Involvement of nicotinic acetylcholine receptors in the regulation of alcohol drinking in Wistar rats.
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The aim of the present study was to determine if nicotinic acetylcholine receptors (nAChRs) might be involved in the regulation of alcohol intake by Wistar rats. A non-selective nAChR agonist, nicotine, and a non-competitive nAChR antagonist, mecamylamine, were tested in alcohol-preferring Wistar rats maintained on a limited access (4 h/24 h) to ethanol (10%, v/v). In addition, the effects of nicotine and mecamylamine on intake of standard laboratory chow were studied in a separate control experiment. Nicotine (0.1-0.6 mg/kg, s.c.) decreased ethanol consumption, but had no effect on food intake. In contrast, mecamylamine (1-3 mg/kg, s.c.) did not alter ethanol drinking even at the dose (3 mg/kg) which significantly decreased food intake. These results suggest that activation of nAChRs may selectively reduce ethanol consumption in outbred Wistar rats. (+info)
Developmental changes in LH secretion by male pituitaries in vitro: from the infantile to adult period.
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The secretion of LH from the anterior pituitary of male rats was studied at different periods of postnatal development. According to an established classification we used rats 14 (infantile), 23 (juvenile), 45 (pubertal) and 90 (adult) days old. By using an in vitro incubation system, both basal and stimulated LH secretion were studied in the same gland. Age-related differences were observed in basal LH secretion, with juvenile and pubertal pituitaries showing higher secretion compared with infantile and adult pituitaries. However, the GnRH-induced secretory response was significantly higher in the infantile rats than in other ages. LH secretion was also studied in primary cultures from infantile or adult pituitaries. In 24 and 48 h cultures, infantile cells showed a significantly larger response to GnRH than that of adult cells. In the infantile pituitary LH-immunopositive cells showed differences in size at different locations in the gland. At the periphery of the lobes the predominant cells were smaller and angular shaped, whereas in the center of the gland the majority of the cells were ovoid shaped. In the adult pituitary, the predominant LH-positive cells were ovoid in shape and larger in size. Furthermore, 10% more LH-positive cells were observed in infantile pituitaries. On the basis of these data we propose that at the infantile period the male rat pituitary has two populations of LH-secreting cells, one with adult secretory function and shape and a second with increased sensitivity to GnRH and with a morphology atypical of the adult cell. The results presented support the hypothesis that the infantile period is a transitional stage in the rat pituitary development. (+info)
Demonstration of in vivo mammogenic and lactogenic effects of recombinant ovine placental lactogen and mammogenic effect of recombinant ovine GH in ewes during artificial induction of lactation.
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The present study demonstrates that ovine placental lactogen (oPL) (ovine chorionic somatotrophin) may have an important role in the mammogenesis and/or lactogenesis of the ewe. Its effects were compared with that already described for ovine growth hormone (oGH). In the first experiment, 40 nulliparous ewes were induced to lactate by means of a 7 day (days 1-7) oestro-progestative treatment (E2+P4). The ewes from Group 1 (n=12) received no further treatment, while those of the other groups received either recombinant oGH (roGH, 28 micrograms/kg, i.m., twice daily, Group 2, n=12) or recombinant oPL (roPL, 79 micrograms/kg, i.m., twice daily, Group 3, n=12) from day 11 to 20. All ewes received 25 mg hydrocortisone acetate (HC) twice daily on days 18-20. Control Group 00 (n=2) received no steroid treatment at all, and the control Group 0 (n=2) received only the E2+P4 treatment. Thirteen ewes (three from each experimental group and the two of each control group) were slaughtered at the end of hormone treatments (day 21) before any milking stimulus. The 27 remaining ewes from Groups 1-3 were machine-milked and milk yields recorded daily from day 21 to 76. The E2+P4 treatment enhanced the plasma levels of oPRL, oGH and IGF-I between days 1 and 7 by 1.5, 2. 3 and 2.6 times respectively (P=0.002); roGH treatment induced a highly significant enhancement of IGF-I plasma levels from day 11 to 20, whereas a similar effect appeared for roPL-treated ewes only from day 17 to 20 (P<0.01). Eight weeks after the last exogenous hormone injections, milk yields of both roGH- and roPL-treated groups progressively rose to twice that of unsupplemented groups (P<0.001). The mammary DNA content on day 21 was higher for animals which received either oGH or oPL but, due to individual variations in so few samples (n=3), this difference was not significant. No beta-casein was measured in mammary tissue from control ewes, whereas steroid-treated ewes (E2+P4+HC) had higher casein concentrations regardless of subsequent hormonal treatment on days 11-20 (P<0.001). beta-Casein concentrations in mammary parenchyma of roGH-treated ewes did not differ from that of ewes which received only E2+P4+HC; roPL supplementation clearly enhanced expression of beta-casein (P<0.001). IGF-I stimulation by either roGH or roPL was more precisely examined during a second experiment, in which two twice-daily i.m. doses (58 or 116 micrograms/kg) of either roGH or roPL were administered to four groups of six ewes that were E2+P4 treated as those of Experiment 1. A control group (n=6) received no exogenous hormone from day 11 to 13. On day 13, hourly blood samples were taken from all ewes over 11 h. Both doses of roGH significantly stimulated IGF-I in a dose-dependent manner. The 58 micrograms/kg dose of roPL did not significantly stimulate IGF-I, but although being somewhat less efficient than the 58 micrograms/kg dose of roGH, the 116 micrograms/kg dose of roPL significantly stimulated IGF-I secretion (P<0. 001). These results suggest that mammogenesis and/or lactogenesis in the ewe is in part controlled by somatotrophic hormones such as oGH and oPL and that IGF-I could be one of the mediators of these hormones. (+info)
Insulin-secreting activity of the traditional antidiabetic plant Viscum album (mistletoe).
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Viscum album (mistletoe) has been documented as a traditional treatment of diabetes. In acute 20-min tests, 1-10 mg/ml aqueous extract of mistletoe evoked a stepwise 1.1- to 12.2-fold stimulation of insulin secretion from clonal pancreatic B-cells. This effect was abolished by 0.5 mM diazoxide and prior exposure to extract did not alter subsequent stimulation of insulin secretion induced by 10 mM L-alanine, thereby negating a detrimental effect on cell viability. The insulin-releasing effect of mistletoe extract was unaltered by 16.7 mM glucose, l-alanine (10 mM), 3-isobutyl-1-methylxanthine (IBMX) (1 mM), or a depolarising concentration of KCl (25 mM). The ability of extract to enhance insulin secretion did not depend upon the use of heat during extract preparation and was not mediated by lectins. These results demonstrate the presence of insulin-releasing natural product(s) in Viscum album which may contribute to the reported antidiabetic property of the plant. (+info)
Stimulation of Na,K-ATPase by hypothyroidism in the thyroid gland.
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Although studies have documented the regulatory effects of thyroid hormones on the Na,K-ATPase in peripheral tissues, there is little information on the regulation of this transporter in the thyroid gland itself. Accordingly, we investigated the effects of thyroid status on Na,K-ATPase specific activity and the abundance of its constituent subunits in rat thyroid. Exogenous tri-iodothyronine (T3) was administered daily to produce hyperthyroidism. 6n-propyl-2-thiouracil (PTU), an inhibitor of thyroid hormone synthesis, was used to induce hypothyroidism. There was a four-fold increase in Na,K-ATPase specific activity in the follicular membranes from PTU-treated animals after 7 days. Enzymatic activities were not changed in the T3-treated glands. Immunoblotting of membranes from T3-treated rats revealed a 75% reduction in alpha1 subunit abundance and a slight, but nonsignificant reduction in beta1 abundance. On the other hand, the membranes from PTU-treated rats displayed 136 and 567% increases in the abundance of the alpha1 and beta1 subunits respectively. These data demonstrate that thyroid hormone status regulates Na,K-ATPase in the gland, but the effects are in direct contrast to those seen in the periphery. (+info)
Reduced health-related quality of life among Hodgkin's disease survivors: a comparative study with general population norms.
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BACKGROUND: Late complications after curative treatment of Hodgkin's disease are of special relevance because most of the cured are young adults. The aims of the present study were: (1) to compare health-related quality of life (HRQOL) in Hodgkin's disease (HD) survivors with normative data from the general Norwegian population and (2) to examine the relations between disease/treatment characteristics and HRQOL in the HD survivors. PATIENTS AND METHODS: 459 HD survivors aged 19-74 years (mean 44.0, SD 11.8) treated at the Norwegian Radium Hospital 1971-1991 were approached in 1994 and compared to norms from 2214 subjects approached in 1996. The norms are representative of the general Norwegian population. HRQOL was assessed by the Short Form 36 (SF-36), which measures HRQOL in eight separate scales (0 = worst health state, 100 = best health state). RESULTS: The HD survivors had lower scores than the normal controls on all scales after adjustment for age, gender and educational levels. Statistically significant differences (P < 0.01) were found in general health (10.4), physical functioning (6.1), role limitations (physical, 9.3), physical functioning (3.6) and in vitality (4.7). Patients with disease stage IB-IIB had the lowest scores on all scales. The differences in relation to stage/substage reached statistical significance (P < 0.01) in physical functioning and in role limitations (physical). Time since diagnosis, types of primary treatment or having relapsed were not associated with statistically significant differences in HRQOL. CONCLUSION: Long-term HD survivors have poorer HRQOL, primarily in physical health, than the general Norwegian population. (+info)
Developing hypothalamic dopaminergic neurones as potential targets for environmental estrogens.
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Environmental chemicals which mimic the actions of estrogen have the potential to affect any estrogen responsive tissue. The aim of the present study was to investigate their potential to mimic the effects of 17beta-estradiol (E2) on developing primary rat hypothalamic dopaminergic (DA) neurones maintained in a chemically defined medium. We now show that both E2 and octylphenol (OP), but not the non-aromatizable androgen, dihydrotestosterone, enhanced the uptake of [3H]DA by the cultured cells, whereas they had no effect on the uptake of [14C]GABA. Although the sensitivity of responses may change with the age of the developing cultures, the dose response curves for E2 and OP were typically 'bell-shaped', with a rise in response followed by a decline to control levels with increasing concentrations. Effects were seen as low as 10(-14) M for E2 and 10(-11) M for OP. Responses to E2 (10(-12) M) and OP (10(-9) M) were reversed in the presence of the antiestrogen, ZM 182780 (10(-5) M). This study thus provides direct evidence, using a mechanistic rather than toxicological end-point, in support of the hypothesis that inappropriate exposure to environmental estrogens at critically sensitive stages of development, could potentially perturb the organisational activities of estrogen on selected neuronal populations in the CNS. (+info)
Superiority of ibutilide (a new class III agent) over DL-sotalol in converting atrial flutter and atrial fibrillation. The Ibutilide/Sotalol Comparator Study Group.
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OBJECTIVE: To compare the efficacy and safety of a single dose of ibutilide, a new class III antiarrhythmic drug, with that of DL-sotalol in terminating chronic atrial fibrillation or flutter in haemodynamically stable patients. DESIGN: Double blind, randomised study. SETTING: 43 European hospitals. PATIENTS: 308 patients (mean age 60 years, 70% men, 48% with heart disease) with sustained atrial fibrillation (n = 251) or atrial flutter (n = 57) (duration three hours to 45 days) were randomised to three groups to receive a 10 minute infusion of 1 mg ibutilide (n = 99), 2 mg ibutilide (n = 106), or 1.5 mg/kg DL-sotalol (n = 103). Infusion was discontinued at termination of the arrhythmia. MAIN OUTCOME MEASURE: Successful conversion of atrial fibrillation or flutter, defined as termination of arrhythmia within one hour of treatment. RESULTS: Both drugs were more effective against atrial flutter than against atrial fibrillation. Ibutilide was superior to DL-sotalol for treating atrial flutter (70% and 56% v 19%), while the high dose of ibutilide was more effective for treating atrial fibrillation than DL-sotalol (44% v 11%) and the lower dose of ibutilide (44% v 20%, p < 0.01). The mean (SD) time to arrhythmia termination was 13 (7) minutes with 2 mg ibutilide, 19 (15) minutes with 1 mg ibutilide, and 25 (17) minutes with DL-sotalol. In all patients, the duration of arrhythmia before treatment was a predictor of arrhythmia termination, although this was less obvious in the group that received 2 mg ibutilide. This dose converted almost 48% of atrial fibrillation that was present for more than 30 days. Concomitant use of digitalis or nifedipine and prolongation of the QTc interval were not predictive of arrhythmia termination. Bradycardia (6.5%) and hypotension (3.7%) were more common side effects with DL-sotalol. Of 211 patients given ibutilide, two (0.9%) who received the higher dose developed polymorphic ventricular tachycardia, one of whom required direct current cardioversion. CONCLUSION: Ibutilide (given in 1 or 2 mg doses over 10 minutes) is highly effective for rapidly terminating persistent atrial fibrillation or atrial flutter. This new class III drug, under monitored conditions, is a potential alternative to currently available cardioversion options. (+info)