Neuroprotective effect of L-carnitine in the 3-nitropropionic acid (3-NPA)-evoked neurotoxicity in rats

A plant and fungal toxin, 3-NPA, acts as an inhibitor of mitochondrial function via irreversible inactivation of the mitochondrial inner membrane enzyme, succinate dehydrogenase (SDH). Inhibition of SDH disturbs electron transport and leads to cellular energy deficits and neuronal injury. We have shown that pretreatment with l-carnitine, while not significantly attenuating SDH inhibition, prevented hypothermia and oxidative stress-associated increased activity of free radical-scavenging enzymes. Here, a neurohistological method was applied to examine the effect of carnitine pretreatment against 3-NPA-induced neurotoxicity. Twenty adult male Sprague-Dawley rats were randomly divided into two groups (n = 10/group). Rats in the first group were injected twice with 3-NPA at 30 mg/kg s.c., 2 days apart, and the second group of animals received l-carnitine pretreatment at 100 mg/kg 30-40 min before 3-NPA administration. Rats in both groups were perfused 7 days later and their brains harvested. Degenerating neurons were identified and localized via the fluorescent marker Fluoro-Jade B. In the three animals that survived 3-NPA dosing, one exhibited no pathology, one exhibited moderate unilateral damage to the striatum, and the third exhibited extensive bilateral neuronal degeneration in multiple forebrain regions. In the seven surviving animals that received l-carnitine prior to 3-NPA insult, six exhibited no lesions, while one exhibited a modest unilateral lesion in the striatum. It appears that l-carnitine is protective against 3-NPA-induced toxicity, as reflected by both reduced mortality and significantly reduced neuronal degeneration.     

Occurrence of <Emphasis Type="BoldItalic">Cryptosporidium</Emphasis> spp. in red foxes and brown bear in the Slovak Republic

Wild animals can be involved in epidemiology of many important diseases and often act as reservoirs of pathogens which cause disease in domestic animals and humans. This paper aims the role of red fox (Vulpes vulpes) and brown bear (Ursus arctos) in the circulation of coccidian parasites from the genus Cryptosporidium. Cryptosporidiosis is known as an important enteric pathogen, clinical symptoms in particular in immune-compromised individuals range from mild to severe diarrhoea and dehydration, which could be fatal. Fecal samples from 62 red foxes shot during September 2010 to February 2011 and 63 brown bears collected during June 2010 to March 2011 in central and eastern Slovakia were examined for the qualitative determination of Cryptosporidium spp. antigens in faeces by sandwich ELISA kit. Overall, 38.7% (24/62) of faecal samples of red foxes and 55.6% (35/63) of faecal samples of brown bear were positive. Our preliminary results emphasize prevalence of Cryptosporidium spp. amongst brown bears and red foxes in Slovakia and highlight the potential risk for transmission of cryptosporidiosis to humans using the countryside for professional or recreational purposes.     

Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Wczesna niehematologiczna toksyczność po chemioterapii w wysokich dawkach i autologicznym przeszczepieniu komórek krwiotwórczych u chorych na nowotwory limfoidalne powyżej 60. roku życia

Early non-haematological toxicity of high dose therapy (HDT) and autologous haematopoietic cell transplantation (autoHCT) can be more hazardous in older patients (pts) with comorbidities. The aim of the study was to analyze incidence and grade of the organ-related early complications up to 30 days post-transplant period in elderly lymphoma patients. Between January 2005 and November 2011, 44 consecutive lymphoma pts underwent HDT followed by autoHCT. Median age of pts was 62 years (range 60–67). Conditioning regimens were: BEAM(carmustine, etoposide, cytarabine, melphalan) in 16, melphalan 200 in 22, cytarabine, melphalan or cyclophosphamide – in 6 pts. 32% pts had comorbidities: in 71% cardiovascular. Early non-haematologic complications within 30 days after autoHCT were reported in 84% of pts. The most common events were gastrointestinal (77%): 55% pts had prolonged (more than 7 days) diarrhoea grade III—IV, nausea and vomiting occurred in 40% of pts, 50% of pts demonstrated mucositis (grade III—IV in 34% of pts). Neutropenic fever was reported in 59% of pts with sepsis in 1.9% of pts. Cardiac events occurred in 9% of pts. Median hospitalization was 21 days (range 16—45). One patient died from transplanted related toxicity. HDT resulted in high incidence of non-hematologic toxicity in elderly patients during early post-transplant period. The toxicity of this procedure is acceptable, with mortality rate of only 2% in the elderly transplanted patients. The most common toxicities were: neutropenic fever, gastrointestinal toxicity and cardiac complications     

Electrophysiological features in patients with sinus node dysfunction and vasovagal syncope

Introduction

Syncope is a common presentation of sinus node dysfunction (SND). Some patients who receive a permanent pacemaker due to SND do not benefit from it and further diagnostic workup leads to the diagnosis of vasovagal syncope (VVS). The aim of the study was to identify electrophysiological criteria that can be used for identification of patients with SND and concurrent VVS.

Material and methods

Transoesophageal atrial pacing (TAP) was performed in 100 patients divided into four groups depending on symptoms and TAP results. Standard electrophysiological parameters of sinus node function and their variability were obtained in the basal state and after pharmacological autonomic blockade (AB).

Results

Patients with concurrent SND and VVS had a greater variability of sinoatrial conduction time assessed by Strauss’ method than patients without incidents of syncope (83.2 ±53.9 vs. 34.1 ±19.6, 47.8 ±33.6 and 32.1 ±22.99). Apart from abnormal sinus node recovery time and second pause, patients with SND had bigger basal state variability of these parameters. In patients with SND and concurrent vasovagal syncope the variability of sinus node recovery time (SNRT), corrected SNRT (cSNRT) and second pause (IIP) decreased after autonomic blockade.

Conclusions

Patients with concurrent SND and VVS have distinct electrophysiological features – greater sinoatrial conduction time (SACT) variability and the decrease of SNRT, cSNRT and IIP variability after AB. However, further studies in larger study groups are needed to validate our findings. Transoesophageal atrial pacing is a useful procedure in patients with syncope, especially when the coexistence of more than one cardiac cause is suspected.     

Mild CFTR mutations and genetic predisposition to lactase persistence in cystic fibrosis

Taking into account the reported incidence of hypolactasia in cystic fibrosis (CF) and the possible impact of milk products on nutritional status we aimed to assess the genetic predisposition to adult-type hypolactasia (ATH) and its incidence in CF. Single nucleotide polymorphism upstream of the lactase gene (LCT) was assessed in 289 CF patients. In subject with -13910C/C genotype (C/C) predisposing to ATH, hydrogen-methane breath test (BT) with lactose loading was conducted and clinical symptoms typical for lactose malabsorption were assessed. The percentage of CF patients with C/C was similar to that observed in healthy subjects (HS) (31.5 vs 32.5% ). Eleven out of 52 (24.5%) CF C/C patients had abnormal BT results. The recalculated frequency of lactose malabsorption was similar for the entire CF and HS populations (6.9 vs 7.2%). Similarly as in the control group, few CF patients have identified and linked to lactose consumption clinical symptoms. The frequency of LCT polymorphic variants in CF patients having and not having severe mutations of CFTR gene showed significant differences. The C allele was more frequent in homozygotes of the severe mutations than in patients carrying at least one mild/unknown mutation (P<0.0028) and in patients with at least one mild mutation (P < 0.0377). In conclusion, CF patients carrying mild CFTR mutations seem to have lower genetic predisposition to ATH. Lactose malabsorption due to ATH in CF is not more frequent than in the general population. Symptomatic assessment of lactose malabsorption in CF is not reliable.     

Innate immune response to influenza A virus in differentiated human alveolar type II cells

Alveolar Type II (ATII) cells are important targets for seasonal and pandemic influenza. To investigate the influenza-induced innate immune response in those cells, we measured the global gene expression profile of highly differentiated ATII cells infected with the influenza A virus at a multiplicity of infection of 0.5 at 4 hours and 24 hours after inoculation. Infection with influenza stimulated a significant increase in the mRNA concentrations of many host defense-related genes, including pattern/pathogen recognition receptors, IFN, and IFN-induced genes, chemokines, and suppressors of cytokine signaling. We verified these changes by quantitative real-time RT-PCR. At the protein level, we detected a robust virus-induced secretion of the three glutamic acid-leucine-arginine (ELR)-negative chemokines CXCL9, CXCL10, and CXCL11, according to ELISA. The ultraviolet inactivation of virus abolished the chemokine and cytokine response. Viral infection did not appear to alter the differentiation of ATII cells, as measured by cellular mRNA and concentrations of surfactant proteins. However, viral infection significantly reduced the secretion of surfactant protein (SP)-A and SP-D. In addition, influenza A virus triggered a time-dependent activation of phosphatidylinositol 3-kinase signaling in ATII cells. The inhibition of this pathway significantly decreased the release of infectious virus and the chemokine response, but did not alter virus-induced cell death. This study provides insights into influenza-induced innate immunity in differentiated human ATII cells, and demonstrates that the alveolar epithelium is a critical part of the initial innate immune response to influenza.     

High prevalence of anti-HEV antibodies among patients with immunosuppression and hepatic disorders in eastern Poland

IntroductionThe incidence of hepatitis E virus (HEV) infections in Poland is largely unknown. This study aimed to describe seroprevalence of markers of HEV infection among patients with immunodeficiency of diverse etiology and patients with advanced chronic liver diseases.Material and methodsFour hundred fifty patients were enrolled; among them, 180 persons were solid organ transplant recipients, 90 patients were HIV-infected and 180 persons had confirmed liver cirrhosis of different etiology. Serum anti-HEV-IgG, IgM antibodies and HEV-antigen were detected by ELISA (Wantai, China).ResultsIn the group of transplant recipients, serum anti-HEV-IgG antibodies were detected in 40.6%, IgM in 1.1% and HEV-Ag in 2.8% of subjects. In the HIV-infected population 37.7% had anti-HEV-IgG, 1.1% had anti-HEV-IgM and none had HEV-Ag. Among patients with advanced chronic liver diseases the highest prevalence of anti-HEV-IgG was recorded in alcohol-related liver cirrhosis (52.1%) (p = 0.049). In the population of all liver cirrhotics anti-HEV-IgG seroprevalence was 48.3%, anti-HEV-IgM seroprevalence was 5.0% and HEV-Ag seroprevalence was 1.7%. Older age and male gender were significant risk factors associated with increased anti-HEV-IgG prevalence, p = 0.0004 and p = 0.02, respectively.ConclusionsIn this large cohort a high seroprevalence of anti-HEV-IgG was detected in comparison to other European countries, with the highest rates in patients with alcoholic liver disease and in transplant recipients.     

Health-related quality of life in children with immunoglobulin A nephropathy – results of a multicentre national study

IntroductionImmunoglobulin A nephropathy (IgAN) may lead to end stage renal disease and severely affect patient functioning and wellbeing. The aim of the study was to evaluate health-related quality of life (HRQoL) in children and adolescents with IgAN, and compare HRQoL in relation to the disease course, social status and psychological factors, such as expressing anger and perceived personal competence.Material and methodsThe multicentre cross-sectional study included 51 patients ≥ 8 years from 7 paediatric nephrology centres in Poland. Psychometric analysis was performed using the Kidscreen-52 questionnaire to evaluate HRQoL, the Anger Expression Scale to evaluate the severity of anger and the Personal Competence Scale to measure general perception of personal competence.ResultsMean age of patients was 14.54 ±3.69 years; duration since the diagnosis of IgAN was 4.98 ±3.9 years. Patients with IgAN rated their psychological wellbeing as significantly worse compared to healthy peers (p < 0.05). The presence of proteinuria was associated with significantly worse physical wellbeing (58.72 ±18.45 vs. 74.44 ±22.97; p < 0.05). Current therapy (steroids/immunosuppressive drugs) had no effect on HRQoL in the study group. Perceived personal competence was rated high by 49% of children in the study group. Children with IgAN were characterized by lower intensity of expressed anger (p < 0.001) and significantly higher intensity of suppressed anger (p < 0.01) compared to reference ranges. Severity of expressed anger correlated positively with the parent relations and school environment dimensions of HRQoL.ConclusionsWe found lower HRQoL in regard to physical and psychological wellbeing in a group of Polish children with IgAN compared to healthy peers. HRQoL should be monitored in this patient group.     

Epstein-Barr virus gene expression and latent membrane protein 1 gene polymorphism in pediatric liver transplant recipients

Immunosuppressed pediatric transplant recipients are at risk of developing Epstein–Barr virus (EBV)‐associated complications (such as post‐transplant lymphoproliferative disorders). Monitoring of the EBV DNA level in blood alone has a low predictive value for the post‐transplant course of EBV infection and its complications. Therefore, additional prognostic markers are widely sought. The study aim was to analyze EBV gene expression patterns and LMP1 polymorphism in relation to EBV DNA levels in pediatric liver transplant recipients. EBV load measurement, LMP1 variant, and gene expression analysis were performed in collected prospectively multiple blood samples from 30 patients. Several distinct patterns of EBV gene expression were identified: latency 2 (71%), latency 3 (13%), latency 0 (11%), and lytic infection (5%). In most children's multiple blood samples, both EBV gene expression patterns and expression levels of individual EBV genes varied significantly over time. EBV gene expression patterns were not associated with the EBV load. However, the viral load correlated with the LMP1 and LMP2 expression (r = 0.34; P = 0.006, and r = 0.45; P = 0.001, respectively). Two variants of the LMP1 gene were detected, and they were consistent over time in individual patients. A wild type of LMP1 was associated with higher EBV‐DNA loads (P = 0.03). This indicates that EBV infection in immunosuppressed patients is a very dynamic process, but changes in the state of EBV infection do not influence significantly the viral load. The latter, however, can be associated with the activity of LMP1 and LMP2 genes, as well as polymorphism of LMP1. J. Med. Virol. 83:2182–2190, 2011. © 2011 Wiley Periodicals, Inc.