Subject(s)
Cannabis/toxicity , Food/toxicity , Marijuana Use/legislation & jurisprudence , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Child, Preschool , Emergency Service, Hospital/statistics & numerical data , Humans , Infant , Marijuana Smoking/adverse effects , Marijuana Smoking/legislation & jurisprudence , Marijuana Use/adverse effects , Michigan/epidemiology , Middle Aged , Retrospective Studies , Young AdultABSTRACT
INTRODUCTION: Chlorine gas is a known irritant of the respiratory tract, which may cause damage to various systems depending on time of exposure and concentration of the gas. Current treatments are mainly supportive. While no definitive studies have been completed to date, it has been noted that treatment with a sodium bicarbonate solution via nebulizer may lead to improved outcomes for patients dealing with chlorine gas exposure. CASE REPORT: We present a case of a nine-year-old child arriving at the emergency department after exposure to chlorine gas. Complete recovery from his symptoms occurred rapidly with the administration of nebulized sodium bicarbonate. DISCUSSION: Inhaled chlorine gas acts as a mucous membrane irritant, with symptoms usually beginning within minutes of exposure. Inhaled nebulized sodium bicarbonate has been suggested as a therapy for chlorine exposure. Although its mechanism of action is not well understood, it is thought that inhaled sodium bicarbonate neutralizes the hydrochloric acid formed when the chlorine gas reacts with the water in the lungs. CONCLUSION: Nebulized sodium bicarbonate solution at a low concentration appeared to rapidly and effectively reverse the symptoms due to chlorine gas inhalation in a young child.
Subject(s)
Antitussive Agents/toxicity , Dextromethorphan/toxicity , Drug Misuse/adverse effects , Substance-Related Disorders/complications , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Drug Misuse/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Infant , Male , Michigan/epidemiology , Middle Aged , Retrospective Studies , Substance-Related Disorders/epidemiology , Young AdultABSTRACT
N, N-diethyl-meta-toluamide (DEET) is an insect repellent currently used by millions of people since 1956. DEET has an excellent safety profile and has remarkable protection against mosquitoes, ticks and various other arthropods. Toxicity is unusual, and is generally associated with incorrect, or overuse of the product. We report a patient with severe toxicity following inhalational exposure to a "bug bomb". containing 98% DEET.
Subject(s)
DEET/poisoning , Inhalation Exposure/adverse effects , Insect Repellents/poisoning , Aged , Humans , MaleSubject(s)
Coercion , Rape/statistics & numerical data , Wounds and Injuries/etiology , Adolescent , Adult , Alcohol Drinking/epidemiology , Child , Female , Humans , Rape/legislation & jurisprudence , Substance-Related Disorders/epidemiology , United States , Vulnerable Populations , Wounds and Injuries/epidemiology , Young AdultABSTRACT
OBJECTIVE: High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. METHODS: We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo. We also examined the effect of oral l-Phe administration on glucose tolerance in rats. RESULTS: Oral administration of l-Phe acutely reduced food intake in rats and mice, and chronically reduced food intake and body weight in diet-induced obese mice. Ileal l-Phe also reduced food intake in rats. l-Phe stimulated GLP-1 and PYY release, and reduced plasma ghrelin, and also stimulated insulin release and improved glucose tolerance in rats. Pharmacological blockade of the CaSR attenuated the anorectic effect of intra-ileal l-Phe in rats, and l-Phe-induced GLP-1 release from STC-1 and primary L cells was attenuated by CaSR blockade. CONCLUSIONS: l-Phe reduced food intake, stimulated GLP-1 and PYY release, and reduced plasma ghrelin in rodents. Our data provide evidence that the anorectic effects of l-Phe are mediated via the CaSR, and suggest that l-Phe and the CaSR system in the GI tract may have therapeutic utility in the treatment of obesity and diabetes. Further work is required to determine the physiological role of the CaSR in protein sensing in the gut, and the role of this system in humans.
Subject(s)
Appetite Depressants/pharmacology , Appetite Regulation/drug effects , Gastrointestinal Hormones/metabolism , Glucose Intolerance , Phenylalanine/pharmacology , Receptors, Calcium-Sensing/metabolism , Satiation/drug effects , Animals , Appetite Depressants/administration & dosage , Disease Models, Animal , Eating/drug effects , Energy Metabolism , Male , Mice , Mice, Inbred C57BL , Phenylalanine/administration & dosage , Rats , Rats, Wistar , Receptors, Gastrointestinal Hormone/metabolismABSTRACT
BACKGROUND: Whole-gland extirpation or irradiation is considered the gold standard for curative oncological treatment for localized prostate cancer, but is often associated with sexual and urinary impairment that adversely affects quality of life. This has led to increased interest in developing therapies with effective cancer control but less morbidity. We aimed to provide details of physician consensus on patient selection for prostate focal therapy (FT) in the era of contemporary prostate cancer management. METHODS: We undertook a four-stage Delphi consensus project among a panel of 47 international experts in prostate FT. Data on three main domains (role of biopsy/imaging, disease and patient factors) were collected in three iterative rounds of online questionnaires and feedback. Consensus was defined as agreement in ⩾80% of physicians. Finally, an in-person meeting was attended by a core group of 16 experts to review the data and formulate the consensus statement. RESULTS: Consensus was obtained in 16 of 18 subdomains. Multiparametric magnetic resonance imaging (mpMRI) is a standard imaging tool for patient selection for FT. In the presence of an mpMRI-suspicious lesion, histological confirmation is necessary prior to FT. In addition, systematic biopsy remains necessary to assess mpMRI-negative areas. However, adequate criteria for systematic biopsy remains indeterminate. FT can be recommended in D'Amico low-/intermediate-risk cancer including Gleason 4+3. Gleason 3+4 cancer, where localized, discrete and of favorable size represents the ideal case for FT. Tumor foci <1.5 ml on mpMRI or <20% of the prostate are suitable for FT, or up to 3 ml or 25% if localized to one hemi-gland. Gleason 3+3 at one core 1mm is acceptable in the untreated area. Preservation of sexual function is an important goal, but lack of erectile function should not exclude a patient from FT. CONCLUSIONS: This consensus provides a contemporary insight into expert opinion of patient selection for FT of clinically localized prostate cancer.
Subject(s)
Patient Selection , Prostatic Neoplasms/radiotherapy , Humans , Male , Prostatic Neoplasms/diagnostic imagingABSTRACT
PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.
Subject(s)
Consensus , Delphi Technique , Prostatic Neoplasms/therapy , Quality of Life , Combined Modality Therapy/standards , Humans , Male , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Surveys and QuestionnairesABSTRACT
AIMS: To investigate the anorectic effect of L-arginine (L-Arg) in rodents. METHODS: We investigated the effects of L-Arg on food intake, and the role of the anorectic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), the G-protein-coupled receptor family C group 6 member A (GPRC6A) and the vagus nerve in mediating these effects in rodents. RESULTS: Oral gavage of L-Arg reduced food intake in rodents, and chronically reduced cumulative food intake in diet-induced obese mice. Lack of the GPRC6A in mice and subdiaphragmatic vagal deafferentation in rats did not influence these anorectic effects. L-Arg stimulated GLP-1 and PYY release in vitro and in vivo. Pharmacological blockade of GLP-1 and PYY receptors did not influence the anorectic effect of L-Arg. L-Arg-mediated PYY release modulated net ion transport across the gut mucosa. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration of L-Arg suppressed food intake in rats. CONCLUSIONS: L-Arg reduced food intake and stimulated gut hormone release in rodents. The anorectic effect of L-Arg is unlikely to be mediated by GLP-1 and PYY, does not require GPRC6A signalling and is not mediated via the vagus. I.c.v. and i.p. administration of L-Arg suppressed food intake in rats, suggesting that L-Arg may act on the brain to influence food intake. Further work is required to determine the mechanisms by which L-Arg suppresses food intake and its utility in the treatment of obesity.
Subject(s)
Appetite Depressants/therapeutic use , Arginine/therapeutic use , Dietary Supplements , Gastrointestinal Agents/therapeutic use , Glucagon-Like Peptide 1/agonists , Obesity/diet therapy , Peptide YY/agonists , Animals , Appetite Depressants/administration & dosage , Appetite Depressants/adverse effects , Appetite Depressants/pharmacology , Arginine/administration & dosage , Arginine/adverse effects , Cells, Cultured , Dietary Supplements/adverse effects , Energy Intake/drug effects , Energy Metabolism/drug effects , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/adverse effects , Gastrointestinal Agents/pharmacology , Glucagon-Like Peptide 1/blood , Glucagon-Like Peptide 1/metabolism , In Vitro Techniques , Injections, Intraperitoneal , Injections, Intraventricular , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Mice, Inbred C57BL , Mice, Knockout , Obesity/drug therapy , Obesity/metabolism , Obesity/pathology , Peptide YY/blood , Peptide YY/metabolism , Random Allocation , Rats, Wistar , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Weight Loss/drug effectsABSTRACT
A shortcut review was carried out to establish whether intravenous lidocaine is effective in the management of renal colic. Two studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these studies are tabulated. The clinical bottom line is that intravenous lidocaine may be of some benefit in renal colic. However, there are other maybe more effective drugs available.
Subject(s)
Administration, Intravenous , Lidocaine/pharmacology , Renal Colic/drug therapy , Analgesics/pharmacology , Analgesics/therapeutic use , Emergency Service, Hospital/organization & administration , Humans , Lidocaine/therapeutic useABSTRACT
Kisspeptin plays a critical role in pubertal timing and reproductive function. In rodents, kisspeptin perikarya within the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV) nuclei are thought to be involved in LH pulse and surge generation, respectively. Using bilateral microinjections of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC or AVPV of female rats at postnatal day 10, we investigated the relative importance of these two kisspeptin populations in the control of pubertal timing, estrous cyclicity, and LH surge and pulse generation. A 37% knockdown of kisspeptin in the AVPV resulted in a significant delay in vaginal opening and first vaginal estrous, abnormal estrous cyclicity, and reduction in the occurrence of spontaneous LH surges, although these retained normal amplitude. This AVPV knockdown had no effect on LH pulse frequency, measured after ovariectomy. A 32% reduction of kisspeptin in the ARC had no effect on the onset of puberty but resulted in abnormal estrous cyclicity and decreased LH pulse frequency. Additionally, the knockdown of kisspeptin in the ARC decreased the amplitude but not the incidence of LH surges. These results might suggest that the role of AVPV kisspeptin in the control of pubertal timing is particularly sensitive to perturbation. In accordance with our previous studies, ARC kisspeptin signaling was critical for normal pulsatile LH secretion in female rats. Despite the widely reported role of AVPV kisspeptin neurons in LH surge generation, this study suggests that both AVPV and ARC populations are essential for normal LH surges and estrous cyclicity.
Subject(s)
Arcuate Nucleus of Hypothalamus/metabolism , Estrous Cycle/genetics , Hypothalamus, Anterior/metabolism , Kisspeptins/genetics , Neurons/metabolism , Puberty/genetics , Sexual Maturation/genetics , Animals , Arcuate Nucleus of Hypothalamus/cytology , Estrous Cycle/metabolism , Female , Gene Knockdown Techniques , Hypothalamus, Anterior/cytology , Kisspeptins/metabolism , Luteinizing Hormone/metabolism , Neurons/cytology , Puberty/metabolism , RatsABSTRACT
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief and Authors. We wish to retract the abstract "The Virtual Cutting Edge: Adolescent Self-injury and YouTube," published in the October 2015 issue of Annals. The abstract excessively borrowed from the text and methodology of a previous study published elsewhere.1 All authors recognize the seriousness of this issue and apologize to the editors and readers of Annals. Jeffrey S. Jones, MD Chad Garthe, MD Lindsey Ouellette, MS Jason Seamon, DO Department of Emergency Medicine MSU College of Human Medicine Grand Rapids, MI 1. Lewis SP, Heath NL, St. Denis JM, et al. The scope of nonsuicidal self-injury on YouTube. Pediatrics. 2011;1127:e552-e557.
ABSTRACT
A shortcut review was carried out to establish whether intraoral ultrasound increased the accuracy of diagnosis and the success of aspiration in adults with suspected peritonsillar abscess (quinsy). Using the reported searches, one paper presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. It is concluded that emergency physician-performed intraoral ultrasound can reliably diagnose peritonsillar abscess and leads to greater success at aspiration when compared with the traditional landmark technique.
Subject(s)
Drainage/methods , Mouth/diagnostic imaging , Peritonsillar Abscess/diagnostic imaging , Peritonsillar Abscess/therapy , Ultrasonography, Doppler/methods , Adult , Anti-Bacterial Agents/therapeutic use , Emergency Service, Hospital , Evidence-Based Emergency Medicine , Female , Humans , Peritonsillar Abscess/diagnosis , Sensitivity and SpecificityABSTRACT
Kisspeptin plays a pivotal role in pubertal onset and reproductive function. In rodents, kisspeptin perikarya are located in 2 major populations: the anteroventral periventricular nucleus and the hypothalamic arcuate nucleus (ARC). These nuclei are believed to play functionally distinct roles in the control of reproduction. The anteroventral periventricular nucleus population is thought to be critical in the generation of the LH surge. However, the physiological role played by the ARC kisspeptin neurons remains to be fully elucidated. We used bilateral stereotactic injection of recombinant adeno-associated virus encoding kisspeptin antisense into the ARC of adult female rats to investigate the physiological role of kisspeptin neurons in this nucleus. Female rats with kisspeptin knockdown in the ARC displayed a significantly reduced number of both regular and complete oestrous cycles and significantly longer cycles over the 100-day period of the study. Further, kisspeptin knockdown in the ARC resulted in a decrease in LH pulse frequency. These data suggest that maintenance of ARC-kisspeptin levels is essential for normal pulsatile LH release and oestrous cyclicity.
Subject(s)
Arcuate Nucleus of Hypothalamus/cytology , Gene Expression Regulation , Kisspeptins/physiology , Neurons/metabolism , Reproduction/physiology , Animals , Estradiol/metabolism , Estrous Cycle , Feedback, Physiological , Female , Green Fluorescent Proteins/metabolism , Immunoassay , Kisspeptins/genetics , Luteinizing Hormone/metabolism , Oligonucleotides, Antisense/genetics , Rats , Rats, Wistar , Recombinant Proteins/genetics , Time FactorsABSTRACT
INTRODUCTION: The outcomes associated with therapeutic hypothermia (TH) after cardiac arrest, while overwhelmingly positive, may be associated with adverse events. The incidence of post-rewarming rebound hyperthermia (RH) has been relatively unstudied and may worsen survival and neurologic outcome. The purpose of this study was to determine the incidence and risk factors associated with RH as well as its relationship to mortality, neurologic morbidity, and hospital length of stay (LOS). METHODS: A retrospective, observational study was performed of adult patients who underwent therapeutic hypothermia after an out-of-hospital cardiac arrest. Data describing 17 potential risk factors for RH were collected. The primary outcome was the incidence of RH while the secondary outcomes were mortality, discharge neurologic status, and LOS. RESULTS: 141 patients were included. All 17 risk factors for RH were analyzed and no potential risk factors were found to be significant at a univariate level. 40.4% of patients without RH experienced any cause of death during the initial hospitalization compared to 64.3% patients who experienced RH (OR: 2.66; 95% CI: 1.26-5.61; p=0.011). The presence of RH is not associated with an increase in LOS (10.67 days vs. 9.45 days; absolute risk increase=-1.21 days, 95% CI: -1.84 to 4.27; p=0.434). RH is associated with increased neurologic morbidity (p=0.011). CONCLUSIONS: While no potential risk factors for RH were identified, RH is a marker for increased mortality and worsened neurologic morbidity in cardiac arrest patients who have underwent TH.
Subject(s)
Cardiopulmonary Resuscitation/methods , Fever/physiopathology , Hypothermia, Induced/methods , Out-of-Hospital Cardiac Arrest/therapy , Rewarming/adverse effects , Adult , Age Factors , Aged , Analysis of Variance , Cardiopulmonary Resuscitation/mortality , Cohort Studies , Combined Modality Therapy , Female , Fever/etiology , Fever/mortality , Follow-Up Studies , Hospital Mortality/trends , Humans , Length of Stay , Male , Middle Aged , Nervous System Diseases/etiology , Nervous System Diseases/mortality , Nervous System Diseases/physiopathology , Out-of-Hospital Cardiac Arrest/mortality , Retrospective Studies , Risk Assessment , Sex Factors , Statistics, Nonparametric , Survival Rate , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Musculoskeletal pain is common after motor vehicle collision (MVC). The study objective was to evaluate distribution of pain and predictors of widespread musculoskeletal pain in the early aftermath (within 48 h) of collision. METHODS: European American adults aged 18-65 years presenting to the emergency department (ED) after collision who were discharged to home after evaluation were eligible. Evaluation included an assessment of reported pre-collision psychological characteristics, crash characteristics, current pain severity and location, and current psychological symptoms. Adjusted risk ratios were estimated using generalized linear models. RESULTS: Among 890 participants included in the study, 589/890 (66%) had pain in three or more regions, and 192/890 (22%) had widespread musculoskeletal pain (pain in seven or more regions). In adjusted analyses, the presence of widespread pain was strongly associated with depressive and somatic symptoms prior to collision, pain catastrophizing, and acute psychological symptoms, and was not associated with most collision characteristics (road speed limit, extent of vehicle damage, collision type, driver vs. passenger, airbag deployment). The reported number of body regions that struck an object during the collision was associated with both reported pre-collision depressive symptoms and with widespread pain. CONCLUSION: More than one in five individuals presenting to the ED in the hours after MVC have widespread pain. Widespread pain is strongly associated with patient characteristics known to be modulated by supraspinal mechanisms, suggesting that stress-induced hyperalgesia may influence acute widespread pain after collision.
Subject(s)
Accidents, Traffic/psychology , Musculoskeletal Pain/psychology , Pain/psychology , Adolescent , Adult , Aged , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Male , Middle Aged , Motor Vehicles , Musculoskeletal Pain/physiopathology , Young AdultABSTRACT
Neurokinin B (NKB) and its receptor (NK3R) are coexpressed with kisspeptin, Dynorphin A (Dyn), and their receptors [G-protein-coupled receptor-54 (GPR54)] and κ-opioid receptor (KOR), respectively] within kisspeptin/NKB/Dyn (KNDy) neurons in the hypothalamic arcuate nucleus (ARC), the proposed site of the GnRH pulse generator. Much previous research has employed intracerebroventricular (icv) administration of KNDy agonists and antagonists to address the functions of KNDy neurons. We performed a series of in vivo neuropharmacological experiments aiming to determine the role of NKB/NK3R signaling in modulating the GnRH pulse generator and elucidate the interaction between KNDy neuropeptide signaling systems, targeting our interventions to ARC KNDy neurons. First, we investigated the effect of intra-ARC administration of the selective NK3R agonist, senktide, on pulsatile LH secretion using a frequent automated serial sampling method to obtain blood samples from freely moving ovariectomized 17ß-estradiol-replaced rats. Our results show that senktide suppresses LH pulses in a dose-dependent manner. Intra-ARC administration of U50488, a selective KOR agonist, also caused a dose-dependent, albeit more modest, decrease in LH pulse frequency. Thus we tested the hypothesis that Dyn/KOR signaling localized to the ARC mediates the senktide-induced suppression of the LH pulse by profiling pulsatile LH secretion in response to senktide in rats pretreated with nor-binaltorphimine, a selective KOR antagonist. We show that nor-binaltorphimine blocks the senktide-induced suppression of pulsatile LH secretion but does not affect LH pulse frequency per se. In order to address the effects of acute activation of ARC NK3R, we quantified (using quantitative RT-PCR) changes in mRNA levels of KNDy-associated genes in hypothalamic micropunches following intra-ARC administration of senktide. Senktide down-regulated expression of genes encoding GnRH and GPR54 (GNRH1 and Kiss1r, respectively), but did not affect the expression of Kiss1 (which encodes kisspeptin). We conclude that NKB suppresses the GnRH pulse generator in a KOR-dependent fashion and regulates gene expression in GnRH neurons.
Subject(s)
Arcuate Nucleus of Hypothalamus/metabolism , Gonadotropin-Releasing Hormone/metabolism , Peptide Fragments/pharmacology , Preoptic Area/metabolism , Receptors, Neurokinin-3/agonists , Receptors, Opioid, kappa/metabolism , Substance P/analogs & derivatives , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Estradiol/blood , Estrous Cycle/drug effects , Estrous Cycle/metabolism , Gonadotropin-Releasing Hormone/genetics , Kisspeptins/genetics , Kisspeptins/metabolism , Luteinizing Hormone/metabolism , Neurokinin B , Preoptic Area/drug effects , Rats , Rats, Sprague-Dawley , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Receptors, Kisspeptin-1 , Substance P/pharmacologyABSTRACT
The bed nucleus of the stria terminalis (BNST) occupies a central position in the neural circuitry regulating the hypothalamic-pituitary-adrenocortical axis response to stress. The potential role of the BNST in stress-induced suppression of the gondotrophin-releasing hormone (GnRH) pulse generator, the central regulator of the reproductive system, was assessed by examining the effects of micro-infusion of corticotrophin-releasing factor (CRF) or its antagonist into the BNST on pulsatile luteinising hormone (LH) secretion or stress-induced inhibition of LH pulses, respectively. Ovariectomised oestrogen-treated rats were implanted chronically with bilateral cannulae in the dorsolateral BNST and i.v. catheters. CRF (25, 50 or 100 pmol in 200 nl of artificial cerebrospinal fluid) administered bilaterally into the BNST resulted in a dose-dependent decrease in LH pulse frequency, and induced Fos expression in glutamic acid decarboxylase immunostained neurones in the medial preoptic area. These results suggest that the activation of hypothalamic GABAergic neurones in response to intra-BNST administration of CRF may be involved in the suppression of LH pulses. Furthermore, administration of CRF antagonist (280 pmol astressin-B, three times at 20-min intervals) into the BNST effectively blocked the suppression of pulsatile LH secretion in response to restraint (1 h) but not hypoglycaemic (0.25 U insulin/kg, i.v.) stress. These data suggest that CRF innervation of the dorsolateral BNST plays a key, but differential, role in stress-induced suppression of the GnRH pulse generator.
Subject(s)
Luteinizing Hormone/antagonists & inhibitors , Septal Nuclei/physiology , Animals , Female , Immunohistochemistry , Luteinizing Hormone/metabolism , Luteinizing Hormone/physiology , Rats , Rats, Sprague-DawleyABSTRACT
Puberty is a developmental process that is dependent upon activation of the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator. It is well established that the stress neuropeptide, corticotrophin-releasing factor (CRF), has a profound inhibitory action on GnRH pulse generator frequency. Although stress is known to affect the timing of puberty, the role of CRF is unknown. The present study aimed to test the hypothesis that CRF plays a critical role in the timing of puberty. On postnatal day (pnd) 28, female rat pups were chronically implanted with i.c.v. cannulae and received 14 days of administration of either CRF, CRF receptor antagonist (astressin-B) or artificial cerebrospinal fluid via an osmotic mini-pump. A separate group of rats served as nonsurgical controls. As a marker of puberty, rats were monitored for vaginal opening and first vaginal oestrus. Levels of CRF, CRF receptor types 1 and 2 (CRF-R1, CRF-R2) mRNA expression in micropunches of the medial preoptic area (mPOA), hypothalamic paraventricular nucleus (PVN) and arcuate nucleus (ARC) were determined across pubertal development; brain tissue was collected from a naive group of rats on pnd 14, 32, on the day of vaginal opening, and pnd 77 (Adult). Administration of CRF resulted in a delay in the onset of puberty, whereas astressin-B advanced pubertal onset. Additionally, CRF and CRF-R1 mRNA expression was reduced in the mPOA, but not ARC, at puberty. In the PVN, expression of CRF, but not CRF-R1 mRNA, was reduced at the time of puberty. These data support the hypothesis that CRF signalling may play an important role in modulating the timing of puberty in the rat.