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Biomedical subjects

J T Bond

Publications and source records attributed to J T Bond.

At least 19 recordsLinked to original sources

The effect of weight cycling on blood lipids and blood pressure in the Multiple Risk Factor Intervention Trial Special Intervention Group.

OBJECTIVE: To assess whether weight cycling has adverse effects on blood lipids or blood pressure. DESIGN: Cohort study, six years of follow-up, comparing net change in blood lipids and blood pressure among weight cyclers and non-cyclers. SUBJECTS: Men (n = 4353), age 35-57 y, at high risk for heart disease because of smoking, high blood pressure, and elevated cholesterol concentration in the Multiple Risk Factor Intervention Trial (MRFIT)--a 22-site, multi-center collaborative primary prevention trial conducted in the US, 1973-1983. MEASUREMENTS: A weight cycle was defined as loss and regain of at least 5% of mean weight. Outcome measures were changes from baseline to year six in total serum cholesterol, high density lipoprotein cholesterol (HDL), the ratio of total cholesterol to HDL, and diastolic blood pressure. ANALYSIS: Analysis of covariance models were developed, with number of weight cycles as the predictor variable. The hypothesis was that men who weight cycled would experience less improvement in blood lipids and blood pressure than those who did not cycle. Adjustments were made for net weight change and other factors affecting each outcome. RESULTS: Men who weight cycled did not have the predicted smaller improvements in total cholesterol, HDL, the ratio of total cholesterol to HDL, or diastolic blood pressure, compared with noncyclers. CONCLUSION: An adverse effect of weight cycling on blood pressure or blood lipids was not found. The excess mortality previously reported among weight cyclers in this population can probably not be attributed to effects on these CVD risk factors.

Adult↗

N-acetylation of aromatic amines: genetic polymorphism in inbred rat strains.

The inheritance of rat liver N-acetyltransferase polymorphism was investigated with reciprocal genetic crosses between slow (NSD/N) and rapid (Peth/N) acetylator strains. Rat liver N-acetyltransferase activity was determined using a spectrophotometric assay which measured the amount of arylamine substrate present after incubation with N-acetyltransferase in vitro. Male N-acetyltransferase activities assayed in liver preparations using p-aminobenzoic acid and p-toluidine as substrates indicate bimodality of the parental strains and unimodality of the F-1 generation; limited data suggest trimodality (not significantly different from a 1:2:1 ratio) of the F-2 generation. Reciprocal crosses of WKY/N, another slow acetylator strain, and the Peth/N strain gave results similar to those of the NSD/N x Peth/N cross. Female N-acetyltransferase activities in all strains studied were lower than male N-acetyltransferase activities, but were similarly distributed in the parental and F-1 generations. The male/female N-acetyltransferase activity ratio was substrate- and genotype-dependent. Results show that regulation of the variation of rat liver N-acetyltransferase activity is consistent with autosomal Mendelian inheritance of two major alleles at a single gene locus.

4-Aminobenzoic Acid↗

Hyperglucagonemia following cisplatin treatment.

These studies were initiated to determine (1) if cisplatin (cis-DDP)-induced hyperglucagonemia is related to decreased hormone degradation, (2) the relationship between impaired kidney function associated with cis-DDP nephrotoxicity and hyperglucagonemia, and (3) the contribution of cis-DDP-induced hyperglucagonemia to disturbances in glucose metabolism in male F-344 rats. Administration of 5 or 7.5, but not 2.5, mg/kg cis-DDP iv increased fasting plasma immunoreactive glucagon (IRG) concentrations. Hyperglucagonemia following cis-DDP treatment was characterized by an increase in the biologically active or true pancreatic form of IRG as well as an increase in an extrapancreatic component. cis-DDP treatment (5 mg/kg) resulted in a prolonged half-life and a reduced rate of plasma disappearance of exogenous glucagon. Reducing cis-DDP nephrotoxicity, via mannitol pretreatment, resulted in a significant reduction in total, true pancreatic, and extrapancreatic plasma IRG. Other nephrotoxicants, such as glycerol or gentamicin, also resulted in hyperglucagonemia, indicating that the effects of cis-DDP on glucagon metabolism are also characteristic of other nephrotoxicants and, therefore, may be secondary to kidney toxicity. Despite marked hyperglucagonemia following cis-DDP treatment, neither severe fasting hyperglycemia nor increased hepatic and renal gluconeogenic enzyme activity was apparent in treated animals. This apparent discrepancy cannot be attributed to glucagon resistance at the target tissue level since cis-DDP-treated animals responded appropriately to exogenous glucagon. These results indicate that hyperglucagonemia following cis-DDP treatment (1) may be related to decreased glucagon degradation associated with impaired renal function and (2) does not markedly disrupt glucose homeostasis.

Animals↗

The effects of cisplatin and other divalent platinum compounds on glucose metabolism and pancreatic endocrine function.

Three divalent platinum compounds, cis-dichlorodiammineplatinum (cis-DDP), trans-dichlorodiammineplatinum (trans-DDP), and ammonium tetrachloroplatinate, were examined for their effects on glucose metabolism in male F-344 rats. Rats were treated with a single iv dose of cis-DDP (0, 2.5, or 5 mg/kg), trans-DDP (0, 5, 7.5, or 15 mg/kg) or tetrachloroplatinate (0, 6, or 18 mg/kg). Glucose tolerance was evaluated 2, 4, 7, and 14 days following platinum treatment by serially measuring plasma glucose before and following an ip glucose load. Administration of 5 mg/kg cis-DDP impaired glucose tolerance on Days 2 and 4, but not on Days 7 and 14. Plasma immunoreactive glucagon (IRG) was elevated at all times following cis-DDP treatment and thus was not correlated with the transient impairment in glucose tolerance. Plasma immunoreactive insulin (IRI) response to a glucose load was deficient relative to the degree of hyperglycemia in cis-DDP-treated (5 mg/kg) animals on Days 2 and 4. However, neither histopathological damage of the pancreas nor pancreatic stores of IRI were affected by cis-DDP treatment. In contrast to cis-DDP, equimolar or greater than equimolar doses of trans-DDP or tetrachloroplatinate did not significantly affect glucose tolerance at any time examined. These results indicate that cis-DDP-mediated glucose intolerance is unique to the geometry of the complex and is related to properties other than the presence of a divalent platinum atom. Furthermore, glucose intolerance following cis-DDP treatment appears to be related to a relative deficiency in insulin secretion.

Animals↗

Paraquat concentration and renal function in mice fed purified and cereal-based diets.

Paraquat, a broad spectrum herbicide, has differential effects in mice depending upon whether a purified or a cereal-based diet is fed. Male ICR mice were fed either a cereal-based closed-formula diet or a purified diet for 7-14 days. After intraperitoneal injection, radiolabeled paraquat was measured in blood, lung, kidney, liver, heart, and urine over a 48-hr period. Accumulation of organic ions was measured in renal tissue slices at 3 hrs after injection of paraquat. Hematocrit, plasma urea nitrogen, and urine volume were measured from 8 to 72 hr after administration of paraquat. From 3 to 12 hr after injection, concentrations of paraquat in plasma, kidney, and liver were greater in mice fed a purified diet than in mice fed a closed-formula diet. Concentration of paraquat in the lung and urine did not differ between dietary groups over a 48-hr period. Three hours after paraquat intake renal tissue organic ion accumulation was higher in mice fed a purified diet. Within 72 hr after paraquat administration plasma urea nitrogen concentration and hematocrit were greater in mice fed a purified diet. Higher tissue concentrations of paraquat in mice fed a purified diet could explain dietary differences previously observed for LD50 and survival time after paraquat injection. While changes in plasma urea and paraquat concentration in the kidney were observed, the effect of a diet-paraquat interaction on renal function was not conclusive, since there was no difference in excretion of paraquat between the dietary groups.

Animals↗

Zinc deficiency and behavior: a development perspective.

Zinc deficiency was induced in 35 and 300 day-old male Holtzman rats. Group ZDA was fed ad lib a diet deficient in zinc (1 ppm), ZSP controls were pair-fed a diet supplemented with zinc (50 ppm) and ZSA controls were fed ad lib a diet supplemented with zinc (50 ppm). Physical status and six open-field behaviors were evaluated. Food intake, body weight and plasma zinc concentrations were significantly reduced in both age groups. Expanded use of the open-field revealed significantly lower latencies to explore the novel environment and significantly lower ambulation scores in the young and older zinc deficient rats. Older rats spent significantly less time grooming than their controls. Rearing was significantly less in young zinc deficient rats and "kangaroo-like" posture was evident. Young rats made deficient during critical periods of growth and development, were at greater risk for most parameters tested, compared to the older deficient rats. These rats do demonstrate, however, that feeding low-zinc diets to older, fully developed animals results in significant physical and behavioral impairment.

Age Factors↗

Glucose intolerance following cis-platinum treatment in rats.

cis-Dichlorodiammineplatinum (cis-Pt) is a heavy metal complex used in cancer chemotherapy. Since this drug has been shown to induce hyperglycemia in rats, these studies were initiated to elucidate the effects of cis-Pt on carbohydrate tolerance and insulin and glucagon secretion. Two days following i.v. cis-Pt (2.5 or 7.5 mg/kg, 5 ml/kg) or vehicle administration to male F-344 rats, plasma glucose, immunoreactive insulin (IRI) and glucagon (IRG) concentrations were determined in the basal state and serially following a glucose load (2 g/kg, i.p.). Since cis-Pt induces a dose-related anorexia, a pair-fed control group was also studied. Administration of 7.5 mg/kg cis-Pt was associated with plasma glucose concentrations 2.5-5 times greater than ad-libitum and pair-fed controls at every time point during the 2-h glucose tolerance test. Although basal plasma IRI concentrations of the 7.5-mg/kg group were comparable to ad-libitum fed controls, they were significantly greater than those of pair-fed partners. Furthermore, the appropriate IRI response to a glucose stimulus observed in both controls and the 2.5-mg/kg group was absent in the 7.5-mg/kg group. Basal plasma IRG concentrations of the 7.5-mg/kg group were approximately 3-4 times greater than ad-libitum and pair-fed controls and were not suppressed following a glucose load. These results suggest that cis-Pt induces marked glucose intolerance in association with an impaired IRI response and abnormal glucagon response to a glucose stimulus.

Animals↗

Lack of effect of a purified diet on carbon tetrachloride or oxygen toxicity.

The study was designed to examine the effect of feeding a purified versus a cereal-based closed formula (control) diet on toxicity to carbon tetrachloride or oxygen. Twenty-eight-day-old male ICR mie were fed a purified or cereal-based closed formula diet for 14 or 84 days. After treatment with carbon tetrachloride or exposure to a 100% oxygen atmosphere, survival time and percentage survival were the same for mice fed either diet. In both dietary groups, carbon tetrachloride injection caused a similar decrease in hepatic nonprotein sulfhydryl compounds and glucose-6-phosphatase activity. It was concluded that, unlike previous findings with the herbicide paraquat, toxicity to carbon tetrachloride or oxygen is not increased by feeding a purified diet compared to a closed formula diet. The results provided further evidence to suggest that a free radical-lipid peroxidation process may not be the primary mechanism of the toxic effects of paraquat.

Animals↗

Zinc deficiency and the kidney. I. Effect on renal carbonic anhydrase activity.

Tissue zinc concentration and the activity of the zinc metalloenzyme, carbonic anhydrase, were quantified in whole blood and kidneys of weanling male Sprague-Dawley rats with diet-induced zinc deficiency. Zinc-deficient rats were fed ad libitum a commercially prepared diet containing less than 1 ppm zinc. Zinc-supplemented rats were ad libitum or pair-fed a control diet containing 60 ppm zinc. All animals were fed their respective diets for 3-6 weeks. Body and kidney growth were severely compromised after 3 and 6 weeks of feeding the zinc-deficient diet. Plasma and kidney zinc concentrations were significantly decreased in zinc-deficient animals after 6 weeks. While whole blood carbonic anhydrase activity of zinc-deficient rats was significantly greater than zinc-supplemented animals after 6 weeks, no differences in renal carbonic anhydrase activity were found between zinc-deficient animals and pair-fed controls. Results reported in this study suggest that zinc deficiency imposed at weaning in rats may be a contributing factor to retarded kidney maturation and alterations in blood carbonic anhydrase activity.

Animals↗

Alteration of toxicity to paraquat in mice fed a purified or cereal-based diet.

Toxicity to several compounds is affected by dietary changes that by themselves do not result in nutrient deficiency or toxicity. The herbicide paraquat was tested to determine whether feeding a cereal-based closed formula diet or a purified diet would affect the sensitivity of mice to paraquat. After an intraperitoneal injection of paraquat, 28-day-old male ICR mice, which had been fed a purified diet for periods of 3 to 84 days, had shorter survival times and lower 7-day percent survivals than mice fed a cereal-base closed formula diet. The median lethal dose of paraquat was significantly lower in mice fed the purified diet rather than the closed formula diet. Median effective time to death was also significantly shorter for male ICR mice fed the purified diet rather than the closed formula diet. Female ICR mice and male B6C3F1 mice fed the purified diet for 7 days were more susceptible to paraquat toxicity than similar mice fed the closed formula diet. Male C57BL/6J mice were more sensitive to the effects of paraquat regardless of the type of diet. Modifying the content of lipid, vitamin E, or selenium, or adding butylated hydroxytoluene to the purified diet did not prevent a decrease in 7-day percent survival and survival time compared to male ICR mice fed a closed formula diet. Male ICR mice fed the purified diet with egg-white protein had significantly longer survival times compared to mice fed the purified diet with casein. It is concluded that strictly defined diets must be used in the study of paraquat toxicity to control for any paraquat-diet interactions.

Animals↗

Zinc deficiency and the kidney. II. Response of zinc-deficient rats to three diuretic drugs.

Carbonic anhydrase is a zinc metalloenzyme whose activity may be affected by zinc deficiency. This investigation was designed to evaluate the effect of zinc deficiency on the response to three diuretic drugs which vary in their capacity to inhibit carbonic anhydrase: acetazolamide, furosemide and hydrochlorothiazide. The response of the zinc-deficient rats was compared to that of pair-fed and ad libitum zinc-supplemented controls. The pattern of electrolyte excretion by zinc-deficient rats in response to the three diuretics was qualitatively similar to that of the pair-fed and zinc-supplemented rats. When corrected for differences in body weight between the three groups, the natriuretic response to the diuretics in zinc-deficient rats was greater than that of either the pair-fed or zinc-supplemented controls. Although administration of the diuretics increased potassium excretion in all groups, the response of the zinc-deficient rats was attenuated. These differences in the response of zinc-deficient rats to diuretics did not appear to be related to the capacity of these drugs to inhibit carbonic anhydrase.

Acetazolamide↗

Bone mineral analysis of the rat femur by direct photon absorptiometry.

This report describes a method using direct photon absorptiometry (DPA) for determination in vivo of the bone mineral content to bone width ratio (BMC/W) in the rat femur. A significant correlation was noted between measurements by DPA and whole femur dry weight and ash weight. Measurements were reproducible within repeated determinations of both the same and successive days. Soft tissue, rotation of the femur, or slight differences in the longitudinal positioning of the femur did not significantly affect usefulness of the measurements. A significant positive correlation was seen between body weight and the femur BMC/W, indicating that the method accurately reflected expected physiological changes in bone mineral. The method is suitable for the rapid, simple, accurate, and reproducible measurement of bone mineral in the anesthetized rat and is applicable to serial measurements.

Animals↗

The effects of maternal protein deprivation on renal development and function in neonatal rats.

This study was undertaken to investigate the effects of pre- and/or postnatal maternal protein deprivation (PD) on renal functional development in the offspring. Pregnant rats were fed either a control (24% protein) or low (8 or 10%) protein diet during gestation and lactation. Progeny of these dams were cross-fostered at birth, yielding four experimental groups: pups born of control dams and nursed by PD or control dams and pups born of PD dams and nursed by control or PD dams. While the effects of prenatal PD on body and kidney growth were negligible, PD during the nursing period appeared to have a more profound effect on body and kidney weight. Renal transport functions, quantified in vitro, were differentially affected by these dietary manipulations. Renal transport capacity for organic acids and bases was depressed in pups nursed by PD dams. Maturation of the renal organic acid transport system was also delayed in these pups. alpha-Aminoisobutyric acid accumulation by renal cortical slices was enhanced only in 10-day old rats stressed by pre- and postnatal maternal PD. Renal gluconeogenic and ammoniagenic capacity was not impaired by these dietary manipulations. No differences in protein or water content of renal cortical slices were observed.

Aminoisobutyric Acids↗