Amphetamines (AMPs) can cause long-term depletions in striatal dopamine (DA) and serotonin (5-HT), and these decrements are often accepted as prima facie evidence of AMP-induced damage to the dopaminergic and serotonergic projections to striatum. Rarely are indices linked to neural damage used to evaluate the neurotoxicity of the AMPs. Here, we determined the potential neurotoxic effects of two substituted AMPs, d-methylenedioxymethamphetamine (d-MDMA) and d-fenfluramine (d-FEN) in group-housed female C57BL6/J mice. Astrogliosis, assessed by quantification of glial fibrillary acidic protein (GFAP), was the main indicator of d-MDMA-induced neural damage. Assays of tyrosine hydroxylase (TH), DA, and 5-HT were used to determine effects on DA and 5-HT systems. Since AMPs are noted for both their stimulatory and hyperthermia-inducing properties, activity, as well as core temperature, was monitored in several experiments. To extend the generality of our findings, these same end points were examined in singly housed female C57bL6/J mice and in group-housed male C57BL6/J or female B6C3F1 mice after treatment with d-MDMA. Mice received either d-MDMA (20 mg/kg) (singly housed mice received dosages of 20, 30, or 40 mg/kg) or d-FEN (25 mg/kg) every 2 h for a total of four sc injections. d-MDMA caused hyperthermia, whereas d-FEN induced hypothermia. d-MDMA cause a large (300%) increase in striatal GFAP that resolved by 3 wk and a 50-75% decrease in TH and DA that was still apparent at 3 wk, d-FEN did not affect any parameters in striatum. d-MDMA is a striatal dopaminergic neurotoxicant in both male and female C57BL6/mice, as evidenced by astrogliosis and depletions of DA in this area in both sexes. The greater lethality to males suggests they may be more sensitive, at least to the general toxicity of d-MDMA, that females. d-MDMA (20 mg/kg) induced the same degree of damage whether mice were housed singly or in groups. Higher dosages in singly housed mice induced greater lethality, but not greater neurotoxicity. d-MDMA was also effective in inducing striatal damage in mice of the B6C3F1 strain. Significant increases in activity were induced by d-MDMA, and these increases were not blocked by pretreatment with MK-801, despite the profound lowering of body temperature induced by this combination. A lowering of body temperature, whether by a 15 degree C ambient temperature (approx 2 degree drop), pretreatment with MK-801 (1.0 mg/kg prior to the first and third d-MDMA injections; approx 5-6 degrees C drop) or restraint (approx 5-6 degrees C drop) was effective in blocking the neurotoxicity of d-MDMA in both C57BL6/J and B6C3F1. The stimulatory effects of d-MDMA appeared to have little impact on the neurotoxicity induced by d-MDMA or the protection conferred by MK-801. These data suggest that in the mouse, the neurotoxic effects of d-MDMA, and most likly other AMPs, are linked to an effect on body temperature.

Animals↗

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Interoceptive conditioning through repeated suppression of morphine-abstinence. II. Relapse-testing.

The reinforcing properties of etonitazene, both conditioned and unconditioned, were measured in rats that had received saline only by continuous intravenous infusion ("saline" group) and in two groups of rats that had been physically dependent on morphine to equal degrees (and presumably had developed equal degrees of tolerance to morphine): one by once daily passive intravenous injection of morphine ("injection" group) and the other by passive continuous intravenous morphine infusion at the same daily doses for approximately the same number of days ("infusion" group). Prior to passive saline and morphine administration, all rats were trained to press right- and left-sided levers for water reinforcement from 1600 to 0800 hrs to a not more than 60-40 split, and these and other measures ("baselines") were repeated after recovery from the early (acute) morphine-abstinence syndromes. Then etonitazene, 5 micrograms/ml, was substituted for water on the nonpreferred side and all measures were repeated from 1600 to 0800 hrs once every two weeks for 20 weeks (10 "relapse" tests). It was postulated that the daily cycles of morphine-abstinence and suppression of abstinence in the injection group only would generate latent interoceptively conditioned reinforcing properties of morphine because of conditioning of suppression of abstinence to the concomitant internal sensorial effects of morphine, which would persist after morphine withdrawal and be transferred to the internal effects of another opioid, etonitazene. It was found that across the first nine relapse tests, the injection group consumed significantly more etonitazene than the infusion group, while there were no significant differences in water consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

The concentration of glial fibrillary acidic protein increases with age in the mouse and rat brain.

The role of aging in the expression of the astrocyte protein, glial fibrillary acidic protein (GFAP), was examined. In both mice and rats the concentration of GFAP increased throughout the brain as a function of aging. The largest increase (2-fold) was observed in striatum for both species. The neuron-specific proteins, synapsin I and neurofilament-200 (Mr 200 kilodaltons), were not altered by aging in any region of the mouse or rat brain. Brains of aged rats, but not mice, showed a decrease in beta-tubulin. The data suggest that astrocytic hypertrophy observed with aging involves an accumulation of glial filaments.

Aging↗

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Increased glial fibrillary acidic protein (GFAP) levels in the brains of transgenic mice expressing the bovine growth hormone (bGH) gene.

Transgenic mice, expressing the gene for bovine growth hormone (bGH), exhibit increased body size, reduced reproductive capacity, and high basal levels of several hormones including corticosterone. Their shortened life span may be indicative of accelerated aging. As prominent astrogliosis of the CNS accompanies aging in rodents, bGH transgenic mice were examined for astrogliosis, as quantified by an ELISA for the astrocyte-localized protein, glial fibrillary acidic protein (GFAP). Transgenic mice were produced by mating C57BL/6 x C3H F1 hybrid females with male descendants of animals produced by microinjection of fertilized eggs with phosphoenolpyruvate carboxykinase (PEPCK)/bGH-hybrid gene. Transgenic mice (approximately 3.5 and approximately 12 months of age) weighed significantly more than same age or older (approximately 20 month) controls. Most of their internal organs, including the heart, kidneys, adrenals, liver, and spleen, were also heavier. In contrast, the thymus was heavier only in the younger transgenic mice. Serum corticosterone was highest in the older transgenic mice. A small but significant increase in whole brain, cortex, and cerebellar weight, relative to controls and the older transgenic mice, was found in the younger transgenic mice. Control mice exhibited large, significant age-related increases in GFAP. Increases of 35, 70, 68, 89, 79, and 95% for cortex, cerebellum, striatum, hippocampus, midbrain, and brain stem, respectively, were found when comparing the oldest (approximately 20 months) control mice to the youngest (approximately 3.5 months). In contrast, in the olfactory bulbs and the hypothalamus there were no age-related changes in the levels of GFAP in control mice. Transgenic mice (approximately 3.5 months) had significantly elevated GFAP levels relative to the same-age controls in all brain areas examined. In some brain areas, the GFAP levels found in the younger transgenic mice were equivalent to those found in the oldest controls. No differences between controls and transgenics were found in tyrosine hydroxylase protein levels of striatum or hypothalamus. The elevated GFAP levels of transgenic mice may reflect increased neural damage due to accelerated aging processes or damage associated with high circulating levels of bGH or corticosterone. Alternatively, the increased expression of GFAP in the transgenic mice may reflect altered regulation of GFAP rather than an increase signaled by neural damage.

Aging↗

PubMedDate not supplied

Profile of a director of nursing service in long-term care.

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Administrative Personnel↗

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Editorial: Transfer agreements and how they don't work.

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Progressive Patient Care↗

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Arthroscopic meniscus repair.

From February 1982 through July 1987, the author studied 87 patients who had a total of 116 meniscus tears, 96 of which were repaired. Seventy patients (79 meniscus repairs) had postoperative followup ranging from 12 months to 5 1/2 years (mean, 39 months). The patients' ages ranged from 14 to 51 years with a mean age of 22. The time from injury to surgery ranged from 1 week to 6 years. Twenty-five percent of the injuries were considered acute, i.e., less than 6 weeks after the injury, and 75% of the injuries were considered chronic. Nineteen patients (27%) had isolated meniscus injuries. All meniscus repairs were done arthroscopically, using an inside-outside technique. Ligament stabilizing procedures were done on all patients who had ACL deficient knees. Forty-seven patients (67%) had postoperative documentation including either an arthroscopic examination or an arthrogram done an average of 5 to 6 months after surgery. There was one case of peroneal nerve palsy from which the patient made a complete recovery in 6 months. There was one case of infection/thrombophlebitis. One patient had paresthesia and numbness along the medial aspect of the left leg corresponding to a saphenous nerve injury. The aim of this investigation was two-fold, consisting of determining if an arthroscopic technique could be used successfully to repair acute as well as chronic vertical tears involving the meniscus, and also, evaluating the relationship between ACL stability and meniscus healing. The overall success rate of retained menisci following repair was 91%. The time from injury to repair did not affect meniscus healing. Associated stabilization of ACL deficiencies is imperative in patients undergoing meniscus repair.

Adolescent↗