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[3H]ouabain binding in skeletal muscle from horses with hyperkalemic periodic paralysis. [English]
1993
Pickar J.G. | Spier S.J. | Harrold D. | Carlsen R.C.
Ouabain, a cardiac glycoside, binds to the Na+-K+i-adenosine triphosphatase (Na+ pump) and prevents active transport of Na+ and K+ across cell membranes. We used [3H]ouabain to quantify the number and affinity of Na+ pumps in skeletal muscle from Quarter Horses with the muscular disorder hyperkalemic periodic paralysis (HYPP). [3H]Ouabain-binding properties of gluteal muscle from clinically normal and affected horses were used to determine whether altered Na+ pump number or affinity could contribute to the pathologic features of muscle in affected horses. Foals and adult horses with HYPP were compared with age-matched clinically normal horses. The number of [3H]ouabain-binding sites in adult gluteal muscle was not different between the 2 types of horses (85.7 +/- 8.9 pmol of [3H]ouabain-binding sites/g [wet muscle weight] in horses with HYPP vs 100.2 +/- 8.8 pmol/g in clinically normal adult horses). Gluteal muscles in HYPP-affected and clinically normal foals also contained a similar number of [3H]ouabain-binding sites (222.3 +/- 21.0 pmol/g vs 225.3 +/- 24.2 pmol/g, respectively). The affinity of these binding sites for ouabain was not different, between adults or foals, in clinically normal or affected horses. Our results indicate that membrane events underlying the periodic episodes of paralysis in horses with HYPP are not attributable to quantitative changes in Na+ pump number or affinity. Our data cannot exclude the possibility that the specific activity of the Na+ pump is altered in muscle from HYPP-affected horses.
显示更多 [+] 显示较少 [-]Effects of sex, age, puncture site, and blood contamination on the clinical chemistry of cerebrospinal fluid in rhesus macaques (Macaca mulatta)
1993
Smith, M.O. | Lackner, A.A.
Paired CSF and serum samples were obtained from 109 rhesus macaques aged 1 to 18 years. The CSF and serum IgG and albumin concentrations were determined, using radial immunodiffusion; CSF total protein and glucose were determined, using colorimetric methods; and Na, K, and Cl concentrations were determined, using ion-specific electrodes. The CSF protein values were lower than those reported for nonhuman primates, and this finding was confirmed by results of agar gel electrophoresis. Animal age and sex had no significant effects on CSF composition, but serum IgG concentration increased with age. Concentrations of total protein, albumin, and IgG were greater, and concentrations of glucose and potassium were lower in CSF obtained from the lumbar rather than the cisternal site. Composition of CSF was not significantly altered by contamination with blood at values up to 10,000 RBC/microliter. The CSF albumin quotient, IgG quotient, and IgG index were determined and differed markedly from values reported for human beings, indicating that the properties and specificity of the blood-brain barrier may be species-specific.
显示更多 [+] 显示较少 [-]Characteristics of L-glutamine transport in equine jejunal brush border membrane vesicles
1993
Salloum, R.M. | Duckworth, D. | Madison, J.B. | Souba, W.W.
The sodium-dependent transporter system responsible for L-glutamine uptake by brush border membrane vesicles prepared from equine jejunum was characterized. Vesicle purity was ascertained by a 14- to 17-fold increase in activity of the brush border enzyme markers. Glutamine uptake was found to occur into an osmotically active space with negligible membrane binding. The sodium-dependent velocity represented approximately 80% of total uptake and demonstrated overshoots. Kinetic studies of sodium-dependent glutamine transport at concentrations between 5 micromolar and 5 mM revealed a single saturable high-affinity carrier with a Michaelis constant of 519 +/- 90 micromolar and a maximal transport velocity of 3.08 +/- 0.97 nmol/mg of protein/10 s. Glutamine uptake was not affected by changes in environmental pH. Lithium could not substitute for sodium as a contransporter ion. 2-Methylaminoisobutyric acid inhibited the sodium-dependent carrier only minimally, but marked inhibition (> 90%) was observed in the presence of histidine, alanine, cysteine, and nonradioactive glutamine. Kinetic analysis of the sodium-independent transporter revealed it to have a Michaelis constant = 260 +/- 47 micromolar and a maximal transport velocity of 0.32 t 0.06 nmol/mg of protein/10 s. We conclude that glutamine transport in equine jejunal brush border membrane vesicles occurs primarily via the system B transporter and, to a lesser extent, by a sodium-independent carrier.
显示更多 [+] 显示较少 [-]Toxicity of desoxycorticosterone pivalate given at high dosages to clinically normal Beagles for six months
1993
Chow, E. | Campbell, W.R. | Turnier, J.C. | Lynn, R.C. | Pavkov, K.L.
Desoxycorticosterone pivalate was administered IM to juvenile Beagles at 0, 2.2, 6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28 days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for 6 months. Polyuria, polydipsia, and decreases in serum potassium and BUN concentrations were detected while the dogs were being treated. Transient increases in serum sodium concentrations also were detected. The treated males had significant decreases in body weight gain, resulting in an 18% decrease in body weight in the 11-mg/kg dosage group, compared with the controls. The weights of the adrenal glands, epididymides, and testes also were lower in the treated males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79, and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%, respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively, of the controls (testes). When normalized to body weight, these decreases in organ weight were still dosage-dependent, but the differences were less remarkable. In contrast, the relative weight (to body weight) of the kidneys (males and females) and of the thyroid and parathyroid glands (males) were higher dosage-dependently. All of the treatment-related effects, other than organ and body weight changes, appeared to be reversible following the cessation of treatment. On the basis of these results, it was concluded that treatment with desoxycorticosterone pivalate could be tolerated, even when given at dosages 15-fold the therapeutic dosage of 2.2 mg/kg every 25 days.
显示更多 [+] 显示较少 [-][3H]ouabain binding in skeletal muscle from horses with hyperkalemic periodic paralysis
1993
Pickar, J.G. | Spier, S.J. | Harrold, D. | Carlsen, R.C.
Ouabain, a cardiac glycoside, binds to the Na+-K+i-adenosine triphosphatase (Na+ pump) and prevents active transport of Na+ and K+ across cell membranes. We used [3H]ouabain to quantify the number and affinity of Na+ pumps in skeletal muscle from Quarter Horses with the muscular disorder hyperkalemic periodic paralysis (HYPP). [3H]Ouabain-binding properties of gluteal muscle from clinically normal and affected horses were used to determine whether altered Na+ pump number or affinity could contribute to the pathologic features of muscle in affected horses. Foals and adult horses with HYPP were compared with age-matched clinically normal horses. The number of [3H]ouabain-binding sites in adult gluteal muscle was not different between the 2 types of horses (85.7 +/- 8.9 pmol of [3H]ouabain-binding sites/g [wet muscle weight] in horses with HYPP vs 100.2 +/- 8.8 pmol/g in clinically normal adult horses). Gluteal muscles in HYPP-affected and clinically normal foals also contained a similar number of [3H]ouabain-binding sites (222.3 +/- 21.0 pmol/g vs 225.3 +/- 24.2 pmol/g, respectively). The affinity of these binding sites for ouabain was not different, between adults or foals, in clinically normal or affected horses. Our results indicate that membrane events underlying the periodic episodes of paralysis in horses with HYPP are not attributable to quantitative changes in Na+ pump number or affinity. Our data cannot exclude the possibility that the specific activity of the Na+ pump is altered in muscle from HYPP-affected horses.
显示更多 [+] 显示较少 [-]Effects of dietary electrolyte balance on subluxation of the femoral head in growing dogs
1993
Kealy, R.D. | Lawler, D.F. | Monti, K.L. | Biery, D. | Helms, R.W. | Lust, G. | Olsson, S.E. | Smith, G.K.
Effects of increased dietary chloride and reduced sodium and potassium ion concentrations on coxofemoral joint conformation, as assessed by radiography, were examined in growing dogs. Dietary electrolyte balance was quantified by dietary anion gap (DAG), defined as Na+ + K+ - Cl- in milliequivalents per 100 g of food. Diets had anion gap ranging from 8 to 41 mEq/100 g of food. One hundred sixty-seven pups from 27 litters representing 5 breeds were studied during the period of rapid growth. The extent of subluxation of the femoral head was measured on radiographs, using the method of Norberg. On average, less subluxation of the femoral head (P < 0.05) was observed when diets with lower DAG were fed. Differences in DAG balance did not result in different rates of weight gain; therefore, the reduction in coxofemoral joint subluxation attributable to low DAG was unrelated to weight gain. Norberg angles measured at 30 weeks of age were highly correlated with coxofemoral joint status at 2 years of age, as measured by the Swedish diagnostic system and the scoring system of the Orthopedic Foundation for Animals (/r/ greater than or equal to 0.70, P < 0.0002, n = 24). This diet-related improvement in coxofemoral joint sub-luxation would be expected, on average, to delay or mitigate the characteristic clinical and radiographic signs of hip dysplasia in growing dogs.
显示更多 [+] 显示较少 [-]Comparison of 0.9, 3.6, and 7.2% NaCl for correction of experimentally induced hypochloremic, hypokalemic metabolic alkalosis in sheep
1993
Ward, J.L. | Smith, D.F. | Fubini, S.L. | Grohn, Y.T.
Nine adult female sheep were each surgically fitted with an Ivan and Johnston reentrant cannula in the cranial part of the duodenum just distal to the pylorus. By diversion (loss) of abomasal outflow, this model has been shown to consistently induce hypochloremic, hypokalemic metabolic alkalosis, accompanied by hyponatremia and dehydration. Each sheep was subjected to 3 treatment trials, each preceded by a 24-hour prediversion period, and a diversion period during which a syndrome of hypochloremia (68 +/- 2 mEq/L), hypokalemia, hyponatremia, and metabolic alkalosis was induced. Development of this syndrome was attributable to losses of large amounts of acid and electrolytes in the abomasal effluent. Mean total electrolyte contents of the effluent were: Cl-, 650 +/- 27 mEq; Na+, 388 +/- 23 mEq; and K+, 123 +/- 12 mEq, with total volume loss ranging from 3.6 to 10.0 L of gastric contents and pH ranging from 3 to 5. Decreases in plasma electrolyte concentrations also can be attributed to decreased intake, because anorexia developed shortly after the onset of diversion. Electrolyte losses in urine during diversion were minimal for Cl-(mean +/- SEM, 12.0 +/- 5.1 mEq), but were greater for Na+ (124.2 +/- 14.5 mEq) and K+ (185.1 +/- 31.2 mEq). Treatments consisted of 0.9% NaCl (300 mosm/ L), 3.6% NaCl (1,200 mosm/L, and 7.2% NaCl (2,400 mosm/L) administered over a 2-hour period, with the administered volume determined by the estimated total extracellular fluid Cl- deficit. Significant difference was not found among treatments, with all solutions resulting in return of clinicopathologic and physical variables to prediversion values within 12 hours of treatment. We concluded that rapid iv replacement of Cl-, with small volumes of hypertonic saline solution, is safe and effective for correction of experimentally induced hypochloremic, hypokalemic, metabolic alkalosis in sheep.
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