Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites

OBJECTIVE: Large volume paracentesis is an effective treatment for refractory ascites, but the need for routine infusion of albumin or other volume expanders remains controversial. The aim of this study was to assess the short term effects of a single 5-L paracentesis without albumin replacement on total central blood volume, systemic and renal hemodynamics, sodium homeostasis, and neurohumoral factors. PATIENTS AND METHODS: Twelve patients with biopsy-proven cirrhosis and tense, diuretic-resistant ascites were studied before and 48 h after a single 5-L paracentesis without albumin infusion. Systemic hemodynamics and total central blood volume were assessed using radionuclide angiography. Glomerular filtration rate and effective renal plasma flow were measured by inulin and para-aminohippurate clearances, respectively. Lithium clearance was used as an index of proximal tubular reabsorption of sodium. In addition, plasma concentrations of neurohumoral factors were determined. RESULTS: Total central blood volume was 2.41 +/- 0.33 L/m2 (mean +/- SEM) before and 2.34 +/- 0.18 L/m2 48 h after large volume paracentesis (p = 0.76). Similarly, no differences were detected in the cardiac index, glomerular filtration rate, effective renal plasma flow, urinary sodium excretion, hematocrit, plasma renin activity, or concentrations of plasma aldosterone, norepinephrine, or atrial natriuretic factor. CONCLUSIONS: A single large volume paracentesis without albumin replacement causes no disturbances in systemic and renal hemodynamics 48 h after the procedure. These results suggest that a single 5-L paracentesis without albumin infusion is a safe and satisfactory short term option for the management of patients with cirrhosis and tense, diuretic-resistant ascites.     

"Even", integral indicators in systemic mathematical analysis of fatigue

The article considers 3 different points of view on systemic mathematical analysis of human fatigue process. In this case, the same physiologic information is processed according to various algorithms for integral and digital estimates of lowered performance and energy expenditure, as well as indirect characteristics of inhibition and excitation processes in the brain cortex. The mathematical results are applied in computer forecasting of individual occupational risk at the specific workplace.     

Differential chromosome sensitivity to 5-azacytidine in Alzheimer''s disease

The chemiluminescence (CL) technique with scavengers for superoxide anion (superoxide dismutase) and hydrogen peroxide (catalase) was used to characterize the generation of reactive oxygen species (ROS) inside and outside the human neutrophil after stimulation with both soluble (formyl-methionyl-leucyl-phenylalanine, FMLP) and particulate (urate crystals, zymosan, oxidized LDL) stimuli. Depending on the stimulus used, ROS generation differed in composition and absolute amounts. The ratio between extracellularly and intracellularly produced ROS ranged from 0.3 (zymosan) to 4.2 (FMLP). While enhancing substantially FMLP-stimulated CL, horseradish peroxidase inhibited CL induced by particulate stimuli by 40-80%. Furthermore, an azide-insensitive and therefore peroxidase-independent part of CL was found in FMLP-, LDL- and zymosan-stimulated cells. The results indicate that different agonists may lead through distinct chemical pathways to neutrophil luminol-amplified light generation.     

Posterodorsal amygdaloid lesions in rats: long-term effects on body weight

Bilateral lesions in the most posterodorsal aspects of the amygdala in female rats resulted in immediate and dramatic weight gains on a standard lab chow diet. The rate of weight gain returned to normal by Day 20, but the difference in body weight between animals with amygdaloid lesions and those with sham lesions was maintained for the duration of the study (60 days). Because rats with posterodorsal amygdaloid lesions have also been found to be hyperinsulinemic, it is hypothesized that the lesions result in a similar, though smaller, version of the syndrome that follows lesions of the ventromedial hypothalamus.     

Mapping the active sites of 3-phosphoglycerate kinase and glycerol kinase with monoammine chromium(III) ATP

The 12 isomers of monoammine chromium(III) ATP have been used to probe the ATP binding sites of yeast 3-phosphoglycerate kinase and glycerol kinase from Candida mycoderma. Inhibition studies of 3-phosphoglycerate kinase show a dramatic decrease in isomer binding only when the ammonia is in the Delta axial facial anti position. This suggests an open site architecture with only one strong contact point between the coordination sphere and the enzyme surface. These results agree well with the computer modeling studies of bidentate chromium ATP into the nucleotide site determined by X-ray crystallography [McPhillips, T., et al. (1996) Biochemistry 35, 4118-4127]. Both methods describe an open site strongly supporting the validity of the inhibition studies. Inhibition studies of glycerol kinase show significant decreases in binding for all the tested ammonia positions, suggesting a closed site architecture with many contacts between the coordination sphere and the surface of the enzyme. This is in good agreement with X-ray studies [Hurley, T., et al. (1993) Science 259, 673-677] on the Escherichia coli glycerol kinase. Inhibition studies of hexokinase previously reported [Rawlings, J., et al. (1993) Biochemistry 32, 11204-11210] more closely resemble those of 3-phosphoglycerate kinase, suggesting the surprising result that however closely hexokinase and glycerol kinase are related structurally the site around the coordination sphere in hexokinase is functionally open like that of 3-phosphoglycerate kinase.     

Growth and function of human parathyroid tissue transplanted to athymic mice

The morphology, cell proliferation and function of transplanted normal, hyperplastic and adenomatous human parathyroid tissue was studied after transplantation to athymic mice. The iPTH was evaluated in relation to morphology. Human parathyroid tissue collected during surgery for hyperparathyroidism was implanted subcutaneously into athymic mice (nu/nu-BALB/cA) and was analysed 1, 4, 7 and 12 weeks after transplantation. The transplants were examined by light and electron microscopy and by autoradiography after continuous infusion of 3H-thymidine. The relative amount of viable tissue was evaluated using a computer image analysing programme. Graft function was evaluated by measuring human iPTH in mouse serum. A transplant take ratio of 93% was observed. The proliferation rate in adenoma grafts at 12 weeks after transplantation was five and fifteen times that observed in normal and hyperplastic transplants, respectively. In normal and adenoma groups, a continuous increase in iPTH concentrations was observed, but in the hyperplastic group the iPTH remained on the same level. The secretion of iPTH in relation to the amount of transplanted tissue and the fraction of viable tissue was at the same level at 12 weeks in normal and adenomatous grafted animals. In conclusion, human parathyroid tissue was successfully transplanted and maintained its original structure. The growth potential, but not the iPTH secretion, was significantly higher in adenoma grafts compared to grafts from hyperplastic and normal glands.     

Correlation between vascular and cellular responses to atrial natriuretic peptide and to sodium nitroprusside

Atrial natriuretic peptide (ANP) and sodium nitroprusside (SNP) increase cGMP in vascular smooth muscle cells and act as vasodilators in some, but not all, blood vessels. In this present study, we attempted to correlate the ability of these two agents to dilate blood vessels with the ability to increase cGMP in cultured vascular smooth muscle cells. In the isolated guinea pig heart, SNP dose-dependently increased coronary flow while ANP was ineffective. In smooth muscle cells cultured from the coronary system, SNP increased intracellular cGMP in a dose-dependent manner while ANP had no effect on cGMP in these cells. In isolated guinea-pig thoracic aorta, precontracted with K+, both ANP and SNP produced relaxation and ANP was the more potent. In smooth muscle cells cultured from the aorta, ANP and SNP increased cGMP and the potency relationship was similar to the intact vessel. These results support the view that phenotypic properties of vascular smooth muscle cells can account for differences in the response of blood vessels to vasodilators.     

Use of the ARPE-19 cell line as a model of RPE polarity: basolateral secretion of FGF5

PURPOSE: To determine the polarity of fibroblast growth factor 5 (FGF5) secretions from retinal pigment epithelium (RPE) cells and to examine the viability and utility of the ARPE-19 cell line as a model for the study of RPE polarity. METHODS: Influenza infection and adenovirus-mediated gene transfer were used to deliver and express genes encoding influenza hemagglutinin (HA), p75-NTR (a neurotrophin receptor), low-density lipoprotein (LDL) receptor (LDLR), and FGF5 in confluent monolayers of ARPE-19 cells. The localization of HA, p75-NTR, and LDLR was determined by confocal microscopy. Domain selective biotinylation assays were used to quantitatively determine the polarities of p75-NTR and LDLR. The secretion of FGF5 into the apical and basal media of ARPE-19 cultures was examined by immunoblot analysis of conditioned media. RESULTS: Hemagglutinin and p75-NTR were found to be localized on the apical surface of infected and transduced ARPE-19 cells. In contrast, LDLR was associated preferentially with the basolateral membrane of ARPE-19 cells. Biotinylation studies indicated that 84% of p75-NTR was present on the apical surface, and 79% of LDLR was basolaterally polarized. Over the course of 6 hours, more than 90% of the total secreted FGF5 protein accumulated in the basolateral media. CONCLUSIONS: ARPE-19 cells exhibit a polarized distribution of cell surface markers when examined by either confocal microscopy or surface-labeling assays. This indicates that the ARPE-19 cell line is a valid model for studies of RPE cell polarity. FGF5, a secreted protein normally produced by RPE cells, is accumulated preferentially in the basal media after only 6 hours, suggesting that it is vectorially secreted from the basolateral surface of ARPE-19 cells.     

MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion

One week after a single administration of 3,4-methylenedioxymethamphetamine (MDMA HCI, 30 mg/kg i.p.), 5-HT1A receptor density was significantly increased by approximately 25-30% in the frontal cortex and hypothalamus of rats. The increased density correlated with the potentiation of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.) or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked the effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-DPAT-induced hypothermia. The protection afforded by drugs against 5-HT loss did not correlate, however, with the antagonism of the acute hyperthermic effect of MDMA. The present results indicate that drugs able to prevent or to attenuate MDMA-induced 5-HT loss also prevent the changes in 5-HT1A receptor density as well as the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT in MDMA-treated rats.