Biomedical subjects

M M Zdanowicz

Publications and source records attributed to M M Zdanowicz.

12 recordsLinked to original sources

PubMed1998

The role of dietary zinc in modifying the onset and severity of spontaneous diabetes in the BB Wistar rat.

The goal of this study was to determine whether zinc supplementation in the diet of diabetes-prone BB Wistar rats will delay or prevent the onset of overt diabetes. Male Wistar BB rats were fed diets containing either 1000 ppm (HZ), 50 ppm (NZ), or 1 ppm zinc (LZ) starting at 30 days of age. Non-diabetes-prone rats were fed NZ and designated as controls (NORM). Beginning at 60 days, the rats were checked for glycosuria and, if positive, were given an i.p. glucose tolerance test (IPGTT). All remaining animals underwent an IPGTT at 100 days and were sacrificed. At 90 days of age HZ rats had a lower incidence of diabetes (19%) than NZ (53%) or LZ (44%) animals (P < 0.015). By age 100 days, for the HZ group, there was a 60% reduction in the number of expected overt diabetic rats. HZ animals also had higher concentrations of both pancreatic and serum insulin and exhibited lower serum glucose and triglycerides. Immunohistochemistry of HZ rats was clearly different from NZ rats and showed evidence of nearly normal pancreatic endocrine activity. Data indicate that dietary treatment of diabetes-prone BB Wistar rats with zinc appears to be an effective approach for delaying or preventing the onset of diabetes in genetically predisposed rodents. This finding may suggest further experimental studies regarding dietary means for preservation of pancreatic function.

Adolescent↗

PubMed1998

Insulin-like growth factor-I and high protein diet decrease calpain-mediated proteolysis in murine muscular dystrophy.

In muscular dystrophy (MD) the imbalance between muscle protein synthesis and degradation may be an important factor leading to muscle wasting. The three major pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet (HPD) have been shown to reduce proteolysis in skeletal muscle. We examined the effect of 6 weeks of recombinant human IGF-I (rhIGF-I) alone or in combination with HPD treatment on the proteolytic pathways in skeletal muscle of 129 ReJ dystrophic (dy) mice. (A group of normal (Norm) nondystrophic (129 J) mice were included as controls). Untreated dy mice exhibited increased net proteolysis (P < 0.05), elevated net calpain activity (P < 0.01), and increased ubiquitin levels when compared to control mice (P < 0.05). Our evidence suggests that HPD and rhIGF-I decrease proteolysis in the 129 ReJ dy mouse. This effect appears attributable, at least in part, to reduced calpain-mediated myofibrillar breakdown (P < 0.05) due to decreased calpain autolysis or increased calpastatin levels. In contrast to calpain, cathepsin B activity was increased in HPD and rhIGF-I + HPD-treated dy muscle (P < 0.05) and unaltered in the rhIGF-I treated animals. Levels of free and protein-conjugated ubiquitin were also increased in rhIGF-I, and rhIGF-I + HPD treated dyanimals (P < 0.05). The amelioration of muscle wasting in the 129 ReJ dy model by HPD and/or rhIGF-I may have potential implications in the treatment of human MD.

Animals↗

PubMed1997

Expression of myogenic regulatory factors in normal and dystrophic mice: effects of IGF-1 treatment.

Myogenic regulatory factors (MRFs) promote differentiation of muscle cells from fibroblasts and are induced by insulin-like growth factor I (IGF-1). Prior studies have shown synthesis of new muscle protein and improved muscle morphology when mature dy mice with muscular dystrophy are treated with IGF-1. We investigated whether these salutary effects of IGF-1 might be attributable to stimulation of MRFs. Male dy (129ReJ) mice and controls (129J) were assigned to IGF-1 treatment (10 micrograms twice daily) or non-treatment at about 5 weeks of life and sacrificed 6 weeks later. RNA was extracted from skeletal muscles, reverse transcribed, and amplified by polymerase chain reaction (PCR) using primers specific for each MRF. Competitive PCR was performed to quantify MyoD expression in response to IGF-1 treatment. Transcripts for myf-5, MRF4, and myogenin were detected in both control and dy mouse muscles; no apparent differences were observed between treatment groups. Quantitative analysis of transcripts for MyoD indicated no significant basal differences between control and dy mice. There was, however, significantly higher MyoD expression in the dy group, and a trend toward significance in the control group, following IGF-1 treatment. These data suggest that IGF-1 exerts its in vivo effects in postembryonal muscle by stimulating MRFs.

Animals↗

PubMed1997

Metabolic and structural effects of insulin-like growth factor-I and high-protein diet on dystrophic hamster skeletal muscle.

In muscular dystrophy (MD) there is an imbalance between muscle protein synthesis and protein degradation, which results in a net muscle catabolism, along with muscle wasting and weakness. Using a dystrophic hamster model (BIO 53.58), we examined the chronic (8 weeks) effects of two factors that may enhance muscle protein synthesis and inhibit protein degradation, namely, insulin-like growth factor-I (rhIGF-I) and high-protein diet (HPD). Protein synthesis was determined by measuring the incorporation of 14C phenylalanine into perfused leg muscle, while protein degradation was calculated from the release of tyrosine from the same perfused muscle. Urinary 3-methylhistidine excretion was used as an indicator of myofibrillar degradation. Treatment of dystrophic hamsters with rhIGF-I, HPD, or a combination of the two for 8 weeks resulted in significant decreases in total and myofibrillar degradation when compared with untreated dystrophic animals (P < 0.05) but had minimal effects on protein synthesis. Significant morphologic improvements (P < 0.05), including a normalization and greater uniformity of muscle fibers, were also seen in rhIGF-I- and rhIGF-I + HPD-treated animals. rhIGF-I and HPD were effective in reducing the excessive proteolysis seen in dystrophic muscle, and this reduced proteolysis resulted in improvement of muscle morphology.

Animals↗

PubMed1995

High protein diet has beneficial effects in murine muscular dystrophy.

In normal muscle there is a delicate balance between muscle protein synthesis and protein degradation. It is believed that this balance is disturbed in muscular dystrophy (MD) by decreased muscle protein synthesis and/or increased muscle protein degradation, resulting in net catabolism. In an attempt to reduce or reverse this catabolism, a high protein diet (HPD, 50% protein) was fed to dystrophic mice (129/ReJ dy) for 4 wk. The effects on muscle biochemistry, muscle function and muscle morphology were compared with those in dystrophic mice fed a normal diet (NPD, 20% protein) and in nondystrophic mice (NORM) also fed the 20% protein diet. Compared with NORM mice, NPD mice demonstrated greater rates of muscle protein synthesis (P < 0.05) as measured by the incorporation of labeled phenylalanine into muscle, greater protein degradation (P < 0.01) as measured by urinary 3-methylhistidine excretion, and lower muscle protein concentration (P < 0.01). When dystrophic mice were fed HPD for 4 wk, protein degradation was lower (P < 0.01) and muscle protein concentration greater (P < 0.01) than in NPD mice. These biochemical improvements were accompanied by greater morphological uniformity of muscle fibers, higher volume density of muscle fibers per unit area of muscle (P < 0.01), and lower shape factor (P < 0.01). Functionally, HPD led to improved muscle endurance (P < 0.01) and increased hind-limb utilization (P 0.01). We conclude that in murine dystrophy, HPD decreases net muscle catabolism, principally by decreasing muscle protein degradation, resulting in improvement in muscle morphology, strength and function.

Animals↗

PubMed1995

Effect of insulin-like growth factor I in murine muscular dystrophy.

In muscular dystrophy there is an imbalance between muscle protein synthesis and protein degradation, resulting in net muscle catabolism and progressive muscle weakness and wasting. Both insulin and insulin-like growth factor I (IGF-I) are known to have an anabolic effect on skeletal muscle, which is believed to be enhanced in the presence of elevated concentrations of amino acids. We examined the effects of 4-week administration of recombinant human IGF-I (rhIGF-I), both alone and supplemented with a high protein diet (HPD), on muscle metabolism, morphology, and function in the 129 ReJ dystrophic mouse. rhIGF-I significantly reduced muscle protein degradation (P < 0.001), increased muscle protein content (P < 0.05), decreased fiber area variability (P < 0.01), and increased hind limb utilization (P < 0.01). Supplementation of rhIGF-I therapy with a HPD resulted in a significant increase in muscle protein synthesis (P < 0.05) in addition to a further increase in the above parameters. We conclude that rhIGF-I causes an improvement in muscle metabolism, morphology, and function in dystrophic mice, and this effect is further enhanced by the presence of a HPD.

Animals↗

PubMed1993

Modification of insulin resistance by diazoxide in obese Zucker rats.

Hyperinsulinism, insulin resistance, and decreased number of insulin receptors are characteristic of obesity in both humans and experimental animals. To assess the role of insulin in developing obesity, diazoxide (DZ), an inhibitor of glucose-stimulated insulin secretion, was administered for 8 weeks to 7-week-old female Zucker rats in two concentrations, 50 mg/kg.day (LD-DZ), and 100 mg/kg.day (HD-DZ). The obese and lean rats were divided into three subgroups: diazoxide (DZ), pair-fed (PF), and control (C) groups (n = 6 rats/subgroup-genotype). Diazoxide-treated obese and lean animals showed significantly lower postabsorptive plasma insulin concentrations (P < 0.005) than their respective obese and lean PF and C subgroups. HD-DZ obese rats consumed more calories (P < 0.001), yet gained less weight (P < 0.05) than PF and C rats. The plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests in HD-DZ obese rats were significantly lower than those in PF and C rats (P < 0.01) despite a decrease in their plasma insulin concentrations (P < 0.01), whereas HD-DZ lean rats displayed a diabetic response (P < 0.01). The adipocyte-specific insulin receptor binding was dose-dependently increased in both lean and obese DZ animals (P < 0.01). DZ had a dual effect on insulin metabolism; it decreased insulin secretion and increased insulin receptor binding. This dual effect was associated with improved glucose tolerance and a decrease in weight gain in obese rats.

Adipose Tissue↗

PubMed1991

Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea.

Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1 +/- 0.62 versus 1.5 +/- 0.48 microliters/[min x cm], p less than 0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p less than 0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5 +/- 0.36 and 2.4 +/- 0.38, respectively, versus 0.87 +/- 0.40 microliters/[min x cm], p less than 0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r = -0.653, p less than 0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will improve water absorption and that rice syrup solids in combination with protein hydrolysates may, in addition, promote better sodium and potassium uptake.

Administration, Oral↗

PubMed1991

Magnesium protection against anthracycline toxicity in vitro.

The clinical usefulness of the antitumour agents daunomycin (DAU) and adriamycin (ADR) is limited by their secondary cardiotoxicity. The anthracycline compounds have a number of detrimental effects on the biochemical and morphological integrity of the cardiac cell which may be related to the accumulation of cellular calcium. Using a model of spontaneously beating, cultured neonatal rat cardiomyocytes, we examined the cardioprotective role of magnesium during 2 hours of exposure to 10, 25 or 50 micrograms/ml DAU. A significant preservation of myocyte membrane integrity and cellular morphology was observed with the addition of equimolar magnesium. Magnesium opposes the actions of calcium in a number of tissues and it may be this calcium antagonist action that makes magnesium effective in DAU toxicity.

Animals↗

PubMed1990

Alanine stimulation of water and sodium absorption in a model of secretory diarrhea.

We investigated the effectiveness of L-alanine (Ala) addition to oral hydration solutions (OHSs) during secretory conditions induced by ileal instillation of 10 mM theophylline in anesthetized rats using a perfusion procedure, and monitoring water and sodium transport. Ala was added to two hypotonic OHSs in which the sodium:glucose ratio was 2:1, and compared with the OHS recommended by the World Health Organization (WHO), which has a sodium:glucose ratio of 0.81:1. Theophylline had the expected secretory effect on water and sodium absorption in the WHO-recommended OHS, and on sodium transport in a formula containing 60 mM sodium and 30 mM glucose. However, an OHS with 90 mM sodium and 45 mM glucose canceled the secretory effect of theophylline and yielded a greater rate of net water absorption than the WHO formula. Addition to this solution of either 15 or 30 mM Ala enhanced water and sodium absorption of both control and theophylline-treated rats. In the hypotonic OHS with 60 mM sodium and 30 mM glucose, Ala had little effect on both sodium and water transport. Therefore, the data support the view that Ala added to solutions with 90 mM sodium, containing sufficient glucose to maintain a sodium:glucose ratio of not less than 2:1, is most effective at compensating fluid and sodium losses under secretory conditions. Ala presumably exerts its sodium-sparing effect because of its cotransport with sodium and the consequent water influx into the intestinal cells.

Absorption↗

PubMed1988

Oral hydration solutions in experimental osmotic diarrhea: enhancement by alanine and other amino acids and oligopeptides.

Improvement of sodium absorption during the administration of oral hydration solutions (OHS) could increase the efficacy of formulations used in the treatment of infantile diarrhea. To test this hypothesis, selected protein breakdown products were evaluated as absorption enhancers in OHS of different osmolalities and Na-to-glucose ratios in an animal model of osmotic diarrhea induced by cathartics. A very significant increase in water and Na absorption occurred in rats with diarrhea when they were perfused with a 90-mmol/L-Na, 111-mmol/L-glucose OHS containing 30 mmol/L of L-alanine (Ala). The same effect on Na retention was observed with a protein hydrolysate (PrH) in rats with diarrhea. Glycine was not effective. Other experimental OHS were ineffective in rats with diarrhea. The data indicate that in this animal model of chronic diarrhea Na transport enhancers, such as Ala and a PrH, are most efficacious in the presence of higher Na concentration.

Absorption↗

PubMedDate not supplied

Protective role of magnesium in catecholamine-induced arrhythmia and toxicity in vitro.

The present study examined the arrhythmogenic and toxic liability of isoprenaline, noradrenaline and adrenaline using a model of spontaneously beating, cultured rat cardiomyocytes. The cardioprotective role of magnesium (Mg) was also evaluated. Following two hours of exposure to 0.1-2.7 mM doses of isoprenaline, noradrenaline or adrenaline, there were dose-dependent increases in the incidence of arrhythmia and decreases in beating activity. Myocyte LDH release increased 64-189% while total myocyte K+ and Mg2+ decreased 13-60% at high catecholamine doses. Levels of the secondary messengers IP3 and cAMP were also increased. Equimolar Mg (0.9 mM) significantly reduced the incidence of catecholamine arrhythmia while preserving beating activity, membrane integrity and electrolyte levels. Mg proved to be in vitro a potent antiarrhythmic and cardioprotective agent which is likely to exert its beneficial effects via antagonism of calcium.

Animals↗