60 research outputs found
Ecto-nucleoside triphosphate diphosphohydrolase 3 in the ventral and lateral hypothalamic area of female rats: morphological characterization and functional implications
<p>Abstract</p> <p>Background</p> <p>Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR) hypothalamic structures in the rat brain, here we investigated: 1.) The cellular and subcellular localization of NTPDase3; 2.) The effects of 17β-estradiol on the expression level of hypothalamic NTPDase3; and 3.) The effects of NTPDase inhibition in hypothalamic synaptosomal preparations.</p> <p>Methods</p> <p>Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode.</p> <p>Results</p> <p>Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD) indicated that γ-amino-butyric-acid- (GABA) ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of mitochondrial respiration rates with and without the inhibition of NTPDases confirmed the presence of NTPDases, including NTPDase3 in neuronal mitochondria and showed that blockade of mitochondrial NTPDase functions decreases state 3 mitochondrial respiration rate and total mitochondrial respiratory capacity.</p> <p>Conclusion</p> <p>Altogether, these results suggest the possibility that NTPDases, among them NTPDase3, may play an estrogen-dependent modulatory role in the regulation of intracellular availability of ATP needed for excitatory neuronal functions including neurotransmission.</p
Neutrophil extracellular traps in thrombi retrieved during interventional treatment of ischemic arterial diseases
IntroductionThe ultrastructure and cellular composition of thrombi has a profound effect on the outcome of acute ischemic stroke (AIS), coronary (CAD) and peripheral artery disease (PAD). Activated neutrophils release a web-like structure composed mainly of DNA and citrullinated histones, called neutrophil extracellular traps (NET) that modify the stability and lysability of fibrin. Here, we investigated the NET-related structural features of thrombi retrieved from different arterial localizations and their interrelations with routinely available clinical data.Patients and methodsThrombi extracted from AIS (n = 78), CAD (n = 66) or PAD (n = 64) patients were processed for scanning electron microscopy, (immune)stained for fibrin, citrullinated histone H3 (cH3) and extracellular DNA. Fibrin fiber diameter, cellular components, DNA and cH3 were measured and analyzed in relation to clinical parameters.ResultsDNA was least present in AIS thrombi showing a 2.5-fold lower DNA/fibrin ratio than PAD, whereas cH3 antigen was unvaryingly present at all locations. The NET content of thrombi correlated parabolically with systemic inflammatory markers and positively with patients' age. The median platelet content was lower in PAD (2.2%) than in either AIS (3.9%) or CAD (3.1%) and thrombi from smokers contained less platelets than non-smokers. Fibrin fibers were significantly thicker in male patients with CAD (median fiber diameter 76.3 nm) compared to AIS (64.1 nm) or PAD (62.1 nm) and their diameter correlated parabolically with systemic inflammatory markers.ConclusionsThe observed NET-related variations in thrombus structure shed light on novel determinants of thrombus stability that eventually affect both the spontaneous progress and therapeutic outcome of ischemic arterial diseases
Genetic Variants in FBN-1 and Risk for Thoracic Aortic Aneurysm and Dissection.
OBJECTIVES: A recent genome wide association study (GWAS) by LeMaire et al. found that two single nucleotide polymorphisms (SNPs), rs2118181 and rs10519177 in the FBN-1 gene (encoding Fibrillin-1), were associated with thoracic aortic dissection (TAD), non-dissecting thoracic aortic aneurysm (TAA), and thoracic aortic aneurysm or dissection (TAAD); the largest effect was observed for the association of rs2118181 with TAD. We investigated whether rs2118181 and rs10519177 were associated with TAD, TAA, and TAAD in the Yale study. METHODS: The genotypes of rs2118181 and rs10519177 were determined for participants in the Yale study: 637 TAAD cases (140 TAD, 497 TAA) and 275 controls from the United States, Hungary, and Greece. The association of the genotypes with TAD, TAA and TAAD were assessed using logistic regression models adjusted for sex, age, study center and hypertension. RESULTS AND CONCLUSIONS: In the Yale study, rs2118181 was associated with TAD: compared with non-carriers, carriers of the risk allele had an unadjusted odds ratio for TAD of 1.80 (95% CI 1.15-2.80) and they had odds ratio for TAD of 1.87 (95% CI 1.09-3.20) after adjusting for sex, age, study center and hypertension. We did not find significant differences in aortic size, a potential confounder for TAD, between rs2118181 risk variant carriers and non-carriers: mean aortic size was 5.56 (95% CI: 5.37-5.73) for risk variant carriers (CC+CT) and was 5.48 (95% CI: 5.36-5.61) for noncarriers (TT) (p = 0.56). rs2118181 was not associated with TAA or TAAD. rs10519177 was not associated with TAD, TAA, or TAAD in the Yale study. Thus, the Yale study provided further support for the association of the FBN-1 rs2118181SNP with TAD
Risk factors for suicide in Hungary: a case-control study
<p>Abstract</p> <p>Background</p> <p>Hungary previously had one of the highest suicide rates in the world, but experienced major social and economic changes from 1990 onwards. We aimed to investigate the antecedents of suicide in Hungary. We hypothesised that suicide in Hungary would be associated with both risk factors for suicide as identified in Western studies, and experiences related to social and economic restructuring.</p> <p>Methods</p> <p>We carried out a controlled psychological autopsy study. Informants for 194 cases (suicide deaths in Budapest and Pest County 2002–2004) and 194 controls were interviewed by clinicians using a detailed schedule.</p> <p>Results</p> <p>Many of the demographic and clinical risk factors associated with suicide in other settings were also associated with suicide in Hungary; for example, being unmarried or having no current relationship, lack of other social contacts, low educational attainment, history of self-harm, current diagnosis of affective disorder (including bipolar disorder) or personality disorder, and experiencing a recent major adverse life event. A number of variables reflecting experiences since economic restructuring were also associated with suicide; for example, unemployment, concern over work propects, changes in living standards, practising religion. Just 20% of cases with evidence of depression at the time of death had received antidepressants.</p> <p>Conclusion</p> <p>Suicide rates in Hungary are falling. Our study identified a number of risk factors related to individual-level demographic and clinical characteristics, and possibly recent societal change. Improved management of psychiatric disorder and self-harm may result in further reductions in suicide rates.</p
17-β estradiol increases parvalbumin levels in Pvalb heterozygous mice and attenuates behavioral phenotypes with relevance to autism core symptoms
Comparative Study on Cardiotoxic Effect of Tinuvin 770: A Light Stabilizer of Medical Plastics in Rat Model
Percutaneous angioplasty of internal mammary artery graft stenosis: Case report and discussion
The pineal gland and breast cancer — the presence and potential role of melatonin receptors
Myoglobin content and citrate synthase activity in different parts of the normal human heart
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