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L Macho

Publications and source records attributed to L Macho.

At least 55 records · Page 3Linked to original sources

Changes of insulin and glucagon binding to receptors in hepatocytes during liver regeneration.

The binding of insulin (INS) and glucagon (GL) on isolated rat hepatocytes during the process of liver regeneration after partial hepatectomy was determined. Adult male rats were subjected to 65-70% partial hepatectomy, control animals were sham-operated. The binding of radioiodine labelled INS and GL to isolated hepatocytes was determined 1, 2, 3 and 5 days after the surgery. The plasma levels of INS and glucose and microviscosity of liver plasma membranes were also measured. The decrease of INS receptor binding capacity was found 1, 2, and 3 days after operation. No differences in sham and partially hepatectomized groups in INS binding were noted 5 days after operation. A single insulin injection during the process of regeneration did not affect these changes of INS binding to hepatocytes. The increase of GL binding was observed on the third day after partial hepatectomy, however, on the 5th day no changes of GL binding to its receptors were noted. The plasma insulin and glucose levels were similar in both hepatectomized and sham-operated rats. The increase of plasma membrane microviscosity of hepatocytes during the process of liver regeneration and a negative correlation between INS binding and membrane microviscosity were found. These results demonstrated significant changes in binding parameters of both INS and GL receptors in hepatocytes during liver regeneration induced by partial hepatectomy.

Animals↗

Dietary fish oil and olive oil improve the liver insulin receptor tyrosine kinase activity in high sucrose fed rats.

In order to shed light on the possible beneficial effect of dietary unsaturated fatty acids on insulin binding, the effect of fish oil and olive oil administration on insulin binding, autophosphorylation and tyrosine kinase activity of partially purified liver insulin receptors were investigated. These data were confronted with the parameters of sugar and lipid metabolism (blood glucose, insulin and triglycerides), with liver plasma membrane fluidity and fatty acid composition. High sucrose feeding resulted in the elevation of blood glucose and triglyceride level, while the supplementation of animals with fish oil reduced that of triglycerides and olive oil that of insulin. Any significant changes between experimental groups were not detected either in insulin binding to partially purified liver insulin receptor nor in receptor autophosphorylation. However, the insulin stimulated tyrosine kinase activity towards an exogenous substrate (poly(Glu,Tyr)) was decreased by about 50% in the receptors solubilized from liver membranes of sucrose fed rats. Increased dietary intake of fish oil or olive oil restored the activity of insulin tyrosine kinase towards control values, half maximal effect being obtained at similar insulin concentration in all groups. Such improvement might be due to the induced increase of membrane fluidity by unsaturated fatty acids, and/or to the decrease of insulinemia.

Animals↗

Effect of dietary fish oil on 2-deoxy-D-3H glucose uptake in isolated adipocytes of rats fed various diets.

High sucrose diet-induced insulin resistance and mild glucose intolerance are associated with decreased insulin binding to isolated adipocytes and reduced insulin action in adipose tissue. Enhanced dietary intake of omega-3 polyunsaturated fatty acids (n-3-FA) counteracts these disorders. To provide more information on the possible role of membrane-related glucose transport processes, basal and insulin-stimulated 2-deoxy-D-3H glucose uptake was evaluated in isolated adipocytes obtained from rats on various dietary regimens. For 2 weeks animals were fed three different isocaloric (18 cal% proteins, 19 cal% fat, and 63 cal% carbohydrate) diets: (1) a standard rat chow (B), (2) a high sucrose diet (S, 63 cal% sucrose), or (3) an S diet supplemented with marine fish oil (S + FO, Martens, 30 wt% of n-3-FA). High dietary n-3-FA intake resulted in a significant decline in both basal (0.05 +/- 0.01 pmol/10(6) fat cells; mean +/- SEM) and insulin-stimulated (10(-6) M) (0.20 +/- 0.01) glucose uptake when compared with the control (basal: 0.12 +/- 0.02; insulin: 0.35 +/- 0.02) and/or the S group (basal: 0.18 +/- 0.03; insulin: 0.43 +/- 0.03), indicating decreases in insulin responsiveness and sensitivity (ED50: B: 0.03 +/- 0.01; S: 0.03 +/- 0.01; S + FO: 0.73 +/- 0.2 nM; p < 0.01 for S + FO vs B and S + FO vs S). Fish oil supplementation induced an increase in adipocyte size (B: 69 +/- 1.6; S: 70 +/- 2.5 and S + FO: 76 +/- 2.2 microns; B: S + FO p < 0.05) and a decrease in plasma membrane microviscosity (B: 4.08 +/- 0.3; S: 5.39 +/- 0.5; S + FO: 3.10 +/- 0.3; p < 0.05). Rates of basal and insulin-stimulated glucose uptake did not correlate with plasma membrane microviscosity; however, a negative relation to fat cell size was found (r = -0.484; p < 0.05). On the other hand, a positive correlation between both basal (r = 0.504; p < 0.05) and insulin-stimulated (10(-6) M, r = 0.640; p < 0.02) glucose uptake and blood glucose levels was observed. In conclusion, these data (a) suggest a less important role of diet-induced changes in plasma membrane microviscosity for glucose uptake in adipose tissue, and (b) leave unclear the mechanism of why dietary fish oil decreases the sensitivity of glucose uptake to insulin in isolated rat adipocytes.

Adipose Tissue↗

Effect of space flight on the development of endocrine functions in rats.

The effects of the exposure to space flights on plasma hormone levels were studied in adult male rats, in pregnant females and in their progeny. An increase of plasma corticosterone (CS) and insulin (I) levels was found in male rats after space flights for a period of 7, 15, 18 and 20 days. Plasma levels of growth hormone (GH) were decreased and those of epinephrine (E) and norepinephrine (NE) were elevated in rats exposed to longer space flights (18 or 20 days). In pregnant female rats no significant changes of plasma concentrations of CS, GH, I, E and NE were noted after short term space flight (5 days). However, the plasma prolactin levels were elevated. In young animals exposed to space flight during fetal development no changes of plasma I and prolactin levels were noted during the period of postnatal growth. However, the plasma CS levels were elevated in these rats and no gradual increase of CS plasma concentration was observed during the postnatal period. The plasma GH levels were reduced in rats exposed to space flight and the levels of catecholamines in plasma and in adrenal glands were elevated in 30 and 100 day old rats exposed to microgravity during the fetal development. These results demonstrated: 1. that exposure of rats to space flight is followed by changes in I and CS plasma levels, but the sympathetic-adrenomedullary system is only slightly activated by longer space flights; 2. that a short term space flight is only a mild stressor for pregnant rats and slightly affects the activity of adrenocortical and sympathetic-adrenomedullary systems during the development of their offsprings.

Animals↗

Changes of hormones regulating electrolyte metabolism after space flight and hypokinesia.

The changes of hormones in plasma involved in the body fluid regulation were studied in human subjects during and after space flights in relation to redistribution of body fluids in the state of weightlessness. Since hypokinesia was used as a model for simulation of some effects of the stay in microgravity the plasma hormone levels in rats exposed to hypokinesia were also investigated. Plasma aldosterone values showed great individual variations during the first inflight days, the increased levels were observed with prolongation of space flights. The important elevation was found in the recovery period, however it was interesting to note, that in some cosmonauts with repeated exposure to space flight, the postflight plasma aldosterone levels were not elevated. The urine excretion of aldosterone was increased inflight, however in postflight period the decrease or increase were found in the first 1-5 days. The increase of plasma renin activity was observed in flight and postflight period. The rats were exposed to hypokinesia (forced restriction of motor activity) for 1, 7 and 60 days and urine was collected during last 24 hours. The animals were sacrificed and the concentration of electrolytes and of levels of corticosterone, aldosterone (A), ANF and plasma-renin activity (PRA) were determined in plasma. In urine excretion of sodium and potassium were estimated. An important increase of plasma renin activity and aldosterone concentration was found after short-term hypokinesia (1 day). These hormonal values appear to decrease with time (7 days) and are not significantly different from controls after long-term hypokinesia (60 days). A decrease of values ANF in plasma was observed after 1 and 7 days hypokinesia. After prolonged hypokinesia a decrease of sodium plasma concentration was observed. The excretion of sodium in urine was higher in long-term hypokinetic animals. There were no significant changes of plasma potassium levels in rats exposed to hypokinesia, however the urinary excretion of potassium was elevated. In rats exposed to hypokinesia for 7 and 60 days an increase of urine osmolality was observed. The results of hormone and electrolyte determination in plasma of cosmonauts after space flight and in experimental animals after hypokinesia suggested that in evaluation of relations between the changes of hormone levels and electrolyte in plasma and urine other factors like emotional stress working load; altered diurnal cycles should be considered in interpretation of homeostatic response of fluid and electrolyte metabolism to space flight conditions.

Aldosterone↗

In vivo role of corticosterone in regulation of insulin receptors in rat adipocytes during hypokinesia.

The role of corticosterone in the changes of insulin receptors of rat adipocytes during hypokinesia was investigated. Three groups of adult male Wistar rats (1. intact; 2. adrenalectomized; 3. dexamethasone treated) were exposed to hypokinesia for various period. The plasma levels of corticosterone, insulin and glucose and the binding of insulin (125I-TyrA-14 monoiodoinsulin) to isolated adipocytes were determined. A significant increase of plasma corticosterone level and a decrease of insulin binding to adipocytes were found in rats exposed to hypokinesia for one day. After 3 and 5 days of hypokinesia the corticosterone level in plasma was decreased to the concentration observed in the control animals. Also the binding of insulin to adipocytes returned to the values found in control group. In adrenalectomized rats exposed to hypokinesia no changes of insulin receptors in adipocytes were noted. The treatment of rats with dexamethasone (both, the intact and adrenalectomize ones) resulted in a decrease of insulin binding in fat cells. These results showed that an increase of corticosterone in plasma after the short term exposure to hypokinesia or the injection of dexamethasone to intact or adrenalectomized animals are followed by the decrease of insulin receptors in adipocytes suggesting that glucocorticoids participate in the regulation of insulin receptors in adipocytes during short term hypokinesia.

Adipose Tissue↗

Activity of the sympathoadrenal system in cosmonauts during 25-day space flight on station Mir.

The activity of the sympathoadrenal system in cosmonauts was studied by measuring plasma and urinary catecholamines and their metabolites and conjugates. The appliance Plasma 02 was used for collecting, processing, and storing blood and urine samples from the cosmonauts during the course of a 25-day flight on board the station Mir. Plasma and urine concentrations of adrenaline (A), noradrenaline (NA), and dopamine (DA) as well as urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA), and plasma levels of catecholamine sulphates were determined before, during and after the space flight. Plasma NA levels were slightly elevated on day 9 and plasma A on day 20, whereas plasma DA levels were unchanged. However, most of the changes were within the normal range of control values. Sulphates of plasma catecholamines did not change during flight but they were significantly elevated after landing. Urinary levels of A, NA, DA, VMA, and HVA were comparable with preflight values but were elevated at the different intervals studied after landing. The results obtained suggest that in the short period of about 9 days of the cosmonaut's stay in space the sympathoadrenal system was slightly activated indicating a mild stressful influence of the initial period of flight. This short-term space flight compared to long-term flight did not as markedly activate the sympathoadrenal system during the process of re-adaptation to Earth's gravity after landing. Our data suggest that weightlessness is not a stressful factor activating the sympathoadrenal system but it sensitizes the responsiveness of this system during the re-adaptation period after space flight.

Adaptation, Physiological↗

Effect of space flights on plasma hormone levels in man and in experimental animal.

An important increase of plasma hormone levels like insulin, TSH and aldosterone was observed in human subjects after space flights, however in the changes of plasma content of ACTH, cortisol, adrenaline and noradrenaline the individual variations were observed in relation to number and duration of space flight. For evaluation of the effects of these changes in plasma hormone levels on metabolic processes also the experiments with small animals subjected to space flights on a board of biosatellite of Cosmos series were running. An elevation of plasma levels of corticosterone, adrenaline, noradrenaline and insulin was found in rats after the space flights of duration from 7 to 20 days. It was demonstrated, that the increase of corticosterone in plasma is followed by the activation of enzymes involved in the amino acid metabolism in rat liver (tyrosine aminotransferase, tryptophanpyrolase, alanine aminotransferase and aspartate aminotransferase). After a short recovery period (2 to 6 days) the plasma corticosterone concentration and also the activity of liver enzymes returned to control levels. The exposition of animals to stress stimuli during this revcovery period showed higher response of corticosterone levels in flight rats as compared to intact controls. The increase of plasma catecholamine levels was not followed by elevation of lipolysis in adipose tissue. This is due to lower response of adipose tissue to catecholamine because a decrease of the stimulation of lipolysis by noradrenaline was observed in animals after space flight. The increase of insulin was not followed by adequate decrease of glucose concentration suggesting a disturbances in glucose utilization similarly as in cosmonauts after a long-term space flight. These results showed that changes in plasma hormone levels, observed after space flight, affected the regulation of metabolic processes in tissues.

Animals↗

The effect of space flight on the board of the satellite Cosmos 2044 on plasma hormone levels and liver enzyme activities of rats.

The aim of present experiment was to study the changes of corticosterone, insulin and glucose levels in plasma, of the activity of enzymes involved in aminoacid metabolism in liver and the binding of insulin to specific receptors of cell membrane from liver and also of adipose tissue of rats exposed to space flight for 14 days on biosatellite Cosmos 2044. Adult male Wistar rats (body mass 300-370 g) were divided into five groups: intact control rats (AC), rats exposed to space flight (F), animals in synchronous model experiment (S), rats in antiorthostatic hypokinesia (A) and so called operated control group (C). Half of all groups (5 animals) except the intact control were operated 3 days before the experiment (fibulas on both hind legs were broken). The flight animals were sacrificed 5-6 hours after landing. It was observed that plasma insulin levels are increased in rat exposed to 14-day space flight and in synchron experiments. A significant increase of plasma glucose levels was found in flight rats in spite of high insulin concentrations suggesting that in rats exposed to 14-day space a deterioration of tissue sensitivity to insulin could by present. No significant differences of specific insulin binding to liver plasma membrane fraction in flight and intact control animals were observed. A decrease of insulin binding capacity in liver was found in rats in antiorthostatic hypokinesia (A). However in the membrane of adipocytes an important increase of insulin receptors was noted in rats subjected to space flight. These results suggest, that the liver and adipocyte insulin receptors of flight rats did not respond to the increased plasma insulin levels by "down regulation". The determination of plasma corticosterone levels showed that in flight rats and animals exposed to antiorthostatic hypokinesia the plasma hormone levels are significantly elevated. A significant increase of tyrosine aminotransferase and tryptophan pyrrolase activities in liver of flight rats and those exposed to hypokinesia was observed. Also the elevation of alanine amino-transferase in liver was observed in flight rats, while, the activity of aspartate aminotransferase in liver was similar in control and flight animals. These results showed that the changes in liver enzyme activities in rats after 14-day space flight are in agreement with the results observed in previous experiments after a shorter space flight (7 days).

Adipose Tissue↗

Intra-arterial cisplatin given prior to surgery in osteosarcoma: grade of necrosis and size of tumor as major prognostic factors.

From January 1983 to August 1987, 29 evaluable patients with high-grade osteosarcoma were treated in our institution with preoperative intra-atrial cisplatin, 100 mg/m2 every 14 days for three courses. Surgery was done on day 42. Surgery consisted of limb salvage in six, amputations in 15, and disarticulations in eight. Postoperative chemotherapy included Adriamycin (ADR), 45 mg/m2 for 2 days every 6 weeks, alternated with cisplatin 120 mg/m2 every 6 weeks. The nephrotoxicity (18 out 29) was reversible in all cases. Cardiotoxicity was prominent; it was observed in 31% of patients. In six, there was congestive heart failure, but there were no fatal cases. The hematological toxicity was severe. There were three patients with fatal infections who had no evidence of disease after they had finished treatment. Seventeen of 29 patients (58.6%) were good responders and showed 60-100% tumoral necrosis after intra-atrial cisplatin. The 6-year, relapse-free survival rate was 58.6%--70.5% for the good responders and 41.6% for the poor responders (p less than 0.05). The size of the tumor was the other important prognostic factor. The rate of 6-year, relapse-free survival was 73.6% for small tumors (those measuring less than 100 cm2) and 33.3% for large tumors (p less than 0.05).

Adolescent↗

Late effects of breast-feeding and early weaning: seven-year prospective study in children.

The effect of breast feeding on some clinical and thyroid function parameters was studied in a prospective longitudinal study from birth up to 7 years of age. At the ages 1-7 years, the obesity rates observed in children breast-fed for less than 3 months were substantially higher than in children who had been breast-fed over longer intervals. Mean age when obesity was reported was similar in all groups (4-5 years). The rates of respiratory tract diseases were found to be highest in children which had been breast-fed for less than 2 weeks. Breast-feeding for more than 6 months had a protective effect against diseases of the gastrointestinal tract. The longitudinal follow-up revealed biphasic changes of thyroid hormones and TSH in sera with a nadir at 2-3 years, followed by an increase at the end of preschool age. Duration of breast-feeding did not affect profoundly these parameters at the ages 1-7 years. Surprisingly, during late preschool age (5-6 years) total serum cholesterol increased with the age at weaning. The atherogenic index in 6-year-old children was most favourable in the group breast-fed over more than 1 but less than 3 months. This was due to the highest levels of HDL-cholesterol in this group. We conclude that the age at weaning may be important for the later development of children.

Body Weight↗

[The effect of chronic stress on the activity of the sympathetic-adrenomedullary system].

Plasma levels of adrenaline (ADR) and noradrenaline (NA) belong to the best parameters of activity of the sympatho-adrenomedullary system (SAS). Introduction of a sensitive radioenzymatic method for the determination of catecholamines in small volumes of plasma (0.05 ml) and observing conditions of stressless blood collection by means of an indwelling catheter made in possible to determine basal plasma catecholamine levels and their dynamics during stress. Changes in plasma catecholamines were studied in acute and chronic stress (continual or intermittently repeated) in three stress models: 60-day hypokinesia, immobilization (IMO) repeated over 30 days, and 14-day or one-day handling of the rat for 1 minute. On first exposure to the given stressor the plasma levels of both catecholamines studied were increased. In the course of 60-day hypokinesia as well as during one- or 14-day handling plasma ADR levels returned to virtually resting values, plasma NA levels, however, remained at equally high values as recorded at the first exposure. During 30-day IMO basal values of ADR and NA in plasma were elevated, yet the catecholamine response to the last IMO was reduced compared to the first exposure. Under the effect of mild chronically acting stressors a dissociation was observed in the changes of plasma catecholamine levels: ADR failed to exhibit further increases, whereas NA kept significantly rising all over the period of the activity of the stressor. This differentiated activation of plasma catecholamines suggests the existence of different regulatory regions in the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

Activation of the sympathoadrenal system in rats during hypokinesia.

The levels of plasma epinephrine (E) and norepinephrine (NE) were examined in rats exposed to hypokinesia in special adjustable cages for 1, 7 and 75 days. One day before the collection of blood an arterial catheter was inserted into the tail artery and blood samples were collected from undisturbed animals on next day at 8 a.m. and after 1, 6, 12 and 24 hours later. The control groups of animals were kept single in standard animals cages. The content of E, NE and corticosterone was determined in plasma. In rats exposed to hypokinesia for the first time a marked increase of plasma E and NE levels were observed at 1 hour in forced restriction and both E and NE remained elevated after 6, 12 and 24 hours of hypokinesia. A permanent increase of NE and E content in plasma was found in rats exposed to hypokinesia for 7 and 75 days. However, the plasma corticosterone levels were increased only during the first day of hypokinesia, at 7 and 75 days no significant changes in plasma corticosterone were noted. These results showed that there is an important increase of plasma catecholamine levels immediately after the beginning of hypokinesia and the activation of sympathoadrenal system is maintained during the whole period of hypokinesia. No significant changes in adrenocortical system activity were noted during the long-term hypokinesia.

Animals↗