Robert W. Phillips

ALTERATIONS IN BODY WATER TURNOVER AND DISTRIBUTION IN NEONATAL CALVES WITH ACUTE DIARRHEA

In neonatal diarrhea the single most outstanding clinical sign is dehydration. However, little quantitative information is available concerning its severity and effect on body water distribution. In fact, many of the classical studies still used to describe water changes were done solely on the basis of fecal loss and plasma concentration values. We have become concerned with relative changes in fluid compartmentalization and water balance as diarrhea and dehydration develop. In an earlier paper the hypothesis was advanced that there were no changes in relative water distribution during diarrhea.l This experiment was designed to expand the earlier work and test this hypothesis. Our experimental animal was the calf. Previous studies using this animal as a biomedical model for the study of diarrheic-induced dysfunction have indicated that there is an increased water turnover,l acidosis,2 and severe electrolyte imbalances.3* There are several important advantages obtained by using calves to study neonatal enteritis. Their size is such that multiple samples may be easily taken without altering fluid dynamics. In addition, they are particularly susceptible to diarrhea. In fact, a greater problem could be to conduct studies on nondiarrheic calves, as the rate of natural occurrenye is quite high. When necessary, the disease may be induced by feeding carbohydrate5 or intestinal contents from calves with naturally occurring diarrhea.6 In addition, several viruses have been shown to initiate the disease.? Undoubtedly there are an infinite variety of physical, chemical, and biological insults capable of damaging the immature intestinal tract of the neonatal calf, pig, and human, causing diarrhea in these susceptible species. Of greater concern than just causing the disease in calves is the establishment of valid biological models for the study of human neonatal diarrhea. The commonly used laboratory animals are not particularly suitable for this purpose, but we feel that calves can effectively serve as such a model.

Fluid Therapy for Diarrheic Calves: What, How, and How Much

The pathophysiologic consequences of neonatal diarrhea in calves are presented. A brief discussion of intestinal nmction, nutrient absorption, and osmolar effects follows. A rationale for appropriate fluid therapy is presented, and comparisons of some currently marketed products are made.

The effects of alloxan diabetes on Yucatan miniature swine and their progeny

Alloxanization as a method to induce diabetes has been successfully undertaken in several laboratory animal models. The genetic transmissibility of the alloxan-diabetic condition has been investigated and confirmed by several studies in rodents. The Yucatan miniature pig is a potential laboratory animal model for diabetes. Studies were conducted to investigate the possibility that alloxan diabetes could be transmitted to subsequent generations in these animals. Diabetic pigs were produced directly with alloxanization, but the genetic transmissibility of this trait was not substantiated through the F2 generation. On the basis of these data, alloxan diabetes is not transmissible in Yucatan pigs in the same way that it is in rats.

Malabsorption Due to Selected Oral Antibiotics

This article represents an overview of recent research conducted on antibiotic-induced malabsorption in calves. The authors feel strongly that this work identifies a serious and ill-defined problem in the management of neonatal calves. Too often the solution utilized by veterinarian and stockmen for controlling neonatal diarrhea has been to administer oral antibiotics. In many cases, this has been done on the basis of antibiotic sensitivity testing, an approach that seems appropriate. Unfortunately, little consideration has been given to the relative sensitivity of the neonatal intestinal mucosa, with its very rapid turnover, to the potentially detrimental effects of oral antimicrobial therapy. The data that we have collected over the past 3 years conclusively demonstrate that high levels of four commonly used oral antibiotics, especially neomycin and chloramphenicol but also tetracycline and ampicillin, can cause a malabsorption diarrhea in normal calves. This action is not due to viral agents or overgrowth of resistant microbes but is the result of direct modification of the intestinal mucosa. Extrapolation of these data to different dose levels may not be accurate. Oral antibiotics may be of value in treating neonatal enteritis. Conversely, there can be too much of a good thing, and many cases of chronic diarrhea following use of oral antibiotics may be the result of an overenthusiastic and prolonged dosage regimen. Be cautious!

Plasma Corticoid Levels During Early Postnatal Life in Calves

There do not appear to be data available on plasma levels of aldosterone and progesterone in the newborn calf. Previous studies on plasma corticoid concentration in the neonate of this species have been confined to the measurement of 17-hydroxycorticosteroids (1-4). In addition, evidence as to whether the calf is born with an adequate or poor supply of circulating adrenocorticoids is controversial. In this regard, several studies (2-4) have shown in normal neonatal calves that plasma cortisol levels vary with age, with the highest concentration seen during the first day following birth. Furthermore, these data (2-4) indicated that the initial high levels of plasma cortisol decreased toward the adult concentration within the next few days. Moll (5), however, favors the view that calves are born with immature adrenals and thus are poorly equipped to cope with environmental changes. There is also disagreement as to whether corticosterone is present in plasma at birth (2, 6). The present study was, therefore, designed to determine if the calf has increased plasma corticoid levels at birth, which may contribute to a rapid adaptation to conditions of extra-uterine life. Materials and methods. Five healthy, male, colostrum-fed dairy calves were utilized. The animals were less than 24 hr old at the start of the trials. They were kept in a room at 22 ± 3° and were fed 1-2 liters of warm milk twice daily after blood collection. Heparinized serial blood samples from catherterized jugular veins were collected at 12-hr intervals. The samples were centrifuged at 14,500g for 20 min, and the plasma was removed and stored at −20° until assayed. Radioimmunoassays for aldosterone (7) and progesterone (8), and competitive protein-binding assays for cortisol and corticosterone (9) were used for the measurement of these hormones in plasma.

Intestinal mucosae enzymatic and histochemical changes during infectious diarrhea in calves

Two, healthy, 4-day-old calves were fed an enteropathogenic agent and fatal diarrhea ensued. Biopsies and mucosal scrapings from the ileum and jejunum were taken before introduction of the agent and at 24, 48 and 72 hours thereafter. The biopsies and scrapings were used to analyze the changes in cytochemical localization and biochemical activity of a variety of phosphataases. Within 24 hours, adenosine triphosphate phosphohydrolase activity was almost totally inhibited while the activity of nonspecific phosphatase and nucleoside phosphatase was only partially inhibited and that of Na+-K+ ATPase not effected at all. In preinoculation control sections, the localization of ATPase activity was heaviest in the apices of absorptive epithelial cells located at the base of the villi. This reaction was completely lost within 24 hours after the inoculation with virus. The enzymatic inhibition occurred 12 to 24 hours before diarrhea became evident.Two, healthy, 4-day-old calves were fed an enteropathogenic agent and fatal diarrhea ensued. Biopsies and mucosal scrapings from the ileum and jejunum were taken before introduction of the agent and at 24, 48 and 72 hours thereafter. The biopsies and scrapings were used to analyze the changes in cytochemical localization and biochemical activity of a variety of phosphataases. Within 24 hours, adenosine triphosphate phosphohydrolase activity was almost totally inhibited while the activity of nonspecific phosphatase and nucleoside phosphatase was only partially inhibited and that of Na+-K+ ATPase not effected at all. In preinoculation control sections, the localization of ATPase activity was heaviest in the apices of absorptive epithelial cells located at the base of the villi. This reaction was completely lost within 24 hours after the inoculation with virus. The enzymatic inhibition occurred 12 to 24 hours before diarrhea became evident.

The effect of age on water metabolism in hens.

Summary Kinetic parameters associated with the body water pool were studied in hens of two age brackets by Isotope Dilution Techniques using tritium-labeled water. The half-life of body water was found to be significantly longer (p < 0.05) in hens than in pullets. It is probable that the difference is due to an increased utilization of body water by the younger birds for their greater anabolic demands. Total body water, expressed as percent of body weight, was significantly higher (p < 0.01) in the pullets than in the hens. The lower water content of the hens appears to be due to a decrease in intra- and extracellular body water with age as previously suggested for mammals. Additionally, the greater fat mass of the older birds may be contributing to the results observed.

In vitro intestinal exchanges of Na+, K+, Cl−3H2O in experimental bovine neonatal enteritis

The pathophysiology of neonatal enteritis was studied using a specially designed in vitro apparatus. Differences were measured in the amounts and transport direction of ions and3H2O across intestinal segments of 4 normal and 4 diarrheic calves, whose ages ranged from 9 to 12 days. Na+ and K+ were quantitated by flame photometry, Cl− by titration, and3H by liquid scintillation. Mucosal and serosal solution electrolyte concentrations in intestinal segments from the 4 control calves remained in balance without net losses or gains. For the 4 diarrheic calves, significant mucosal solution gains and serosal solution losses occurred for Na+ (16–20 mEq/liter) and K+ (0.8–1.1 mEq/liter), but Cl− concentrations remained in equilibrium, and HCO 3 − loss was inferred. Specific activity of3H2O in the mucosal solution at the end of the trial was 9–13×10−4 μCi/ml and 11–21×10−4 μCi/ml for the control and diarrheic calves, respectively. Hence, Na+, K+ and3H2O were being transferred into the intestinal lumen of diarrheic calves, representing substantial body losses. Distinct histopathologic differences were found between the 2 groups.The pathophysiology of neonatal enteritis was studied using a specially designed in vitro apparatus. Differences were measured in the amounts and transport direction of ions and3H2O across intestinal segments of 4 normal and 4 diarrheic calves, whose ages ranged from 9 to 12 days. Na+ and K+ were quantitated by flame photometry, Cl− by titration, and3H by liquid scintillation. Mucosal and serosal solution electrolyte concentrations in intestinal segments from the 4 control calves remained in balance without net losses or gains. For the 4 diarrheic calves, significant mucosal solution gains and serosal solution losses occurred for Na+ (16–20 mEq/liter) and K+ (0.8–1.1 mEq/liter), but Cl− concentrations remained in equilibrium, and HCO3− loss was inferred. Specific activity of3H2O in the mucosal solution at the end of the trial was 9–13×10−4μCi/ml and 11–21×10−4μCi/ml for the control and diarrheic calves, respectively. Hence, Na+, K+ and3H2O were being transferred into the intestinal lumen of diarrheic calves, representing substantial body losses. Distinct histopathologic differences were found between the 2 groups.

Intracellular redox state and stimulation of gluconeogenesis and glycogenolysis in isolated hepatocytes from the pig (Sus scrofa)

Abstract 1. 1. Isolated pig hepatocytes were prepared and the effects of changes in the cytoplasmic [NADH]/[NAD + ] ratio on the efficacy of glucagon to alter rates of metabolism were examined. 2. 2. With hepatocytes from fed pigs 1 μM-glucagon stimulated glucose output. The response to glucagon was similar in magnitude regardless of whether 10 mM-lactate or 10 mM-pyruvate was present in incubations. 3. 3. With hepatocytes from 72-hr fasted pigs, glucagon (1 μM) increased the rate of gluconeogenesis from 10 mM-pyruvate but was without effect on the rate from 10 mM-lactate. These results differed from those obtained using rat hepatocytes where 1 μM-glucagon increased gluconeogenesis from 10 mM-lactate and inhibited gluconeogenesis from 10 mM-pyruvate. 4. 4. Intracellular concentrations of lactate and pyruvate were measured following 10 min incubations of pig hepatocytes with 10 mM-lactate or 10 mM-pyruvate. Comparisons with similar experiments conducted using rat hepatocytes indicated that both lactate and pyruvate entered the cells of both species and significantly altered the lactate/pyruvate ratio. 5. 5. Properties of the membrane-bound low K m cyclic AMP phosphodiesterase from pig and rat liver were compared. The activity of the enzyme in each species was similar and was inhibited to the same extent by NADH. 6. 6. The inability of pyruvate to inhibit the stimulatory effect of glucagon on glucose output and gluconeogenesis in pig hepatocytes does not appear to result from differences in the permeation of substrate into the cells or the sensitivity of cyclic AMP phosphodiesterase to altered cytoplasmic [NADH]/[NAD + ] ratio mediated by pyruvate or lactate addition.

Body water kinetics in vitamin A-deficient chickens.

Summary The effect of mild vitamin A deficiency on kinetic parameters associated with the body water pool was studied in five-month-old pullets by isotope dilution techniques, using tritium-labeled water. The body water T 1/2 was significantly shorter (p < 0.01) and the flux through the body water pool greatly increased (p < 0.01) in the A-deficient chicks indicating that even under mild vitamin A deficiency, water turnover rates are significantly altered. These changes appear to be due to alterations in the stability and permeability of the cells involved in water transport in the A-deficient chicken, through mechanisms yet to be elucidated.