The influence of air pollution on respiratory allergies, asthma and wheeze in childhood in Hungary.

BACKGROUND: Higher exposure to air pollution may contribute to the increased prevalence of allergic diseases in children. The study investigated the associations between the prevalence of childhood respiratory diseases and long-term exposure to NO2, SO2, PM10, especially some surrogates in schoolchildren in Hungary. We also analyzed the possible modification effects of some confounders by interaction analysis. METHODS: A total of 6771 children aged 8-9-year-old residing at their current addresses since their births with air pollution monitoring stations were selected into this analysis. Health outcomes and their possible determinants, as well as surrogates of air pollution were surveyed by using a standardized questionnaire. Long-term exposure to PM10, NO2, and SO2 was calculated at settlement level derived from daily average concentrations of pollutants. Descriptive and analytical statistical methods were applied. RESULTS: NO2 levels were positively associated with respiratory allergies and asthma. Decreased risk for ragweed, any other pollen, house dust mite and animal fur allergy was detected with PM10 level. There were significant associations between respiratory allergies to ragweed, any other pollen, house dust mite, animal fur, wheeze symptoms and living or attending school nearby a factory, power station or bus station as well as living in a home with intensive noise or vibration. Gender, parental atopy, home mold and early respiratory infection were significant effect modifiers in some cases. CONCLUSIONS: The results of this study indicate that respiratory health in children is adversely affected by air pollutants.

Environmental characteristics and taxonomy of microscopic fungi isolated from washing machines.

Washing machines (WMs) are convenient places for fungal colonization. This study is focused on fungal diversity of WMs, and investigates relationships between habits of WM users and colonising species. Housekeeping conditions and habits were assessed in Hungary with a questionnaire. Several fungal species were identified by microscopy and sequence analysis of diagnostic loci. Based on the results, 32 % of the sampled WMs were highly polluted with various species of fungi. Forty six percent of them were colonised also by opportunistically human pathogenic species. In total, 32 yeast and 39 filamentous fungal strains were isolated. Growth tests were conducted with five selected taxa (Cutaneotrichosporon dermatis, Cystobasidium slooffiae, Meyerozyma guilliermondii, Candida parapsilosis and the Fusarium oxysporum species complex (FOSC)) to ascertain their tolerance ranges. None of the examined isolates were able to grow >50 °C, 4.10 < pH < 10.88. FOSC could grow at high salinity. More species were detected in WMs operated in rooms without heating systems (p = 0.0025). The number of species was higher in WMs located in the kitchen than the ones kept in bathroom or in other rooms (p = 0.0205). WMs may serve as a reservoir of pathogenic fungi, the presence of which may depend on the usage of these devices.

Impacts of long-term ragweed pollen load and other potential risk factors on ragweed pollen allergy among schoolchildren in Hungary.

INTRODUCTION AND OBJECTIVE: Hungary is one of the areas in Europe most infected with ragweed (Ambrosia artemisiifolia L.) and its pollen, and is the most important cause of seasonal allergic rhinoconjunctivitis in the country. The aim of the study was to investigate the association between ragweed pollen allergy and long-term ragweed pollen load, as well as analysis of the the impacts of additional potential risk factors on health outcomes. MATERIAL AND METHODS: A modified version of standardized questionnaires, based on the International Study of Asthma and Allergy in Childhood, were completed by the parents of schoolchildren aged 8 - 9 attending 3rd grade classes throughout the country. Pollen load was calculated for each settlement from daily ragweed pollen concentrations monitored by 19 monitoring stations in the country. Descriptive and analytical statistical methods were applied. RESULTS: At national level there was a significant inverse association between prevalence of ragweed allergy and its pollen load, but significance was lost after excluding data from Budapest, the capital city, due to the impact of urbanization. In the adjusted model, parental atopic disease was the strongest risk factor (either parent had atopic disease aOR=2.60; 95% CI=2.31-2.93 or both parents had atopic disease aOR=4.56; 95% CI=3.71-5.60). Further significant risk factors were male gender (aOR=1.52; 95% CI=1.36-1.71), lower respiratory infection in the first two years of life (aOR=1.91; 95% CI=1.70-2.16), and unshared children's room (aOR=1.22; 95% CI=1.09-1.37). Allergy was significantly less common among children whose parents received social aid (aOR=0.83; 95% CI=0.72-0.97) and whose mother smoked during pregnancy (aOR=0.80; 95% CI=0.64-0.99). CONCLUSIONS: Higher ragweed pollen exposure was not found to be associated with higher risk of ragweed allergy.

Evidence for Infection and Inflammation in Infant Deaths in a Country with Historically Low Incidences of Sudden Infant Death Syndrome.

Total infant mortality in Hungary has been higher than other European countries; however, the reported incidence of sudden infant death syndrome (SIDS) has been lower. The low incidence of SIDS in Hungary has been supported by evidence obtained from the high rate of scene of death investigation and medico-legal autopsy mandatory since the 1950s. In this study, we compared the incidence of explained and unexplained infant deaths in Hungary for three periods: 1979-1989 when the incidence of SIDS was high in western Europe; 1990-1999 when the incidence of infant deaths was falling following introduction of the public health campaigns to reduce the risk factors associated with SIDS; and 2000-2012 to determine if introduction of Haemophilus influenzae type b or pneumococcal vaccines or introduction of an earlier immunization schedule during this period had an effect on SIDS. Explained infant deaths fell consistently during this period; however, SIDS rose during the second period when the incidence of SIDS was falling in other European countries. Evidence for infection and/or inflammation was observed for the majority of SIDS during each period. The results are discussed in relation to campaigns to reduce infant mortality in Hungary and the introduction of new vaccines and an earlier immunization schedule in 2006.

Examination of the Suicide Characteristics Based on the Scene Investigation in Capital Budapest (2009-2011).

Medicolegal evaluation of postmortem findings at the death scene represents an important part of forensic medicine. The aim of this study was to investigate the occurrence and characteristics of suicide events. Data collection was performed from the police scene investigation reports in capital Budapest between 2009 and 2011. In this study, epidemiological parameters such as age, gender, time and place of death, postmortem changes, suicidal method, seasonal and daily distribution, natural diseases, earlier psychiatric treatment, socioeconomic risks, supposed cause of death, final notes, earlier suicide attempts, and suicide ideations were analyzed. There were 892 suicide cases (619 males, 273 females) detected in the investigated period. Hanging, overdose of prescription medications, jumping, use of firearms, drowning, and electrotrauma showed statistical differences among genders (p<0.05). The most common methods of suicide among men and women were hanging (57.4%) and overdose of prescription medications (33%), respectively. Death scene characteristics represent the important factors for forensic medicine.

A Common Polymorphism of the Human Cardiac Sodium Channel Alpha Subunit (SCN5A) Gene Is Associated with Sudden Cardiac Death in Chronic Ischemic Heart Disease.

Cardiac death remains one of the leading causes of mortality worldwide. Recent research has shed light on pathophysiological mechanisms underlying cardiac death, and several genetic variants in novel candidate genes have been identified as risk factors. However, the vast majority of studies performed so far investigated genetic associations with specific forms of cardiac death only (sudden, arrhythmogenic, ischemic etc.). The aim of the present investigation was to find a genetic marker that can be used as a general, powerful predictor of cardiac death risk. To this end, a case-control association study was performed on a heterogeneous cohort of cardiac death victims (n=360) and age-matched controls (n=300). Five single nucleotide polymorphisms (SNPs) from five candidate genes (beta2 adrenergic receptor, nitric oxide synthase 1 adaptor protein, ryanodine receptor 2, sodium channel type V alpha subunit and transforming growth factor-beta receptor 2) that had previously been shown to associate with certain forms of cardiac death were genotyped using sequence-specific real-time PCR probes. Logistic regression analysis revealed that the CC genotype of the rs11720524 polymorphism in the SCN5A gene encoding a subunit of the cardiac voltage-gated sodium channel occurred more frequently in the highly heterogeneous cardiac death cohort compared to the control population (p=0.019, odds ratio: 1.351). A detailed subgroup analysis uncovered that this effect was due to an association of this variant with cardiac death in chronic ischemic heart disease (p=0.012, odds ratio = 1.455). None of the other investigated polymorphisms showed association with cardiac death in this context. In conclusion, our results shed light on the role of this non-coding polymorphism in cardiac death in ischemic cardiomyopathy. Functional studies are needed to explore the pathophysiological background of this association.

Full-length PGC-1α salvages the phenotype of a mouse model of human neuropathy through mitochondrial proliferation.

Increased mitochondrial mass, commonly termed mitochondrial proliferation, is frequently observed in many human diseases directly or indirectly involving mitochondrial dysfunction. Mitochondrial proliferation is thought to counterbalance a compromised energy metabolism, yet it might also be detrimental through alterations of mitochondrial regulatory functions such as apoptosis, calcium metabolism or oxidative stress. Here, we show that prominent mitochondrial proliferation occurs in Cramping mice, a model of hereditary neuropathy caused by a mutation in the dynein heavy chain gene Dync1h1. The mitochondrial proliferation correlates with post-prandial induction of full-length (FL) and N-terminal truncated (NT) isoforms of the transcriptional co-activator PGC-1α. The selective knock-out of FL-PGC-1α isoform, preserving expression and function of NT-PGC-1α, led to a complete reversal of mitochondrial proliferation. Moreover, FL-PGC-1α ablation potently exacerbated the mitochondrial dysfunction and led to severe weight loss. Finally, FL-PGC-1α ablation triggered pronounced locomotor dysfunction, tremors and inability to rear in Cramping mice. In summary, endogenous FL-PGC-1α activates mitochondrial proliferation and salvages neurological and metabolic health upon disease. NT-PGC-1α cannot fulfil this protective action. Activation of this endogenous salvage pathway might thus be a valuable therapeutic target for diseases involving mitochondrial dysfunction.

The role of PGC-1α in the pathogenesis of neurodegenerative disorders.

Mitochondrial dysfunction is a common hallmark of ageing-related diseases involving neurodegeneration. Huntington's disease (HD) is one of the most common monogenetic forms of neurodegenerative disorders and shares many salient features with the major sporadic disease of neurodegeneration, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD) and Parkinson's disease (PD). Recent evidence from the study of transgenic and knockout animal models of HD has stimulated new perspectives on mitochondrial dysfunction in HD and possibly other neurodegenerative diseases. The transcriptional co-activator PGC-1α, originally described as a metabolic master regulator in peripheral tissues such as brown adipose tissue (BAT) and muscle, has emerged as a molecular link between transcriptional dysregulation and mitochondrial dysfunction in the brain. PGC-1α knockout mice display many phenotypic similarities to transgenic mouse models of HD and the gene-expression analysis of tissues from HD patients revealed a disruption of the PGC-1α regulatory pathway. Hence, mitochondrial and transcriptional dysregulation in HD - previously thought to be unrelated mechanisms of neurodegeneration - appear to be directly linked at the molecular level. The clinical and therapeutic potential of targeting the PGC-1α in HD is further highlighted by the finding that common genetic variations in the PGC-1α gene significantly modify the disease onset, delaying the onset of motor symptoms by several years. The present review provides an overview of the advances in the understanding of the role of the PGC-1α system in HD pathogenesis and explores the implications for ALS, AD and PD.

A point mutation in the dynein heavy chain gene leads to striatal atrophy and compromises neurite outgrowth of striatal neurons.

The molecular motor dynein and its associated regulatory subunit dynactin have been implicated in several neurodegenerative conditions of the basal ganglia, such as Huntington's disease (HD) and Perry syndrome, an atypical Parkinson-like disease. This pathogenic role has been largely postulated from the existence of mutations in the dynactin subunit p150(Glued). However, dynactin is also able to act independently of dynein, and there is currently no direct evidence linking dynein to basal ganglia degeneration. To provide such evidence, we used here a mouse strain carrying a point mutation in the dynein heavy chain gene that impairs retrograde axonal transport. These mice exhibited motor and behavioural abnormalities including hindlimb clasping, early muscle weakness, incoordination and hyperactivity. In vivo brain imaging using magnetic resonance imaging showed striatal atrophy and lateral ventricle enlargement. In the striatum, altered dopamine signalling, decreased dopamine D1 and D2 receptor binding in positron emission tomography SCAN and prominent astrocytosis were observed, although there was no neuronal loss either in the striatum or substantia nigra. In vitro, dynein mutant striatal neurons displayed strongly impaired neuritic morphology. Altogether, these findings provide a direct genetic evidence for the requirement of dynein for the morphology and function of striatal neurons. Our study supports a role for dynein dysfunction in the pathogenesis of neurodegenerative disorders of the basal ganglia, such as Perry syndrome and HD.

Neuroprotective effects of L-carnitine in a transgenic animal model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage, mitochondrial dysfunction and altered membrane transport may have important roles in the pathogenesis of HD. L-carnitine plays a role in facilitating the mitochondrial transport of fatty acids, but it also protects the cells from oxidative damage. The aim of our study was to examine the effects of the intraperitoneally administered L-carnitine on the survival, behaviour and immunohistochemical changes in the N171-82Q transgenic mouse model of HD. Following L-carnitine administration the survival was improved by 14.9%. The motor activity was significantly ameliorated as compared with the control transgenic group. The L-carnitine treatment significantly reduced the neuronal loss and the number of neuronal intranuclear aggregates. These results suggest that L-carnitine may exert a neuroprotective effect by decreasing the oxidative damage.

Neuroprotective effects of probenecid in a transgenic animal model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominantly inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage and altered membrane transport may have an important role in the pathogenesis of HD. Probenecid is a non-selective inhibitor of multidrug resistance-associated proteins, but it also inhibits organic anion transporters. In this study, we examined the effects of probenecid on the survival, behaviour and immunohistochemical changes in the N171-82Q transgenic mouse model of HD. After probenecid administration, the duration of survival improved by 35%. The motor activity was significantly ameliorated as compared with the control transgenic group. Probenecid treatment significantly reduced the neuronal loss and the number of neuronal intranuclear aggregates. These results suggest that probenecid may exert a neuroprotective effect by increasing the membrane transport of protective compounds, and/or inhibiting the toxic compounds.