Arginine vasotocin and renal function in the conscious dog

The effects of arginine vasotocin (AVT), 4–6 ng/kg, on renal function and plasma prolactin (PRL) were determined in conscious American foxhounds undergoing a water diuresis. Intravenous AVT produced an antidiuresis, kaliuresis and inconsistent natriuresis, independently of changes in GFR, blood pressure, heart rate and plasma PRL.     

Effects of age on thermoregulatory responses during cold exposure in a nonhuman primate, Microcebus murinus

Cold resistance appears altered with aging. Among existing hypotheses, the impaired capacity in response to cold could be related to an altered regulation of plasma IGF-1 concentration. The combined effects of age and cold exposure were studied in a short-living primate, the gray mouse lemur (Microcebus murinus), which adjusts its energy balance using a daily torpor phase, to avoid high energy cost of normothermia maintenance. Changes in body mass, core temperature, locomotor activity, and caloric intake were monitored under 9-day exposures to 25 degrees C and 12 degrees C in captive animals in winter conditions. Short-term (after 2 days) and long-term (after 9 days) cold-induced changes in IGF-1 levels were also evaluated. In thermoneutral conditions (25 degrees C), general characteristics of the daily rhythm of core temperature were preserved with age. At 12 degrees C, age-related changes were mainly characterized by a deeper hypothermia and an increased frequency of torpor phases, associated with a loss of body mass. A short-term cold-induced decrease in plasma IGF-1 levels was observed. IGF-1 levels returned to basal values after 9 days of cold exposure. No significant effect of age could be evidenced on IGF-1 response. However, IGF-1 levels of cold-exposed aged animals were negatively correlated with the frequency of daily torpor. Responses exhibited by aged mouse lemurs exposed to cold revealed difficulties in the maintenance of normothermia and energy balance and might involve modulations of IGF-1 levels.     

Polymorphism of glycophorins in nonhuman primate erythrocytes

Using immunoblotting techniques and polyclonal antisera to human erythrocyte glycophorin, we show that erythrocytes of several species of nonhuman primates, including representatives of anthropoid apes (19 chimpanzees, 3 gorillas, 6 orangutans, and 3 gibbons) and Old World monkeys (3 baboons, 5 rhesus monkeys, and 6 cynomologus macaques), contain human glycophorin-like molecules. Each species displays a unique glycophorin profile; in anthropoid apes the profile is more complex than in Old World monkeys and more similar to that seen in humans. The chimpanzee was the only species in which human -like glycophorin was detected but it differed from its human counterpart in electrophoretic mobility and reaction with M-specific monoclonal antibody. In contrast to humans, highly polymorphic glycophorin profiles were observed in each species of anthropoid apes and three distinct patterns were defined in each. No such polymorphism has been found so far among the Old World monkeys in the limited number of animals studied. The major glycophorins in all species but the chimpanzees failed to react with M- or N-specific monoclonal antibodies, suggesting structural differences from the human within the amino terminal regions. The reaction with the minor glycophorins showed inter- and intraspecies variability. All glycophorins, except -like glycophorin in the chimpanzee, reacted with the antiserum to the carboxyl terminal fragment of human glycophorin, indicating a structural relation to the human in this region. An unexpected correlation was observed, in the chimpanzee, between the patterns of electrophoretically resolved glycophorins and the V-A-B-D blood-group phenotypes, allowing the assignment of each determinant to specific glycophorin bands. The basis for the differences observed between human and nonhuman primate glycophorins is not clear but the possibilities include a common nonpolymorphic ancestor and differences in selective pressures.This research was supported by National Institutes of Health Grant 5 RO1 GM16389.     

Models of focal cerebral ischemia in the nonhuman primate

Ischemic stroke is a uniquely human disease syndrome. Models of focal cerebral ischemia developed in nonhuman primates provide clinically relevant platforms for investigating pathophysiological alterations associated with ischemic brain injury, microvascular responses, treatment responses, and clinically relevant outcomes that may be appropriate for ischemic stroke patients. A considerable number of advantages attend the use of nonhuman primate models in cerebral vascular research. Appropriate development of such models requires neurosurgical expertise to produce single or multiple vascular occlusions. A number of experimentally and clinically accessible outcomes can be measured, including neurological deficits, neuron injury, evidence of non-neuronal cell injury, infarction volume, real-time imaging of injury development, vascular responses, regional cerebral blood flow, microvascular events, the relation between neuron and vascular events, and behavioral outcomes. Nonhuman primate models of focal cerebral ischemia provide excellent opportunities for understanding the vascular and cellular pathophysiology of cerebral ischemic injury, which resembles human ischemic stroke, and the appropriate study of pharmacological interventions in a human relevant setting.     

Tissue distribution,binding properties and lesions produced by dehydroretronecine in the nonhuman primate

Four-month-old rhesus monkeys were injected with 65 mg of [³H]dehydroretronecine per kg body weight and sacrificed at 6, 12 and 24 h following injection. By the 24th h 13% of the dose had been eliminated in the urine. Although there were no feces, the extremely high radioactivity of the bile and intestinal contents suggested this route was a major one for the excretion of this compound. The³H was distributed throughout the body by the 6th h with the greatest percentage being in the skin and muscle. However, per gram of tissue the gastric mucosa and bile showed the highest radioactivity. Likewise, it was in the gastric mucosa that the lesions produced by dehydroretronecine were the most severe. High levels of radioactivity persisted in the gastric mucosal lysates after washings with trichloroacetic acid (TCA) while only a small percentage of the³H remained in the washed liver lysate. It was determined that over 20% of the³H was bound to mucosal protein and less than 1% to the nucleic acids.     

HIV vaccine development in the nonhuman primate model of AIDS

Development of a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine is a leading priority in biomedical research. Much of this work has been done with the nonhuman primate model of AIDS. In a historical context, vaccine studies, which use this model, are summarized and discussed.     

Extrasynaptic action of vasopressin,oxytocin, and vasotocin neuropeptides on electrically operated ionic channels at the mollusk neuronal membrane

Techniques of intracellular dialysis and neuronal perfusion in the visceral ganglion ofLymnaea stagnalis used during voltage-clamping at the neuronal membrane helped to ascertain that a concentration of 1×10^–16–1×10^–6 M neuroactive peptides (vasopressin, oxytocin, and vasotocin) alter the amplitude of electrically-operated transmembrane ionic currents considerably without affecting the kinetics of current activation and inactivation and surface potential at the membrane. The experimental conditions applying made it possible to record incoming sodium and calcium currents separated from each other as well as outward delayed and transient potassium currents. It was found that electrically-operated cerebral currents could either increase or decline in amplitude under the effects of peptides applied at different concentrations to the membrane of the same unit. Receptors of the peptides investigated in this study are thought to be located within the structure of electrically-operated channels at the neuronal membrane.A. I. Gertsen Teaching Institute, Leningrad. Translated from Neirofiziologiya, Vol. 22, No. 4, pp. 526–533, July–August, 1990.     

Effects of oxytocin on cloprostenol-induced luteolysis, follicular growth, ovulation and corpus luteum function in heifers

Twenty-five normally cyclic Holstein heifers were used to examine the effects of oxytocin on cloprostenol-induced luteolysis, subsequent ovulation, and early luteal and follicular development. The heifers were randomly assigned to 1 of 4 treatments: Group SC-SC (n=6), Group SC-OT (n=6), Group OT-SC (n=6) and Group OT-OT (n=7). The SC-SC and SC-OT groups received continuous saline infusion, while Groups OT-SC and OT-OT received continuous oxytocin infusion (1:9 mg/d) on Days 14 to 26 after estrus. All animals received 500 microg, i.m. cloprostenol 2 d after initiation of infusion (Day 16) to induce luteolysis. Groups SC-OT and OT-OT received oxytocin twice daily (12 h apart) (0.33 USP units/kg body weight, s.c.) on Days 3 to 6 of the estrous cycle following cloprostenol-induced luteolysis, while Groups SC-SC and OT-SC received an equivalent volume of saline. Daily plasma progesterone (P4) concentrations prior to cloprostenol-induced luteolysis and rates of decline in P4 following the induced luteolysis did not differ between oxytocin-infused (OT-OT and OT-SC) and saline-infused (SC-SC and SC-OT) groups (P >0.1). Duration of the estrous cycle was shortened in saline-infused heifers receiving oxytocin daily during the first week of the estrous cycle. In contrast, oxytocin injections did not result in premature inhibition of luteal function and return to estrus in heifers that received oxytocin infusion (OT-OT). Day of ovulation, size of ovulating follicle and time of peak LH after cloprostenol administration for oxytocin and saline-treated control heifers did not differ (P >0.1). During the first 3 d of the estrous cycle following luteal regression, fewer (P <0.01) follicles of all classes were observed in the oxytocin-infused animals. Day of emergence of the first follicular wave in heifers treated with oxytocin was delayed (P <0.05). The results show that continuous infusion of oxytocin during the mid-luteal stage of the estrous cycle has no effect on cloprostenol-induced luteal regression, timing of preovulatory LH peak or ovulation. Further, the finding support that an episodic rather than continuous administration of oxytocin during the first week of the estrous cycle results in premature loss of luteal function. The data suggest minor inhibitory effects of oxytocin on follicular growth during the first 3 d of the estrous cycle following cloprostenol-induced luteolysis.     

Progress and challenges in therapies for AIDS in nonhuman primate models

Efforts to develop animal models for human immunodeficiency virus type-1 (HIV-1) vaccine testing have focused on lentivirus infection of nonhuman primates. A long-term goal of this primate research is to utilize the models to understand the mechanisms of pathogenesis leading to AIDS. Because the time to disease is compressed relative to HIV infection in humans, therapeutic strategies and compounds can be tested in nonhuman primate models in a shorter time frame and under more controlled conditions than are possible in many clinical studies. Recent interventive studies in primates using antiviral drugs or passive immune globulin (IgG) have demonstrated that multiple log reductions in plasma virus can be achieved and sustained, with accompanying health benefits. Information gained about timing and dosage may be of utility in designing clinical studies. The development of reliable and predictable animal models for effective therapies and vaccines against AIDS remains a critical priority for primate research.