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Biomedical subjects

J Bacher

Publications and source records attributed to J Bacher.

69 records · Page 4Linked to original sources

Calcium antagonist binding in cat brain tolerant to electroconvulsive shock.

Cats subjected to daily (25-30 days) electroconvulsive shock (ECS) demonstrated an elevation of their electroconvulsive threshold or tolerance to ECS. [3H] Nitrendipine binding was measured to brain regions from non-tolerant (sham shocked) and ECS tolerant cats 24 hr following the last shock. ECS produced a significant increase (45%) in the density of [3H] nitrendipine binding sites in the cerebral cortex and a significant decrease (33%) in the apparent affinity of [3H] nitrendipine in the cerebellum. No changes in binding were observed in the hippocampus. The effects of ECS were also investigated in the rat, an animal not displaying tolerance to repeated ECS. [3H] Nitrendipine binding to rat brain was measured 10 min and 24 hr following one shock (acute) or ten shocks delivered transauricularly once daily (chronic). Twenty-four hours following chronic ECS, there was a significant increase (19%) and decrease (11%) in the density, but no change in the apparent affinity of [3H] nitrendipine binding sites in the cerebral cortex and hippocampus respectively. No significant change in [3H] nitrendipine binding was observed in rat cerebellum 24 hr following chronic ECS. There were no changes in [3H] nitrendipine binding in the cerebral cortex and hippocampus 10 min and 24 hr following acute ECS. These results indicate that ECS can alter [3H] nitrendipine binding to calcium channel linked dihydropyridine binding sites in the central nervous system. It is suggested that changes in [3H] nitrendipine binding in the cat cerebellum may be involved in the development of tolerance to ECS.

Animals↗

Electroconvulsive shock increases endogenous monoamine oxidase inhibitor activity in brain and cerebrospinal fluid.

Chronic daily administration of electroconvulsive shock (ECS) to cats resulted in a progressive elevation of seizure threshold which was accompanied by a sustained elevation in the activity of an endogenous monoamine oxidase inhibitor (EMAOI) present in cerebrospinal fluid (CSF). The increase in EMAOI activity in CSF following chronic ECS was observed maximally at 24-48 h. In rats, a single application of ECS resulted in a rapid but short-lasting increase in EMAOI activity present in the crude membrane fraction from brain. These findings demonstrate that both acute and chronic ECS modify the activity of an EMAOI in brain and CSF which may contribute to both the antidepressant and anticonvulsant effects of ECS treatment.

Animals↗

Thymic regulation of primate fetal ovarian-adrenal differentiation.

We report that fetal thymectomy inhibits oogenesis and induces abnormal ovarian differentiation in rhesus monkeys. In utero thymectomy (n = 5) elevated plasma follicle-stimulating hormone (7.8 +/- 1.1 microgram/ml vs. 4.2 +/- 0.5 microgram/ml; P less than 0.05) and decreased plasma prolactin (24.5 +/- 3.3 ng/ml vs. 76.3 +/- 11.2 ng/ml; P less than 0.05) concentrations compared with intact controls (n = 12), but did not change plasma luteinizing hormone, estradiol, cortisol, dehydroepiandrosterone sulfate, or thymosin-alpha 1 concentrations. In utero thymectomy reduced the weight of neonatal ovaries and adrenal glands, but not hepatic, renal, splenic, or total body weights. After fetal thymectomy, newborn ovaries (n = 8) contained a reduced total number of germ cells (123,926 +/- 11,651 vs. 432,034 +/- 40,311; P less than 0.001). The percentages of individual germ cell types were similar between thymectomized and intact groups (n = 11) except for an increased percentage of preantral-antral follicles in the thymectomy group (P less than 0.01). Our results indicate that the primate fetal thymus regulates antenatal ovarian follicular development, perhaps by interactions between the nascent immunologic and pituitary-ovarian systems.

Adrenal Glands↗

Hemodynamic and endocrine parameters in the anesthetized cynomolgus monkey: a primate model.

Hemodynamic and endocrine parameters were determined in nine anesthetized adult male cynomolgus monkeys. Simultaneous phasic and mean pressures were measured in the right atrium, pulmonary artery, and abdominal aorta. Intermittent pulmonary artery wedge pressures and mean cardiac output measured by the thermal dilution method were used to calculate stroke volume, systemic vascular resistance, and pulmonary vascular resistance. Plasma adrenocorticotropic hormone (ACTH), cortisol, and plasma renin activity were measured throughout the procedure. Technical aspects, data in the anesthetized monkey, and comparison with previously reported data are presented.

Adrenocorticotropic Hormone↗

A method of thymectomy in macaques.

The aim of this study was to develop an operation for total thymectomy suitable for nonhuman primates. The thymus was removed from 24 macaque monkeys from fetal to adult life by a cervicothoracotomy and blunt gauze dissection. Mean wet weight of the thymus rose from 150 mg (range 50-250 mg) in fetal animals to 2.5 gm (range 0.3-4.2 gm) in prepubertal monkeys. Nonhuman primate thymic weight fell steadily and uniformly with age by over 300% when plotted as a function of body weight. This surgical technique appears to be a valid method of total thymectomy in macaque monkeys.

Age Factors↗

In utero allogeneic bone transplantation in primates: roentgenographic and histological observations.

Intrauterine allogeneic bone transplantation was performed on 25 monkey fetuses at 120 to 135 days of gestation. Two surgical techniques for orthotopic transplantation of the humeral midshaft were utilized: (1) A segment (5 to 7 mm) of fetal humerus was transplanted from fetus (donor) to fetus (recipient). An intramedullary pin (Kirschner orthopedic wire) was used for fixation of the severed humerus. (2) Without severing the humerus, a midshaft area (5 to 7 mm X 5 to 6 mm) was surgically ablated. A bone paste composed of crushed bone particles mixed with an agar-enriched culture medium was sculpted to fill this lesion. We used fresh frozen or fresh allograft tissue with equal success. Postsurgical observations included serial roentgenographic and histological evaluation of humeral osteogenesis, as well as postnatal assessment of limb use. The contralateral arm served as a control. Our findings indicate that the immune surveillance system of fetal monkeys may be tolerant of these bone allografts; alternatively, healing by substitution may also occur. The roentgenographic and histological results demonstrate that both of the transplantation procedures used here achieved restoration of the long bone. The use of bone paste allowed us to sculpt the allograft to the desired conformation. These results from laboratory primate models encourage continued investigation of fetal allogeneic bone transplantation, because of its ultimate potential for intrauterine repair of skeletal anomalies in man.

Animals↗

Surgical approaches in fetal radiography and the study of skeletal age in Macaca mulatta.

The fetal surgery and fetal radiography utilized in longitudinal radiographic study of bone maturation in Macaca mulatta and their implications for fetal surgery are discussed. The novel technique of serial uterotomies and multiple exposure of the same fetus (two-week intervals) starting on 120 days of gestation as well as anesthesia and surgical procedures are presented.

Abortion, Veterinary↗

Estimation of gestational and skeletal age in Macaca mulatta.

Results of qualitative and quantitative studies of prenatal skeletal development in Macaca mulatta are presented. Longitudinal radiographic observations were carried out on 20 monkeys of known gestational age, beginning on 120 days of gestation until the neonatal stage of skeletal development. These studies were based on multiple uterotomies on each pregnant female. The technique described provides accurate data on prenatal bone ossification, and permits an accurate estimation of fetal age in pregnant rhesus monkeys with unknown conception dates.

Age Determination by Skeleton↗

Hemodynamic effects of corticotropin releasing hormone in the anesthetized cynomolgus monkey.

Right atrial bolus administration of rat/human corticotropin releasing hormone (r/hCRH) at a dose of 90 micrograms/kg to anesthetized cynomolgus monkeys caused a dramatic and prolonged fall in both the peripheral vascular resistance (48% reduction) and mean systemic blood pressure (36% reduction). An associated tachycardia could be blocked with prior propranolol administration and thus was probably reflexic. A mean 43 and 37% increase in the flow of the superior mesenteric and common iliac arteries, respectively, was demonstrated with electromagnetic flow probes. These changes were associated with a concomitant 38 and 40% diminution in the respective vascular resistance. Similar blood flow changes were noted in the carotid artery, however, these were of a much shorter duration. None of these changes occurred in placebo-treated animals. Plasma adrenocorticotropic hormone and cortisol concentrations were elevated basally and throughout the procedure and were similar in the experimental and control groups, suggesting maximal activity of the hypothalamic-pituitary-adrenal axis. Plasma renin activity, however, gradually increased in the r/hCRH-treated animals, probably as a result of the systemic hypotension. We speculate that CRH or a CRH-like substance may function as a paracrine hormone modulating local blood vessel tone and may be important in directing blood flow during stress and injury. The vasoactive properties of exogenous r/hCRH may be of clinical use in man.

Animals↗

Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts.

To determine the potential for the use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, we investigated its activity and pharmacokinetics in models of acute, subacute, and chronic forms of disseminated candidiasis in persistently granulocytopenic rabbits. Fluconazole was administered for systemic prophylaxis, early treatment, and delayed treatment. Single-dose and steady-state plasma pharmacokinetics, tissue penetration, and dose-response studies of the investigational compound were studied in subacutely infected granulocytopenic rabbits. Fluconazole was more effective when used for systemic prophylaxis or early treatment of disseminated candidiasis than for delayed treatment. Fluconazole was as effective as amphotericin B plus flucytosine in preventive and early treatment of disseminated candidiasis but was significantly less effective than amphotericin plus flucytosine in the treatment of chronic candidiasis. Dose-response studies demonstrated that the antifungal effect of fluconazole was dose- and time-dependent. Studies of the pharmacokinetics of fluconazole in rabbits demonstrated a long half-life in plasma and a large volume of distribution, properties that correspond to the attainment of high levels of penetration into tissues at multiple organ sites. We conclude that fluconazole is effective for prevention and early treatment of disseminated candidiasis in persistently granulocytopenic rabbits and that the evaluation of its use in preventive or early treatment of disseminated candidiasis in carefully designed clinical trials is warranted.

Acute Disease↗

Functional and anatomic recovery in the monkey brain following excision of fetal encephalocele.

Teratogen-induced herniation of the occipital lobes (encephalocele) in monkey fetuses was repaired by amputation and cranioplasty in utero or postnatally. The in utero-treated animals had normal vision, CT scans indicated normal brain density, and autoradiographic visualization of the striate cortex by the [14C]-2-deoxyglucose mapping revealed almost complete functional and anatomic recovery. The animals treated postnatally were blind, and exhibited significant structural deficit in the operated area.

Age Factors↗