Role of allopregnanolone on cerebellar granule cells neurogenesis.

The role of allopregnanolone on immature cerebellar granule cells (CGC) proliferation was studied. Allopregnanolone (0.1-1 microM) increased [(3)H]thymidine incorporation and cell number determined by neuronal counting and by an MTT colorimetric assay. The effect of the neurosteroid was completely prevented by preincubation with 10 mM MgCl(2), 10 microM nifedipine, 10 microM picrotoxin or by 50 microM bicuculine. We conclude that ALLO affects cerebellar neurogenesis by increasing calcium influx through voltage-gated calcium channels and GABA(A) receptors activation.

A comparison of Guatemalan and USA nurses' attitudes towards nursing.

BACKGROUND: Student nurses from the United States of America (USA) spent 5 weeks working with Guatemalan nurses in an acute care setting in Guatemala. This experience led to a heightened awareness of the global scope of nurses' discontent and a desire to better understand the driving factors and drawbacks to practising nursing in both the USA and Guatemala. AIM: The purpose of this research was to identify those factors that discourage nurses and those that motivate nurses to continue in their practice despite the drawbacks. METHOD: Qualitative interviews using field notes were conducted with five Guatemalan and five USA nurses. Themes were derived through qualitative content analysis. FINDINGS: Nurses in both the USA and Guatemala had similar reasons for choosing and staying in nursing. The different health care systems presented different problems resulting in different discontents. CONCLUSION: The two groups of nurses had much in common, especially in their reasons for staying in nursing. The Guatemalan nurses were most discontent with the lack of resources to treat patients, while the USA nurses focused on work environment drawbacks. IMPLICATIONS FOR PRACTICE: Strategies to support nurses and nursing in developing countries need to be developed and implemented. As nurses reach out to their colleagues in other nations, understanding our commonalities and differences will help us to support each other in improving health throughout the world.

Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic rats.

The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water; 35.2+/-7.8 ml/100 g body weight mean daily dose) as a drinking-water substitute for about 1 month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats were investigated. The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum triglycerides and cholesterol, plasma glucose, urinary glucose and urea, and the weight of epididymal and retroperitoneal adipose tissue and soleus and extensor digitorum longus muscles. The STZ-diabetic rats treated with decoction showed a significant reduction in serum and urinary glucose and urinary urea as compared to the STZ-diabetic control, no difference being seen between decoction-treated and -untreated non-diabetic rats. The other physico-metabolic factors showed no changes in treated STZ-diabetic rats. The improvement in carbohydrate metabolism seen in the rats treated with Bauhinia forficata decoction does not appear to be linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor does it appear to act in a way similar to insulin or the sulfonylureas, although it may act by the inhibition of neoglycogenesis in a manner similar to that of the biguanides.

[Critical involvement of the specific neuroendocrine profile for an adequate T-dependent immune response]. / El perfil neuroendocrino específico es crítico para una correcta respuesta inmune T-dependiente.

A functional relationship between the neuroendocrine and immune systems has been clearly established. We examined the role of neuroendocrine changes, particularly thyrotropin-releasing hormone (TRH) and prolactin (PRL), during the T cell-dependent immune response. After immunization of rats with sheep red blood cells (SRBC, a T cell-dependent antigen) we observed: a) an increase of hypothalamic TRH mRNA at 4 to 24 h post-immunization (i.e.: SRBC vs saline: 4 h, 2.8x), in contrast to the decrease of TRH mRNA observed following treatment with LPS, a T-independent antigen (LPS vs saline: 4 h, 1.6x); b) an increase in pituitary TRH receptor mRNA and plasma PRL levels but no changes in thyroid-stimulating hormone and growth hormone plasma levels. Intracerebroventricular (icv) injection in conscious freely-moving rats of antisense oligonucleotide complementary to rat TRH mRNA resulted in: a) a significant inhibition of specific antibody production [ELISA 7 days: Ig(M/G): TRH sense vs TRH-antisense: 384 +/- 27 (n = 11) vs 193 +/- 22 (n = 11); p < 0.001]b) an inability to produce the peak in plasma PRL levels in rats immunized with SRBC [(12h post-immunization, TRH-sense vs TRH-antisense: 8.3 +/- 1.4 (n = 6) vs 2.2 +/- 0.5 (n = 6); p < 0.01]; c) a decrease in hypothalamic TRH mRNA (TRH-sense vs TRH-antisense: 12h, 1.7x). These studies demonstrate that the T-cell antigen needs an early activation of TRH and PRL for an adequate immune response, in contrast to the inhibition induced by a T-cell independent antigen.

Opiate agonist-induced changes in behavioral sensitivity to clonidine are observed in perinatally malnourished rats exposed to chronic stress.

Sensitivity of alpha2-adrenoceptors following repeated immobilization sessions plus morphine (MOR) or beta-endorphin (BETA) was assayed by examining clonidine (CLO)-induced hypoactivity in adult malnourished rats at perinatal age. As previously described, chronic restraint did not attenuate the hypoactivity elicited by CLO in malnourished rats, although chronic restraint did have such an effect on motor activity in control animals. MOR and BETA administration prior to each restraint session induced subsensitivity of alpha2-adrenoceptors in malnourished rats as determined by a blunted response to clonidine challenge. An injection of naloxone (NAL) prior to BETA before each stress session fully antagonized the subsensitivity to clonidine observed in malnourished animals. A possible deficiency in the functional role of the opiate system in the process of adaptation to chronic stress in perinatal malnourished rats is suggested.

Analgesic response to stress is reduced in perinatally undernourished rats.

Stress-induced analgesia was evaluated in adult rats submitted early in life to a protein deprivation schedule. Rats were undernourished with a hypoproteic diet containing 80 g casein/kg diet from d 14 of gestation until 50 days of age. Rats were thereafter fed a balanced nonpurified diet until 140 days of age, when they were exposed to two stressors: forced swimming and acute restraint, after which the analgesic response was evaluated. In addition, the analgesic response induced by different morphine doses was determined in another group of rats. Basal latency was not different in deprived and control rats. Undernourished rats presented a significantly lower analgesic response in both stress situations. However, when the analgesic response induced by different morphine doses (1, 2, 4 and 8 mg/kg, s.c.) was assessed, a significantly higher response occurred in undernourished rats compared to control rats. This lower stress-induced analgesia in undernourished rats may account for the behavioral alterations attributed to early undernutrition.

Effect of perinatal malnutrition on the inactive behavior induced by long-term shock and conditioned analgesia.

Inactive behavior in response to long-term inescapable foot shock (IS) and conditioned analgesia were evaluated in adult rats perinatally undernourished. During the IS session, control rats exhibited first a period of vigorous activity and then inactive behavior, during which they accepted the shock more passively. Moreover, when these same animals were subsequently placed in the environment associated with shock application, they showed an increase in the paw lick latency. Conversely, in malnourished rats, this IS schedule induced lower behavioral inactivity and rats failed to develop conditioned analgesia. When undernourished rats were injected with morphine (MOR) before IS exposure, it was observed that both phenomena--inactivity during shock and analgesia conditioned by submission to the shock context--were normalized. A possible alteration in the activation of an opiate process implicated in the stress response in early undernourished rats is suggested.

Evaluation of diagnostic criteria for analgesic nephropathy in patients with end-stage renal failure: results of the ANNE study. Analgesic Nephropathy Network of Europe.

It was found that in Belgium, renal imaging techniques, demonstrating a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications, were the only methods to reliably diagnose analgesic nephropathy (AN) in patients with end-stage renal failure. However, these criteria were selected in an area with a high prevalence of this disease (15.6% of the dialysis population at December 1990). To evaluate the criteria selected to diagnose AN in populations with lower or unknown prevalences of AN, the Analgesic Nephropathy Network of Europe (ANNE) was formed, consisting of 23 dialysis units from 14 European countries and Brazil. During 1991-1992, 598 new patients with equivocal diagnosis of renal disease (excluding biopsy-proven glomerulonephritis, polycystic disease, diabetic nephropathy and other systemic diseases) and who began renal replacement therapy in the ANNE centres were evaluated by a short questionnaire and two renal imaging techniques: sonography and either tomography or computed tomography (CT) scan. A comparison of 82 abusers (daily use of analgesic mixtures for at least 5 years) and 495 controls corroborated the excellent diagnostic performance of the renal imaging techniques for AN. We recommend the use of these renal imaging criteria in all patients without a clear renal diagnosis in order to obtain a more reliable insight into the magnitude of the AN problem in different countries.

Lack of adaptive changes in 5-HT sites in perinatally undernourished rats after chronic stress: opioid influence.

The reactivity of 5-HT receptors following repeated immobilization sessions or after immobilization plus morphine was measured through 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) or 8-hydroxy-2-(dipropyl-amino)tetralin (8-OH-DPAT)-induced serotonergic syndrome in adult rats undernourished at perinatal age. Repeated stress enhanced the scores of forepaw treading and hindlimb abduction elicited by 5-MeODMT in control animals. In a similar way, forepaw treading induced by 8-OH-DPAT was enhanced in chronically stressed control rats. These results indicate the development of supersensitivity in 5-HT1 receptors. Conversely, this effect was not observed in undernourished animals. Morphine injections before each stress session instaured the increased reactivity to 5-HT1 sites in malnourished animals. An injection of naloxone prior to morphine before each stress session fully antagonized the increased behavioral reactivity to 5-MeODMT observed in deprived animals. A possible deficiency in the functional role of the opiate system involved in the process of adaptation to chronic stress in early undernourished rats is suggested.

Gangliosides facilitate the recovery of behavioral response mediated by dopaminergic sites following their irreversible blockade.

The effect of acute and chronic exogenous ganglioside (G) administration on the functional recovery of dopaminergic receptors following their blockade by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was investigated by means of apomorphine (APO)-induced stereotyped behavior. Animals previously treated with EEDQ exhibited a lack of behavioral response to APO 6 or 24 h later. A progressive behavioral recovery was already evident at day 3 and reached control values at day 7. G pretreatment accelerated the behavioral recovery after EEDQ administration, because a higher behavioral response to APO in these animals as compared with rats treated with EEDQ alone at the same time was observed. These findings indicate that G accelerates the functional recovery of dopaminergic sites following their irreversible blockade.

The learning capacity of high or low performance rats is related to the hippocampus NMDA receptors.

The hippocampal synaptic plasticity of rats with an inborn high (HP) or low (LP) learning capacity to perform in a shuttle box is closely related to their percentage of conditioned responses (Crs). HP rats show less sensitivity to the blocking effect of 2-aminophosphonopentanoic acid (AP5) on the generation of long-term potentiation (LTP) than do LP rats. Results described in the present report are indicative of an increased density of N-methyl-D-aspartate (NMDA) receptors in HP rats compared to control and LP rats. We postulate that the differential pharmacological sensitivity of LTP in these rats is a reflection of this biochemical difference. Also, from these results we suggest that the learning capacity may be related to the density of glutamate NMDA receptors of HP, LP and control rats.

Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult rats.

Adult offsprings of Wistar female rats treated during pregnancy (days 1-20) with nicotine (1 mg/kg s.c.,b.i.d.), were tested in order to detect possible alterations in the reactivity of the cardiovascular system to sympathetic agonists. Dose-response curves to the pressor response of noradrenaline (NA) did not show any differences between control and experimental animals. However, cumulative dose-response curves to the chronotropic effect of NA on isolated atria were significantly shifted to the right in nicotine prenatal treated rats than in controls. Accordingly, 3H-dihydroalprenolol binding was significantly reduced in hearts of experimental animals as compared with controls, without any change in affinity. These data demonstrate long lasting deleterious effects induced by prenatal nicotine exposure, probably resulting from alterations in the sympathetic system during the developing stage.

Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult rats.

Adult offsprings of Wistar female rats treated during pregnancy (days 1-20) with nicotine (1 mg/kg s.c.,b.i.d.), were tested in order to detect possible alterations in the reactivity of the cardiovascular system to sympathetic agonists. Dose-response curves to the pressor response of noradrenaline (NA) did not show any differences between control and experimental animals. However, cumulative dose-response curves to the chronotropic effect of NA on isolated atria were significantly shifted to the right in nicotine prenatal treated rats than in controls. Accordingly, 3H-dihydroalprenolol binding was significantly reduced in hearts of experimental animals as compared with controls, without any change in affinity. These data demonstrate long lasting deleterious effects induced by prenatal nicotine exposure, probably resulting from alterations in the sympathetic system during the developing stage.

Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult rats.

Adult offsprings of Wistar female rats treated during pregnancy (days 1-20) with nicotine (1 mg/kg s.c.,b.i.d.), were tested in order to detect possible alterations in the reactivity of the cardiovascular system to sympathetic agonists. Dose-response curves to the pressor response of noradrenaline (NA) did not show any differences between control and experimental animals. However, cumulative dose-response curves to the chronotropic effect of NA on isolated atria were significantly shifted to the right in nicotine prenatal treated rats than in controls. Accordingly, 3H-dihydroalprenolol binding was significantly reduced in hearts of experimental animals as compared with controls, without any change in affinity. These data demonstrate long lasting deleterious effects induced by prenatal nicotine exposure, probably resulting from alterations in the sympathetic system during the developing stage.

Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult rats

Adult offsprings of Wistar female rats treated during pregnancy (days 1-20) with nicotine (1 mg/kg s.c.,b.i.d.), were tested in order to detect possible alterations in the reactivity of the cardiovascular system to sympathetic agonists. Dose-response curves to the pressor response of noradrenaline (NA) did not show any differences between control and experimental animals. However, cumulative dose-response curves to the chronotropic effect of NA on isolated atria were significantly shifted to the right in nicotine prenatal treated rats than in controls. Accordingly, 3H-dihydroalprenolol binding was significantly reduced in hearts of experimental animals as compared with controls, without any change in affinity. These data demonstrate long lasting deleterious effects induced by prenatal nicotine exposure, probably resulting from alterations in the sympathetic system during the developing stage.

Prenatal nicotine exposure induces cardiac adrenergic subsensitivity in adult rats

Adult offsprings of Wistar female rats treated during pregnancy (days 1-20) with nicotine (1 mg/kg s.c.,b.i.d.), were tested in order to detect possible alterations in the reactivity of the cardiovascular system to sympathetic agonists. Dose-response curves to the pressor response of noradrenaline (NA) did not show any differences between control and experimental animals. However, cumulative dose-response curves to the chronotropic effect of NA on isolated atria were significantly shifted to the right in nicotine prenatal treated rats than in controls. Accordingly, 3H-dihydroalprenolol binding was significantly reduced in hearts of experimental animals as compared with controls, without any change in affinity. These data demonstrate long lasting deleterious effects induced by prenatal nicotine exposure, probably resulting from alterations in the sympathetic system during the developing stage.

Lack of neuronal adaptive changes following chronic treatments in perinatally undernourished rats.

Reactivity of presynaptic dopaminergic and alpha 2-adrenoceptors following repeated stress or desipramine treatment was investigated by means of apomorphine (APO)- or clonidine (CLO)-induced hypoactivity, respectively, in adult rats undernourished at perinatal age. Under basal conditions, a comparable hypoactive response was observed in control and experimental animals following either APO or CLO administration. Chronic DMI or repeated immobilization sessions attenuated the hypoactivity elicited by APO or CLO in control animals; however, this effect was not observed in experimental rats. These findings demonstrate that deprived animals show impairment to produce neuronal adaptive changes in response to appropriate stimuli, which may account for the behavioral alterations attributed to early undernutrition.

Perinatal undernutrition affects brain modulatory capacity of beta-adrenergic receptors in adult rats.

Rats submitted to a protein deprivation schedule from the perinatal period until 50 d of age (dams and/or rats fed an 8% casein diet) and then fed a commercial nonpurified diet for at least 90 d were assayed to evaluate the up- and down-regulation of beta-adrenergic receptors in brain structures following prolonged (7 d) treatment with propranolol or desipramine, drugs that induce changes in receptor density. Propranolol produced up-regulation (increased Bmax) in the frontal cortex of both control and deprived animals, whereas desipramine treatment did not induce down-regulation in the frontal cortex or hippocampus of experimental rats, as it did in control rats. The lack of the down-regulation effect in response to desipramine treatment in deprived rats may be an alteration of adaptive mechanisms, which may contribute to the behavioral abnormalities attributed to early undernutrition.

Effect of chronic variable stress on monoamine receptors: influence of imipramine administration.

Adult male rats were exposed to a series of unpredictable stressors, a paradigm considered to be a model of experimental depression, with or without concurrent administration of imipramine. One day after the last stress event of the chronic regime, binding of cortical beta-adrenoreceptors and the behavioral serotonin (5-HT) syndrome induced by 5-methoxy-N,N,dimethyltryptamine (5-MeODMT) were determined in all the experimental groups. Stressed rats showed an "up-regulation" of cortical beta-adrenergic sites, while similar values to control rats were observed when stressed animals were administered imipramine. Regarding the behavioral 5-HT syndrome, comparable behavioral scores were observed between controls and chronically stressed rats. The combination of chronic exposure to different stressors with imipramine treatment resulted in a significant increase of forepaw treading and Straub tail scores. The probable facilitation of behavioral deficits induced by this scheme of chronic stress and the recovery following concurrent administration of imipramine are discussed.

Gangliosides enhance behavioral and neurochemical effects induced by chronic desipramine (DMI) treatment.

Rats pretreated with gangliosides showed a significant enhancement of the anti-immobility effect of desipramine (DMI) in the forced swimming test. Accordingly, an associated treatment of gangliosides and DMI for 7 days significantly enhanced beta-adrenergic down-regulation in the frontal cortex as compared with the effect of DMI alone. Gangliosides exerted an accelerating effect on the decrease of beta-adrenoceptor density induced by DMI, since the down-regulation phenomenon appeared after 3 days of treatment. Gangliosides did not affect the pharmacokinetics of DMI, since associated acute or prolonged treatments did not modify the brain levels of DMI as compared to the levels of animals that had received DMI alone. These results evidence a stimulating effect of gangliosides on the development of adaptative receptor changes induced by chronic DMI treatment.