Relationship between serum albumin level before initiating haemodialysis and angiographic severity of coronary atherosclerosis in end-stage renal disease patients.

BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.     

Changes in central dopaminergic systems with the expression of Shh or GDNF in mice perinatally exposed to bisphenol-A.

In the previous study, we reported that exposure to bisphenol-A induced the potentiation of dopamine receptor functions in the mouse limbic area, resulting in supersensitivity to methamphetamine-induced pharmacological actions. The present study was undertaken to investigate whether prenatal exposure to bisphenol-A could produce morphological change in dopaminergic neuron and the pattern of expression of genes regulating the dopaminergic neuron development. Here we found that prenatal and neonatal exposures to bisphenol-A increased the tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the adult mouse limbic area. The present molecular biological study shows that chronic bisphenol-A treatment produced a significant decrease in the dopaminergic neuron development factors, sonic hedgehog and glial cell line-derived neurotrophic factor, which were also decreased by prenatal exposure to bisphenol-A. These results suggest that chronic exposure to bisphenol-A could disrupt the dopaminergic neurotransmission in the process of dopaminergic neuron development.     

The role of purinergic neurotransmission in various cardiovascular reflexes.

In urethane-anaesthetized rats the effects of alpha-adrenoceptor antagonists and desensitization of P2-purinoceptors with alpha,beta-methylene ATP on the pressor reflex responses were investigated. Pressor responses were elicited by electrical stimulation of the central end of the sciatic nerve, by asphyxia and by occlusion of the common carotid artery. Responses to sciatic nerve stimulation and to asphyxia, but not those to carotid artery occlusion were entirely suppressed by dihydroergotamine and phentolamine. Under the action of dihydroergotamine the sinocarotid reflex decreased by over 70% in 40% of the experiments. In 60% of experiments the response was only slightly reduced or even augmented, but it was entirely inhibited by subsequent desensitization with alpha,beta-methylene ATP. The magnitude of response to sciatic nerve stimulation was almost unaffected by alpha,beta-methylene ATP, while the response to carotid occlusion was decreased by 40-50%. The recovery of purinoceptor sensitivity to alpha,beta-methylene ATP was accompanied by restoration of the sinocarotid reflex. It is suggested that purinergic neurotransmission plays a considerable role in the pressor sinocarotid reflex, while in the pressor response to stimulation of somatic afferents its role is negligible.     

Role of macrophage and smooth muscle cell apoptosis in association with oxidized low-density lipoprotein in the atherosclerotic development.

To examine the role of the apoptosis of macrophages and smooth muscle cells in the development of atherosclerosis, human aortic tissues with intimal lesions were immunostained with antibodies against terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL), single-stranded DNA (clone F7-26), and active caspase-3. Apoptotic cells were detected in the intima using both TUNEL and single-stranded DNA, however, the latter method was the more sensitive one for detecting apoptotic cells in the early stages of atherosclerosis. The number of apoptotic cells increased as the disease progressed. It implies that the apoptosis of intimal cells is involved in the formation of atherosclerotic lesions. In addition, quantitative analyses of the cell types undergoing apoptosis using double-immunostaining revealed that the susceptibility of macrophages and smooth muscle cells to apoptosis was greater specifically in atheroma than in the other atherosclerotic lesions, and macrophages were more susceptible to apoptosis than smooth muscle cells. The frequency and spatial distribution of oxidized low-density lipoprotein (oxLDL) (FOH1a/DLH3)-positive cells were examined by immunohistochemistry, and the results resembled those of apoptotic cells. The number of oxLDL-positive cells in the intima significantly correlated with the susceptibility of smooth muscle cells, but not with that of macrophages, to apoptosis. These results suggest that oxLDL affects the apoptosis of smooth muscle cells during the atherosclerotic development.     

Activated caspase expression and apoptosis increase in keloids: cytochrome c release and caspase-9 activation during the apoptosis of keloid fibroblast lines

To characterize apoptosis in keloids and the mechanisms responsible for this process, the expression of activated caspase-9 and -3 in fibroblasts obtained from keloids was analyzed. Immunohistochemistry revealed that the number of fibroblasts positive for terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) or activated caspase-9 or -3 was low but was significantly higher in keloid tissues than in normal scar tissues. Significant relationships between the number of caspase-positive fibroblasts and TUNEL-positive fibroblasts suggested that the activation of caspase-9 and -3 induces apoptosis in a subpopulation of keloid fibroblasts. All keloid fibroblast cell lines established in this study showed activation of caspase-9 and -3 after serum deprivation for 3 or 4 hours, as shown using Western blotting. Furthermore, serum deprivation-induced apoptosis in a keloid fibroblast line was blocked by a caspase-9 inhibitor (acetyl-Leu-Glu-His-Asp-al), indicating that activation of caspase-9 was necessary for the process of apoptosis in keloid fibroblasts. Although serum deprivation did not significantly change the level of apoptosis protease activating factor-1 in any of the lines, cytochrome c release was detected in cytosolic fractions of the lines after serum deprivation for 3 or 4 hours. These results strongly suggest that keloid fibroblasts are predisposed to apoptosis and cytochrome c release and that caspase-9 activation may underlie regulation of apoptosis in keloid fibroblasts in vivo.     

Perceived effects of rotating shift work on nurses' sleep quality and duration

The aim of this longitudinal study was to assess the effect of rotating shift work on perceived sleep quality and sleep duration of nurses at Queen Elizabeth Central Hospital, Blantyre, Malawi. Twenty four female nurses were recruited at random from among personnel engaged in rotating shift work. The nurses worked a three-phase schedule: five day shifts (7.00 – 17.00) followed by three night shifts (17.00 – 7.00) and five days off. Controls were 22 female nurses who did not perform night duties. Sleep quality and duration was assessed using standardized and validated questionnaires on sleep duration and subjective sleep quality (SSQ). One-way analysis of variance revealed a significant effect of shift phase on total sleep duration (F = 36.8, d.f. = 8, P < 0.000) and perceived sleep quality (F = 8.81, d.f. = 3, P < 0.000). Night shift work was associated with reduction of sleep quality and duration. The after effects of night shifts persisted during days of the recovery period indicating accumulation of fatigue.     

Risk factors for wheezing in Ukrainian children: Ukraine European Longitudinal Study of Pregnancy and Childhood Group

The prevalence of wheezing in children varies widely around the world. The reasons for this geographic variability remain unclear but may be related in part to exposures in the home environment during pregnancy and early childhood. We investigated the prenatal and early childhood risk factors for wheezing symptoms among 2127 children aged 6–8 years who were participants in the Ukrainian component of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). Cases included the 169 children whose parents answered yes to the International Study of Asthma and Allergy in Children (ISAAC) question: 'Has your child had wheezing or whistling in the chest in the past 12 months' during the ELSPAC assessment of the children at age 7. These were compared with the 1861 children in the cohort whose parents answered 'no' to this question.
Factors significantly associated with increased risk of wheezing illness at age 7 in adjusted analyses included mother's asthma [adjusted odds ratio (OR) 3.46, 95% confidence interval (CI) 1.22, 9.85]; mother's allergy problems (OR 1.43, [1.00, 2.05]); rarely playing with other children at age 3 (OR 1.84, [1.09, 3.11]); water intrusion (OR 1.62, [1.09, 2.39]) and inadequate heating of the home (OR 1.52, [1.06, 2.16]) during pregnancy. Factors protective of wheezing at age 7 included being first-born (adjusted OR 0.70, 95% CI 0.50, 0.98); living in the city of Dniprodzerzynsk as compared with Kyiv (OR 0.36, [0.24, 0.54]) and weekly contact with furry animals (OR 0.44, [0.20, 0.97]) before age 3. The constellation of risk factors for wheezing in Ukrainian children is similar to that of children in other parts of the world. Known risk factors do not account for the significant between-city variability of wheezing in Ukrainian children.     

A comparative study of the pharmacokinetics and pharmacodynamics of bonnecor]

The pharmacokinetics and pharmacodynamics of bonnecor were studied simultaneously in animals with experimental arrhythmia. It was shown that irrespective of the animal species and individual features of the drug elimination kinetics the level of bonnecor concentration correlated with the antiarrhythmic effect. The data on the excretion of bonnecor and its metabolites in the urine in the dog and man were obtained. The decrease of bioavailability at oral administration of bonnecor was demonstrated to be related to its intensive conversion in metabolite M-I.