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Biomedical subjects

M J Fettman

Publications and source records attributed to M J Fettman.

At least 37 records · Page 2Linked to original sources

Effects of dietary protein conditioning on gentamicin pharmacokinetics in dogs.

Eighteen, six-month-old male Beagles with normal renal function were randomly divided into three groups of 6. Each group was fed a diet that was similar except for protein content (high = 26%, medium = 13% and low = 9%, all on an as fed basis) throughout the experimental period. After a 21 day dietary protein conditioning period (including a terminal 2 day testing period), gentamicin was administered at a dosage of 10 mg/kg q. 8 h for 8 days. The first dose on days 1 and 7 was administered i.v. and all others were given i.m. Pharmacokinetic parameters were determined using blood samples collected over an 8 h period following the i.v. dose on day 1. The elimination rate constant was calculated on days 1 and 7. The data best fit a two-compartment open model for all dogs on day 1. The volume of distribution was higher and the clearance greater in the high protein group compared to the other two groups. No difference was found in the rate of elimination between days 1 and 7 for the high protein group; however, in the medium and low protein groups the rate of elimination decreased over the 7 days of treatment. Therefore, high dietary protein prior to and during gentamicin administration induced faster gentamicin clearance and a larger volume of distribution and preserved the ability to eliminate gentamicin in dogs with normal renal function.

Animals↗

Effects of dietary protein conditioning on gentamicin-induced nephrotoxicosis in healthy male dogs.

Eighteen 6-month-old male Beagles with normal renal function were allotted at random to 3 groups of 6 dogs each. For 21 days, each group was fed a diet that was similar except for protein content (high protein, 27.3%; medium protein, 13.7%; and low protein, 9.4%). After the conditioning period, gentamicin was administered at a dosage of 10 mg/kg of body weight, IM, every 8 hours for 8 days, and the respective diet was continued. Clearance of endogenous creatinine, 24-hour urinary excretion of protein and enzymes (gamma-glutamyltransferase, and N-acetyl-beta-D-glucosaminidase, and fractional clearance of sodium and potassium (%) were determined before and after dietary protein conditioning and on days 2, 4, 6, and 8 of gentamicin administration. Additionally, trough serum gentamicin concentration was determined on days 2, 4, 6, and 8 of gentamicin administration. At the end of the study, all dogs were euthanatized; renal histologic features were graded, using a continuous ranking scale, and renal cortical gentamicin concentrations were measured. Data were ranked and analyzed, using a nonparametric equivalent of a two-way ANOVA; P < 0.05 was considered significant. After the dietary conditioning period (prior to gentamicin), dogs fed the high-protein diet had higher endogenous creatinine clearance and urinary excretion of protein, compared with dogs fed the low-protein diet. Differences existed among groups after 8 days of gentamicin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

Energy expenditure in dogs with lymphoma fed two specialized diets.

BACKGROUND: Cancer-caused cachexia has been reported to be caused in part by an increase in energy expenditure, and diets with nutrient profiles containing 30-50% nonprotein calories as fat instead of carbohydrate may exacerbate this state of inefficient energy utilization. METHODS: Indirect calorimetry was performed on 22 dogs with high-grade lymphoblastic lymphoma that were randomized into a blind study and fed isocaloric amounts of a high-fat diet (Diet A) or a high-carbohydrate diet (Diet B) before and after remission was attained with up to five doses of doxorubicin chemotherapy (30 mg/m2 intravenously). Indirect calorimetry was also performed on 30 normal dogs for comparison. RESULTS: During the initial evaluation period, the resting energy expenditure (REE/kg0.75, P < 0.05) and respiratory quotient (RQ, P < 0.05) were significantly lower than in the controls. Six weeks after the start of the study, the REE/kg0.75 and oxygen consumption (VO2/kg0.75) were significantly (P < 0.05) lower in both groups of dogs with lymphoma compared with the controls. The RQ determined 6 weeks after the start of the study for the dogs fed Diet A was significantly (P < 0.05) lower compared with that in the controls evaluated at the same time. When the two groups of dogs with lymphoma were compared with each other, there was no significant difference in any of the outcomes. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group fed Diet A after the third evaluation period compared with the second evaluation. The REE/kg0.75 and VO2/kg0.75 values were significantly lower (P < 0.05) in the group given Diet B at the fourth evaluation period compared with the fifth. CONCLUSIONS: These data suggest that energy expenditure of dogs with lymphoma decreases transiently in response to chemotherapy and remission, but these values are less than those determined in normal dogs and not altered significantly by diet.

Animals↗

Repeatability of energy expenditure measurements in clinically normal dogs by use of indirect calorimetry.

Energy expenditure (EE) was determined, using an open-flow indirect calorimetry system in a group of 20 clinically normal, apparently resting, client-owned dogs. Five evaluations were performed over an 8-hour period to determine reliability of the method. The intraclass correlation coefficient was calculated as the ratio of within- and between-subject variances, using repeated-measures ANOVA. When only the middle 3 evaluations were included, the intraclass correlation coefficient was 0.87, indicating good reliability. The first evaluation was higher than the subsequent 4 evaluations for rate of O2 consumption (Vo2/kg and Vo2/kg0.75; (P < or = 0.01), and EE/kg and EE/kg0.75 (P < or = 0.005). The respiratory quotients at the first (P = 0.004) and second (P = 0.013) evaluations were different from the respiratory quotient at the fourth evaluation. Therefore, the first evaluation may not be representative of the actual EE. The mean value of at least 3 subsequent evaluations after an adequate adaptation period (5 to 10 minutes) to the equipment will be useful for predicting energy requirements of apparently resting, clinically normal dogs.

Animals↗

Effects of chemotherapy and remission on carbohydrate metabolism in dogs with lymphoma.

After a 12-hour fast, blood samples were obtained from 27 dogs with previously untreated lymphoma before and 5, 15, 30, 45, and 60 minutes after an intravenous (IV) challenge with 500 mg/kg dextrose. This procedure was done for each dog before up to five treatments with the IV doxorubicin (30 mg/m2 every 3 weeks). All dogs achieved a complete remission. Samples were assayed for glucose, lactate, and insulin concentrations, and results were compared statistically with those from 16 normal control dogs of similar weight and age undergoing an identical dextrose challenge before and 3 weeks after receiving one dose of IV doxorubicin (30 mg/m2). Glucose, lactate, and insulin concentrations did not change significantly in response to glucose challenge in control dogs after doxorubicin chemotherapy. Lactate and insulin concentrations in untreated dogs with lymphoma were significantly higher than controls. This hyperlactatemia and hyperinsulinemia did not improve when dogs with lymphoma were put into remission with doxorubicin chemotherapy. The results indicate that carbohydrate metabolism is altered in dogs with lymphoma, and that these abnormalities do not improve when a complete remission is obtained with doxorubicin chemotherapy.

Animals↗

Glucose metabolism in proliferating epithelial cells from the rat colon.

1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pentose pathway (OPP) and the tricarboxylic acid cycle (TCA) in isolated rat colonocytes were estimated by the rate of production of 14CO2 from [1-14C]glucose and [6-14C]glucose, respectively. 2. Refeeding after a fast induced a 2-3-fold increase in glucose flux through the OPP and TCA cycle and the degree of change was similar in colonocytes from the proximal and distal colon. 3. Butyrate at a concentration of 40 mM inhibited the OPP by 20-30% (P less than 0.05) but had no effect on the activity of the TCA cycle. Glutamine at a concentration of 2 mM decreased the glucose flux through both the OPP and the TCA cycle by 30-50% (P less than 0.05). 4. Production of 14CO2 from the oxidation of butyrate or glucose indicated that the former was 5-7 times more active in colonocytes from fasted rats. After refeeding, however, butyrate utilization was similar to fasting values in the proximal colon but significantly lower (P less than 0.05) in the distal colon.

Animals↗

Hematologic features of iron deficiency anemia in llamas.

Iron deficiency anemia was identified and characterized in three 14 to 29-month-old male llamas (llama Nos. 1-3) from separate herds in Colorado. The identification of iron deficiency anemia was based on hypoferremia (serum iron = 20-60 micrograms/dl), erythrocytic features, and hematologic response to iron therapy. The anemia was moderate and nonregenerative and characterized by erythrocyte hypochromia, microcytosis (mean cell volume = 15-18 fl), and decreased mean corpuscular hemoglobin concentration (36.0-41.0 g/dl). Morphologic features unique to llamas with iron deficiency anemia included irregular distribution of hypochromia within erythrocytes and increased folded cells and dacryocytes. The cause of iron deficiency was not determined. The llamas were treated with various doses and schedules of parenteral iron dextran. Two of the llamas were monitored for up to 14 months after the start of iron therapy and experienced increases in hematocrit and mean cell volume values. In one llama, progressive replacement of microcytic cells with normal cells was visualized on sequential erythrocyte volume distribution histograms following iron therapy.

Anemia, Hypochromic↗

Regional factors affecting proliferation in the large intestine of the rat.

Colonic neoplasia is more frequent in the distal colon than in the proximal colon in spontaneous human disease and in carcinogen-induced tumors in rodents. The possibility that this may reflect regional differences in morphology and in proliferative responses to fasting and refeeding was explored in this study in rats. Scanning electron microscopy revealed that the density of colonic crypts was 36% higher in the distal than in the proximal colon, while light microscopy revealed that distal crypts had 70% more colonocytes than proximal crypts. Thus, the number of colonocytes per unit area in the distal colon is approximately twice that in the proximal colon. Proliferation was assessed by the uptake of bromodeoxyuridine in vivo and showed that regions of the distal colon had greater suppression of proliferation during fasting than the cecum, and greater enhancement of proliferation during refeeding than that observed in the cecum or the proximal colon. Changes in proliferation associated with fasting and refeeding were accompanied by changes in the concentrations of short chain fatty acids, but the data did not support the hypothesis of a direct relationship between increasing concentrations of short chain fatty acids and enhanced proliferation. Regional differences in morphology and proliferation could be relevant to the greater susceptibility of the distal colon to neoplasia.

Animals↗

Evaluation of a one-hour saline diuresis protocol for administration of cisplatin to dogs.

A study was undertaken to determine the toxic effects of cisplatin, an antineoplastic agent, when administered immediately after a 1-hour saline diuresis. Four treatments with cisplatin (70 mg/m2 of body surface, q 3 wk) were administered IV to 6 healthy dogs over a 20-minute period after 0.9% NaCl (saline) solution was administered IV for 1 hour at a volume of 132 ml (kg)0.75. Each dog vomited at least once within 8 hours after each treatment was administered. Clinical status, body weight, and food consumption were normal throughout the 12-week study for 5 of the 6 dogs. The sixth dog developed acute renal failure and became acutely blind and deaf within 3 days after the fourth treatment with cisplatin. Serum electrolyte, creatinine, and urea nitrogen values remained within established normal limits in all dogs immediately prior to each treatment, and in 5 of 6 dogs evaluated 3 weeks after the final treatment. The serum creatinine value (3.3 mg/dl) obtained from the Beagle euthanatized 2 weeks after the fourth treatment was above established normal values. Despite normalcy for all but 1 of the creatinine values, serum creatinine concentration obtained 3 weeks after the final treatment with cisplatin was significantly (P = 0.0001) higher than pretreatment values. When compared with data from all other evaluation periods, significant decreases in glomerular filtration rate, as determined by exogenous (P less than or equal to 0.0001) and endogenous (P less than or equal to 0.0001) creatinine clearance testing, were identified 3 weeks after the fourth treatment with cisplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Characterization of erythrocytic indices and serum iron values in healthy llamas.

An electronic particle counter with attached particle-size analyzer was configured to directly determine concentration, mean cell volume, and volume distribution of erythrocytes in llama blood. Blood from 38 healthy llamas was used to characterize erythrocytic measurements and serum iron values for this species. Volume distribution curves for llama erythrocytes were similar in shape to those of other species. These curves had a unimodal, symmetric shape with a tail skewed to the right. Reference ranges for directly measured mean cell volume, erythrocyte concentration, hemoglobin concentration, and mean cell hemoglobin concentration were 21 to 28 fl, 11.3 x to 17.5 x 10(6) cells/microliters, 12.8 to 17.6 g/dl, and 43.2 to 46.6 g/dl, respectively. Reference ranges for serum iron concentration, total iron-binding capacity, and transferrin saturation were determined to be 70 to 148 micrograms/dl, 230 to 370 micrograms/dl, and 22 to 50%, respectively.

Animals↗

Effect of dietary phosphoric acid supplementation on acid-base balance and mineral and bone metabolism in adult cats.

Experimental evidence indicates that maintenance of urinary pH < or = 6.4 is the single most effective means of preventing feline struvite crystalluria or urolithiasis of noninfectious causes. This may be accomplished by dietary acidification, but must be moderated to avoid potential adverse effects of excessive acidification, including bone demineralization, negative calcium balance, potassium depletion, and renal disease. Effects of chronic dietary phosphoric acid supplementation on acid-base balance and on mineral and bone metabolism were investigated in adult, domestic cats. One group of 6 cats was fed a basal, naturally acidifying diet without added acidifiers, and another group of 6 cats was fed 1.7% dietary phosphoric acid. Changes observed during 12 months of study included development of noncompensated metabolic acidosis, increased urinary calcium excretion, and lower but positive calcium balance in cats of both groups. Urinary pH decreased in cats of both groups, but was significantly (P < 0.05) and consistently maintained < or = 6.4 in cats given dietary phosphoric acid. Urinary phosphorus excretion increased in cats of both groups, but was significantly (P < 0.05) greater in phosphoric acid-supplemented cats, leading to lower overall phosphorus balance as well. Potassium balance decreased in cats of both groups, but was only transiently negative in the phosphoric acid-supplemented cats midway through the study, and normalized at positive values thereafter. Plasma taurine concentration was not affected by dietary acidification, and remained well within the acceptable reference range for taurine metabolism. Double labeling of bone in vivo with fluorescent markers was followed by bone biopsy and histomorphometric measurement of several static and dynamic variables of bone formation. Overall indices of bone formation decreased in cats of both groups with age and confinement, but were not affected by dietary phosphoric acid supplementation. Dietary supplementation with phosphoric acid used as the principal inorganic P source to achieve moderate and stable degree of urinary acidification, did not appear over the course of 1 year, to have induced adverse effects on mineral, bone, or taurine balance in these adult domestic cats.

Acid-Base Equilibrium↗

Taurine depletion and cardiovascular disease in adult cats fed a potassium-depleted acidified diet.

Although low plasma taurine concentrations have been associated with congestive cardiomyopathy in cats, the cause of taurine depletion in cats consuming adequate quantities of taurine is unknown. Taurine depletion and cardiovascular disease (cardiomyopathy and thromboembolism) developed unexpectedly in 3 of 6 healthy adult cats during a potassium-depletion study. Plasma taurine concentration decreased significantly (P less than 0.05) and rapidly over an 8-week period (from 98 to 36 nmol/ml) in 6 cats that consumed a potassium-deficient diet (0.20% potassium, dry matter basis) that was acidified with 0.8% ammonium chloride, despite containing dietary taurine concentrations (0.12% dry matter basis) in excess of amounts currently recommended. Taurine concentrations were significantly lower in cats fed the acidified diet than in 6 cats fed a potassium-deficient diet that was not acidified (36 nmol/ml vs 75 nmol/ml) after 8 weeks. In addition, plasma taurine concentrations did not decrease over a 6-month period in 8 cats that were fed a potassium-replete diet with acidifier. Plasma taurine concentrations were lowest in 3 cats that died of cardiovascular disease in the group receiving potassium-deficient, acidified diets. These data indicated an association between taurine and potassium balance in cats and suggested that development of taurine depletion and cardiovascular disease may be linked to concurrent potassium depletion.

Ammonium Chloride↗

Bioelectrical impedance and zoometry for body composition analysis in domestic cats.

Zoometric measurements and bioelectrical impedance analysis were evaluated as methods of body composition determination in healthy cats. Zoometric and impedance measurements were taken on 22 anesthetized adult cats of various ages, genders, breeds, and body weights. The cats were then euthanatized. The bodies were processed through a tissue homogenizer and free-catch specimens were taken, freeze-dried, and analyzed for total body water, protein, fat, potassium, and ash content. Stepwise regression analysis was implemented to identify statistically significant relationships between the chemically determined dependent variables (total body water, protein, potassium, fat-free mass, fat mass, and percent body fat) and the zoometric measurements, with or without bioelectrical impedance analysis. Statistical analysis revealed high correlations between the dependent variables and the corresponding predicted values of those variables. Body weight alone was a poor predictor of body composition in these cats. On the basis of these findings, we suggest that zoometric and bioelectrical impedance measurements may serve as practical, noninvasive, simple, and accurate methods for estimating body composition in domestic cats.

Animals↗

The effect of glutathione depletion by buthionine sulphoximine on 1-cyano-3,4-epithiobutane toxicity.

The effect of glutathione (GSH) depletion by buthionine sulphoximine (BSO) on the nephrotoxicity and GSH-enhancing effect of the naturally occurring, crucifer-derived nitrile 1-cyano-3.4-epithiobutane (CEB), was investigated. Male Fischer 344 rats were administered 50 or 125 mg CEB/kg body weight by gavage with or without prior ip treatment with 550 mg/kg body weight L-BSO. One group of control animals was treated with water only by gavage, while another group was pretreated with BSO and then given water by gavage. Liver and kidney samples were taken 48 hr after CEB treatment for GSH determinations and histological examination. The high-dose CEB without BSO resulted in increased GSH in liver and kidney, marked karyomegaly in the pars recta of renal proximal tubules and tubular epithelial necrosis, which was limited to a few renal tubules. The low-dose CEB alone resulted in increased hepatic GSH and mild karyomegaly. Pretreatment with BSO abrogated the tubular necrosis and karyomegaly induced by either CEB dose. BSO pretreatment inhibited low-dose CEB-induced GSH enhancement in the liver. The combined BSO and high-dose CEB treatment still resulted in increased hepatic GSH, although the increase was less than that observed with high-dose CEB alone. In the kidney, BSO pretreatment abrogated the high-dose CEB-induced increase in GSH, but GSH content was not significantly different from that with high- or low-dose CEB alone. These results provide evidence that CEB conjugation may be a bioactivation reaction with the conjugate involved in nephrotoxicity. The conjugate may also be involved in increasing renal and hepatic GSH.

Animals↗

Screening of anionic salts for palatability, effects on acid-base status, and urinary calcium excretion in dairy cows.

Six anionic salts [MgCl2.6H2O, MgSO4.7H2O, CaCl2.2H2O, CaSO4.2H2O, NH4Cl, and (NH4)2SO4] were evaluated for their effects on dietary DM intake, systemic acid-base balance, and urinary excretion of Ca. Each of the six salts was fed to 12 nonlactating, nonpregnant Holstein cows for 1-wk periods in two replicates of a 6 x 6 Latin square design. All salts were fed at the rate of two equivalents cow-1 d-1. Anionic salt treatments did not decrease DM intake compared with the control diet fed without salts. Blood pH was not affected by any of the salt treatments; however, mild, compensated metabolic acidosis was evidenced by decreased blood bicarbonate concentrations and decreased blood base excess when any of the salts was fed. Urinary pH and urinary base excess also were lowered by all of the salts. Fractional excretion of urinary Ca was increased by all salt treatments. All six anionic salts tested were of similar value in their acidifying effects and in their ability to increase urinary excretion of Ca.

Acid-Base Equilibrium↗

Trabecular bone remodeling and bone mineral density in the adult cat during chronic dietary acidification with ammonium chloride.

Ammonium chloride (NH4Cl) is used as a urinary acidifier in the treatment and prevention of feline urologic syndrome. It is reported to cause alterations in calcium and bone metabolism in humans, dogs, and rats. Adult cats with normal renal function were fed 1.5% NH4Cl for 6 months to study the effects of chronic dietary acidification on trabecular bone remodeling of the iliac crest and bone mineral density (BMD) of lumbar vertebral trabecular bone and femoral cortex. Histomorphometric analyses of iliac crest biopsies were performed before and after treatment. Static and dynamic parameters of bone resorption and formation were determined. Single-energy quantitative computed tomography (SEQCT) was used to measure lumbar trabecular and femoral cortical BMD. There were no significant treatment effects in iliac crest trabecular bone remodeling or BMD of the vertebrae and femora. Bone remodeling activity decreased with time in both acidotic and control cats. Vertebral BMD increased with time in both groups of cats, whereas no change was seen in the femora. Thus, chronic dietary acidification for 6 months with therapeutic levels of NH4Cl produced no significant changes in trabecular bone remodeling or bone mineral density in adult cats.

Acidosis↗

Pyruvate sparing by butyrate and propionate in proliferating colonic epithelium.

1. The effects of fasting and fasting followed by refeeding on the relative activities of the pyruvate dehydrogenase (PDH) complex and the tricarboxylic acid (TCA) cycle in isolated rat colonocytes were estimated by the rate of production of 14CO2 from [1-14C]pyruvate and [3-14C]pyruvate, respectively. 2. Decarboxylation of pyruvate by the PDH complex exceeded that by the TCA cycle in both fasted and fasted/refed colonocytes, was higher in distal than in proximal colon, and was stimulated by refeeding following a fast. 3. Oxidation of pyruvate by both the PDH complex and the TCA cycle was inhibited by butyrate. 4. Propionate alone had no effect, but synergized with butyrate to further reduce pyruvate decarboxylation by the TCA cycle. 5. Preferential utilization of butyrate by proliferating colonic epithelial cells is postulated to maximize the energy yield and spare pyruvate and its precursors for alternative synthetic roles necessary for active cell division.

Animals↗