Effects of growth hormone on neuroendocrine function

Although the role of growth hormone (GH) in the control of reproductive functions is not well understood, there is considerable evidence that the states of both GH deficiency and GH excess are typically associated with reproductive deficits. To identify the possible involvement of functional alterations in the hypothalamic-pituitary system in producing these deficits, we are studying neuroendocrine function related to reproduction in transgenic animals overexpressing GH, in animals with congenital GH deficiency, and in animals with selective immunoneutralization of GH. The results indicate that GH acts on the hypothalamus to alter dopaminergic and noradrenergic control of prolactin and gonadotropin release. Life-long elevation of GH levels outside the physiological ranges disrupts feedback control of luteinizing hormone (LH) release by gonadal streroids. Plasma LH and follicle-stimulating hormone (FSH) levels and feedback control of LH release are also abnormal in GH-deficient animals indicating that physiological levels of endogenous GH are normally involved in the control of gonadotropin release. Differences between the effects of bovine vs. human GH in transgenic mice and differential effects of GH deficiency in mice and rats should facilitate identification of the mechanisms involved in the actions of GH on the hypothalamic-pituitary system.     

Effects of nitric oxide on neuroendocrine function and behavior

Nitric oxide (NO) is an unusual chemical messenger. NO mediates blood vessel relaxation when produced by endothelial cells. When produced by macrophages, NO contributes to the cytotoxic function of these immune cells. NO also functions as a neurotransmitter and neuromodulator in the central and peripheral nervous systems. The effects on blood vessel tone and neuronal function form the basis for an important role of NO on neuroendocrine function and behavior. NO mediates hypothalamic portal blood flow and, thus, affects oxytocin and vasopression secretion; furthermore, NO mediates neuroendocrine function in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes. NO influences several motivated behaviors including sexual, aggressive, and ingestive behaviors. Learning and memory are also influenced by NO. Taken together, NO is emerging as an important chemical mediator of neuroendocrine function and behavior.     

Effect of pancreatic ductal and parenchymal changes on exocrine function in chronic pancreatitis

The effect of pancreatic ductal and parenchymal changes on exocrine pancreatic function was analyzed prospectively in 75 patients with chronic pancreatitis (CP). Endoscopic retrograde pancreatography (ERP), computed tomography (CT), and serum pancreolauryl test (PLT) were performed to evaluate the degree of ductal, parenchymal, and functional changes, respectively. Results were evaluated by stepwise multivariate logistic regression and are expressed as the odds ratio (OR). A strong association was found between the degree of ductal changes in ERP and the degree of exocrine functional impairment (OR = 5.8). However, the association between the degree of parenchymal changes in CT and the degree of pancreatic dysfunction was weaker and was clearly confounded by the degree of ductal changes. On the basis of these findings, we suggest that the development of exocrine pancreatic functional impairment in patients with CP depends primarily on the degree of ductal changes, while parenchymal abnormalities play a less important role.     

Effect on verapamil on ventricular function: studies in denervated human heart

Verapamil has complex influences on ventricular function owing to its direct myocardial effects, vasodilation, and reflex activation of the sympathetic nervous system. To investigate the direct myocardial effects of verapamil in humans independent of reflex sympathetic stimulation, we administered the drug to 13 recent heart transplant recipients with denervated ventricles. Hemodynamics and radionuclide angiograms were recorded at baseline, with altered loading conditions, and after intravenous (i.v.) verapamil (median dose 4 mg). Left ventricular (LV) systolic and diastolic function was analyzed by systolic pressure-volume relations (SPVR) and peak filling rate (PFR), respectively. Verapamil caused a decrease in blood pressure (BP) and heart rate (HR) with increases in right atrial pressure (RAP 6 +/- 3-8 +/- 3, p < 0.01) and pulmonary artery wedge pressure (PAWP, 9 +/- 3-11 +/- 3 mm Hg, p < 0.01) pressures. LV ejection fraction (EF) decreased (69 +/- 7-66 +/- 8%, p < 0.02) in association with an increase in LV end-systolic counts (3.45 +/- 1.27 to 4.72 +/- 1.78 kcts, p < 0.001). In 11 of 13 patients, the SPV point after verapamil administration was decreased from the line established during altered loading conditions. PFR (4.05 +/- 0.81 to 4.11 +/- 0.76 EDV/s) was unchanged. In the denervated ventricle, verapamil has negative chronotropic and inotropic effects with minimal effects on PFR.     

Effects of suprachiasmatic transplants on circadian rhythms of neuroendocrine function in golden hamsters

A number of kinetic measurements of peptide dissociation from class II MHC-peptide complexes provide compelling evidence for the existence of conformational isomers in solution. There is evidence that T-lymphocytes can distinguish such isomers. However, virtually nothing is known about the structure of these isomers. Accordingly, we have investigated a water-soluble version of the murine class II MHC molecule I-Ek complexed with an antigenic peptide derived from pigeon cytochrome c residues 89-104 (PCC) by 19F-NMR. Two fluorine labels were placed on the PCC peptide; one fluorine label was placed at a MHC contact site, the other at a position involved in T-cell receptor (TCR) recognition. Introduction of these labels did not alter the observed kinetics of the PCC/I-Ek complex. The NMR data show two conformational isomers of this immunogenic complex. The presence of conformational isomers at a TCR contact site suggests that these structures may be recognized differently by the TCR. The agreement between the dissociation kinetics and the 19F-NMR data demonstrate that kinetic heterogeneity is correlated with structural counterparts observed by NMR. Dissociations in the presence of dimethyl sulfoxide were used to show that the rate of interconversion of these conformational isomers at pH 7.0 is low, with a lifetime on the order of hours or more. Modification of a peptide residue of PCC occupying the minor MHC binding pocket P6 alters the 19F-NMR spectra of both labels. This demonstrates that distant changes of amino acid residues can influence the conformation of the whole antigenic peptide inside the MHC binding cleft.     

Parental reports of seasonal mood and behavior changes in children

This paper reviews the therapeutics of migraine in the context of the clinical problem and its prevalence. General principles of pharmacotherapy for symptomatic and preventive medications are provided. Two new drugs, sumatriptan (recommended for acute symptomatic therapy), and valproic acid (recommended for migraine prevention), are reviewed. The clinical effectiveness and the mechanisms of action of these drugs are discussed.     

Effect of distension and feeding on phasic changes in human proximal gastric tone

BACKGROUND: Proximal stomach by virtue of its property of accommodation acts as a reservoir for the ingested food, but its role in emptying and the factors modulating it remain unexplored. AIM: To assess the effects of distension and of feeding on proximal gastric tone. SUBJECTS: 14 healthy volunteers with no current or past history of any gastro-intestinal symptoms. METHODS: Isobaric changes in volume of the proximal stomach were recorded both during fasting and for the first 30 minutes after a meal. RESULTS: For a given degree of distension, the mean (SEM) intragastric pressure was consistently lower, immediately after meal ingestion (9.8 (1.1), mm Hg) than during fasting (12.9 (0.6) mm Hg; p < 0.01). Proximal gastric tone was continuously variable with a frequency of fluctuation of 0.9-1.3/minute and an amplitude of 16.8 (2.2) ml, superimposed upon slower higher amplitude fluctuations in baseline tone. These variations in tone were unaffected by the degree of gastric distension or by food. CONCLUSIONS: While proximal gastric tone decreases after meal ingestions consistent with accommodation, the fluctuations in tone are not an importance factor in the modulation of nutrient emptying from the proximal stomach in the immediate postprandial period.     

Effect of restricted daylength during the growing period on semen quality and fertility of turkey toms

Two trials were conducted in which three daylength and light intensity treatments were applied to 144 growing turkey toms from 8 to 28 weeks of age. Treatments were (1) six hours of artificial light, (2) natural light and daylength, and (3) simulated natural daylength. At 28 weeks of age all toms were placed on 14 hours of daily light. Individual tom semen quality was evaluated every two weeks for six months, and on alternate weeks, eight hens were inseminated with semen pooled by treatment replicate to obtain fertility (May to December). Seasonal decline in semen production, sperm concentration, semen volume, and fertility was observed for toms on natural daylength after three months of production. Toms on six hours of light and those on simulated natural light maintained high levels of production and quality for the entire six month period. Semen production expressed as the average number of toms producing semen, sperm concentration, and fertily were significantly lower (P less than .01), and semen volume was significantly lower (P less than .05) for toms on natural light after six months. It was concluded that natural light was less desirable than controlled light for "off season" growing of toms.     

Effect of ethanol on monocytic function in human immunodeficiency virus type 1 infection

We have developed a novel system to study monocytic function after human immunodeficiency virus type 1 (HIV-1) infection by infecting a series of human macrophage hybridoma cell lines with HIV-1. Since ethanol has detrimental effects on immune function, we investigated the effect of ethanol and its metabolites acetaldehyde and acetate on monocytic function by utilizing one human macrophage hybridoma cell line, clone 43, as well as primary monocytes. Pretreatment of clone 43 and primary monocytes with ethanol and its metabolites resulted in diminished accessory cell function for mitogen-, anti-CD3-, and antigen-induced T-cell proliferation. The decreased accessory cell function was associated with reduced interleukin 1alpha (IL-1alpha), IL-1beta, and tumor necrosis factor alpha production with loss of intracellular cytokine and mRNA production and the induction of transforming growth factor beta. In ethanol-, acetaldehyde-, and acetate-treated HIV-1-infected clone 43 cells (43HIV), there was a more rapid loss (3 days after infection) of accessory cell function at a lower infecting dose of HIV-1 than that in untreated 43HIV cells. We also observed a more rapid loss of surface class II antigen expression in the ethanol-, acetaldehyde-, and acetate-treated 43HIV cells, but no change in surface expression of CD80 or CD86. Ethanol-induced impairment of monocytic function may compound the immunologic defects of AIDS, making the infected individual more susceptible to the complications of the disease.     

Effect of fexofenadine on eosinophil-induced changes in epithelial permeability and cytokine release from nasal epithelial cells of patients with seasonal allergic rhinitis

Recent studies have suggested that antihistamines, widely used in the treatment of symptoms of patients with allergic rhinitis, may also possess antiinflammatory properties. The mechanisms underlying this property, however, are not clearly understood. We have cultured epithelial cells from nasal biopsy specimens from patients with seasonal allergic rhinitis outside the pollen season and studied the effect of 0 to 10(-3) mol/L fexofenadine, the main active metabolite of terfenadine, on eosinophil-induced changes in electrical resistance (measure of permeability) and release of proinflammatory mediators from these cells. Additionally, we have studied the effect of this drug on eosinophil chemotaxis and adherence to endothelial cells induced by conditioned medium from these human nasal epithelial cell (HNEC) cultures. Incubation of HNEC in the presence of eosinophils treated with opsonized latex beads significantly decreased the electrical resistance of these cultures, an effect that was abrogated by treatment of the cultures with 10(-9) to 10(-3) mol/L fexofenadine. Similarly, incubation of HNEC in the presence of eosinophils treated with latex beads also significantly increased the basal release of the chemokine "regulated upon activation, normal T cell expressed and secreted" (RANTES) (from 96.0 to 613.0 fg/microg cellular protein; p < 0.05), IL-8 (from 42.0 to 198.5 pg/microg cellular protein; p < 0.05), granulocyte-macrophage colony-stimulating factor (GM-CSF) (from 0.54 to 3.4 pg/microg cellular protein; p < 0.05), and soluble intercellular adhesion molecule-1 (sICAM-1) (from 7.8 to 18.4 pg/microg cellular protein; p < 0.05) from HNEC. The eosinophil-induced release of IL-8, GM-CSF, and sICAM-1 from the HNEC was significantly attenuated by treatment with fexofenadine. Analysis of the effects of conditioned medium from HNEC demonstrated that this significantly increased both eosinophil chemotaxis and adherence to endothelial cells. Addition of 10(-6) to 10(-3) mol/L fexofenadine to the conditioned medium significantly attenuated eosinophil chemotaxis and adherence to endothelial cells. These results suggest that fexofenadine may reduce nasal inflammation by modulating the release of proinflammatory mediators and adhesion molecules from HNEC.     

Evaluation of changes in the course of seasonal allergic nasal mucosa inflammation

The efficacy, safety and diagnostic usefulness of adenosine in the treatment of supraventricular tachycardia in children were prospectively studied over a 2-year period. Only patients who were stable and without hypotension were included. Adenosine was given at a dose of 0.1 mg/kg and increased to 0.2 mg/kg for the second and third doses if there was no response. Adenosine was used on 5 occasions in 5 patients. Adenosine was found to be effective in terminating supraventricular tachycardia in all 5 patients; 4 responded to a dose of 0.2 mg/kg while 1 responded to 0.1 mg/kg. Wolff-Parkinson White Syndrome was detected in 2 patients after termination of supraventricular tachycardia. Transient hypotension was noted in 1 patient lasting 45 seconds with no haemodynamic consequences. Two patients had transient ventricular ectopics lasting 3 to 5 seconds. One out of 3 patients who were old enough to report side-effects, experienced chest discomfort and dizziness lasting 5 seconds. All side-effects were transient and mild. We concluded that adenosine is effective and safe in terminating supraventricular tachycardia in children after vagal manoeuvres have failed.     

Behavioural correlates of testosterone and seasonal changes of steroids in red-winged blackbirds

I studied the relationship between behaviour and plasma testosterone level (T) and the seasonal changes in T and plasma corticosterone levels (B) in male red-winged blackbirds, Agelaius phoeniceus. I measured T and B using radioimmunoassay, and on the day after taking blood, I observed each male's behaviour for 60 min. The time that males spent conspicuously perched and the number of songs were positively correlated with T, but the proportion of time spent conspicuously perched and the frequency of song were not correlated with T. The frequency of aggressive encounters, sexual chases, epaulet exposure when singing and flights within the territory were positively correlated with T, suggesting a direct role for circulating testosterone influencing male aggressive behaviour. Both T and B increased early in the breeding season, peaked when the first females were receptive, and decreased through the remainder of the breeding season. Late in the season, the presence of a receptive female caused males to have increased T. The peak in T when the first females were receptive, the positive correlation between aggression and T, and the response to a receptive female with increased T support predictions of the challenge hypothesis. T was positively correlated with B, suggesting a cost to the males of maintaining high T. When a receptive female was present on the male's territory, T was negatively correlated with date. Male red-winged blackbirds in Indiana may respond less to receptive females late in the season when benefits associated with protecting paternity and gaining extra-pair fertilizations decrease.Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.     

Are duodenal ulcer seasonal fluctuations paralleled by seasonal changes in 24-hour gastric acidity and Helicobacter pylori infection?

Short-term cultures from two histologically benign chemodectomas, one from the carotid body and one from the vagal nerve, were analyzed cytogenetically. The former had a small abnormal clone with the karyotype 46,XX,t(3;19)(q21;q13),t(12;15) (p13;q12-14), whereas the majority of the cells from the latter tumor displayed two related abnormal clones: 46,XY,i(I)(q10)/ 46,iderm,add(2)(q37). The findings add to the evidence that chemodectomas are heterogeneous neoplasms and suggest that the heterogeneity may possibly be associated with the site of origin.     

Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function

1. Polymorphonuclear leukocytes (PMN) may contribute to the pathogenesis of acute coronary heart disease (CHD). 2. Epidemiological and laboratory evidence suggests that red wine, by virtue of its polyphenolic constituents, may be more effective than other alcoholic beverages in reducing the risk of CHD mortality. 3 The aim of the present study was to investigate the effects of trans-resveratrol (3,4',5-trihydroxy-trans-stilbene), a polyphenol present in most red wines, on functional and biochemical responses of PMN, upon in vitro activation. 4. trans-Resveratrol exerted a strong inhibitory effect on reactive oxygen species produced by PMN stimulated with 1 microM formyl methionyl leucyl phenylalamine (fMLP) (IC50 1.3+/-0.13 microM, mean+/-s.e.mean), as evaluated by luminol-amplified chemiluminescence. 5. trans-Resveratrol prevented the release of elastase and beta-glucuronidase by PMN stimulated with the receptor agonists fMLP (1 microM, IC50 18.4+/-1.8 and 31+/-1.8 microM), and C5a (0.1 microM, IC50 41.6+/-3.5 and 42+/-8.3 microM), and also inhibited elastase and beta-glucuronidase secretion (IC50 37.7+/-7 and 25.4+/-2.2 microM) and production of 5-lipoxygenase metabolites leukotriene B4 (LTB4), 6-trans-LTB4 and 12-trans-epi-LTB4 (IC50 48+/-7 microM) by PMN stimulated with the calcium ionophore A23187 (5 microM). 6. trans-Resveratrol significantly reduced the expression and activation of the beta2 integrin MAC-1 on PMN surface following stimulation, as revealed by FACS analysis of the binding of an anti-MAC-1 monoclonal antibody (MoAb) and of the CBRM1/5 MoAb, recognizing an activation-dependent epitope on MAC-1. Consistently, PMN homotypic aggregation and formation of mixed cell-conjugates between PMN and thrombin-stimulated fixed platelets in a dynamic system were also prevented by transresveratrol. 7. These results, indicating that trans-resveratrol interferes with the release of inflammatory mediators by activated PMN and down-regulates adhesion-dependent thrombogenic PMN functions, may provide some biological plausibility to the protective effect of red wine consumption against CHD.     

Brain serotonin (5-HT) neuroendocrine function in patients taking cholesterol-lowering drugs

Brain serotonin (5-HT) neuroendocrine function, plasma tryptophan, and platelet 5-HT content were examined in 20 patients treated in a lipid clinic for hypercholesterolaemia with combined drug and diet therapy and in 20 healthy matched controls. Treatment had produced a substantial decrease in total cholesterol concentrations in the patients, but they still had higher cholesterol and triglyceride levels than control subjects. The patients were somewhat more depressed than controls but did not differ from them in degree of hostility, free or total plasma tryptophan, or prolactin response to 30 mg of d-fenfluramine. This study does not reveal evidence of abnormal brain 5-HT neuroendocrine function in hypercholesterolaemic patients receiving cholesterol-lowering medications and diet.     

Effect of aging on detrusor function in males

Some of the most dramatic advances in the treatment of cancer have used the immune system in combination with conventional or transplantation chemotherapy. Adoptive immunotherapy has been used for relapses after allogeneic bone marrow transplantation, and it has been particularly effective for chronic myeloid leukemia. Adoptive immunotherapy also has been used for Epstein-Barr virus-related lymphomas developing after allogeneic marrow transplantations. Cellular therapy, including the infusion of tumor-reactive immune cells, has been used to mediate response of established solid tumors. This has been used for therapeutic benefit for renal cell carcinoma, melanoma, lung cancer, and breast cancer. Current research is focusing on reducing the toxicity of these approaches as well as further defining the appropriate target tissue.     

Effect of pentachlorophenol on immune function

The organochlorine compound, pentachlorophenol, was evaluated for effects on immune system function in male Fisher 344 rats. Pentachlorophenol was prepared in an olive oil vehicle and was administered by oral gavage twice weekly for 28 days at a dose of 2.0 mg/kg per treatment. Exposure to pentachlorophenol increased body weight gains (P=0.024) during the treatment period. Liver (P=0.034) and kidney (P=0.012) body weight ratios were also increased. Pentachlorophenol exposure enhanced T-lymphocyte blastogenesis induced by concanavalin A (Con A)(P=0.0001) and phytohemagglutinin (PHA)(P=0.048) evaluated using stimulation indices. Corresponding B-lymphocyte blastogenesis induced by lipopolysaccharide/dextran (LPS/dex)(P=0.0034) was also enhanced by pentachlorophenol exposure. Pentachlorophenol suppressed the antibody response against sheep red blood cells (SRBCs) by 39% when the response was expressed per viable spleen cell (P=0.006). This suppression was not evident when the response was expressed per spleen (P=0.22), suggesting that a compensatory mechanism or extramedullary splenic hemopoiesis was occurring minimizing the overall impact on humoral immunity. The enhanced B- and T-lymphocyte blastogenesis may also reflect compensatory or hemopoietic activity. Pentachlorophenol exposure had no effect on peritoneal macrophage phagocytosis (P=0.31) or lymphocyte cell surface antigen expression. The observed alterations in lymphocyte blastogenesis and humoral immunity subsequent to pentachlorophenol exposure do not appear to be associated with phagocytosis or lymphocyte cell surface antigen expression.