using simulated gastric juice, comparing it with the tolerance of free bacteria. The three microencapsulated strains displayed time-dependent acid sensitivity at pH values under 3.0. At pH 2.0, a dramatic reduction in bacterial survival occurred after 5?min, with only L. casei surviving after 30?min, with 75% survival. At pH 2.5 microencapsulated L. casei survived for 90?, L. reuteri survived for 60?and L. bulgaricus survived for only 30?min, respectively. The microencapsulation technology used in this study may effectively protect Lactobacillus from gastric conditions and permit comparisons between strains.     

Epidermal growth factor: the driving force in initiation of RPE cell proliferation

Background  

To analyze whether epidermal growth factor (EGF) exerts regulatory effects on proliferation and differentiation in ARPE19 cells after different incubation periods (24 vs. 48 h) for obtaining ideal conditions for feasible rejuvenation and autologous transplantation of retinal pigment epithelial cells (RPE cells).     

Metric properties of the mini‐mental Parkinson and SCOPA‐COG scales for rating cognitive deterioration in Parkinson's disease

Parkinson's disease (PD) is a chronic neurodegenerative disorder that causes cognitive impairment and dementia in ～30% of patients. Objective: Compare metric qualities of Mini‐Mental Parkinson (MMP) and scales for outcomes in Parkinson's disease‐cognition (SCOPA‐COG) with respect to their relative reliability, validity and ability to predict symptoms (mobility, quality of life, social repercussions, and mood) in PD patients. Outpatients (n=123, 78 males/45 females) diagnosed with PD were included in the study. A multilevel (hierarchical) modeling analysis was performed along with tests of reliability and validity to ascertain which of the two models better predicts symptoms related to PD. Results: The MMP differed significantly between patients with Hoehn and Yahr (H&Y) stages 1, 2 or versus 4/5 (grouped together). The SCOPA‐COG showed differences only between patients in H&Y stages 2 versus 4/5. Both scales were dependent on educational background and age. The SCOPA‐COG had a higher coefficient of variation (0.303) than the MMP (0.184), indicating that it was the more discriminative of the two. Conclusions: The SCOPA‐COG has some advantages over the MMP, the most important being a greater discriminative ability. Multilevel hierarchical analysis clarified the necessity of stratifying the PD population according to educational background, years of illness, and H&Y stage when using these scales. © 2010 Movement Disorder Society     

Measurements in the peripheral retina using LDF and laser interferometry are mainly influenced by the choroidal circulation

PURPOSE: Two laser based methods for the assessment of ocular hemodynamics in humans have been investigated: laser Doppler flowmetry (LDF) and laser interferometric measurement of fundus pulsation amplitude (FPA). When the laser with either of the two methods is focused onto the fovea it is obvious that only choroidal blood flow contributes to the signals. When the laser is, however, directed to other parts of the retina the situation is more complex. Whereas the retina shows a pronounced vasoconstrictor response to systemic hyperoxia the effect in the choroid is small. We therefore investigated the effect of 100% O2 breathing on results as obtained with the above mentioned techniques at different fundus locations. METHODS: Twelve healthy subjects were included. Four 15-minutes 100% O2 breathing periods were scheduled for each subject. During two of these breathing periods LDF was performed at the fovea (ChBFf) and at a fundus location approximately 7.5 degrees nasally to the fovea (ChBFp), respectively. During the other two periods FPA was assessed at the same fundus locations (FPAf, FPAp). RESULTS: ChBFf tended to decrease during 100% oxygen breathing (6 +/- 4%), but this effect was not significant. The decrease in ChBFp (10 +/- 4%), was comparable. FPAf (10 +/- 2%; P < 0.001) and FPAp (13 +/- 2%; P < 0.001) decreased significantly during systemic hyperoxia, but again there was no difference in the response obtained at the two fundus locations. CONCLUSION: When LDF and FPA are applied at the peripheral retina the obtained signal is mainly influenced by the choroidal circulation.     

Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems

The influence of pentylenetetrazol (PTZ)-induced kindling of seizures on the rat emotional behavior, the brain monoamine turnover rate measured in vitro, and correlation between behavioral and biochemical parameters, were examined in rats. The repeated administration of PTZ (35 mg/kg, ip) evoked kindled seizures in rats (Stage 4 or 5 of clonic-tonic convulsions-maximum). PTZ kindling caused selective changes in the rat emotional behavior, present in some models of anxiety only (a decreased freezing time in the conditioned freezing test and a decreased spontaneous and aversively conditioned ultrasonic vocalization). Simultaneously, PTZ kindling decreased the concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the prefrontal cortex, decreased the DA (HVA/DA ratio) turnover rate in the striatum, and inhibited the serotonin (5-HT) metabolism (5-HIAA/5-HT ratio) in the hippocampus and the prefrontal cortex. Correlations between dopamine (DA) or 5-HT regional metabolic rates in brain structures and animal behavior were either abolished or reversed in PTZ-kindled animals. It is concluded that both DA and 5-HT systems contribute to the emotional effects of PTZ-induced kindling of seizures. The hypothesis is put forward that PTZ kindling-induced inhibition of the serotonergic innervation may lead to the compensatory increase in 5-HT(1A) receptors in the dentate gyrus of the hippocampus, thus evoking the anxiolytic-like changes in animal behavior.     

Rapid desensitization of receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) in chick cerebral cortex

Pituitary adenylate cyclase-activating polypeptide (PACAP38) potently stimulates cyclic AMP formation in slices of chick cerebral cortex. One- to fifteen-minute pretreatment of slices with 30 nM PACAP38 led to a time-dependent attenuation (when compared with values observed in the control tissue) of the cyclic AMP response produced by subsequent re-stimulation with 1 microM PACAP38. Concentration-response curve for restimulation with PACAP38 applied at 0.01-1 microM to tissue slices preincubated for 15 min with 30 nM PACAP38 revealed dose-dependent decreases in subsequent cyclic AMP responses by 16-37%. It is concluded that in chick cerebral cortex, the receptors mediating PACAP-driven cyclic AMP responses (PAC1 receptors) undergo rapid homologous desensitization.     

The importance of intraoperative angiographic findings for predicting long-term patency in coronary artery bypass operations

BACKGROUND: The quality of anastomosis is the cornerstone in coronary artery bypass operations. Intraoperative coronary angiography confirms graft patency with the possibility to revise graft failure. The aim of this study was to describe the lesions found at "on-table" angiography, and to evaluate the significance of these immediate angiographic findings for the long-term patency. METHODS: A total of 57 grafts (42 left internal mammary artery grafts and 15 saphenous vein grafts) in 45 patients who underwent off-pump coronary artery bypass operations were included. On-table angiography was carried out with fixed angiographic equipment installed in the operating room. Follow-up angiographies were performed at 3 months and at 12 months. RESULTS: The most frequent finding in an on-table angiogram was spasm, which was not present at follow-up. Out of nine kinks, only one developed into a significant stenosis at follow-up. Of 44 grafts that were normal on-table, 37 (84%) were normal at the follow-up. Of 11 grafts with significant lesions on-table, eight (73%) were normal at the follow-up. Five percent of the grafts were revised because of the on-table angiography. CONCLUSIONS: On-table angiograms can be occasionally difficult to interpret because not all findings are important for later patency. Optimal results on-table predict good long-term results with a negative predictive value of 0.84, whereas significant lesions on-table have less impact on the follow-up results because the positive predictive value was only 0.38.