Neuromedin B stimulates the hypothalamic-pituitary-gonadal axis in male rats.

Neuromedin B (NMB) is a highly conserved bombesin-related peptide found in mammals. NMB mRNA is detected in the central nervous system (CNS) and is highly expressed in the rat hypothalamus, in particular the medial preoptic area and the arcuate nucleus. The mammalian bombesin family of receptors consists of three closely related G protein coupled receptors, BB1, BB2 and BB3. The BB1 receptor subtype has the highest affinity for NMB. NMB has well documented roles in the regulation of the thyroid axis and the stress axis in rats. However, there is little available data regarding the role of NMB in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. It is known that the NMB receptor is expressed in immortalised gonadotrophin releasing hormone (GnRH) releasing GT1-7 cells and murine forebrain GnRH neurons, and that anterior pituitary NMB-immunoreactivity is altered by changes in the sex steroid environment. The objective of these studies was thus to further investigate the effects of NMB on the HPG axis. Intracerebroventricular (ICV) administration of NMB (10 nmol) to adult male rats significantly increased plasma luteinising hormone (LH) levels 30 min after injection (plasma LH ng/ml; saline 0.69±0.07, 10 nmol NMB 1.33±0.17, P<0.01). In vitro, NMB stimulated GnRH release from hypothalamic explants from male rats and from hypothalamic GT1-7 cells. NMB had no significant effect on LH release from anterior pituitary explants from male rats, or from pituitary LßT2 cells in vitro. These results suggest a previously unreported role for NMB in the stimulation of the HPG axis via hypothalamic GnRH. Further work is now required to determine the receptor mediating the effects of NMB on the reproductive axis and the physiological role of NMB in reproduction.

Code status discussions and goals of care among hospitalised adults.

BACKGROUND AND OBJECTIVE: Code status discussions may fail to address patients' treatment-related goals and their knowledge of cardiopulmonary resuscitation (CPR). This study aimed to investigate patients' resuscitation preferences, knowledge of CPR and goals of care. Design, setting, patients and measurements: 135 adults were interviewed within 48 h of admission to a general medical service in an academic medical centre, querying code status preferences, knowledge about CPR and its outcome probabilities and goals of care. Medical records were reviewed for clinical information and code status documentation. RESULTS: 41 (30.4%) patients had discussed CPR with their doctor, 116 (85.9%) patients preferred full code status and 11 (8.1%) patients expressed code status preferences different from the code status documented in their medical record. When queried about seven possible goals of care, patients affirmed an average of 4.9 goals; their single most important goals were broadly distributed, ranging from being cured (n = 36; 26.7%) to being comfortable (n = 8; 5.9%). Patients' mean estimate of survival to discharge after CPR was 60.4%. Most patients believed it was helpful to discuss goals of care (n = 95; 70.4%) and the chances of surviving in hospital CPR (n = 112; 83.0%). Some patients expressed a desire to change their code status after receiving information about survival following in hospital CPR (n = 11; 8.1%) or after discussing goals of care (n = 2; 1.5%). CONCLUSIONS: Doctors need to address patients' knowledge about CPR and take steps to avoid discrepancies between treatment orders and patients' preferences. Addressing CPR outcome probabilities and goals of care during code status discussions may improve patients' knowledge and influence their preferences.

Kisspeptin-54 at high doses acutely induces testicular degeneration in adult male rats via central mechanisms.

BACKGROUND AND PURPOSE: The kisspeptins are critical regulators of reproduction and a therapeutic target for reproductive disease. Intracerebroventricular (i.c.v.) or peripheral injection of kisspeptin potently stimulates the hypothalamic-pituitary gonadal (HPG) axis via gonadotrophin-releasing hormone (GnRH). However, little is known regarding the effects of kisspeptin administration on testicular function. We investigated the mechanism(s) of kisspeptin-induced testicular degeneration in the rat. EXPERIMENTAL APPROACH: Kisspeptin-54 (50 nmol.day(-1)) was continuously administered subcutaneously (6 h to 3 days) to male Wistar rats and reproductive hormones and testicular histology analysed. We also investigated the effects of a single subcutaneous injection of 0.5, 5 or 50 nmol kisspeptin-54. In order to determine whether the testicular degeneration observed is peripherally or centrally mediated, we investigated effects of i.c.v. injections of 5 nmol kisspeptin-54 and pre-administered a GnRH-receptor antagonist (cetrorelix) to rats peripherally treated with kisspeptin-54. KEY RESULTS: Continuous subcutaneous administration of kisspeptin-54 caused testicular degeneration after only 12 h, when gonadotrophins were still markedly raised, suggesting that the degeneration is independent of the desensitization of the HPG axis to kisspeptin-54. Furthermore, a single subcutaneous injection of kisspeptin-54 caused dose-dependent testicular degeneration. Continuous kisspeptin-54 administration is thus not required to cause testicular degeneration. Pretreatment with cetrorelix blocked kisspeptin-induced testicular degeneration, and a single i.c.v. injection of kisspeptin-54 caused testicular degeneration, suggesting it is GnRH-mediated. CONCLUSIONS AND IMPLICATIONS: Kisspeptin-induced testicular degeneration appears to be centrally mediated, and result from acute hyper-stimulation of the HPG axis. Doses must be carefully considered if kisspeptin is to be used therapeutically.

Effects of "binge" pattern cocaine on stereotypy and locomotor activity in C57BL/6J and 129/J mice.

This study characterized the behavioral response to cocaine in two strains of mice, the C57BL/6J and 129/J strains, commonly utilized as host strains for transgenic and "knockout" mice. The psychomotor stimulating effects of four doses of cocaine (2.5, 5.0, 10.0, and 15.0 mg/kg/injection) with a saline control, administered in a "binge" pattern (three equal injections at hourly intervals) for 3 days were examined in adult male C57BL/6J and 129/J mice. Behavioral stereotypy in the home cage, was rated 15, 30, and 45 min following each injection. Spontaneous locomotor activity in the home cage was also monitored. Cocaine, at doses of 10.0 or 15.0 mg/kg, produced behavioral stereotypy in both C57BL/6J mice (p < 0.0001) and 129/J mice (p < 0.0001), whereas lower doses did not. The magnitude of stereotypy was significantly lower in 129/J mice than in C57BL/6J mice receiving identical doses of cocaine. C57BL/6J mice also demonstrated a dose-dependent cocaine-induced stimulation of locomotor activity following administration of 10.0 or 15.0 mg/kg of cocaine (p < 0.0005). In contrast, 129/J mice did not exhibit increased locomotion in response to any dose of cocaine tested. These results demonstrate that strain differences in drug-induced behavior may be more pronounced in one measure (i.e., locomotor activity) than in another (i.e., stereotypy) and indicate the importance of multiple behavioral measures.

Quality of life of oncology hospice patients: a comparison of patient and primary caregiver reports.

Promoting quality of life is a major goal of hospice nursing. Because family primary caregivers (PCGs) are responsible for and interact closely with patients, they greatly influence patients' quality of life. Disparities between patient and primary caregiver views may reflect misunderstanding, leading to inadequate symptom control, dissatisfaction with the caregiver role, and diminished psychological and physical well-being for both. This descriptive study compared patient and PCG views of the quality of life of hospice patients with cancer. A convenience sample of 23 patient-PCG pairs, selected from a home-based hospice, completed the Quality of Life Index (QLI). Computation of two-tailed paired t tests revealed that, with the exception of pain, there was no statistically significant difference between patient and PCG responses. Patients acknowledged significantly less pain than their PCGs reported for them. This difference has important clinical implications because effective pain control, a critical component of quality of life, is best achieved when patients and primary caregivers share a common perception of the patients' pain experience.