Effects of therapeutic paracentesis on systemic and hepatic hemodynamics and on renal and hormonal function

Thirteen patients with cirrhosis and tense ascites (six with and seven without peripheral edema) underwent 4- to 15-liter paracentesis without intravenous "colloid" replacement. Cardiac output increased from 6.6 +/- 0.7 liters per min at baseline to 8.2 +/- 0.7 liters per min (p less than 0.003) 1 hr after large-volume paracentesis completion and fell to 7.5 +/- 0.69 liters per min (p less than 0.05 vs. baseline, p less than 0.02 vs. 1 hr) 24 hr after large-volume paracentesis completion. There was no change in mean arterial pressure or mean pulmonary artery pressure. Central venous pressure fell from 9.1 +/- 0.8 mm Hg at baseline to 8.6 +/- 1.4 mm Hg 1 hr post-large-volume paracentesis to 6.8 +/- 1.0 mm Hg (p less than 0.005 vs. baseline, p less than 0.02 vs. 1 hr value) at 24 hr, and pulmonary capillary wedge pressure fell from 13.1 +/- 0.9 to 11.1 +/- 1.3 mm Hg 1 hr after large-volume paracentesis and to 9.89 +/- 1.2 (p less than 0.01 vs. baseline, p less than 0.03 vs. 1 hr after large-volume paracentesis) at 24 hr. Heart rate fell from 90 +/- 3.0 to 85 +/- 2.9 beats per min (p less than 0.01) 1 hr after large-volume paracentesis completion, but increased to 89 +/- 2.5 beats per min (p less than 0.02 vs. 1 hr after large-volume paracentesis) at 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)     

锌、铜对染砷小鼠肝及肾毒作用的干预研究

为观察补充锌、铜对染砷小鼠的肝、肾脏组织超氧化物歧化酶 (SOD)水平、丙二醛 (MDA)含量并初步探讨其作用机制 ,对染砷小鼠同步进行锌、铜干预试验 ,同时作肝脏、肾脏组织SOD活性及MDA含量测定和病理学观察。干预后 ,与阳性对照组相比 ,锌干预组肝脏、肾脏SOD活性升高 ,MDA含量下降 (P <0 .0 1) ,锌加铜组仅肾脏SOD活性升高 (P <0 .0 1) ,铜组肝、肾脏SOD活性及MDA含量均无显著性差异 (P >0 .0 5 )。病理学观察可见 ,锌干预组效果最好 ,其次为锌加铜组 ,而铜组无干预效果。提示补充一定剂量锌对染砷小鼠的脂质过氧化程度、抗氧化能力以及组织病理改变均有一定的干预效应。铜在该剂量下与锌起拮抗作用。     

Effect of particle size on quartz-induced hemolysis and on lung inflammation and fibrosis

To assess the role of crystal size in biologic responses, we quantitated red blood cell lysis and lung inflammation and fibrosis in the mouse using 4 alpha-quartz preparations with average diameters of 1, 5, 7.8, and 11.2 microns. When compared on the basis of identical crystal surface areas, the 1-micron fraction was more hemolytic than the other 3 fractions. The three larger fractions had equivalent membranolytic activities. After 6 weeks of postintratracheal instillation of the crystals into mice, the 1-micron-diameter crystal fraction increased wet lung weights by 1.25 x that of saline controls, while a 1.75 x increase was found for the three larger crystal fractions. A similar response was found when evaluating fibrosis development by determining lung hydroxyproline levels. Measurement of the percentage of the crystal dose remaining in the lungs revealed that the biologic differences observed were not due to a difference in the clearance of the smaller crystal fraction. Thus, larger crystals of alpha-quartz produce a greater degree of inflammation and fibrosis when instilled into the lung than those of 1 micron diameter, even though the smaller crystals are more membranolytic in vitro and appear to be cleared from the lung at the same rate as the larger crystals.     

Influence of Smoking on Basal and on Vagally and Maximally Stimulated Gastric Acid and Pepsin Secretion

Published data show that smokers have greater basal or peak acid and pepsin outputs, but the mechanisms underlying these effects are unknown. To confirm this and to determine whether these findings extend to, and implicate, any vagal overactivity, gastric secretions collected for 1 h basally, 1 h after 15 min of modified sham feeding (MSF), and 1 h after pentagastrin (6 μg/kg subcutaneously) were analyzed for acid and pepsin content in 204 subjects, 104 with duodenal ulcer (66 smokers) and 101 without (57 smokers). Maximal acid outputs (MAO, μeq/kg/h, x + SEM) were higher in smokers than in non-smokers in both duodenal ulcer (DU) (623 + 35 versus 491 + 35, p < 0.005) and non-DU (502 + 32 versus 376 + 20, p < 0.005). Basal and MSF secretions were generally increased in smokers but, when expressed as a percentage of MAO, were not different in smokers and non-smokers (18% versus 17% and 43% versus 39%, respectively, in DU, and 13% versus 16% and 40% versus 36% in non-DU). Maximal pepsin outputs (units + 10 ²/kg/h) were also higher in smokers than in non-smokers (DU, 129 + 7.9 versus 105 + 9.5, p = 0.05, and non-DU, 101 + 7.5 versus 77 + 10, p = 0.05). Basal and MSF secretions as a percentage of maximal pepsin output were not different in smokers versus non-smokers. Multivariate logistic regression shows that smoking was most strongly associated with MAO and sham feeding outputs, but the duration-intensity (pack-years) of smoking was associated only with elevated MAO. We conclude that smoking is associated with increased maximal acid and pepsin output in both DU and non-DU populations. Smoking does not seem to affect independently vagal stimulation of gastric secretion.     

Effects of trenbolone acetate and testosterone on growth and on plasma concentrations of corticosterone and ACTH in rats

The effects of trenbolone acetate (TBA) on growth and on plasma concentrations of corticosterone were examined in male and female rats. At 5 weeks of age, rats were injected with TBA (0.8 mg/kg) dissolved in peanut oil, or with oil alone, daily for 10 days. In female rats, TBA caused an increase in weight gain (20-38%), a reduction in adrenal weight (19%) and a reduction in plasma concentrations of corticosterone (55%). In contrast, TBA-treated male rats showed no significant increase in weight gain, no significant change in adrenal weight and no reduction in plasma concentrations of corticosterone. The mechanism by which adrenal activity was suppressed in TBA-treated female rats was examined and the response compared with that to testosterone. Female rats (8 weeks old) were injected daily either with oil vehicle, TBA (0.8 mg/kg) or testosterone propionate (0.8 mg/kg). Testosterone increased weight gain (24%), but the growth response to TBA treatment was significantly greater (97%). A reduction in plasma concentrations of corticosterone (45%) was again observed in response to TBA. However, testosterone increased plasma concentrations of corticosterone (52%) above those of control values. Neither androgen affected plasma concentrations of ACTH. Finally, the effects of TBA were examined in 6-week-old female rats, to characterize further the apparent age-related increase in responsiveness. The growth response of 6-week-old rats (60-74%) was intermediate between that seen in 5- and 8-week-old animals. It is concluded that part of the anabolic activity of TBA may be related to a reduction in circulating concentrations of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of adiponectin and ghrelin on incident glucose intolerance and on weight change

Objectives Adiponectin and ghrelin are associated with adiposity and type 2 diabetes in several studies. We sought to prospectively determine the interaction of adiponectin and ghrelin in the development of adiposity and hyperglycaemia. Design Prospective observational study. Participants 393 community‐dwelling Afro‐Jamaicans (mean age 47 ± 13 years; BMI 27·3 ± 6·3 kg/m²; 63% women) without glucose intolerance at baseline. Measurements Anthropometry, fasting plasma glucose, 2‐h plasma glucose, insulin resistance (HOMA‐IR), adiponectin and ghrelin concentrations were measured at baseline and 4·1 ± 0·9 years later. Multivariate analyses were used to explore the associations of HOMA‐IR, adiponectin and ghrelin with weight change and glycaemia. Results The mean weight change was 2·6 ± 5·5 kg. There were 114 incident cases of impaired glucose tolerance (IGT) and 35 cases of diabetes mellitus. Adiponectin was positively correlated with age and female sex (P‐values < 0·01). After adjusting for age and sex, adiponectin and ghrelin were significantly correlated with weight at baseline and follow‐up. However, they were not associated with weight change even after further adjustment for baseline weight. Adiponectin, but not ghrelin, was associated with 2‐h glucose concentrations at follow‐up even after adjusting for age, sex, HOMA‐IR and BMI (P = 0·04). In the fully adjusted logistic regression model, adiponectin predicted incident IGT (OR 0·93; 95% CI: 0·87–0·99) and attenuated the effect of BMI on incident IGT. Conclusions These longitudinal data show that adiponectin and ghrelin may not be causally involved in the development of obesity. However, adiponectin is independently associated with decreased risk of incident IGT.     

Influence of food on the effect of propantheline and L-hyoscyamine on salivation

The absorption of a quartenary (propantheline, 30 mg) and a tetiary (1-hyoscyamine, 0.8 mg) anticholinergic compound was studied in 8 healthy volunteers by measuring the effects on salivation. Both compounds were administered as rapidly disintegrating tablets, 1-hyoscyamine also in a slow-release formulation (Egazil Durules). The three preparations and placebo were administered under fasting conditions and with a standardized light meal using a randomized cross-over design. Salivation measurement were performed with a citric acid stimulation method every hour for 10 hours. In the fasting patient, all three anticholinergic test preparations decreased the salivation significantly. When taken with food, the effect of propantheline was almost abolished, while the effects of the 1-hyoscyamine preparations were uninfluenced. It was concluded that the clinical effects of proprantheline might be extremely varying depending how the drug is taken in relation to meals. In contrast the clinical effects of 1-hyoscyamine seem to be independent of food intake.     

Effect of paraformaldehyde on platelet size and on measurement of surface IgG

In many platelet assays, as in measurement of platelet-adherent IgG (PAIgG), platelets are fixed in paraformaldehyde (PFA). To better clarify the effect of PFA on platelet size and on PAIgG measurement we compared PAIgG levels in a series of 40 samples, with or without PFA fixing. We used an ELISA which was set up on unfixed platelets and gave excellent results in terms of linearity (r = 0.923), precision (mean CV = 5%) and correlation with a platelet suspension immunofluorescence test. We found PAIgG values in unfixed platelets were about 10-fold higher than in PFA-fixed (0.411 +/- 0.172 fg/platelet vs. 0.035 +/- 0.019 fg/platelet). This discrepancy could be a consequence of the smaller mean platelet volume (MPV) of washed platelets when fixed in PFA (8.0 +/- 0.8 fl as compared to 10.1 +/- 1.07). This effect of PFA could decrease the amount of binding sites for IgG exposed on the platelet membrane and hence explain the significantly lower PAIgG values observed in fixed platelets. The PAIgG measurements on unfixed platelets from 200 healthy subjects displayed a Gaussian distribution with a mean +/- SD of 0.32 +/- 0.13 fg/platelet, i.e., 1200 +/- 500 molecules/platelet.     

Preliminary observations on the effects of acute infusion of growth hormone on coronary vasculature and on myocardial function and energetics of an isolated and blood-perfused heart

Recent studies have shown that growth hormone (GH) deficiency may deteriorate post-ischemic myocardial reperfusion damage. Furthermore, GH has been reported to be a promising therapeutic option in the treatment of chronic myocardial dysfunction. However, the exact mechanisms of action of GH on the cardiovascular system, particularly in the acute setting, are still unclear. The aim of our study consisted of monitoring the acute effects of GH infusion on isolated blood-perfused rabbit heart according to dose-response pattern and during ischemic conditions to test its anti-ischemic property. Seven blood-donors perfused isolated hearts were used as experimental model. The mechanical and metabolic data of the isolated organs were continuously monitored. Under aerobic conditions, dose-response curves were initially tested after intracoronary infusion of GH at increasing dosages (1, 2, 3 mg/l). After a stabilization period, the effects of GH infusion (5 mg/kg) administered 30 minutes prior to acute global myocardial ischemia (30 minutes) were also investigated. At the doses tested, GH did not induce any changes either in the developed or in the diastolic pressures of the isolated organ. However, transient reduction of the coronary perfusion pressure was observed at the dosage of 3 mg/l. During the ischemia/reperfusion study, at the dosages used in this study, GH did not modify either the degree of stunning in the early reperfusion or the recovery of the developed pressure at the end of reperfusion. In addition, GH did not prevent either the increase of diastolic pressure during ischemia or the release of lactate and CPK during reperfusion. Tissue content of high-energy phosphates was also not changed by GH infusion. In our experimental model, acute GH infusion did not reduce the ischemic/reperfusion damage of the myocardium. However, GH transiently induced coronary vasodilation without modifying the myocardial contractility. Acute effects of GH appear, therefore, to predominantly relate to vascular dilation suggesting that the effects on myocardial contractility may require long-lasting intake being likely linked to enhancement of specific protein synthesis or gene expression of cardiac myocytes.