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Biomedical subjects

V Blaha

Publications and source records attributed to V Blaha.

At least 19 recordsLinked to original sources

Biochemical profile and survival in nonagenarians.

OBJECTIVES: Old age is associated with an increase in frequency of disorders involving virtually all organ systems, resulting in a rise of mortality. The aim of the project was to study the relationship between biochemical markers and all-cause mortality in a defined age group. DESIGN AND METHODS: Thirty-eight nonagenarians, aged 92 +/- 2 (range 90-100) years entered the study. At the start of the study, a sample of peripheral blood and urine were obtained for analysis of 50 basic biochemical, hematologic and biologic parameters. The assessment was then repeated in 6 to 12 months intervals. The significance of difference between surviving subjects and those who died was examined by Mann-Whitney U test and the correlation between the variables was studied by Spearman rank correlation coefficient. RESULTS: During the observation period, 21 of the studied subjects died leaving 17 persons still alive at the end of the study. The mean time from the first measurement to the death was 12 +/- 10 (range 0-33) months. The mean follow-up time in surviving subjects was 31 +/- 12 (range 4-45) months. Serum vitamin E and calcium were significantly higher, and serum alanine aminotransferase (ALT) and urinary neopterin were significantly lower in survivors compared to the subjects who died. No other parameters were significantly different in survivors and in persons who died. Urinary neopterin exhibited a significant negative correlation with serum sodium concentration (RS = -0.50, p < 0.01), but the other parameters did not correlate significantly. CONCLUSION: In conclusion, among the parameters studied, differences between survivors and nonsurvivors were observed only for serum vitamin E, calcium, ALT and urinary neopterin. These findings may form a basis for prospective interventional trials in this group of patients.

Aged↗

Bioanalysis of age-related changes of lipid metabolism in nonagenarians.

The aim of the present study was the bioanalysis of lipid metabolism in the aged patients and to study the relationship between these biochemical markers and longevity. Eleven nonagenarians, nine women and two men, aged 94+/-3 years and ten control patients, six women and four men, aged 84+/-5 years, followed at the Department of Metabolic Care and Gerontology, Charles University, Teaching Hospital entered the study. All subjects were self-sufficient, without major illnesses and free living. At the start of the project the free fatty acids (FFA), thiobarbituric reactive substances (TBARS), retinol, alpha tocopherol, ascorbic acid, cholesterol, triacylglycerols, phospholipids in serum, in lipoprotein fractions and fatty acids (FA) and phospholipids in erythrocyte membrane were determined. We used capillary gas chromatography for determination of fatty acids. Retinol and alpha tocopherol were analysed by reversed-phase high-performance liquid chromatography, other parameters were determined spectrophotometrically or spectrofluorometrically. We found significantly higher LDL polyunsaturated fatty acids (PUFA) 22:4n--3 (P=0.028) and 22:6n--3 (P=0.018) and a significant increase of HDL alpha tocopherol/cholesterol ratio (P=0.034) in nonagenarians. There were not any significant differences in erythrocyte membrane fatty acids and phospholipids. In serum we found significantly higher level of TBARS (3.22+/-1.22 vs 1.98+/-0.71 micromol/l, P=0.012) in nonagenarians, other parameters were not changed significantly. The higher concentration of PUFAs in LDL and alpha tocopherol in HDL might be parameters related to longevity.

Aged↗

Dopamine and serotonin VMN release is related to feeding status in obese and lean Zucker rats.

Study of neurotransmitter role in food intake regulation in a leptin signaling deficient model, such as the Zucker rat, would benefit in the understanding of mechanisms of human obesity, in which leptin resistance is a common syndrome. We studied dopamine (DA) and serotonin (5-HT) concentrations in vivo in the ventromedial nucleus (VMN) of the hypothalamus, as they relate to eating after food deprivation in obese and lean 9-week-old male Zucker rats. DA and 5-HT concentrations were measured by HPLC via microdialysis before and during refeeding in 24-h food-deprived rats. Before food was provided, mean baseline DA and 5-HT levels were lower in obese than in lean rats (9.2 +/- 0.9 vs 15.1 +/- 1.9 pg/10 microl, p < 0.01, and 0.68 +/- 0.05 vs 1.17 +/- 0.02 pg/10 microl, p < 0.001, respectively). Food intake was accompanied by a decrease in DA levels in both obese and lean rats to 64% (p < 0.01) and 65% (p < 0.02) of their baseline levels respectively. 5-HT levels were significantly increased during eating by 41% in obese and 35% in lean rats (p < 0.01) from the baseline levels. Thus in obese rats with altered leptin signaling we found an unaltered pattern of DA and 5-HT release associated with food deprivation and refeeding, but with presence of their low levels. This points to an impaired postsynaptic monoaminergic action to produce an adequate metabolic response in obese Zucker rats in response to feeding state.

Animals↗

Potential strategies for ameliorating early cancer anorexia.

BACKGROUND: Normally the lateral hypothalamic area (LHA) and the ventromedial nucleus (VMN) interact to regulate food intake (FI), the product of meal number (MN) and meal size (MZ), by changes in neurotransmitters, mainly dopamine and serotonin. Change in LHA dopamine influences meal size; while in VMN, decreasing dopamine and increasing serotonin levels influence meal number. Whether this situation exists in early cancer anorexia was tested in a series of studies to examine the role of the hypothalamus in the pathogenesis of early cancer anorexia. MATERIALS AND METHODS: In experiment 1, male Fischer tumor-bearing (TB) rats and weight-matched controls had FI, MN, and MZ measured continuously via a computerized rat eater meter. At onset of anorexia, feeding patterns were measured. In experiment 2, the VMN was temporarily blocked with 0.32 microgram of colchicine in TB rats, while TB controls had an equal volume of intra-VMN saline, and changes in feeding patterns were measured. In experiment 3, changes in VMN dopamine and serotonin were measured via microdialysis at anorexia and after tumor resection. RESULTS: In experiment 1, with the onset of anorexia, food intake decreased significantly in TB rats, initially by a decrease in MN and then by a decrease in both MN and MZ. No change occurred in controls, suggesting that VMN versus LHA played a more significant role in mediation of cancer anorexia. In experiment 2, following VMN block, FI increased significantly in anorectic TB rats, achieved by an almost exclusive increase in MN with minimal change in MZ, thus supporting the role of the VMN in anorexia. In experiment 3, at the onset of anorexia, FI decreased significantly in TB rats versus controls. TB rats had a significant increase in VMN serotonin and a significant decrease in VMN dopamine. After tumor resection, food intake improved and high levels of serotonin normalized with no change in dopamine. CONCLUSION: Serotoninergic and dopaminergic systems are involved in the etiology of cancer anorexia. The changes in food intake are mediated via the VMN by a decrease in meal number.

Animals↗

Interleukin-1alpha injection into ventromedial hypothalamic nucleus of normal rats depresses food intake and increases release of dopamine and serotonin.

A microdialysis injector probe administered IL-1alpha into ventromedial hypothalamus (VMN) and concurrently measured release of dopamine (DA), DOPAC, 5-HT, and 5-HIAA. After baseline dialyses, six rats received 2-ng IL-1alpha and six rats received vehicle (1 microl saline) into VMN. Sixty minutes later, food was provided for 40 min while VMN monoamines were measured every 20 min. Vehicle had no significant effect on monoamines, their metabolites, or food intake. Food intake was significantly lower in IL-1alpha rats vs. controls (p < 0.01). Baseline levels of VMN monoamines (pg/10 microl dialysate) in IL-1alpha and vehicle groups were similar. DA and 5-HT rose immediately on injecting IL-1alpha and remained higher (p < 0.05) than basal during the first 60 min and 40 min sampling period, respectively. Levels of 5-HIAA also increased (p < 0.01). Eating decreased VMN DA in controls, and decreased VMN DOPAC in IL-1alpha-treated rats. During eating, VMN 5-HT in control rats significantly increased while increasing VMN 5-HIAA occurred in IL-1alpha rats. Findings show that an IL-1alpha pathophysiological dose injected into the VMN was associated with anorexia and significantly increased dopaminergic and serotonergic activities and suggest that enhanced VMN DA and 5-HT activities may be part of an IL-1alpha-initiated cascade involved in IL-1alpha-associated anorexia.

Animals↗

Infusion of nicotine into the LHA enhances dopamine and 5-HT release and suppresses food intake.

Nicotine administration induces hypophagia. Because of the involvement of hypothalamic neurotransmitters in food intake control, we hypothesized that increased activity of the lateral hypothalamic dopamine (LHA-DA) and/or serotonin (LHA-5-HT) may be responsible for nicotine-induced hypophagia. Either 4 mM nicotine or vehicle was administered via reverse microdialysis technique into the LHA of overnight food-deprived rats for 60 min; then food was provided for 40 min. The LHA-DA, 5-HT and their intermediate metabolites, DOPAC and 5-HIAA, were continuously measured during 20-min intervals before, during, and after nicotine administration. Continuous nicotine administration for 60 min increased LHA-DA and DOPAC concentrations during the first 40 min, and induced a long-lasting increase in LHA-5-HT release, until 120 min after the start nicotine administration, even when nicotine administration was stopped. The food intake during the 40-min refeeding period was significantly lower when rats received nicotine. Eating induced a significant and short-lasting increase in the LHA-DA and a long-lasting increase in the LHA-5-HT. These findings indicate that nicotine enhances dopaminergic and serotonergic activity in the LHA, and that the enhanced LHA-5-HT activity may contribute to nicotine-induced hypophagia.

3,4-Dihydroxyphenylacetic Acid↗

Use of orchiectomy and testosterone replacement to explore meal number-to-meal size relationship in male rats.

Because food intake is a function of meal number and meal size and because gender-related hormones are involved in feeding regulation, we explored effects of orchiectomy and testosterone replacement on the relationship between meal number and size and changes in resulting feeding patterns in adult male rats, randomized into orchiectomy and sham-operation groups. A rat eater meter measured feeding indexes for 1 wk before and 2 wk after castration and during 8 days of testosterone replacement. Orchiectomy leads to an immediate change in the meal number-to-size relationship, resulting in 1) change in pattern of feeding; 2) a significant decrease in dark-phase meal number; 3) a significant increase in dark-phase meal size, but insufficient to offset decrease in meal number, so total food intake significantly decreased during dark phase; 4) no significant change in light-phase meal number; and 5) an increase in meal size leading to an increased food intake during light phase, which offset decreased food intake in dark cycle and resulted in no net significant change in food intake after orchiectomy. Testosterone replacement acutely reversed effects of orchiectomy on meal number-to-meal size relationship, restoring feeding pattern. Data suggest that androgens immediately influence the meal number-to-meal size relationship. The speed of onset seen after orchiectomy suggests that the influence of testosterone on food intake may also occur partially via a nongenomic effect.

Animals↗

Pyrophosphate heart scan in patients with progressive systemic sclerosis.

Scintigraphic examination of the myocardium, using 99mTc-labelled pyrophosphate, was carried out in 17 patients suffering from systemic sclerosis. This connective tissue disorder very often affects the myocardium secondarily. The results of the cardiac scan were compared with the information obtained from the electrocardiogram of systolic time intervals. In addition, spirometry was undertaken to detect a potential relation between cardiac and pulmonary involvement. The scan was found to be positive in seven patients and electrocardiographic findings were pathological in five patients only. The systolic time intervals were abnormal in three patients only. A ventilation disturbance was recorded in 10 patients. No clear relation was found between the results of the individual examinations. It is concluded that pyrophosphate heart scintigraphy may detect myocardial impairment in some cases of systemic sclerosis before it is manifested by heart failure. Examination of systolic time intervals is of little importance.

Adult↗

Morphology of the bentonite and kaolin-induced rat-paw oedemas.

The bentonite and kaolin oedemas were simultaneously induced in the rat hind paws and their courses and morphological patterns were observed under the conditions of the same biological background. Gross examination has confirmed the former experience that the kaolin oedema has a more pronounced acute phase (maximum after five to seven hours) followed by subsequent spontaneous regression of the oedema, while the bentonite oedema has its acute phase less pronounced, attains its peak only on the second day, maintaining this same size over several weeks without substantial changes. The courses of the two oedemas were in correlation with the results of histological evaluation (oedematous exudation, polymorphonuclear and mononuclear infiltration and the phagocytic activity of the latter). Resorption of kaolin in the newly-developed non-specific granulation tissue was much faster than that of bentonite (after about three weeks, while bentonite was not resorbed even after six weeks). Further, pharmacological and histological examination was performed of the effects on the bentonite oedema of sodium salicylate and Prednisone during the first 24 hours. Both substances suppressed the oedema, sodium salicylate delayed both polymorphonuclear and mononuclear infiltration, Prednisone delayed only mononuclear infiltration. The presence of mononuclear population was confirmed also by means of the positive activity of non-specific esterase and the negative activity of alkaline phosphatase. The bentonite rat-paw oedema has thus been proved to be a suitable model of inflammatory reaction for testing anti-inflammatory drugs not only in short-term (acute) tests, but also in long-term ones, where it yields a uniform picture of non-specific foreign-body low-turnover granuloma.

Acute Disease↗