Supplementation with L-arginine favorably influences plasminogen activator inhibitor type 1 concentration in obese patients. A randomized, double blind trial.

BACKGROUND: Elevated plasminogen activator inhibitor type 1 (PAI 1) plays an important role in the pathogenesis of excess blood coagulability in obese patients. L-arginine supplementation has shown to be associated with enhanced cardiovascular and metabolic health. The aim of the study was to assess the effect of L-arginine supplementation on PAI 1 concentration and to evaluate the relation to changes in nitric oxide (NO) plasma level, insulin sensitivity (M value), and total antioxidant status (TAS) in obese patients. MATERIAL/SUBJECTS AND METHODS: A randomized, double-blind, placebo-controlled study was conducted from March 2010 to June 2011. Eightyeight obese patients were randomly assigned to receive either 9 g of L-arginine or placebo daily for 6 months. At baseline and after 6 months, selected anthropometrical measurements and blood biochemical analyses were performed, and PAI 1, NO, TAS levels were assessed. Insulin sensitivity was evaluated using the hyperinsulinemic euglycemic clamp technique. RESULTS: We found that 6-month L-arginine supplementation resulted in significant decrease of PAI 1. Significant increase of NO, TAS, and insulin sensitivity level were noticed. In a group of patients treated with L-arginine, negative correlation between a change of insulin sensitivity value and a change of PAI 1 concentration was found. CONCLUSIONS: The present findings demonstrate favorable influence of L-arginine supplementation on PAI 1 concentration in obese patients. Beneficial influence is related to insulin sensitivity improvement. The potential therapeutic role of L-arginine administration in patients with obesity needs further investigation.

The effects of neurotensin on selected parameters of lipid metabolism in rats.

15 nM/kg b.m. of neurotensin (NT) caused a significant inhibition of LMA within 30 min of administration and this effect persisted up for to the 240 th minute of the experiment. A 15 nM/kgb.m. dose also caused a reduction in SLA which persisted up to the 120 th minute. Sixty minutes after an intraperitoneal administration of NT a decrease in the cholesterol and NEFA levels and an increase in the TG and glycerol levels were observed. These effects were inhibited by the NTR2-blocker (levocabastine) and were not subject to change after an in vivo application of SR 48692.

Age dependent changes of insulin receptors in rat tissues.

Aging is associated with insulin resistance but the exact molecular mechanism is still unknown. Tissue insulin resistance can be evoked by the decreased sensitivity to insulin, the decreased responsiveness to hormone or both. As the first step in insulin action is its binding to alfa subunits of the receptor we, therefore, studied the insulin binding kinetics in plasma membranes of the liver, heart and skeletal muscle in order to establish whether their ability to bind the hormone is altered with aging. Plasma membranes were prepared and purified according to Havrankowa and binding assay was performed using (125I)-iodoinsulin. The kinetic parameters of the hormone-receptor interaction were analysed by the method of Scatchard using the LIGAND-Pc v.3.1. computer program. The binding potency of insulin was calculated as IC50 using ALLFIT-Pc v.2.7. computer program. We have shown that there are striking differences in insulin binding kinetics in newborn and old rats, depending on kind of tissue tested. The liver plasma membranes ability for insulin binding, number of high (HAIR) and low (LAIR) affinity insulin receptors, values of the dissociation constants and products of association constants and number of insulin receptors, were almost the same, being not dependent on age of the rats. By contrast, there is less high affinity insulin receptors in skeletal muscle of the old animals. The most dramatic changes in insulin binding occur in the heart where both high and low affinity insulin receptors are greatly affected by aging. Our results indicate that the response of the three tissues tested to hyperglycemia and hyperinsulinemia, observed in the old rats, has not been identical and probably can be accounted for by the different distribution of insulin receptor isoforms in the liver, heart and skeletal muscles as shown recently by Vidal et al.

Pressure-controlled reperfusion improves postischemic recovery of LV-hypertrophied rat hearts.

The influence of pressure-controlled postischemic reperfusion (Rp) on functional and metabolic parameters in hearts of sham-operated rats and hypertrophied hearts of rats with aortic constriction were studied. Hypertrophied hearts are considered to be more susceptible to ischemia. The hearts were perfused in the Langendorff-technique for thirty minutes at 35 degrees C with Krebs-Henseleit bicarbonate buffer at a perfusion pressure (PP) of 75 mmHg and for five minutes at 15 degrees C with St. Thomas' Hospital cardioplegic solution at a PP of 60 mmHg. After a period of global ischemia of forty minutes' duration at 15 degrees C, reperfusion was started either abruptly (aRp: PP 75 mmHg immediately) or gently (gRp: PP 75 mmHg within thirty minutes); it lasted for forty-five minutes. Intraventricular peak systolic pressure (ISP) was monitored and energy-rich compounds (ATP, ADP, AMP, CrP, free Cr) were analyzed. In normal hearts, metabolic recovery was not affected by the mode of reperfusion, but functional recovery (ISP) averaged 88% of the preischemic control value after gRp as compared with 73% after aRp. In hypertrophied hearts, gentle reperfusion ameliorated both metabolic and functional recovery. At forty-five minute recovery, CrP averaged 5.1 mumol/g ww after aRp and 6.6 mumol/g ww after gRp (p less than 0.01), and ISP amounted to 73% of the preischemic control after aRp and to 85% after gRp.

Alternations in free radical erythrocyte-defense mechanisms in streptozotocin induced diabetic rats - effect of antioxidant treatment.

The activities of superoxide dismutase, glutathione peroxidase and the contents of glutathione, malondialdehyde were examined in erythrocytes of streptozotocin induced diabetic rats. The above mentioned antioxidant systems of erythrocyte were determined after treatment of diabetic rats with superoxide dismutase, trolox, catalase and allopurinol. In erythrocytes of streptozotocin induced diabetic rats the activities of superoxide dismutase, glutathione peroxidase as well as the levels of reduced glutathione were lower whereas the contents of oxidized glutathione and malondialdehyde were higher than in controls. Superoxide dismutase and trolox treatment of diabetic rats resulted in an increase of erythrocyte glutathione peroxidase activities and in reduced glutathione levels. However the levels of oxidized glutathione decreased after treatment of diabetic rats with superoxide dismutase and trolox. Catalase and allopurinol administration did not have any influence on the activities of the investigated enzymes nor on the levels of glutathione in diabetic rats. The antioxidants under study did not cause any changes in the increased level of malondialdehyde in erythrocytes.

Artificial conditioner for stored organs.

We have developed an artificial organ conditioning system in order not only to condition but also evaluate the viability for transplant graft of kidneys which have been stored for a long time and damaged by warm ischaemia following cardiac arrest. The conditioning system consisted of an artificial lung, a roller pump, an organ chamber and perfusate. The perfusate was prepared with electrolytes, fluorocarbon, amino acid, glucose, an oxygen scavenger and so on. Conditioning was performed by continuous perfusion under mild hypothermia at 24 degrees C. Mildly damaged kidneys (0 and 30 minutes warm ischaemia rabbit kidneys) were well conditioned but severely damaged kidneys failed to produce urination. Our device successfully exposed the viability of stored kidneys and the successful conditioning of damaged kidneys due to warm ischaemia avoiding transplantation. By establishing our method, the harvesting of kidneys following cardiac arrest will be feasible.

[Effect of tolbutamide on lipolytic processes in blood and fat tissue of rats maintained in normothermic and hypothermic conditions]. / Wplyw tolbutamidu na procesy lipolityczne we krwi i tkance tluszczowej szczurów przebywajacych w warunkach normotermii i hipotermii.

The effect of tolbutamide administered in vivo or added to the incubation medium on lipolysis in adipose tissue and in blood has been studied in rats. Tissue lipolysis was lowered by 118 to 156% in groups of rats receiving tolbutamide in vivo. The addition of tolbutamide directly to the incubation medium caused an increase in the lipid mobilizing activity, while the addition of insulin inhibited lipolysis in each case. The effect of tolbutamide administered in vivo may be indirect through an increase in insulin binding and/or the drug may influence directly the permeability of cell membrane for ions and glucose. An increase in the lipid mobilizing activity observed in experiments consisting in the addition of tolbutamide to the incubation medium may be linked to the low glucose level and greater demand for free fatty acids or to the low level of insulin in the incubation medium.

Effect of 2-deoxy-D-glucose on lipolytic processes in blood and adipose tissue of rat.

The effect of 2-deoxy-D-glucose on lipolytic processes in the blood and adipose tissue was studied. Rats treated with this antimetabolite showed a significant increase in serum glucose, FFA and glycerol level, as well as in the lipid mobilizing activity. On the other hand, the lipolytic activity of rat serum decreased when compared to control group. From these results it may be concluded that during hypothermia induced by administration of 2-deoxy-D-glucose intracellular, but not intravascular, lipolysis is enhanced.

In vitro serum glycogenolytic activity in rats during hypothermia induced with 2-deoxy-D-glucose.

During hypothermia induced by intraperitoneal administration of 2-deoxy-D-glucose (600 mg/kg of body weight) the serum levels of glucose and FFA rise and the hepatic glycogen content falls in relation to rats in control group. The glycogenolytic activity of the serum in vitro determined against liver slices is also higher in the group of rats receiving 2-DG. The obtained results point to an activation of the glycogenolysis process and glycolysis in the organism of rats after administration of hypothermia-inducing doses of 2-DG.

Inhibition of endogenous pancreatic enzyme secretion by oral pancreatic enzyme treatment.

BACKGROUND: The existence of a feedback mechanism for exocrine pancreatic secretion in humans is controversial. Exclusion of proteases from the duodenum stimulates exocrine pancreatic secretion. Conversely, addition of exogenous enzymes could reduce the enzyme secretion. Further investigation of the feedback mechanism should be performed under the most physiological conditions. In the present study we investigated exocrine pancreatic function by measuring fecal enzyme output in healthy volunteers consuming a normal diet, before and during a time course of exogenous pancreatic enzyme supplementation. MATERIAL AND METHODS: Twenty-five healthy subjects (HS) were given two different doses (30 and 60 FIP proteases kg(-1) d(-1)) divided by the number of meals. In all subjects, fecal elastase-1 (E1) concentrations and chymotrypsin (ChT) activities were measured without and with enzyme supplements after 7 days of treatment. In eight subjects, E1 concentrations and ChT activities were measured daily for 10 consecutive days. The subjects were given a dose regimen of 100 FIP proteases kg(-1) d(-1)(divided by the number of meals) for the first 7 days. RESULTS: Oral pancreatic treatment dose-dependently inhibited endogenous pancreatic secretion measured with the use of E1 concentrations. In both regimen groups, the differences were statistically significant. The exogenous enzymes, which interfere with colorimetric method for ChT, dose-dependently increased ChT output. However, only the higher dose resulted in a statistically significant difference. In the subgroup of eight HS, time-dependent changes of fecal enzyme output occurred with a decrease of E1 concentrations and an increase of ChT activity from the second up to eighth or ninth day of the experiment. CONCLUSION: Exogenous applied pancreatic enzymes, dose- and time-dependently inhibited endogenous pancreatic secretion. The obtained results strongly support the existence of a protease mediated feedback mechanism in humans.