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Biomedical subjects

Z Madar

Publications and source records attributed to Z Madar.

At least 55 records · Page 3Linked to original sources

A double-blind trial of a celandin, aloevera and psyllium laxative preparation in adult patients with constipation.

The aim of this study was to evaluate the effect of a novel laxative preparation, composed of celandin, aloevera and psyllium in patients with chronic constipation. Thirty-five men and women were randomized to receive capsules containing celandin-aloevera-psyllium, or placebo, in a double-blind trial lasting 28 days. Symptoms in the last 2 weeks of the treatment period were compared to those in the 14-day pre-trial basal period. In the celandin, aloevera and psyllium group, bowel movements became more frequent, the stools were softer and laxative dependence was reduced. In the placebo group, all these parameters were unchanged. Abdominal pain was not reduced in either group. The results of this study show that the preparation is an effective laxative in the treatment of constipation.

Adult↗

Pyruvate dehydrogenase and glycogen synthase activity at transition from fasted to fed state.

The aim of the present study was to evaluate whether the PDC and GS activities at the transition from fasted into fed state are consistent with indirect pathway for glycogen synthesis, as suggested previously. Refeeding of glucose given to rats after 72 hr of starvation did not reactivate PDC in the liver; however, the PDC activity in the muscle was increased. In comparison to PDC, glucose refeeding leads to an opposite effect on GS in both liver and muscle as evidenced by the immediate increase in the active form of GS. The low activity of liver PDC restricts 3-carbon flux through the Krebs cycle and enables their transfer to the gluconeogenic pathway for glycogen synthesis. In contrast, an immediate activation of muscle PDC following refeeding indicates that 3-carbon flux will be oxidized in the citric acid cycle, which thereby eliminates the indirect pathway for glycogen synthesis in this tissue. Glucose infusion increased plasma lactate, insulin, and glycogen content in the liver and muscle to the same extent as observed in the fed rats. The results are in agreement with the suggestion that at the transition from fasted to fed state, liver glycogen synthesis occurs mainly from 3-carbon precursors.

Animals↗

Metabolic consequences of the alpha-glucosidase inhibitor BAY-M-1099 given to nondiabetic and diabetic rats fed a high-carbohydrate diet.

The effect of a new alpha-glucosidase inhibitor BAY-M-1099 on postprandial glucose levels in nondiabetic and diabetic rats after sucrose loading was studied. Evaluation was also made of the metabolic consequences of the addition of BAY-M-1099 to a high-carbohydrate diet consisting of equal quantities of wheat starch and sucrose (Diet A). This drug significantly reduced (p less than 0.05) postprandial glucose levels in nondiabetic and diabetic rats after sucrose loading. BAY-M-1099 led to a significant reduction in urinary glucose loss (177.8 +/- 54.2 vs 98.9 +/- 35.6 mmol/L) and in postprandial plasma glucose levels in diabetic rats fed diet A. Addition of BAY-M-1099 to the diet of nondiabetic rats significantly (p less than 0.05) decreased the postprandial plasma glucose level at 45, 90, 180, and 225 min after a meal test. Addition of BAY-M-1099 to a diet containing starch plus sucrose led to reduced glycosuria and serum glucose levels and may have potential benefit in the management of diabetes mellitus.

1-Deoxynojirimycin↗

The effect of acarbose and miglitol (BAY-M-1099) on postprandial glucose levels following ingestion of various sources of starch by nondiabetic and streptozotocin-induced diabetic rats.

The effect of two alpha-glucosidase inhibitors, acarbose (BAY-G-5421) and miglitol (BAY-M-1099), on postprandial glucose levels following intubation of corn, rice, spaghetti and potato (0.5 g/100 g body wt) was evaluated in nondiabetic and diabetic rats. The peak plasma glucose level and total incremental glucose were significantly decreased following ingestion of each starch source when acarbose (8 mg/100 g body wt) or BAY-M-1099 (2 mg/100 g body wt) were simultaneously intubated. The effect of both inhibitors was more pronounced in diabetic rats than in nondiabetic rats, and their effect on digestion was in a substrate-specific manner. Potato starch digestion was inhibited 58 +/- 11% by BAY-M-1099, and by acarbose, 38 +/- 9%. Rice starch digestion was inhibited by 65 +/- 2% by acarbose, and by BAY-M-1099, only 30 +/- 9%. Both drugs had a similar inhibitory effect when corn or spaghetti was ingested. BAY-M-1099 appears to be more potent than acarbose on both a weight-per-weight basis and on a molar basis. When corn or rice was used, only 2 mg of BAY-M-1099 was required to achieve a similar inhibitory effect to that of 8 mg of acarbose (9.7 X 10(-3) M) vs. 12.2 X 10(-3) M). Since both drugs blunted to varying degrees the rise in glucose level following starch ingestion, they may be a useful adjuvant in the treatment of diabetic subjects. Simultaneous use of both drugs in therapeutic treatment should be seriously considered.

1-Deoxynojirimycin↗

Effect of prolactin on casein and fat synthesis and casein secretion in explants of bovine mammary tissue pretreated in athymic nude mice.

Bovine mammary gland tissue from 4- to 6-mo-old calves was grafted s.c. (dorsum) to 7- to 9-wk-old female athymic "nude" mice. The graft-bearing mice were divided into three groups and were treated with the following hormonal combinations: 1) implantation of a pellet containing estrogen and progesterone followed by injection of estrogen and progesterone, 2) injections of estrogen and progesterone, and 3) injections of estrogen, progesterone, and prolactin. Following in vivo treatment, the grafts were removed and prepared for organ culture. Explants from each treatment were subdivided into two hormonal regimens: 1) insulin and cortisol; 2) insulin, cortisol, and prolactin. An increase in in vitro fat synthesis was observed in explants cultured in the presence of prolactin. This increase was not affected by previous in vivo hormonal treatment. In vitro casein synthesis was not stimulated by the presence of prolactin in the culture medium; however, casein secretion was elevated in explants from grafts from animals that were treated in vivo with estrogen, progesterone, and prolactin. Casein secretion was further increased in explants cultured in the presence of prolactin but rapidly dropped in its absence. Explants that were not implanted in mice responded in long-term organ culture similarly to explants pretreated in vivo.

Animals↗

Effects of cottonseed dietary fiber on metabolic parameters in diabetic rats and non-insulin-dependent diabetic humans.

The objective of this study was to evaluate the effect of gland cottonseed dietary fiber (CSDF) containing 86% dietary fiber (mainly cellulose) on serum glucose levels in diabetic rats and in non-insulin-dependent diabetes mellitus (NIDDM) patients. A diet containing 15% CSDF given to streptozotocin-induced diabetic rats for 30 d tended to reduce the postprandial plasma glucose level curve. Alternatively, CSDF significantly increased fecal weight (15 +/- 3 vs. 5 +/- 2 g; P less than 0.01) and shortened transit time (20 +/- 2.24 vs. 11.2 +/- 0.8 h). CSDF had no effect on body weight and serum lipid levels. Twelve NIDDM subjects were given a meal tolerance test (MTT) with or without CSDF before and after daily supplementation of CSDF (16.5 g) in pita twice a day for a month. Incremental glucose levels were significantly (P less than 0.05) lower at 30, 60 and 180 min after the MTT containing CSDF than in subjects consuming a meal without CSDF. The insulin levels also tended to be lower. The NIDDM subjects tolerated the CSDF well. No flatulence or other side effects were exhibited. Plasma lipid levels remained unchanged. We therefore concluded that CSDF may have a potential benefit in the management of NIDDM.

Adult↗

Glucose-lowering effect of fenugreek in non-insulin dependent diabetics.

The effect of fenugreek on postprandial glucose and insulin levels following the meal tolerance test (MTT) was studied in non-insulin dependent diabetics (NIDDM). The addition of powdered fenugreek seed (15 g) soaked in water significantly reduced the subsequent postprandial glucose levels. The plasma insulin also tended to be lower in NIDDM given fenugreek but without a statistical difference. Fenugreek had no effect on lipid levels 3 h following the MTT. Fenugreek may have a potential benefit in the treatment of NIDDM.

Adult↗

Glycemic indices of various foods given to pregnant diabetic subjects.

The applicability of the glycemic index concept in pregnancy has not been established. The postprandial glucose curves were measured for nine foods (glucose, bread, raisins, dates, sweet corn, bananas, oranges, spaghetti, and green peas) in 28 gestational diabetic subjects. Uniform glycemic indices were observed for each food, similar to those reported by others in nonpregnant subjects. Postprandial glucose levels reached their peak later after glucose and bread ingestion than after the remaining seven foods. These results demonstrate that despite known changes in gastrointestinal function in pregnancy, glycemic indices are uniform after the ingestion of foods. Pregnancy does not appear to alter the glycemic indices of the foods tested.

Adult↗

Partial purification and characterization of bovine mammary gland prolactin receptor.

Prolactin (PRL) receptors from the mammary gland of the lactating cow were solubilized with 3-[(3-cholamidopropyl)dimethylamonio]-1-propane sulfonate (CHAPS). Affinite chromatography on human growth hormone (hGH) coupled to Affi-Gel 10 resulted in over 500-fold purification, as compared to microsomal fractions. Scatchard analysis of the binding of hGH indicated an increase in the affinity constant of 2.5-fold after solubilization and of further 2-fold after the affinity purification. The specific binding activity of the affinity-purified fraction was 9000 fmol hGH/mg protein. Complexes of Triton X-100-solubilized receptors with [125I]hGH were analyzed by gel filtration on Sephadex G-150, in the presence of Triton X-100. A minor fraction of the complexes eluted as high molecular weight (Mr) aggregates, whereas a major fraction eluted as a 150 kDa peak. Assuming a contribution of approximately 30% to the Mr by the bound detergent and a hormone: receptor ratio of 1:1 in the complex, a Mr of 80-85 kDa can be calculated for the receptor molecule. Affinity labelling of the receptor with [125I]hGH revealed a Mr of 37 +/- 0.5 kDa (n = 7) for the binding subunit. Specific high Mr aggregates were also observed after crosslinking; however, the size of the labelled species was not affected by reducing agents. Homologous and heterologous competitive binding studies with ovine PRL (oPRL) or hGH revealed a considerably higher affinity for hGH as compared to oPRL. The competitive displacement patterns obtained with oPRL or hGH as tracers were similar, indicating that both hormones bound to the same receptor sites with different affinities. A similar difference in affinity was retained by the affinity-purified receptors.

Affinity Labels↗

Glycogen synthase kinetics in isolated human adipocytes: an in vitro model for the effects of insulin on glycogen synthase.

Glycogen synthase which catalyzes the incorporation of uridine dipophosphate glucose into glycogen is found in muscle, liver, and fat. The activity of this enzyme is increased by insulin through a dephosphorylation mechanism. Because of the critical role of glycogen synthase in glucose storage and overall glucose metabolism, it is important to assess the status of the activity of this enzyme in normal humans as well as in individuals with pathological conditions, such as non-insulin-dependent diabetes mellitus. However, in human subjects, studies of the regulation of glycogen synthase in vivo are time consuming and tedious. The present study was, therefore, undertaken to establish whether adipocytes isolated from subcutaneous adipose tissue biopsies from normal human subjects could be used to assess the effect of insulin in vitro on glycogen synthase activity. Regulation of glycogen synthase in human adipocytes by glucose 6-phosphate and uridine disphosphate glucose was found to be somewhat different than that reported for the regulation of this enzyme in tissues from other species. The adipocyte was found to be a sensitive model for insulin activation of this enzyme. Glycogen synthase was stimulated twofold by an insulin concentration of as low as 1 ng/ml, while half-maximal activation of enzyme activity occurred at 0.4 +/- 0.1 ng insulin/ml. The present studies indicate that the isolated human subcutaneous adipocyte may serve as a useful model for in vitro investigation of the effects of insulin on glycogen synthase.

Adipose Tissue↗

Dietary fiber.

Studies done on dietary fiber (DF) over the past five years are presented in this Review. The involvement of dietary fiber in the control of plasma glucose and lipid levels is now established. Two dietary fiber sources (soybean and fenugreek) were studied in our laboratory and are discussed herein. These sources were found to be potentially beneficial in the reduction of plasma glucose in non-insulin dependent diabetes mellitus subjects. They are shown to be acceptable by human subjects and are easy to use either in a mixture of milk products and in cooking. The mechanism by which dietary fiber alters the nutrient absorption is also discussed. The effect of DF on gastric emptying, transit time, adsorption and glucose transport may contribute to reducing plasma glucose and lipid levels. DF was found to be effective in controlling blood glucose and lipid levels of pregnant diabetic women. Dietary fiber may also be potentially beneficial in the reduction of exogenous insulin requirements in these subjects. However, increased consumption of DF may cause adverse side effects; the binding capabilities of fiber may affect nutrient availability, particularly that of minerals and prolonged and high DF dosage supplementation must be regarded cautiously. This is particularly true when recommending such a diet for pregnant or lactating women, children or subjects with nutritional disorders. Physiological effects of DF appear to depend heavily on the source and composition of fiber. Using a combination of DF from a variety of sources may reduce the actual mass of fiber required to obtain the desired metabolic effects and will result in a more palatable diet. Previously observed problems, such as excess flatus, diarrhea and mineral malabsorption would also be minimized.

Blood Glucose↗

New sources of dietary fibre.

Two sources of dietary fibre were discussed in this presentation: soybean and fenugreek. Soybean dietary fibre (SDF) was found to be effective in reducing plasma glucose levels in diabetic and fa/fa rats, ob/ob mice and in non-insulin dependent diabetes mellitus (NIDDM) subjects. Supplementation of SDF in bread was more effective in glucose reduction than powder. SDF was also found to be more effective in subjects with fasting blood glucose levels above 7.2 mmol/l. SDF had no effect on insulin levels in rats or NIDDM subjects although the insulin levels in ob/ob mice were lower after 180 d feeding. SDF had no effect on body weight or lipid levels in rats and human subjects. However, in diabetic rats with high levels of blood cholesterol, SDF feeding decreased the cholesterol levels after 45 d SDF administration. Addition of powdered fenugreek to an oral glucose tolerance test significantly reduced the subsequent postprandial blood glucose level in diabetic rats. Inclusion of fenugreek to the meal tolerance test given to NIDDM also decreased the postprandial blood glucose levels. Fenugreek was found to reduce the rate of gastric emptying and to inhibit glucose transport, indicating the blood modulating effect of fenugreek to be due mainly to delayed gastric emptying with direct interference with intestinal glucose absorption. Soybean and fenugreek dietary fibres reveal a potential benefit for the control of glucose metabolism in diabetes with additional advantages resulting from their ease in usage either in a mixture of water or milk products or in cooking.

Animals↗

Short-term regulation of prolactin receptors in the liver, mammary gland and kidney of pregnant and lactating rats infused with ovine prolactin or human growth hormone.

Short-term regulation of prolactin (PRL) receptors was studied in ketamine-anaesthetized 18-day pregnant or 7-day lactating female rats, by infusing them with various doses of oPRL or human growth hormone (hGH) for 0-3 h and measuring the binding of [125I]oPRL of [125I]hGH to the microsomal fractions prepared from the liver, mammary gland and kidneys of animals sacrificed at various states of infusion. Our main findings are: In pregnant rats, only 30% of liver receptors are unoccupied and infusion with 25 micrograms/h for 3 h of either oPRL of hGH decreased both free and total receptors by 22-30% while infusion with 250 micrograms/ml caused an additional decrease only in the free receptors. In the mammary gland and the kidney of pregnant rats, all receptors seem to be unoccupied; infusion with 25 micrograms/ml had none or a slight elevating effect on the number of both free and total receptors in the mammary gland but caused a significant 3-fold increase in the kidney; infusion with 250 micrograms/ml, however, resulted in a slight decrease in the mammary gland and a significant decrease in the kidney in both total and free receptors. In the liver of the lactating rats, there was no significant difference between the number of free and total receptors, but in mammary gland, specific binding to the total receptor was higher than to the free ones indicating partial occupancy; infusion with 25 micrograms/ml caused a significant decrease in free and total liver receptors without a remarkable change in the mammary gland and some decrease (by infusion with hGH only) in the kidney. In all cases, the changes in the specific binding resulted from the increase or decrease in receptor number and not from the change in receptor-hormone affinity. In almost all cases, infusion with oPRL or hGH yielded similar results. Infusion with both hormones did not affect the level of the endogenous rat prolactin. In conclusion, our results indicate the short-term regulation of PRL receptors by exogenous hormones is a complicated process which is affected by the level of the infused hormone, physiological state of the animal and may yield, simultaneously, different or even opposite changes in receptor number in various organs.

Animals↗

Effect of the alpha-glucosidase inhibitor Bay-O-1248 on the metabolic response of nondiabetic and diabetic rats to a high-carbohydrate diet.

The metabolic consequences of the addition of a new alpha-glucosidase inhibitor (BAY-O-1248) to a high carbohydrate diet (67% by calories) in which the carbohydrate comprised equal quantities (50% wt/wt) of wheat starch and sucrose (Diet A) or 100% glucose (Diet B) was studied in diabetic and nondiabetic rats. BAY-O-1248 led to a significant reduction in daily food intake and weight gain in rats fed Diet A but not Diet B. In diabetic rats fed Diet A with BAY-O-1248, daily urinary glucose was significantly diminished (6820 +/- 402 vs 3796 +/- 210 mg), while the postprandial plasma glucose excursions were similar. In nondiabetic rats, the addition of BAY-O-1248 decreased the postprandial plasma glucose level with no change in urine glucose. In summary, addition of an alpha-glucosidase inhibitor to a starch plus sucrose containing diet led to reductions in glycosuria (diabetic rats) and serum glucose levels (normal rats).

1-Deoxynojirimycin↗

Adipocyte glycogen synthase and pyruvate dehydrogenase in obese and type II diabetic subjects.

To determine whether 1) insulin stimulates pyruvate dehydrogenase (PDH) and glycogen synthase (GS) in isolated human adipocytes and 2) adipocytes from subjects with obesity or noninsulin-dependent diabetes mellitus (NIDDM) are resistant to the effects of insulin, PDH and GS were assayed in adipocytes from 11 control, 8 obese, and 9 NIDDM subjects. Basal PDH activities were 123 +/- 20, 129 +/- 21, and 128 +/- 25 pmol pyruvate oxidized/min per 2 X 10(5) adipocytes in these groups. Insulin stimulated PDH activity to a maximum of 223 +/- 38 pmol/min per 2 X 10(5) in adipocytes from control subjects, but did not significantly increase values from obese subjects. Insulin significantly decreased PDH activity in cells from NIDDM subjects (99 +/- 20 pmol/min per 2 X 10(5) cells, P less than 0.05). PDH activity assayed with high magnesium and calcium concentrations was significantly stimulated by insulin in adipocytes from control, but not obese or NIDDM subjects. GS assayed with 1 mM glucose 6-phosphate did not differ significantly among control, obese, or NIDDM subjects (446 +/- 110, 451 +/- 156, and 291 +/- 35 pmol incorporated into glycogen, respectively). Insulin significantly stimulated glycogen synthase in all three groups (827 +/- 179, 764 +/- 177, and 569 +/- 51 pmol incorporated) to a similar extent. Glycogen synthase assayed with 10 mM glucose 6-phosphate was decreased in NIDDM (1,335 +/- 131 pmol incorporated) compared with obese or control subjects (2,512 +/- 451 and 2,239 +/- 230 pmol incorporated, respectively, P less than 0.01).

Adipose Tissue↗

Pilot study of the efficacy of spent grain dietary fiber in the treatment of constipation.

Spent grain is the crude fiber obtained by decanting the fermented distillate of barley. The spent grain was processed to yield dietary fiber composed of: cellulose and hemicellulose 65.6% (by weight), lignin 5.2%, pectin 2.2%, protein 10.9% and lipid 8.0%. Biscuits and scones were prepared by 25% substitution of wheat flour by fiber, yielding 7 to 8 g fiber per biscuit/scone. Nineteen ambulatory patients with chronic, laxative-dependent constipation were treated in a pilot study for 4 weeks with 20 to 25 g fiber daily. Fifteen patients (79%) showed improvement in some or all of five factors, while four patients were largely unresponsive to fiber. Specific symptoms improved as follows: bowel movement frequency in 15 patients (79%), flatulence in 12 (63%), abdominal pain in 10 (53%), stool consistency in 8 (42%) and laxative dependence in 14 (74%). A 4-week post-treatment follow-up showed a return to prefiber status in 11 of 13 improved subjects. This preliminary study suggests a role for spent grain fiber in the treatment of constipated patients, and a comparative study with placebo and wheat fiber is now warranted.

Adult↗

The fate of [125I]-labeled human leukocyte-derived alpha interferon in the rat.

In order to follow the catabolic fate of interferon in the body, [125I]-labeled human alpha interferon was infused into rats. Interferon activity and TCA-precipitable radioactivity in the blood reached a steady state after 60 min of infusion, while TCA-soluble radioactivity continued to increase during the entire infusion period. A massive accumulation of both active interferon and degradation products of interferon were found in the kidney at the end of the infusion. Most of the interferon activity was found in the mitochondrial-lysosomal fraction, while most of the interferon degradation products were found in the supernatant fraction. Ligation of the kidney's blood vessels resulted in a large increase of interferon activity in the blood. Only a small increase was found in other organs, with no increase at all in radioactive degradation products. Our results suggest the kidney to be the main site of interferon catabolism. Low molecular weight degradation products are excreted from the kidney into the blood and are at least partially secreted in the urine and also taken up by other organs.

Animals↗