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PubMed1985

Time-dependent effect of sectioning carotid sinus nerves on the vagally mediated baroreflex.

The purpose of the reported experiments was to examine whether the vagally mediated baroreflex system (V-system) increases its feedback gain with time after sectioning of the carotid sinus nerves (CSN). In 10 dogs anesthetized with Nembutal, we determined the overall open-loop gain (G) of the rapidly acting arterial pressure control system. G was assessed as (delta API/delta APs)-1, where delta API and delta APs represent the immediate and steady-state decreases in arterial pressure at the aortic arch following a fast step-wise reduction in blood volume. delta API, delta APs and GINTACT in the intact condition (30th min before sectioning of the CSN) were -1.8 +/- 0.1 kPa, -0.20 +/- 0.01 kPa and 8.4 +/- 0.3 (mean +/- SE), respectively. The mean values of delta API, delta APs and G after sectioning of the CSN (Gv), first averaged within individual dogs and then averaged for ten dogs, were -2.53 +/- 0.07 kPa, -1.1 +/- 0.05 kPa, and 1.5 +/- 0.1, respectively. Gv did not change with time over about 4 h after sectioning of the CSN. It is concluded that the V-system cannot augment its ability to restore arterial pressure in compensation for the lost function of the carotid sinus baroreflex system over 4 h after sectioning of the CSN in the anesthetized dog.

Animals↗

PubMed2000

ICTS, an interventional cardiology training system.

In this article, we present an Interventional Cardiology Training System developed by the Medical Application Group at Mitsubishi Electric in collaboration with the Center for Innovative Minimally Invasive Therapy. The core of the ICTS is a computer simulation of interventional cardiology catheterization. This simulation integrates clinical expertise, research in learning, and technical innovations to create a realistic simulated environment. The goal of this training system is to augment the training of new cardiology fellows as well as to introduce cardiologists to new devices and procedures. To achieve this goal, both the technical components and the educational content of the ICTS bring new and unique features: a simulated fluoroscope, a physics model of a catheter, a haptic interface, a fluid flow simulation combined with a hemodynamic model and a learning system integrated in a user interface. The simulator is currently able to generate--in real-time--high quality x-ray images from a 3D anatomical model of the thorax, including a beating heart and animated lungs. The heart and lung motion is controlled by the hemodynamic model, which also computes blood pressure and EKG. The blood flow is then calculated according to the blood pressure and blood vessel characteristics. Any vascular tool, such as a catheter, guide wire or angioplasty balloon can be represented and accurately deformed by the flexible tool physics model. The haptics device controls the tool and provides appropriate feedback when contact with a vessel wall is detected. When the catheter is in place, a contrast agent can be injected into the coronary arteries; blood and contrast mixing is computed and a visual representation of the angiogram is displayed by the x-ray renderer. By bringing key advances in the area of medical simulation--with the real-time x-ray renderer for instance--and by integrating in a single system both high quality simulation and learning tools, the ICTS opens new perspectives for computer based training systems.

Angioplasty, Balloon, Coronary↗

PubMed1987

Attenuation of pituitary polyphosphoinositide metabolism by protein kinase C activation.

Phorbol myristate acetate (PMA) stimulates pituitary hormone release by activating protein kinase C (PKC). By doing so, PMA mimics the diacylglycerol (DAG) produced by the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). The present study demonstrates that PMA and DAG augment prolactin release and attenuate the elevations of inositol phosphates (IPX) elicited by thyrotropin-releasing hormone (TRH), angiotensin II, neurotensin, bombesin and gonadotropin-releasing hormone (GnRH) in normal anterior pituitary and prolactin-secreting 7315a tumor cells. 4 alpha-Phorbol 12,13-didecanoate (PDD), an inactive analog of PMA, was found to have no effect on IPX levels; the PKC inhibitor H-7 attenuated the PMA-related inhibition of TRH-induced IPX. To examine whether PMA attenuates IPX generation or increases IPX metabolism, the effects of PMA on the levels of inositol phosphates and phosphoinositides were determined. TRH increased inositol trisphosphate, inositol bisphosphate and inositol monophosphate, and decreased PIP2 and phosphatidylinositol 4-phosphate levels. PMA had no effect on basal phosphoinositide or inositol phosphate levels, but attenuated the effects of TRH on these parameters. Thus PMA and DAG, by a mechanism involving PKC-mediated attenuation of secretagogue-induced hydrolysis of PIP2, decreases IPX production, and therefore PKC activation may exert negative feedback regulation on anterior pituitary secretory activity.

Animals↗

PubMed1991

Regulation of intracellular Ca2+ and gene expression by endothelin-1.

In addition to its powerful vasoconstrictive activity, endothelin-1 (ET-1) is a potent agonist for stimulating a multitude of second messenger pathways. In the Rat-1 fibroblastic cell line, ET-1 induces a robust elevation of the intracellular levels of Ca2+, diacylglycerols (DGs), and inositol trisphosphate (IP3). Although low concentrations of ET-1 stimulate a significant increase in the rate of Ca2+ influx, this Ca2+ influx is not required for the observed increases in either IP3 or DG levels following ET-1 treatment, as both of these effects are observed even in the absence of extracellular Ca2+. The ability of ET-1 to stimulate Ca2+ influx shows a biphasic pattern, such that Ca2+ influx is stimulated at low ET-1 concentrations and inhibited at high concentrations. Investigations of the molecular mechanisms underlying this biphasic response indicate that elevated intracellular Ca2+ levels exert a negative feedback inhibition on Ca2+ influx, which can be relieved by the chelation of intracellular Ca2+. The ability of ET-1 to activate a number of distinct signal transduction pathways appears to have direct functional significance in determining the targeting of ET-1 activation. Short-term effects of ET-1 stimulation such as the induction of gene expression appear to be independent of ET-1's ability to activate protein kinase C (PKC) by elevating DG levels, as depletion of PKC activity has little or no effect on gene expression. In contrast, the ability of ET-1 to induce the rapid expression of the VL30 gene is totally dependent upon the ability of ET-1 to elevate intracellular Ca2+ levels above a specific threshold. Activation of PKC by ET-1, however, is essential for the long-term effects of ET-1 on cell proliferation and anchorage-independent growth, as the ability of ET-1 to promote DNA synthesis and to synergize with epidermal growth factor in augmenting anchorage-independent growth is significantly inhibited by prior PKC depletion. Thus, in fibroblasts, ET-1 appears to activate at least two bifurcating pathways: a Ca(2+)-sensitive pathway involved in the regulation of gene expression, and a PKC-dependent pathway required for the mitogenic effects of ET-1.

Animals↗

PubMed1987

Steroid-independent endogenous opioid peptide suppression of pulsatile luteinizing hormone release between estrus and diestrus in the rat estrous cycle.

We have previously demonstrated an absence of ovarian steroid negative feedback on pulsatile luteinizing hormone (LH) release between estrus and early diestrus 1 (D1) in the rat estrous cycle. The object of the present study was to determine if there was a steroid-independent endogenous opioid peptide (EOP) suppression of pulsatile LH release in this same 24-h interval, and if so, which parameter(s) of pulsatile LH release were affected. Rats were bled on estrus, or 24 h following sham ovariectomy (OVX), or OVX at 08.30-10.00 h on estrus. At the time of bleeding all rats were infused i.v. for 4 h either with 0.9% saline (0.5 ml/h) or naloxone (0.005, 0.05, 0.5, or 2 mg/kg/h). At 1 h after the infusion began, rats were bled for 3 h (40 or 50 microliters whole blood/5 min) between 09.30 and 12.30 h. Mean blood LH levels increased between estrus and early D1 due to increases in LH pulse amplitude and frequency. OVX on estrus decreased plasma levels of estradiol and progesterone 24 h later, but did not augment the increase in pulsatile LH release. However, naloxone infusion augmented the increase in pulsatile LH secretion in sham ovariectomized rats in a dose-dependent fashion. While infusion of 0.005 or 0.05 mg/kg/h had no effect, 0.5 or 2 mg/kg/h increased blood LH levels by increasing both LH pulse amplitude and frequency. The stimulatory effect of naloxone on pulsatile LH release was blocked by simultaneous infusion of morphine, demonstrating that the effect was mediated by EOP receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

Effects of hypoxia and putative transmitters on [Ca2+]i of rat glomus cells.

Dissociated rat glomus cells were loaded with Fura-2 AM to study the effects of hypoxia, and carotid body transmitters on intracellular calcium, [Ca2+]i. The mean control [Ca2+]i was 55 nM in isolated cells and 67 nM in clusters. The following procedures changed [Ca2+]i:0[Ca2+]o+EGTA reduced [Ca2+]i by about 50%, suggesting that the remaining calcium originated from intracellular organelles. [Ca2+]i increased when [Ca2+]o was doubled. Hypoxia by sodium dithionite (Na2S2O4) induced large [Ca2+]i increases in clustered and isolated cells. Smaller rises occurred with 100% N2 hypoxia. The augmented [Ca2+]i, induced by Na2S2O4, was reduced (not eliminated) in 0[Ca2+]o+EGTA, suggesting that some calcium was intracellularly released. Nifedipine depressed (did not block) the Na2S2O4-induced calcium increase, implying some inflow via other (N, T or P/Q) voltage-dependent or voltage-independent calcium channels.Cholinergic agents (ACh, nicotine, muscarine, bethanechol and pilocarpine) increased [Ca2+]i. The ACh effect was produced exclusively by calcium inflow since it was eliminated in 0[Ca2+]o+EGTA. Cholinergic effects were depressed (not obliterated) by D-tubocurarine (D-TC), hexamethonium (C6) and atropine.ACh, nicotine and pilocarpine potentiated the excitatory effect of Na2S2O4 on [Ca2+]i. Bethanechol depressed this excitation whereas muscarine had inconsistent effects. Atropine and C6 depressed [Ca2+]i increases elicited by Na2S2O4 but the effects of D-TC were variable. Dopamine (DA) had variable effects. It increased [Ca2+]i in 75% of cases, and reduced the Na2S2O4 -induced calcium increase.Thus, calcium increases during Na2S2O4 occur by direct effects on the glomus cells and feedback action through released ACh and DA.

Animals↗

PubMed1988

Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer's and Parkinson's disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia.

This study summarizes the findings from postmortem examination of the brains of 22 control cases without neurological deficit, 12 cases of senile dementia of the Alzheimer type (SDAT), and nine cases of Parkinson's disease (three without signs of intellectual deterioration, four with dementia, and two atypical with dementia nonresponsive to L-dopa treatment). The aim of this study was to find the similarities and differences in galanin innervation of the cholinergic basal nucleus neurons in these dementing disorders as compared with controls. Immunocytochemistry with antibodies against galanin peptide and against choline acetyltransferase was applied on perfused brain preparations. Galanin peptide is present in the basal nucleus of Meynert neuron networks in the normal human brain: in local circuit neurons, in a number of galanin/cholinergic neurons, and in a feedback circuit via collaterals) that terminate upon the cholinergic neuronal somata and dendrites. Thus, peptide galanin circuits could function as powerful modulators of the activities of basal nucleus cholinergic neurons, both within the basal forebrain and in their wider projections to the neocortex and amygdala. As galanin has been shown to inhibit cholinergic activity, this galanin network could suppress the activity of cholinergic neurons. In SDAT, there is a primary loss of cholinergic neurons compounded by a secondary reaction of the remaining cholinergic neurons to the terminal degeneration in the cortex. Galanin networks demonstrate an inverse relationship to the cholinergic cell loss. Galanin axons hypertrophy and hyperinnervate the remaining cholinergic neurons. In Parkinson's disease the loss of cholinergic neurons is accentuated by the presence of dementia: the hypertrophy of the galanin axonal networks on cholinergic neurons is dramatic in Parkinson's disease with dementia. These observations throw new light on the neurotransmitter bases for these dementias. Galanin controls cholinergic mechanisms in the basal nucleus of Meynert, and dementia is accompanied by augmentation of galanin innervation onto an already depressed population of cholinergic neurons, thus demonstrating an appreciable amount of plasticity even in aged brain. These findings suggest that the present therapy of cholinergic enhancement as a means to retard intellectual deterioration can by itself have little effect at best, in these dementias. The suppressive effect of galanin peptide has to be reduced or curtailed, perhaps concurrently with the treatment of the cholinergic deficit.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗

PubMedDate not supplied

Haptics-based dynamic implicit solid modeling.

This paper systematically presents a novel, interactive solid modeling framework, Haptics-based Dynamic Implicit Solid Modeling, which is founded upon volumetric implicit functions and powerful physics-based modeling. In particular, we augment our modeling framework with a haptic mechanism in order to take advantage of additional realism associated with a 3D haptic interface. Our dynamic implicit solids are semi-algebraic sets of volumetric implicit functions and are governed by the principles of dynamics, hence responding to sculpting forces in a natural and predictable manner. In order to directly manipulate existing volumetric data sets as well as point clouds, we develop a hierarchical fitting algorithm to reconstruct and represent discrete data sets using our continuous implicit functions, which permit users to further design and edit those existing 3D models in real-time using a large variety of haptic and geometric toolkits, and visualize their interactive deformation at arbitrary resolution. The additional geometric and physical constraints afford more sophisticated control of the dynamic implicit solids. The versatility of our dynamic implicit modeling enables the user to easily modify both the geometry and the topology of modeled objects, while the inherent physical properties can offer an intuitive haptic interface for direct manipulation with force feedback.

Algorithms↗

PubMed2005

Short communication: Short-day photoperiod during the dry period decreases expression of suppressors of cytokine signaling in mammary gland of dairy cows.

Suppressors of cytokine signaling (SOCS) are induced by prolactin and act through negative feedback to inhibit cytokine signaling. We hypothesized that lower prolactin concentrations in cows exposed to short-day photoperiod (SD; 8 h light:16 h dark) lead to decreased expression of SOCS, which mediate the effects of SD on mammary proliferation during the dry period. Multiparous Holstein cows were dried off 60 d before expected calving and were assigned to long-day photoperiod (LD; 16 h light:8 h dark) or SD during the dry period. Mammary biopsies were obtained at -40, -20, -10, and +10 d relative to expected calving, and expression of SOCS-1, SOCS-2, SOCS-3, and cytokine-inducible SH2-containing protein (CIS) mRNA was assessed by real-time, quantitative, reverse transcription-PCR. Expression of all SOCS increased over time and expression of SOCS-3, SOCS-2, and CIS mRNA was lower in mammary gland of SD cows. These data suggest that lower SOCS expression in cows exposed to SD during the dry period may enhance prolactin signaling to the mammary gland, thereby augmenting mammary development during pregnancy and milk production in the subsequent lactation. Changes in SOCS expression during pregnancy and lactation imply that SOCS may regulate mammary gland development and function in dairy cows.

Animals↗

PubMed1986

Pre- and postjunctional alpha-adrenoceptors at sympathetic neuroeffector junction in bovine mesenteric lymphatics.

We studied isolated bovine mesenteric lymphatics to elucidate the pharmacological characteristics of pre- and postjunctional alpha-adrenoceptors at the sympathetic neuroeffector junction. Cylindrical strips were incubated with [3H]-noradrenaline and mounted for superfusion. Electrical stimulation (2 Hz, 0.5 msec, 50 V) augmented the fractional release of labeled noradrenaline. Exogenous noradrenaline and clonidine caused a depression of the evoked tracer release. Phenoxybenzamine and yohimbine markedly enhanced the evoked overflow of adrenergic transmitter. Rings of lymphatic vessels were mounted for isometric tension recording in organ chambers filled with Krebs-Ringer bicarbonate solution. The vessels contracted when exposed to phenylephrine and clonidine. The ED50 of clonidine was significantly lower than that of phenylephrine. Prazosin caused a parallel shift to the right of the dose-response curve to phenylephrine. The antagonist, however, suppressed the magnitude of the maximum response to clonidine. Yohimbine caused parallel shift to the right of the dose-response curves to phenylephrine and clonidine, respectively. The Schild plots for yohimbine demonstrated that the drug was a competitive antagonist to phenylephrine and clonidine. The pA2 value of yohimbine to clonidine (7.6 +/- 0.4) was larger than that to phenylephrine (6.2 +/- 0.4). The pA2 value of prazosin to phenylephrine was 7.2 +/- 0.3. These results suggest that prejunctional alpha-adrenoceptors are involved in the negative feedback mechanism for autoregulation of noradrenaline release during postganglionic sympathetic nerve stimulation, and that both alpha 1- and alpha 2-like adrenoceptors do exist on lymphatic smooth muscle cells.

Adrenergic Fibers↗

PubMed1975

Gastrin cell hyperplasia in rats with chronic antral stimulation.

Rats surgically prepared with the antrum transposed onto the colon were compared with suitable control rats, to investigate whether chronic antral stimulation modifies gastrin cell and other endocrine cell populations. Gastrin cell and argyrophil cell density per unit area were studied in antrum using a quantitative method after staining by immunofluorescence and Grimelius argyrophily, respectively. Both gastrin cells and argyrophil cells increased significantly in density per unit area after antrocolic transposition (P smaller than 0.001). The augmentation of gastrin cells per glandular tube (78%) was also significant (P smaller than 0.001). Electron-microscopic observations confirmed these results. On the other hand, in each group, the topographic distribution of the two categories of cells was different, and the number of gastrin cells was statistically greater than that of the argyrophil cells. Thus, it appeared evident that gastrin cells were not argyrophilic. Several hypotheses to explain the mechanism of this hyperplasia of endocrine cells are discussed. It is concluded that the increase in the gastrin cell density could be one possible explanation for the hypergastrinemia observed in the antrocolic transposition model.

Animals↗

PubMed2003

Androgen regulates follicle-stimulating hormone beta gene expression in an activin-dependent manner in immortalized gonadotropes.

Little is known about the molecular mechanisms of androgen regulation of the FSHbeta gene; however, studies suggest that it consists of a complex feedback loop that involves multiple mechanisms acting at both the level of the hypothalamus and the pituitary. In the present study, we address androgen regulation of the FSHbeta gene in immortalized gonadotrope cells and investigate the roles of activin and GnRH in androgen action. Using transient transfection assays in the FSHbeta-expressing mouse gonadotrope cell line, LbetaT2, we demonstrate that androgens stimulate expression of an ovine FSHbeta reporter gene in a dose-dependent manner. Mutation of either of two conserved androgen response elements at -245/-231 and -153/-139 within the proximal region of the ovine FSHbeta gene promoter abolishes this stimulation, and androgen receptor binds directly to the -244 ARE in vitro. Androgen induction of the FSHbeta reporter gene is also dependent upon the activin autocrine loop present in the LbetaT2 cells, as well as an activin-response element at -138/-124 of the FSHbeta gene. However, activin regulation of other genes remains unaffected by androgens. In addition, androgens stimulate expression of a mouse GnRH receptor reporter gene, and thus may indirectly augment the response of the FSHbeta gene to GnRH. Taken together, these data demonstrate that, in mouse gonadotropes, androgens act directly on the ovine FSHbeta gene to stimulate expression by a mechanism that is dependent upon activin, as well as acting indirectly, potentially through a second mechanism that may be dependent upon induction of GnRH receptor.

Activins↗

PubMed2005

[Quality measurement between illusion and reality--is the quality of medical care measurable?].

The current implementation of external quality assurance focuses on identical, albeit simple univariate procedures. This approach proves to be inefficient, exhibiting low specificity. Definitions of performance indicators were classified by the local steering committee and applied to Bavarian obstetric data augmented with multivariate and confidence interval analyses as well as statistical simulations. A highly selected group of units with multivariate extreme values was audited. Blind application of federal regimes without further in-depth analysis of concomitant data is inefficient and may lead to wrong conclusions. Exclusive univariate analyses of performance indicators are not enough. Multivariate analyses have a higher specificity. Classification reveals an imbalance in the indicator set with respect to varying degrees of coverage as well as a bias towards outcome. Deficiencies in the organisational processes crucial for quality of care are often only revealed by dedicated cause and effect analyses within the hospital, thus constituting an essential prerequisite for desired changes in health care policies. It is unlikely that mere publication of performance indicators in the impending quality report will generate lucidity in spite of abundant structure. The installation of standardised programmes with identical computation rules may appear convincing as long as no doubt is cast upon the efficacy of the performance indicators in respect to their intended usage as well as upon the expected feedback effects. The experience so far however teaches us that these elements may be essential yet although not sufficient.

Benchmarking↗

PubMedDate not supplied

Dopamine D2 receptor signaling via the arachidonic acid cascade: modulation by cAMP-dependent protein kinase A and prostaglandin E2.

Recent studies have shown that, in Chinese hamster ovary cells transfected with D2-receptor cDNA, CHO(D2) cells, D2 agonists are potent in enhancing the release of [3H]arachidonic acid (AA) induced by stimulation of constitutive purinergic receptors or by application of Ca2+ ionophores. This facilitatory action is further amplified by the concomitant activation of D1 receptors, which per se have no effect on evoked [3H]AA release. Here, we review a series of experiments aimed at examining the molecular mechanism of this synergistic interaction. The results show that, in CHO(D2) cells: (a) application of 8-Br-cAMP or stimulation of constitutive prostaglandin (PG)E2 receptors augment the AA response produced by D2 agonists; (b) in CHO(D2) cells transfected with human beta 2-receptor cDNA, the beta-agonist, isoproterenol, produces a similar effect; (c) the potentiation of [3H]AA release produced by PGE2 and 8-Br-cAMP is prevented by overexpressing either a protein inhibitor of cAMP-dependent protein kinase (PKA) or a mutated form of pKA regulatory subunit incapable of binding cAMP; (d) mock-synergism is obtained in CHO(D2) cells overexpressing the catalytic subunit of PKA; (e) PGE2 is a major AA metabolite in stimulated CHO(D2) cells and its formation may contribute to the effect of D2 agonists on AA release. The results indicate that cAMP-induced activation of PKA represents a likely molecular basis for D1/D2 receptor synergism on AA release. They also suggest that additional membrane receptors, colocalized with D2 and positively linked to adenylyl cyclase, may exert a similar action. Furthermore, stimulation of PGE2 receptors by endogenously produced prostaglandin may participate in AA signaling at the D2 receptor, by providing a paracrine positive feedback loop.

Animals↗

PubMed1991

Cardiac contractile function, oxygen consumption rate and cytosolic phosphates during inhibition of electron flux by amytal--a 31P-NMR study.

In order to investigate the potential role of cytosolic phosphates ([ATP], [ADP] and [Pi]) in the integration of mitochondrial respiration and mechanical function in the perfused heart, inhibition of the substrate end of the respiratory chain by amytal has been employed. A stepwise increase in amytal concentration (from 0.2 to 1.2 mM) resulted in the progressive abolition of the cardiac oxygen consumption, rate (VO2) in hearts oxidizing pyruvate (5 mM). The inhibition curve for VO2 was S-shaped, with K0.5 = 1.1 mM, and independent of the initial VO2 values varied by coronary flow and isoproterenol (Iso) addition. ADP-stimulated respiration of isolated mitochondria (malate + pyruvate) was twice as sensitive to amytal inhibition, whereas state 2 respiration (before ADP addition) had the same sensitivity as cardiac VO2. Decrease in VO2 was followed by a decline in phosphocreatine (PCr) content and augmentation of Pi at nearly constant ATP level and intracellular pH as assessed by the 31P-NMR method. These changes were associated with an elevation of cytosolic free [ADP] and a reduction of the [ATP]/[ADP] ratio and ATP affinity calculated from creatine kinase equilibrium. Concomitantly, pressure-rate product (PRP), maximal rates of contraction and relaxation fell down and the end diastolic pressure (EDP) rose at all initial loads. Amytal-inhibited hearts retained the capability to respond to Iso stimulation (0.1 microM, about 50% enhancement of PRP) even at 1 mM amytal, but their response to elevation of coronary flow was greatly diminished. Alterations in the PRP value induced by the inhibitor at a fixed coronary flow correlated negatively with cytosolic [ADP] and [Pi], and positively with [ATP]/[ADP] and A(ATP). In contrast, EDP correlated with all these parameters in the opposite manner. However, when PRP was varied by coronary flow in the absence of the inhibitor or at its fixed concentrations, such correlations were absent. These data imply that cytosolic phosphates can serve as a feedback between energy production and utilization when the control point(s) is (are) at the mitochondria. In contrast, other regulatory mechanisms should be involved when control is distributed among different steps located both in energy producing and utilizing systems.

Adenosine Triphosphate↗

PubMed1993

Effects of neuropeptide Y on gonadotropin and prolactin release in normal, castrated or flutamide-treated male rats.

This study was carried out to clarify the central effects of neuropeptide Y (NPY) on gonadotropin and prolactin (PRL) release in the male rat and to evaluate the hypothesis that it may play a role in negative feedback regulation of gonadotropin secretion in the male. NPY (4 micrograms in 2 microliters 0.9% NaCl) or an equal volume of saline was microinjected into the third cerebral ventricle of conscious, unrestrained rats and its effects on plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH) and PRL concentrations, and the gonadotropin response to LH-releasing hormone (LHRH) were measured by radioimmunoassay in noncastrated, castrated (3 days before the experiment) rats or animals treated with flutamide, an androgen receptor blocker (10 mg/kg b.w. per day subcutaneously for 3 days). Blood samples were drawn periodically from a Silastic catheter in the external jugular vein just before and for 120 min after intraventricular injections. At 90 min after injection 25 ng of LHRH were infused intravenously and 3 additional blood samples were withdrawn at 10-min intervals after the injection. Normal male rats responded to NPY with a decrease in plasma LH concentrations at 60 min. Plasma LH was significantly lower at 120 min than values in the saline-injected controls. At that time there was a significant 2-fold augmentation of their response to LHRH. In contrast, NPY elevated plasma FSH significantly versus values in controls at 15 and 30 min after injection, but the FSH release in response to LHRH was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Human immunodeficiency virus infection of monocytes: relationship to Fc-gamma receptors and antibody-dependent viral enhancement.

Antibodies that augment human immunodeficiency virus (HIV) infectivity of monocytes through Fc receptor (FcR) type III for IgG have been found in the blood of sero-positive patients and immunized chimpanzees. This study investigated the effect of acute and chronic HIV infection, as well as protein kinase C activators capable of up-regulating latent HIV, on the expression of these receptors. In addition, the frequency of this antibody-dependent enhancement (ADE) phenomenon was estimated using purified IgG from HIV-1 seropositive individuals at various clinical stages of infection. The existence of an FcR-dependent pathway for ADE of HIV-1 infection in peripheral blood monocytes and promonocytic U937 cells was confirmed in sera from a small subset of patients, and the phenomenon extended to FcR types I and II. The level of ADE activity was minimal, however, and no relationship between the presence or magnitude of the ADE phenomenon and clinical stage was uncovered. Finally, perturbations which activate a latent HIV infection were shown to concomitantly up-regulate FcR on infected and uninfected cells. This suggests a positive feedback loop linking up-regulation of latent infection, enhanced expression of low affinity HIV receptors such as FcR, and viral spread.

Acquired Immunodeficiency Syndrome↗

PubMed2001

Protein kinase epsilon dampens the secretory response of model intestinal epithelia during ischemia.

BACKGROUND: Luminal fluid sequestration and diarrhea are early manifestations of mesenteric ischemia. This can be modeled in vitro with the use of T84 intestinal epithelia, where ischemia induces Cl(-) secretion with adenosine-mediated autocrine feedback. Protein kinase C (PKC) regulates epithelial transport and, in some organ systems, is involved in the response to ischemic stress. The purpose of this study was to define the role of PKC on epithelial transport during ischemia. METHODS: By voltage-current clamp, short-circuit current (Isc) equals Cl(-) secretion. Ischemic conditions were simulated with the use of a well-established chemical hypoxia protocol. RESULTS: Chemical hypoxia briskly activated Isc. Gö6850, an antagonist of novel and conventional PKC isoforms, markedly enhanced the ischemia-induced Isc response, although Gö6976 (which inhibits only conventional isoforms) had no effect. Rottlerin, a specific inhibitor of PKC delta, did not attenuate ischemic Isc. Both phorbol 12-myristate, 13-acetate and bryostatin-1, which selectively activate PKC epsilon in T84 cells, markedly attenuated the Isc response to ischemia. Both agents also inhibited the Isc response to exogenous adenosine. CONCLUSIONS: PKC (likely the novel epsilon isoform) in intestinal epithelia modulates ischemia-induced alterations in ion transport. Inhibition of PKC epsilon exaggerates the secretory response that is induced by ischemia and by authentic adenosine; conversely, augmented activation of PKC epsilon inhibits secretion. Manipulation of PKC epsilon could limit luminal fluid sequestration during mesenteric ischemia.

Biological Transport↗