Thyrotrophin-releasing hormone decreases feeding and increases body temperature, activity and oxygen consumption in Siberian hamsters.

PubMed

Schuhler, S; Warner, A; Finney, N; Bennett, G W; Ebling, F J P; Brameld, J M

2007-04-01

Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5-50 mg/kg body weight; i.p.) and central (0.5 microg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function.

Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.

PubMed

Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I; Bíró, Tamás; Paus, Ralf

2012-03-01

Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion. Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis. Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h. TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation. These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.

Biochemical and pharmacological characterization of the thyrotropin releasing hormone (TRH) receptor from clonal GH sub 4 C sub 1 pituitary cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phillips, W.J.

1987-01-01

The effect of drugs with anesthetic properties on the activity of the pituitary thyrotropin-releasing hormone (TRH) receptor was determined in the clonal GH{sub 4}C{sub 1} somatomammotropic cell line. Classic local anesthetics and other drugs with anesthetic activity inhibited binding of ({sup 3}H)methyl-TRH to cell receptors at concentrations known to produce anesthetic effects on the membrane. The inhibition of TRH receptor binding by tetracaine was competitive and temperature and pH dependent. Verapamil and tetracaine inhibited TRH-stimulated prolactin secretion at concentrations that inhibited peptide binding. TRH-stimulated prolactin secretion was equivalent with or without Ca{sup 2+} channel activity. Verapamil and tetracaine also inhibitedmore » basal prolactin and secretion stimulated by drugs that bypass membrane receptors, db-cAMP and TPA. These results indicate that inhibition of TRH binding and responses by diverse drugs results from an anesthetic effect on the cell membrane.« less

Roles of thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) in Vibrio parahaemolyticus

PubMed Central

Raghunath, Pendru

2015-01-01

Vibrio parahaemolyticus is the leading cause of seafood borne bacterial gastroenteritis in the world, often associated with the consumption of raw or undercooked seafood. However, not all strains of V. parahaemolyticus are pathogenic. The thermostable direct hemolysin (TDH) or TDH-related hemolysin (TRH) encoded by tdh and trh genes, respectively, are considered major virulence factors in V. parahaemolyticus. However, about 10% of clinical strains do not contain tdh and/or trh. Environmental isolates of V. parahaemolyticus lacking tdh and/or trh are also highly cytotoxic to human gastrointestinal cells. Even in the absence of these hemolysins, V. parahaemolyticus remains pathogenic indicating other virulence factors exist. This mini review aims at discussing the possible roles of tdh and trh genes in clinical and environmental isolates of V. parahaemolyticus. PMID:25657643

Roles of thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) in Vibrio parahaemolyticus.

PubMed

Raghunath, Pendru

2014-01-01

Vibrio parahaemolyticus is the leading cause of seafood borne bacterial gastroenteritis in the world, often associated with the consumption of raw or undercooked seafood. However, not all strains of V. parahaemolyticus are pathogenic. The thermostable direct hemolysin (TDH) or TDH-related hemolysin (TRH) encoded by tdh and trh genes, respectively, are considered major virulence factors in V. parahaemolyticus. However, about 10% of clinical strains do not contain tdh and/or trh. Environmental isolates of V. parahaemolyticus lacking tdh and/or trh are also highly cytotoxic to human gastrointestinal cells. Even in the absence of these hemolysins, V. parahaemolyticus remains pathogenic indicating other virulence factors exist. This mini review aims at discussing the possible roles of tdh and trh genes in clinical and environmental isolates of V. parahaemolyticus.

Absence of TRH receptor 1 in male mice affects gastric ghrelin production.

PubMed

Mayerl, Steffen; Liebsch, Claudia; Visser, Theo J; Heuer, Heike

2015-02-01

TRH not only functions as a thyrotropin releasing hormone but also acts as a neuropeptide in central circuits regulating food intake and energy expenditure. As one suggested mode of action, TRH expressed in the caudal brainstem influences vagal activity by activating TRH receptor 1 (TRH-R1). In order to evaluate the impact of a diminished medullary TRH signaling on ghrelin metabolism, we analyzed metabolic changes of TRH-R1 knockout (R1ko) mice in response to 24 hours of food deprivation. Because R1ko mice are hypothyroid, we also studied eu- and hypothyroid wild-type (wt) animals and R1ko mice rendered euthyroid by thyroid hormone treatment. Independent of their thyroidal state, R1ko mice displayed a higher body weight loss than wt animals and a delayed reduction in locomotor activity upon fasting. Ghrelin transcript levels in the stomach as well as total ghrelin levels in the circulation were equally high in fasted wt and R1ko mice. In contrast, only wt mice responded to fasting with a rise in ghrelin-O-acyltransferase mRNA expression and consequently an increase in serum levels of acylated ghrelin. Together, our data suggest that an up-regulation of medullary TRH expression and subsequently enhanced activation of TRH-R1 in the vagal system represents a critical step in the stimulation of ghrelin-O-acyltransferase expression upon starvation that in turn is important for adjusting the circulating levels of acylated ghrelin to the fasting condition.

Thyrotropin-Releasing Hormone Loaded and Chitosan Engineered Polymeric Nanoparticles: Towards Effective Delivery of Neuropeptides.

PubMed

Kaur, Sarabjit; Bhararia, Avani; Sharma, Krishna; Mittal, Sherry; Jain, Rahul; Wangoo, Nishima; Sharma, Rohit K

2016-05-01

Thyrotropin-Releasing Hormone (TRH), a tripeptide amide with molecular formula L-pGlu-L-His-L- Pro-NH2, is used in the treatment of brain/spinal injury and certain central nervous system (CNS) disorders, including schizophrenia, Alzheimer's disease, epilepsy, depression, shock and ischemia due to its profound effects on the CNS. However, TRH's therapeutic activity is severely hampered because of instability and hydrophilicity owing to its peptidic nature which results into ineffective penetration into the blood brain barrier. In the present study, we report the synthesis and stability studies of novel chitosan engineered TRH encapsulated poly(lactide-co-glycolide) (PLGA) based nanoformulation. The aim of such an encapsulation is to allow effective delivery of TRH in biological systems as the peptidase degrade naked TRH. The synthesis of TRH was carried out manually in solution phase followed by its encapsulation using PLGA to form polymeric nanoparticles (NPs) via nanoprecipitation technique. Different parameters such as type of organic phase, concentration of stabilizer, ratio of organic phase and aqueous phase, rate of addition of organic phase were optimized, tested and evaluated for particle size, encapsulation efficiency, and stability of NPs. The TRH-PLGA NPs were then surface modified with chitosan to achieve positive surface charge rendering them potential membrane penetrating agents. PLGA, PLGA-TRH, Chitosan-PLGA and Chitosan-PLGA-TRH NPs were characterized and analyzed using Dynamic Light Scattering (DLS), Transmissiom Electron Microscopy (TEM) and Infra-red spectroscopic techniques.

Characterization of a Vibrio alginolyticus Strain, Isolated from Alaskan Oysters, Carrying a Hemolysin Gene Similar to the Thermostable Direct Hemolysin-Related Hemolysin Gene (trh) of Vibrio parahaemolyticus▿

PubMed Central

González-Escalona, Narjol; Blackstone, George M.; DePaola, Angelo

2006-01-01

A Vibrio strain isolated from Alaskan oysters and classified by its biochemical characteristics as Vibrio alginolyticus possessed a thermostable direct hemolysin-related hemolysin (trh) gene previously reported only in Vibrio parahaemolyticus. This trh-like gene was cloned and sequenced and was 98% identical to the trh2 gene of V. parahaemolyticus. This gene seems to be functional since it was transcriptionally active in early-stationary-phase growing cells. To our knowledge, this is the first report of V. alginolyticus possessing a trh gene. PMID:17056701

Congenital isolated thyrotrophin releasing hormone deficiency

PubMed Central

Niimi, H; Inomata, H; Sasaki, N; Nakajima, H

1982-01-01

A 4⅓-year-old girl with congenital thyrotrophin-releasing hormone (TRH) deficiency is described. Oral TRH administration led to normal thyroid hormone and TRH levels in the blood; favourable growth and development was achieved. PMID:6816148

The TRH neuron: a hypothalamic integrator of energy metabolism.

PubMed

Lechan, Ronald M; Fekete, Csaba

2006-01-01

Thyrotropin-releasing hormone (TRH) has an important role in the regulation of energy homeostasis not only through effects on thyroid function orchestrated through hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN), but also through central effects on feeding behavior, thermogenesis, locomotor activation and autonomic regulation. Hypophysiotropic TRH neurons are located in the medial and periventricular parvocellular subdivisions of the PVN and receive direct monosynaptic projections from two, separate, populations of leptin-responsive neurons in the hypothalamic arcuate nucleus containing either alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART), peptides that promote weight loss and increase energy expenditure, or neuropeptide Y (NPY) and agouti-related protein (AGRP), peptides that promote weight gain and reduce energy expenditure. During fasting, the reduction in TRH mRNA in hypophysiotropic neurons mediated by suppression of alpha-MSH/CART simultaneously with an increase in NPY/AGRP gene expression in arcuate nucleus neurons contributes to the fall in circulating thyroid hormone levels, presumably by increasing the sensitivity of the TRH gene to negative feedback inhibition by thyroid hormone. Endotoxin administration, however, has the paradoxical effect of increasing circulating levels of leptin and melanocortin signaling and CART gene expression in arcuate nucleus neurons, but inhibiting TRH gene expression in hypophysiotropic neurons. This may be explained by an overriding inhibitory effect of endotoxin to increase type 2 iodothyroine deiodinase (D2) in a population of specialized glial cells, tanycytes, located in the base and infralateral walls of the third ventricle. By increasing the conversion of T4 into T3, tanycytes may increase local tissue concenetrations of thyroid hormone, and thereby induce a state of local tissue hyperthyroidism in the region of hypophysisotrophic TRH neurons. Other regions of the brain may also serve as metabolic sensors for hypophysiostropic TRH neurons including the ventrolateral medulla and dorsomedial nucleus of the hypothalamus that have direct monosynaptic projections to the PVN. TRH also exerts a number of effects within the central nervous system that may contribute to the regulation of energy homeostasis. Included are an increase in core body temperature mediated through neurons in the anterior hypothalamic-preoptic area that coordinate a variety of autonomic responses; arousal and locomotor activation through cholinergic and dopaminergic mechanisms on the septum and nucleus accumbens, respectively; and regulation of the cephalic phase of digestion. While the latter responses are largely mediated through cholinergic mechanisms via TRH neurons in the brainstem medullary raphe and dorsal motor nucleus of the vagus, effects of TRH on autonomic loci in the hypothalamic PVN may also be important. Contrary to the actions of T3 to increase appetite, TRH has central effects to reduce food intake in normal, fasting and stressed animals. The precise locus where TRH mediates this response is unknown. However, evidence that an anatomically separate population of nonhypophysiotropic TRH neurons in the anterior parvocellular subdivision of the PVN is integrated into the leptin regulatory control system by the same arcuate nucleus neuronal populations that innervate hypophysiotropic TRH neurons, raises the possibility that anterior parvocellular TRH neurons may be involved, possibly through interactions with the limbic nervous system.

Protective effects of TRH and its analogues against various cytotoxic agents in retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells.

PubMed

Jaworska-Feil, L; Jantas, D; Leskiewicz, M; Budziszewska, B; Kubera, M; Basta-Kaim, A; Lipkowski, A W; Lason, W

2010-12-01

TRH (thyroliberin) and its analogues were reported to possess neuroprotective effects in cellular and animal experimental models of acute and chronic neurodegenerative diseases. In the present study we evaluated effects of TRH and its three stable analogues, montirelin (CG-3703), RGH-2202 and Z-TRH (N-(carbobenzyloxy)-pGlutamyl-Histydyl-Proline) on the neuronally differentiated human neuroblastoma SH-SY5Y cell line, which is widely accepted for studying potential neuroprotectants. We found that TRH and all the tested analogues at concentrations 0.1-50 μM attenuated cell damage induced by MPP(+) (2 mM), 3-nitropropionate (10 mM), hydrogen peroxide (0.5 mM), homocysteine (250 μM) and beta-amyloid (20μM) in retinoic acid differentiated SH-SY5Y cells. Furthermore, we demonstrated that TRH and its analogues decreased the staurosporine (0.5 μM)-induced LDH release, caspase-3 activity and DNA fragmentation, which indicate the anti-apoptotic proprieties of these peptides. The neuroprotective effects of TRH (10 μM) and RGH-2202 (10 μM) on St-induced cell death was attenuated by inhibitors of PI3-K pathway (wortmannin and LY294002), but not MAPK/ERK1/2 (PD98059 and U0126). Moreover, TRH and its analogues at neuroprotective concentrations (1 and 10 μM) increased expression of Bcl-2 protein, as confirmed by Western blot analysis. All in all, these results extend data on neuroprotective properties of TRH and its analogues and provide evidence that mechanism of anti-apoptotic effects of these peptides in SH-SY5Y cell line involves induction of PI3K/Akt pathway and Bcl-2. Furthermore, the data obtained on human cell line with a dopaminergic phenotype suggest potential utility of TRH and its analogues in the treatment of some neurodegenerative diseases including Parkinson's disease. Copyright © 2010 Elsevier Ltd. All rights reserved.

Intravenous and Intratracheal Thyrotropin Releasing Hormone and Its Analog Taltirelin Reverse Opioid-Induced Respiratory Depression in Isoflurane Anesthetized Rats.

PubMed

Boghosian, James D; Luethy, Anita; Cotten, Joseph F

2018-07-01

Thyrotropin releasing hormone (TRH) is a tripeptide hormone and a neurotransmitter widely expressed in the central nervous system that regulates thyroid function and maintains physiologic homeostasis. Following injection in rodents, TRH has multiple effects including increased blood pressure and breathing. We tested the hypothesis that TRH and its long-acting analog, taltirelin, will reverse morphine-induced respiratory depression in anesthetized rats following intravenous or intratracheal (IT) administration. TRH (1 mg/kg plus 5 mg/kg/h, i.v.) and talitrelin (1 mg/kg, i.v.), when administered to rats pretreated with morphine (5 mg/kg, i.v.), increased ventilation from 50% ± 6% to 131% ± 7% and 45% ± 6% to 168% ± 13%, respectively (percent baseline; n = 4 ± S.E.M.), primarily through increased breathing rates (from 76% ± 9% to 260% ± 14% and 66% ± 8% to 318% ± 37%, respectively). By arterial blood gas analysis, morphine caused a hypoxemic respiratory acidosis with decreased oxygen and increased carbon dioxide pressures. TRH decreased morphine effects on arterial carbon dioxide pressure, but failed to impact oxygenation; taltirelin reversed morphine effects on both arterial carbon dioxide and oxygen. Both TRH and talirelin increased mean arterial blood pressure in morphine-treated rats (from 68% ± 5% to 126% ± 12% and 64% ± 7% to 116% ± 8%, respectively; n = 3 to 4). TRH, when initiated prior to morphine (15 mg/kg, i.v.), prevented morphine-induced changes in ventilation; and TRH (2 mg/kg, i.v.) rescued all four rats treated with a lethal dose of morphine (5 mg/kg/min, until apnea). Similar to intravenous administration, both TRH (5 mg/kg, IT) and taltirelin (2 mg/kg, IT) reversed morphine effects on ventilation. TRH or taltirelin may have clinical utility as an intravenous or inhaled agent to antagonize opioid-induced cardiorespiratory depression. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

[Distribution of thermostable direct hemolysin (TDH)- and TDH-related hemolysin (TRH)-producing Vibrio parahaemolyticus in coastal Shimane Prefecture and TDH and TRH V parahaemolyticus contamination of retail shellfish].

PubMed

Fukushima, Hiroshi

2007-03-01

We studied distribution of thermostable direct hemolysin (TDH)- and TDH-related hemolysin (TRH)-producing Vibrio parahaemolyticus in coastal sea water, sediment, and shellfish and related retail shellfish contamination in Shimane Prefecture, Japan, between 2002 and 2004. V. parahaemolyticus was isolated from > 80% of sea water, sediment, and shellfish. The detection of TDH gene (tdh) and TRH gene (trh)-positive V parahaemolyticus in sea water was 11%, in sediment 16%, and in shellfish 26%. The number of genes and gene-related in seawater was 23 MPN/L, in sediment 29 MPN/100 g, and in shellfish 460 MPN/10 g. TDH- and TRH-producing V. parahaemolyticus detected in seawater was 5%, in sediment 11% and in shellfish 14%. The continuous distribution of TDH-producing O2:K28, O4:K88, O4:K37, and O4:KUT organisms on the western coast and TRH2-producing O5:k30, O5:K43, O10:K19, O10:KUT, O11:K40, O11:KUT, and OUT:KUT organisms on the Oki Island coast suggested the settlement of these organisms in these coastal environments. From 7 (12%) of 59 retail short-necked clam samples, we isolated TDH-producing O 1:KUT, O3:K6 (2 strains from 2 samples imported from Korea), O4:K12, OUT:K8, and TRH2-producing OUT:K40 and OUT:K51 organisms. These findings suggested that TDH- and TRH-producing V. parahaemolyticus are widely distributed along the coast of this prefecture and are transported by contaminated retail shellfish from other areas.

Effects of hyperthyroidism and hypothyroidism on rat growth hormone release induced by thyrotropin-releasing hormone.

PubMed

Chihara, K; Kato, Y; Ohgo, S; Iwasaki, Y; Maeda, K

1976-06-01

The effect of synthetic thyrotropin-releasing hormone (TRH) on the release of growth hormone (GH) and thyroid-stimulating hormone (TSH) was investigated in euthyroid, hypothyroid, and hyperthyroid rats under urethane anesthesia. In euthyroid control rats, intravenous injection of TRH (200 ng/100 g BW) resulted in a significant increase in both plasma GH and TSH. In rats made hypothyroid by treatment with propylthiouracil or by thyroidectomy, basal GH and TSH levels were significantly elevated with exaggerated responses to TRH. In contrast, plasma GH and TSH responses to TRH were both significantly inhibited in rats made hyperthyroid by L-thyroxine (T4) treatment. These results suggest that altered thyroid status influences GH release as well as TSH secretion induced by TRH in rats.

Intracellular postsynaptic cannabinoid receptors link thyrotropin-releasing hormone receptors to TRPC-like channels in thalamic paraventricular nucleus neurons.

PubMed

Zhang, L; Kolaj, M; Renaud, L P

2015-12-17

In rat thalamic paraventricular nucleus of thalamus (PVT) neurons, activation of thyrotropin-releasing hormone (TRH) receptors enhances excitability via concurrent decrease in G protein-coupled inwardly-rectifying potassium (GIRK)-like and activation of transient receptor potential cation (TRPC)4/5-like cationic conductances. An exploration of intracellular signaling pathways revealed the TRH-induced current to be insensitive to phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitors, but reduced by D609, an inhibitor of phosphatidylcholine-specific PLC (PC-PLC). A corresponding change in the I-V relationship implied suppression of the cationic component of the TRH-induced current. Diacylglycerol (DAG) is a product of the hydrolysis of PC. Studies focused on the isolated cationic component of the TRH-induced response revealed a reduction by RHC80267, an inhibitor of DAG lipase, the enzyme involved in the hydrolysis of DAG to the endocannabinoid 2-arachidonoylglycerol (2-AG). Further investigation revealed enhancement of the cationic component in the presence of either JZL184 or WWL70, inhibitors of enzymes involved in the hydrolysis of 2-AG. A decrease in the TRH-induced response was noted in the presence of rimonabant or SR144528, membrane permeable CB1 and CB2 receptor antagonists, respectively. A decrease in the TRH-induced current by intracellular, but not by bath application of the membrane impermeable peptide hemopressin, selective for CB1 receptors, suggests a postsynaptic intracellular localization of these receptors. The TRH-induced current was increased in the presence of arachidonyl-2'-chloroethylamide (ACEA) or JWH133, CB1 and CB2 receptor agonists, respectively. The PI3-kinase inhibitor LY294002, known to inhibit TRPC translocation, decreased the response to TRH. In addition, a TRH-induced enhancement of the low-threshold spike was prevented by both rimonabant, and SR144528. TRH had no influence on excitatory or inhibitory miniature postsynaptic currents, suggesting presynaptic CB receptors are not involved in this situation. Collectively, the data imply that activation of TRH receptors in these midline thalamic neurons engages novel signaling pathways that include postsynaptic intracellular CB1 and CB2 receptors in the activation of TRPC4/5-like channels. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Treatment-resistant hypertension and the incidence of cardiovascular disease and end-stage renal disease: results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

PubMed

Muntner, Paul; Davis, Barry R; Cushman, William C; Bangalore, Sripal; Calhoun, David A; Pressel, Sara L; Black, Henry R; Kostis, John B; Probstfield, Jeffrey L; Whelton, Paul K; Rahman, Mahboob

2014-11-01

Apparent treatment-resistant hypertension (aTRH) is defined as uncontrolled hypertension despite the use of ≥3 antihypertensive medication classes or controlled hypertension while treated with ≥4 antihypertensive medication classes. Although a high prevalence of aTRH has been reported, few data are available on its association with cardiovascular and renal outcomes. We analyzed data on 14 684 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants to determine the association between aTRH (n=1870) with coronary heart disease, stroke, all-cause mortality, heart failure, peripheral artery disease, and end-stage renal disease. We defined aTRH as blood pressure not at goal (systolic/diastolic blood pressure ≥140/90 mm Hg) while taking ≥3 classes of antihypertensive medication or taking ≥4 classes of antihypertensive medication with blood pressure at goal during the year 2 ALLHAT study visit (1996-2000). Use of a diuretic was not required to meet the definition of aTRH. Follow-up occurred through 2002. The multivariable adjusted hazard ratios (95% confidence intervals) comparing participants with versus without aTRH were as follows: coronary heart disease (1.44 [1.18-1.76]), stroke (1.57 [1.18-2.08]), all-cause mortality (1.30 [1.11-1.52]), heart failure (1.88 [1.52-2.34]), peripheral artery disease (1.23 [0.85-1.79]), and end-stage renal disease (1.95 [1.11-3.41]). aTRH was also associated with the pooled outcomes of combined coronary heart disease (hazard ratio, 1.47; 95% confidence interval, 1.26-1.71) and combined cardiovascular disease (hazard ratio, 1.46; 95% confidence interval, 1.29-1.64). These results demonstrate that aTRH increases the risk for cardiovascular disease and end-stage renal disease. Studies are needed to identify approaches to prevent aTRH and reduce risk for adverse outcomes among individuals with aTRH. © 2014 American Heart Association, Inc.

Effects of thyrotrophin-releasing hormone, and methionine-enkephalin on gastric acid and pepsin secretion in the cat.

PubMed

Gascoigne, A D; Hirst, B H; Reed, J D; Shaw, B

1980-07-01

1 The effect of intravenous administration of thyrotrophin-releasing hormone (TRH) and methionine-enkephalin on gastric acid and pepsin secretions was investigated in conscious cats prepared with chronic gastric fistulae.2 TRH, 20 mug kg(-1) h(-1), did not influence unstimulated gastric acid secretion, nor gastric acid secretion stimulated by submaximal doses of pentagastrin or histamine. Pepsin secretion stimulated by pentagastrin was not influenced by TRH.3 TRH, 20 mug kg(-1) h(-1), significantly reduced the gastric acid and pepsin responses to intravenous infusion of insulin. TRH also significantly reduced the degree of hypoglycaemia seen in response to insulin. TRH, 20 mug kg(-1) h(-1), but not 5 mug kg(-1) h(-1), infused alone resulted in a significant hyperglycaemia.4 It is concluded that the reduction of insulin-stimulated gastric secretion by TRH is not dependent on the hyperglycaemic action of the peptide. The mechanism of action of TRH on insulin-stimulated secretion is discussed with respect to its site of action.5 Methionine-enkephalin or the potent analogue, D-Ala(2), Met-enkephalinamide were without effect on unstimulated gastric secretion, or secretion stimulated by pentagastrin, histamine, and insulin. The opiate receptor antagonist, naloxone, did not significantly alter the gastric acid or pepsin response to insulin.6 It is concluded that there is no evidence that opiates stimulate oxyntic glands directly, nor that the oxyntic cells may possess high affinity binding sites for opiates, nor that endogenous opiates are involved in the control of gastric secretion.

Binding of Thyrotropin-Releasing Hormone to Plasma Membranes of Bovine Anterior Pituitary Gland

PubMed Central

Labrie, Fernand; Barden, Nicholas; Poirier, Guy; De Lean, Andre

1972-01-01

An assay for the binding of [3H]thyrotropin-releasing hormone ([3H]TRH) is described. Plasma membranes isolated from bovine anterior pituitary gland bind about 600 femtomoles of this hormone per mg of protein, as compared to 15 femtomoles per mg of protein in the total adenohypophyseal homogenate (40-fold purification). The equilibrium constant of membrane receptor-[3H]TRH binding at 0°C is 4.3 × 107 L·M-1, or a half-maximal binding of this hormone at 23 nM. The binding is time-dependent; addition of unlabeled hormone induces dissociation of the receptor-[3H]TRH complex with a half-life of 14 min. The binding of TRH is not altered by 10 μM melanocyte-stimulating hormone-release inhibiting hormone, lysine-vasopressin, adrenocorticotropin, growth hormone, prolactin, luteinizing hormone, insulin, glucagon, L-thyroxine, or L-triiodothyronine. K+ and Mg++ increase formation of the receptor-TRH complex at optimal concentrations of 5-25 mM and 0.5-2.5 mM, respectively, with inhibition at higher concentrations. Ca++ inhibits binding of TRH at all concentrations tested. PMID:4621548

Resistant Hypertension, Time-Updated Blood Pressure Values and Renal Outcome in Type 2 Diabetes Mellitus.

PubMed

Viazzi, Francesca; Piscitelli, Pamela; Ceriello, Antonio; Fioretto, Paola; Giorda, Carlo; Guida, Pietro; Russo, Giuseppina; De Cosmo, Salvatore; Pontremoli, Roberto

2017-09-22

Apparent treatment resistant hypertension (aTRH) is highly prevalent in patients with type 2 diabetes mellitus (T2D) and entails worse cardiovascular prognosis. The impact of aTRH and long-term achievement of recommended blood pressure (BP) values on renal outcome remains largely unknown. We assessed the role of aTRH and BP on the development of chronic kidney disease in patients with T2D and hypertension in real-life clinical practice. Clinical records from a total of 29 923 patients with T2D and hypertension, with normal baseline estimated glomerular filtration rate and regular visits during a 4-year follow-up, were retrieved and analyzed. The association between time-updated BP control (ie, 75% of visits with BP <140/90 mm Hg) and the occurrence of estimated glomerular filtration rate <60 and/or a reduction ≥30% from baseline was assessed. At baseline, 17% of patients had aTRH. Over the 4-year follow-up, 19% developed low estimated glomerular filtration rate and 12% an estimated glomerular filtration rate reduction ≥30% from baseline. Patients with aTRH showed an increased risk of developing both renal outcomes (adjusted odds ratio, 1.31 and 1.43; P <0.001 respectively), as compared with those with non-aTRH. No association was found between BP control and renal outcomes in non-aTRH, whereas in aTRH, BP control was associated with a 30% ( P =0.036) greater risk of developing the renal end points. ATRH entails a worse renal prognosis in T2D with hypertension. BP control is not associated with a more-favorable renal outcome in aTRH. The relationship between time-updated BP and renal function seems to be J-shaped, with optimal systolic BP values between 120 and 140 mm Hg. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Differences in recurrent prolapse at 1 year after total vs supracervical hysterectomy and robotic sacrocolpopexy.

PubMed

Myers, Erinn M; Siff, Lauren; Osmundsen, Blake; Geller, Elizabeth; Matthews, Catherine A

2015-04-01

Optimal management of the cervix at the time of hysterectomy and sacrocolpopexy for primary uterovaginal prolapse is unknown. Our hypothesis was that recurrent prolapse at 1 year would be more likely after a supracervical robotic hysterectomy (SRH) compared with a total robotic hysterectomy (TRH) at the time of robotic sacrocolpopexy (RSCP) for uterovaginal prolapse. This was a retrospective cohort analysis of 83 women who underwent hysterectomy with RSCP over a 24-month period (40 with TRH and 43 with SRH). At 1 year post-procedure, subjects completed validated questionnaires regarding pelvic floor symptoms, sexual function, and global satisfaction, and underwent a pelvic examination to identify mesh exposure and evaluate pelvic floor support. Demographics of the two groups were similar, except for a higher mean body mass index in the TRH group (31.9 TRH vs 25.8 SRH kg/m(2), p < 0.001). The rate of recurrent prolapse ≥ stage II was higher for women who underwent SRH compared with TRH (41.9 % vs 20.0 %, p = 0.03; OR 2.8, 95 % CI, 1.07-7.7). However, when this was analyzed as recurrence ≥ hymen, there was no difference between groups (12.5 % TRH vs 18.6 % SRH, p = 0.45). Likewise, there was no difference between groups when a composite measure of success was used (30 out of 40 [75 %] TRH vs 29 out of 43 [67.4 %] SRH, p = 0.45). Women who underwent an SRH were 2.8 times more likely to have a recurrent prolapse, ≥ stage II, at 1 year, compared with those who underwent a TRH, but when composite assessment scores were used there was no difference between the groups.

Coarse-Grained Molecular Dynamics Simulations of Membrane-Trehalose Interactions.

PubMed

Kapla, Jon; Stevensson, Baltzar; Maliniak, Arnold

2016-09-15

It is well established that trehalose (TRH) affects the physical properties of lipid bilayers and stabilizes biological membranes. We present molecular dynamics (MD) computer simulations to investigate the interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH. Both atomistic and coarse-grained (CG) interaction models were employed, and the coarse graining of DMPC leads to a reduction in the acyl chain length corresponding to a 1,2-dilauroyl-sn-glycero-3-phosphocholine lipid (DLPC). Several modifications of the Martini interaction model, used for CG simulations, were implemented, resulting in different potentials of mean force (PMFs) for DMPC bilayer-TRH interactions. These PMFs were subsequently used in a simple two-site analytical model for the description of sugar binding at the membrane interface. In contrast to that in atomistic MD simulations, the binding in the CG model was not in agreement with the two-site model. Our interpretation is that the interaction balance, involving water, TRH, and lipids, in the CG systems needs further tuning of the force-field parameters. The area per lipid is only weakly affected by TRH concentration, whereas the compressibility modulus related to the fluctuations of the membrane increases with an increase in TRH content. In agreement with experimental findings, the bending modulus is not affected by the inclusion of TRH. The important aspects of lipid bilayer interactions with biomolecules are membrane curvature generation and sensing. In the present investigation, membrane curvature is generated by artificial buckling of the bilayer in one dimension. It turns out that TRH prefers the regions with the highest curvature, which enables the most favorable situation for lipid-sugar interactions.

The contributions of unhealthy lifestyle factors to apparent resistant hypertension: findings from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.

PubMed

Shimbo, Daichi; Levitan, Emily B; Booth, John N; Calhoun, David A; Judd, Suzanne E; Lackland, Daniel T; Safford, Monika M; Oparil, Suzanne; Muntner, Paul

2013-02-01

Unhealthy lifestyle factors may contribute to apparent treatment resistant hypertension (aTRH). We examined associations of unhealthy lifestyle factors with aTRH in individuals taking antihypertensive medications from three or more classes. Participants (n = 2602) taking three or more antihypertensive medication classes were identified from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was defined as having SBP/DBP at least 140/90 mmHg despite the use of three or more antihypertensive medication classes or the use of four or more classes to achieve blood pressure control. Lifestyle factors included obesity, physical inactivity, current smoking, heavy alcohol consumption, a low Dietary Approaches to Stop Hypertension (DASH) diet score and high sodium-to-potassium (Na/K) intake. Among participants taking three or more antihypertensive medication classes, 1293 (49.7%) participants had aTRH. The prevalence of unhealthy lifestyle factors in participants with and without aTRH was 55.2 and 51.7%, respectively, for obesity, 42.2 and 40.5% for physical inactivity, 11.3 and 11.5% for current smoking, 3.1 and 4.0% for heavy alcohol consumption, 23.1 and 21.5% for low-DASH diet score, and 25.4 and 24.4% for high Na/K intake. After adjustment for age, sex, race, and geographic region of residence, none of the unhealthy lifestyle factors were associated with aTRH. The associations between each unhealthy lifestyle factor and aTRH remained nonsignificant after additional adjustment for education, income, depressive symptoms, total calorie intake, and comorbidities. Unhealthy lifestyle factors did not have independent associations with aTRH among individuals taking three or more antihypertensive medication classes.

The Contributions of Unhealthy Lifestyle Factors to Apparent Resistant Hypertension: Findings from the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

PubMed Central

Shimbo, Daichi; Levitan, Emily B.; Booth, John N.; Calhoun, David A.; Judd, Suzanne E.; Lackland, Daniel T.; Safford, Monika M.; Oparil, Suzanne; Muntner, Paul

2013-01-01

Objectives Unhealthy lifestyle factors may contribute to apparent treatment resistant hypertension (aTRH). We examined associations of unhealthy lifestyle factors with aTRH in individuals taking antihypertensive medications from three or more classes. Methods Participants (n=2,602) taking three or more antihypertensive medication classes were identified from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was defined as having systolic/diastolic blood pressure ≥140/90 mmHg despite the use of three or more antihypertensive medication classes or the use of four or more classes to achieve blood pressure control. Lifestyle factors included obesity, physical inactivity, current smoking, heavy alcohol consumption, a low DASH diet score and high sodium-to-potassium (Na/K) intake. Results Among participants taking three or more antihypertensive medication classes, 1,293 (49.7%) participants had aTRH. The prevalence of unhealthy lifestyle factors in participants with and without aTRH was 55.2% and 51.7% respectively for obesity, 42.2% and 40.5% for physical inactivity, 11.3% and 11.5% for current smoking, 3.1% and 4.0% for heavy alcohol consumption, 23.1% and 21.5% for low DASH diet score, and 25.4% and 24.4% for high Na/K intake. After adjustment for age, sex, race, and geographic region of residence, none of the unhealthy lifestyle factors was associated with aTRH. The associations between each unhealthy lifestyle factor and aTRH remained non-significant after additional adjustment for education, income, depressive symptoms, total calorie intake, and co-morbidities. Conclusions Unhealthy lifestyle factors did not have independent associations with aTRH among individuals taking three or more antihypertensive medication classes. PMID:23303356

Prevalence and clinical characteristics of apparent therapy-resistant hypertension in patients with cardiovascular disease: a cross-sectional cohort study in secondary care

PubMed Central

de Beus, Esther; van der Sande, Nicolette G C; Bots, Michiel L; Spiering, Wilko; Voskuil, Michiel; Visseren, Frank L J; Blankestijn, Peter J

2017-01-01

Objectives Our aim was to investigate the prevalence of apparent therapy-resistant hypertension (aTRH) in patients with clinical manifest cardiovascular disease (CVD), and to study clinical characteristics related to aTRH in this population. Setting The SMART (Second Manifestations of ARTerial disease) study is a large, single-centre cohort study in secondary care. Participants Office blood pressure (BP) at inclusion was used to evaluate BP control in 6191 hypertensive patients with clinical manifest (cardio)vascular disease. Therapy-resistant hypertension was defined as BP ≥140/90 mm Hg despite use of antihypertensive drugs from ≥3 drug classes including a diuretic or use of ≥4 antihypertensive drugs irrespective of BP. Logistic regression analysis was used to explore the relationship between clinical characteristics measured at baseline and presence of aTRH. Results The prevalence of aTRH was 9.1% (95% CI 8.4 to 9.8). Prevalence increased with age and when albuminuria was present and was higher in patients with lower estimated glomerular filtration rate (eGFR). Presence of aTRH was related to diabetes, female sex, duration and multiple locations of vascular disease, body mass index and waist circumference. Carotid intima-media thickness was higher (0.99±0.28 vs 0.93±0.28 mm) and ankle-brachial index lower (1.07±0.20 vs 1.10±0.19) in patients with aTRH compared with patients without aTRH. Conclusion aTRH is prevalent in patients with clinical manifest CVD and is related to clinical factors known to be related with increased vascular risk, and with lower eGFR. PMID:28882918

Comparison of TRH and anorexigenic peptide on food intake and gastrointestinal secretions.

PubMed

Konturek, S J; Tasler, J; Jaworek, J; Dobrzańska, M; Coy, D H; Schally, A V

1981-01-01

Thyrotropin releasing hormone (TRH), distributed throughout the gastrointestinal tract, and anorexigenic peptide (AP), isolated recently from the urine of females with "hypothalamic" anorexia nervosa, have been shown to affect food intake but no study has been performed to compare their action on gastrointestinal secretions. This report shows that both TRH and AP reduce dose-dependently the food intake during sham-feeding and inhibit gastric and pancreatic secretions in response to various exogenous and endogenous stimulants in conscious dogs. The results indicate that TRH and AP have similar inhibitory action on feeding and gastrointestinal secretory activity and that they may be involved in peptidergic mediation of satiety and gastrointestinal secretion.

Use of basal and TRH-stimulated plasma growth hormone concentrations to differentiate between primary hypothyroidism and nonthyroidal illness in dogs.

PubMed

Pijnacker, Tera; Kooistra, Hans S; Vermeulen, Cathelijne F; van der Vinne, Merel; Prins, Marrit; Galac, Sara; Mol, Jan A

2018-05-07

A low plasma total thyroxine (TT 4 ) concentration in combination with a plasma TSH concentration within reference range does not distinguish between hypothyroidism and nonthyroidal illness (NTI) in dogs. Hypothyroidism is associated with TSH-releasing hormone (TRH)-induced increased release of growth hormone (GH). Basal and TRH-induced plasma GH concentrations can be used to distinguish hypothyroid dogs from NTI dogs. Twenty-one dogs with signs consistent with hypothyroidism, a low plasma TT 4 concentration, and a plasma TSH concentration within reference interval. Case control study. Thyroid scintigraphy was performed to classify dogs as having hypothyroidism or NTI. All dogs underwent a TRH stimulation test with measurement of plasma concentrations of GH and TSH before and 30 and 45 minutes after IV administration of TRH. Eleven of the dogs were classified as hypothyroid and 10 as having NTI. Basal plasma GH concentration in the hypothyroid dogs (3.2 μg/l; range, 2.0 to 12.5 μg/l) was significantly higher (p<0.001) than that in the NTI dogs (.73 μg/l; range, .45 to 2.3 μg/l), with minimal overlap, and increased (p=.009) after TRH administration in hypothyroid dogs, whereas it did not change in NTI dogs. At T=45, plasma GH concentrations in hypothyroid dogs and NTI dogs did not overlap. The plasma TSH concentration did not change significantly after TRH administration in hypothyroid dogs, whereas it increased (p<.001) in NTI dogs. At T=45, there was no overlap in percentage TSH increase from baseline between hypothyroid dogs. Measurement of basal plasma GH concentration and concentrations of GH and TSH after TRH stimulation can distinguish between hypothyroidism and NTI in dogs. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Prevalence and clinical characteristics of patients with true resistant hypertension in central and Eastern Europe: data from the BP-CARE study.

PubMed

Brambilla, Gianmaria; Bombelli, Michele; Seravalle, Gino; Cifkova, Renata; Laurent, Stephane; Narkiewicz, Krzysztof; Facchetti, Rita; Redon, Josep; Mancia, Giuseppe; Grassi, Guido

2013-10-01

Scanty information is available on the clinical characteristics of resistant hypertension in Central and East European countries. The Blood Pressure (BP) control rate and CArdiovascular Risk profilE (BP-CARE) study allowed us to assess the prevalence and the main clinical features of resistant hypertension in this population. The study was carried out in 1312 treated hypertensive patients living in nine Central and East European countries. Four hundred and twenty-three patients had apparent resistant hypertension, of whom 168 had pseudo-resistant hypertension (noncompliant/white-coat) and 255 were true treatment-resistant hypertension patients (TRH). Clinical BP values in TRH amounted to 157.4±16.9/91.8±10.0 mmHg despite the daily use of 3.6±0.7 drugs. Their 24-h BP values were 149.5±16.5/97.5±9.8 mmHg. Compared to controlled hypertensive patients (n=368) and uncontrolled nonresistant hypertensive patients (n=521), TRH were older with a greater prevalence of women. They showed a higher rate of previous cardiovascular events and a very high cardiovascular risk profile. Estimated glomerular filtration rate was significantly lower in TRH as compared to controlled hypertensive patients and uncontrolled nonresistant hypertensive patients. Overall, target organ damage was more frequently detected in TRH than in controlled hypertensive patients and uncontrolled nonresistant hypertensive patients. The factor most frequently associated with TRH was severity of hypertension followed by age, total cholesterol, BMI and history of heart failure. The present study provides evidence that the prevalence of TRH in Central and East European countries is similar to that found in Western Europe and USA. It also shows the very high cardiovascular risk of TRH and the elevated association of this condition with obesity, renal failure, organ damage and history of cardiovascular events.

Prevalence and clinical characteristics of apparent therapy-resistant hypertension in patients with cardiovascular disease: a cross-sectional cohort study in secondary care.

PubMed

de Beus, Esther; van der Sande, Nicolette G C; Bots, Michiel L; Spiering, Wilko; Voskuil, Michiel; Visseren, Frank L J; Blankestijn, Peter J

2017-09-06

Our aim was to investigate the prevalence of apparent therapy-resistant hypertension (aTRH) in patients with clinical manifest cardiovascular disease (CVD), and to study clinical characteristics related to aTRH in this population. The SMART (Second Manifestations of ARTerial disease) study is a large, single-centre cohort study in secondary care. Office blood pressure (BP) at inclusion was used to evaluate BP control in 6191 hypertensive patients with clinical manifest (cardio)vascular disease. Therapy-resistant hypertension was defined as BP ≥140/90 mm Hg despite use of antihypertensive drugs from ≥3 drug classes including a diuretic or use of ≥4 antihypertensive drugs irrespective of BP. Logistic regression analysis was used to explore the relationship between clinical characteristics measured at baseline and presence of aTRH. The prevalence of aTRH was 9.1% (95% CI 8.4 to 9.8). Prevalence increased with age and when albuminuria was present and was higher in patients with lower estimated glomerular filtration rate (eGFR). Presence of aTRH was related to diabetes, female sex, duration and multiple locations of vascular disease, body mass index and waist circumference. Carotid intima-media thickness was higher (0.99±0.28 vs 0.93±0.28 mm) and ankle-brachial index lower (1.07±0.20 vs 1.10±0.19) in patients with aTRH compared with patients without aTRH. aTRH is prevalent in patients with clinical manifest CVD and is related to clinical factors known to be related with increased vascular risk, and with lower eGFR. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Characterization and distribution of GHRH, PACAP, TRH, SST and IGF1 mRNAs in the green iguana.

PubMed

Ávila-Mendoza, José; Pérez-Rueda, Ernesto; Urban-Sosa, Valeria; Carranza, Martha; Martínez-Moreno, Carlos G; Luna, Maricela; Arámburo, Carlos

2018-01-01

The somatotropic axis (SA) regulates numerous aspects of vertebrate physiology such as development, growth, and metabolism and has influence on several tissues including neural, immune, reproductive and gastric tract. Growth hormone (GH) is a key component of SA, it is synthesized and released mainly by pituitary somatotrophs, although now it is known that virtually all tissues can express GH, which, in addition to its well-described endocrine roles, also has autocrine/paracrine/intracrine actions. In the pituitary, GH expression is regulated by several hypothalamic neuropeptides including GHRH, PACAP, TRH and SST. GH, in turn, regulates IGF1 synthesis in several target tissues, adding complexity to the system since GH effects can be exerted either directly or mediated by IGF1. In reptiles, little is known about the SA components and their functional interactions. The aim of this work was to characterize the mRNAs of the principal SA components in the green iguana and to develop the tools that allow the study of the structural and functional evolution of this system in reptiles. By employing RT-PCR and RACE, the cDNAs encoding for GHRH, PACAP, TRH, SST and IGF1 were amplified and sequenced. Results showed that these cDNAs coded for the corresponding protein precursors of 154, 170, 243, 113, and 131 amino acids, respectively. Of these, GHRH, PACAP, SST and IGF1 precursors exhibited a high structural conservation with respect to its counterparts in other vertebrates. On the other hand, iguana's TRH precursor showed 7 functional copies of mature TRH (pyr-QHP-NH 2 ), as compared to 4 and 6 copies of TRH in avian and mammalian proTRH sequences, respectively. It was found that in addition to its primary production site (brain for GHRH, PACAP, TRH and SST, and liver for IGF1), they were also expressed in other peripheral tissues, i.e. testes and ovaries expressed all the studied mRNAs, whereas TRH and IGF1 mRNAs were observed ubiquitously in all tissues considered. These results show that the main SA components in reptiles of the Squamata Order maintain a good structural conservation among vertebrate phylogeny, and suggest important physiological interactions (endocrine, autocrine and/or paracrine) between them due to their wide peripheral tissue expression. Copyright © 2017 Elsevier Inc. All rights reserved.

Differential response of TRHergic neurons of the hypothalamic paraventricular nucleus (PVN) in female animals submitted to food-restriction or dehydration-induced anorexia and cold exposure.

PubMed

Jaimes-Hoy, Lorraine; Joseph-Bravo, Patricia; de Gortari, Patricia

2008-02-01

TRH neurons of the hypothalamic paraventricular nucleus (PVN), regulate pituitary-thyroid axis (HPT). Fasting activates expression of orexigenic peptides from the arcuate nucleus, increases corticosterone while reduces leptin, and pro-TRH mRNA levels despite low serum thyroid hormone concentration (tertiary hypothyroidism). TRH synthesis is positively regulated by anorexigenic peptides whose expression is reduced in fasting. The model of dehydration-induced anorexia (DIA) leads to decreased voluntary food intake but peptide expression in the arcuate is similar to forced-food restriction (FFR), where animals remain hungered. We compared the response of HPT axis of female Wistar rats submitted to DIA (2.5% saline solution, food ad libitum, 7 days) with FFR (provided with the amount of food ingested by DIA) and naïve (N) group fed ad libitum, as well as their response to acute cold exposure. Pro-TRH and pro-CRH mRNA levels in the PVN were measured by RT-PCR, TRH content, serum concentration of TSH and thyroid hormones by radioimmunoassay. DIA rats reduced 80% their food consumption compared to N, decreased PVN pro-CRH expression, serum estradiol and leptin levels, increased corticosterone similar to FFR. HPT axis of DIA animals failed to adapt: FFR presented tertiary hypothyroidism and DIA, primary. Response to cold stimulation leading to increased pro-TRH mRNA levels and TRH release was preserved under reduced energy availability in FFR rats but not in DIA, although the dynamics of hormonal release differed: TSH release augmented only in naïve; thyroxine in all but highest in DIA, and triiodothyronine in FFR and DIA suggesting a differential regulation of deiodinases.

Prevalence of treatment-resistant hypertension after considering pseudo-resistance and morbidity: a cross-sectional study in Irish primary care.

PubMed

Hayes, Peter; Casey, Monica; Glynn, Liam G; Molloy, Gerard J; Durand, Hannah; O'Brien, Eoin; Dolan, Eamon; Newell, John; Murphy, Andrew W

2018-06-01

To confirm treatment-resistant hypertension (TRH), ambulatory blood pressure measurement (ABPM) must exclude white-coat hypertension (WCH), three or more medications should be prescribed at the optimal doses tolerated, and non-adherence and lifestyle should be examined. Most previous studies have not adequately considered pseudo-resistance and merely provide an apparent TRH (aTRH) prevalence figure. To conduct a cross-sectional study of the prevalence of aTRH in general practice, and then consider pseudo-resistance and morbidity. With support, 16 practices ran an anatomical therapeutic chemical (ATC) drug search, identifying patients on any possible hypertensive medications, and then a search of individual patients' electronic records took place. ABPM was used to rule out WCH. The World Health Organization-defined daily dosing guidelines determined adequate dosing. Adherence was defined as whether patients requested nine or more repeat monthly prescriptions within the past year. Sixteen practices participated ( n = 50 172), and 646 patients had aTRH. Dosing was adequate in 19% of patients, 84% were adherent to medications, as defined by prescription refill, and 43% had ever had an ABPM. Using a BP cut-off of 140/90 mmHg, the prevalence of aTRH was 9% (95% confidence interval [CI] = 9.0 to 10.0). Consideration of pseudo-resistance further reduced prevalence rates to 3% (95% CI = 3.0 to 4.0). Reviewing individual patient records results in a lower estimate of prevalence of TRH than has been previously reported. Further consideration for individual patients of pseudo-resistance additionally lowers these estimates, and may be all that is required for management in the vast majority of cases. © British Journal of General Practice 2018.

Proceedings from Duke resistant hypertension think tank.

PubMed

Vemulapalli, Sreekanth; Ard, Jamy; Bakris, George L; Bhatt, Deepak L; Brown, Alan S; Cushman, William C; Ferdinand, Keith C; Flack, John M; Fleg, Jerome L; Katzen, Barry T; Kostis, John B; Oparil, Suzanne; Patel, Chet B; Pepine, Carl J; Piña, Ileana L; Rocha-Singh, Krishna J; Townsend, Raymond R; Peterson, Eric D; Califf, Robert M; Patel, Manesh R

2014-06-01

To identify patients at increased risk for cardiovascular outcomes, apparent treatment resistant hypertension (aTRH) is defined as having a blood pressure (BP) above goal despite the use of ≥3 antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. In light of growing scientific interest in the treatment of this group, a multistakeholder think tank was convened to discuss the current state of knowledge, improve the care of these patients, and identify appropriate study populations for future observational and randomized trials in the field. Although recent epidemiologic studies in selected populations estimate that the prevalence of aTRH is 10% to 15% of hypertensive patients, further large-scale observational studies will be needed to better elucidate risk factors. To spur the development of therapies for aTRH, the development of an "aTRH" label for pharmacologic and device therapies with a developmental pathway including treatment added to the use of existing therapies is favored. Although demonstration of adequate BP lowering should be sufficient to gain Food and Drug Administration approval for therapies targeting aTRH, assessment of improvement in quality of life and cardiovascular outcomes is also desirable and considered in Centers for Medicare and Medicaid Services coverage decisions. Device trials under the aTRH label will need uniform and consistent processes for defining appropriate patient populations as well as postapproval registries assessing both long-term safety and duration of responses. Finally, patients with aTRH are likely to benefit from evaluation by a hypertension team to assure proper patient identification, diagnostic work-up, and therapeutic management before consideration of advanced or novel therapies to lower BP. Copyright © 2014 Mosby, Inc. All rights reserved.

Genetic diversity of clinical and environmental Vibrio parahaemolyticus strains from the Pacific Northwest.

PubMed

Paranjpye, Rohinee; Hamel, Owen S; Stojanovski, Asta; Liermann, Martin

2012-12-01

Since 1997, cases of Vibrio parahaemolyticus-related gastroenteritis from the consumption of raw oysters harvested in Washington State have been higher than historical levels. These cases have shown little or no correlation with concentrations of potentially pathogenic V. parahaemolyticus (positive for the thermostable direct hemolysin gene, tdh) in oysters, although significant concentrations of tdh(+) V. parahaemolyticus strains were isolated from shellfish-growing areas in the Pacific Northwest (PNW). We compared clinical and environmental strains isolated from the PNW to those from other geographic regions within the United States and Asia for the presence of virulence-associated genes, including the thermostable direct hemolysin (tdh), the thermostable-related hemolysin (trh), urease (ureR), the pandemic group specific markers orf8 and toxRS, and genes encoding both type 3 secretion systems (T3SS1 and T3SS2). The majority of clinical strains from the PNW were positive for tdh, trh, and ureR genes, while a significant proportion of environmental isolates were tdh(+) but trh negative. Hierarchical clustering grouped the majority of these clinical isolates into a cluster distinct from that including the pandemic strain RIMD2210633, clinical isolates from other geographical regions, and tdh(+), trh-negative environmental isolates from the PNW. We detected T3SS2-related genes (T3SS2β) in environmental strains that were tdh and trh negative. The presence of significant concentrations of tdh(+), trh-negative environmental strains in the PNW that have not been responsible for illness and T3SS2β in tdh- and trh-negative strains emphasizes the diversity in this species and the need to identify additional virulence markers for this bacterium to improve risk assessment tools for the detection of this pathogen.

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity.

PubMed

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-08-03

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9-5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r(2) = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r(2) = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies.

Pituitary response to thyrotropin releasing hormone in children with overweight and obesity

PubMed Central

Rijks, Jesse; Penders, Bas; Dorenbos, Elke; Straetemans, Saartje; Gerver, Willem-Jan; Vreugdenhil, Anita

2016-01-01

Thyroid stimulating hormone (TSH) concentrations in the high normal range are common in children with overweight and obesity, and associated with increased cardiovascular disease risk. Prior studies aiming at unravelling the mechanisms underlying these high TSH concentrations mainly focused on factors promoting thyrotropin releasing hormone (TRH) production as a cause for high TSH concentrations. However, it is unknown whether TSH release of the pituitary in response to TRH is affected in children with overweight and obesity. Here we describe TSH release of the pituitary in response to exogenous TRH in 73 euthyroid children (39% males) with overweight or (morbid) obesity. Baseline TSH concentrations (0.9–5.5 mU/L) were not associated with BMI z score, whereas these concentrations were positively associated with TSH concentrations 20 minutes after TRH administration (r2 = 0.484, p < 0.001) and the TSH incremental area under the curve during the TRH stimulation test (r2 = 0.307, p < 0.001). These results suggest that pituitary TSH release in response to TRH stimulation might be an important factor contributing to high normal serum TSH concentrations, which is a regular finding in children with overweight and obesity. The clinical significance and the intermediate factors contributing to pituitary TSH release need to be elucidated in future studies. PMID:27485208

Effects of long-term intraperitoneal injection of thyrotropin-releasing hormone (TRH) on aging- and obesity-related changes in body weight, lipid metabolism, and thyroid functions.

PubMed

Pierpaoli, Walter; Lesnikov, Vladimir A

2011-02-01

Adult adipose mice, high fat diet-fed (HFD) mice, anterior hypothalamus-lesioned obese mice and genetically obese mice, were injected daily with thyrotropin releasing hormone (TRH). The treatment provoked a mobilization of triglycerides in the peripheral blood, a decrease of leptin and a loss of body weight. The weight loss did not depend on TSH-mediated stimulation of thyroid hormone secretion with consequent metabolic hyperthyroidism. The levels of blood cholesterol were not affected or even suppressed. Even at a very high dosage TRH did not affect the obesity of genetically obese mice. The ubiquitous tripeptide TRH may thus constitute a key element in the hormone-controlled regulation of body weight and fat stores in the adult and aging body.

Acute response of hypophysiotropic thyrotropin releasing hormone neurons and thyrotropin release to behavioral paradigms producing varying intensities of stress and physical activity.

PubMed

Gutiérrez-Mariscal, Mariana; Sánchez, Edith; García-Vázquez, Arlene; Rebolledo-Solleiro, Daniela; Charli, Jean-Louis; Joseph-Bravo, Patricia

2012-11-10

The activity of the hypothalamus-pituitary-thyroid (HPT) axis is essential for energy homeostasis and is differentially modulated by physical and by psychological stress. Contradictory effects of stressful behavioral paradigms on TSH or thyroid hormone release are due to type, length and controllability of the stressor. We hypothesized that an additional determinant of the activity of the HPT axis is the energy demand due to physical activity. We thus evaluated the response of thyrotropin releasing hormone (TRH) neurons of the hypothalamic paraventricular nucleus (PVN) in Wistar male rats submitted to the elevated plus maze (EPM), the open field test (OFT), or restraint, and sacrificed within 1h after test completion; the response to OFT was compared during light (L) or dark (D) phases. Locomotion and anxiety behaviors were similar if animals were tested in L or D phases but their relation to the biochemical parameters differed. All paradigms increased serum corticosterone concentration; the levels of corticotropin releasing hormone receptor 1 and of glucocorticoid receptor (GR) mRNAs in the PVN were enhanced after restraint or OFT-L. Levels of proTRH mRNA increased in the PVN after exposure to EPM-L or OFT-D; serum levels of thyrotropin (TSH) and T(4) only after OFT-D. In contrast, restraint decreased TRH mRNA and serum TSH levels, while it increased TRH content in the mediobasal hypothalamus, implying reduced release. Expression of proTRH in the PVN varied proportionally to the degree of locomotion in OFT-D, while inversely to anxiety in the EPM-L, and to corticosterone in EPM-L and OFT-D. TRH mRNA levels were analyzed by in situ hybridization in the rostral, middle and caudal zones of the PVN in response to OFT-D; they increased in the middle PVN, where most TRH hypophysiotropic neurons reside; levels correlated positively with the velocity attained in the periphery of the OF and negatively, with anxiety. Variations of serum TSH levels correlated positively with locomotor activity in EPM-L and OFT-L or -D, while negatively to serum corticosterone levels in all paradigms. These results support the proposal that the hypophysiotropic PVN TRH neurons are activated by short term physical activity but that this response may be blunted by the inhibitory effect of stress. Copyright © 2012 Elsevier B.V. All rights reserved.

Taltirelin alleviates fatigue-like behavior in mouse models of cancer-related fatigue.

PubMed

Dougherty, John P; Wolff, Brian S; Cullen, Mary J; Saligan, Leorey N; Gershengorn, Marvin C

2017-10-01

Fatigue affects most cancer patients and has numerous potential causes, including cancer itself and cancer treatment. Cancer-related fatigue (CRF) is not relieved by rest, can decrease quality of life, and has no FDA-approved therapy. Thyrotropin-releasing hormone (TRH) has been proposed as a potential novel treatment for CRF, but its efficacy against CRF remains largely untested. Thus, we tested the TRH analog, taltirelin (TAL), in mouse models of CRF. To model fatigue, we used a mouse model of chemotherapy, a mouse model of radiation therapy, and mice bearing colon 26 carcinoma tumors. We used the treadmill fatigue test to assess fatigue-like behavior after treatment with TAL. Additionally, we used wild-type and TRH receptor knockout mice to determine which TRH receptor was necessary for the actions of TAL. Tumor-bearing mice displayed muscle wasting and all models caused fatigue-like behavior, with mice running a shorter distance in the treadmill fatigue test than controls. TAL reversed fatigue-like behavior in all three models and the mouse TRH 1 receptor was necessary for the effects of TAL. These data suggest that TAL may be useful in alleviating fatigue in all cancer patients and provide further support for evaluating TAL as a potential therapy for CRF in humans. Published by Elsevier Ltd.

Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats.

PubMed

Yang, H; Taché, Y

1997-05-01

Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L.

PubMed

Lee, You-Jeong; Kim, Chung-Hoon; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

2014-11-01

To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH.

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with basal thyroid-stimulating hormone levels of 2.5 to 5.0 mIU/L

PubMed Central

Lee, You-Jeong; Kwack, Jae-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

2014-01-01

Objective To investigate the prevalence of subclinical hypothyroidism (SH) diagnosed by thyrotropin-releasing hormone (TRH) stimulating test in infertile women with basal thyroid-stimulating hormone (TSH) levels of 2.5 to 5.0 mIU/L. Methods This study was performed in 39 infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) who had basal serum TSH levels of 2.5 to 5.0 mIU/L and a TRH stimulating test. Serum TSH levels were measured before TRH injection (TSH0) and also measured at 20 minutes (TSH1) and 40 minutes (TSH2) following intravenous injection of 400 µg TRH. Exaggerated TSH response above 30 mIU/L following TRH injection was diagnosed as SH. Group 1 was composed of poor responders (subgroup A), patients with polycystic ovary syndrome (subgroup B) and patients with WHO group II anovulation except poor responder or polycystic ovary syndrome (subgroup C). Results The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (P=0.001). TSH0, TSH1, and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (P<0.001, P<0.001, P<0.001). In group 1, TSH1 and TSH2 levels were significantly lower in subgroup C compared with those in subgroup A and B (P=0.008, P=0.006, respectively). Conclusion TRH stimulation test had better be performed in infertile women with ovulatory disorders who have TSH levels between 2.5 and 5.0 mIU/L for early detection and appropriate treatment of SH. PMID:25469340

Calcium signaling properties of a thyrotroph cell line, mouse TαT1 cells.

PubMed

Tomić, Melanija; Bargi-Souza, Paula; Leiva-Salcedo, Elias; Nunes, Maria Tereza; Stojilkovic, Stanko S

2015-12-01

TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs. Spontaneous electrical activity is coupled to small amplitude fluctuations in intracellular calcium, whereas TRH stimulates both calcium mobilization from intracellular pools and calcium influx. Non-receptor-mediated depletion of intracellular pool also leads to a prominent facilitation of calcium influx. Both receptor and non-receptor stimulated calcium influx is substantially attenuated but not completely abolished by inhibition of voltage-gated calcium channels, suggesting that depletion of intracellular calcium pool in these cells provides a signal for both voltage-independent and -dependent calcium influx, the latter by facilitating the pacemaking activity. These cells also express purinergic P2Y1 receptors and their activation by extracellular ATP mimics TRH action on calcium mobilization and influx. The thyroid hormone triiodothyronine prolongs duration of TRH-induced calcium spikes during 30-min exposure. These data indicate that TαT1 cells are capable of responding to natively feed-forward TRH signaling and intrapituitary ATP signaling with acute calcium mobilization and sustained calcium influx. Amplification of TRH-induced calcium signaling by triiodothyronine further suggests the existence of a pathway for positive feedback effects of thyroid hormones probably in a non-genomic manner. Published by Elsevier Ltd.

FOOD-INTAKE DYSREGULATION IN TYPE 2 DIABETIC GOTO-KAKIZAKI RATS: HYPOTHESIZED ROLE OF DYSFUNCTIONAL BRAINSTEM THYROTROPIN-RELEASING HORMONE AND IMPAIRED VAGAL OUTPUT

PubMed Central

Zhao, K.; Ao, Y.; Harper, R.M.; Go, V. L.W.; Yang, H.

2013-01-01

Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56–81% in GK rats. Fasting (48 h) and refeeding (2 h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. PMID:23701881

Food-intake dysregulation in type 2 diabetic Goto-Kakizaki rats: hypothesized role of dysfunctional brainstem thyrotropin-releasing hormone and impaired vagal output.

PubMed

Zhao, K; Ao, Y; Harper, R M; Go, V L W; Yang, H

2013-09-05

Thyrotropin-releasing hormone (TRH), a neuropeptide contained in neural terminals innervating brainstem vagal motor neurons, enhances vagal outflow to modify multisystemic visceral functions and food intake. Type 2 diabetes (T2D) and obesity are accompanied by impaired vagal functioning. We examined the possibility that impaired brainstem TRH action may contribute to the vagal dysregulation of food intake in Goto-Kakizaki (GK) rats, a T2D model with hyperglycemia and impaired central vagal activation by TRH. Food intake induced by intracisternal injection of TRH analog was reduced significantly by 50% in GK rats, compared to Wistar rats. Similarly, natural food intake in the dark phase or food intake after an overnight fast was reduced by 56-81% in GK rats. Fasting (48h) and refeeding (2h)-associated changes in serum ghrelin, insulin, peptide YY, pancreatic polypeptide and leptin, and the concomitant changes in orexigenic or anorexigenic peptide expression in the brainstem and hypothalamus, all apparent in Wistar rats, were absent or markedly reduced in GK rats, with hormone release stimulated by vagal activation, such as ghrelin and pancreatic polypeptide, decreased substantially. Fasting-induced Fos expression accompanying endogenous brainstem TRH action decreased by 66% and 91%, respectively, in the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) in GK rats, compared to Wistar rats. Refeeding abolished fasting-induced Fos-expression in the NTS, while that in the DMV remained in Wistar but not GK rats. These findings indicate that dysfunctional brainstem TRH-elicited vagal impairment contributes to the disturbed food intake in T2D GK rats, and may provide a pathophysiological mechanism which prevents further weight gain in T2D and obesity. Published by Elsevier Ltd.

Thyrotropin-releasing hormone-induced growth hormone secretion in dogs with primary hypothyroidism.

PubMed

Diaz-Espiñeira, M M; Galac, S; Mol, J A; Rijnberk, A; Kooistra, H S

2008-02-01

Primary hypothyroidism in dogs is associated with increased release of growth hormone (GH). In search for an explanation we investigated the effect of intravenous administration of thyrotropin-releasing hormone (TRH, 10 microg/kg body weight) on GH release in 10 dogs with primary hypothyroidism and 6 healthy control dogs. The hypothyroid dogs had a medical history and physical changes compatible with hypothyroidism and were included in the study on the basis of the following criteria: plasma thyroxine concentration < 2 nmol/l and plasma thyrotropin (TSH) concentration > 1 microg/l. In addition, (99m)TcO(4)(-) uptake during thyroid scintigraphy was low or absent. TRH administration caused plasma TSH concentrations to rise significantly in the control dogs, but not in the hypothyroid dogs. In the dogs with primary hypothyroidism, the mean basal plasma GH concentration was relatively high (2.3+/-0.5 microg/l) and increased significantly (P=0.001) 10 and 20 min after injection of TRH (to 11.9+/-3.5 and 9.8+/-2.7 microg/l, respectively). In the control dogs, the mean basal plasma GH concentration was 1.3+/-0.1 microg/l and did not increase significantly after TRH administration. We conclude that, in contrast to healthy control dogs, primary hypothyroid dogs respond to TRH administration with a significant increase in the plasma GH concentration, possibly as a result of transdifferentiation of somatotropic pituitary cells to thyrosomatotropes.

Thyrotropin-Releasing Hormone (TRH) Promotes Wound Re-Epithelialisation in Frog and Human Skin

PubMed Central

Zhang, Guo-You; Emelianov, Vladimir; Paredes, Roberto; Debus, Sebastian; Augustin, Matthias; Funk, Wolfgang; Amaya, Enrique; Kloepper, Jennifer E.; Hardman, Matthew J.; Paus, Ralf

2013-01-01

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters. PMID:24023889

Ophthalmic Graves's disease: natural history and detailed thyroid function studies.

PubMed Central

Teng, C S; Yeo, P P

1977-01-01

Of 27 patients with ophthalmic Graves's disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH. PMID:576414

Cloning, expression and mutation of a triazophos hydrolase gene from Burkholderia sp. SZL-1.

PubMed

Zhang, Hao; Li, Qiang; Guo, Su-Hui; Cheng, Ming-Gen; Zhao, Meng-Jun; Hong, Qing; Huang, Xing

2016-06-01

Triazophos is a broad-spectrum and highly effective insecticide, and the residues of triazophos have been frequently detected in the environment. A triazophos-degrading bacterium, Burkholderia sp. SZL-1, was isolated from a long-term triazophos-polluted soil. Strain SZL-1 could hydrolyze triazophos to 1-phenyl-3-hydroxy-1,2,4-triazole, which was further utilized as the carbon sources for growth. The triazophos hydrolase gene trhA, cloned from strain SZL-1, was expressed and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. TrhA is 55 kDa and displays maximum activity at 25°C, pH 8.0. This enzyme still has nearly 60% activity at the range of 15°C-50°C for 30 min. TrhA was mutated by sequential error prone PCR and screened for improved activity for triazophos degradation. One purified variant protein (Val89-Gly89) named TrhA-M1 showed up to 3-fold improvement in specific activity against triazophos, and the specificity constants of Kcat and Kcat/Km for TrhA-M1 were improved up to 2.3- and 8.28-fold, respectively, compared to the wild-type enzyme. The results in this paper provided potential material for the contaminated soil remediation and hydrolase genetic structure research. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Environmental parameters influence on the dynamics of total and pathogenic Vibrio parahaemolyticus densities in Crassostrea virginica harvested from Mexico's Gulf coast.

PubMed

López-Hernández, Karla M; Pardío-Sedas, Violeta T; Lizárraga-Partida, Leonardo; Williams, José de J; Martínez-Herrera, David; Flores-Primo, Argel; Uscanga-Serrano, Roxana; Rendón-Castro, Karla

2015-02-15

The influence of environmental parameters on the total and pathogenic Vibrio parahaemolyticus seasonal densities in American oysters (Crassostrea virginica) was evaluated for 1 year. Harvesting site A yielded the highest mean densities of V. parahaemolyticus tlh+, tdh+/trh-, tdh-/trh+ and tdh+/trh+ during spring season at 2.57, 1.74, 0.36, and -0.40 log10 MPN/g, respectively, and tdh+/orf8+ during winter season (0.90 log10 MPN/g). V. parahaemolyticus tlh+ densities were associated to salinity (R(2)=0.372, P<0.022), tdh+/trh+ to turbidity (R(2)=0.597, P<0.035), and orf8+ to temperature, salinity, and pH (R(2)=0.964, P<0.001). The exposure to salinity and temperature conditions during winter and spring seasons regulated the dynamics of V. parahaemolyticus harboring potentially pathogenic genotypes within the oyster. The adaptive response of V. parahaemolyticus to seasonal environmental changes may lead to an increase in survival and virulence, threatening the seafood safety and increasing the risk of illness. Copyright © 2014 Elsevier Ltd. All rights reserved.

Root gravitropism and root hair development constitute coupled developmental responses regulated by auxin homeostasis in the Arabidopsis root apex.

PubMed

Rigas, Stamatis; Ditengou, Franck Anicet; Ljung, Karin; Daras, Gerasimos; Tietz, Olaf; Palme, Klaus; Hatzopoulos, Polydefkis

2013-03-01

Active polar transport establishes directional auxin flow and the generation of local auxin gradients implicated in plant responses and development. Auxin modulates gravitropism at the root tip and root hair morphogenesis at the differentiation zone. Genetic and biochemical analyses provide evidence for defective basipetal auxin transport in trh1 roots. The trh1, pin2, axr2 and aux1 mutants, and transgenic plants overexpressing PIN1, all showing impaired gravity response and root hair development, revealed ectopic PIN1 localization. The auxin antagonist hypaphorine blocked root hair elongation and caused moderate agravitropic root growth, also leading to PIN1 mislocalization. These results suggest that auxin imbalance leads to proximal and distal developmental defects in Arabidopsis root apex, associated with agravitropic root growth and root hair phenotype, respectively, providing evidence that these two auxin-regulated processes are coupled. Cell-specific subcellular localization of TRH1-YFP in stele and epidermis supports TRH1 engagement in auxin transport, and hence impaired function in trh1 causes dual defects of auxin imbalance. The interplay between intrinsic cues determining root epidermal cell fate through the TTG/GL2 pathway and environmental cues including abiotic stresses modulates root hair morphogenesis. As a consequence of auxin imbalance in Arabidopsis root apex, ectopic PIN1 mislocalization could be a risk aversion mechanism to trigger root developmental responses ensuring root growth plasticity. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat

PubMed Central

Puissant, Madeleine M; Echert, Ashley E; Yang, Chun; Mouradian, Gary C; Novotny, Tyler; Liu, Pengyuan; Liang, Mingyu; Hodges, Matthew R

2015-01-01

Raphé-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé-derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl salt-sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high-performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague–Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague–Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex. PMID:25630262

First series of total robotic hysterectomy (TRH) using new integrated table motion for the da Vinci Xi: feasibility, safety and efficacy.

PubMed

Giannini, Andrea; Russo, Eleonora; Mannella, Paolo; Palla, Giulia; Pisaneschi, Silvia; Cecchi, Elena; Maremmani, Michele; Morelli, Luca; Perutelli, Alessandra; Cela, Vito; Melfi, Franca; Simoncini, Tommaso

2017-08-01

To present the first case series of total robotic hysterectomy (TRH), using integrated table motion (ITM), which is a new feature comprising a unique operating table by Trumpf Medical that communicates wirelessly with the da Vinci Xi surgical system. ITM has been specifically developed to improve multiquadrant robotic surgery such as that conducted in colorectal surgery. Between May and October 2015, a prospective post-market study was conducted on ITM in the EU in 40 cases from different specialties. The gynecological study group comprised 12 patients. Primary endpoints were ITM feasibility, safety and efficacy. Ten patients underwent TRH. Mean number of ITM moves was three during TRH; there were 31 instances of table moves in the ten procedures. Twenty-eight of 31 ITM moves were made to gain internal exposure. The endoscope remained inserted during 29 of the 31 table movements (94%), while the instruments remained inserted during 27 of the 31 moves (87%). No external instrument collisions or other problems related to the operating table were noted. There were no ITM safety-related observations and no adverse events. This preliminary study demonstrated the feasibility, safety and efficacy of ITM for the da Vinci Xi surgical system in TRH. ITM was safe, with no adverse events related to its use. Further studies will be useful to define the real role and potential benefit of ITM in gynecological surgery.

Hyperthyroidism caused by a pituitary thyrotrophin-secreting tumour with excessive secretion of thyrotrophin-releasing hormone and subsequently followed by Graves' disease in a middle-aged woman.

PubMed

Kamoi, K; Mitsuma, T; Sato, H; Yokoyama, M; Washiyama, K; Tanaka, R; Arai, O; Takasu, N; Yamada, T

1985-11-01

A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its alpha-subunit increased in the presence of high serum triiodothyronine (T3), thyroxine (T4), and free T4 concentrations, whereas beta-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. L-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH. Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T3, T4 free T4, TSH, alpha-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T4 concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its alpha-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour. It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.

Substance P, thyrotropin-releasing hormone, and monoamine metabolites in cerebrospinal fluid in sleep apnea patients.

PubMed

Gislason, T; Hedner, J; Terenius, L; Bisette, G; Nemeroff, C B

1992-09-01

The cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone (TRH), substance P (SP), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) were measured in 15 consecutive patients with the sleep apnea syndrome (SAS) and in healthy control subjects. Second measurements were performed 6 months after surgical treatment in 10 of the patients. The mean (+/- SD) concentration of TRH-like immunoreactive material (TRH-LIM) (pg/ml) did not differ significantly between patients with SAS (8.1 +/- 2.8) and control subjects (7.5 +/- 2.2). However, postoperatively, this concentration was increased in the six clinically cured patients with SAS, from 6.9 +/- 2.7 to 9.4 +/- 1.6 (p less than 0.03). Substance P-like immunoreactive material (SP-LIM) was higher in untreated patients with SAS than in control subjects: 19.2 +/- 6.7 versus 14.4 +/- 4.2 fmol/ml (p less than 0.02), and the level remained high after operation in the group treated surgically. The HVA, 5-HIAA, and MHPG concentrations were similar in patients with SAS and control subjects, and no consistent changes were found postoperatively. The CSF deviations in TRH-LIM and SP-LIM concentrations in the patients may reflect a primary central nervous system defect or they may be secondary to intermittent nocturnal hypoxia, progressive hypercapnia, and/or sleep fragmentation. In this sense, both these systems may be markers of SAS-SP as a "trait" marker and TRH as an indicator of the current state.

Relative Humidity Has Uneven Effects on Shifts From Snow to Rain Over the Western U.S.

NASA Astrophysics Data System (ADS)

Harpold, A. A.; Rajagopal, S.; Crews, J. B.; Winchell, T.; Schumer, R.

2017-10-01

Predicting the phase of precipitation is fundamental to water supply and hazard forecasting. Phase prediction methods (PPMs) are used to predict snow fraction, or the ratio of snowfall to total precipitation. Common temperature-based regression (Dai method) and threshold at freezing (0°C) PPMs had comparable accuracy to a humidity-based PPM (TRH method) using 6 and 24 h observations. Using a daily climate data set from 1980 to 2015, the TRH method estimates 14% and 6% greater precipitation-weighted snow fraction than the 0°C and Dai methods, respectively. The TRH method predicts four times less area with declining snow fraction than the Dai method (2.1% and 8.1% of the study domain, respectively) from 1980 to 2015, with the largest differences in the Cascade and Sierra Nevada mountains and southwestern U.S. Future Representative Concentration Pathway (RCP) 8.5 projections suggest warming temperatures of 4.2°C and declining relative humidity of 1% over the 21st century. The TRH method predicts a smaller reduction in snow fraction than temperature-only PPMs by 2100, consistent with lower humidity buffering declines in snow fraction caused by regional warming.

Cloning, expressing, and hemolysis of tdh, trh and tlh genes of Vibrio parahaemolyticus

NASA Astrophysics Data System (ADS)

Zhao, Yonggang; Tang, Xiaoqian; Zhan, Wenbin

2011-09-01

Vibrio parahaemolyticus (VP) is one of the pathogenic vibrios endangering net-cage cultured Pseudosciaena crocea, Fennerpenaeus chinensis, and shellfish in coastal areas of China. Several types of hemolysins produced by Vp have been characterized as major virulence factors. They are thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH) and thermolabile hemolysin (TLH). In this study, we cloned tdh, trh, and tlh genes from the genome DNA of VP by polymerase chain reaction (PCR). We ligated the three genes into prokaryotic expression vector pET-28a (+), and transformed the recombinant plasmids into Escherichia coli BL21 (DE3). The expression of recombinant proteins was induced by isopropyl-β-D-thiogalacto-pyranoside (IPTG). The recombinant proteins were expressed in a form of inclusion bodies and thus purified with Ni-NTA affinity chromatography. Western blotting results showed that recombinant proteins, TDH, TRH and TLH, could be recognized by rabbit anti-VP serum. The three purified proteins were renatured by gradient dialysis. The renatured proteins exhibited hemolytic activity except for TLH in the presence of phosphatidylcholine. These results not only are helpful for better understanding these genes' functions under a single factor level, but also provide evidence for VP vaccine engineering.

[Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation].

PubMed

Schally, Andrew V; Gual, Carlos

2002-01-01

Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

Thyroid function during the spontaneous course of subacute thyroiditis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teixeira, V.L.; Romaldini, J.H.; Rodrigues, H.F.

1985-05-01

A study of changes in serum T/sub 4/, T/sub 3/, and Tg as well as of serum TSH response to TRH was done in ten patients with subacute thyroiditis, from the acute phase up to 56 mo. All patients had symptoms of thyrotoxicosis. The mean serum T/sub 4/, T/sub 3/, and Tg concentration were significantly higher than in normal subjects. The basal TSH concentrations failed to increase in response to TRH. Mean serum T/sub 3/ and serum Tg levels remained higher than in normal subjects until 4 to 5 mo after the acute phase. Thyroid autoantibodies were absent during themore » whole period of study. An exaggerated response of TSH to TRH in six out of seven patients was observed from a 2 to 3 mo period until the end of follow-up. All patients with T/sub 3/ to T/sub 4/ ratio above the normal range (7-24 ng/..mu..g) showed also an exaggerated response of TSH to TRH. These data suggest that the spontaneous course of subacute thyroiditis may lead to a low thyroid reserve detectable even 5 yr following the acute phase of the disease.« less

Stability of CIGS Solar Cells and Component Materials Evaluated by a Step-Stress Accelerated Degradation Test Method: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pern, F. J.; Noufi, R.

A step-stress accelerated degradation testing (SSADT) method was employed for the first time to evaluate the stability of CuInGaSe2 (CIGS) solar cells and device component materials in four Al-framed test structures encapsulated with an edge sealant and three kinds of backsheet or moisture barrier film for moisture ingress control. The SSADT exposure used a 15oC and then a 15% relative humidity (RH) increment step, beginning from 40oC/40%RH (T/RH = 40/40) to 85oC/70%RH (85/70) as of the moment. The voluminous data acquired and processed as of total DH = 3956 h with 85/70 = 704 h produced the following results. Themore » best CIGS solar cells in sample Set-1 with a moisture-permeable TPT backsheet showed essentially identical I-V degradation trend regardless of the Al-doped ZnO (AZO) layer thickness ranging from standard 0.12 μm to 0.50 μm on the cells. No clear 'stepwise' feature in the I-V parameter degradation curves corresponding to the SSADT T/RH/time profile was observed. Irregularity in I-V performance degradation pattern was observed with some cells showing early degradation at low T/RH < 55/55 and some showing large Voc, FF, and efficiency degradation due to increased series Rs (ohm-cm2) at T/RH ≥ 70/70. Results of (electrochemical) impedance spectroscopy (ECIS) analysis indicate degradation of the CIGS solar cells corresponded to increased series resistance Rs (ohm) and degraded parallel (minority carrier diffusion/recombination) resistance Rp, capacitance C, overall time constant Rp*C, and 'capacitor quality' factor (CPE-P), which were related to the cells? p-n junction properties. Heating at 85/70 appeared to benefit the CIGS solar cells as indicated by the largely recovered CPE-P factor. Device component materials, Mo on soda lime glass (Mo/SLG), bilayer ZnO (BZO), AlNi grid contact, and CdS/CIGS/Mo/SLG in test structures with TPT showed notable to significant degradation at T/RH ≥ 70/70. At T/RH = 85/70, substantial blistering of BZO layers on CIGS cell pieces was observed that was not seen on BZO/glass, and a CdS/CIGS sample displayed a small darkening and then flaking feature. Additionally, standard AlNi grid contact was less stable than thin Ni grid contact at T/RH ≥ 70/70. The edge sealant and moisture-blocking films were effective to block moisture ingress, as evidenced by the good stability of most CIGS solar cells and device components at T/RH = 85/70 for 704 h, and by preservation of the initial blue color on the RH indicator strips. The SSADT experiment is ongoing to be completed at T/RH = 85/85.« less

Diagnostic accuracy of basal TSH determinations based on the intravenous TRH stimulation test: an evaluation of 2570 tests and comparison with the literature.

PubMed

Moncayo, Helga; Dapunt, Otto; Moncayo, Roy

2007-08-02

Basal TSH levels reflect the metabolic status of thyroid function, however the definition and interpretation of the basal levels of TSH is a matter of controversial debate. The aim of this study was to evaluate basal TSH levels in relation to the physiological response to i.v. TRH stimulation. A series of 2570 women attending a specialized endocrine unit were evaluated. A standardized i.v. TRH stimulation test was carried out by applying 200 mug of TRH. TSH levels were measured both in the basal and the 30 minute blood sample. The normal response to TRH stimulation had been previously determined to be an absolute value lying between 2.5 and 20 mIU/l. Both TSH values were analyzed by cross tabulation. In addition the results were compared to reference values taken from the literature. Basal TSH values were within the normal range (0.3 to 3.5 mIU/l) in 91,5% of cases, diminished in 3,8% and elevated in 4.7%. Based on the response to TRH, 82.4% were considered euthyroid, 3.3% were latent hyperthyroid, and 14.3% were latent hypothyroid. Combining the data on basal and stimulated TSH levels, latent hypothyroidism was found in the following proportions for different TSH levels: 5.4% for TSH < 2.0 mIU/l, 30.2% for TSH between 2.0 and 3.0 mIU/l, 65,5% for TSH between 3.0 and 3.50 mIU/l, 87.5% for TSH between 3.5 and 4.0 mIU/l, and 88.2% for TSH between 4 and 5 mIU/l. The use of an upper normal range for TSH of 2.5 mIU/l, as recommended in the literature, misclassified 7.7% of euthyroid cases. Our analysis strategy allows us to delineate the predictive value of basal TSH levels in relation to latent hypothyroidism. A grey area can be identified for values between 3.0 and 3.5 mIU/l.

Transducin β-like 1, X-linked and nuclear receptor co-‍repressor cooperatively augment the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors.

PubMed

Takamizawa, Tetsuya; Satoh, Tetsurou; Miyamoto, Tomoko; Nakajima, Yasuyo; Ishizuka, Takahiro; Tomaru, Takuya; Yoshino, Satoshi; Katano-Toki, Akiko; Nishikido, Ayaka; Sapkota, Santosh; Watanabe, Takuya; Okamura, Takashi; Ishida, Emi; Horiguchi, Kazuhiko; Matsumoto, Syunichi; Ishii, Sumiyasu; Ozawa, Atsushi; Shibusawa, Nobuyuki; Okada, Shuichi; Yamada, Masanobu

2018-05-23

Mutations in TBL1X, a component of the nuclear receptor co-repressor (N-CoR) and silencing mediator of retinoic acid and thyroid hormone receptor co-repressor complexes, have recently been implicated in isolated central hypothyroidism (CeH). However, the mechanisms by which TBL1X mutations affect negative feedback regulation in the hypothalamus-pituitary-thyroid axis remain unclear. N-CoR was previously reported to paradoxically enhance the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors (TR) in cell culture systems. We herein investigated whether TBL1X affects the unliganded TR-mediated stimulation of the promoter activities of genes negatively regulated by T3 in cooperation with N-CoR. In a hypothalamic neuronal cell line, the unliganded TR-mediated stimulation of the TRH gene promoter was significantly enhanced by co-transfected TBL1X, and the co-transfection of TBL1X with N-CoR further enhanced promoter activity. In contrast, the knockdown of endogenous Tbl1x using short interfering RNA significantly attenuated the N-CoR-mediated enhancement of promoter activity in the presence of unliganded TR. The co-transfection of N365Y or Y458C, TBL1X mutants identified in CeH patients, showed impaired co-activation with N-CoR for the ligand-independent stimulation of the TRH promoter by TR. In the absence of T3, similar or impaired enhancement of the TSHβ gene promoter by the wild type or TBL1X mutants, respectively, was observed in the presence of co-transfected TR and N-CoR in CV-1 cells. These results suggest that TBL1X is needed for the full activation of TRH and TSHβ gene promoters by unliganded TR. Mutations in TBL1X may cause CeH due to the impaired up-regulation of TRH and/or TSHβ gene transcription despite low T3 levels.

Further investigation about inflation and reheating stages based on the Planck and WMAP-9

NASA Astrophysics Data System (ADS)

Ghayour, Basem

The potential V (ϕ) = λϕn is responsible for the inflation of the universe as scalar field ϕ oscillates quickly around some point where V (ϕ) has a minimum. The end of this stage has an important role on the further evolution stages of the universe. The created particles are responsible for reheating the universe at the end of this stage. The behavior of the inflation and reheating stages are often known as power law expansion S(η) ∝ η1+β, S(η) ∝ η1+βs, respectively. The reheating temperature (Trh) and βs give us valuable information about the reheating stage. Recently, people have studied about the behavior of Trh based on slow-roll inflation and initial condition of quantum normalization. It is shown that there is some discrepancy on Trh due to the amount of βs under the condition of slow-roll inflation and quantum normalization [M. Tong, Class. Quantum Grav. 30 (2013) 055013.]. Therefore, the author is believed in [M. Tong, Class. Quantum Grav. 30 (2013) 055013.] that the quantum normalization may not be a good initial condition but it seems that, we can remove this discrepancy by determining the appropriate parameter βs and hence the obtained temperatures based on the calculated βs are in favor of both mentioned conditions. Then from given βs, we can calculate Trh, tensor-to-scalar ratio r and parameters β,n based on the Planck and WMAP-9 data. The observed results of r,βs,β and n have consistency with their constrains. Also the results of Trh are in agreement with its general range and special range based on the DECIGO and BBO detectors.

Chronic exposure to hypergravity affects thyrotropin-releasing hormone levels in rat brainstem and cerebellum

NASA Technical Reports Server (NTRS)

Daunton, N. G.; Tang, F.; Corcoran, M. L.; Fox, R. A.; Man, S. Y.

1998-01-01

In studies to determine the neurochemical mechanisms underlying adaptation to altered gravity we have investigated changes in neuropeptide levels in brainstem, cerebellum, hypothalamus, striatum, hippocampus, and cerebral cortex by radioimmunoassay. Fourteen days of hypergravity (hyperG) exposure resulted in significant increases in thyrotropin-releasing hormone (TRH) content of brainstem and cerebellum, but no changes in levels of other neuropeptides (beta-endorphin, cholecystokinin, met-enkephalin, somatostatin, and substance P) examined in these areas were found, nor were TRH levels significantly changed in any other brain regions investigated. The increase in TRH in brainstem and cerebellum was not seen in animals exposed only to the rotational component of centrifugation, suggesting that this increase was elicited by the alteration in the gravitational environment. The only other neuropeptide affected by chronic hyperG exposure was met-enkephalin, which was significantly decreased in the cerebral cortex. However, this alteration in met-enkephalin was found in both hyperG and rotation control animals and thus may be due to the rotational rather than the hyperG component of centrifugation. Thus it does not appear as if there is a generalized neuropeptide response to chronic hyperG following 2 weeks of exposure. Rather, there is an increase only of TRH and that occurs only in areas of the brain known to be heavily involved with vestibular inputs and motor control (both voluntary and autonomic). These results suggest that TRH may play a role in adaptation to altered gravity as it does in adaptation to altered vestibular input following labyrinthectomy, and in cerebellar and vestibular control of locomotion, as seen in studies of ataxia.

[Beneficial effect of thyrotropin-releasing hormone in combination with HSD on hemorrhagic shock with pulmonary edema at high altitude in the rat].

PubMed

Hu, De-yao; Liu, Liang-ming; Li, Ping; Liu, Jian-cang; Liu, Hou-dong; He, Yan-mei; Huo, Xiao-ping; Tian, Kun-lun; Shi, Quan-gui; Xiao, Nan; Zhou, Xue-wu

2003-05-01

To study the effects of thyrotropin-releasing hormone (TRH) in combination with hypertonic saline/dextran (7.5% NaCl + 6% Dextran 40, HSD ) on hemorrhagic shock with pulmonary edema in the rats which were recently brought to high altitude. Forty-nine SD rats, transported to Lasa, Tibet, which was 3,760 meters above the sea level, were anesthetized one week later with sodium pentobarbital (30 mg/kg, intraperitoneal). Hemorrhagic shock with pulmonary edema was induced by hemorrhage (50 mm Hg maintained for 1 hour,1 mm Hg=0.133 kPa) plus intravenous injection of oleic acid (50 microl/kg). They were equally divided into seven groups (n=7): normal control, hemorrhagic shock, hemorrhagic shock with pulmonary edema (HSPE), HSPE plus TRH (5 mg/kg), HSPE plus HSD (4 ml/kg), and HEPE plus TRH and HSD in combination. Hemodynamic parameters including mean arterial blood pressure(MAP), left intraventricular systolic pressure (LVSP) and the maximal change rate of intraventricular pressure rise or decline (+/- dp/dt max) were observed at 15, 30, 60 and 120 minutes, blood gases were analyzed at 30 and 120 minutes, and the water content of lung and brain was determined at 120 minutes after drug administration. TRH or HSD used alone or in combination significantly increased MAP, LVSP and +/- dp/dt max (P<0.05 or P<0.01 ), ameliorated acid-base imbalance, and decreased the water content of lung and brain. The effect of the two in combination was superior to either drug used alone. TRH in combination with HSD can be used in the treatment of hemorrhagic shock with pulmonary edema at high altitude.

Cocaine- and Amphetamine-Regulated Transcript (CART) Expression is Differentially Regulated in the Hypothalamic Para ventricular Nucleus of Lactating Rats Exposed to Suckling or Cold Stimulation

PubMed Central

Sánchez, Edith; Fekete, Csaba; Lechan, Ronald M.; Joseph-Bravo, Patricia

2007-01-01

Neural stimuli, such as suckling or cold exposure, increase TRH mRNA in the paraventricular nucleus (PVN) of the rat hypothalamus, yet only suckling induces prolactin secretion. As TRH co-localizes with cocaine-and amphetamine-regulated transcript (CART) in hypophysiotropic neurons of the PVN, and CART inhibits TRH-induced prolactin release but not TRH-induced TSH release in adenohypophyseal cell cultures, we raised the possibility that differential regulation of CART gene expression in the PVN may explain the differences in prolactin secretion following each of the two stimuli. Primiparous female rats were mated and handled daily during the pre- and postpartum periods. After delivery, the litter was adjusted to 8 pups and at mid-lactation, dams were separated from their pups for 8 hours and exposed to either 1h of cold or 30 min of suckling. Long term effects of suckling were studied by separating pups from their mothers for 24h, followed by a 12h period of continuous suckling. Serum TSH levels increased in response to cold exposure, while prolactin levels were increased by suckling and diminished by cold exposure. CART mRNA levels increased in rostral and mid parts of the medial parvocellular PVN following cold exposure but not after suckling stimulation. These data demonstrate a differential regulation of CART gene expression in hypophysiotropic neurons in response to stimuli that increase TRH mRNA levels, and suggest that CART activation in the PVN may contribute to the decrease in PRL release when the thyroid axis is activated by cold exposure. Section: Regulatory systems PMID:17174283

Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

PubMed Central

Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

2004-01-01

Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (P<0.01). Less potent nootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (P<0.001). Piracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

Luteal phase hyperprolactinemia.

PubMed

Falk, R J; Anderson, L

1994-01-01

To determine the incidence of both isolated and repetitive prolactin elevations in the luteal phase of otherwise normoprolactinemic women. To see if sporadic luteal-phase hyperprolactinemia is associated with progesterone deficiency, and to explore a possible physiological basis for sporadic hyperprolactinemia by TRH challenge. Hospital-based reproductive endocrinology/infertility service. Prospective measurement of luteal phase serum progesterone and prolactin in normoprolactinemic ovulatory women. TRH stimulation testing in volunteers with repetitive luteal phase hyperprolactinemia and normoprolactinemic controls. 133 sequentially selected infertile, ovulatory women with normal prolactin levels in the proliferative phase of the cycle. Measurement of serum progesterone and prolactin during the luteal phase, based on the day of the LH surge. TRH testing in the midluteal phase of the cycle in patients with two or more luteal phase prolactin elevations, and in five normoprolactinemic volunteers in both the preovulatory and midluteal phase. Of 133 subjects, 85 (64%) had no prolactin level exceeding 20 ng/mL in the luteal phase. Thirty-three (25%) had two or more elevated levels, and were considered to have repetitive luteal phase hyperprolactinemia (LPH). TRH testing in control subjects resulted in a greater prolactin response in the preovulatory phase. The group with LPH demonstrated an initial elevation of prolactin greater than that of the normoprolactinemic controls, but a subsequent drop to levels lower than both preovulatory and midluteal normoprolactinemic controls by 45 minutes. Sporadic luteal-phase hyperprolactinemia is a relatively common event (36% of 133 subjects in the present series). Of these 48 women, 33 (69%) had repetitive elevations, suggesting the elevation in these subjects to be more than a random event. The physiological validity of this observation is further demonstrated by an abnormal response to TRH stimulation, but the normal levels of luteal phase progesterone leave questions as to its pathological importance.

Multiplex PCR for the detection and differentiation of Vibrio parahaemolyticus strains using the groEL, tdh and trh genes.

PubMed

Hossain, Muhammad Tofazzal; Kim, Young-Ok; Kong, In-Soo

2013-01-01

Vibrio parahaemolyticus is a significant cause of human gastrointestinal disorders worldwide, transmitted primarily by ingestion of raw or undercooked contaminated seafood. In this study, a multiplex PCR assay for the detection and differentiation of V. parahaemolyticus strains was developed using primer sets for a species-specific marker, groEL, and two virulence markers, tdh and trh. Multiplex PCR conditions were standardised, and extracted genomic DNA of 70 V. parahaemolyticus strains was used for identification. The sensitivity and efficacy of this method were validated using artificially inoculated shellfish and seawater. The expected sizes of amplicons were 510 bp, 382 bp, and 171 bp for groEL, tdh and trh, respectively. PCR products were sufficiently different in size, and the detection limits of the multiplex PCR for groEL, tdh and trh were each 200 pg DNA. Specific detection and differentiation of virulent from non-virulent strains in shellfish homogenates and seawater was also possible after artificial inoculation with various V. parahaemolyticus strains. This newly developed multiplex PCR is a rapid assay for detection and differentiation of pathogenic V. parahaemolyticus strains, and could be used to prevent disease outbreaks and protect public health by helping the seafood industry maintain a safe shellfish supply. Copyright © 2013 Elsevier Ltd. All rights reserved.

Serologic and Molecular Characterization of Vibrio parahaemolyticus Strains Isolated from Seawater and Fish Products of the Gulf of Mexico

PubMed Central

Cabrera-García, María Eugenia; Vázquez-Salinas, Carlos; Quiñones-Ramírez, Elsa Irma

2004-01-01

The thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH) are the main virulence factors of Vibrio parahaemolyticus. We isolated V. parahaemolyticus from seawater, fish, and oysters obtained from the Pueblo Viejo Lagoon in Veracruz, determined the serogroups, phenotypically and genotypically characterized TDH and TRH, and investigated the presence of the toxR gene. A total of 46 V. parahaemolyticus strains were isolated, and all of them amplified the 368-bp toxR gene fragment. The trh gene was not identified in any of the strains; 4 of the 46 strains were Kanagawa phenomenon (KP) positive and amplified the 251-bp tdh gene fragment. The most frequent serogroup was serogroup O3. This is the first report of the presence of KP-positive tdh-positive environmental V. parahaemolyticus strains in Mexico. PMID:15528498

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog

PubMed Central

Ohuchi, Kazuki; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. PMID:26683872

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog.

PubMed

Ohuchi, Kazuki; Funato, Michinori; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-02-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance: Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. ©AlphaMed Press.

Response to luteinizing releasing hormone, thyrotrophic releasing hormone, and human chorionic gonadotropin administration in healthy men at different risks for prostatic cancer and in prostatic cancer patients.

PubMed

Hill, P; Wynder, E L; Garbaczewski, L; Garnes, H; Walker, A R

1982-05-01

A comparative study of the pituitary and testicular response to luteinizing releasing hormone (LHRH), thyrotrophic releasing hormone (TRH), and human chorionic gonadotrophin (HCG) administration was carried out in (a) low-risk young South African black men and high-risk North American black men for prostatic cancer and (b) healthy elderly South African men and South African black men with prostatic cancer. A comparable HCG response occurred in young South African and North American black men, while a greater release of prolactin, but a lesser release of luteinizing hormone in response to LHRH:TRH occurred in South African black men. The response to HCG was comparable in elderly and young South African black men, although the prolactin release in response to TRH was greater in elderly men. A more prolonged release of luteinizing hormone was evident in men with prostatic cancer. Higher estradiol and estrone but lower androstenedione levels occurred in men with prostatic cancer. Data suggest that, in the elderly South African black men with prostatic cancer, estrogen metabolism is modified and that either the estrogen level or the higher estrogen:androgen levels modify the pituitary response to LHRH:TRH. A Western diet enhanced the changes in hormone profiles evident in black South African men with prostatic cancer.

Ecology of pathogenic and non-pathogenic Vibrio parahaemolyticus on the French Atlantic coast. Effects of temperature, salinity, turbidity and chlorophyll a.

PubMed

Julie, Deter; Solen, Lozach; Antoine, Véron; Jaufrey, Chollet; Annick, Derrien; Dominique, Hervio-Heath

2010-04-01

Vibrio parahaemolyticus is one of the principal bacterial causes for seafood-borne gastroenteritis in the world. In the present study, three sites located on the French Atlantic coast were monitored monthly for environmental parameters over 1 year. The presence of total and pathogenic V. parahaemolyticus in sediment, water and mussel samples was detected following enrichment by culture and real-time PCR (toxR gene, tdh, trh1 and trh2 virulence genes). Using generalized linear models, we showed that the presence of V. parahaemolyticus in water could be explained by a combination of mean temperature over the 7 days before the day of sampling (P < 0.001) and turbidity (P = 0.058). In mussels, an effect of chlorophyll a (P = 0.005) was detected when an effect of the mean salinity over the 7 days before sampling was significant for the sediment (P < 0.001). We did not detect any significant effect of phytoplanktonic blooms or of the number of culturable bacteria on V. parahaemolyticus presence. No sample was revealed positive for tdh. The presence of trh1 and trh2 was positively influenced by the mean temperature during the 2 days before the day of sampling (P < 0.001 and P = 0.032). The importance of these ecological parameters is discussed in relation to the biology of V. parahaemolyticus.

Adjusted drug treatment is superior to renal sympathetic denervation in patients with true treatment-resistant hypertension.

PubMed

Fadl Elmula, Fadl Elmula M; Hoffmann, Pavel; Larstorp, Anne C; Fossum, Eigil; Brekke, Magne; Kjeldsen, Sverre E; Gjønnæss, Eyvind; Hjørnholm, Ulla; Kjaer, Vibeke N; Rostrup, Morten; Os, Ingrid; Stenehjem, Aud; Høieggen, Aud

2014-05-01

We aimed to investigate for the first time the blood pressure (BP)-lowering effect of renal sympathetic denervation (RDN) versus clinically adjusted drug treatment in true treatment-resistant hypertension (TRH) after excluding patients with confounding poor drug adherence. Patients with apparent TRH (n=65) were referred for RDN, and those with secondary and spurious hypertension (n=26) were excluded. TRH was defined as office systolic BP (SBP) >140 mm Hg, despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic. In addition, ambulatory daytime SBP >135 mm Hg after witnessed intake of antihypertensive drugs was required, after which 20 patients had normalized BP and were excluded. Patients with true TRH were randomized and underwent RDN (n=9) performed with Symplicity Catheter System versus clinically adjusted drug treatment (n=10). The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect. Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg (±SD) at baseline to 132±10/77±8 mm Hg at 6 months (P<0.0005 and P=0.02, SBP and diastolic BP, respectively) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg (P=0.42 and P=0.48, SBP and diastolic BP, respectively). SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months (P=0.002 and P=0.004, respectively), and absolute changes in SBP were larger in the drug-adjusted group (P=0.008). Ambulatory BPs changed in parallel to office BPs. Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01673516.

EXPOSURE TO DEXAMETHASONE DURING LATE GESTATION CAUSES FEMALE-SPECIFIC DECREASES IN CORE BODY TEMPERATURE AND PREPRO-THYROTROPIN-RELEASING HORMONE EXPRESSION IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS IN RATS

PubMed Central

Carbone, David L.; Zuloaga, Damian G.; Lacagnina, Anthony F.; McGivern, Robert F.; Handa, Robert J.

2012-01-01

Synthetic glucocorticoids (GC) have been used to promote lung development in preterm infants, thereby decreasing respiratory distress syndrome and mortality, yet, concern has arisen from reports that such treatment predisposes individuals to disease in adulthood. Given the variety of preclinical studies that show metabolic and behavioral abnormalities in adulthood following fetal exposure to synthetic GC, we examined the effect of in utero exposure to the synthetic GC, dexamethasone (DEX), on hypothalamic expression of thyrotropin-releasing hormone (TRH) a central neuropeptide involved in mediating behavior and metabolic balance. Pregnant Sprague-Dawley rats were administered 0.4 mg/kg DEX on gestational days 18–21. As adults (postnatal day (PD) 60), the offspring were fitted with temperature sensing transmitters allowing real-time monitoring of core body temperature (CBT) across the 24 hr light dark period. This revealed a significant decrease in CBT throughout the day in prenatal DEX-treated females on estrus and diestrus, but not in male offspring. The reduction in CBT by prenatal DEX exposure was accompanied by a significant decrease in the expression of Trh transcript in the paraventricular nucleus of the hypothalamus (PVN) of female rats at PD 60 and this effect was also present on PD7. There was also a female-specific reduction in the number of preproTRH -immunoreactive (ir) neurons in the PVN, with ppTRH-ir nerve fibers decreases that were present in both male and female offspring. No changes in thyroid hormone (triiodothyronine, T3; thyroxine, T4) were observed in adult offspring, but during development, both males and females (PD14) had lower T3 and T4 levels. These data indicate abnormal expression of TRH results from fetal DEX exposure during late gestation, possibly explaining the decreased CBT observed in the female offspring. PMID:22884559

Characterization of In Vitro Release of Neurochemicals from the Intermediate Area of the Rat Thoracic Spinal Cord: Regulation by Coexisting Neurochemical and Presynaptic Autoreceptors

DTIC Science & Technology

1995-06-16

university of the Health Sciences ABSTRACT serotonin (5-HT), substance P (SP), neurokinin A (NKA) and thyrotropin-releasing hormone (TRH) coexist in the...intermediolateral cell column IML pars funiculars IML pars principal is immunoreactivity mean arterial pressure neurokinin A neurokinin B nucleus tractus...thyrotropin-releasing hormone (TRH) and neurokinin A (NKA) coexist in these IML-projecting neurons. We propose that each of these colocalized

Growth phase-dependent control of R27 conjugation is mediated by the interplay between the plasmid-encoded regulatory circuit TrhR/TrhY-HtdA and the cAMP regulon.

PubMed

Gibert, Marta; Paytubi, Sonia; Beltrán, Sergi; Juárez, Antonio; Balsalobre, Carlos; Madrid, Cristina

2016-12-01

Plasmids of the incompatibility group HI1 (IncHI1) have been isolated from several Gram-negative pathogens and are associated with the spread of multidrug resistance. Their conjugation is tightly regulated and it is inhibited at temperatures higher than 30°C, indicating that conjugation occurs outside warm-blooded hosts. Using R27, the prototype of IncHI1 plasmids, we report that plasmid transfer efficiency in E. coli strongly depends on the physiological state of the donor cells. Conjugation frequency is high when cells are actively growing, dropping sharply when cells enter the stationary phase of growth. Accordingly, our transcriptomic assays show significant downregulation of numerous R27 genes during the stationary phase, including several tra (transfer) genes. Growth phase-dependent regulation of tra genes transcription is independent of H-NS, a silencer of horizontal gene transfer, and ppGpp and RpoS, regulators of the stationary phase, but highly dependent on the plasmid-encoded regulatory circuit TrhR/TrhY-HtdA. The metabolic sensor cAMP, whose synthesis is chromosomally encoded, is also involved in the growth phase regulation of R27 conjugation by modulating htdA expression. Our data suggest that the involvement of regulators encoded by both chromosome and plasmid are required for efficient physiological control of IncHI1 plasmid conjugation. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

PubMed Central

Gershengorn, M C; Weintraub, B D

1975-01-01

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed. PMID:1159077

Effects of forced swimming stress on thyroid function, pituitary thyroid-stimulating hormone and hypothalamus thyrotropin releasing hormone expression in adrenalectomy Wistar rats.

PubMed

Sun, Qiuyan; Liu, Aihua; Ma, Yanan; Wang, Anyi; Guo, Xinhong; Teng, Weiping; Jiang, Yaqiu

2016-11-01

In order to study the impact that is imposed on the hypothalamic-pituitary-thyroid (HPT) axis of adrenalectomy male Wistar rats by stress caused by swimming, the blood level of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), the expression of TSHβ mRNA at the pituitary and thyrotropin releasing hormone (TRH) expression at the paraventricular nucleus (PVN) were measured. A total of 50 male Wistar rats of 6-8 weeks of age and with an average weight of 190-210 grams were randomly divided into the following two groups: The surgical (without adrenal glands) and non-surgical (adrenalectomy) group. These two groups were then divided into the following five groups, according to the time delay of sacrifice following forced swim (10 min, 2 h, 12 h and 24 h) and control (not subjected to swimming) groups. A bilateral adrenalectomy animal model was established. Serum TSH in the blood was measurement by chemiluminescent immunoassay, and cerebrum tissue were excised for the measurement of TRH expression using an immunohistochemistry assay. In addition, pituitaries were excised for the extraction of total RNA. Finally, reverse transcription-quantitative polymerase chain reaction was performed for quantitation of TSHβ. Following swimming, the serum T3, T4 and TSH, the TSHβ mRNA expression levels in the pituitary and the TRH expression in the PVN of the surgical group were gradually increased. In the non-surgical group, no significant differences were observed in the serum T3, T4 and TSH levels compared with the control group. The TSHβ mRNA expression at the pituitary showed a similar result. Furthermore, the TRH expression at PVN was gradually increased and stress from swimming could increase the blood T4, T3 and TSH levels, TSHβ mRNA expression at the pituitary and TRH expression at the PVN in adrenalectomy Wistar rats. Moreover, the index in the surgical group changed significantly compared with the non-surgical group. In conclusion, the results suggest that there is a positive correlation between stress from forced swimming and the variation of the HPT axis.

Uninhibited thyroidal uptake of radioiodine despite iodine excess in amiodarone-induced hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiersinga, W.M.; Touber, J.L.; Trip, M.D.

1986-08-01

Iodine excess is associated with a low thyroidal radioiodine uptake due to dilution of the radioisotope by the increased stable iodide pool. We studied thyroidal uptake of radioisotopes in cardiac patients with iodine excess due to amiodarone treatment. /sup 99m/Tc-pertechnetate scintigraphy was performed in 13 patients receiving long term amiodarone therapy. Five patients had a clearly visible thyroid gland, and 8 patients had no or a very faint thyroid image. All patients with positive scans had an increased plasma TSH level, whereas all patients with negative scans had a normal or absent TSH response to TRH. Thyroidal uptake and dischargemore » of 123I were studied in 30 other patients. Group I (n = 11) had normal plasma TSH responses to TRH and no iodine excess, group II (n = 7) had normal TSH responses to TRH and excess iodine from metrizoate angiography in the previous month, group III (n = 7) had normal or decreased TSH responses to TRH while receiving long term amiodarone therapy, and group IV (n = 5) had increased TSH responses to TRH while receiving long term amiodarone therapy. The mean radioiodine uptake value in group I (5.4 +/- 0.8% (+/- SE) at 60 min) was higher than those in group II (2.3 +/- 0.7%; P = 0.009) and group III (0.8 +/- 0.3%; P = 0.0005), but not different from that in group IV (5.3 +/- 1.2%; P = NS). Radioiodine discharge after perchlorate (expressed as a percentage of the 60 min uptake) in group I (10.1 +/- 2.2%) was lower than those in group II (24.9 +/- 10.6%; P = 0.05) and group III (28.8 +/- 5.3%; P less than 0.005), whereas discharge in group IV (58.0 +/- 6.1%) was greater than those in group II (P less than 0.05) and group III (P less than 0.01). In conclusion, 1) thyroid visualization by /sup 99m/Tc-pertechnetate and thyroid radioiodine uptake during iodine excess are decreased in euthyroid and hyperthyroid patients, but preserved in hypothyroid patients.« less

Metabolome response to temperature-induced virulence gene expression in two genotypes of pathogenic Vibrio parahaemolyticus.

PubMed

Feng, Bo; Guo, Zhuoran; Zhang, Weijia; Pan, Yingjie; Zhao, Yong

2016-04-26

Vibrio parahaemolyticus is a main causative agent of serious human seafood-borne gastroenteritis disease. Many researchers have investigated its pathogenesis by observing the alteration of its virulence factors in different conditions. It was previously known that culture conditions will influence the gene expression and the metabolic profile of V. parahaemolyticus, but little attention has been paid on the relationship between them. In this study, for the first time, the metabolomics response in relation to the expression of two major virulence genes, tdh and trh, induced at three temperatures (4, 25 and 37 °C) was examined in two genotypes of pathogenic Vibrio parahaemolyticus (ATCC33846 (tdh+/trh-/tlh+) and ATCC17802 (tdh-/trh+/tlh+)). Reverse transcription real-time PCR (RT-qPCR) analysis illustrated that the expression levels of tdh and trh induced at 25 °C in V. parahaemolyticus were significantly higher than those induced at 4 and 37 °C. Principal components analysis (PCA) based on the UPLC & Q-TOF MS data presented clearly distinct groups among the samples treated by different temperatures. Metabolic profiling demonstrated that 179 of 1,033 kinds of identified metabolites in ATCC33846 changed significantly (p <0.01) upon culturing at different temperatures, meanwhile 101 of 930 kinds of metabolites changed (p <0.01) in ATCC17802. Pearson's correlation analysis highlighted the correlation between metabolites and virulence gene expression levels. At the threshold of | r | = 1, p <0.01, 12 kinds of metabolites showed extremely significant correlations with tdh expression, and 4 kinds of metabolites significantly correlated with trh expression. It is interesting that 3D, 7D, 11D-Phytanic acid showed the same trend with pyrophosphate, whose derivative could activate the degradation of phytanic acid. Several metabolites could be sorted into the same class by the method of chemical taxonomy, by assuming that they are involved in the same metabolic pathways. This research can help to find biomarkers to monitor virulence gene expression, and can further help laboratory and clinical research of V. parahaemolyticus from the perspective of metabolomics.

The Thr92Ala 5′ Type 2 Deiodinase Gene Polymorphism Is Associated with a Delayed Triiodothyronine Secretion in Response to the Thyrotropin-Releasing Hormone–Stimulation Test: A Pharmacogenomic Study

PubMed Central

Butler, Peter W.; Smith, Sheila M.; Linderman, Joyce D.; Brychta, Robert J.; Alberobello, Anna Teresa; Dubaz, Ornella M.; Luzon, Javier A.; Skarulis, Monica C.; Cochran, Craig S.; Wesley, Robert A.; Pucino, Frank

2010-01-01

Background The common Thr92Ala D2 polymorphism has been associated with changes in pituitary–thyroid axis homeostasis, but published results are conflicting. To investigate the effects of the Thr92Ala polymorphism on intrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion, we designed prospective pharmacogenomic intervention aimed to detect differences in T3 levels after thyrotropin (TSH)-releasing hormone (TRH)–mediated TSH stimulation of the thyroid gland. Methods Eighty-three healthy volunteers were screened and genotyped for the Thr92Ala polymorphism. Fifteen volunteers of each genotype (Thr/Thr, Thr/Ala, and Ala/Ala) underwent a 500 mcg intravenous TRH stimulation test with serial measurements of serum total T3 (TT3), free T4, and TSH over 180 minutes. Results No differences in baseline thyroid hormone levels were seen among the study groups. Compared to the Thr/Thr group, the Ala/Ala group showed a significantly lower TRH-stimulated increase in serum TT3 at 60 minutes (12.07 ± 2.67 vs. 21.07 ± 2.86 ng/dL, p = 0.029). Thr/Ala subjects showed an intermediate response. Compared to Thr/Thr subjects, the Ala/Ala group showed a blunted rate of rise in serum TT3 as measured by mean time to 50% maximum delta serum TT3 (88.42 ± 6.84 vs. 69.56 ± 6.06 minutes, p = 0.028). Subjects attained similar maximal (180 minutes) TRH-stimulated TT3 levels. TRH-stimulated TSH and free T4 levels were not significantly different among the three genotype groups. Conclusions The commonly occurring Thr92Ala D2 variant is associated with a decreased rate of acute TSH-stimulated T3 release from the thyroid consistent with a decrease in intrathyroidal deiodination. These data provide a proof of concept that the Thr92Ala polymorphism is associated with subtle changes in thyroid hormone homeostasis. PMID:21054208

Molecular characterizations of Vibrio parahaemolyticus in seafood from the Black Sea, Turkey.

PubMed

Terzi Gulel, G; Martinez-Urtaza, J

2016-06-01

Vibrio parahaemolyticus is a marine bacterium that is considered as one of the major causes of bacterial food-borne outbreaks at a global scale. A total of 114 samples including mussel (n = 42), seawater (n = 22) and fish (n = 50) samples were collected and subjected to investigation. Vibrio parahaemolyticus was detected in 45 (39%) of 114 samples with an occurrence in mussel, seawater and fish samples of 76, 40·9 and 8% respectively. A total of 96 isolates were positive for the species-specific genes toxR and tlh and confirmed as V. parahaemolyticus. Presence of the virulence marker gene tdh was not identified in any of the strains investigated; however, four of strains were positive for the trh gene. Serological analysis of eight randomly selected trh-negative isolates identified three different serotypes: O4:K untypeable (KUT), O2:KUT, O3:KUT. Conversely, all four trh-positive strains belonged to a single serotype (O1:K1) and share an undistinguishable genetic profile by PFGE analysis, suggesting the existence of a dominant clone for the trh-positive strains in the region. Vibrio parahaemolyticus is the most prevalent food-poisoning bacterium associated with seafood consumption. The number of infections is increasing worldwide and is being reported in areas with no previous incidence. This study provides the first instance of the occurrence of V. parahaemolyticus strains with virulence traits in the Black Sea, contributing to gain a better understanding about potential risk associated with this pathogen in the region. © 2016 The Society for Applied Microbiology.

The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

PubMed

Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

1993-09-01

In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

Single-Cell Phenotypic Characterization of Human Pituitary GHomas and Non-Functioning Adenomas Based on Hormone Content and Calcium Responses to Hypothalamic Releasing Hormones

PubMed Central

Senovilla, Laura; Núñez, Lucía; de Campos, José María; de Luis, Daniel A.; Romero, Enrique; García-Sancho, Javier; Villalobos, Carlos

2015-01-01

Human pituitary tumors are generally benign adenomas causing considerable morbidity due to excess hormone secretion, hypopituitarism, and other tumor mass effects. Pituitary tumors are highly heterogeneous and difficult to type, often containing mixed cell phenotypes. We have used calcium imaging followed by multiple immunocytochemistry to type growth hormone secreting (GHomas) and non-functioning pituitary adenomas (NFPAs). Individual cells were typed for stored hormones and calcium responses to classic hypothalamic releasing hormones (HRHs). We found that GHomas contained growth hormone cells either lacking responses to HRHs or responding to all four HRHs. However, most GHoma cells were polyhormonal cells responsive to both thyrotropin-releasing hormone (TRH) and GH-releasing hormone. NFPAs were also highly heterogeneous. Some of them contained ACTH cells lacking responses to HRHs or polyhormonal gonadotropes responsive to LHRH and TRH. However, most NFPAs were made of cells storing no hormone and responded only to TRH. These results may provide new insights on the ontogeny of GHomas and NFPAs. PMID:26106585

Omega-conotoxin- and nifedipine-insensitive voltage-operated calcium channels mediate K(+)-induced release of pro-thyrotropin-releasing hormone-connecting peptides Ps4 and Ps5 from perifused rat hypothalamic slices.

PubMed

Valentijn, K; Tranchand Bunel, D; Vaudry, H

1992-07-01

The rat thyrotropin-releasing hormone (TRH) precursor (prepro-TRH) contains five copies of the TRH progenitor sequence linked together by intervening sequences. Recently, we have shown that the connecting peptides prepro-TRH-(160-169) (Ps4) and prepro-TRH-(178-199) (Ps5) are released from rat hypothalamic neurones in response to elevated potassium concentrations, in a calcium-dependent manner. In the present study, the role of voltage-operated calcium channels in potassium-induced release of Ps4 and Ps5 was investigated, using a perifusion system for rat hypothalamic slices. The release of Ps4 and Ps5 stimulated by potassium (70 mM) was blocked by the inorganic ions Co2+ (2.6 mM) and Ni2+ (5 mM). In contrast, the stimulatory effect of KCl was insensitive to Cd2+ (100 microM). The dihydropyridine antagonist nifedipine (10 microM) had no effect on K(+)-evoked release of Ps4 and Ps5. Furthermore, the response to KCl was not affected by nifedipine (10 microM) in combination with diltiazem (1 microM), a benzothiazepine which increases the affinity of dihydropyridine antagonists for their receptor. The dihydropyridine agonist BAY K 8644, at concentrations as high as 1 mM, did not stimulate the basal secretion of Ps4 and Ps5. In addition, BAY K 8644 had no potentiating effect on K(+)-induced release of Ps4 and Ps5. The marine cone snail toxin omega-conotoxin, a blocker of both L- and N-type calcium channels had no effect on the release of Ps4 and Ps5 stimulated by potassium. Similarly, the omega-conopeptide SNX-111, a selective blocker of N-type calcium channels, did not inhibit the stimulatory effect of potassium. The release of Ps4 and Ps5 evoked by high K+ was insensitive to the non-selective calcium channel blocker verapamil (20 microM). Amiloride (1 microM), a putative blocker of T-type calcium channels, did not affect KCl-induced secretion of the two connecting peptides. Taken together, these results indicate that two connecting peptides derived from the pro-TRH, Ps4 and Ps5, are released by K(+)-induced depolarization through activation of voltage-sensitive calcium channels. The calcium channels appear to have a pharmacological profile different from that of L- and N-type channels. Although, their insensitivity to low Cd2+ concentrations and sensitivity to Ni2+ ions would support the involvement of T-type calcium channels, the lack of effect of amiloride suggests that they belong to a yet undefined class of calcium channels.

Long-Term Study of Vibrio parahaemolyticus Prevalence and Distribution in New Zealand Shellfish

PubMed Central

Hedderley, D.; Fletcher, G. C.

2015-01-01

The food-borne pathogen Vibrio parahaemolyticus has been reported as being present in New Zealand (NZ) seawaters, but there have been no reported outbreaks of food-borne infection from commercially grown NZ seafood. Our study determined the current incidence of V. parahaemolyticus in NZ oysters and Greenshell mussels and the prevalence of V. parahaemolyticus tdh and trh strains. Pacific (235) and dredge (21) oyster samples and mussel samples (55) were obtained from commercial shellfish-growing areas between December 2009 and June 2012. Total V. parahaemolyticus numbers and the presence of pathogenic genes tdh and trh were determined using the FDA most-probable-number (MPN) method and confirmed using PCR analysis. In samples from the North Island of NZ, V. parahaemolyticus was detected in 81% of Pacific oysters and 34% of mussel samples, while the numbers of V. parahaemolyticus tdh and trh strains were low, with just 3/215 Pacific oyster samples carrying the tdh gene. V. parahaemolyticus organisms carrying tdh and trh were not detected in South Island samples, and V. parahaemolyticus was detected in just 1/21 dredge oyster and 2/16 mussel samples. Numbers of V. parahaemolyticus organisms increased when seawater temperatures were high, the season when most commercial shellfish-growing areas are not harvested. The numbers of V. parahaemolyticus organisms in samples exceeded 1,000 MPN/g only when the seawater temperatures exceeded 19°C, so this environmental parameter could be used as a trigger warning of potential hazard. There is some evidence that the total V. parahaemolyticus numbers increased compared with those reported from a previous 1981 to 1984 study, but the analytical methods differed significantly. PMID:25616790

Fenugreek, A Potent Hypoglycaemic Herb Can Cause Central Hypothyroidism Via Leptin - A Threat To Diabetes Phytotherapy.

PubMed

Majumdar, Jayjeet; Chakraborty, Pratip; Mitra, Analava; Sarkar, Nirmal Kumar; Sarkar, Supriti

2017-07-01

Fenugreek ( Trigonella foenum graecum) , a medicinal herb with potent antihyperglycaemic and hypoglycaemic effects, is used to treat diabetes. This study is aimed to explore the interaction of fenugreek seed extract (FSE) and HPT (hypothalamic-pituitary-thyroid) axis in context of leptin secretion which have important role in normal and type-1 diabetic subjects. FSE (confirmed to contain trigonelline, diosgenin, 4 hydroxyisoleucine) was gavaged (0.25 gm/kg body weight/day) to normal and alloxan-induced type-1 diabetic rats for 4 weeks. Expression of hypothalamic prepro-TRH (Thyrotropin releasing hormone) mRNA, serum levels of TRH, TSH (Thyroid stimulating hormone), fT 3 , fT 4 , insulin, leptin, glucose; thyroperoxidase activity and growth of thyroid gland, food intake, adiposity index were also studied FSE significantly down regulated prepro-TRH mRNA expression; decreased serum TRH, TSH, fT 3 , fT 4 levels, and regressed thyroid gland in FSE-fed normal and diabetic rats than those observed in normal diet-fed control and diabetic rats. FSE decreased (p<0.005-0.001) adiposity index and leptin secretion, increased food intake and body weight in all FSE-fed rats. FSE improved insulin secretion, decreased glucose level but impaired HPT axis in diabetic rats, indicating insulin-independent central hypothyroidism. Results suggested that the dominant signal to hypothalamus suppressing HPT axis is the fall in leptin level which i resulted from decreased adiposity index following FSE feeding. Fenugreek simultaneously having hypoglycaemic and hypothyroidal actions raises questions whether it can be safely used to treat diabetes and/or hyperthyroidism as was suggested by many workers. © Georg Thieme Verlag KG Stuttgart · New York.

Development of a Multiplex Real-Time PCR Assay with an Internal Amplification Control for the Detection of Total and Pathogenic Vibrio parahaemolyticus Bacteria in Oysters▿

PubMed Central

Nordstrom, Jessica L.; Vickery, Michael C. L.; Blackstone, George M.; Murray, Shelley L.; DePaola, Angelo

2007-01-01

Vibrio parahaemolyticus is an estuarine bacterium that is the leading cause of shellfish-associated cases of bacterial gastroenteritis in the United States. Our laboratory developed a real-time multiplex PCR assay for the simultaneous detection of the thermolabile hemolysin (tlh), thermostable direct hemolysin (tdh), and thermostable-related hemolysin (trh) genes of V. parahaemolyticus. The tlh gene is a species-specific marker, while the tdh and trh genes are pathogenicity markers. An internal amplification control (IAC) was incorporated to ensure PCR integrity and eliminate false-negative reporting. The assay was tested for specificity against >150 strains representing eight bacterial species. Only V. parahaemolyticus strains possessing the appropriate target genes generated a fluorescent signal, except for a late tdh signal generated by three strains of V. hollisae. The multiplex assay detected <10 CFU/reaction of pathogenic V. parahaemolyticus in the presence of >104 CFU/reaction of total V. parahaemolyticus bacteria. The real-time PCR assay was utilized with a most-probable-number format, and its results were compared to standard V. parahaemolyticus isolation methodology during an environmental survey of Alaskan oysters. The IAC was occasionally inhibited by the oyster matrix, and this usually corresponded to negative results for V. parahaemolyticus targets. V. parahaemolyticus tlh, tdh, and trh were detected in 44, 44, and 52% of the oyster samples, respectively. V. parahaemolyticus was isolated from 33% of the samples, and tdh+ and trh+ strains were isolated from 19 and 26%, respectively. These results demonstrate the utility of the real-time PCR assay in environmental surveys and its possible application to outbreak investigations for the detection of total and pathogenic V. parahaemolyticus. PMID:17644647

Long-term study of Vibrio parahaemolyticus prevalence and distribution in New Zealand shellfish.

PubMed

Cruz, C D; Hedderley, D; Fletcher, G C

2015-04-01

The food-borne pathogen Vibrio parahaemolyticus has been reported as being present in New Zealand (NZ) seawaters, but there have been no reported outbreaks of food-borne infection from commercially grown NZ seafood. Our study determined the current incidence of V. parahaemolyticus in NZ oysters and Greenshell mussels and the prevalence of V. parahaemolyticus tdh and trh strains. Pacific (235) and dredge (21) oyster samples and mussel samples (55) were obtained from commercial shellfish-growing areas between December 2009 and June 2012. Total V. parahaemolyticus numbers and the presence of pathogenic genes tdh and trh were determined using the FDA most-probable-number (MPN) method and confirmed using PCR analysis. In samples from the North Island of NZ, V. parahaemolyticus was detected in 81% of Pacific oysters and 34% of mussel samples, while the numbers of V. parahaemolyticus tdh and trh strains were low, with just 3/215 Pacific oyster samples carrying the tdh gene. V. parahaemolyticus organisms carrying tdh and trh were not detected in South Island samples, and V. parahaemolyticus was detected in just 1/21 dredge oyster and 2/16 mussel samples. Numbers of V. parahaemolyticus organisms increased when seawater temperatures were high, the season when most commercial shellfish-growing areas are not harvested. The numbers of V. parahaemolyticus organisms in samples exceeded 1,000 MPN/g only when the seawater temperatures exceeded 19°C, so this environmental parameter could be used as a trigger warning of potential hazard. There is some evidence that the total V. parahaemolyticus numbers increased compared with those reported from a previous 1981 to 1984 study, but the analytical methods differed significantly. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Differences in receptor-evoked membrane electrical responses in native and mRNA-injected Xenopus oocytes.

PubMed

Oron, Y; Gillo, B; Gershengorn, M C

1988-06-01

Xenopus laevis oocytes are giant cells suitable for studies of plasma membrane receptors and signal transduction pathways because of their capacity to express receptors after injection of heterologous mRNA. We studied depolarizing chloride currents evoked by acetylcholine (AcCho) in native oocytes ("intrinsic AcCho response"), by thyrotropin-releasing hormone (TRH) in oocytes injected with pituitary (GH3) cell RNA ("acquired TRH response"), and by AcCho in oocytes injected with rat brain RNA ("acquired AcCho response"). We found differences in the latencies and patterns of these responses and in the responsiveness to these agonists when applied to the animal or vegetal hemisphere, even though all of the responses are mediated by the same signal transduction pathway. The common intrinsic response to AcCho is characterized by minimal latency (0.86 +/- 0.05 sec), a rapid, transient depolarization followed by a distinct prolonged depolarization, and larger responses obtained after AcCho application at the vegetal rather than the animal hemisphere. By contrast, the acquired responses to TRH and AcCho are characterized by much longer latencies, 9.3 +/- 1.0 and 5.5 +/- 0.8 sec, respectively, and large rapid depolarizations followed by less distinct prolonged depolarizations. The responsiveness on the two hemispheres to TRH and AcCho in mRNA-injected oocytes is opposite to that for the common intrinsic AcCho response in that there is a much greater response when agonist is applied at the animal rather than the vegetal hemisphere. We suggest that the differences in these responses are caused by differences in the intrinsic properties of these receptors. Because different receptors appear to be segregated in the same oocyte in distinct localizations, Xenopus oocytes may be an important model system in which to study receptor sorting in polarized cells.

TSH and prolactin responses to thyrotropin releasing hormone (TRH) and domperidone in patients with empty sella syndrome.

PubMed

Valensi, P; Combes, M E; Perret, G; Attali, J R

1996-05-01

The aim of this study was to investigate TSH and PRL response to TRH and domperidone, an antidopaminergic drug which does not cross the blood-brain barrier, in 16 patients with primary empty sella (PES) and either normal or elevated plasma PRL level and to compare it with the response observed in 8 patients with prolactinoma. In the patients with PES and hyperprolactinemia, the PRL response to TRH was significantly lower than in the controls and the patients with PES and normal PRL, which suggests there is impaired PRL synthesis and release in cases of PES with hyperprolactinemia. The TSH response to domperidone was significantly elevated in patients with PES and either normal or elevated PRL, as in patients with prolactinoma. The PRL response to domperidone was significantly reduced in patients with PES and hyperprolactinemia as in patients with prolactionoma. These results suggestthat in PES with prolactinoma the inhibiting dopaminergic tone is increased on the thyrotropic cells and reduced on the lactotropic cells in PES with elevated PRL and that some patients with PES might bear a microprolactinoma in the bottom of the sella which remained undetected by the CT scan.

Gauge coupling unification and nonequilibrium thermal dark matter.

PubMed

Mambrini, Yann; Olive, Keith A; Quevillon, Jérémie; Zaldívar, Bryan

2013-06-14

We study a new mechanism for the production of dark matter in the Universe which does not rely on thermal equilibrium. Dark matter is populated from the thermal bath subsequent to inflationary reheating via a massive mediator whose mass is above the reheating scale T(RH). To this end, we consider models with an extra U(1) gauge symmetry broken at some intermediate scale (M(int) ≃ 10(10)-10(12) GeV). We show that not only does the model allow for gauge coupling unification (at a higher scale associated with grand unification) but it can provide a dark matter candidate which is a standard model singlet but charged under the extra U(1). The intermediate scale gauge boson(s) which are predicted in several E6/SO(10) constructions can be a natural mediator between dark matter and the thermal bath. We show that the dark matter abundance, while never having achieved thermal equilibrium, is fixed shortly after the reheating epoch by the relation T(RH)(3)/M(int)(4). As a consequence, we show that the unification of gauge couplings which determines M(int) also fixes the reheating temperature, which can be as high as T(RH) ≃ 10(11) GeV.

Altered time structure of neuro-endocrine-immune system function in lung cancer patients.

PubMed

Mazzoccoli, Gianluigi; Vendemiale, Gianluigi; De Cata, Angelo; Carughi, Stefano; Tarquini, Roberto

2010-06-21

The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. The nervous, endocrine and immune system might act as an integrated unit to maintain body defense against this pathological process and reciprocal influences have been evidenced among hypothalamus, pituitary, thyroid, adrenal, pineal gland and immune system. In this study we evaluated differences among healthy subjects and subjects suffering from lung cancer in the 24-hour secretory profile of melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 and circadian variations of lymphocyte subpopulations. In ten healthy male volunteers (age range 45-66) and ten male patients with untreated non small cell lung cancer (age range 46-65) we measured melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 serum levels and percentages of lymphocyte subpopulations on blood samples collected every four hours for 24 hours. One-way ANOVA between the timepoints for each variable and each group was performed to look for a time-effect, the presence of circadian rhythmicity was evaluated, MESOR, amplitude and acrophase values, mean diurnal levels and mean nocturnal levels were compared. A clear circadian rhythm was validated in the control group for hormone serum level and for lymphocyte subsets variation. Melatonin, TRH, TSH, GH, CD3, CD4, HLA-DR, CD20 and CD25 expressing cells presented circadian rhythmicity with acrophase during the night. Cortisol, CD8, CD8(bright), CD8(dim), CD16, TcRdelta1 and deltaTcS1 presented circadian rhythmicity with acrophase in the morning/at noon. FT4, IGF-1 and IL-2 variation did not show circadian rhythmicity. In lung cancer patients cortisol, TRH, TSH and GH serum level and all the lymphocyte subsubsets variation (except for CD4) showed loss of circadian rhythmicity. MESOR of cortisol, TRH, GH, IL-2 and CD16 was increased, whereas MESOR of TSH, IGF-1, CD8, CD8(bright), TcRdelta1 and deltaTcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients. The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system.

Season-Specific Occurrence of Potentially Pathogenic Vibrio spp. on the Southern Coast of South Korea.

PubMed

Di, Doris Y W; Lee, Anna; Jang, Jeonghwan; Han, Dukki; Hur, Hor-Gil

2017-02-01

Vibrio species are widely distributed in warm estuarine and coastal environments, and they can infect humans through the consumption of raw and mishandled contaminated seafood. In this study, we aimed to isolate and observe the distribution of enteropathogenic Vibrio spp. from environments of the southern coast of South Korea over a season cycle. A total of 10,983 isolates of Vibrio spp. were obtained from tidal water and mud samples over a 1-year period from five sampling sites along the southwest coast of South Korea. We found that Vibrio alginolyticus (n = 6,262) and Vibrio parahaemolyticus (n = 1,757) were ubiquitous in both tidal water and mud year round, whereas Vibrio cholerae (n = 24) and Vibrio vulnificus (n = 130) were seasonally specific to summer. While all V. cholerae isolates were nontoxigenic (non-O1 and non-O139), more than 88% of V. vulnificus isolates possessed the virulence factor elastolytic protease (encoded by vvp). Interestingly, V. parahaemolyticus, which was omnipresent in all seasons, contained the virulence factors thermostable direct hemolysin (encoded by tdh) and thermostable direct hemolysin-related hemolysin (encoded by trh) in larger amounts in June (29 trh-positive strains) and September (14 tdh-, 36 trh-, and 12 tdh- and trh-positive strains) than in December (4 trh-positive strains) and February (3 tdh-positive strains), and virulence factors were absent from isolates detected in April. To understand why virulence factors were detected only in the warm season and were absent in the cold season although the locations are static, long-term monitoring and particularly seasonal study are necessary. The presence of enteropathogenic Vibrio species (Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus), which cause acute diarrheal infection, septicemia, and wound infections upon ingestion through food and water, is usually associated with temperature. The World Health Organization (WHO) has estimated that there are 1.4 to 4.3 million cases and 28,000 to 142,000 deaths per year worldwide caused by cholera disease. In South Korea alone, consumption is as much as 52.4 kg of fish and shellfish per year per capita. Our findings suggested that seasonally specific acceleration of these possible pathogenic Vibrio spp. may threaten seafood safety and increase the risk of illness in South Korea, where local people consume raw fish during warmer months. Copyright © 2017 American Society for Microbiology.

Season-Specific Occurrence of Potentially Pathogenic Vibrio spp. on the Southern Coast of South Korea

PubMed Central

Di, Doris Y. W.; Lee, Anna; Jang, Jeonghwan; Han, Dukki

2016-01-01

ABSTRACT Vibrio species are widely distributed in warm estuarine and coastal environments, and they can infect humans through the consumption of raw and mishandled contaminated seafood. In this study, we aimed to isolate and observe the distribution of enteropathogenic Vibrio spp. from environments of the southern coast of South Korea over a season cycle. A total of 10,983 isolates of Vibrio spp. were obtained from tidal water and mud samples over a 1-year period from five sampling sites along the southwest coast of South Korea. We found that Vibrio alginolyticus (n = 6,262) and Vibrio parahaemolyticus (n = 1,757) were ubiquitous in both tidal water and mud year round, whereas Vibrio cholerae (n = 24) and Vibrio vulnificus (n = 130) were seasonally specific to summer. While all V. cholerae isolates were nontoxigenic (non-O1 and non-O139), more than 88% of V. vulnificus isolates possessed the virulence factor elastolytic protease (encoded by vvp). Interestingly, V. parahaemolyticus, which was omnipresent in all seasons, contained the virulence factors thermostable direct hemolysin (encoded by tdh) and thermostable direct hemolysin-related hemolysin (encoded by trh) in larger amounts in June (29 trh-positive strains) and September (14 tdh-, 36 trh-, and 12 tdh- and trh-positive strains) than in December (4 trh-positive strains) and February (3 tdh-positive strains), and virulence factors were absent from isolates detected in April. To understand why virulence factors were detected only in the warm season and were absent in the cold season although the locations are static, long-term monitoring and particularly seasonal study are necessary. IMPORTANCE The presence of enteropathogenic Vibrio species (Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus), which cause acute diarrheal infection, septicemia, and wound infections upon ingestion through food and water, is usually associated with temperature. The World Health Organization (WHO) has estimated that there are 1.4 to 4.3 million cases and 28,000 to 142,000 deaths per year worldwide caused by cholera disease. In South Korea alone, consumption is as much as 52.4 kg of fish and shellfish per year per capita. Our findings suggested that seasonally specific acceleration of these possible pathogenic Vibrio spp. may threaten seafood safety and increase the risk of illness in South Korea, where local people consume raw fish during warmer months. PMID:27836844

Altered time structure of neuro-endocrine-immune system function in lung cancer patients

PubMed Central

2010-01-01

Background The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. The nervous, endocrine and immune system might act as an integrated unit to mantain body defense against this pathological process and reciprocal influences have been evidenced among hypothalamus, pituitary, thyroid, adrenal, pineal gland and immune system. In this study we evaluated differences among healthy subjects and subjects suffering from lung cancer in the 24-hour secretory profile of melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 and circadian variations of lymphocyte subpopulations. Methods In ten healthy male volunteers (age range 45-66) and ten male patients with untreated non small cell lung cancer (age range 46-65) we measured melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 serum levels and percentages of lymphocyte subpopulations on blood samples collected every four hours for 24 hours. One-way ANOVA between the timepoints for each variable and each group was performed to look for a time-effect, the presence of circadian rhythmicity was evaluated, MESOR, amplitude and acrophase values, mean diurnal levels and mean nocturnal levels were compared. Results A clear circadian rhythm was validated in the control group for hormone serum level and for lymphocyte subsets variation. Melatonin, TRH, TSH, GH, CD3, CD4, HLA-DR, CD20 and CD25 expressing cells presented circadian rhythmicity with acrophase during the night. Cortisol, CD8, CD8bright, CD8dim, CD16, TcRδ1 and δTcS1 presented circadian rhythmicity with acrophase in the morning/at noon. FT4, IGF-1 and IL-2 variation did not show circadian rhythmicity. In lung cancer patients cortisol, TRH, TSH and GH serum level and all the lymphocyte subsubsets variation (except for CD4) showed loss of circadian rhythmicity. MESOR of cortisol, TRH, GH, IL-2 and CD16 was increased, whereas MESOR of TSH, IGF-1, CD8, CD8bright, TcRδ1 and δTcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients. Conclusion The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system PMID:20565977

Comparison of the Effects of Environmental Parameters on the Growth Variability of Vibrio parahaemolyticus Coupled with Strain Sources and Genotypes Analyses.

PubMed

Liu, Bingxuan; Liu, Haiquan; Pan, Yingjie; Xie, Jing; Zhao, Yong

2016-01-01

Microbial growth variability plays an important role on food safety risk assessment. In this study, the growth kinetic characteristics corresponding to maximum specific growth rate (μmax) of 50 V. parahaemolyticus isolates from different sources and genotypes were evaluated at different temperatures (10, 20, 30, and 37°C) and salinity (0.5, 3, 5, 7, and 9%) using the automated turbidimetric system Bioscreen C. The results demonstrated that strain growth variability increased as the growth conditions became more stressful both in terms of temperature and salinity. The coefficient of variation (CV) of μmax for temperature was larger than that for salinity, indicating that the impact of temperature on strain growth variability was greater than that of salinity. The strains isolated from freshwater aquatic products had more conspicuous growth variations than those from seawater. Moreover, the strains with tlh (+) /tdh (+) /trh (-) exhibited higher growth variability than tlh (+) /tdh (-) /trh (-) or tlh (+) /tdh (-) /trh (+), revealing that gene heterogeneity might have possible relations with the growth variability. This research illustrates that the growth environments, strain sources as well as genotypes have impacts on strain growth variability of V. parahaemolyticus, which can be helpful for incorporating strain variability in predictive microbiology and microbial risk assessment.

Hypothalamic control of pituitary and adrenal hormones during hypothermia.

PubMed

Okuda, C; Miyazaki, M; Kuriyama, K

1986-01-01

In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus.

Effects of oral administration of levothyroxine sodium on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone in healthy adult mares.

PubMed

Sommardahl, Carla S; Frank, Nicholas; Elliott, Sarah B; Webb, Latisha L; Refsal, Kent R; Denhart, Joseph W; Thompson, Donald L

2005-06-01

To determine the effects of levothyroxine sodium (L-T4) on serum concentrations of thyroid gland hormones and responses to injections of thyrotropin-releasing hormone (TRH) in euthyroid horses. 12 healthy adult mares. 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provided for 2 weeks. Four additional horses remained untreated. Serum concentrations of total triiodothyronine (tT3), total thyroxine (tT4), free T3 (fT3), free T4 (fT4), and thyroid-stimulating hormone (TSH) were measured in samples obtained at weeks 0, 2, 4, 6, and 8; 1.2 mg of TRH was then administered i.v., and serum concentrations of thyroid gland hormones were measured 2 and 4 hours after injection. Serum reverseT3 (rT3) concentration was also measured in the samples collected at weeks 0 and 8. Treated horses lost a significant amount of weight (median, 19 kg). Significant treatment-by-time effects were detected for serum tT3, tT4, fT3, fT4, and TSH concentrations, and serum tT4 concentrations were positively correlated (r, 0.95) with time (and therefore dosage) in treated horses. Mean +/- SD serum rT3 concentration significantly increased in treated horses (3.06 +/- 0.51 nmol/L for week 8 vs 0.74 +/- 0.22 nmol/L for week 0). Serum tT3, tT4, fT3, and TSH concentrations in response to TRH injections differed significantly between treated and untreated horses. Administration of levothyroxine sodium increased serum tT4 concentrations and blunted responses toTRH injection in healthy euthyroid horses.

A receptor-G protein coupling-independent step in the internalization of the thyrotropin-releasing hormone receptor.

PubMed

Petrou, C; Chen, L; Tashjian, A H

1997-01-24

To determine whether functional receptor-G protein coupling or signaling are required for internalization of the thyrotropin-releasing hormone receptor (TRHR), we compared the endocytosis of Gq-coupled and uncoupled receptors. A hemagglutinin epitope-tagged TRHR (HA-TRHR) was in the Gq-coupled state when bound to the agonist, MeTRH, and in a nonsignaling state when bound to the HA antibody (12CA5). 12CA5 did not induce an increase in [Ca2+]i or inositol phosphates and did not inhibit [3H]MeTRH binding or MeTRH-induced production of second messengers. Both agonist- and antibody-bound HA-TRHRs were rapidly internalized via the same pathway; internalization was sensitive to hypertonic shock, and both types of internalized receptors were sorted into lysosomes. In addition, the amino acid sequence CNC (positions 335-337) in the C-terminal tail of the TRHR, which is important in ligand-induced receptor internalization as determined by deletion mutagenesis (Nussenzveig, D. R., Heinflink, M., and Gershengorn, M. C. (1993) J. Biol. Chem. 268, 2389-2392), was also important for 12CA5-induced internalization. We expressed two truncated receptors, HA-K338STOP and HA-C335STOP, in GH12C1 pituitary cells. Both HA-TRHR and HA-K338STOP were localized at the plasma membrane of untreated cells and were translocated to intracellular vesicles after MeTRH or 12CA5 binding; however, HA-C335STOP was internalized and recycled constitutively. The intracellular localization of HA-C335STOP was not altered by MeTRH; however, 12CA5 binding induced the disappearance of internalized HA-C335STOP and caused its localization at the plasma membrane, indicating that constitutively cycling HA-C335STOP cannot be reinternalized after antibody binding. Thus, amino acids 335-337, which are important for the internalization of Gq-coupled TRHRs, are also required for the sequestration of functionally uncoupled TRHRs, and in addition, they act as an inhibitory signal that prevents constitutive receptor internalization. Specifically, the Cys residues at positions 335 and 337 are important for preventing constitutive TRHR internalization, because a mutant HA-C335S/C337S receptor was sequestered constitutively. We conclude that release from a negative regulatory internalization sequence or domain is important for HA-TRHR internalization and that the role of the CNC sequence in internalization is independent of functional TRHR-Gq coupling.

Hyperfunctioning thyroid nodules in children.

PubMed

Abe, K; Konno, M; Sato, T; Matsuura, N

1980-10-01

We studied two cases of hyperfunctioning thyroid nodules in children. A 9-year-old girl and an 11-year-old girl had thyroid masses in otherwise nonpalpable thyroid glands. Scintiscan showed hyperfunctioning thyroid nodules. The former patient had elevated values for T4 and T3, and plasma thyrotropin (TSH) level failed to respond to stimulation with thyrotropin releasing hormone (TRH), whereas the latter patient had normal values for T4, and T3 and plasma TSH response to TRH was normal. After the surgical removal of nodules, scintiscan exhibited radioactivity in the contralateral lobe of the thyroid gland in the former and in the ectopic thyroid tissue in the latter. Results of microscopic examinations of thyroid nodules were consistent with adenomatous goiter.

Ammonium-induced loss of root gravitropism is related to auxin distribution and TRH1 function, and is uncoupled from the inhibition of root elongation in Arabidopsis.

PubMed

Zou, Na; Li, Baohai; Dong, Gangqiang; Kronzucker, Herbert J; Shi, Weiming

2012-06-01

Root gravitropism is affected by many environmental stresses, including salinity, drought, and nutrient deficiency. One significant environmental stress, excess ammonium (NH(4)(+)), is well documented to inhibit root elongation and lateral root formation, yet little is known about its effects on the direction of root growth. We show here that inhibition of root elongation upon elevation of external NH(4)(+) is accompanied by a loss in root gravitropism (agravitropism) in Arabidopsis. Addition of potassium (K(+)) to the treatment medium partially rescued the inhibition of root elongation by high NH(4)(+) but did not improve gravitropic root curvature. Expression analysis of the auxin-responsive reporter gene DR5::GUS revealed that NH(4)(+) treatment delayed the development of gravity-induced auxin gradients across the root cap but extended their duration once initiated. Moreover, the β-glucuronidase (GUS) signal intensity in root tip cells was significantly reduced under high NH(4)(+) treatment over time. The potassium carrier mutant trh1 displayed different patterns of root gravitropism and DR5::GUS signal intensity in root apex cells compared with the wild type in response to NH(4)(+). Together, the results demonstrate that the effects of NH(4)(+) on root gravitropism are related to delayed lateral auxin redistribution and the TRH1 pathway, and are largely independent of inhibitory effects on root elongation.

The hypothalamic-pituitary-thyroid axis and melatonin in humans: possible interactions in the control of body temperature.

PubMed

Mazzoccoli, G; Giuliani, A; Carughi, S; De Cata, A; Puzzolante, F; La Viola, M; Urbano, N; Perfetto, F; Tarquini, R

2004-10-01

Melatonin plays a role in the regulation of biological rhythms, body temperature presents circadian variations with lower levels during nighttime, when melatonin levels are very high, and thyroid hormones influence shiver independent thermogenesis. We have investigated on possible interactions between the hypothalamic-pituitary-thyroid axis and melatonin in the control of body temperature in humans. Peripheral blood samples for thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free-thyroxine (FT4), melatonin levels determination and body temperature measurements were obtained every four hours for 24-hours starting at 0600 h in a controlled temperature and light-dark environment from ten healthy males, aged 38-65 (mean age +/-s.e. 57.4+/-3.03, mean body mass index +/-s.e. 25.5+/-0.75). We calculated fractional variation and correlation on single time point hormone serum levels and tested whether the time-qualified data series showed consistent pattern of circadian variation. A statistically significant difference was evidenced for the fractional variation of daytime TSH serum levels (0600 h-1000 h vs. 1000 h-1400 h, p=0.01, 1000 h-1400 h vs. 1400 h-1800 h, p=0.0001, 1400 h-1800 h vs. 1800 h-2200 h, p=0.001) and for the fractional variation of FT4 serum levels at 1800 h-2200 h vs. 2200 h-0200 h (p=0.02). FT4 serum levels correlated positively with TRH serum levels at 1000 h (r=0.67, P=0.03) and at 1400 h (r=0.63, p=0.04), negatively with TSH serum levels at 2200 h (r=-0.67, p=0.03), negatively with melatonin serum levels at 2200 h (r=-0.64, p=0.04) and at 0200 h (r=-0.73, p=0.01). TRH serum levels correlated positively with TSH serum levels at 0200 h (r=0.65, p=0.04) and at 0600 h (r=0.64, p=0.04). Body temperature correlated positively with FT4 serum levels at 1000 h (r=0.63, p=0.04) and negatively with melatonin serum levels at 0200 h (r=-0.64, p=0.04). A clear circadian rhythm was validated for body temperature (with acrophase in the morning) and melatonin, TRH and TSH secretion (with acrophase at night), while FT4 serum level changes presented ultradian periodicity (with acrophase in the morning). Changes of TSH serum levels are smaller and those of FT4 are greater at night, when melatonin levels are higher, so that the response of anterior pituitary to hypothalamic TRH and of thyroid to hypophyseal TSH may be influenced by the pineal hormone that may modulate the hypothalamic-pituitary-thyroid axis function and influence the circadian rhythm of body temperature.

Anomalous Change of Hall Coefficient in Overdoped La2-xSrxCu1-yZnyO4 around x = 0.2

NASA Astrophysics Data System (ADS)

Tonishi, Jun; Suzuki, Takao; Goto, Takayuki

2006-09-01

The Hall coefficient (RH) has been measured in 0.5% Zn-doped La2-xSrxCu0.995Zn0.005O4 under high magnetic fields up to 12 T. With decreasing temperature, RH increases and begins to decrease below a temperature TRH. This characteristic temperature TRH has the local maximum around x = 0.195, and this Sr-concentration coincides with that the superconducting transition temperature is slightly suppressed. This behavior is quite similar to the phenomena observed in the stripe phase in x ˜ 0.12. These results suggest that the anomalous decrease of RH around x = 0.195 observed in this study is responsible for the "1/4"-anomaly [as reported by Kakinuma et al., Phys. Rev. B 59, 1491 (1999).].

HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters.

PubMed

Jokinen, Jussi; Samuelsson, Mats; Nordström, Anna-Lena; Nordström, Peter

2008-11-01

A lower thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in depressed women has been associated with violent suicide attempts, suicidal intent, higher lethality and suicide risk. The cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels are related to suicidal behaviour. We studied the HPT axis function in twelve male suicide attempters and eight healthy volunteers submitted to lumbar puncture and to TRH test. Suicidal behaviour and depression severity were assessed. There was no association between deltamaxTSH and violent suicidality or subsequent suicide. The deltamaxTSH correlated with CSF HVA in suicide attempters. The plasma T3 showed a negative correlation with the Beck Suicide Intent Scale and the Montgomery Asberg Depression rating scale. Dopaminergic regulatory mechanisms on the thyroid hormone activity may be altered in male suicide attempters.

Genome sequencing and analysis of a highly virulent Vibrio parahaemolyticus strain isolated from the marine environment

NASA Astrophysics Data System (ADS)

Parks, M. C.; Moreno, E.

2016-02-01

Vibrio parahaemolyticus [Vp] is a Gram-negative bacterium and a natural inhabitant of coastal marine ecosystems worldwide. Vp is also a coincidental pathogen of humans. Virulent strains are commonly identified by the presence of the thermostable direct (tdh) or tdh-related (trh) hemolysin genes. However, virulence is multifaceted and many clinical Vp isolates do not carry tdh or trh. In this study, we sequenced and assembled the draft genome of a tdh- and trh-negative environmental isolate (805) shown previously to be highly virulent in zebrafish. To investigate potential mechanisms of virulence, we compared 805 to the clinical V. parahaemolyticus type strain (RIMD2210633). Pairwise comparison revealed the presence of multiple genomic regions including an IncF conjugative pilus (1.3 Kb) and a colicin V plasmid (1.49 Kb). These features are homologous to genomic regions present in clinical V. vulnificus and V. cholerae strains. Genome comparison also revealed the presence of five toxin-antitoxin systems. Isolate 805 likely attained these new features through the lateral acquisition of mobile genomic material - a hypothesis supported by the aberrant GC content of these regions. Colicin V plasmids are a diverse group of IncF plasmids found in invasive bacterial strains. Similarly, an abundance of toxin-antitoxin systems have been linked to virulence in Gram-negative bacteria. Current efforts are focused on characterizing 142 coding features present in 805 but absent from the type strain.

Maturation of human hypothalamic-pituitary-thyroid function and control.

PubMed

Fisher, D A; Nelson, J C; Carlton, E I; Wilcox, R B

2000-03-01

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.

PubMed

Alcántara-Alonso, Viridiana; Alvarez-Salas, Elena; Matamoros-Trejo, Gilberto; de Gortari, Patricia

2017-10-18

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

Prevalence and antimicrobial susceptibility of Vibrio parahaemolyticus isolated from retail shrimps in Malaysia.

PubMed

Letchumanan, Vengadesh; Yin, Wai-Fong; Lee, Learn-Han; Chan, Kok-Gan

2015-01-01

Vibrio parahaemolyticus is a marine and estuarine bacterium that has been the leading cause of foodborne outbreaks which leads to a significant threat to human health worldwide. Consumption of seafood contaminated with V. parahaemolyticus causes acute gastroenteritis in individuals. The bacterium poses two main virulence factor including the thermostable direct hemolysin (tdh) which is a pore-forming protein that contributes to the invasiveness of the bacterium in humans and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. This study aimed to investigate the antimicrobial resistance V. parahaemolyticus strains in shrimps purchased from wetmarkets and supermarkets. The toxR-based PCR assay indicated that a total of 57.8% (185/320) isolates were positive for V. parahaemolyticus. Only 10% (19/185) toxR-positive isolate exhibit the trh gene and none of the isolates were tested positive for tdh. The MAR index was measured for 14 common antimicrobial agents. The results indicated 98% of the isolates were highly susceptible to imipenem, ampicillin sulbactam (96%), chloramphenicol (95%), trimethoprim-sulfamethoxazole (93%), gentamicin (85%), levofloxacin (83%), and tetracycline (82%). The chloramphenicol (catA2) and kanamycin (aphA-3) resistance genes were detected in the resistant V. parahaemolyticus isolates. Our results demonstrate that shrimps are contaminated with V. parahaemolyticus, some of which carry the trh-gene thus being potential to cause food borne illness. The occurrence of multidrug resistance strains in the environment could be an indication of excessive usage of antibiotics in agriculture and aquaculture fields.

SEPARATION BY ADSORPTION

DOEpatents

Lowe, C.S.

1959-06-16

Separation of Pu from fission products by adsorption on hydrous aluminum silicate is described. The Pu in a HNO/sub 3/ solution is oxidized to the hexavalent state and contacted with the silicate which adsorbs fission products. (T.R.H.)

DRIFT COMPENSATED DIRECT COUPLED AMPLIFIER

DOEpatents

Windsor, A.A.

1959-05-01

An improved direct-coupled amplifier having zerolevel drift correction is described. The need for an auxiliary corrective-potential amplifier is eliminated thereby giving protection against overload saturation of the zero- level drift correcting circuit. (T.R.H.)

Chronodisruption in lung cancer and possible therapeutic approaches.

PubMed

Mazzoccoli, Gianluigi; Tarquini, Roberto; Durfort, Tiphanie; Francois, Jean-Christophe

2011-10-01

A customary temporal organization of physiological functions and biological processes is necessary to maintain body homeostasis and an altered body time structure may favour carcinogenesis. There is growing evidence that GH stimulates cancer growth, IGF1 may have a role in carcinogenesis and cancer promotion, GH-IGF1 axis, TRH, TSH, thyroxine, melatonin and cortisol modulate immune cell function and the immune system is often dysfunctional in patients with malignancies. The aim of our study was to evaluate GH-IGF1 axis, hypothalamus-pituitary-thyroid axis, melatonin, cortisol, lymphocyte subsets and IL2 in lung cancer patients. Peripheral blood samples were collected at 4-hour intervals in a 24-hour period from eleven healthy male subjects (age range 35-53 years) and nine male patients suffering from non-small cell lung cancer (age range 43-63 years). In each blood sample, lymphocyte subpopulations (CD3+, CD4+, CD8+, CD16+, CD20+, CD25+, HLA-DR+, γδTcR bearing cells) were analyzed and GH, IGF1, TRH, TSH, FT4, melatonin, cortisol and IL2 were measured. Circadian rhythmicity was evaluated and MESOR, amplitude and acrophase values were compared. In healthy subjects a significant circadian rhythm could be demonstrated with midday peaks for CD8+, CD16+, γδTCR expressing cells and cortisol, and peaks during the night for CD3+, CD4+, GH, TSH and melatonin. A borderline significant rhythm was also observed for CD20+, with a peak late in the evening. IGF1, TRH, FT4 and IL2 values did not show rhythmic variation. In cancer patients a significant circadian rhythm could be demonstrated with diurnal peak for CD16+ and peaks during the night for CD4+ and melatonin. GH, IGF1, TRH, TSH, FT4, cortisol and IL2 values did not show rhythmic variation. MESOR of CD8+ (P<0.0001), CD20+ (P=0.05), γδTCR expressing cells (P=0.01), IGF1 (P<0.001) and TSH (P=0.032) was higher in healthy subjects, whereas MESOR of CD16+ (P<0.0001), CD25+ (P=0.001), GH (P<0.001), TRH (P=0.002), FT4 (P=0.030), cortisol (P=0.01) and IL2 (P=0.02) was higher in cancer patients. Amplitude of circadian variation of γδTCR expressing cells (P=0.01), TSH (P<0.001) and cortisol (P=0.01) was higher in healthy subjects, whereas amplitude of circadian variation of CD4+ was higher in cancer patients (P=0.02). In conclusion, non-small cell lung cancer patients show severe alterations of periodic and quantitative characteristics of neuroendocrine and immune parameters with loss of circadian rhythmicity and internal desynchronization, leading to chronodisruption. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

LOW-LEVEL DIRECT CURRENT AMPLIFIER

DOEpatents

Kerns, Q.A.

1959-05-01

A d-c amplifier is described. Modulation is provided between a d-c signal and an alternating current to give an output signal proportional to the d- c signal. The circuit has high sensitivity and accuracy. (T.R.H.)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finzi, S.; Marchetti, C.; Renzoni, R.

The first of four reports on the design of a plant for producing 99.75 mole% D/sub 2/O from preconcentrated solutions is presented. The isotopic and chemicophysical design is treated, all the necessary theoretical considerations for the calculations being given. (T.R.H.)

Characterization of clinical Vibrio parahaemolyticus strains in Zhoushan, China, from 2013 to 2014.

PubMed

Wang, Hongling; Tang, Xiaoyang; Su, Yi-Cheng; Chen, Jiabei; Yan, Jianbo

2017-01-01

Vibrio parahaemolyticus is recognized as major cause of foodborne illness of global public health concern. This study collected 107 strains of V. parahaemolyticus during active surveillance of diarrheal diseases in hospitals in Zhoushan during 2013 to 2014 and investigated their serotypes, virulence genes (tdh, trh, and orf8), antimicrobial resistance, and genotypes. The dominant serotypes of the 107 clinical strains were O3:K6, O4:K8, and O4:KUT with 87.9% and 3.7% of the strains carrying the virulence genes tdh and trh, respectively. Molecular typing by pulsed-field gel electrophoresis indicated divergence among the clinical strains. Most isolates were sensitive to the common antimicrobial agents used against the Vibrio species except ampicillin. We conclude that continuous surveillance of V. parahaemolyticus in diarrhea patients is a public health priority and is useful for conducting risk assessment of foodborne illnesses caused by V. parahaemolyticus.

Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement

PubMed Central

Sun, Yu; Bak, Beata; Schoenmakers, Nadia; van Trotsenburg, A.S. Paul; Oostdijk, Wilma; Voshol, Peter; Cambridge, Emma; White, Jacqueline K.; le Tissier, Paul; Gharavy, S. Neda Mousavy; Martinez-Barbera, Juan P.; Stokvis-Brantsma, Wilhelmina H.; Vulsma, Thomas; Kempers, Marlies J.; Persani, Luca; Campi, Irene; Bonomi, Marco; Beck-Peccoz, Paolo; Zhu, Hongdong; Davis, Timothy M.E.; Hokken-Koelega, Anita C.S.; Del Blanco, Daria Gorbenko; Rangasami, Jayanti J.; Ruivenkamp, Claudia A.L.; Laros, Jeroen F.J.; Kriek, Marjolein; Kant, Sarina G.; Bosch, Cathy A.J.; Biermasz, Nienke R.; Appelman-Dijkstra, Natasha M.; Corssmit, Eleonora P.; Hovens, Guido C.J.; Pereira, Alberto M.; den Dunnen, Johan T.; Wade, Michael G.; Breuning, Martijn H.; Hennekam, Raoul C.; Chatterjee, Krishna; Dattani, Mehul T.; Wit, Jan M.; Bernard, Daniel J.

2012-01-01

Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified eight distinct mutations and two deletions in IGSF1 in males from eleven unrelated families with central hypothyroidism, testicular enlargement, and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary gland and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations, and increased body mass. Collectively, our observations delineate a novel X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling. PMID:23143598

Antimicrobial resistance and potential virulence of Vibrio parahaemolyticus isolated from water and bivalve mollusks from Bahia, Brazil.

PubMed

Silva, Irana Paim; Carneiro, Camila de Souza; Saraiva, Margarete Alice Fontes; Oliveira, Thiago Alves Santos de; Sousa, Oscarina Viana de; Evangelista-Barreto, Norma Suely

2018-06-01

The aim of the present study was to verify the antimicrobial susceptibility profile and virulence factors of Vibrio parahaemolyticus isolated from water and bivalve mollusks. A high percentage of V. parahaemolyticus was isolated in natura, processed bivalves tissues, and surrounding water (75%, 20%, and 59%, respectively). The most potential virulence phenotype in V. parahaemolyticus isolates was amylase production (97%) followed by DNase (83%), phospholipase (70%), β-hemolytic activity (57%). The tdh and trh genes were not detected. Besides, a high antimicrobial resistance was observed for ampicillin (97%), minimum inhibitory concentration [MIC] = 400 μg and cephalothin (93%, MIC ≤ 100 μg). The absence of expression of tdh and trh virulence genes excluded the toxigenic potential of V. parahaemolyticus isolates; however, the high prevalence of antimicrobial resistance among the environmental strains is a risk to human health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prevalence and antimicrobial susceptibility of Vibrio parahaemolyticus isolated from retail shrimps in Malaysia

PubMed Central

Letchumanan, Vengadesh; Yin, Wai-Fong; Lee, Learn-Han; Chan, Kok-Gan

2015-01-01

Vibrio parahaemolyticus is a marine and estuarine bacterium that has been the leading cause of foodborne outbreaks which leads to a significant threat to human health worldwide. Consumption of seafood contaminated with V. parahaemolyticus causes acute gastroenteritis in individuals. The bacterium poses two main virulence factor including the thermostable direct hemolysin (tdh) which is a pore-forming protein that contributes to the invasiveness of the bacterium in humans and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. This study aimed to investigate the antimicrobial resistance V. parahaemolyticus strains in shrimps purchased from wetmarkets and supermarkets. The toxR-based PCR assay indicated that a total of 57.8% (185/320) isolates were positive for V. parahaemolyticus. Only 10% (19/185) toxR-positive isolate exhibit the trh gene and none of the isolates were tested positive for tdh. The MAR index was measured for 14 common antimicrobial agents. The results indicated 98% of the isolates were highly susceptible to imipenem, ampicillin sulbactam (96%), chloramphenicol (95%), trimethoprim-sulfamethoxazole (93%), gentamicin (85%), levofloxacin (83%), and tetracycline (82%). The chloramphenicol (catA2) and kanamycin (aphA-3) resistance genes were detected in the resistant V. parahaemolyticus isolates. Our results demonstrate that shrimps are contaminated with V. parahaemolyticus, some of which carry the trh-gene thus being potential to cause food borne illness. The occurrence of multidrug resistance strains in the environment could be an indication of excessive usage of antibiotics in agriculture and aquaculture fields. PMID:25688239

Relationships between environmental factors and pathogenic Vibrios in the Northern Gulf of Mexico.

PubMed

Johnson, C N; Flowers, A R; Noriea, N F; Zimmerman, A M; Bowers, J C; DePaola, A; Grimes, D J

2010-11-01

Although autochthonous vibrio densities are known to be influenced by water temperature and salinity, little is understood about other environmental factors associated with their abundance and distribution. Densities of culturable Vibrio vulnificus containing vvh (V. vulnificus hemolysin gene) and V. parahaemolyticus containing tlh (thermolabile hemolysin gene, ubiquitous in V. parahaemolyticus), tdh (thermostable direct hemolysin gene, V. parahaemolyticus pathogenicity factor), and trh (tdh-related hemolysin gene, V. parahaemolyticus pathogenicity factor) were measured in coastal waters of Mississippi and Alabama. Over a 19-month sampling period, vibrio densities in water, oysters, and sediment varied significantly with sea surface temperature (SST). On average, tdh-to-tlh ratios were significantly higher than trh-to-tlh ratios in water and oysters but not in sediment. Although tlh densities were lower than vvh densities in water and in oysters, the opposite was true in sediment. Regression analysis indicated that SST had a significant association with vvh and tlh densities in water and oysters, while salinity was significantly related to vibrio densities in the water column. Chlorophyll a levels in the water were correlated significantly with vvh in sediment and oysters and with pathogenic V. parahaemolyticus (tdh and trh) in the water column. Furthermore, turbidity was a significant predictor of V. parahaemolyticus density in all sample types (water, oyster, and sediment), and its role in predicting the risk of V. parahaemolyticus illness may be more important than previously realized. This study identified (i) culturable vibrios in winter sediment samples, (ii) niche-based differences in the abundance of vibrios, and (iii) predictive signatures resulting from correlations between environmental parameters and vibrio densities.

Prevalences of pathogenic and non-pathogenic Vibrio parahaemolyticus in mollusks from the Spanish Mediterranean Coast

PubMed Central

Lopez-Joven, Carmen; de Blas, Ignacio; Furones, M. Dolores; Roque, Ana

2015-01-01

Vibrio parahaemolyticus is a well-recognized pathogen of humans. To better understand the ecology of the human-pathogenic variants of this bacterium in the environment, a study on the prevalence in bivalves of pathogenic variants (tlh+ and tdh+ and/or trh+) versus a non-pathogenic one (only tlh+ as species marker for V. parahaemolyticus), was performed in two bays in Catalonia, Spain. Environmental factors that might affect dynamics of both variants of V. parahaemolyticus were taken into account. The results showed that the global prevalence of total V. parahaemolyticus found in both bays was 14.2% (207/1459). It was, however, significantly dependent on sampling point, campaign (year) and bivalve species. Pathogenic variants of V. parahaemolyticus (tdh+ and/or trh+) were detected in 3.8% of the samples (56/1459), meaning that the proportion of bivalves who contained tlh gene were contaminated by pathogenic V. parahaemolyticus strains is 27.1% (56/207). Moreover, the presence of pathogenic V. parahaemolyticus (trh+) was significantly correlated with water salinity, thus the probability of finding pathogenic V. parahaemolyticus decreased 1.45 times with every salinity unit (ppt) increased. Additionally, data showed that V. parahaemolyticus could establish close associations with Ruditapes spp. (P-value < 0.001), which could enhance the transmission of illness to human by pathogenic variants, when clams were eaten raw or slightly cooked. This study provides information on the abundance, ecology and characteristics of total and human-pathogenic V. parahaemolyticus variants associated with bivalves cultured in the Spanish Mediterranean Coast. PMID:26284033

Prevalence and quantification of pathogenic Vibrio parahaemolyticus during shrimp culture in Thailand.

PubMed

Yingkajorn, Mingkwan; Mitraparp-Arthorn, Pimonsri; Nuanualsuwan, Suphachai; Poomwised, Ratanaruji; Kongchuay, Noochanat; Khamhaeng, Natchaya; Vuddhakul, Varaporn

2014-12-02

Vibrio parahaemolyticus is a major cause of seafood-borne gastroenteritis. The human pathogenic strains possess tdh or trh or both genes. In Thai shrimp farming, the level of pathogenic V. parahaemolyticus contamination has not been completely characterized, although it has been identified as a risk for people who consume undercooked shrimp. In this study, the prevalence and concentration of V. parahaemolyticus (total Vp) and pathogenic V. parahaemolyticus (tdh+ Vp and trh+ Vp) were investigated during shrimp culture cycles using the most probable number (MPN) method and were confirmed by PCR and the loop-mediated isothermal amplification (LAMP) techniques. The prevalence and concentration of total Vp were high in broodstock and egg samples at the start of the hatchery cycle, but the organism decreased in the subsequent larval and postlarval stages. In contrast, total Vp was low at the beginning of the pond cycle and dramatically increased during the later stages of culture. Broodstock and fresh feed were important sources of V. parahaemolyticus. Numbers of tdh+ Vp and trh+ Vp detected by the LAMP technique were much greater than those detected by the PCR technique, especially in the late stages of the pond cycle. A direct correlation between total Vp and pathogenic Vp was demonstrated only during the harvest stage. This study will be useful as a guideline to establish levels of V. parahaemolyticus presence which can be considered as safe during shrimp culture. In addition, it could be used to identify the source of V. parahaemolyticus, which has recently been reported to be one of the etiologic agents of acute hepatopancreatic necrosis disease.

MINING AND PROCESSING AT THE MARY KATHLEEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1959-03-01

Ore mining and processing to the yellow cake at Mary Kathleen, Queensland, Australia, are described. The mining, crushlng, grinding, leaching, solids separation, ion exchange, purification, and final precipitation procedures and equipment are discussed in some detail. (T.R.H.)

ION BEAM FOCUSING MEANS FOR CALUTRON

DOEpatents

Backus, J.G.

1959-06-01

An ion beam focusing arrangement for calutrons is described. It provides a virtual focus of origin for the ion beam so that the ions may be withdrawn from an arc plasma of considerable width providing greater beam current and accuracy. (T.R.H.)

Leptin levels in protracted critical illness: effects of growth hormone-secretagogues and thyrotropin-releasing hormone.

PubMed

Van den Berghe, G; Wouters, P; Carlsson, L; Baxter, R C; Bouillon, R; Bowers, C Y

1998-09-01

Prolonged critical illness is characterized by feeding-resistant wasting of protein, whereas reesterification, instead of oxidation of fatty acids, allows fat stores to accrue and associate with a low-activity status of the somatotropic and thyrotropic axis, which seems to be partly of hypothalamic origin. To further unravel this paradoxical metabolic condition, and in search of potential therapeutic strategies, we measured serum concentrations of leptin; studied the relationship with body mass index, insulin, cortisol, thyroid hormones, and somatomedins; and documented the effects of hypothalamic releasing factors, in particular, GH-secretagogues and TRH. Twenty adults, critically ill for several weeks and supported with normocaloric, continuously administered parenteral and/or enteral feeding, were studied for 45 h. They had been randomized to receive one of three combinations of peptide infusions, in random order: TRH (one day) and placebo (other day); TRH + GH-releasing peptide (GHRP)-2 and GHRP-2; TRH + GHRH + GHRP-2 and GHRH + GHRP-2. Peptide infusions were started after a 1-microgram/kg bolus at 0900 h and infused (1 microgram/kg.h) until 0600 h the next morning. Serum concentrations of leptin, insulin, cortisol, T4, T3, insulin-like growth factor (IGF)-I, IGF-binding protein-3 and the acid-labile subunit (ALS) were measured at 0900 h, 2100 h, and 0600 h on each of the 2 study days. Baseline leptin levels (mean +/- SEM: 12.4 +/- 2.1 micrograms/L) were independent of body mass index (25 +/- 1 kg/m2), insulin (18.6 +/- 2.9 microIU/mL), cortisol (504 +/- 43 mmol/L), and thyroid hormones (T4: 63 +/- 5 nmol/L, T3: 0.72 +/- 0.08 nmol/L) but correlated positively with circulating levels of IGF-I [86 +/- 6 micrograms/L, determination coefficient (R2) = 0.25] and ALS (7.2 +/- 0.6 mg/L, R2 = 0.32). Infusion of placebo or TRH had no effect on leptin. In contrast, GH-secretagogues elevated leptin levels within 12 h. Infusion of GHRP-2 alone induced a maximal leptin increase of +87% after 24 h, whereas GHRH + GHRP-2 elevated leptin by up to +157% after 24 h. The increase in leptin within 12 h was related (R2 = 0.58) to the substantial rise in insulin. After 45 h, and having reached a plateau, leptin was related to the increased IGF-I (R2 = 0.37). In conclusion, circulating leptin levels during protracted critical illness were linked to the activity state of the GH/IGF-I axis. Stimulating the GH/IGF-I axis with GH-secretagogues increased leptin levels within 12 h. Because leptin may stimulate oxidation of fatty acids, and because GH, IGF-I, and insulin have a protein-sparing effect, GH-secretagogue administration may be expected to result in increased utilization of fat as preferential substrate and to restore protein content in vital tissues and, consequently, has potential as a strategy to reverse the paradoxical metabolic condition of protracted critical illness.

PROCESS FOR RECOVERY OF CONSTITUENTS OF ORES

DOEpatents

McCullough, R.F.

1959-05-01

A process for U recovery from leached zone material is described. Calcination with alkali metal carbonate at 600 to 2000 deg F followed by digestion with H/sub 2/SO/sub 4/ and filtration forms the basis of the process. (T.R.H.)

CALUTRON ION SOURCE

DOEpatents

Oppenheimer, F.F.

1959-06-01

A shielding arrangement for eliminating oscillating electrons in the ion source region of calutrons is offered. Metal plates are attached to the ion generator so as to intercept the magnetic field between ion generator and accelerating electrode. The oscillating electrons are discharged on the plates. (T.R.H.)

Exploring the Genomic Traits of Non-toxigenic Vibrio parahaemolyticus Strains Isolated in Southern Chile

PubMed Central

Castillo, Daniel; Pérez-Reytor, Diliana; Plaza, Nicolás; Ramírez-Araya, Sebastián; Blondel, Carlos J.; Corsini, Gino; Bastías, Roberto; Loyola, David E.; Jaña, Víctor; Pavez, Leonardo; García, Katherine

2018-01-01

Vibrio parahaemolyticus is the leading cause of seafood-borne gastroenteritis worldwide. As reported in other countries, after the rise and fall of the pandemic strain in Chile, other post-pandemic strains have been associated with clinical cases, including strains lacking the major toxins TDH and TRH. Since the presence or absence of tdh and trh genes has been used for diagnostic purposes and as a proxy of the virulence of V. parahaemolyticus isolates, the understanding of virulence in V. parahaemolyticus strains lacking toxins is essential to detect these strains present in water and marine products to avoid possible food-borne infection. In this study, we characterized the genome of four environmental and two clinical non-toxigenic strains (tdh-, trh-, and T3SS2-). Using whole-genome sequencing, phylogenetic, and comparative genome analysis, we identified the core and pan-genome of V. parahaemolyticus of strains of southern Chile. The phylogenetic tree based on the core genome showed low genetic diversity but the analysis of the pan-genome revealed that all strains harbored genomic islands carrying diverse virulence and fitness factors or prophage-like elements that encode toxins like Zot and RTX. Interestingly, the three strains carrying Zot-like toxin have a different sequence, although the alignment showed some conserved areas with the zot sequence found in V. cholerae. In addition, we identified an unexpected diversity in the genetic architecture of the T3SS1 gene cluster and the presence of the T3SS2 gene cluster in a non-pandemic environmental strain. Our study sheds light on the diversity of V. parahaemolyticus strains from the southern Pacific which increases our current knowledge regarding the global diversity of this organism. PMID:29472910

Relationships between Environmental Factors and Pathogenic Vibrios in the Northern Gulf of Mexico ▿ †

PubMed Central

Johnson, C. N.; Flowers, A. R.; Noriea, N. F.; Zimmerman, A. M.; Bowers, J. C.; DePaola, A.; Grimes, D. J.

2010-01-01

Although autochthonous vibrio densities are known to be influenced by water temperature and salinity, little is understood about other environmental factors associated with their abundance and distribution. Densities of culturable Vibrio vulnificus containing vvh (V. vulnificus hemolysin gene) and V. parahaemolyticus containing tlh (thermolabile hemolysin gene, ubiquitous in V. parahaemolyticus), tdh (thermostable direct hemolysin gene, V. parahaemolyticus pathogenicity factor), and trh (tdh-related hemolysin gene, V. parahaemolyticus pathogenicity factor) were measured in coastal waters of Mississippi and Alabama. Over a 19-month sampling period, vibrio densities in water, oysters, and sediment varied significantly with sea surface temperature (SST). On average, tdh-to-tlh ratios were significantly higher than trh-to-tlh ratios in water and oysters but not in sediment. Although tlh densities were lower than vvh densities in water and in oysters, the opposite was true in sediment. Regression analysis indicated that SST had a significant association with vvh and tlh densities in water and oysters, while salinity was significantly related to vibrio densities in the water column. Chlorophyll a levels in the water were correlated significantly with vvh in sediment and oysters and with pathogenic V. parahaemolyticus (tdh and trh) in the water column. Furthermore, turbidity was a significant predictor of V. parahaemolyticus density in all sample types (water, oyster, and sediment), and its role in predicting the risk of V. parahaemolyticus illness may be more important than previously realized. This study identified (i) culturable vibrios in winter sediment samples, (ii) niche-based differences in the abundance of vibrios, and (iii) predictive signatures resulting from correlations between environmental parameters and vibrio densities. PMID:20817802

Prevalence, Molecular Characterization, and Antibiotic Susceptibility of Vibrio parahaemolyticus from Ready-to-Eat Foods in China

PubMed Central

Xie, Tengfei; Xu, Xiaoke; Wu, Qingping; Zhang, Jumei; Cheng, Jianheng

2016-01-01

Vibrio parahaemolyticus is the leading cause of foodborne outbreaks, particularly outbreaks associated with consumption of fish and shellfish, and represents a major threat to human health worldwide. This bacterium harbors two main virulence factors: the thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH). Additionally, various serotypes have been identified. The extensive use of antibiotics is a contributing factor to the increasing incidence of antimicrobial-resistant V. parahaemolyticus. In the current study, we aimed to determine the incidence and features of V. parahaemolyticus in ready-to-eat (RTE) foods in China. We found 39 V. parahaemolyticus strains on Chinese RTE foods through investigation of 511 RTE foods samples from 24 cities in China. All isolates were analyzed for the presence of tdh and trh gene by PCR, serotyping was performed using multiplex PCR, antibiotic susceptibility analysis was carried out using the disk diffusion method, and molecular typing was performed using enterobacterial repetitive intergenic consensus sequence PCR (ERIC-PCR) typing and multilocus sequence typing (MLST). The results showed that none of the isolates were positive for tdh and trh. Most of the isolates (33.3%) were serotype O2. Antimicrobial susceptibility results indicated that most strains were resistant to streptomycin (89.7%), cefazolin (51.3%), and ampicillin (51.3%). The isolates were grouped into five clusters by ERIC-PCR and four clusters by MLST. We updated 10 novel loci and 33 sequence types (STs) in the MLST database. Thus, our findings demonstrated the presence of V. parahaemolyticus in Chinese RTE foods, provided insights into the dissemination of antibiotic-resistant strains, and improved our knowledge of methods of microbiological risk assessment in RTE foods. PMID:27148231

Arrestin binds to different phosphorylated regions of the thyrotropin-releasing hormone receptor with distinct functional consequences.

PubMed

Jones, Brian W; Hinkle, Patricia M

2008-07-01

Arrestin binding to agonist-occupied phosphorylated G protein-coupled receptors typically increases the affinity of agonist binding, increases resistance of receptor-bound agonist to removal with high acid/salt buffer, and leads to receptor desensitization and internalization. We tested whether thyrotropin-releasing hormone (TRH) receptors lacking phosphosites in the C-terminal tail could form stable and functional complexes with arrestin. Fibroblasts from mice lacking arrestins 2 and 3 were used to distinguish between arrestin-dependent and -independent effects. Arrestin did not promote internalization or desensitization of a receptor that had key Ser/Thr phosphosites mutated to Ala (4Ala receptor). Nevertheless, arrestin greatly increased acid/salt resistance and the affinity of 4Ala receptor for TRH. Truncation of 4Ala receptor just distal to the key phosphosites (4AlaStop receptor) abolished arrestin-dependent acid/salt resistance but not the effect of arrestin on agonist affinity. Arrestin formed stable complexes with activated wild-type and 4Ala receptors but not with 4AlaStop receptor, as measured by translocation of arrestin-green fluorescent protein to the plasma membrane or chemical cross-linking. An arrestin mutant that does not interact with clathrin and AP2 did not internalize receptor but still promoted high affinity TRH binding, acid/salt resistance, and desensitization. A sterically restricted arrestin mutant did not cause receptor internalization or desensitization but did promote acid/salt resistance and high agonist affinity. The results demonstrate that arrestin binds to proximal or distal phosphosites in the receptor tail. Arrestin binding at either site causes increased agonist affinity and acid/salt resistance, but only the proximal phosphosites evoke the necessary conformational changes in arrestin for receptor desensitization and internalization.

Mechanistic insights into PEPT1-mediated transport of a novel antiepileptic, NP-647.

PubMed

Khomane, Kailas S; Nandekar, Prajwal P; Wahlang, Banrida; Bagul, Pravin; Shaikh, Naeem; Pawar, Yogesh B; Meena, Chhuttan Lal; Sangamwar, Abhay T; Jain, Rahul; Tikoo, K; Bansal, Arvind K

2012-09-04

The present study, in general, is aimed to uncover the properties of the transport mechanism or mechanisms responsible for the uptake of NP-647 into Caco-2 cells and, in particular, to understand whether it is a substrate for the intestinal oligopeptide transporter, PEPT1 (SLC15A1). NP-647 showed a carrier-mediated, saturable transport with Michaelis-Menten parameters K(m) = 1.2 mM and V(max) = 2.2 μM/min. The effect of pH, sodium ion (Na(+)), glycylsarcosine and amoxicillin (substrates of PEPT1), and sodium azide (Na(+)/K(+)-ATPase inhibitor) on the flux rate of NP-647 was determined. Molecular docking and molecular dynamics simulation studies were carried out to investigate molecular interactions of NP-647 with transporter using homology model of human PEPT1. The permeability coefficient (P(appCaco-2)) of NP-647 (32.5 × 10(-6) cm/s) was found to be four times higher than that of TRH. Results indicate that NP-647 is transported into Caco-2 cells by means of a carrier-mediated, proton-dependent mechanism that is inhibited by Gly-Sar and amoxicillin. In turn, NP-647 also inhibits the uptake of Gly-Sar into Caco-2 cells and, together, this evidence suggests that PEPT1 is involved in the process. Docking and molecular dynamics simulation studies indicate high affinity of NP-647 toward PEPT1 binding site as compared to TRH. High permeability of NP-647 over TRH is attributed to its increased hydrophobicity which increases its affinity toward PEPT1 by interacting with the hydrophobic pocket of the transporter through hydrophobic forces.

[Psychosomatic aspects of hyperthyroidism with special reference to Basedow's disease. An overview].

PubMed

Rodewig, K

1993-08-01

The following paper deals with the current research in hyperthyroidism, with special accent to Graves' disease. Besides severe psychological trauma a breakdown of neurotic defense mechanism on the ground of a special personality structure was thought to be the trigger of the disease. The metabolic changes became the main point of interest. The influence of thyrostatic, surgical and radioactive therapies on psychological symptoms, was investigated. Thereby, the previously anticipated emotional factors became less significant in the aetiology of the disease. A recent study (Paschke 1990) suggests that patient with hyperthyroidism have, even in an euthyrotic state, an increased vulnerability to anxiety provoking situations. At this point it is not clear, due to the retrospective nature of the study, whether the vulnerability exists prior to the unset of the disease or is a result of the metabolic disorder. Both thyroxin and TRH are being successfully used in the treatment of major depression. TRH acts as a neurotransmitter in the autonomic nervous system and can be demonstrated in the peripheral lymphocytes. However, the exact mechanisms of action of thyroxin and TRH are still unknown. Graves' disease is an autoimmune disease, that can be caused by specific HLA antigens. Thereby, a changed subpopulation of lymphocytes can be demonstrated, as well as there disturbed functions. A correlation between high scores for anxiety and depression on one hand and the occurrence of an abnormal T4/T8 ratio on the other hand, have been reported in a small number of cases (Paschke 1990). The psychological symptoms in hyperthyroidism are similar to the symptomatology of neurotic anxiety and the anxious depressive syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug adherence in treatment resistant and in controlled hypertension-Results from the Swedish Primary Care Cardiovascular Database (SPCCD).

PubMed

Holmqvist, Lina; Boström, Kristina Bengtsson; Kahan, Thomas; Schiöler, Linus; Qvarnström, Miriam; Wettermark, Björn; Hjerpe, Per; Hasselström, Jan; Manhem, Karin

2018-03-01

To assess drug adherence in patients treated with ≥3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. Patients with hypertension, without cardiovascular comorbidity, aged >30 years treated with ≥3 antihypertensive drug classes were followed for 2 years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level ≥ 80% were included. We found 5846 patients treated ≥3 antihypertensive drug classes, 3508 with TRH (blood pressure ≥ 140/90), and 2338 with controlled blood pressure (<140/90 mm Hg). TRH patients were older (69.1 vs 65.8 years, P < .0001) but had less diabetes (28.5 vs 31.7%, P < .009) compared with patients with controlled blood pressure. The proportion of patients with PDC ≥ 80% declined with 11% during the first year in both groups. Having diabetes was associated with staying adherent at 1 year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82). Patients with multiple antihypertensive drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment. Copyright © 2018 John Wiley & Sons, Ltd.

Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells

PubMed Central

Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

2016-01-01

Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction. PMID:27144291

Preservation of Food by Means of Radiation; PRESERVACAO DE ALIMENTOS POR MEIO DA RADIACAO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aghina, L.O.B.; Chimbleris, B.

The destruction of food by different organisms is described and methods of preventing this destruction are outlined and compared with the radiation method. A survey is made of the various sources available for food processing. (T.R.H.)

Application of polymerase chain reaction for detection of Vibrio parahaemolyticus associated with tropical seafoods and coastal environment.

PubMed

Dileep, V; Kumar, H S; Kumar, Y; Nishibuchi, M; Karunasagar, Indrani; Karunasagar, Iddya

2003-01-01

To study the incidence of Vibrio parahaemolyticus in seafoods, water and sediment by molecular techniques vs conventional microbiological methods. Of 86 samples analysed, 28 recorded positive for V. parahaemolyticus by conventional microbiological method, while 53 were positive by the toxR-targeted PCR, performed directly on enrichment broth lysates. While one sample of molluscan shellfish was positive for tdh gene, trh gene was detected in three enrichment broths of molluscan shellfish. Direct application of PCR to enrichment broths will be useful for the rapid and sensitive detection of potentially pathogenic strains of V. parahemolyticus in seafoods. Vibrio parahaemolyticus is an important human pathogen responsible for food-borne gastroenteritis world-wide. As, both pathogenic and non-pathogenic strains of V. parahaemolyticus exist in the seafood, application of PCR specific for the virulence genes (tdh & trh) will help in detection of pathogenic strains of V. parahaemolyticus and consequently reduce the risk of food-borne illness.

Virulence of thermolable haemolysi tlh, gastroenteritis related pathogenicity tdh and trh of the pathogens Vibrio Parahemolyticus in Viable but Non-Culturable (VBNC) state.

PubMed

Zhong, Huamin; Zhong, Yukui; Deng, Qiulian; Zhou, Zhenwen; Guan, Xiaoshan; Yan, Muxia; Hu, Tingting; Luo, Mingyong

2017-10-01

In the Viable but Non-Culturable (VBNC) state, microorganisms may survive under severe external environment. In this study, the specificity and sensitivity of PMA-LAMP assay on the detection of Vibrio Parahemolyticus (V. parahemolyticus) has been developed and evaluated, with further application on a number of food-borne V. parahemolyticus strains. Six primers were designed for recognizing 8 distinct targeting on tlh, tdh and trh gene. Through specific penetration through the damaged cell membrane of dead cells and intercalating into DNA, PMA could prevent DNA amplification of dead bacteria from LAMP, which enabled the differentiation of bacteria between VBNC state and dead state. The established PMA-LAMP showed significant advantage in rapidity, sensitivity and specificity, compared with regular PCR assay. The applicability had also been verified, demonstrating the PMA-LAMP was capable of detection on V. parahaemolyticus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

PubMed

Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

2001-12-01

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Magnetic properties of Co/Rh (001) multilayers studied by x-ray magnetic-circular dichroism

NASA Astrophysics Data System (ADS)

Tomaz, M. A.; Mayo, E.; Lederman, D.; Hallin, E.; Sham, T. K.; O'brien, W. L.; Harp, G. R.

1998-11-01

The layer-averaged magnetic moments of Co and Rh have been measured in sputter deposited Co/Rh (001) multilayer thin films using the x-ray magnetic circular dichroism. The Rh moments were measured at both the L and M absorption edges, where we find that the Rh moment decreases as a function of increasing Rh layer thickness (tRh). The decline of the layer-averaged Rh moment is well described in terms of a simple dilution, implying that the Rh moment is confined to the interfacial region. We find that the Co moment remains largely unaffected, maintaining a bulklike value of 1.7μB in the region preceding the first antiferromagnetic coupling peak where tRh ranges from 0 to 4 Å. We also find, via application of the dichroism sum rules, that the ratio / for Co increases ~10% for this same region. Finally, we contrast the magnetic behavior of the Co/Rh (001) and Fe/Rh (001) multilayer systems.

ION PRODUCING MECHANISM

DOEpatents

Oppenheimer, F.F.

1959-06-01

A calutron ion source is described which masks the ends of the arc to provide a more stable beam from the middle portion. The masking is effected by milling the arc slit in a single sheet of material which is secured to the open face of the arc block. (T.R.H.)

Influence of hyperthyroidism on growth hormone secretion.

PubMed

Valcavi, R; Dieguez, C; Zini, M; Muruais, C; Casanueva, F; Portioli, I

1993-05-01

Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue. Study 1: GHRH (1 microgram/kg b.w.) was injected i.v. in 38 hyperthyroid patients and in 30 normal subjects; in 11 of the patients the GHRH test was repeated following methimazole-induced remission of hyperthyroidism. Study 2: hGH (2 U i.v.) or saline were administered 3 hours prior to GHRH; six hyperthyroid patients and six normal subjects were studied. Study 3: ten normal subjects and ten hyperthyroid patients were given 75 g oral glucose or water 30 minutes before GHRH. Study 4: 11 normal subjects and eight hyperthyroid patients were studied. TRH or vehicle were dissolved in 250 ml of saline solution and infused at a rate of 400 micrograms/h for 150 minutes. Thirty minutes after the beginning of the infusions, L-arginine (30 g infused over 45 min i.v.) was administered. Hyperthyroid patients were compared to normal subjects. Growth hormone was measured by RIA at 15-minute intervals. GH responses to GHRH were subnormal in hyperthyroid patients. Following antithyroid drug treatment with methimazole, GH responses to GHRH increased in these patients in comparison to pretreatment values. Serum IGF-I levels, which were elevated before treatment, decreased after methimazole administration. Exogenous GH administration induced a clear decrease of GH responses to GHRH in both control and hyperthyroid subjects. On the other hand, oral glucose load decreased the GH responses to GHRH in normal but not in hyperthyroid subjects. TRH administration did not modify the GH responses to arginine in either normal subjects or hyperthyroid patients. Hyperthyroidism is associated with increased serum IGF-I levels and marked alterations in the neuroregulation of GH secretion. These changes involve decreased GH responsiveness to GHRH at the pituitary level and, at the hypothalamic level, a lack of suppressive effect of an oral glucose load. The normal inhibitory effect of exogenous GH administration but not of an oral glucose load in hyperthyroid patients suggests that these two feedback signals act through different mechanisms. The lack of effect of a TRH infusion on GH responses to L-arginine in normal and hyperthyroid patients makes an inhibitory role for TRH in GH secretion unlikely, at least in Caucasian subjects.

Characterization of substance P release from the intermediate area of rat thoracic spinal cord.

PubMed

Yang, L; Thomas, N D; Helke, C J

1996-08-01

Substance P (SP) nerve terminals innervate the intermediolateral cell column (IML) of the thoracic spinal cord, where SP coexists with serotonin (5-HT), neurokinin A (NKA) and thyrotropin-releasing hormone (TRH). Neither the depolarization-induced release of SP nor the presence of other neurochemicals in the regulation of SP release has been directly studied in this system. In the present study, basal and K(+)-stimulated release of SP from the microdissected intermediate area (including the IML, intercalated nucleus and central autonomic nucleus) of the rat thoracic spinal cord, and the regulation of SP release by presynaptic autoreceptors and by coexisting neurochemicals (5-HT, NKA and TRH) were studied using an in vitro superfusion system. Potassium evoked a concentration- and extracellular Ca(2+)-dependent release of SP. In rats pretreated with the serotoninergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), both SP content and the absolute amount of SP released were decreased. However, the fraction of the remaining tissue content of SP released by K+ depolarization was not changed subsequent to 5,7-DHT treatment. Moreover, 5-HT, 5-HT1B agonists (CGS-12066B and RU 24969) and a 5-HT3 agonist (2-methyl-5-HT) did not alter the K(+)-evoked release of SP. These data demonstrate that SP is released from the intermediate area of the rat thoracic spinal cord and some of the SP released comes from serotoninergic nerve terminals. Although 5-HT coexists with SP in the IML, neither endogenous 5-HT nor 5-HT receptor ligands appear to regulate the release of SP. Other colocalized neuropeptides (NKA and TRH) are not involved in the regulation of SP release because neither NKA, a NK2 agonist (GR 64349) nor a TRH analog (MK-771) changed the K(+)-evoked release of SP. A neurokinin-1 (NK1) antagonist (GR 82334) dose-dependently (10(-9)-10(-7) M) increased the K(+)-stimulated release of SP. These data suggest the presence of presynaptic inhibitory NK1 autoreceptors. Whereas, NK1 agonists, [GR 73632 (10(-9)-10(-6) M) and [Sar9, Met (O2)11]SP (10(-8)-10(-6) M)], increased the basal and K(+)-stimulated release of SP, the excitatory effects of GR 73632 were not blocked by the NK1 antagonist. Moreover, GR 73632 increased the efflus of SP to a greater extent in the absence of peptidase inhibitors. Thus, the effect of NK1 agonists on the release of SP may be related to an inhibition of peptide degradation rather than activation of NK1 autoreceptors.

Symposium on the peaceful uses of atomic energy in Australia, 1958, held in Sydney, in June 1958

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Thirty-nine papers presented at the conference are collected here. The papers are divided into five sections: Materials, Power Engineering, Power Auxiliaries and Research Reactors, Basic Sciences, and Associated Techniques. Separate abstracts of each section have been prepared. (T.R.H.)

Index to Benet Weapons Laboratory (LCWSL) Technical Reports - 1979

DTIC Science & Technology

1980-09-01

Breech Machanisms Breech Seals Breeches, Cannon Cadmium Sulfide Calibration Cannon Auto Loader Cannon Tube Chemical Vapor Deposition REPORT NUMBER...PAGE(Trh«n Data SntaracQ (Con1t from block #20) Three basic specimen geometries were studied: 1. A symetric specimen; 2. A specimen with +5% wall

NEUTRONIC REACTOR FUEL PUMP

DOEpatents

Cobb, W.G.

1959-06-01

A reactor fuel pump is described which offers long life, low susceptibility to radiation damage, and gaseous fission product removal. An inert-gas lubricated bearing supports a journal on one end of the drive shsft. The other end has an impeller and expansion chamber which effect pumping and gas- liquid separation. (T.R.H.)

Prevalence and molecular typing of Vibrio parahaemolyticus isolated from seafood in Shanghai using multilocus sequence typing (MLST)

USDA-ARS?s Scientific Manuscript database

Vibrio parahaemolyticus is a gram-negative bacterium that inhabits coastal and marine environments. Thermostable direct hemolysin (tdh), tdh-related hemolysin (trh) and the type III secretion system are considered the potential virulent factors of pathogenic V. parahaemolyticus. The frequency of str...

Critical Amounts of Uranium Compounds

DOE R&D Accomplishments Database

Konopinski, E.; Metropolis, N.; Teller, E.; Woods, L.

1943-03-19

The method of calculation of critical masses of oxides and fluorides of U is given. The geometry assumed is a sphere and the calculations hold only in the absence of hydrogenous materials. Calculations are carried out which are applicable to materials containing form 20 to 100% U{sup 235}. (T.R.H.)

PORTABLE SOURCE OF RADIOACTIVITY

DOEpatents

Goertz, R.C.; Ferguson, K.R.; Rylander, E.W.; Safranski, L.M.

1959-06-16

A portable source for radiogiaphy or radiotherapy is described. It consists of a Tl/sup 170/ or Co/sup 60/ source mounted in a rotatable tungsten alloy plug. The plug rotates within a brass body to positions of safety or exposure. Provision is made for reloading and carrying the device safely. (T.R.H.)

CALUTRON

DOEpatents

Brobeck, W.M.; Lofgren, E.J.; Thornton, R.L.

1959-06-01

A calutron improved in liner and capacity is offered. The liner is a hollow insulated structure at high negative potential with respect to the vessel. The liner has delimiting vanes to prevent ions from one beam scattering into the receiver from another beam. The double beam-double receiver feature is thus made possible, increasing the capacity of the calutron. (T.R.H.)

CALUTRON PLANT ARRANGEMENT

DOEpatents

Waite, L.O.

1959-06-01

A description is given of an arrangement for calutrons in which the tanks and magnets are placed alternately in a race track'' figure. Pump connections are through the floor to the pumps below where roughing and finishing headers are provided. The arrangement provides more efficient and exonomical operaton, economy of construction, and saving of space. (T.R.H.)

Functional central hypothyroidism in the elderly.

PubMed

Sell, Maren A; Schott, Matthias; Tharandt, Lutz; Cissewski, Klaus; Scherbaum, Werner A; Willenberg, Holger S

2008-06-01

Previous studies have shown that blood concentrations of free thyroxin and basal thyroid-stimulating hormone (TSH) decrease during adult life. Suggested mechanisms include reduced thyroid activity resulting from decreased serum TSH concentrations, impairment of peripheral 5'-deiodinase, and an increase in reverse 3,5,3'-triiodothyronine due to non-thyroidal illness. However, testing of pituitary reserves leads to contradictory results and has infrequently been evaluated in studies. We investigated whether the response of TSH to thyrotropin-releasing hormone (TRH) is preserved during aging. This was tested in a cohort of 387 subjects aged 13 to 100 years in whom thyroid disease was excluded by normal thyroid ultrasound, normal values for free thyroxin, free triiodothyronin, TSH, and negative thyroid peroxidase antibodies. Serum concentrations of free thyroxin remained almost unchanged, whereas free triiodothyronin and TSH levels were lower in older subjects. In addition, the TSH response to TRH was blunted in older subjects, especially in male individuals. There is evidence that the decreased thyroid hormone levels observed in aging are due to lower TSH concentrations, and that lower TSH concentrations may be linked to an impaired pituitary activity.

Glassy vortex behavior in superconducting SrPd2Ge2 single crystals

NASA Astrophysics Data System (ADS)

Sung, N. H.; Jo, Y. J.; Cho, B. K.

2012-07-01

In this study we report the vortex-glass behavior of superconducting ternary germanide SrPd2Ge2 single crystals with a ThCr2Si2-type structure. We observed flux trapping and its nonexponential decay with time after the magnetic field was turned off at T = 2 K. In addition, we found that the diamagnetism in the zero field cooling (ZFC) mode below Tc was irreversible, depending on the temperature and field history, whereas the diamagnetism in the field-cooled warming (FCW) mode was reversible if the applied magnetic field was parallel to the c-axis. An irreversibility line Tr(H) was determined by the ZFC and FCW measurements at various magnetic fields, and the temperature dependence of Tr(H) was found to agree with the de Almeida-Thouless relation, H = H0[1-Tr(H)/Tc(0)]γ, where γ = 3/2. Including these vortex-glass behaviors, we discuss the critical current density, Jc(T), determined from isothermal magnetization measurements at various temperatures, and the pinning potential, determined from the slope of an Arrhenius plot, lnR(T,B) versus 1/T.

Flatfish metamorphosis: a hypothalamic independent process?

PubMed

Campinho, Marco A; Silva, Nadia; Roman-Padilla, Javier; Ponce, Marian; Manchado, Manuel; Power, Deborah M

2015-03-15

Anuran and flatfish metamorphosis are tightly regulated by thyroid hormones that are the necessary and sufficient factors that drive this developmental event. In the present study whole mount in situ hybridization (WISH) and quantitative PCR in sole are used to explore the central regulation of flatfish metamorphosis. Central regulation of the thyroid in vertebrates is mediated by the hypothalamus-pituitary-thyroid (HPT) axis. Teleosts diverge from other vertebrates as hypothalamic regulation in the HPT axis is proposed to be through hypothalamic inhibition although the regulatory factor remains enigmatic. The dynamics of the HPT axis during sole metamorphosis revealed integration between the activity of the thyrotrophes in the pituitary and the thyroid follicles. No evidence was found supporting a role for thyroid releasing hormone (trh) or corticotrophin releasing hormone (crh) in hypothalamic control of TH production during sole metamorphosis. Intriguingly the results of the present study suggest that neither hypothalamic trh nor crh expression changes during sole metamorphosis and raises questions about the role of these factors and the hypothalamus in regulation of thyrotrophs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Characterization of Vibrio parahaemolyticus isolated from oysters in Korea: Resistance to various antibiotics and prevalence of virulence genes.

PubMed

Kang, Chang-Ho; Shin, YuJin; Jang, SeokCheol; Yu, HongSik; Kim, SuKyung; An, Sera; Park, Kunbawui; So, Jae-Seong

2017-05-15

Vibrio parahaemolyticus, found frequently in oysters, is the most prevalent gastroenteritis-causing pathogen in Korea and in several other Asian countries. This study monitored changes in the environmental parameters and occurrence of V. parahaemolyticus in oyster aquaculture sites. Of the 44 presumed V. parahaemolyticus isolates obtained, when tested against 16 antibiotics, 90.9, 86.4, and 75.0% of the 44 isolates exhibited resistance to vancomycin, ampicillin, and streptomycin, respectively. PCR analysis for the presence of the toxR gene confirmed 31 of the 44 isolates as being positive V. parahaemolyticus strains. The toxR positive isolates were tested for the presence of thermostable direct hemolysin (tdh) and tdh-related hemolysin (trh) virulence genes. Only 9.1% toxR positive isolate exhibit the trh gene and none of the isolates were tested positive for tdh. The occurrence of multi drug resistance strains in the environment could be an indication of excessive usage of antibiotics in agriculture and aquaculture fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

On ultraviolet freeze-in dark matter during reheating

NASA Astrophysics Data System (ADS)

Chen, Shao-Long; Kang, Zhaofeng

2018-05-01

The absence of any confirmative signals from extensive DM searching motivates us to go beyond the conventional WIMPs scenario. The feebly interacting massive particles (FIMPs) paradigm provides a good alternative which, despite of its feebly interaction with the thermal particles, still could correctly produce relic abundance without conventional DM signals. The Infrared-FIMP based on the renormalizable operators is usually suffering the very tiny coupling drawback, which can be overcome in the UltraViolet-FIMP scenario based on high dimensional effective operators. However, it is sensitive to the history of the very early Universe. The previous works terminates this sensitivity at the reheating temperature TRH. We, motivated by its UV-sensitivity, investigate the effects from the even earlier Universe, reheating era. We find that in the usual case with TRHgg mDM, the production rate during reheating is very small as long as the effective operators dimension d <= 8. Besides, we consider the contribution from the mediator, which may be produced during reheating. Moreover, we study the situation when TRH is even lower than mDM and DM can be directly produced during reheating if its mass does not exceed TMAX.

Functional and morphological changes in the adenohypophysis of dogs with induced primary hypothyroidism: loss of TSH hypersecretion, hypersomatotropism, hypoprolactinemia, and pituitary enlargement with transdifferentiation.

PubMed

Diaz-Espiñeira, M M; Mol, J A; van den Ingh, T S G A M; van der Vlugt-Meijer, R H; Rijnberk, A; Kooistra, H S

2008-07-01

From case studies in humans it is known that primary hypothyroidism (PH) may be associated with morphological and functional changes of the pituitary. There is no insight into the time scale of these changes. In this study, seven beagle dogs were followed up for 3 years after the induction of primary hypothyroidism. Three of these dogs were followed up for another 1.5 years while receiving l-thyroxine. Adenohypophyseal function was investigated at 2-month intervals with the combined intravenous injection of CRH, GHRH, GnRH, and TRH, and measurement of the plasma concentrations of ACTH, GH, LH, PRL, and TSH. In addition, after 2 years of hypothyroidism a single TRH-stimulation test and a somatostatin test were performed, with measurements of the same pituitary hormones. Every 6 months the pituitary gland was visualized by computed tomography (CT). Induction of PH led to high plasma TSH concentrations for a few months, where after concentrations gradually declined to values no longer significantly different from pre-PH values. A blunted response to stimulation of TSH release preceded this decline. Basal plasma GH concentrations increased during PH and there was a paradoxical hyperresponsiveness to TRH stimulation. Basal GH concentrations remained elevated and returned only to low values during l-thyroxine treatment. Basal PRL concentrations decreased significantly during PH and normalized after several months of l-thyroxine treatment. The pituitary gland became enlarged in all dogs. Histomorphology and immunohistochemical studies in 4 dogs, after 3 years of PH, revealed thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and decreased numbers of mammotrophs. Several cells stained for both GH and TSH. In conclusion, with time PH led to a loss of the TSH response to low T4 concentrations, hypersecretion of GH, and hyposecretion of PRL. The enlarged pituitaries were characterized by thyrotroph hyperplasia, large vacuolated thyroid deficiency cells, and double-staining cells, which are indicative of transdifferentiation.

Variations of rat thyroid activity during exposure to high environmental temperature (34 degrees C). Relation between hypothalamic pituitary and thyroid hormone levels.

PubMed

Rousset, B; Cure, M

1975-01-01

Changes in thyroid activity and variations in the hypthalamo-pituitary-thyroid hormone levels were examined in rats exposed to heat (34 degrees C)for3 weeks. Thyroid activity evaluated histologically (epithelium/colloid ratio, nuclear size) by radioiodine exploration (24 hrs 125 I uptake, ratio of mono- to di-125 iodotyrosines - MIT/DIT, ratio of tri- to tetra-125 iodothyronines-T3/T4, and plasma 125I-T4 and assay of plasma T4, evolves in a triphasic manner. 1.a depression phase between day 0 and day 2.5. 2. a rebound of thyroid activity between day 2.5 and day 9.3 a stabilization of thyroid parameters from day 9 to day 24. These results indicate adaptation of thyroid function to heat after 3 weeks. In phase i, plasma TSH )MeKenzie bioassay) fell to undectable levels concurrent with a 50% decrease in hypothalamic TRH (in vitro assay). Plasma TSH peaked on day 4.5, fell on day 9.5 and returned progressively to initial levels. Hypothalamic TRH returned to initial levels after 6.5 days. The rapid and simultaneous decrease in hypothalamic TRH, plasma TSH, plasma T4 and thyroid activity by the 36th hour of heat exposure (34 degrees C) suggests initiation at the hypothalamic level. In the secound phase, the rebound in thyroid activity is presumably due to the peak in circulating TSH in ralation to the marked decrease in plasma T4. The oscillations of phase 2 and the stabilization of all the thyroid parameters in phase 3 may be the reflection of an apparent discrepancy remains between a low plasma T4 and a normal or subnormal plasma TSH. A modification in the "set point" for the control of TSH secretion is discussed.

Development of a colony hybridization method for the enumeration of total and potentially enteropathogenic Vibrio parahaemolyticus in shellfish.

PubMed

Suffredini, Elisabetta; Cozzi, Loredana; Ciccaglioni, Gianni; Croci, Luciana

2014-09-01

Vibrio parahaemolyticus is a marine microorganism, recognized as cause of gastroenteritis outbreaks associated with seafood consumption. In this study the development and the in-house validation of a colony hybridization method for the enumeration of total and potentially pathogenic V. parahaemolyticus is reported. The method included a set of three controls (process, hybridization and detection control) for the full monitoring of the analytical procedure. Four digoxigenin-labeled probes were designed for pathogenic strains enumeration (tdh1, tdh2, trh1 and trh2 probes) and one for total V. parahaemolyticus count (toxR probe). Probes were tested on a panel of 70 reference strains and 356 environmental, food and clinical isolates, determining the inclusivity (tdh: 96.7%, trh: 97.8%, toxR: 99.4%) and the exclusivity (100% for all probes). Accuracy and linearity of the enumeration were evaluated on pure and mixed cultures: slopes of the regression lines ranged from 0.957 to 1.058 depending on the target gene and R(2) was greater than or equal to 0.989 for all reactions. Evaluation was also carried on using four experimentally contaminated seafood matrices (shellfish, finfish, crustaceans and cephalopods) and the slopes of the curves varied from 0.895 (finfish) to 0.987 (cephalopods) for the counts of potentially pathogenic V. parahaemolyticus (R(2)≥0.965) and from 0.965 to 1.073 for total V. parahaemolyticus enumeration (R(2)≥0.981). Validation was performed on 104 naturally contaminated shellfish samples, analyzed in parallel by colony hybridization, ISO/TS 21872-1 and MPN enumeration. Colony hybridization and ISO method showed a relative accuracy of 86.7%, and a statistically significant correlation was present between colony hybridization enumeration and MPN results (r=0.744, p<0.001). The proposed colony hybridization can be a suitable alternative method for the enumeration of total and potentially pathogenic V. parahaemolyticus in seafood. Copyright © 2014 Elsevier B.V. All rights reserved.

A Comprehensive Epidemiological Research for Clinical Vibrio parahaemolyticus in Shanghai

PubMed Central

Li, Huan; Tang, Rong; Lou, Yang; Cui, Zelin; Chen, Wenjing; Hong, Qing; Zhang, Zhaohuan; Malakar, Pradeep K.; Pan, Yingjie; Zhao, Yong

2017-01-01

Vibrio parahaemolyticus is one of the most important pathogen for seafood-borne gastroenteritis in Shanghai and the rest of the world. A total of 42 V. parahaemolyticus strains were isolated from 1900 fecal specimens collected from patients in Shanghai hospital presenting from January 2014 to December 2015. All isolates were evaluated for potential virulence factors [tdh, trh, and type three secretion system (T3SS) genes], typed using multilocus sequence typing (MLST) and screened for antimicrobial resistance phenotype and genotype. And for the first time, the relationship between virulence, genetic diversity and antimicrobial resistance of these isolates were identified. The results showed that 37 isolates carried the tdh gene (88.1%) and only seven isolates were positive for the trh gene. The T3SS1 and T3SS2 genes were detected in all strains and only trh-positive isolates are also containing the T3SS2β genes. MLST analysis of the 42 Shanghai isolates identified 20 sequence types (STs) with 16 novel STs and that these clinical V. parahaemolyticus strains showed high degrees of genetic diversity. All isolates expressed high levels of resistance against Ampicillin (100.0%), Streptomycin (100.0%), Cephazolin (92.9%), Kanamycin (92.8%) and Amikacin (90.5%), and eight out of 38 resistance genes (SHV, tet(B), strA, qnrA, gryA, qnrB, sulI, sulII) were detected in at least two isolates. This study confirms that antimicrobial resistance of clinical V. parahaemolyticus isolates is greater than those of environmental isolates. Furthermore, no clear correlation between antimicrobial resistance and virulence or genetic diversity was found in this study. These results add to epidemiological data of clinical V. parahaemolyticus isolates in Shanghai and highlight the need for additional mechanistic studies, especially antimicrobial resistance, to reduce the burden of disease caused by this pathogen in China. PMID:28642752

The −258 A/G (SNP rs12885300) polymorphism of the human type-2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH

PubMed Central

Peltsverger, Maya Y.; Butler, Peter W.; Alberobello, Anna Teresa; Smith, Sheila; Guevara, Yanina; Dubaz, Ornella M.; Luzon, Javier A.; Linderman, Joyce; Celi, Francesco S.

2012-01-01

Objective Type-2 deiodinase gene (DIO2) polymorphisms have been associated with changes in pituitary-thyroid axis homeostasis. The −258 A/G (SNP rs12885300) polymorphism has been associated with increased enzymatic activity, but data are conflicting. To characterize the effects of the −258 A/G polymorphism on intra-thyroidal T4 to T3 conversion and thyroid hormone secretion pattern we studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland. Design Retrospective analysis. Methods The thyroid hormone secretion in response to 500 mcg iv TRH injection was studied in 45 healthy volunteers. Results Twenty-six subjects (16 females, 10 males, 32.8±10.4 years) were homozygous for the ancestral (−258 A/A) allele, 19 (11 females, 8 males, 31.1±10.9 years) were carrier of the (−258 G/x) variant. While no differences in the peak TSH and T3 levels were observed, carriers of the −258G/x allele showed a blunted rise in free T4 (p<0.01). The −258G/x 92Thr/Thr haplotype, compared to the other groups, had lower TSH values at 60' (p<0.03). No differences were observed between genotypes in baseline thyroid hormone levels. Conclusions The −258G/x DIO2 polymorphism variant is associated with a decreased rate of acute TSH-stimulated free T4 secretion with a normal T3 release from the thyroid consistent with a shift in the reaction equilibrium toward the product. These data indicate that the −258G DIO2 polymorphism cause changes in the pattern of hormonal secretion. These findings are a proof-of-concept that common polymorphisms in the DIO2 can subtly affect the circulating levels of thyroid hormone and might modulate the thyroid hormone homeostasis. PMID:22307573

Effects of Dry Storage and Resubmersion of Oysters on Total Vibrio vulnificus and Total and Pathogenic (tdh+/trh+) Vibrio parahaemolyticus Levels.

PubMed

Kinsey, Thomas P; Lydon, Keri A; Bowers, John C; Jones, Jessica L

2015-08-01

Vibrio vulnificus (Vv) and Vibrio parahaemolyticus (Vp) are the two leading causes of bacterial illnesses associated with raw shellfish consumption. Levels of these pathogens in oysters can increase during routine antifouling aquaculture practices involving dry storage in ambient air conditions. After storage, common practice is to resubmerge these stored oysters to reduce elevated Vv and Vp levels, but evidence proving the effectiveness of this practice is lacking. This study examined the changes in Vv and in total and pathogenic (thermostable direct hemolysin gene and the tdh-related hemolysin gene, tdh+ and trh+) Vp levels in oysters after 5 or 24 h of dry storage (28 to 32°C), followed by resubmersion (27 to 32°C) for 14 days. For each trial, replicate oyster samples were collected at initial harvest, after dry storage, after 7 days, and after 14 days of resubmersion. Oysters not subjected to dry storage were collected and analyzed to determine natural undisturbed vibrio levels (background control). Vibrio levels were measured using a most-probable-number enrichment followed by real-time PCR. After storage, vibrio levels (excluding tdh+ and trh+ Vp during 5-h storage) increased significantly (P < 0.001) from initial levels. After 7 days of resubmersion, Vv and total Vp levels (excluding total Vp in oysters stored for 5 h) were not significantly different (P < 0.1) from levels in background oysters. Vv and total and pathogenic Vp levels were not significantly different (P > 0.1) from levels in background oysters after 14 days of resubmersion, regardless of dry storage time. These data demonstrate that oyster resubmersion after dry storage at elevated ambient temperatures allows vibrio levels to return to those of background control samples. These results can be used to help minimize the risk of Vv and Vp illnesses and to inform the oyster industry on the effectiveness of routine storing and resubmerging of aquaculture oysters.

METHOD FOR ELECTRO-NICKEL PLATING WOLFRAM CARBIDE

DOEpatents

Slatin, H.L.

1959-05-01

A WC body can be electroplated with Ni after anodic etching in Na/sub 4/ P/sub 2/O/sub 7/ solution (200 g/l) with a Pb cathode. A current density of 2 amp/in./sup 2/ for 10 min is sufficient. This allows Ni to be electrodeposited in an adherent coating which is weldable. (T.R.H.)

Absence of specific binding of several putative neuro-transmitters to human fibroblasts.

PubMed

Berrettini, W H; Nadi, N S; Gershon, E S

1983-01-01

Fibroblasts were examined for specific binding sites of ten putative neurotransmitters to determine whether this tissue could be used in receptor studies of neurologic and psychiatric disorders. Stereospecific saturable binding was not found for any of the ligands: arginine vasopressin, neurotensin, somatostatin, angiotensin II, thyrotropin-releasing hormone (TRH), alpha-bungarotoxin, LSD, dihydromorphine, muscimol and spiperone.

Rapid detection and E-test antimicrobial susceptibility testing of Vibrio parahaemolyticus isolated from seafood and environmental sources in Malaysia.

PubMed

Al-Othrubi, Saleh M; Hanafiah, Alfizah; Radu, Son; Neoh, Humin; Jamal, Rahaman

2011-04-01

To find out the prevalence and antimicrobial susceptibility of Vibrio parahaemolyticus in seafoods and environmental sources. The study was carried out at the Center of Excellence for Food Safety Research, University Putra Malaysia; Universiti Kebangsaan Malaysia; Medical Molecular Biology Institute; and University Kebansaan Malaysia Hospital, Malaysia between January 2006 and August 2008. One hundred and forty-four isolates from 400 samples of seafood (122 isolates) and seawater sources (22 isolates) were investigated for the presence of thermostable direct hemolysin (tdh+) and TDH-related hemolysin (trh+) genes using the standard methods. The E-test method was used to test the antimicrobial susceptibility. The study indicates low occurrence of tdh+ (0.69%) and trh+ isolates (8.3%). None of the isolates tested posses both virulence genes. High sensitivity was observed against tetracycline (98%). The mean minimum inhibitory concentration (MIC) of the isolates toward ampicillin increased from 4 ug/ml in 2004 to 24 ug/ml in 2007. The current study demonstrates a low occurrence of pathogenic Vibrio parahaemolyticus in the marine environment and seafood. Nonetheless, the potential risk of vibrio infection due to consumption of Vibrio parahaemolyticus contaminated seafood in Malaysia should not be neglected.

Hyperfunctioning thyroid nodules in children and adolescents.

PubMed

de Luca, F; Chaussain, J L; Job, J C

1986-01-01

Eight children and adolescents, seven female and one male, aged 7.1 to 15.0 years, referred over a 12-year period for a solitary mass in an otherwise normal thyroid gland, exhibited a hyperfunctioning nodule on thyroid scintiscan. Tracer uptake in the surrounding thyroid tissue was reduced or completely suppressed, but could be restored after TSH stimulation. Only one patient had mild clinical hyperthyroidism with normal T4 but increased T3 serum levels and blunted TSH responsiveness to TRH. A similar hormonal pattern suggestive of subclinical hyperthyroidism was found in three other subjects who were clinically euthyroid. One patient initially euthyroid progressed to subclinical hyperthyroidism two years later. In the whole group a significant negative relationship was found between serum T3 level and TRH-stimulated TSH peak (r = -0.829, p less than 0.02). All the patients underwent selective surgery after a 3-month to 2-year period of follow-up. Microscopic examination was consistent with adenoma in seven patients, while in one case a well-encapsulated papillary adenocarcinoma was found. Though hyperfunctioning nodules are seldom malignant, their surgical removal must be recommended when they become thyrotoxic, exceed 3 cm or show progressive enlargement.

RADIATION STERILIZATION OF COCOA POWDERS. Report No. 2 (Progress) for May 17, 1959-August 17, 1959

DOE Office of Scientific and Technical Information (OSTI.GOV)

McComb, C.

1961-10-31

A study was made of the effects of O.l, 0.3, and 0.6 megarad of gamma radiation on microflora, flavor, and vitamin content of chocolate syrup. A dose of 0.3 was found to be the minimum useful dose bacteriologically. Vitamin content was not reduced, and no off-flavor was reported. (T.R.H.)

Mechanics of Thin Films

DTIC Science & Technology

1992-02-06

dependence of the dimensions H, D of the results of Lau et al. [14] in which the angular the plastic zone on the hardening exponent n for variation of the...01 0. 03 04MMS 10I Trh~knea (m) l| Thcrm (a-) FIG. 8. Variation of k., and t/kf, vst for EBE TiO1/AO at5- and 10-g films deposited on silicon [Table

THE EXTENSION OF STORAGE LIFE OF FRESH FRUITS AND VEGETABLES BY IONIZING RADIATION. Report No. 5 (Progress) for Period April 17, 1959-July 26, 1959

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, D.C.

1961-10-31

The irradiation of strawberries to 10/sup 6/ and 2.5 x 10/sup 6/ rads and storage at 45/sup o/F are described. At 16 days the berries had lost color and were softer and less acceptable compared to blanched and unblanched controls. (T.R.H.)

EFFECT OF THERMIONIC EMISSION AT ROOM TEMPERATURES IN PHOTOSENSITIVE GEIGERMULLER TUBES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grotowski, K.; Hrynkiewicz, A.Z.; Niewodniczanski, H.

1953-01-01

The temperature-dependence of the background of Geiger-Mueller counting tubes was compared for nonsensitized and sensitized (treated by electric discharge) tubes. A strong increase of background with increasing temperature was observed for phatosensitive counters, while no change was observed in nonsensetized counters. It is shown that the increase is due to thermionic emission of the brass cathode. (T.R.H.)

CALUTRON

DOEpatents

Clark, A.F.

1959-06-16

A means of eliminating oscillating electrons from the arc slit region of calutron ion sources is offered. Free electrons and ions generated by the beam bombarding atoms of ambient atmosphere are discharged by a fin arrangement which sets up an electric field. The discharged ions travel toward a recess in which a fin and blister'' effect limits oscillations to one region from which they are removed by reversed electric fields. (T.R.H.)

CALUTRON

DOEpatents

Parkins, W.E.

1959-06-16

A calutron target arrangement is described which follows the shifting focus of the beam. Four magnets attached to the face of the receiver are arranged so that they are in magnetic equilibrium when the beam focus is properly aligned. Twisting of the beam causes heating of some of the magnets disturbing the equilibrium by permeability changes. The magnets restore equilibrium by moving the receiver face to proper alignment. (T.R.H.)

Action of specific thyroid hormone receptor α(1) and β(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat.

PubMed

van Beeren, Hermina C; Kwakkel, Joan; Ackermans, Mariëtte T; Wiersinga, Wilmar M; Fliers, Eric; Boelen, Anita

2012-12-01

The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) α(1) and β(1) antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a selective TRα(1) antagonist. In the present study, Amio and Dron were used as tools to discriminate between TRα(1) or TRβ(1) regulated genes in central and peripheral thyroid hormone metabolism. Three groups of male rats received either Amio, Dron, or vehicle by daily intragastric administration for 2 weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3 mRNA expressions and activities, and thyroid hormone transporters monocarboxylate transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion transporter 1C1 (OATP1C1). Amio treatment decreased serum T(3), while serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression, while increasing pituitary TSHβ and MCT10 mRNA expression. Amio decreased the pituitary D2 activity. By contrast, Dron treatment resulted in decreased hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3) concentration decreased substantially compared to Dron and control rats (50%, p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1, mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. Our results suggest an important role for TRα1 in the regulation of hypothalamic TRH mRNA expression, whereas TRβ plays a dominant role in pituitary and liver thyroid hormone metabolism.

Interleukin 6 deficiency modulates the hypothalamic expression of energy balance regulating peptides during pregnancy in mice.

PubMed

Pazos, Patricia; Lima, Luis; Casanueva, Felipe F; Diéguez, Carlos; García, María C

2013-01-01

Pregnancy is associated with hyperphagia, increased adiposity and multiple neuroendocrine adaptations. Maternal adipose tissue secretes rising amounts of interleukin 6 (IL6), which acts peripherally modulating metabolic function and centrally increasing energy expenditure and reducing body fat. To explore the role of IL6 in the central mechanisms governing dam's energy homeostasis, early, mid and late pregnant (gestational days 7, 13 and 18) wild-type (WT) and Il6 knockout mice (Il6-KO) were compared with virgin controls at diestrus. Food intake, body weight and composition as well as indirect calorimetry measurements were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy) and agouti-related peptide (Agrp); and catabolic and anorectic neuropeptides: proopiomelanocortin (Pomc), corticotrophin and thyrotropin-releasing hormone (Crh and Trh) mRNA levels were determined by in situ hybridization. Real time-PCR and western-blot were used for additional tissue gene expression and protein studies. Non-pregnant Il6-KO mice were leaner than WT mice due to a decrease in fat but not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despite similar body weight gain than WT controls. A decreased fat utilization in absence of Il6 might explain this effect, as shown by increased respiratory exchange ratio (RER) in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in adipose tissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh expression was also stimulated at gestational day 13 and lack of Il6 blunted this effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor alpha (Il6ra), Pomc and Crh mRNA were observed. Il6 deficiency during this stage up-regulated Npy and Agrp expression, while restoring Pomc mRNA levels to virgin values. Together these results demonstrate that IL6/IL6Ra system modulates Npy/Agrp, Pomc and Trh expression during mouse pregnancy, supporting a role of IL6 in the central regulation of body fat in this physiological state.

[Clinical studies on regulatory system of thyroid hormone secretion and serum triiodothyronine. Part. I. Solid-state radioimmunoassy for human serum TSH and its clinical application (author's transl)].

PubMed

Takeda, Y

1975-01-20

A solid-state RIA method using a plastic microtiter plate for human TSH was developed: 1) The choice of carrier protein for standard TSH was critical in this method and pooled sera from untreated Graves patients was found to be suitable for this purpose. The mean lowest detectable TSH level was 0.2 muU/assay, which was almost equal to those reported by other methods. This method is superior in simple assay procedure, especially in the separation of bound and free TSH and in the shorter incubation time required in the double antibody method. 2) Serum TSH concentration in 22 normal subjects, 17 patients with Graves' disease, 35 Hashimoto's thyroiditis, 18 primary hypothyrodism, 16 simple goiter, 4 nodular goiter and 7 secondary hypothyroidism was estimated as 4.7 +/- 2.0 muU/ml (mean +/- s.d.), 2.1 +/- 0.2 mu/U/ml, 14.1 +/- 26.5 muU/ml, 211 +/- 177 muU/ml, 3.6 +/- 2.4 muU/ml, 3.2 +/- 2.4 muU/ml and 2.6 +/- 1.0 muU/ml, respectively. 3) A statistically significant and hyperbolic inverse correlation (r= --0.37, N=90) was found between TSH and T4 levels. Some cases with normal T4 level were found to be high in TSH levels. It was also noted that 36 of 65 euthyroid cases (55.4%) who had been treated with 131I for Graves' disease showed elevated TSH levels. 4) After intravenous injection of 500 mug TRH, TSH level reached its peak value of 8 to 32 muU/ml at 15 to 45 minutes in normal subjects. Low to no response was found in patients with Graves' disease. An exaggerated response in patients with primary hypothyroidism to TRH was observed and an inhibitory process in TSH production at the pituitary level was suggested in patients with Cushing syndrome. Hypothyroid patients with pituitary lesion showed low or no response, on the other hand some hypothyroid patients with lesions around the pituitary and hypothalamus showed high basal TSH and exaggerated response to TRH.

Breastfeeding and Complementary Feeding Practices among HIV-Exposed Infants in Coastal Tanzania.

PubMed

Williams, Anne M; Chantry, Caroline; Geubbels, Eveline L; Ramaiya, Astha K; Shemdoe, Aloisia I; Tancredi, Daniel J; Young, Sera L

2016-02-01

Appropriate infant feeding is a persistent challenge for human immunodeficiency virus (HIV)-infected mothers in sub-Saharan Africa. This study aimed to describe correlates of infant feeding among HIV-infected mothers in coastal Tanzania. HIV-infected women (n = 400) with infants younger than 18 months were enrolled from June to November 2011 from 3 public health facilities in Pwani, Tanzania: Tumbi Regional Hospital (TRH), Chalinze Health Center (CHC), and Bagamoyo District Hospital (BDH). Participants were surveyed about sociodemographics and infant feeding behavior at enrollment; infant feeding data were collected prospectively and retrospectively in the month of study follow-up. Statistically significant correlates of exclusive breastfeeding (EBF) were infant age (months) (adjusted odds ratio [AOR] = 0.6; 95% confidence interval [CI], 0.5-0.9), enrollment facility (TRH: reference; CHC: AOR = 5.0, 95% CI, 1.2-20.8; BDH: AOR = 11.6, 95% CI, 2.3-59.9), and HIV disclosure to one's mother (AOR = 0.2; 95% CI, 0.1-0.6). Exclusive breastfeeding prevalence among infants younger than 6 months was 77%, but 50% of infants older than 6 months no longer receiving breast milk did not receive animal source foods (ASF) daily. Enrollment facility (TRH: reference; CHC: AOR = 0.2, 95% CI, 0.1-1.0; BDH: AOR = 0.1, 95% CI, 0.01-0.4) and HIV disclosure (to mother-in-law: AOR = 0.2, 95% CI, 0.1-0.8; to brother: AOR = 0.3, 95% CI, 0.1-0.8) were negatively associated with ASF provision. High prevalence of EBF suggests that it is an attainable behavior, whereas low prevalence of daily ASF provision suggests that adequate diets are difficult to achieve after breastfeeding cessation. These findings support current recommendations for HIV-infected mothers in resource-poor regions to continue breastfeeding for at least 1 year and suggest the need for greater support with complementary feeding. Associations between HIV disclosure and infant feeding merit further exploration, and correlations between enrollment facility and infant feeding highlight the potential influence of clinics on achieving infant feeding recommendations. © The Author(s) 2015.

Occurrence and molecular characterisation of Vibrio parahaemolyticus in crustaceans commercialised in Venice area, Italy.

PubMed

Caburlotto, Greta; Suffredini, Elisabetta; Toson, Marica; Fasolato, Luca; Antonetti, Paolo; Zambon, Michela; Manfrin, Amedeo

2016-03-02

Infections due to the pathogenic human vibrios, Vibrio parahaemolyticus, Vibrio cholerae and Vibrio vulnificus, are mainly associated with consumption of raw or partially cooked bivalve molluscs. At present, little is known about the presence of Vibrio species in crustaceans and the risk of vibriosis associated with the consumption of these products. The aim of the present study was to evaluate the prevalence and concentration of the main pathogenic Vibrio spp. in samples of crustaceans (n=143) commonly eaten in Italy, taking into account the effects of different variables such as crustacean species, storage conditions and geographic origin. Subsequently, the potential pathogenicity of V. parahaemolyticus strains isolated from crustaceans (n=88) was investigated, considering the classic virulence factors (tdh and trh genes) and four genes coding for relevant proteins of the type III secretion systems 2 (T3SS2α and T3SS2β). In this study, the presence of V. cholerae and V. vulnificus was never detected, whereas 40 samples (28%) were positive for V. parahaemolyticus with an overall prevalence of 41% in refrigerated products and 8% in frozen products. The highest prevalence and average contamination levels were detected in Crangon crangon (prevalence 58% and median value 3400 MPN/g) and in products from the northern Adriatic Sea (35%), with the samples from the northern Venetian Lagoon reaching a median value of 1375 MPN/g. While genetic analysis confirmed absence of the tdh gene, three of the isolates contained the trh gene and, simultaneously, the T3SS2β genes. Moreover three possibly clonal tdh-negative/trh-negative isolates carried the T3SS2α apparatus. The detection of both T3SS2α and T3SS2β apparatuses in V. parahaemolyticus strains isolated from crustaceans emphasised the importance of considering new genetic markers associated with virulence besides the classical factors. Moreover this study represents the first report dealing with Vibrio spp. in crustaceans in Italy, and it may provide useful information for the development of sanitary surveillance plans to prevent the risk of vibriosis in seafood consumers. Copyright © 2016 Elsevier B.V. All rights reserved.

Early effects of cranial irradiation on hypothalamic-pituitary function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, K.S.; Tse, V.K.; Wang, C.

1987-03-01

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

Characterization of Pathogenic Vibrio parahaemolyticus from the Chesapeake Bay, Maryland

PubMed Central

Chen, Arlene J.; Hasan, Nur A.; Haley, Bradd J.; Taviani, Elisa; Tarnowski, Mitch; Brohawn, Kathy; Johnson, Crystal N.; Colwell, Rita R.; Huq, Anwar

2017-01-01

Vibrio parahaemolyticus is the leading cause of bacterial gastroenteritis associated with seafood consumption in the United States. Here we investigated the presence of virulence factors and genetic diversity of V. parahaemolyticus isolated from water, oyster, and sediment samples from the Chesapeake Bay, Maryland. Of more than 2,350 presumptive Vibrio collected, more than half were confirmed through PCR as V. parahaemolyticus, with 10 encoding both tdh and trh and 6 encoding only trh. Potentially pathogenic V. parahaemolyticus were then serotyped with O1:KUT and O3:KUT predominant. Furthermore, pulsed-field gel electrophoresis was performed and the constructed dendrogram displayed high diversity, as did results from multiple-locus VNTR analysis. Vibrio parahaemolyticus was readily isolated from Chesapeake Bay waters but was less frequently isolated from oyster and sediment samples collected during this study. Potentially pathogenic V. parahaemolyticus was isolated in fewer numbers and the isolates displayed expansive diversity. Although characteristics of the pathogenic V. parahaemolyticus were highly variable and the percent of pathogenic V. parahaemolyticus detected was low, it is important to note that, pathogenic V. parahaemolyticus are present in the Chesapeake Bay, warranting seafood monitoring to minimize risk of disease for the public, and to reduce the economic burden of V. parahaemolyticus related illness. PMID:29375492

Characterization of Pathogenic Vibrio parahaemolyticus from the Chesapeake Bay, Maryland.

PubMed

Chen, Arlene J; Hasan, Nur A; Haley, Bradd J; Taviani, Elisa; Tarnowski, Mitch; Brohawn, Kathy; Johnson, Crystal N; Colwell, Rita R; Huq, Anwar

2017-01-01

Vibrio parahaemolyticus is the leading cause of bacterial gastroenteritis associated with seafood consumption in the United States. Here we investigated the presence of virulence factors and genetic diversity of V. parahaemolyticus isolated from water, oyster, and sediment samples from the Chesapeake Bay, Maryland. Of more than 2,350 presumptive Vibrio collected, more than half were confirmed through PCR as V. parahaemolyticus , with 10 encoding both tdh and trh and 6 encoding only trh . Potentially pathogenic V. parahaemolyticus were then serotyped with O1:KUT and O3:KUT predominant. Furthermore, pulsed-field gel electrophoresis was performed and the constructed dendrogram displayed high diversity, as did results from multiple-locus VNTR analysis. Vibrio parahaemolyticus was readily isolated from Chesapeake Bay waters but was less frequently isolated from oyster and sediment samples collected during this study. Potentially pathogenic V. parahaemolyticus was isolated in fewer numbers and the isolates displayed expansive diversity. Although characteristics of the pathogenic V. parahaemolyticus were highly variable and the percent of pathogenic V. parahaemolyticus detected was low, it is important to note that, pathogenic V. parahaemolyticus are present in the Chesapeake Bay, warranting seafood monitoring to minimize risk of disease for the public, and to reduce the economic burden of V. parahaemolyticus related illness.

The occurrence of Vibrio species in tropical shrimp culture environments; implications for food safety.

PubMed

Gopal, Shubha; Otta, Subhendu K; Kumar, Sanath; Karunasagar, Indrani; Nishibuchi, Matsuaki; Karunasagar, Iddya

2005-07-15

The occurrence of various Vibrio species in water, sediment and shrimp samples from multiple shrimp farm environments from the east and west coast of India was studied. The relative abundance was higher in west coast farms (ca. 10(4) cfu/ml water) when compared to the east coast (ca. 10(2) cfu/ml water). Vibrio alginolyticus (3-19%), V. parahaemolyticus (2-13%), V. harveyi (1-7%) and V. vulnificus (1-4%) were the predominant Vibrio species identified by standard biochemical testing. In some cases, V. cholerae could be found, but all isolates were negative for the cholera toxin (ctx) gene that is associated with choleragenic strains. The biochemical identification of V. parahaemolyticus, the other human pathogen among the species mentioned above, was confirmed by PCR targeting the toxR gene and a 387 bp chromosomal locus specific for this species. Furthermore, the presence of the virulence-associated tdh (thermostable direct haemolysin) and trh (TDH-related haemolysin) genes in the V. parahaemolyticus isolates was also detected by PCR. Only 2 out of 47 isolates were tdh positive and one contained the trh gene. However, since V. cholerae, V. parahaemolyticus and V. vulnificus species are recognized as a major cause of seafood-borne illness, it is important to pay attention to post-harvest handling and adequate cooking.

FINAL REPORT--PART I. EFFECT OF IONIZED RADIATION ON THE NUTRITIVE VALUE OF FOOD (TUNA FISH) AS DETERMINED BY GROWTH, REPRODUCTION, AND LACTATION STUDIES WITH DOGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCay, C.M.; Rumsey, G.L.

1960-03-15

A study was made of the effects of radiation on the nutritive value of tuna fish in the diet of beagle dogs. A study of the data pertaining to hematology, x-ray photographs of the bones, growth, and reproduction indicates that irradiated tuna fish is satisfactory in the diet of a dog. (T.R.H.)

AFRRI Reports, Third-Fourth Quarters

DTIC Science & Technology

1998-02-01

structural changes de- induce CPEs, and CPE was blocked by amantadine. N- scribed here for the effect of IV on J774.1 cells were Acetylcysteine and pyrrolidine...assayed. Inhibitors were N- acetylcysteine (NAC, 50 mM), pyrrolidine block CPEs (data not shown). dithiocarbamate (PDTC, 100 mM), deferoximine nesyiate (DEF...thyroid axis (34-39), partly due to suppression of TRH gene expression in the hypothala- mus (39). This inhibition may account for the depression of

PARTICLE BEAM TRACKING CIRCUIT

DOEpatents

Anderson, O.A.

1959-05-01

>A particle-beam tracking and correcting circuit is described. Beam induction electrodes are placed on either side of the beam, and potentials induced by the beam are compared in a voltage comparator or discriminator. This comparison produces an error signal which modifies the fm curve at the voltage applied to the drift tube, thereby returning the orbit to the preferred position. The arrangement serves also to synchronize accelerating frequency and magnetic field growth. (T.R.H.)

Draft Genome Sequence of trh+ Vibrio parahaemolyticus VP-49, Isolated from Seafood Harvested along the Mangalore Coast, India.

PubMed

Kumar, Ballamoole Krishna; Deekshit, Vijaya Kumar; Rai, Praveen; Gurtler, Volker; Karunasagar, Iddya; Karunasagar, Indrani

2014-06-26

Vibrio parahaemolyticus is a seafood-borne pathogen autochthonous to the marine and estuarine ecosystem, which is responsible for gastroenteritis due to the consumption of contaminated raw seafood. Here, we report the draft genome sequence of V. parahaemolyticus VP-49, isolated from seafood, to identify the different virulence attributes and to study the mechanisms that enhance its environmental fitness. Copyright © 2014 Kumar et al.

Somatotroph Hyperplasia

PubMed Central

Thorner, M. O.; Perryman, R. L.; Cronin, M. J.; Rogol, A. D.; Draznin, M.; Johanson, A.; Vale, W.; Horvath, E.; Kovacs, K.

1982-01-01

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95±9.4 ng/ml; mean±SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm3) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified. Images PMID:6290540

Radioactive Strontium in Soil, Crops, Foodstuffs, and Human Bones in the Netherlands. Part I; RADIOACTIEF STRONTIUM IN GROND, GEWASSEN, VOEDINGSMIDDELEN EN MENSELUK BOT IN NEDERLAND. DEEL I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barendsen, G.W.; Beusker, T.L.J.; Bleichrodt, J.F.

1959-02-01

Measurements of Sr/sup 89/ and Sr/sup 89/ in soil, grass, milk, and foodstuff samples are reported. Analyses of human urine were made which show wide daily variations. Human bone samples from children up to 15 yr age were studied. The results agree with those from the U.K. and the U.S.A. (T.R.H.)

METHOD OF PREPARING PROTACTINIUM VALUES

DOEpatents

Katzin, L.I.; Larson, R.G.; Thompson, R.C.; Van Winkle, Q.

1959-05-19

Separation and purification from initial acid leaches of pitchblende of Pa is described. This supernatant acid solution is treated with alkali metal carbonates to precipitate Pa. Silica is removed from the precipitate by hydroxide treatment. The Pa residue is dissolved in HNO/sub 3/ and Pa is concentrated by cyclic precipitations with MnO/sub 2/. The last solution is hydrolyzed to precipitate Pa. The Pa precipitate contains Ti and Zr which are removed by ion exchange. (T.R.H.)

The Role of Limited Proteolysis of Thyrotropin-Releasing Hormone in Thermoregulation.

DTIC Science & Technology

1982-01-01

exogenously. The limited proteolysis of TRH by pyroglutamate aminopeptidase from CNS results into formation of a new cyclic dipeptide, cyclo (His-Pro...amino acids (L-histidine and L-proline), and two analogues of cyclo (His-Pro), cyclo (Pro-Gly) and cyclo . (Ala-Gly). Cyclo (His-Pro) cross-reacted only...cyclo (His-Pro). Figure 3 shows the chromato- graphic profile obtained when a neutralized perchloric acid extract of rat brain was passed through DEAE

The clinical presentation and biochemical diagnosis of acromegaly and gigantism.

PubMed

Jialal, I; Nathoo, B C; Joubert, S; Asmal, A C; Pillay, N L

1982-04-24

Over a 5-year period 14 patients with acromegaly and gigantism were seen at the endocrine clinic of King Edward VIII Hospital: 9 were Blacks and 5 Indians; 8 of the patients were women. The mean age of the patients was 46 years. Surprisingly, only 2 patients complained of acral overgrowth. Symptomatology was varied and not characteristic of the condition. On examination all patients had unequivocal signs of soft-tissue and bony overgrowth, 64% had visual abnormalities and 50% hypertension. Radiologically, 88% showed an enlarged pituitary fossa. On biochemical investigation, the fasting levels of growth hormone (GH) were increased in 12 patients and during oral glucose tolerance tests, the GH levels in these 12 patients were not suppressed. One patient in whom the fasting GH level was not increased had progressed to the stage of panhypopituitarism, in the remaining patient challenge with thyrotrophin-releasing hormone (TRH) led to increased GH levels and L-dopa challenge resulted in a paradoxical decrease in GH levels. Seven patients with increased GH levels who were challenged with L-dopa showed the typical decrease in GH levels found in this condition; in 5 of these patients, challenged with TRH, GH levels increased. The findings emphasize that despite the ease of clinical diagnosis, appropriate biochemical investigations are necessary to confirm the exact status of the disease, which is rare in the population studied.

Central administration of orexin A suppresses basal and domperidone stimulated plasma prolactin.

PubMed

Russell, S H; Kim, M S; Small, C J; Abbott, C R; Morgan, D G; Taheri, S; Murphy, K G; Todd, J F; Ghatei, M A; Bloom, S R

2000-12-01

Orexin immunoreactive fibres are abundant in the hypothalamus suggesting a neuroendocrine regulatory role. Intracerebroventricular (ICV) administration of orexin A suppressed plasma prolactin in male rats by 71% at 20 min post-injection and 83% at 90 min post-injection (P < 0.005 vs saline at both time points). To investigate whether this effect was through the tuberoinfundibular dopaminergic (TIDA) system, a supra-maximal dose of domperidone, a dopamine receptor antagonist, was injected intraperitoneally (i.p.) prior to ICV injection of orexin A. ICV orexin A significantly suppressed domperidone (9 mg/kg)-stimulated plasma prolactin levels, by up to 40% (i.p. domperidone + ICV orexin A 3 nmol 34.5 +/- 7.4 ng/ml and i.p. domperidone + ICV orexin A 20 nmol 43.5 +/- 4.3 ng/ml, both P < 0.005 vs i.p. domperidone + ICV saline 57.9 +/- 2.7 ng/ml). Orexin A, 100 nM, significantly stimulated release of neurotensin, vasoactive intestinal polypeptide, somatostatin, corticotropin releasing factor and luteinizing hormone releasing hormone, but had no effect on release of dopamine, thyrotropin releasing hormone (TRH), vasopressin or melanin-concentrating hormone from hypothalamic explants in vitro. Orexin A did not alter basal or TRH stimulated prolactin release in dispersed pituitary cells harvested from male rats. The data suggest that ICV administration of orexin A suppresses plasma prolactin in part through a pathway independent of the dopaminergic system.

REDUCTION OF PLUTONIUM VALUES IN AN ACIDIC AQUEOUS SOLUTION WITH FORMALDEHYDE

DOEpatents

Olson, C.M.

1959-06-01

A method is given for reducing Pu to the tetravalent state and lowering the high acidity of dissolver solutions containing U and Pu. Formaldehyde is added to the HNO/sub 3/ solution of U and Pu to effect a formaldehyde to HNO/sub 3/ molar ratio of 0.375:1 to 1.5:1. The Pu can then be removed from the solution by carrier precipitation using BiPO/sub 4/ or by ion exchange. (T.R.H.)

Plasma GH responses to GHRH, arginine, L-dopa, pyridostigmine, sequential administrations of GHRH and combined administration of PD and GHRH in Turner's syndrome.

PubMed

Hanew, K; Tanaka, A; Utsumi, A

1998-02-01

To investigate GH secretory capacities in patients with Turner's syndrome, GHRH, arginine, L-dopa and pyridostigmine (PD) were administered singly and GHRH was administered sequentially for 3 days. In addition, plasma GH and TSH responses to GHRH and TRH after pretreatment with PD were analyzed to investigate whether the hypothalamic cholinergic somatostatinergic system functioned normally. The maximal GH responses to GHRH, L-dopa and PD were significantly smaller in Turner's syndrome (no.=14) than in normal short children (NSC, no.=14). However, there was no difference in plasma GH responses to arginine between the two groups. In ten patients with Turner's syndrome, the plasma GH response to GHRH did not improve even after the sequential 3-day administrations. Although plasma GH and TSH responses to GHRH and TRH were significantly enhanced by the pretreatment of PD in NSC (no.=12), these responses were not enhanced in Turner's syndrome. Plasma GH response to GHRH in Turner's syndrome with normal body fat was still significantly lower than in NSC. It is therefore concluded that somatotroph sensitivity to GHRH is decreased in Turner's syndrome and that this may be due to the primary defects of the somatotrophs rather than to the increased body fat. In addition, the network of cholinergic-somatostatinergic systems seemed to be impaired in these patients, while the activity of hypothalamic somatostatin neurons was thought to be maintained.

From Consternation to Revelation: Discovery of a Role for IGSF1 in Pituitary Control of Thyroid Function.

PubMed

Bernard, Daniel J; Brûlé, Emilie; Smith, Courtney L; Joustra, Sjoerd D; Wit, Jan M

2018-03-01

Immunoglobulin superfamily, member 1 (IGSF1) is a transmembrane glycoprotein highly expressed in the mammalian pituitary gland. Shortly after its discovery in 1998, the protein was proposed to function as a coreceptor for inhibins (and was even temporarily renamed inhibin binding protein). However, subsequent investigations, both in vitro and in vivo , failed to support a role for IGSF1 in inhibin action. Research on IGSF1 nearly ground to a halt until 2011, when next-generation sequencing identified mutations in the X-linked IGSF1 gene in boys and men with congenital central hypothyroidism. IGSF1 was localized to thyrotrope cells, implicating the protein in pituitary control of the thyroid. Investigations in two Igsf1 knockout mouse models converged to show that IGSF1 deficiency leads to reduced expression of the receptor for thyrotropin-releasing hormone (TRH) and impaired TRH stimulation of thyrotropin secretion, providing a candidate mechanism for the central hypothyroidism observed in patients. Nevertheless, the normal functions of IGSF1 in thyrotropes and other cells remain unresolved. Moreover, IGSF1 mutations are also commonly associated with other clinical phenotypes, including prolactin and growth hormone dysregulation, and macroorchidism. How the loss of IGSF1 produces these characteristics is unknown. Although early studies of IGSF1 ran into roadblocks and blind alleys, armed with the results of detailed clinical investigations, powerful mouse models, and new reagents, the field is now poised to discover IGSF1's function in endocrine tissues, including the pituitary and testes.

Effects of neonatal hyperthyroidism on the development of the hypothalamic-pituitary-thyroid axis in the rat.

PubMed

Dussault, J H; Coulombe, P; Walker, P

1982-03-01

The acute and latent effects of neonatal hyperthyroidism (NH) on the hypothalamic-pituitary-thyroid axis were studied in the rat after treatment of newborn animals with L-T4 (0.4 microgram/g BW, daily) for a period of 12 days. NH was associated with a permanent reduction in body weight in both male and female rats, in addition to a delay in the attainment of peak concentrations of hypothalamic TRH and pituitary and serum TSH. Serum TSH, T4, and T3 concentrations also were significantly and permanently reduced in NH animals (P less than 0.01) after cessation of L-T4 treatment. The serum TSH secretory response to 1 microgram synthetic TRH also was evaluated in 120-day-old control and NH rats, before and after the administration of L-T4 (0.6 microgram/100 g BW for 7 days) or propylthiouracil (0.05% in the drinking water for 14 days). In the baseline state, adult NH rats had a net secretory response similar to that of controls (189.0 +/- 31.3 vs. 227.0 +/- 29.3 microgram/ml . min). Administration of T4 significantly decreased while propylthiouracil treatment significantly increased the net TSH secretory response of NH rats compared to similarly treated control rats. These data are compatible with the hypothesis that NH leads to a permanent resetting of the regulatory set-point for pituitary TSH secretion and to increased sensitivity to the feedback inhibitory effects of thyroid hormones.

Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis.

PubMed

Hernandez, Arturo; Martinez, M Elena; Liao, Xiao-Hui; Van Sande, Jacqueline; Refetoff, Samuel; Galton, Valerie Anne; St Germain, Donald L

2007-12-01

The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild-type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro-TRH mRNA in the paraventricular nucleus of the hypothalamus. Finally, treatment with T(3) results in a serum T(3) level in D3KO mice that is much higher than that in wild-type mice. This is accompanied by significant weight loss and lethality in mutant animals. In conclusion, the absence of D3 activity results in impaired clearance of T(3) and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid.

Association of TSH With Cardiovascular Disease Risk in Overweight and Obese Children During Lifestyle Intervention.

PubMed

Rijks, Jesse M; Plat, Jogchum; Dorenbos, Elke; Penders, Bas; Gerver, Willem-Jan M; Vreugdenhil, Anita C E

2017-06-01

Overweight and obese children have an increased risk to develop cardiovascular diseases (CVDs) in which thyroid-stimulating hormone (TSH) has been suggested as an intermediary factor. However, results of cross-sectional studies are inconclusive, and intervention studies investigating changes in TSH concentrations in association with changes in cardiovascular risk parameters in overweight and obese children are scarce. To gain insight in associations of circulating TSH concentrations and cardiovascular risk parameters in overweight and obese children. Nonrandomized lifestyle intervention. Centre for Overweight Adolescent and Children's Healthcare. Three hundred thirty euthyroid overweight and obese children. Long-term lifestyle intervention. TSH concentrations, pituitary TSH release in response to thyrotropin-releasing hormone (TRH), and cardiovascular risk parameters. At baseline, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG), and monocyte chemotactic protein 1 concentrations were significantly associated with serum TSH concentrations. TSH release by the pituitary in response to exogenous TRH was not associated with cardiovascular risk parameters. During lifestyle intervention, several cardiovascular risk parameters significantly improved. In children whose body mass index z score improved, changes in TSH concentrations were significantly associated with changes in TC, LDL-C, and TAG concentrations. In euthyroid overweight and obese children, circulating TSH concentrations are positively associated with markers representing increased CVD risk. Changes in TSH concentrations are also associated with changes in lipid concentrations in children with successful weight loss, which is consistent with TSH being an intermediary factor in modulating lipid and lipoprotein metabolism. Copyright © 2017 Endocrine Society

Dynamics of Vibrio with virulence genes detected in Pacific harbor seals (Phoca vitulina richardii) off California: implications for marine mammal health.

PubMed

Hughes, Stephanie N; Greig, Denise J; Miller, Woutrina A; Byrne, Barbara A; Gulland, Frances M D; Harvey, James T

2013-05-01

Given their coastal site fidelity and opportunistic foraging behavior, harbor seals (Phoca vitulina) may serve as sentinels for coastal ecosystem health. Seals using urbanized coastal habitat can acquire enteric bacteria, including Vibrio that may affect their health. To understand Vibrio dynamics in seals, demographic and environmental factors were tested for predicting potentially virulent Vibrio in free-ranging and stranded Pacific harbor seals (Phoca vitulina richardii) off California. Vibrio prevalence did not vary with season and was greater in free-ranging seals (29 %, n = 319) compared with stranded seals (17 %, n = 189). Of the factors tested, location, turbidity, and/or salinity best predicted Vibrio prevalence in free-ranging seals. The relationship of environmental factors with Vibrio prevalence differed by location and may be related to oceanographic or terrestrial contributions to water quality. Vibrio parahaemolyticus, Vibrio alginolyticus, and Vibrio cholerae were observed in seals, with V. cholerae found almost exclusively in stranded pups and yearlings. Additionally, virulence genes (trh and tdh) were detected in V. parahaemolyticus isolates. Vibrio cholerae isolates lacked targeted virulence genes, but were hemolytic. Three out of four stranded pups with V. parahaemolyticus (trh+ and/or tdh+) died in rehabilitation, but the role of Vibrio in causing mortality is unclear, and Vibrio expression of virulence genes should be investigated. Considering that humans share the environment and food resources with seals, potentially virulent Vibrio observed in seals also may be of concern to human health.

Distribution and growth of Vibrio parahaemolyticus in southern Chilean clams (Venus antiqua) and blue mussels (Mytilus chilensis).

PubMed

Aranda, Carlos P; Yévenes, Marco; Rodriguez-Benito, Cristina; Godoy, Félix A; Ruiz, Magdalena; Cachicas, Viviana

2015-01-01

We evaluated the distribution and growth of Vibrio parahaemolyticus in the inland sea of southern Chile, where the world's largest foodborne gastroenteritis outbreak by the pandemic strain O3:K6 occurred in 2005. Intertidal samples of Mytilus chilensis and Venus antiqua were collected around port towns between 41°28'S and 43°07'S, during April to May 2011 and January to March 2012. We used most probable number real-time polymerase chain reaction (MPN-PCR) for enumeration of the tlh, tdh, and trh genes in freshly harvested bivalves and after a controlled postharvest temperature abuse. Pathogenic markers (tdh+ or trh+) were not detected. Total V. parahaemolyticus (tlh+) in freshly harvested samples reached up to 0.38 and 3.66 log MPN/g in 2011 and 2012, respectively, with values close to or above 3 log MPN/g only near Puerto Montt (41°28'S, 72°55'W). Enrichments by temperature abuse (>2 log MPN/g) occurred mainly in the same zone, regardless of the year, suggesting that both natural or anthropogenic exposure to high temperatures were more critical. Lower salinity and higher sea surface temperature in Reloncaví Sound and Reloncaví Estuary were consistent with our observations and allowed confirmation of the existence of a high-risk zone near Puerto Montt. Based on the results, a strategy focused on risk management inside this defined hazard zone is recommended.

Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism.

PubMed

Russo, Marco; Scollo, Claudia; Pellegriti, Gabriella; Cotta, Oana Ruxandra; Squatrito, Sebastiano; Frasca, Francesco; Cannavò, Salvatore; Gullo, Damiano

2016-04-01

Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC. In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 μg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10). Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in vitro studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition. © 2015 John Wiley & Sons Ltd.

The latest development of antihypertensive medication

NASA Astrophysics Data System (ADS)

Nasution, S.; Rey, I.; Effendi-YS, R.

2018-03-01

Hypertension is the most common risk factor for cardiovascular disease, stroke, renal failure, and death. Recent drug monitoring studies found non-adherence to BP lowering therapy in 25% to 65% of patients with apparent treatment-resistant hypertension (TRH). This review focuses on the latest development of antihypertensive medication, such as vasopeptidase inhibitors, aldosterone synthase inhibitors, Soluble Epoxide Hydrolase Inhibitors, agonists of natriuretic peptide receptor, Vasoactive Intestinal Peptide Receptor Agonist, a novel mineralocorticoid receptor antagonist, inhibitors of aminopeptidase A, dopamine β-hydroxylase inhibitor, intestinal Na+/H+ exchanger 3 inhibitor and other agents.

PRODUCTION OF PLUTONIUM FROM PLUTONIUM FLUORIDE

DOEpatents

Baker, R.D.

1959-06-01

Reduction of PuF/sub 4/ to metal is described. In the example given, PuF/sub 4/ is mixed with 0.3 mole I/sub 2/ per mole of Pu and Ca powder 25% in excess of that required for eduction of the Pu salt, and I/sub 2/ is added. The mixture is charged to a magnesia-lined steel bomb which is heated until reacted in a furnace. The Pu is reduced to metal and recovered as a slug after the bomb is cooled and opened. About 90% yield is obtained. (T.R.H.)

RECOVERY OF URANIUM VALUES FROM URANIUM BEARING RAW MATERIALS

DOEpatents

Michal, E.J.; Porter, R.R.

1959-06-16

Uranium leaching from ground uranium-bearing raw materials using MnO/sub 2/ in H/sub 2/SO/sub 4/ is described. The MnO/sub 2/ oxidizes U to the leachable hexavalent state. The MnO/sub 2/ does not replace Fe normally added, because the Fe complexes P and catalyzes the MnO/sub 2/ reaction. Three examples of continuous processes are given, but batch operation is also possible. The use of MnO/sub 2/ makes possible recovery of very low U values. (T.R.H.)

Detection Performance of Horizontal Linear Hydrophone Arrays in Shallow Water.

DTIC Science & Technology

1980-12-15

random phase G gain G angle interval covariance matrix h processor vector H matrix matched filter; generalized beamformer I unity matrix 4 SACLANTCEN SR...omnidirectional sensor is h*Ph P G = - h [Eq. 47] G = h* Q h P s The following two sections evaluate a few examples of application of the OLP. Following the...At broadside the signal covariance matrix reduces to a dyadic: P 󈧬 s s*;therefore, the gain (e.g. Eq. 37) becomes tr(H* P H) Pn * -1 Q -1 Pn G ~OQp

PLUTONIUM ALLOYS

DOEpatents

Chynoweth, W.

1959-06-16

The preparation of low-melting-point plutonium alloys is described. In a MgO crucible Pu is placed on top of the lighter alloying metal (Fe, Co, or Ni) and the temperature raised to 1000 or 1200 deg C. Upon cooling, the alloy slug is broke out of the crucible. With 14 at. % Ni the m.p. is 465 deg C; with 9.5 at. % Fe the m.p. is 410 deg C; and with 12.0 at. % Co the m.p. is 405 deg C. (T.R.H.) l6262 l6263 ((((((((Abstract unscannable))))))))

Corticotropin-releasing factor accelerates metamorphosis in Bufo arenarum: effect on pituitary ACTH and TSH cells.

PubMed

Miranda, L A; Affanni, J M; Paz, D A

2000-04-01

The actions of several neuropeptides as hypothalamic mediators in the regulation of Bufo arenarum metamorphosis were investigated. Prometamorphic larvae were injected with 1.5 microg thyrotropin-releasing hormone (TRH), 2 microg ovine corticotropin-releasing factor (oCRF), 2 microg mammalian gonadotropin-releasing hormone (mGnRH), 2 microg human growth hormone-releasing hormone (hGHRH), or Holtfreter solution (control group). Larvae received two injections with the same dose: one at the beginning of the experiment and the other 7 days later. Several morphologic parameters (total length, tail length, wet weight, hind limb length, and metamorphic stages) were measured as indicators of growth and metamorphic development. These measurements were taken in 20 larvae per treatment or control group at the beginning of the experiment, at day 7 and at day 14 when the experiment ended. We observed that only the administration of exogenous CRF stimulated resorption of the tail and accelerated the rate of metamorphosis. In the pituitary of CRF-treated larvae we observed that thyrotropin (TSH) and adrenocorticotropic hormone (ACTH) producing cells showed a weaker immunoreactivity, a decrease in cell number and a reduction of volume density when compared with normal larvae. In conclusion, the results obtained indicate a possible role for CRF in Bufo arenarum metamorphosis. CRF may regulate interrenal and thyroid activity by acting directly upon TSH and ACTH cells. On the other hand, TRH, GnRH and GHRH were inactive in stimulating growth or metamorphosis of Bufo arenarum. J. Exp. Zool. 286:473-480, 2000. Copyright 2000 Wiley-Liss, Inc.

Water vapour condensation in a partly closed structure. Comparison between results obtained with an inside wet or dry bottom wall

NASA Astrophysics Data System (ADS)

Batina, Jean; Peyrous, René

2018-04-01

We are interested in the determination of the more significant parameters acting on the water vapour condensation in a partly closed structure, submitted to external constraints (temperature and humidity), in view to recover the generated droplets as an additional source of potable water. External temperature variations, by inducing temperature differences between outside and inside of the structure, lead to convective movements and thermal variations inside this structure. Through an orifice, these movements permit a renewing of the humid inner air and can lead to the condensation of the water vapour initially contained in the inner air volume and/or on the walls. With the above hypotheses, and by using a numerical simulation [1] based on the ambient air characteristics and a finite volumes method, it appears that condensed water quantities are mainly depending on the boundary conditions imposed. These conditions are: 1) dimensions of the structure; 2) external temperature and relative hygrometry; 3) the phase φ (T/RH) linking thermal and hydrometric conditions; 4) the air renewing and its hygrometry for each phase; and 5) for each case, the fact that the inside bottom wall can be wet or dry. The resulting condensed water vapour quantities obtained, for the width section, point out clearly that they are very depending on this phase φ (T/RH) which appears as the more significant parameter and can be modified by the presence or not of a thin layer of water vapour on the inside bottom wall. Condensation phenomenon could be increased if φ could be optimized.

Thyroid Hormone Regulation of Metabolism

PubMed Central

Mullur, Rashmi; Liu, Yan-Yun

2014-01-01

Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

Isolation and molecular characterization of Vibrio parahaemolyticus from fresh, low-temperature preserved, dried, and salted seafood products in two coastal areas of eastern China.

PubMed

Yang, Zhen-Quan; Jiao, Xin-An; Zhou, Xiao-Hui; Cao, Guo-Xiang; Fang, Wei-Ming; Gu, Rui-Xia

2008-07-31

A total of 1293 seafood samples from fishing farm, retail markets, restaurants and cooking rooms of hotels in Jiangsu province and Shanghai city of China were collected and analyzed for the prevalence of Vibrio parahaemolyticus during July to October in 2007. Two hundred and fifty one isolates of V. parahaemolyticus were identified, of which 8 isolates were positive for tdh and 2 were positive for trh gene. Three tdh positive isolates were identified from low-temperature preserved seafood samples and 5 isolates from fresh seafood samples, of these tdh positive isolates, 3 were positive in ORF8-PCR test. The genetic diversity among V. parahaemolyticus isolates was assessed using random amplified polymorphic DNA (RAPD)-PCR and the results showed that there were 33 different genetic patterns that were clustered into nine groups (groups A to I) at 82% similarity level. About 31.9% of the isolates belong to type III9d that were widely distributed in fresh, iced, frozen, dried and salted seafood samples. Seven tdh positive isolates belonged to group A and one belonged to group C, 2 trh positive isolates were type I10d belonging to group F, which was identical to that of reference strains isolated from patients. This study demonstrated genetic variability within V. parahaemolyticus isolates from seafood in Chinese markets and confirmed the presence of toxigenic V. parahaemolyticus not only in fresh but also in iced and frozen seafood products indicating that low-temperature preserved seafood might be also a vehicle for transmitting pathogenic V. parahaemolyticus.

Central regulation of the hypothalamo-pituitary-thyroid (HPT) axis: focus on clinical aspects.

PubMed

Fliers, E; Boelen, A; van Trotsenburg, A S P

2014-01-01

The hypothalamus is the most prominent brain region involved in setpoint regulation of the thyroid axis. It generates the diurnal thyroid-stimulating hormone (TSH) rhythm, and it plays a central role in the adaptation of the thyroid axis to environmental factors such as caloric deprivation or infection. Many studies, including studies in human post-mortem tissue samples, have confirmed a key role for the thyrotropin-releasing hormone (TRH) neuron in the hypothalamic paraventricular nucleus (PVN) in thyroid axis regulation. In addition to their negative feedback action on TRH neurons in the hypothalamus, intrahypothalamic thyroid hormones can also modulate metabolism in adipose tissue and the liver via the autonomic nervous system. Congenital or acquired dysfunction of the hypothalamus or pituitary gland may result in central hypothyroidism (CeH). In the Netherlands, the prevalence of permanent congenital CeH as detected by neonatal screening is approximately 1 in 18000. In most neonates congenital CeH is accompanied by additional anterior pituitary hormone deficiencies, and many show clear morphological abnormalities such as a small anterior gland, a thin or absent pituitary stalk, or an ectopic posterior pituitary gland. Recently, a mutation in the immunoglobulin superfamily member 1 (IGSF1) gene was reported as a novel cause of X-linked, apparently isolated CeH occurring in neonates, children and adults. In adults, the most frequent cause of acquired CeH is a pituitary macroadenoma, usually accompanied by other pituitary hormone deficiencies. Central hyperthyroidism is a rare disorder, especially in children. In adults, it is mostly caused by a TSH-secreting pituitary adenoma. © 2014 Elsevier B.V. All rights reserved.

METHOD OF FORMING ELONGATED COMPACTS

DOEpatents

Larson, H.F.

1959-05-01

A powder compacting procedure and apparatus which produces elongated compacts of Be is described. The powdered metal is placed in a thin metal tube which is chemically compatible to lubricant, powder, atmosphere, and die material and will undergo a high degree of plastic deformation and have intermediate hardness. The tube is capped and placed in the die, and punches are applied to the ends. During the compacting stroke the powder seizes the tube and a thickening and shortening of the tube occurs. The tube is easily removed from the die, split, and peeled from the compact. (T.R.H.)

A SIMPLE RADIO-CHROMATOGRAM SCANNER

DOE Office of Scientific and Technical Information (OSTI.GOV)

McWeeny, D.J.; Burton, H.S.

1962-07-01

A sturdy, simple, and reliable radiochromatogram scanner is described. It is constructed from a Panax Universal Castle, a Panax 5054 rate meter, and a recording milliamometer. The castle houses 2 thin endwindows, G--M tubes type GE- EHM-2 mounted one above the other, windows 1/4 in. apart. The 1-in. chromatogram passes continuously thru a selection of slits permitting a choice of views by the G-M tubes. The background count is 10.5 counts per minute and the detection limit for S/sup 35/ as a 3 mm spot on Whatman no. 1 paper is less than 0.2 nc. (T.R.H.)

Effects of Intertidal Harvest Practices on Levels of Vibrio parahaemolyticus and Vibrio vulnificus Bacteria in Oysters.

PubMed

Jones, J L; Kinsey, T P; Johnson, L W; Porso, R; Friedman, B; Curtis, M; Wesighan, P; Schuster, R; Bowers, J C

2016-08-01

Vibrio parahaemolyticus and Vibrio vulnificus can grow rapidly in shellfish subjected to ambient air conditions, such as during intertidal exposure. In this study, levels of total and pathogenic (tdh(+) and/or trh(+)) V. parahaemolyticus and total V. vulnificus were determined in oysters collected from two study locations where intertidal harvest practices are common. Samples were collected directly off intertidal flats, after exposure (ambient air [Washington State] or refrigerated [New Jersey]), and after reimmersion by natural tidal cycles. Samples were processed using a most-probable-number (MPN) real-time PCR method for total and pathogenic V. parahaemolyticus or V. vulnificus In Washington State, the mean levels of V. parahaemolyticus increased 1.38 log MPN/g following intertidal exposure and dropped 1.41 log MPN/g after reimmersion for 1 day, but the levels were dependent upon the container type utilized. Pathogenic V. parahaemolyticus levels followed a similar trend. However, V. vulnificus levels increased 0.10 log MPN/g during intertidal exposure in Washington but decreased by >1 log MPN/g after reimmersion. In New Jersey, initial levels of all vibrios studied were not significantly altered during the refrigerated sorting and containerizing process. However, there was an increase in levels after the first day of reimmersion by 0.79, 0.72, 0.92, and 0.71 log MPN/g for total, tdh(+) and trh(+) V. parahaemolyticus, and V. vulnificus, respectively. The levels of all targets decreased to those similar to background after a second day of reimmersion. These data indicate that the intertidal harvest and handling practices for oysters that were studied in Washington and New Jersey do not increase the risk of illness from V. parahaemolyticus or V. vulnificus Vibrio parahaemolyticus and Vibrio vulnificus are the leading causes of seafood-associated infectious morbidity and mortality in the United States. Vibrio spp. can grow rapidly in shellfish subjected to ambient air conditions, such as during periods of intertidal exposure. When oysters are submersed with the incoming tide, the vibrios can be purged. However, data on the rates of increase and purging during intertidal harvest are scarce, which limits the accuracy of risk assessments. The objective of this study was to help fill these data gaps by determining the levels of total and pathogenic (tdh(+) and/or trh(+)) V. parahaemolyticus and V. vulnificus in oysters from two locations where intertidal harvest practices are common, using the current industry practices. The data generated provide insight into the responses of Vibrio spp. to relevant practices of the industry and public health, which can be incorporated into risk management decisions. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Occurrence of Virulence Genes Associated with Human Pathogenic Vibrios Isolated from Two Commercial Dusky Kob (Argyrosmus japonicus) Farms and Kareiga Estuary in the Eastern Cape Province, South Africa

PubMed Central

Fri, Justine; Ndip, Roland Ndip; Njom, Henry Akum; Clarke, Anna Maria

2017-01-01

Background: Seafood-borne Vibrio infections, often linked to contaminated seafood and water, are of increasing global public health concern. The aim of this study was to evaluate the prevalence of human pathogenic vibrios and their associated virulence genes isolated from fish and water samples from 2 commercial dusky kob farms and Kareiga estuary, South Africa. Methods: A total of 200 samples including dusky kob fish (n = 120) and seawater (n = 80) were subjected to Vibrio screening on thiosulfate-citrate-bile salts-sucrose agar (TCBS). Presumptive isolates were confirmed and delineated to V. cholerae, V. parahaemolyticus, V. vulnificus, and V. fluvialis by PCR. Various pathogenic gene markers were screened: V. parahaemolyticus (trh and tdh), V. vulnificus (vcgE and vcgC) and V. fluvialis (stn, vfh, hupO, vfpA). Restriction Fragment Length Polymorphism (RFLP) of the vvhA gene of V. vulnificus strains was performed to determine the associated biotypes. Results: Total Vibrio prevalence was 59.4% (606/1020) of which V. fluvialis was the most predominant 193 (31.85%), followed by Vibrio vulnificus 74 (12.21%) and V. parahaemolyticus 33 (5.45%). No V. cholerae strain was detected. One of the V. parahaemolyticus strains possessed the trh gene 7 (9.46%) while most (91.9%; 68/74) V. vulnificus isolates were of the E-type genotype. V. fluvialis virulence genes detected were stn (13.5%), hupO (10.4%) and vfpA (1.0%). 12.16% (9/74) of V. vulnificus strains exhibited a biotype 3 RFLP pattern. Conclusions: This is the first report of potentially pathogenic vibrios from healthy marine fish in the study area, and therefore a public health concern. PMID:28946684

Improvement of the quantitation method for the tdh+ Vibrio parahaemolyticus in molluscan shellfish based on most-probable- number, immunomagnetic separation, and loop-mediated isothermal amplification

PubMed Central

Escalante-Maldonado, Oscar; Kayali, Ahmad Y.; Yamazaki, Wataru; Vuddhakul, Varaporn; Nakaguchi, Yoshitsugu; Nishibuchi, Mitsuaki

2015-01-01

Vibrio parahaemolyticus is a marine microorganism that can cause seafood-borne gastroenteritis in humans. The infection can be spread and has become a pandemic through the international trade of contaminated seafood. Strains carrying the tdh gene encoding the thermostable direct hemolysin (TDH) and/or the trh gene encoding the TDH-related hemolysin (TRH) are considered to be pathogenic with the former gene being the most frequently found in clinical strains. However, their distribution frequency in environmental isolates is below 1%. Thus, very sensitive methods are required for detection and quantitation of tdh+ strains in seafood. We previously reported a method to detect and quantify tdh+ V. parahaemolyticus in seafood. This method consists of three components: the most-probable-number (MPN), the immunomagnetic separation (IMS) targeting all established K antigens, and the loop-mediated isothermal amplification (LAMP) targeting the tdh gene. However, this method faces regional issues in tropical zones of the world. Technicians have difficulties in securing dependable reagents in high-temperature climates where we found MPN underestimation in samples having tdh+ strains as well as other microorganisms present at high concentrations. In the present study, we solved the underestimation problem associated with the salt polymyxin broth enrichment for the MPN component and with the immunomagnetic bead-target association for the IMS component. We also improved the supply and maintenance of the dependable reagents by introducing a dried reagent system to the LAMP component. The modified method is specific, sensitive, quick and easy and applicable regardless of the concentrations of tdh+ V. parahaemolyticus. Therefore, we conclude this modified method is useful in world tropical, sub-tropical, and temperate zones. PMID:25914681

Antibiotic resistance and molecular typing among cockle (Anadara granosa) strains of Vibrio parahaemolyticus by polymerase chain reaction (PCR)-based analysis.

PubMed

Sahilah, A M; Laila, R A S; Sallehuddin, H Mohd; Osman, H; Aminah, A; Ahmad Azuhairi, A

2014-02-01

Genomic DNA of Vibrio parahaemolyticus were characterized by antibiotic resistance, enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) analysis. These isolates originated from 3 distantly locations of Selangor, Negeri Sembilan and Melaka (East coastal areas), Malaysia. A total of 44 (n = 44) of tentatively V. parahaemolyticus were also examined for the presence of toxR, tdh and trh gene. Of 44 isolates, 37 were positive towards toxR gene; while, none were positive to tdh and trh gene. Antibiotic resistance analysis showed the V. parahaemolyticus isolates were highly resistant to bacitracin (92%, 34/37) and penicillin (89%, 33/37) followed by resistance towards ampicillin (68%, 25/37), cefuroxime (38%, 14/37), amikacin (6%, 2/37) and ceftazidime (14%, 5/37). None of the V. parahaemolyticus isolates were resistant towards chloramphenicol, ciprofloxacin, ceftriaxone, enrofloxacin, norfloxacin, streptomycin and vancomycin. Antibiogram patterns exhibited, 9 patterns and phenotypically less heterogenous when compared to PCR-based techniques using ERIC- and RAPD-PCR. The results of the ERIC- and RAPD-PCR were analyzed using GelCompare software. ERIC-PCR with primers ERIC1R and ERIC2 discriminated the V. parahaemolyticus isolates into 6 clusters and 21 single isolates at a similarity level of 80%. While, RAPD-PCR with primer Gen8 discriminated the V. parahaemolyticus isolates into 11 clusters and 10 single isolates and Gen9 into 8 clusters and 16 single isolates at the same similarity level examined. Results in the presence study demonstrated combination of phenotypically and genotypically methods show a wide heterogeneity among cockle isolates of V. parahaemolyticus.

Characterization of Vibrio parahaemolyticus clinical strains from Maryland (2012-2013) and comparisons to a locally and globally diverse V. parahaemolyticus strains by whole-genome sequence analysis.

PubMed

Haendiges, Julie; Timme, Ruth; Allard, Marc W; Myers, Robert A; Brown, Eric W; Gonzalez-Escalona, Narjol

2015-01-01

Vibrio parahaemolyticus is the leading cause of foodborne illnesses in the US associated with the consumption of raw shellfish. Previous population studies of V. parahaemolyticus have used Multi-Locus Sequence Typing (MLST) or Pulsed Field Gel Electrophoresis (PFGE). Whole genome sequencing (WGS) provides a much higher level of resolution, but has been used to characterize only a few United States (US) clinical isolates. Here we report the WGS characterization of 34 genomes of V. parahaemolyticus strains that were isolated from clinical cases in the state of Maryland (MD) during 2 years (2012-2013). These 2 years saw an increase of V. parahaemolyticus cases compared to previous years. Among these MD isolates, 28% were negative for tdh and trh, 8% were tdh positive only, 11% were trh positive only, and 53% contained both genes. We compared this set of V. parahaemolyticus genomes to those of a collection of 17 archival strains from the US (10 previously sequenced strains and 7 from NCBI, collected between 1988 and 2004) and 15 international strains, isolated from geographically-diverse environmental and clinical sources (collected between 1980 and 2010). A WGS phylogenetic analysis of these strains revealed the regional outbreak strains from MD are highly diverse and yet genetically distinct from the international strains. Some MD strains caused outbreaks 2 years in a row, indicating a local source of contamination (e.g., ST631). Advances in WGS will enable this type of analysis to become routine, providing an excellent tool for improved surveillance. Databases built with phylogenetic data will help pinpoint sources of contamination in future outbreaks and contribute to faster outbreak control.

Characterization of Vibrio parahaemolyticus clinical strains from Maryland (2012–2013) and comparisons to a locally and globally diverse V. parahaemolyticus strains by whole-genome sequence analysis

PubMed Central

Haendiges, Julie; Timme, Ruth; Allard, Marc W.; Myers, Robert A.; Brown, Eric W.; Gonzalez-Escalona, Narjol

2015-01-01

Vibrio parahaemolyticus is the leading cause of foodborne illnesses in the US associated with the consumption of raw shellfish. Previous population studies of V. parahaemolyticus have used Multi-Locus Sequence Typing (MLST) or Pulsed Field Gel Electrophoresis (PFGE). Whole genome sequencing (WGS) provides a much higher level of resolution, but has been used to characterize only a few United States (US) clinical isolates. Here we report the WGS characterization of 34 genomes of V. parahaemolyticus strains that were isolated from clinical cases in the state of Maryland (MD) during 2 years (2012–2013). These 2 years saw an increase of V. parahaemolyticus cases compared to previous years. Among these MD isolates, 28% were negative for tdh and trh, 8% were tdh positive only, 11% were trh positive only, and 53% contained both genes. We compared this set of V. parahaemolyticus genomes to those of a collection of 17 archival strains from the US (10 previously sequenced strains and 7 from NCBI, collected between 1988 and 2004) and 15 international strains, isolated from geographically-diverse environmental and clinical sources (collected between 1980 and 2010). A WGS phylogenetic analysis of these strains revealed the regional outbreak strains from MD are highly diverse and yet genetically distinct from the international strains. Some MD strains caused outbreaks 2 years in a row, indicating a local source of contamination (e.g., ST631). Advances in WGS will enable this type of analysis to become routine, providing an excellent tool for improved surveillance. Databases built with phylogenetic data will help pinpoint sources of contamination in future outbreaks and contribute to faster outbreak control. PMID:25745421

Molecular Typing of Vibrio parahaemolyticus Strains Isolated from Mollusks in the North Adriatic Sea.

PubMed

Rahman, Mohammad Shamsur; Carraro, Roberta; Cardazzo, Barbara; Carraro, Lisa; Meneguolo, Davide Boscolo; Martino, Maria Elena; Andreani, Nadia Andrea; Bordin, Paola; Mioni, Renzo; Barco, Lisa; Novelli, Enrico; Balzan, Stefania; Fasolato, Luca

2017-08-01

Vibrio parahaemolyticus is an emerging foodborne pathogen in the Mediterranean, usually associated with shellfish consumption. The increase in the number of outbreaks in Europe is primarily associated with the global warming of the ocean that has a great impact on the spread and genetic selection of waterborne pathogens. The primary role of Italy in Europe's mollusk production, together with the fact that cases of infections with V. parahaemolyticus are not always notified to the European community, highlighted the necessity of acquiring new information about the epidemiological involvement of shellfish products. The aim of the study was to provide useful insights into the first steps of the Risk Assessment associated with V. parahaemolyticus through the molecular characterization of isolates from commercialized mollusks. A total of 102 strains identified as V. parahaemolyticus were investigated as part of a larger sampling (1-year survey) from several shellfish species collected from the Venice lagoon and the North Adriatic sea. All strains were characterized by multilocus sequence typing and tested for the presence of virulence genes (trh and tdh). The study of sampling/environmental factors and epidemiological analyses was performed to describe the behaviors of the different genetic populations. The population structure analysis highlighted three genetic clusters that could be subject to temperature selection during cold (≤15°C) and warm (>16°C) seasons. Moreover, other factors, such as molluscan species (clams/mussels), probably played a role in the distribution of genetic clusters. Although few strains carried the virulence factors (n = 6 trh + ), epidemiological links with clinical isolates and a local dissemination of some sequence types were underlined. This work provides a useful background on the genotype spread as a first step in the Hazard Identification in light of future climate changes.

Effects of a 5-day treatment with the UV-filter octyl-methoxycinnamate (OMC) on the function of the hypothalamo-pituitary-thyroid function in rats.

PubMed

Klammer, Holger; Schlecht, Christiane; Wuttke, Wolfgang; Schmutzler, Cornelia; Gotthardt, Inka; Köhrle, Josef; Jarry, Hubertus

2007-09-05

Octyl-methoxycinnamate (OMC) is one of the most frequently used UV-filters in sunscreens to protect the skin against the noxious influence of UV radiation. Recently, OMC was suspected to act as an "endocrine active chemical" (EAC) with estrogenic actions. While EACs have been investigated thoroughly for interference with reproductive function in mammalians, surprisingly little efforts have been made to investigate an interference of EACs with the hypothalamo-pituitary-thyroid (HPT) axis despite the expression of estrogen receptors in all parts of this axis. Therefore, we conducted an in vivo study with ovariectomised rats treated for 5 days with different doses of OMC or 17beta-estradiol (E2) as a control. Determined parameters comprised serum levels of TSH, T4 and T3, hypothalamic TRH mRNA expression, protein-expression of the sodium-iodide-symporter (NIS) and the TSH receptor and the activities of thyroid peroxidase (TPO) in the thyroid and the T3-responsive hepatic type I 5'deiodinase (Dio1) in the liver. While E2 did not affect TSH-, T4- or T3-levels, OMC caused a dose-dependent decrease of serum concentrations of all of these hormones. TRH expression remained unaffected, while in the thyroid, expression of the TSH receptor but not of NIS was stimulated by OMC. TPO activity was unaltered but Dio1 activity was reduced by OMC. Thus, our results demonstrate a non-estrogenic interference of OMC within the rodent HPT axis with inadequate feedback response to impaired thyroid hormone status, indicated by decreased serum thyroid hormone and hepatic Dio1 levels.

Mid-Term Vascular Safety of Renal Denervation Assessed by Follow-up MR Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmid, Axel, E-mail: axel.schmid@uk-erlangen.de; Schmieder, Raphael; Lell, Michael

Background/AimsRenal denervation (RDN) emerged as a treatment option for reducing blood pressure (BP) in patients with treatment-resistant hypertension (TRH). However, concerns have been raised regarding the incidence of late renal artery stenosis or thromboembolism after RDN. The goal of the current study was, therefore, to conduct a prospective clinical trial on the mid-term vascular integrity of the renal arteries and the perfusion of the renal parenchyma assessed by magnetic resonance imaging (MRI) in the follow-up after catheter-based RDN.MethodsIn our single-centre investigator initiated study, 51 patients with true TRH underwent catheter-based RDN using the Symplicity Flex{sup TM} catheter (Medtronic Inc., Palomore » Alto, CA). Follow-up MRI was performed at a median of 11 months (interquartile range 6–18 months) after RDN on a 1.5T MR unit. High-resolution MR angiography (MRA) and MRI results were compared to the baseline digital angiography of renal arteries obtained at time of RDN. In case of uncertainties (N = 2) catheter angiography was repeated.ResultsBoth office and 24-h ambulatory BP were significantly reduced 6 and 12 months after RDN. Renal function remained unchanged 6 and 12 months after RDN. In all patients, MRA excluded new or progression of pre-existing low grade renal artery stenosis as well as focal aneurysms at the sites of radiofrequency ablation. In none of the patients new segmental perfusion deficits in either kidney were detected on MRI.ConclusionsNo vascular or parenchymal complications after radiofrequency-based RDN were detected in 51 patients followed up by MRI.« less

[Repeated dose toxicity studies of taltirelin tetrahydrate(TA-0910) by oral administration to rats].

PubMed

Inui, T; Fujiwara, T; Susami, M; Hishida, N; Kuwamura, Y; Kuse, H; Kawai, Y; Kudow, S

1997-11-01

Four-, 13- and 52-week repeated dose toxicity studies of taltirelin tetrahydrate(TA-0910), a thyrotropin-releasing hormone(TRH) analogue, were carried out in rats. Through the three studies, TA-0910 solution was administered orally at doses of 3, 30 and 300 mg/kg/day. The animals receiving TA-0910 showed hyperlocomotion, grooming and wet dog shaking which were attributable to the central effects similar to those of TRH, but there was no death nor obvious deterioration of health caused by the treatment. Body weights decreased in males of 300 mg/kg group, and food consumption was on the upward trend in females in 300 mg/kg group. In 13- and 52-week studies, females receiving 300 mg/kg showed elongated estrous cycle, although it was not an evident change. Blood examinations revealed increases in erythrocyte count, hemoglobin and hematocrit in 300 mg/kg group. Reductions in serum(plasma) proteins and lipids, and drug-metabolizing enzyme activity of the liver were regarded as non-specific changes, as they were sporadic and slight in 300 mg/kg group. Salivary gland and adrenal weights increased in 300 mg/kg group. For the thyroid, weights increased in 300 mg/kg group in the 4- and 13-week studies, and increases of microfollicles and cell debris were observed microscopically in each treated group in the 52-week study. These changes seemed to be related with hormonal action of TA-0910, but the effects on animals were judged slight from plasma TSH and thyroid hormone levels after 4 weeks of dosing. The non-toxic dose was estimated to be 30 mg/kg/day, through the rat repeated dose toxicity studies. All the above changes were alleviated or abolished by 4-week recovery period.

Tripeptide amide L-pyroglutamyl-histidyl-L-prolineamide (L-PHP-thyrotropin-releasing hormone, TRH) promotes insulin-producing cell proliferation.

PubMed

Luo, LuGuang; Luo, John Z Q; Jackson, Ivor

2013-02-01

A very small tripeptide amide L-pyroglutamyl-L-histidyl-L-prolineamide (L-PHP, Thyrotropin-Releasing Hormone, TRH), was first identified in the brain hypothalamus area. Further studies found that L-PHP was expressed in pancreas. The biological role of pancreatic L-PHP is still not clear. Growing evidence indicates that L-PHP expression in the pancreas may play a pivotal role for pancreatic development in the early prenatal period. However, the role of L-PHP in adult pancreas still needs to be explored. L-PHP activation of pancreatic β cell Ca2+ flow and stimulation of β-cell insulin synthesis and release suggest that L-PHP involved in glucose metabolism may directly act on the β cell separate from any effects via the central nervous system (CNS). Knockout L-PHP animal models have shown that loss of L-PHP expression causes hyperglycemia, which cannot be reversed by administration of thyroid hormone, suggesting that the absence of L-PHP itself is the cause. L-PHP receptor type-1 has been identified in pancreas which provides a possibility for L-PHP autocrine and paracrine regulation in pancreatic function. During pancreatic damage in adult pancreas, L-PHP may protect beta cell from apoptosis and initiate its regeneration through signal pathways of growth hormone in β cells. L-PHP has recently been discovered to affect a broad array of gene expression in the pancreas including growth factor genes. Signal pathways linked between L-PHP and EGF receptor phosphorylation suggest that L-PHP may be an important factor for adult β-cell regeneration, which could involve adult stem cell differentiation. These effects suggest that L-PHP may benefit pancreatic β cells and diabetic therapy in clinic.

A Selective TSH Receptor Antagonist Inhibits Stimulation of Thyroid Function in Female Mice

PubMed Central

Neumann, Susanne; Nir, Eshel A.; Eliseeva, Elena; Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andrés E.

2014-01-01

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease. PMID:24169564

A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice.

PubMed

Neumann, Susanne; Nir, Eshel A; Eliseeva, Elena; Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andrés E; Gershengorn, Marvin C

2014-01-01

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.

Prevalence of Vibrio spp. in Retail Seafood in Berlin, Germany.

PubMed

Vu, Thi Thu Tra; Alter, Thomas; Huehn, Stephan

2018-04-01

This study was conducted to determine the prevalence of Vibrio spp. in retail seafood in Berlin, Germany. A total of 160 raw seafood samples from supermarkets and seafood shops, consisting of shrimp ( n = 80) and bivalves ( n = 80), were investigated for the presence of Vibrio spp. using the International Organization for Standardization ISO/TS 21872 method and a multiplex PCR. The overall prevalence of Vibrio spp. in retail seafood was 55% (95% CI: 47.2 to 62.8%). The prevalence of Vibrio spp. in shrimp was slightly higher than in bivalves (57.5 versus 52.5%); however, the difference was not statistically significant. Vibrio alginolyticus was the most prevalent species (35.6%), followed by Vibrio parahaemolyticus (27.5%), Vibrio cholerae (6.3%), and Vibrio vulnificus (0.6%). None of the V. parahaemolyticus ( n = 110) isolates encoded tdh/ trh genes, whereas all V. cholerae isolates ( n = 27) were lacking ctxA. Among the chilled samples ( n = 105), the prevalence of Vibrio spp. in unpacked samples was significantly higher than in packed samples ( P = 0.006). Among the packed samples ( n = 55), no significant difference in the prevalence of Vibrio spp. was observed between chilled or frozen products. The results of this study indicated a high prevalence of Vibrio spp. in retail seafood in Germany; positive samples were detected in all types of seafood investigated. The detection of tdh/ trh-negative V. parahaemolyticus isolates should not be neglected because of previous findings on pathogenic strains lacking these virulence markers. Even though thorough cooking might limit the risk of foodborne illness caused by Vibrio, potential cross-contamination during preparation or consumption of raw and undercooked seafood might represent a risk of Vibrio infections.

Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.

PubMed

Sliutz, G; Speiser, P; Schultz, A M; Spona, J; Zeillinger, R

1993-05-01

In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnus castus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.

HEAVY WATER PRODUCTION--DESCRIPTION OF PROCESS FOR THE PRODUCTION OF HYDROGEN AND WATER ENRICHED IN HEAVY WATER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chrones, J.

1951-05-29

A process which produces H/sub 2/ water enriched in D is described. Natural gas is oxidized to CO and H/sub 2/. These gases at 600 C reduce FeO in a fluidized bed regenerator, and the mixture of gases leaving the regenerator is burned in the boiler which supplies steam at 600 C. This steam reacts with iron dust from the regenerator to produce FeO and H/sub 2/ The deuterium is stripped from the H/sub 2/ with water in a catalytic exchange tower. The water thus enriched passes to an electrolytic step which concentrates D/sub 2/O to 99.8%. (T.R.H.)

Comparison of Naloxone and Thyrotropin-Releasing Hormone in the Treatment of Experimental Spinal Injury: Endogenous Opioids and Experimental Spinal Injury.

DTIC Science & Technology

1983-09-30

BETHESDA ND A I FADEN 38 SEP 83 UNCLASSIFIED MPR-2509 FG 6/15 NL EIihlllIEllllI EIIhlEEE~llllE E/I/I/IEE/IlhI EIIIEEEEEEIIE = " W lo 111.2.0 1111IL25 LA 11_L...blood flow related to the release of endogenous opioi 1 ,,;. I LCV;0,,;’ ’ W i-’, ; . .- I:I, opiate receptor antagonist naloxone improve,; 1,ou- spinal...34iorl-one (TRH), which acts in part as a physiologic antaT-, iL endogenous opicii’ -;’’,tems, also significantly" i -rov s bloo (l Fo., .-,nd netir

Prolactin-secreting pituitary adenoma in a man with gigantism: a case report.

PubMed

Peillon, F; Philippon, J; Brandi, A M; Fohanno, D; Laplane, D; Dubois, M P; Decourt, J

1979-12-01

A prolactin-secreting pituitary adenoma was removed trans-sphenoidally from a 37 years old man with gigantism (218 cm). Serum levels of prolactin (PRL) were elevated pre-operatively and decreased after administration of L-Dopa with no increase after TRH as is usually observed in PRL-secreting adenomas. Growth hormone (GH) and somatomedin serum levels were normal with no modification of GH after insulin hypoglycemia, oral glucose loading or L-Dopa. Morphological examination of the tumour demonstrated the presence of lactotrophs by light and electron microscopy and by immunofluorescense staining. No somatotrophs were found. In this unique case, the relationship between a PRL-secreting adenoma and gigantism is discussed.

[Renal sympathetic denervation (RSD): a new, non-pharmacologic therapeutic strategy for treatment-resistant hypertension (TRH). Report of the first procedure in Mexico].

PubMed

Gaspar Hernández, Jorge; Eid-Lidt, Guering; Payró Ramírez, Gerardo; Ricalde Alcocer, Alejandro; Martínez Ríos, Marco A

2012-01-01

A patient with resistant hypertension successfully treated with sympathetic renal denervation (SRD) is reported. This novel therapy is based on the partial ablation of the renal nerves by applying radiofrequency to the luminal surface of the renal arteries using vascular catheterization techniques. This first case performed in Mexico has two particular features: (i) an electrophysiology ablation catheter was employed due to the unavailability of the system specifically designed for SDR, and (ii) under current denervation protocols, the anatomical complexity of the targeted renal arteries would have excluded our patient from this procedure and thus deprived her of the benefit provided.

ELECTRIC PULSE GENERATOR

DOEpatents

Buntenbach, R.W.

1959-06-01

S>An electro-optical apparatus is described which produces electric pulses in programmed sequences at times and durations controlled with great accuracy. An oscilloscope CRT is supplied with signals to produce a luminous spot moving in a circle. An opaque mask with slots of variable width transmits light from the spot to a photoelectric transducer. For shorter pulse decay times a CRT screen which emits UV can be used with a UVtransmitting filter and a UV- sensitive photoelectric cell. Pulses are varied by changing masks or by using masks with variable slots. This device may be used in multiple arrangements to produce other pulse aT rangements, or it can be used to trigger an electronic pulse generator. (T.R.H.)

Assessment of thyroid function in dogs with low plasma thyroxine concentration.

PubMed

Diaz Espineira, M M; Mol, J A; Peeters, M E; Pollak, Y W E A; Iversen, L; van Dijk, J E; Rijnberk, A; Kooistra, H S

2007-01-01

Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Chronic glue sniffing with transient central hypothyroidism and hypergonadotropism.

PubMed

Chen, Hua-Fen; Chen, Shwe-Winn; Chen, Peter; Su, Mei-Chin; See, Ting-Ting; Lee, Hsin-Yu

2003-12-01

Neuropsychiatric, gastrointestinal and muscular disorders associated with glue sniffing have been widely reported, but endocrinologic abnormalities of glue exposure are rarely mentioned in the literature. We report a 26-year old male patient, a chronic glue sniffer, who presented with weakness of both lower limbs. On physical examination, he had reduced muscle strength of his 4 limbs, especially in his lower limbs. Laboratory examination revealed hypokalemia with hyperchloremic metabolic acidosis. His thyroid function showed low TSH, T4, T3, free T4 and reverse T3 level. Other pituitary functions were normal apart from high FSH and LH level. TSH response to TRH stimulation was normal, but there was impaired T3 response to TRH. MRI of pituitary showed no significant changes. He continued glue sniffing after discharge. He repeatedly came to our hospital for recurrent hypokalemic paralysis. His serum T4 and free T4 level were low when he had certain amount of glue sniffing and it returned to normal after he stopped sniffing or sniffed less amount of glue. His serum T3 concentrations were normal most of the times thereafter. His FSH and LH level were persistently elevated, even after he did not sniff glue for 2 weeks. Low free T4, TSH and reverse T3 level associated with glue sniffing in our patient were compatible with central hypothyroidism. Toluene, a neurotoxic organic solvent, is present in glues. Being highly lipophilic, it can easily enter and is retained within the lipid-rich nervous system after being inhaled. Like other organic solvents, toluene has been shown to affect dopaminergic and adrenergic turnover within various parts of the brain. The effects on these neurotransmitters could lead to abnormal secretion of pituitary hormones resulting in transient central hypothyroidism and abnormal gonadotropin levels. Long-term harmful effect of central hypothyroidism and chronic influence of abnormal gonadotropins to reproduction function needs further observation.

Pharmacology of bovine and human thyrotropin: an historical perspective.

PubMed

Robbins, J

1999-05-01

Before the induction of a brief period of hypothyroidism became the standard method for inducing 131I uptake in thyroid cancer diagnosis and therapy, several other methods were explored and used. At the dawn of this new era of recombinant human thyrotropin (TSH) it is of interest to reflect briefly on some of this work. Partially purified bovine TSH (bTSH) was supplied for many years by the Armour Company as Thytropar for intramuscular injection and was first used in thyroid cancer 50 years ago at the Montefiore Hospital and at the Memorial Sloan Kettering Cancer Center in New York City. Most of the patients were already hypothyroid and bTSH induced further 131I uptake in only a few. Experience over the next 30 years revealed frequent allergic reactions, occasionally serious ones, and in 1961 it was shown that prolonged use could result in resistance to both bTSH and human TSH. bTSH was, therefore, reserved for thyroid cancer patients unable to increase endogenous TSH when hypothyroid. bTSH also was used widely as a test to distinguish between hypothyroidism caused by thyroid or pituitary failure until it was replaced by thyrotropin-releasing hormone (TRH). In a few studies, TRH was also tested as an adjuvant to increase endogenous TSH and thus help to stimulate function in thyroid cancer, but this attracted little interest. Prolonged hypothyroidism, enhanced by antithyroid drugs, was used early on, but this very effective stimulant of thyroid cancer function was, for multiple reasons, discarded. Beginning interest 15 to 25 years ago in obtaining TSH from human pituitary glands, a byproduct of growth hormone production, was interrupted when this product was found to risk development of Creutzfeld-Jakob disease. Recombinant human TSH, a safe and effective substitute, is now ready for widespread use and development in thyroid cancer management.

Relationship Between the Thyroid Axis and Alcohol Craving

PubMed Central

Aoun, Elie G.; Lee, Mary R.; Haass-Koffler, Carolina L.; Swift, Robert M.; Addolorato, Giovanni; Kenna, George A.; Leggio, Lorenzo

2015-01-01

Aims: A few studies have suggested a relationship between thyroid hormones and alcohol dependence (AD) such as a blunted increase of thyroid stimulating hormone (TSH) in response to thyrotropin-releasing hormone (TRH), lower levels of circulating free triiodothyronine (fT3) and free thyroxine (fT4) levels and down regulation of the TRH receptors. The current study aimed to explore the relationship between the hormones of the thyroid axis and alcohol-seeking behaviors in a sample of alcohol-dependent patients. Methods: Forty-two treatment-seeking alcohol-dependent individuals enrolled in a 12-week treatment study were considered. The Timeline Follow Back (TLFB) was used to assess the number of drinks consumed during the 12-week period. Blood levels of thyroid hormones (TSH, fT3 and fT4) were measured prior to and at the end of treatment. Questionnaires were administered to evaluate craving for alcohol [Penn Alcohol Craving Scale (PACS) and the Obsessive Compulsive Drinking Scale (OCDS) and its two subscales ODS for obsessions and CDS for compulsions] as well as anxiety [State and Trait Inventory (STAI)], depression [the Zung Self-Rating Depression Scale (Zung)] and aggression [the Aggressive Questionnaire (AQ)]. Results: At baseline, we found significant positive correlations between fT3 and OCDS (r = 0.358, P = 0.029) and CDS (r = 0.405, P = 0.013) and negative correlations between TSH levels and STAI (r = −0.342, P = 0.031), and AQ (r = −0.35, P = 0.027). At the end of the 12-week study period, abstinent patients had a greater change in TSH than those who relapsed (−0.4 vs. −0.25, F(1,24) = 5.4, P = 0.029). Conclusion: If confirmed in larger samples, these findings could suggest that the thyroid axis might represent a biomarker of alcohol craving and drinking. PMID:25433251

Prevalence and Antimicrobial Susceptibility of Vibrio parahaemolyticus Isolated from Short Mackerels (Rastrelliger brachysoma) in Malaysia

PubMed Central

Tan, Chia W.; Malcolm, Tan T. H.; Kuan, Chee H.; Thung, Tze Y.; Chang, Wei S.; Loo, Yuet Y.; Premarathne, Jayasekara M. K. J. K.; Ramzi, Othman B.; Norshafawatie, Mohd F. S.; Yusralimuna, Nordin; Rukayadi, Yaya; Nakaguchi, Yoshitsugu; Nishibuchi, Mitsuaki; Radu, Son

2017-01-01

Numerous prevalence studies and outbreaks of Vibrio parahaemolyticus infection have been extensively reported in shellfish and crustaceans. Information on the quantitative detection of V. parahaemolyticus in finfish species is limited. In this study, short mackerels (Rastrelliger brachysoma) obtained from different retail marketplaces were monitored with the presence of total and pathogenic strains of V. parahaemolyticus. Out of 130 short mackerel samples, 116 (89.2%) were detected with the presence of total V. parahaemolyticus and microbial loads of total V. parahaemolyticus ranging from <3 to >105 MPN/g. Prevalence of total V. parahaemolyticus was found highest in wet markets (95.2%) followed by minimarkets (89.1%) and hypermarkets (83.3%). Pathogenic V. parahaemolyticus strains (tdh+ and/or trh+) were detected in 16.2% (21 of 130) of short mackerel samples. The density of tdh+ V. parahaemolyticus strains were examined ranging from 3.6 to >105 MPN/g and microbial loads of V. parahaemolyticus strains positive for both tdh and trh were found ranging from 300 to 740 MPN/g. On the other hand, antibiotic susceptibility profiles of V. parahaemolyticus strains isolated from short mackerels were determined through disc diffusion method in this study. Assessment of antimicrobial susceptibility profile of V. parahaemolyticus revealed majority of the isolates were highly susceptible to ampicillin sulbactam, meropenem, ceftazidime, and imipenem, but resistant to penicillin G and ampicillin. Two isolates (2.99%) exhibited the highest multiple antibiotic resistance (MAR) index value of 0.41 which shown resistance to 7 antibiotics. Results of the present study demonstrated that the occurrence of pathogenic V. parahaemolyticus strains in short mackerels and multidrug resistance of V. parahaemolyticus isolates could be a potential public health concerns to the consumer. Furthermore, prevalence data attained from the current study can be further used to develop a microbial risk assessment model to estimate health risks associated with the consumption of short mackerels contaminated with pathogenic V. parahaemolyticus. PMID:28659901

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice.

PubMed

Cao, Xin-Yuan; Hua, Xu; Xiong, Jian-Wei; Zhu, Wen-Ting; Zhang, Jun; Chen, Ling

2018-01-01

Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone ( GnRH ) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function.

Impact of Triclosan on Female Reproduction through Reducing Thyroid Hormones to Suppress Hypothalamic Kisspeptin Neurons in Mice

PubMed Central

Cao, Xin-Yuan; Hua, Xu; Xiong, Jian-Wei; Zhu, Wen-Ting; Zhang, Jun; Chen, Ling

2018-01-01

Triclosan (TCS), a broad-spectrum antimicrobial agent, is widely used in clinical settings and various personal care products. The aim of this study was to evaluate the influence of TCS on reproductive endocrine and function. Here, we show that the exposure of adult female mice to 10 or 100 mg/kg/day TCS caused prolongation of diestrus, and decreases in antral follicles and corpora lutea within 2 weeks. TCS mice showed decreases in the levels of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and progesterone, and gonadotrophin-releasing hormone (GnRH) mRNA with the lack of LH surge and elevation of prolactin (PRL). TCS mice had lower kisspeptin immunoreactivity and kiss1 mRNA in anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Moreover, the estrogen (E2)-enhanced AVPV-kisspeptin expression was reduced in TCS mice. In addition, the serum thyroid hormones (triiodothyronine (T3) and thyroxine (T4)) in TCS mice were reduced with increases in levels of thyroid stimulating hormone (TSH) and thyroid releasing hormone (TRH). In TCS mice, the treatment with Levothyroxine (L-T4) corrected the increases in PRL, TSH and TRH; the administration of L-T4 or type-2 dopamine receptors agonist quinpirole inhibiting PRL release could rescue the decline of kisspeptin expression in AVPV and ARC; the treatment with L-T4, quinpirole or the GPR45 agonist kisspeptin-10 recovered the levels of serum LH and FSH and progesterone, and GnRH mRNA. Furthermore, TCS mice treated with L-T4 or quinpirole resumed regular estrous cycling, follicular development and ovulation. Together, these results indicate that exposing adult female mice to TCS (≥10 mg/kg) reduces thyroid hormones causing hyperprolactinemia that then suppresses hypothalamic kisspeptin expression, leading to deficits in reproductive endocrine and function. PMID:29403355

The reliability of a single protocol to determine endothelial, microvascular and autonomic functions in adolescents.

PubMed

Bond, Bert; Williams, Craig A; Barker, Alan R

2017-11-01

Impairments in macrovascular, microvascular and autonomic function are present in asymptomatic youths with clustered cardiovascular disease risk factors. This study determines the within-day reliability and between-day reliability of a single protocol to non-invasively assess these outcomes in adolescents. Forty 12- to 15-year-old adolescents (20 boys) visited the laboratory in a fasted state on two occasions, approximately 1 week apart. One hour after a standardized cereal breakfast, macrovascular function was determined via flow-mediated dilation (FMD). Heart rate variability (root mean square of successive R-R intervals; RMSSD) was determined from the ECG-gated ultrasound images acquired during the FMD protocol prior to cuff occlusion. Microvascular function was simultaneously quantified as the peak (PRH) and total (TRH) hyperaemic response to occlusion in the cutaneous circulation of the forearm via laser Doppler imaging. To address within-day reliability, a subset of twenty adolescents (10 boys) repeated these measures 90 min afterwards on one occasion. The within-day typical error and between-day typical error expressed as a coefficient of variation of these outcomes are as follows: ratio-scaled FMD, 5·1% and 10·6%; allometrically scaled FMD, 4·4% and 9·4%; PRH, 11% and 13·3%; TRH, 29·9% and 23·1%; and RMSSD, 17·6% and 17·6%. The within- and between-day test-retest correlation coefficients for these outcomes were all significant (r > 0·54 for all). Macrovascular, microvascular and autonomic functions can be simultaneously and non-invasively determined in adolescents using a single protocol with an appropriate degree of reproducibility. Determining these outcomes may provide greater understanding of the progression of cardiovascular disease and aid early intervention. © 2016 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Prevalence and Antimicrobial Susceptibility of Vibrio parahaemolyticus Isolated from Short Mackerels (Rastrelliger brachysoma) in Malaysia.

PubMed

Tan, Chia W; Malcolm, Tan T H; Kuan, Chee H; Thung, Tze Y; Chang, Wei S; Loo, Yuet Y; Premarathne, Jayasekara M K J K; Ramzi, Othman B; Norshafawatie, Mohd F S; Yusralimuna, Nordin; Rukayadi, Yaya; Nakaguchi, Yoshitsugu; Nishibuchi, Mitsuaki; Radu, Son

2017-01-01

Numerous prevalence studies and outbreaks of Vibrio parahaemolyticus infection have been extensively reported in shellfish and crustaceans. Information on the quantitative detection of V. parahaemolyticus in finfish species is limited. In this study, short mackerels ( Rastrelliger brachysoma ) obtained from different retail marketplaces were monitored with the presence of total and pathogenic strains of V. parahaemolyticus . Out of 130 short mackerel samples, 116 (89.2%) were detected with the presence of total V. parahaemolyticus and microbial loads of total V. parahaemolyticus ranging from <3 to >10 5 MPN/g. Prevalence of total V. parahaemolyticus was found highest in wet markets (95.2%) followed by minimarkets (89.1%) and hypermarkets (83.3%). Pathogenic V. parahaemolyticus strains ( tdh + and/or trh +) were detected in 16.2% (21 of 130) of short mackerel samples. The density of tdh + V. parahaemolyticus strains were examined ranging from 3.6 to >10 5 MPN/g and microbial loads of V. parahaemolyticus strains positive for both tdh and trh were found ranging from 300 to 740 MPN/g. On the other hand, antibiotic susceptibility profiles of V. parahaemolyticus strains isolated from short mackerels were determined through disc diffusion method in this study. Assessment of antimicrobial susceptibility profile of V. parahaemolyticus revealed majority of the isolates were highly susceptible to ampicillin sulbactam, meropenem, ceftazidime, and imipenem, but resistant to penicillin G and ampicillin. Two isolates (2.99%) exhibited the highest multiple antibiotic resistance (MAR) index value of 0.41 which shown resistance to 7 antibiotics. Results of the present study demonstrated that the occurrence of pathogenic V. parahaemolyticus strains in short mackerels and multidrug resistance of V. parahaemolyticus isolates could be a potential public health concerns to the consumer. Furthermore, prevalence data attained from the current study can be further used to develop a microbial risk assessment model to estimate health risks associated with the consumption of short mackerels contaminated with pathogenic V. parahaemolyticus .

Detection of Total and Pathogenic Vibrio parahaemolyticus in Shellfish Growing along the South Yellow Sea and the East China Sea.

PubMed

Han, Feng; Gu, Run-Run; Shen, Xiao-Sheng; Chen, Yuan-Ge; Tian, Liang-Liang; Zhou, Wei-Feng; Cai, You-Qiong

2017-10-17

This study was conducted to monitor the densities of total and pathogenic Vibrio parahaemolyticus in 300 samples of nine shellfish species harvested from the coasts of the South Yellow Sea and the East China Sea (N 23° to 34°, E 116° to 124°), People's Republic of China, between May and October 2015. Total V. parahaemolyticus densities were measured, and V. parahaemolyticus isolates were biochemically identified with probes for the thermostable direct hemolysin gene (tdh) and the thermostable direct hemolysin-related hemolysin gene (trh). We found that 202 of the 300 samples were positive for V. parahaemolyticus from all the sites: 58 of the 100 samples from the Fujian province, 71 of the 100 samples from the Zhejiang province, and 73 of the 100 samples from the Jiangsu province. In most (170) of the 300 samples, V. parahaemolyticus densities were 0.3 to 10 most probable number (MPN)/g; five lots exceeded 110 MPN/g, and two lots were estimated at 110 MPN/g. Among the 202 V. parahaemolyticus strains, only one was trh positive. Densities of V. parahaemolyticus in these shellfish were temperature dependent, with highest densities in June and July. Among the nine mollusk species, V. parahaemolyticus was most abundant in the agemaki clam (Sinonovacula constricta). The highest and lowest V. parahaemolyticus prevalences were found in oriental cyclina (Cyclina sinensis, 93.8%) and mussels (Mytilus edulis, 28.1%), respectively. Overall, although V. parahaemolyticus is widely distributed in marine environments, the density of V. parahaemolyticus was low and the prevalence of the main virulence factor was very low in shellfish along the coasts of the South Yellow Sea and East China Sea, which is important from a public health perspective. Data presented here will be useful for correlational research and can be utilized for developing risk management plans that establish food safety guidelines for V. parahaemolyticus in Chinese shellfish.

DRY FLUORINE SEPARATION METHOD

DOEpatents

Seaborg, G.T.; Gofman, J.W.; Stoughton, R.W.

1959-05-19

Preparation and separation of U/sup 233/ by irradiation of ThF/sub 4/ is described. During the neutron irradiation to produce Pa/sup 233/ a fluorinating agent such as HF, F/sub 2/, or HF + F/sub 2/ is passed through the ThF/sub 4/ powder to produce PaF/sub 5/. The PaF/sub 5/, being more volatile, is removed as a gas and allowed to decay radioactively to U/sup 233/ fluoride. A batch procedure in which ThO/sub 2/ or Th metal is irradiated and fluorinated is suggested. Some Pa and U fluoride volatilizes away. Then the remainder is fluorinated with F/sub 2/ to produce very volatile UF/sub 6/ which is recovered. (T.R.H.)

Neuromodulation of hypoglossal motoneurons: cellular and developmental mechanisms.

PubMed

Bayliss, D A; Viana, F; Talley, E M; Berger, A J

1997-11-01

Hypoglossal motoneurons (HMs) in the caudal brainstem have a respiratory-related activity pattern and contribute to control of upper airway resistance. In this review, we focus primarily on signalling mechanisms utilized by neurotransmitters to enhance HM excitability. In particular, we consider: (1) the membrane depolarization induced by a number of different putative transmitters [thyrotropin-releasing hormone (TRH), serotonin (5-HT), norepinephrine (NE)]; and (2) the inhibition of a calcium-dependent spike after hyperpolarization (AHP) by 5-HT and its effect on firing behavior. Potential functional consequences on HM behavior of these different neurotransmitter effects is discussed. In addition, we describe postnatal changes in transmitter effects and suggest potential cellular mechanisms to explain those developmental changes. Most of the data discussed are derived from in vitro electrophysiological recordings performed in preparations from neonatal and adult rats.

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure.

PubMed

Pivnick, E K; Burstein, S; Wilroy, R S; Kaufman, R A; Ward, J C

1991-12-15

A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.

METHOD FOR DECONTAMINATION OF REACTOR SOLUTIONS

DOEpatents

Maraman, W.J.; Baxman, H.R.; Baker, R.D.

1959-05-01

A process for U recovery from phosphate fuel solutions is described. To fuel solution drawn from the reactor is added Fe(NO/sub 3/)/sub 3/ which destroys the U complex and forms ferric phosphate complex. The UO/sub 2/(NO/sub 3/)/sub 2/ formed is extracted into TBP-kerosene in a countercurrent column. The TBP contalning UO/sub 2/(NO/sub 3/)/sub 2/ is further purified by an aqueous Al(NO/ sub 3/)/sub 3/ scrub solution. The pregnant solution then goes to an H/sub 3/PO/ sub 4/ stripping and kerosene washing column. The H/sub 3/PO/sub 4/--uranyl phosphate solution is separated at the bottom and boiled to remove HNO/sub 3/ then diluted to fuel solution make-up strength. (T.R.H.)

The environmental contaminant tributyltin leads to abnormalities in different levels of the hypothalamus-pituitary-thyroid axis in female rats.

PubMed

Andrade, Marcelle Novaes; Santos-Silva, Ana Paula; Rodrigues-Pereira, Paula; Paiva-Melo, Francisca Diana; de Lima Junior, Niedson Correa; Teixeira, Mariana Pires; Soares, Paula; Dias, Glaecir Roseni Munstock; Graceli, Jones Bernardes; de Carvalho, Denise Pires; Ferreira, Andrea Claudia Freitas; Miranda-Alves, Leandro

2018-06-11

Tributyltin is a biocide used in nautical paints, aiming to reduce fouling of barnacles in ships. Despite the fact that many effects of TBT on marine species are known, studies in mammals have been limited, especially those evaluating its effect on the function of the hypothalamus-pituitary-thyroid (HPT) axis. The aim of this study was to investigate the effects of subchronic exposure to TBT on the HPT axis in female rats. Female Wistar rats received vehicle, TBT 200 ng kg -1 BW d -1 or 1000 ng kg -1 BW d -1 orally by gavage for 40 d. Hypothalamus, pituitary, thyroid, liver and blood samples were collected. TBT200 and TBT1000 thyroids showed vacuolated follicular cells, with follicular hypertrophy and hyperplasia. An increase in epithelial height and a decrease in the thyroid follicle and colloid area were observed in TBT1000 rats. Moreover, an increase in the epithelium/colloid area ratio was observed in both TBT groups. Lower TRH mRNA expression was observed in the hypothalami of TBT200 and TBT1000 rats. An increase in Dio1 mRNA levels was observed in the hypothalamus and thyroid in TBT1000 rats only. TSH serum levels were increased in TBT200 rats. In TBT1000 rats, there was a decrease in total T4 serum levels compared to control rats, whereas T3 serum levels did not show significant alterations. We conclude that TBT exposure can promote critical abnormalities in the HPT axis, including changes in TRH mRNA expression and serum TSH and T4 levels, in addition to affecting thyroid morphology. These findings demonstrate that TBT disrupts the HPT axis. Additionally, the changes found in thyroid hormones suggest that TBT may interfere with the peripheral metabolism of these hormones, an idea corroborated by the observed changes in Dio1 mRNA levels. Therefore, TBT exposition might interfere not only with the thyroid axis but also with thyroid hormone metabolism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transmission of influenza A viruses between pigs and people, Iowa, 2002-2004.

PubMed

Terebuh, Pauline; Olsen, Christopher W; Wright, Jennifer; Klimov, Alexander; Karasin, Alexander; Todd, Karla; Zhou, Hong; Hall, Henrietta; Xu, Xiyan; Kniffen, Tim; Madsen, David; Garten, Rebecca; Bridges, Carolyn B

2010-11-01

Triple-reassortant (tr) viruses of human, avian, and swine origin, including H1N1, H1N2, and H3N2 subtypes, emerged in North American swine herds in 1998 and have become predominant. While sporadic human infections with classical influenza A (H1N1) and with tr-swine influenza viruses have been reported, relatively few have been documented in occupationally exposed swine workers (SW). We conducted a 2-year (2002-2004) prospective cohort study of transmission of influenza viruses between pigs and SW from a single pork production company in Iowa. Respiratory samples were collected and tested for influenza viruses from SW and from pigs under their care through surveillance for influenza-like illnesses (ILI). Serial blood samples from study participants were tested by hemagglutination inhibition (HI) for antibody seroconversion against human and swine influenza viruses (SIV), and antibody seroprevalence was compared to age-matched urban Iowa blood donors. During the first year, 15 of 88 SW had ILI and were sampled; all were culture-negative for influenza. During the second year, 11 of 76 SW had ILI and were sampled; one was culture-positive for a human seasonal H3N2 virus. Among 20 swine herd ILI outbreaks sampled, influenza A virus was detected by rRT-PCR from 17 with 11 trH1N1 and five trH3N2 virus isolates cultured. During both years, HI geometric mean titers were significantly higher among SW compared to blood donor controls for three SIV: classical swine Sw/WI/238/97 (H1N1), tr Sw/IN/9K035/99 (H1N2), and trSw/IA/H02NJ56371/02 (H1N1)] (P < 0·0001). SW had serologic evidence for infection with both swine and human influenza viruses and were exposed to diverse influenza virus strains circulating in pigs. Influenza virus surveillance among pigs and SW should be encouraged to better understand cross-species transmission and diversity of influenza viruses at the human-swine interface. © 2010 Blackwell Publishing Ltd.

Evaluation of short purification cycles in naturally contaminated Mediterranean mussels (Mytilus galloprovincialis) harvested in Sardinia (Italy).

PubMed

Sferlazzo, Giovanni; Meloni, Domenico; Lamon, Sonia; Marceddu, Marta; Mureddu, Anna; Consolati, Simonetta Gianna; Pisanu, Margherita; Virgilio, Sebastiano

2018-09-01

The aim of the present study was to investigate the effect of short purification cycles on the safety of naturally contaminated Mytilus galloprovincialis from harvesting areas of the Gulf of Olbia (Sardinia, Italy). Samples from ten batches of mussels were collected before, during and after purification treatment at two purification centres (A-B). All the samples were analysed for Escherichia coli and Salmonella spp according to Council Regulation (EC) 2285/2015. Detection and enumeration of Vibrio spp were performed according to previously published methods. Presumptive identification of Vibrio spp isolates were performed by means of conventional biochemical tests and polymerase chain reaction. The presence of Hepatitis A virus was detected by nested reverse transcriptase-polymerase chain reaction. Environmental parameters (water temperature and salinity) were also recorded. The results of Escherichia coli counts showed the overall efficacy of the short purification cycles; a purification cycle of 8 h led to a rapid decline in the concentration. The decrease in Escherichia coli counts does not correlate with the presence of naturally occurring vibrios, the decline of which occurs at an even slower rate. The average contamination levels for Vibrio spp before purification were 8.20 ± 0.47 and 7.99 ± 0.62 Log 10  CFU/g in samples collected at purification plants A and B, respectively. After purification, the average contamination levels were 8.10 ± 0.60 Log 10  CFU/g at purification plant A and 7.85 ± 0.57 Log 10  CFU/g at purification plant B. The contaminated samples revealed the presence of Vibrio alginolyticus (n=21), Vibrio fluvialis (n=12), Vibrio cholerae (n=4), Vibrio parahaemolyticus (n=2) and Vibrio vulnificus (n=1). The Vibrio parahaemolyticus isolates carried the tdh or the trh genes. None of the isolates was tdh+/trh+. Salmonella spp and Hepatitis A virus were not detected. The adoption of short purification cycles for Mytilus galloprovincialis in the presence of pathogenic vibrios might not be sufficient to guarantee the safety of consumers. Copyright © 2018 Elsevier Ltd. All rights reserved.

Recombinant expression, isolation, and proteolysis of extracellular matrix-secreted phosphoprotein-24 kDa.

PubMed

Murray, Elsa J Brochmann; Murray, Samuel S; Simon, Robert; Behnam, Keyvan

2007-01-01

Secreted phosphoprotein-24 kDa (spp24) is an extracellular matrix protein first cloned from bone. Bovine spp24 is transcribed as a 203 amino acid residue protein that undergoes cleavage of a secretory peptide to form the mature protein (spp24, residues 24 to 203). While not osteogenic itself, spp24 is degraded to a pro-osteogenic protein, spp18.5, in bone. Both spp18.5 and spp24 contain a cyclic TRH1 (TGF-beta receptor II homology-1) domain similar to that found in the receptor itself and in fetuin. A synthetic peptide corresponding to the TRH1 domain of spp18.5 and spp24 specifically binds BMP-2 and enhances the rate and magnitude of BMP-2-induced ectopic bone formation in vivo. The parental protein, spp24, exhibits a high affinity for bone and mineral complexes, but its abundance there is low, suggesting that it is rapidly degraded. The availability of recombinant spp24 and its degradation products would facilitate the elucidation of their structure:function relationships. We describe here the expression of His(6)-tagged bovine spp24 (residues 24 to 203) in E. coli, its purification by high-resolution IMAC (immobilized metal affinity chromatography), and the characterization of the full-length recombinant 21.5 kDa protein and its two major 16 kDa and 14.5 kDa degradation products (spp24, residues 24 to 157, and spp24, residues 24 to 143) by mass spectroscopy. The recombinant spp24 protein was resistant to proteolysis by MC3T3-E1 osteoblastic cell extracts in the absence of calcium; however, in the presence of 4 mM Ca, it can undergo essentially complete proteolysis to small peptides, bypassing the 16 kDa and 14.5 kDa intermediates. This confirms the proteolytic susceptibility of spp24. It also suggests that the levels of spp24 in bone may be regulated, in part, by calcium-dependent proteolysis mediated by osteoblastic cells.

Nonequilibrium electroweak baryogenesis at preheating after inflation

NASA Astrophysics Data System (ADS)

García-Bellido, Juan; Grigoriev, Dmitri; Kusenko, Alexander; Shaposhnikov, Mikhail

1999-12-01

We present a novel scenario for baryogenesis in a hybrid inflation model at the electroweak scale, in which the standard model Higgs field triggers the end of inflation. One of the conditions for successful baryogenesis, the departure from thermal equilibrium, is naturally achieved at the stage of preheating after inflation. The inflaton oscillations induce large occupation numbers for long-wavelength configurations of the Higgs and gauge fields, which leads to a large rate of sphaleron transitions. We estimate this rate during the first stages of reheating and evaluate the amount of baryons produced due to a particular type of higher-dimensional CP violating operator. The universe thermalizes through fermion interactions, at a temperature below critical, Trh<~100 GeV, preventing the wash-out of the produced baryon asymmetry. Numerical simulations in 1+1 dimensions support our theoretical analyses.

Congenital hypothyroidism of dogs and cats: a review.

PubMed

Bojanic, K; Acke, E; Jones, B R

2011-05-01

Congenital hypothyroidism is a rare and underdiagnosed congenital endocrine disorder in dogs and cats and the true incidence is unknown. The disorder may cause a range of clinical signs depending on the primary defect, which affect production of thyroid hormones; some cases present when adult. Hallmark clinical signs of congenital hypothyroidism are mental impairment and skeletal developmental abnormalities, resulting in disproportionate dwarfism; goitre may or may not be present. Documented causes of congenital hypothyroidism in dogs include deficiency of, or unresponsiveness to, thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH), thyroid dysgenesis, dyshormonogenesis and iodine deficiency. In cats, TSH unresponsiveness, thyroid dysgenesis, dyshormonogenesis and iodine deficiency have been confirmed. Adequate replacement therapy results in a successful outcome in the majority of cases, especially when started early in life, as permanent developmental abnormalities can be prevented. This review describes reported cases in dogs and cats, diagnostic investigation, and recommendations for treatment.

Vibrio parahaemolyticus: a review on the pathogenesis, prevalence, and advance molecular identification techniques

PubMed Central

Letchumanan, Vengadesh; Chan, Kok-Gan; Lee, Learn-Han

2014-01-01

Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that is found in estuarine, marine and coastal environments. V. parahaemolyticus is the leading causal agent of human acute gastroenteritis following the consumption of raw, undercooked, or mishandled marine products. In rare cases, V. parahaemolyticus causes wound infection, ear infection or septicaemia in individuals with pre-existing medical conditions. V. parahaemolyticus has two hemolysins virulence factors that are thermostable direct hemolysin (tdh)-a pore-forming protein that contributes to the invasiveness of the bacterium in humans, and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. In addition, the bacterium is also encodes for adhesions and type III secretion systems (T3SS1 and T3SS2) to ensure its survival in the environment. This review aims at discussing the V. parahaemolyticus growth and characteristics, pathogenesis, prevalence and advances in molecular identification techniques. PMID:25566219

Thyroid Hormones and Growth in Health and Disease

PubMed Central

Tarım, Ömer

2011-01-01

Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared. PMID:21750631

A case of methimazole-induced hypothyroidism in a patient with endemic goiter: effects of endogenous TSH hyperstimulation after discontinuation of the drug.

PubMed

Messina, M; Manieri, C; Spagnuolo, F; Sardi, E; Allegramente, L; Monaco, A; Ciccarelli, E

1989-04-01

Serum thyroid hormone and TSH concentrations were monitored in a patient with multinodular endemic goiter and severe methimazole (MMI) induced hypothyrodism up to 190 days after drug withdrawal. Serum concentrations of TT3, TT4 and TSH returned to normal values at the 6th., the 140th, and the 120th. day respectively. Within the first 20 days after MMI withdrawal the increase of serum T3 levels was correlated with the observed decrease of serum TSH concentrations. Successively T3 values decreased and T4 levels progressively increased. Six months after MMI withdrawal basal serum TSH concentration was normal while an exaggerated response to TRH was observed. We think that this peculiar hormone pattern is due to iodine depletion. In this case TSH hyperstimulation increases predominantly T3 secretion demonstrating the reduced thyroidal ability to produce T4 when hyperstimulated.

Bacterial and viral pathogens detected in sea turtles stranded along the coast of Tuscany, Italy.

PubMed

Fichi, G; Cardeti, G; Cersini, A; Mancusi, C; Guarducci, M; Di Guardo, G; Terracciano, G

2016-03-15

During 2014, six loggerhead turtles, Caretta caretta and one green turtle, Chelonia mydas, found stranded on the Tuscany coast of Italy, were examined for the presence of specific bacterial and viral agents, along with their role as carriers of fish and human pathogens. Thirteen different species of bacteria, 10 Gram negative and 3 Gram positive, were identified. Among them, two strains of Vibrio parahaemolyticus and one strain of Lactococcus garviae were recovered and confirmed by specific PCR protocols. No trh and tdh genes were detected in V. parahaemolyticus. The first isolation of L. garviae and the first detection of Betanodavirus in sea turtles indicate the possibility for sea turtles to act as carriers of fish pathogens. Furthermore, the isolation of two strains of V. parahaemolyticus highlights the possible role of these animals in human pathogens' diffusion. Copyright © 2016 Elsevier B.V. All rights reserved.

Congenital hypothyroidism from complete iodide transport defect: long-term evolution with iodide treatment.

PubMed Central

Albero, R.; Cerdan, A.; Sanchez Franco, F.

1987-01-01

Hypothyroidism from iodide transport deficiency is a rare disease, especially when found in two affected siblings. Treatment with high doses of iodide has been recommended, but no long term results have been reported. Two siblings with congenital hypothyroidism due to total failure to transport iodide have been followed up during twelve and a half years of treatment with oral potassium iodide. Iodine doses varied between 10.3 and 22 mg/day, and serum total iodine concentrations between 100 and 210 micrograms/dl. Total triiodothyronine (T3), thyroxine (T4) and free T4 were in the normal range during the time of study. Basal thyroid stimulating hormones (TSH) and maximum TSH response to thyrotrophin releasing hormone (TRH) were also in the range of normal values. These data along with clinical findings confirmed the potential usefulness of iodine in hypothyroidism due to complete iodide transport defect. PMID:3451231

Contributions of 5-HT neurons to respiratory control: neuromodulatory and trophic effects.

PubMed

Hodges, Matthew R; Richerson, George B

2008-12-10

Serotonin (5-hydroxytryptamine; 5-HT) is a neurotransmitter produced by a small number of neurons in the midbrain, pons and medulla. These neurons project widely throughout the neuraxis, where they release 5-HT and co-localized neuropeptides such as substance P (SP) and thyrotropin-releasing hormone (TRH). Each of these chemicals produce effects largely through G protein-coupled receptors, second messenger systems and subsequent neuromodulatory effects on target neurons. Emerging evidence suggests that 5-HT has additional modes of action during development and in adult mammals, including trophic effects (neurogenesis, cell differentiation, proliferation, migration and maturation) and influences on synaptic plasticity. Here, we discuss some of the neuromodulatory and trophic roles of 5-HT in general and in the context of respiratory control, as well as the regulation of release of modulatory neurotransmitters from 5-HT neurons. Future directions of study are also discussed.

Occurrence and Antibiotic Resistance of Vibrio parahaemolyticus from Shellfish in Selangor, Malaysia

PubMed Central

Letchumanan, Vengadesh; Pusparajah, Priyia; Tan, Loh Teng-Hern; Yin, Wai-Fong; Lee, Learn-Han; Chan, Kok-Gan

2015-01-01

High consumer demand for shellfish has led to the need for large-scale, reliable shellfish supply through aquaculture or shellfish farming. However, bacterial infections which can spread rapidly among shellfish poses a major threat to this industry. Shellfish farmers therefore often resort to extensive use of antibiotics, both prophylactically and therapeutically, in order to protect their stocks. The extensive use of antibiotics in aquaculture has been postulated to represent a major contributing factor in the rising incidence of antimicrobial resistant pathogenic bacteria in shellfish. This study aimed to investigate the incidence of pathogenic Vibrio parahaemolyticus and determine the antibiotic resistance profile as well as to perform plasmid curing in order to determine the antibiotic resistance mediation. Based on colony morphology, all 450 samples tested were positive for Vibrio sp; however, tox-R assay showed that only 44.4% (200/450) of these were V. parahaemolyticus. Out of these 200 samples, 6.5% (13/200) were trh-positive while none were tdh-positive. Antibiotic resistance was determined for all V. parahaemolyticus identified against 14 commonly used antibiotics and the multiple antibiotic resistance index (MAR) was calculated. The isolates demonstrated high resistance to several antibiotics tested- including second and third-line antibiotics- with 88% resistant to ampicillin, 81% to amikacin,70.5% to kanamycin, 73% to cefotaxime, and 51.5% to ceftazidime. The MAR index ranged from 0.00 to 0.79 with the majority of samples having an index of 0.36 (resistant to five antibiotics). Among the 13 trh-positive strains, almost 70% (9/13) demonstrated resistance to 4 or more antibiotics. Plasmid profiling for all V. parahaemolyticus isolates revealed that 86.5% (173/200) contained plasmids - ranging from 1 to 7 plasmids with DNA band sizes ranging from 1.2 kb to greater than 10 kb. 6/13 of the pathogenic V. pathogenic strains contained plasmid. After plasmid curing, the plasmid containing pathogenic strains isolated in our study have chromosomally mediated ampicillin resistance while the remaining resistance phenotypes are plasmid mediated. Overall, our results indicate that while the incidence of pathogenic V. parahaemolyticus in shellfish in Selangor still appears to be at relatively reassuring levels, antibiotic resistance is a real concern and warrants ongoing surveillance. PMID:26697003

Effects of ambient exposure, refrigeration, and icing on Vibrio vulnificus and Vibrio parahaemolyticus abundances in oysters.

PubMed

Jones, J L; Lydon, K A; Kinsey, T P; Friedman, B; Curtis, M; Schuster, R; Bowers, J C

2017-07-17

Vibrio vulnificus (Vv) and V. parahaemolyticus (Vp) illnesses are typically acquired through the consumption of raw molluscan shellfish, particularly oysters. As Vibrio spp. are naturally-occurring bacteria, one means of mitigation of illness is achieved by limiting post-harvest growth. In this study, effects of ambient air storage, refrigeration, and icing of oysters on Vibrio spp. abundances were examined at two sites in Alabama (AL) [Dog River (DR) and Cedar Point (CP)] and one site in Delaware Bay, New Jersey (NJ). As the United States shellfish program recommendations include testing for total these organisms and gene targets, Vv and total (tlh) and pathogenic (tdh+ and trh+) Vp were enumerated from samples using MPN-real-time-PCR approaches. Mean Vv and Vp abundances in oysters from AL-DR were lowest in immediately iced samples (2.3 and -0.1 log MPN/g, respectively) and highest in the 5h ambient then refrigerated samples (3.4 and 0.5 log MPN/g, respectively). Similarly, in AL-CP Vv and Vp mean levels in oysters were lowest in immediately iced samples (3.6 and 1.2 log MPN/g, respectively) and highest in 5h ambient then refrigerated samples (5.1 and 3.2 log MPN/g, respectively). Mean levels of pathogenic Vp from AL sites were frequently below the limit of detection (<0.3 MPN/g). In NJ, Vv and Vp mean abundances in oysters were highest in samples which were held for 7h in the shade (5.3 and 4.8 log MPN/g, respectively). Mean pathogenic Vp levels in oysters at initial harvest were also highest in oysters 7h in the shade (2.1 and 2.2 log MPN/g for tdh+ and trh+ Vp). Regardless of sampling location, Vibrio spp. levels were generally significantly (p<0.05) greater in oysters exposed to 5h of air storage compared to the initially harvested samples. In addition, the data demonstrated that the use of layered ice resulted in lower Vibrio spp. levels in oysters, compared to those that were refrigerated post-harvest. These results suggest vibriosis risk can be mitigated by shorter storage times and more rapid cooling of oysters, providing data regulatory authorities can use to evaluate Vibrio spp. control plans. Published by Elsevier B.V.

Environmental determinants of Vibrio parahaemolyticus in the Chesapeake Bay.

PubMed

Davis, Benjamin J K; Jacobs, John M; Davis, Meghan F; Schwab, Kellogg J; DePaola, Angelo; Curriero, Frank C

2017-08-25

Vibrio parahaemolyticus naturally-occurs in brackish and marine waters and is one of the leading causes of seafood-borne illness. Previous work studying the ecology of V. parahaemolyticus is often limited in geographic extent and lacking a full range of environmental measures. This study used a unique, large dataset of surface water samples in the Chesapeake Bay ( n =1,385) collected from 148 monitoring stations from 2007 to 2010. Water was analyzed for over 20 environmental parameters with additional meteorological and surrounding land use data. V. parahaemolyticus -specific genetic markers thermolabile hemolysin ( tlh ), thermostable direct hemolysin ( tdh ), and tdh -related hemolysin ( trh ) were assayed using quantitative PCR (qPCR), and interval-censored regression models with non-linear effects were estimated to account for limits of detection and quantitation. tlh was detected in 19.6% of water samples; tdh or trh markers were not detected. Results confirmed previously reported positive associations for V. parahaemolyticus abundance with temperature and turbidity and negative associations with high salinity (> 10-23‰). Furthermore, the salinity relationship was determined to be a function of both low temperature and turbidity, with an increase of either nullifying the high salinity effect. Associations with dissolved oxygen and phosphate also appeared stronger when samples were taken nearby human developments. Renewed focus on the V. parahaemolyticus ecological paradigm is warranted to protect public health. Importance Vibrio parahaemolyticus is one of the leading causes of seafood-borne illness in the United States and across the globe. Exposure is often through consuming raw or undercooked shellfish. Given the natural presence of the bacterium in the marine environment, improved understanding of its environmental determinants is necessary for future preventative measures. This analysis of environmental Vibrio parahaemolyticus is one of only a few that utilize a large dataset measured over a wide geographic and temporal range. The analysis also includes a large number of environmental parameters for Vibrio modeling, many of which have previously only been tested sporadically, and some of which have not been considered before. The results of the analysis revealed previously unknown relationships between salinity, turbidity, and temperature that provide significant insight into the abundance and persistence of V. parahaemolyticus bacterium in the environment. This information will be essential for developing environmental forecast models for the bacterium. Copyright © 2017 American Society for Microbiology.

Seasonal abundance of total and pathogenic Vibrio parahaemolyticus isolated from American oysters harvested in the Mandinga Lagoon System, Veracruz, Mexico: implications for food safety.

PubMed

Flores-Primo, Argel; Pardío-Sedas, Violeta; Lizárraga-Partida, Leonardo; López-Hernández, Karla; Uscanga-Serrano, Roxana; Flores-Hernández, Reyna

2014-07-01

The abundance of total and pathogenic Vibrio parahaemolyticus (Vp) strains in American oysters (Crassostrea virginica) harvested in two different harvest sites from the Mandinga lagoon System was evaluated monthly for 1 year (January through December 2012). Frequencies of species-specific genes and pathogenic genes exhibited a seasonal distribution. The annual occurrence of Vp with the species-specific tlh gene (tlh(+)) was significantly higher during the winter windy season (32.50%) and spring dry season (15.0%), with the highest densities observed during spring dry season at 283.50 most probable number (MPN)/g (lagoon bank A, near human settlements), indicating the highest risk of infection during warmer months. Pathogenic Vp tlh(+)/tdh(+) frequency was significantly higher during the winter windy and the spring dry seasons at 22.50 and 10.00%, respectively, with highest densities of 16.22 and 41.05 MPN/g (bank A), respectively. The tlh/trh and tdh/trh gene combinations were also found in Vp isolates during the spring dry season at 1.25 and 1.3%, respectively, with densities of 1.79 and 0.4 MPN/g (bank A), respectively. The orf8 genes were detected during the winter windy season (1.25%) with highest densities of 5.96 MPN/g (bank A) and 3.21 MPN/g (bank B, near mangrove islands and a heron nesting area). Densities of Vp tdh(+) were correlated (R(2) = 0.245, P < 0.015) with those of Vp orf8(+). The seasonal dynamics of Vp harboring pathogenic genes varied with seasonal changes, with very high proportions of Vp tdh(+) and Vp orf8(+) isolates in the winter windy season at 46.2 and 17.0%, respectively, which suggests that environmental factors may differentially affect the abundance of pathogenic subpopulations. Although all densities of total Vp (Vp tlh(+)) were lower than 10(4) MPN/g, thus complying with Mexican regulations, the presence of pathogenic strains is a public health concern. Our results suggest that total Vp densities may not be appropriate for assessing oyster contamination and predicting the risk of infection. Evaluation of the presence of pathogenic strains would be a better approach to protecting public health.

Presence of T3SS2β genes in trh⁺ Vibrio parahaemolyticus isolated from seafood harvested along Mangalore coast, India.

PubMed

Kumar, B K; Deekshit, V K; Rai, P; Shekar, M; Karunasagar, I; Karunasagar, I

2014-05-01

Vibrio parahaemolyticus is a seafood-borne pathogen autochthonous to the marine and estuarine ecosystem, responsible for gastroenteritis when contaminated raw seafood is consumed. The pathogenicity has been associated with thermostable direct haemolysin (TDH) and TDH-related haemolysin (TRH). Of late, the presence of T3SS2α and T3SS2β gene clusters has been well documented in clinical isolates of Vibrio parahaemolyticus and known to play an essential role in pathogenesis. However, reports on the presence of T3SSβ genes in V. parahaemolyticus isolated from the seafood and/or environmental samples are scanty. In this study, we have identified and analysed the distribution of the T3SS2β genes in V. parahaemolyticus isolated from seafood harvested along southwest coast of India. Results showed that T3SS2β genes are solely associated with trh⁺ and tdh⁺ /trh⁺ strains of V. parahaemolyticus. Reverse transcriptase PCR (RT-PCR) showed that the T3SS2β genes identified in trh⁺ V. parahaemolyticus were transcriptionally active. To our knowledge, this study appears to be the first description on the presence of T3SS2β-positive V. parahaemolyticus isolated from seafood in India. The study of T3SS2 along with other virulence factors will help in better understanding of the risk of seafood-borne illness due to V. parahaemolyticus. T3SSs (α or β) are the important virulence factors of Vibrio parahaemolyticus that contribute to their pathogenicity in humans. This study demonstrated the presence of T3SS2β genes in V. parahaemolyticus isolated from the seafood harvested along Mangalore coast. RT-PCR showed that the T3SS2β genes identified in seafood isolates of V. parahaemolyticus were found to be functional. To the best of our knowledge, this is the first description of T3SS2β genes in trh⁺ V. parahaemolyticus isolated from seafood in India. The presence of T3SS2 along with other virulence factors such as TDH and/or TRH highlights a potential health risk for seafood consumers. © 2013 The Society for Applied Microbiology.

Expansion of the gateway multisite recombination cloning toolkit.

PubMed

Shearin, Harold K; Dvarishkis, Alisa R; Kozeluh, Craig D; Stowers, R Steven

2013-01-01

Precise manipulation of transgene expression in genetic model organisms has led to advances in understanding fundamental mechanisms of development, physiology, and genetic disease. Transgene construction is, however, a precondition of transgene expression, and often limits the rate of experimental progress. Here we report an expansion of the modular Gateway MultiSite recombination-cloning platform for high efficiency transgene assembly. The expansion includes two additional destination vectors and entry clones for the LexA binary transcription system, among others. These new tools enhance the expression levels possible with Gateway MultiSite generated transgenes and make possible the generation of LexA drivers and reporters with Gateway MultiSite cloning. In vivo data from transgenic Drosophila functionally validating each novel component are presented and include neuronal LexA drivers, LexAop2 red and green fluorescent synaptic vesicle reporters, TDC2 and TRH LexA, GAL4, and QF drivers, and LexAop2, UAS, and QUAS channelrhodopsin2 T159C reporters.

Expansion of the Gateway MultiSite Recombination Cloning Toolkit

PubMed Central

Shearin, Harold K.; Dvarishkis, Alisa R.; Kozeluh, Craig D.; Stowers, R. Steven

2013-01-01

Precise manipulation of transgene expression in genetic model organisms has led to advances in understanding fundamental mechanisms of development, physiology, and genetic disease. Transgene construction is, however, a precondition of transgene expression, and often limits the rate of experimental progress. Here we report an expansion of the modular Gateway MultiSite recombination-cloning platform for high efficiency transgene assembly. The expansion includes two additional destination vectors and entry clones for the LexA binary transcription system, among others. These new tools enhance the expression levels possible with Gateway MultiSite generated transgenes and make possible the generation of LexA drivers and reporters with Gateway MultiSite cloning. In vivo data from transgenic Drosophila functionally validating each novel component are presented and include neuronal LexA drivers, LexAop2 red and green fluorescent synaptic vesicle reporters, TDC2 and TRH LexA, GAL4, and QF drivers, and LexAop2, UAS, and QUAS channelrhodopsin2 T159C reporters. PMID:24204935

Central hypothyroidism in adults: better understanding for better care.

PubMed

Grunenwald, Solange; Caron, Philippe

2015-02-01

Central hypothyroidism (CH) is a rare cause of hypothyroidism generally related to a hypothalamic-pituitary disorder or arising as an iatrogenic complication. In adults, CH may be secondary to quantitative and/or qualitative alterations in thyroid-stimulating hormone (TSH) secretion. The disease is difficult to diagnose clinically because it lacks specific clinical signs and these may be masked by other anterior pituitary hormone secretion deficiencies. In patients with long-standing and marked CH, a diagnosis may be made based on low free T4 levels and normal, low or moderately increased TSH levels. In patients with early-stage or moderate CH, exploration of the circadian TSH cycle, determination of TSH response after a TRH test or recombinant TSH injection, estimation of TSH index, or evaluation of peripheral indexes of thyroid hormone metabolism may be required to establish a diagnosis. Regarding treatment, patients should receive levothyroxine replacement therapy, but hormone objectives during follow-up need to be precisely determined in order to reduce cardiovascular risks and to improve the quality of life of patients.

Regulation of hormone release by cultured cells from a thyrotropin-growth hormone-secreting pituitary tumor. Direct inhibiting effects of 3,5,3'-triiodothyronine and dexamethasone on thyrotropin secretion.

PubMed

Lamberts, S W; Oosterom, R; Verleun, T; Krenning, E P; Assies, H

1984-08-01

The regulation of TSH and GH secretion was investigated in cultured tumor cells prepared from a mixed TSH/GH secreting pituitary tumor. The tumor tissue had been removed transsphenoidally from a patient with hyperthyroidism and inappropriately high serum TSH levels and acromegaly. TSH and GH secretion by cultured cells were stimulated in a parallel way by TRH (300 nM) and LHRH (50 nM), but were unaffected by bromocriptine (10 nM). Exposure of the tumor cells to dexamethasone (0.1 microM) or T3 (50 nM) had differential effects on hormone secretion. GH secretion was greatly stimulated by dexamethasone, but unaffected by T3. TSH secretion was inhibited both by T3 and by dexamethasone. So, T3 and glucocorticoids inhibit TSH release by the human pituitary tumor cells studied at least partly by means of a direct effect.

LARGE SCALE METHOD FOR THE PRODUCTION AND PURIFICATION OF CURIUM

DOEpatents

Higgins, G.H.; Crane, W.W.T.

1959-05-19

A large-scale process for production and purification of Cm/sup 242/ is described. Aluminum slugs containing Am are irradiated and declad in a NaOH-- NaHO/sub 3/ solution at 85 to 100 deg C. The resulting slurry filtered and washed with NaOH, NH/sub 4/OH, and H/sub 2/O. Recovery of Cm from filtrate and washings is effected by an Fe(OH)/sub 3/ precipitation. The precipitates are then combined and dissolved ln HCl and refractory oxides centrifuged out. These oxides are then fused with Na/sub 2/CO/sub 3/ and dissolved in HCl. The solution is evaporated and LiCl solution added. The Cm, rare earths, and anionic impurities are adsorbed on a strong-base anfon exchange resin. Impurities are eluted with LiCl--HCl solution, rare earths and Cm are eluted by HCl. Other ion exchange steps further purify the Cm. The Cm is then precipitated as fluoride and used in this form or further purified and processed. (T.R.H.)

Occurrence of Vibrio parahaemolyticus and Vibrio vulnificus in retail raw oysters from the eastern coast of Thailand.

PubMed

Changchai, Nuttawee; Saunjit, Sudarat

2014-05-01

Occurrence, population density and virulence of Vibrio parahaemolyticus and V. vulnificus in 240 retail raw oysters collected monthly between March 2010 and February 2011 from Ang Sila coast, Chon Buri Province, Thailand were determined using most probable number (MPN) multiplex PCR. Multiplex PCR detected V. parahaemolyticus in 219 raw oyster samples, of which 29 samples contained the virulence tdh. MPN values for V. parahaemolyticus and pathogenic strains in most samples ranged from 10 to 10(2) and from 3 to 10 MPN/g, respectively. The presence of V. vulnificus was found in 53 oyster samples in amounts between 10 and 10(2) MPN/g. Of 1,087 V. parahaemolyticus isolates, 14 and 2 isolates carried tdh and virulence trh, respectively but none with both genes. However, none of the presumptive isolates was shown to be V. vulnificus. The detection of pathogenic V. parahaemolyticus and V. vulnificus in raw oysters has rendered high awareness of risk in consumption of raw or undercooked oysters.

Taimyr Reindeer and Environmental Change: Monitoring Wild Reindeer Migration in Changing Natural and Social Environments

NASA Astrophysics Data System (ADS)

Petrov, A. N.

2016-12-01

The Taimyr Reindeer Herd (TRH) is both the largest and the longest monitored wild reindeer herd in Eurasia. An important part of Arctic ecosystems and Indigenous livelihood, wild reindeer have been continuously monitored for almost 50 years. During this time, herds have exhibited large changes in size and these changes have been recorded in almost all herds across the animal's range. An increasing number of wild reindeer in the Soviet times was followed by a significant population loss in the last decade. In addition, recent monitoring revealed substantial shifts in the distribution of wild populations. The decline in wild reindeer is likely related to natural cycles and changes in the Arctic environment caused by climate variability and anthropogenic activity. This study investigates patterns and possible drives of reindeer population dynamics in space and time. We identify key climatic factors, possible relationships with biomass dynamics, as well as with hunting practices and other human impacts.

Peptide-induced emesis in dogs: possible relevance to radiation-induced emesis. Final report Oct 80-Sep 81

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carpenter, D.O.

1982-09-01

Results of earlier investigators indicate that radioemesis is mediated by some humoral agent(s). Peptides are likely candiates since they exert a number of biological effects and are released from storage sites by various stimuli, including radiation. Peptides at various concentrations were injected singly intravenously into conscious dogs, and the dog's emetic response was observed. Of the peptides tested, neurotensin, angiotensin II, vasopressin, oxytocin, and TRH produced consistent emetic responses. Inhibition of drug-induced emesis was studied both centrally (chlorpromazine) and peripherally (domperidone) acting dopamine antagonists. Results indicate inhibition by chlorpromazine, which crosses the blood brain barrier, but only partial blockade bymore » domperidone, which does not cross the blood brain barrier. Preliminary studies were conducted attempting to characterize types of receptors on area postrema neurons. Single-cell recordings from these neurons, challenged by iontophoretic administration of various neurotransmitters, show stimulation by glutamic acid and serotonin and inhibiiton by norepinephrine.« less

Effect of added weight on landing kinematics in jumping horses.

PubMed

Clayton, H M

1997-05-01

Six event horses jumped a 1.10 m high table fence 4 times under each of 2 conditions; the rider weight condition involved carrying the weight of the rider and saddle (61 kg), whereas the added weight condition included an additional 18 kg weight cloth. Sagittal view, 60 Hz video recordings were analysed using standard methods. Comparisons between the rider weight and added weight conditions using paired t tests (P<0.05) showed a number of significant differences. In the added weight condition the leading forelimb landed closer to the fence, and there were increases in the maximal extension of the fetlock and carpal joints in this limb during the landing phase. In the first departure stride, the stance durations of both hindlimbs increased, and the advanced placement between them was reduced for the added weight condition. The head was significantly further ahead of the vertical in the added weight condition at the instants of ground contact of the TrH, LdH and TrF in the first departure stride.

A novel integrated care concept (NICC) versus standard care in the treatment of chronic cardiovascular diseases: protocol for the randomized controlled trial CardioCare MV.

PubMed

Schmidt, Christian; Öner, Alper; Mann, Miriam; Krockenberger, Katja; Abbondanzieri, Melanie; Brandewiede, Bernard; Brüge, Armin; Hostenkamp, Gisela; Kaiser, Axel; Neumeyer, Henriette; Ziegler, Andreas

2018-02-20

Cardiovascular diseases are the major cause of death globally and represent a major economic burden on health care systems. Positive effects of disease management programs have been shown for patients with heart failure (HF). Remote monitoring and telemonitoring with active intervention are beneficial in atrial fibrillation (AF) and therapy-resistant hypertension (TRH), respectively. For these patients, we have developed a novel integrated care concept (NICC) which combines telemedicine with intensive support by a care center, including a call center, an integrated care network including inpatient and outpatient care providers and guideline therapy for patients. The aim of the study is to demonstrate the superiority of NICC over guideline therapy alone. The trial is designed as open-label, bi-center, parallel-group design with two groups and a blinded observer. Patients will be included if they are either inpatients or if they are referred to the outpatient clinic of the hospitals by their treating physician. Randomization will be done individually with stratification by cardiovascular disease (AF, HF, TRH), center and admission type. Primary endpoints are based on the 1-year observation period after randomization. The first primary endpoint is the composite endpoint consisting of mortality, stroke and myocardial infarction. The number of hospitalizations form the second primary endpoint. The third primary endpoint is identical to the first primary endpoint plus cardiac decompensation. Adjustments for multiple testing are done using a fall-back strategy. Secondary endpoints include patient adherence, health care costs, quality of life, and safety. A sample size of 2930 gives 80% power at the two-sided 2.5% test level for the first primary endpoint. The power for the second primary endpoint is 99.8% at this sample size, and it is 80% with 1086 patients. This study will inform care providers whether quality of care can be improved by an integrated care concept providing telemedicine through a round-the-clock call center approach. We expect that cost of the NICC will be lower than standard care because of reduced hospitalizations. If the study has a positive result, NICC is planned to be immediately rolled out in the federal state of Mecklenburg-West Pomerania and other federal states in Germany. The trial will also guide additional research to disentangle the effects of this complex intervention. DRKS, ID: DRKS00013124 . Registered on 5 October 2017; ClinicalTrials.gov , ID: NCT03317951. Registered on 17 October 2017.

[Cardiotoxicity of lindane, a gamma isomer of hexachlorocyclohexane].

PubMed

Sauviat, Martin-Pierre; Pages, Nicole

2002-01-01

The goal of the present review is to collect information concerning membrane effects induced by lindane intoxication, a y isomer of hexachiorocyclohexane (gamma-HCH) that has been largely used as an insecticide and disinfectant in agriculture and entered also in the composition of some lotions, creams and shampoos used against parasites (lice and scabies). Absorbed through respiratory, digestive or transcutaneous pathways, lindane accumulates within lipid rich tissues. Lindane accumulation depends on the duration of the exposure and affects tissues in the following order: adipose tissues > brain > kidney > muscle > lungs > heart > liver > blood. Whatever the mode of lindane absorption, it accumulates in blood and is distributed throughout the body. It may affect human health by exerting systemic, immunologic, teratogenic, and/or cancerogenic effects. The symptoms of lindane intoxication are different according to the mode of intoxication, acute or chronic. The absorption of high doses of gamma-HCH is particularly toxic for the central nervous system and for the female and male reproduction apparatus in mammals where lindane is considered as an endocrine disruptor. Lindane is highly lipophilic and incorporates into biological membranes according to the following sequence: mitochondria > sarcoplasmic reticulum > myelin > brain microsomes > erythrocytes. Lindane exerts a stimulating action on synaptic transmission and inhibits the chloride current activated by gamma-amino butyric acid (GABA) of many muscular and nervous preparations by interacting with the receptors GABA-chloride channel complex. It seems to affect calcium homeostasis of many tissues. The similarity between lindane and inositol (1, 4, 5) phosphate (IP3) suggested that lindane releases Ca2+ from IP3-sensitive intracellular stores in macrophages and myometrial cells. Ca2+ release from reticulum endoplasmic, mitochondria and other Ca2+ stores has been reported in cat kidney cells. Lindane altered energetic metabolism of hepatic mitochondria and the inositol-phosphate synthesis in neuronal cells. However, lindane does not compete with the IP3 receptor. Lindane produces a Ca2+ influx in mice peritoneal macrophage cells responsible for the Ca2+ induced Ca2+ release produced by phospholipase C via IP3 pathway and resulting in a maintained increase of the free cytosolic Ca2+ concentration. Lindane decreased the membrane erythrocyte and cerebral cell concentration of phosphatidyl inositol PI, PIP and PIP2 in rats repetitively exposed to lindane for 3 or 6 months. Lindane induces oxidative stress; it modifies the activity of the scavenger enzymes. This effect is involved in the inhibition of intercellular gap junctions. Modifications of the electrocardiogram (ECG), sinusal rhythm alteration and negative and dysphasic variations of T wave, similar to those produced by hyperkaliemia, have been reported after lindane absorption. During acute lindane poisoning, the activities of serum transaminases (SGOT, SGTP), and lactate deshydrogenase (LDH) increase. Lindane produces histological alterations of cardiac tissues and a cardio-vascular dystrophy (contracture, degenerescence and necrosis) mainly in the left ventricular wall and a hypertrophy of the left ventricle. Chronic application of residual doses of lindane shortened the action potential duration in rat papillary muscle. These effects were similar to those induced by hyperthyroidism. Lindane increases the triiodothyronine (T3) serum level in hyperthyroid rats. T3 plays an important role in the postnatal development of the rat ventricle by increasing the density of potassium channels which contribute to action potential shortening during the development. Thyroid hormones influence the regulation and the expression of messengers ARN which encode different potassium channels involved in action potential repolarization (Kvl.2; Kvl.4; Kvl.5; Kv2.1; Kv4; HCN2). The thyrotropine-releasing hormone (TRH) modulates the HERG-type rapid delayed potassium channel (IKr) encoded by the human gene ether-a-go-go in rat anterior pituitary cells GH3/B6. This channel is involved in the cardiac long QT syndrome. TRH modifies the current kinetics of human HERG potassium channel co-expressed in Xenopus oocytes with the TRH receptor, whose activity is modulated via the protein kinase C pathway linked to a G protein-coupled receptor and is regulated by changes in the PIP2 concentration in the membrane. IKr channels regulation is also dependent on sexual hormones. In conclusion, lindane affects the excitable membranes and the cardio circulatory system. These alterations (may) represent a potential risk for human health.

Triple points and phase diagrams in the extended phase space of charged Gauss-Bonnet black holes in AdS space

NASA Astrophysics Data System (ADS)

Wei, Shao-Wen; Liu, Yu-Xiao

2014-08-01

We study the triple points and phase diagrams in the extended phase space of the charged Gauss-Bonnet black holes in d-dimensional anti-de Sitter space, where the cosmological constant appears as a dynamical pressure of the system and its conjugate quantity is the thermodynamic volume of the black holes. Employing the equation of state T=T(v,P), we demonstrate that the information of the phase transition and behavior of the Gibbs free energy are potential encoded in the T-v (T-rh) line with fixed pressure P. We get the phase diagrams for the charged Gauss-Bonnet black holes with different values of the charge Q and dimension d. The result shows that the small/large black hole phase transitions appear for any d, which is reminiscent of the liquid/gas transition of a Van der Waals type. Moreover, the interesting thermodynamic phenomena, i.e., the triple points and the small/intermediate/large black hole phase transitions are observed for d=6 and Q ∈(0.1705,0.1946).

PRECISION TIME-DELAY GENERATOR

DOEpatents

Carr, B.J.; Peckham, V.D.

1959-06-16

A precision time-delay generator circuit with low jitter is described. The first thyratron has a series resonant circuit and a diode which is connected to the second thyratron. The first thyratron is triggered at the begin-ning of a time delay and a capacitor is discharged through the first thyratron and the diode, thereby, triggering the second thyratron. (T.R.H.) l6l9O The instrument described can measure pressures between sea level and 300,000 ft. The pressure- sensing transducer of the instrument is a small cylindrical tube with a thin foil of titanium-tritium fastened around the inside of the tube. Output is a digital signal which can be used for storage or telemetering more conveniently than an analog signal. (W.D.M.) l6l9l An experimental study was made on rolling contacts in the temperature range of 550 to 1000 deg F. Variables such as material composition, hardness, and operating conditions were investigated in a rolling test stand. Ball bearing tests were run to determine the effect of design parameters, bearing materials, lubricants, and operating conditions. (auth)

Multiplex real-time PCR assay for detection of pathogenic Vibrio parahaemolyticus strains.

PubMed

He, Peiyan; Chen, Zhongwen; Luo, Jianyong; Wang, Henghui; Yan, Yong; Chen, Lixia; Gao, Wenjie

2014-01-01

Foodborne disease caused by pathogenic Vibrio parahaemolyticus has become a serious public health problem in many countries. Rapid diagnosis and the identification of pathogenic V. parahaemolyticus are very important in the context of public health. In this study, an EvaGreen-based multiplex real-time PCR assay was established for the detection of pathogenic V. parahaemolyticus. This assay targeted three genetic markers of V. parahaemolyticus (species-specific gene toxR and virulence genes tdh and trh). The assay could unambiguously identify pathogenic V. parahaemolyticus with a minimum detection limit of 1.4 pg genomic DNA per reaction (concentration giving a positive multiplex real-time PCR result in 95% of samples). The specificity of the assay was evaluated using 72 strains of V. parahaemolyticus and other bacteria. A validation of the assay with clinical samples confirmed its sensitivity and specificity. Our data suggest the newly established multiplex real-time PCR assay is practical, cost-effective, specific, sensitive and capable of high-throughput detection of pathogenic V. parahaemolyticus. Copyright © 2014. Published by Elsevier Ltd.

Molecular characterization, antibiotic resistance pattern and biofilm formation of Vibrio parahaemolyticus and V. cholerae isolated from crustaceans and humans.

PubMed

Ahmed, Heba A; El Bayomi, Rasha M; Hussein, Mohamed A; Khedr, Mariam H E; Abo Remela, Etab M; El-Ashram, Ahmed M M

2018-06-02

Human infection with pathogenic vibrios is associated with contaminated seafood consumption. In the present study, we examined 225 crustaceans collected from retail markets in Egypt. Stool samples from gastroenteritis patients were also examined. Bacteriological and molecular examinations revealed 34 (15.1%) V. parahaemolyticus and 2 (0.9%) V. cholerae from crustaceans, while V. parahaemolyticus isolates were identified in 3 (3%) of the human samples. The virulence-associated genes tdh and/or trh were detected in 5.9% and 100% of the crustacean and human samples, respectively, whereas the two V. cholerae isolates were positive for the ctx and hlyA genes. Antibiotic sensitivity revealed high resistance of the isolates to the used antibiotics and an average MAR index of 0.77. Biofilm formation at different temperatures indicated significantly higher biofilm formation at 37 °C and 25 °C compared with 4 °C. Frequent monitoring of seafood for Vibrio species and their antibiotic, molecular and biofilm characteristics is essential to improve seafood safety. Copyright © 2018 Elsevier B.V. All rights reserved.

Inherited hypothyroidism.

PubMed

Jackson, I M

1976-03-01

Familial hypothyroidism results from both thyroidal and extrathyroidal dysfunction. Specific intrathyroidal abnormalities in thyroid hormone synthesis causing goitrous hypothyroidism are iodide trap defect, organification defect, "coupling" defect, iodoprotein defect, and dehalogenase defect. The diagnostic studies for each are outlined utilizing radioiodine(131I) studies. Other causes of cretinism include failure of the thyroid gland to respond to TSH and lack of pituitary TSH (or hypothalamic TRH). The syndrome of peripheral resistance to thyroid hormone is discussed. The diagnosis of inherited hypothyrodism rests on an adequate family history and measurement of both T4 and TSH levels which can be determined in cord blood or peripheral blood from the infant. The importance of early treatment of hypothyroidism in the neonatal period to prevent brain damage is emphasized. The rec:nt discovery of the importance of reverse T3 (RT3) in fetal thyroid metabolism is described, and the possibility of amniocentesis as an aid in prenatal diagnosis is considered. The place of intrauterine administration of thyroid hormone to the fetus at risk from hypothyroidism is uncertain at this time and requires carefully controlled studies and long-term follow-up.

A study of so-called hypochondriasis.

PubMed

von Scheele, C; Nordgren, L; Kempi, V; Hetta, J; Hallborg, A

1990-01-01

Twenty-four patients with unexplained somatic complaints were subjected to a thorough somatic examination. Only when the examination proved negative was the patient entered into the study. The patients were clinically appraised according to criteria given in DSM-III. Generalized anxiety disorder (GAD) was diagnosed in 12, somatization disorder (SD) in 8, and hypochondriasis in 4 patients. Seventeen of the 24 patients agreed to participate in biochemical investigations including a TRH load, a dexamethasone test, and a determination of the monoamine metabolites 5-HIAA and HVA in cerebrospinal fluid (CSF). A normal TSH increase and a normal suppression of cortisol were registered. The HVA values correlated significantly with the 5-HIAA values as well as with the alexithymia scores. Concerning alexithymia and maturity level, no difference as to social class was found. The patients filled in a Zung depression chart. The Zung scale and the 5-HIAA values were both inconsistent with depressive illness. In so-called hypochondriasis a long-term relationship, including selected somatic and biochemical examinations and thorough information, was crucial in abating the patient's distrust and thus the need for health care.

Gigantism associated with a pituitary tumour secreting growth hormone and prolactin and cured by transsphenoidal hypophysectomy.

PubMed

Favre, L; Rogers, L M; Cobb, C A; Rabin, D

1979-06-01

An 18-year old male is reported who presented with a history of a growtn spurt over the year preceding his admission. His height was above the 97th percentile, and he had incompletely developed secondary sexual characters. Pituitary evaluation demonstrated a moderately elevated level of growth hormone (hGH) not suppressible by a glucose load and not stimulable by TRH or by L-DOPA. Serum prolactin (PRL) concentration was also increased while gonadotrophin, thyroid and adrenal function were all subnormal. There was clear radiological evidence of a large pituitary tumour with suprasellar extension and transsphenoidal total hypophysectomy was performed. A mixed chromophobe and acidophilic adenoma was found and both growth hormone and prolactin were demonstrable in different cells of the tumour by the immunoperoxidase technique. Post-operatively the patient has hypopituitarism and levels of growth hormone and prolactin have remained low or undetectable after 6 months. Thus early diagnosis and surgical treatment of gigantism of this mixed hGH-PRL secreting pituitary tumour was associated with a cure, which contrasts with the unfavourable outcome of many of the patients previously reported.

[Unconsciousness due to hyponatremia in a patient with short stature with panhypopituitarism].

PubMed

Notsu, K; Takagi, C; Umaki, I

1995-03-20

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.

Parallel Evolution of Two Clades of an Atlantic-Endemic Pathogenic Lineage of Vibrio parahaemolyticus by Independent Acquisition of Related Pathogenicity Islands

PubMed Central

Xu, Feng; Drees, Kevin P.; Sebra, Robert P.; Jones, Stephen H.

2017-01-01

ABSTRACT Shellfish-transmitted Vibrio parahaemolyticus infections have recently increased from locations with historically low disease incidence, such as the Northeast United States. This change coincided with a bacterial population shift toward human-pathogenic variants occurring in part through the introduction of several Pacific native lineages (ST36, ST43, and ST636) to nearshore areas off the Atlantic coast of the Northeast United States. Concomitantly, ST631 emerged as a major endemic pathogen. Phylogenetic trees of clinical and environmental isolates indicated that two clades diverged from a common ST631 ancestor, and in each of these clades, a human-pathogenic variant evolved independently through acquisition of distinct Vibrio pathogenicity islands (VPaI). These VPaI differ from each other and bear little resemblance to hemolysin-containing VPaI from isolates of the pandemic clonal complex. Clade I ST631 isolates either harbored no hemolysins or contained a chromosome I-inserted island we call VPaIβ that encodes a type 3 secretion system (T3SS2β) typical of Trh hemolysin producers. The more clinically prevalent and clonal ST631 clade II had an island we call VPaIγ that encodes both tdh and trh and that was inserted in chromosome II. VPaIγ was derived from VPaIβ but with some additional acquired elements in common with VPaI carried by pandemic isolates, exemplifying the mosaic nature of pathogenicity islands. Genomics comparisons and amplicon assays identified VPaIγ-type islands containing tdh inserted adjacent to the ure cluster in the three introduced Pacific and most other emergent lineages that collectively cause 67% of infections in the Northeast United States as of 2016. IMPORTANCE The availability of three different hemolysin genotypes in the ST631 lineage provided a unique opportunity to employ genome comparisons to further our understanding of the processes underlying pathogen evolution. The fact that two different pathogenic clades arose in parallel from the same potentially benign lineage by independent VPaI acquisition is surprising considering the historically low prevalence of community members harboring VPaI in waters along the Northeast U.S. coast that could serve as the source of this material. This illustrates a possible predisposition of some lineages to not only acquire foreign DNA but also become human pathogens. Whereas the underlying cause for the expansion of V. parahaemolyticus lineages harboring VPaIγ along the U.S. Atlantic coast and spread of this element to multiple lineages that underlies disease emergence is not known, this work underscores the need to define the environment factors that favor bacteria harboring VPaI in locations of emergent disease. PMID:28687650

Vibrio parahaemolyticus and Vibrio vulnificus Recovered from Oysters during an Oyster Relay Study.

PubMed

Elmahdi, Sara; Parveen, Salina; Ossai, Sylvia; DaSilva, Ligia V; Jahncke, Michael; Bowers, John; Jacobs, John

2018-02-01

Vibrio parahaemolyticus and Vibrio vulnificus are naturally occurring estuarine bacteria and are the leading causes of seafood-associated infections and mortality in the United States. Though multiple-antibiotic-resistant V. parahaemolyticus and V. vulnificus strains have been reported, resistance patterns in vibrios are not as well documented as those of other foodborne bacterial pathogens. Salinity relaying (SR) is a postharvest processing (PHP) treatment to reduce the abundances of these pathogens in shellfish harvested during the warmer months. The purpose of this study was to evaluate the antimicrobial susceptibility (AMS), pathogenicity, and genetic profiles of V. parahaemolyticus and V. vulnificus recovered from oysters during an oyster relay study. Isolates ( V. parahaemolyticus [ n = 296] and V. vulnificus [ n = 94]) were recovered from oysters before and during the 21-day relaying study to detect virulence genes ( tdh and trh ) and genes correlated with virulence ( vcgC ) using multiplex quantitative PCR (qPCR). AMS to 20 different antibiotics was investigated using microbroth dilution, and pulsed-field gel electrophoresis (PFGE) was used to study the genetic profiles of the isolates. Twenty percent of V. vulnificus isolates were vcgC + , while 1 and 2% of V. parahaemolyticus were tdh + and trh + , respectively. More than 77% of the V. vulnificus isolates and 30% of the V. parahaemolyticus isolates were resistant to at least one antimicrobial. Forty-eight percent of V. vulnificus and 8% of V. parahaemolyticus isolates were resistant to two or more antimicrobials. All isolates demonstrated a high genetic diversity, even among those isolated from the same site and having a similar AMS profile. No significant effects of the relaying process on AMS, virulence genes, or PFGE profiles of V. vulnificus and V. parahaemolyticus were observed. IMPORTANCE Analysis of the antibiotic resistance profiles of V. vulnificus and V. parahaemolyticus isolated from oysters during this study indicated that more than 48% of V. vulnificus isolates were resistant to two or more antimicrobials, including those recommended by the CDC for treating Vibrio infections. Also, the V. parahaemolyticus isolates showed high MICs for some of the Vibrio infection treatment antibiotics. Monitoring of AMS profiles of this bacterium is important to ensure optimal treatment of infections and improve food safety. Our study showed no significant differences in the AMS profiles of V. vulnificus ( P = 0.26) and V. parahaemolyticus ( P = 0.23) isolated from the oysters collected before versus after relaying. This suggests that the salinity of the relaying sites did not affect the AMS profiles of the Vibrio isolates, although it did reduce the numbers of these bacteria in oysters (S. Parveen et al., J Food Sci 82:484-491, 2017, https://doi.org/10.1111/1750-3841.13584). Copyright © 2018 American Society for Microbiology.

RECOVERY OF URANIUM FROM LOW GRADE URANIUM BEARING ORES

DOEpatents

Rhodes, H.B.; Pesold, W.F.; Hirshon, J.M.

1959-06-01

Recovery of U, Fe, and Al from Chattanooga shale is described. Ground shale (-4 to +325 mesh) is roasted to remove organic and volatile matter. The heated shale is then reacted with a chlorinating agent (CCl/sub 4/, COCl/sub 2/, Cl, and SCl) at 600 to 1000 C. The metal chloride vapor is separated from entrained solids and then contacted with a liquid alkali metal chloride which removes U. The U is reeovered by cooling and dissolving the bath followed by acidification and solvent extraction. A condensed phase of Al, Fe, and K chlorides is treated to separate Al as alumina by passing through a Fe/sub 2/O/ sub 3/ bed. The remaining FeCl/sub 3/ is oxidized by O/sub 2/ at 1000 C to form Fe/sub 2/O/sub 3/ and Cl/sub 2/. Alternatively, vapor from the U separation step may be passed to a liquid KCl bath at 500 to 650 C. The resulting mixture is oxidized to form Cl/sub 2/ and Fe/sub 2/O/sub 3/ + Al/sub 2/O/sub 3/. The Al and Fe are separated by reaction with NaOH at high temperatures and pressures. (T.R.H.)

Contamination of community water sources by potentially pathogenic vibrios following sea water inundation.

PubMed

Kanungo, Reba; Shashikala; Karunasagar, I; Srinivasan, S; Sheela, Devi; Venkatesh, K; Anitha, P

2007-12-01

Potentially pathogenic members of the Vibrionaceae family including Vibrio cholerae and Vibrio parahemolyticus were isolated from domestic sources of drinking water in coastal villages following sea water inundation during the tsunami in Southern India. Phenotypic and genotypic studies were done to confirm the identity and detection of toxins. Vibrio-gyr (gyrase B gene) was detected in all sixteen vibrio isolates. Toxin regulating genes i.e.: ctx gene, tdh gene, and trh gene, however were not detected in any of the strains, thereby ruling out presence of toxins which could endanger human life. Other potentially pathogenic bacteria Aeromonas and Plesiomonas were also isolated from hand pumps and wells, in a few localities. There was no immediate danger in the form of an outbreak or sporadic gastroenteritis at the time of the study. Timely chlorination and restoration of potable water supply to the flood affected population by governmental and nongovernmental agencies averted waterborne gastroenteritis. Assessment of quality of water and detection of potential virulent organisms is an important public health activity following natural disasters. This work highlights the importance of screening water sources for potentially pathogenic microorganisms after natural disasters to avert outbreaks of gastroenteritis and other infectious diseases.

Identification and expression analysis of the genes involved in serotonin biosynthesis and transduction in the field cricket Gryllus bimaculatus.

PubMed

Watanabe, T; Sadamoto, Hitoshi; Aonuma, H

2011-10-01

Serotonin (5-HT) modulates various aspects of behaviours such as aggressive behaviour and circadian behaviour in the cricket. To elucidate the molecular basis of the cricket 5-HT system, we identified 5-HT-related genes in the field cricket Gryllus bimaculatus DeGeer. Complementary DNA of tryptophan hydroxylase and phenylalanine-tryptophan hydroxylase, which convert tryptophan into 5-hydroxy-L-tryptophan (5-HTP), and that of aromatic L-amino acid decarboxylase, which converts 5-HTP into 5-HT, were isolated from a cricket brain cDNA library. In addition, four 5-HT receptor genes (5-HT(1A) , 5-HT(1B) , 5-HT(2α) , and 5-HT(7) ) were identified. Expression analysis of the tryptophan hydroxylase gene TRH and phenylalanine-tryptophan hydroxylase gene TPH, which are selectively involved in neuronal and peripheral 5-HT synthesis in Drosophila, suggested that two 5-HT synthesis pathways co-exist in the cricket neuronal tissues. The four 5-HT receptor genes were expressed in various tissues at differential expression levels, suggesting that the 5-HT system is widely distributed in the cricket. © 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.

The nature of neuroendocrine abnormalities in depression: a controversial issue in contemporary psychiatry.

PubMed

von Zerssen, D; Berger, M; Dose, M; Doerr, P; Krieg, C; Bossert, S; Riemann, D; Pirke, K M; Dolhofer, R; Müller, O A

1986-01-01

Neuroendocrine abnormalities in depression have been regarded, by many authors, as relatively specific markers of nosological subtypes of the disorder, e.g. primary vs. secondary, endogenous vs. non-endogenous or unipolar vs. bipolar depression. They should reflect the same changes in central neurotransmitters (e.g. noradrenergic insufficiency and/or cholinergic hyperactivity) that were hypothesized as the cause of clinical symptoms. This view is challenged on the basis of our own neuroendocrine investigations in 317 psychiatric patients and 103 normal controls. According to these studies the abnormalities are nosologically rather unspecific. They are induced by a large variety of factors, e.g. emotional stress associated with the clinical symptomatology, weight loss due to malnutrition as a consequence of reduced appetite, medication and drug withdrawal. Stress-induced hypercortisolism appears to be the most common abnormality that may trigger other neuroendocrine dysfunctions, such as a blunted TSH response to TRH. Differences in neuroendocrine abnormalities of depressives are probably due to variations in the manifold factors influencing the hormonal axes involved, to temporal changes in hormonal patterns (e.g. one abnormality triggering another) and to individual differences in the basic activity and the responsiveness of the various axes.

Characterization of a novel zinc transporter ZnuA acquired by Vibrio parahaemolyticus through horizontal gene transfer

PubMed Central

Liu, Ming; Yan, Meiying; Liu, Lizhang; Chen, Sheng

2013-01-01

Vibrio parahaemolyticus is a clinically important foodborne pathogen that causes acute gastroenteritis worldwide. It has been shown that horizontal gene transfer (HGT) contributes significantly to virulence development of V. parahaemolyticus. In this study, we identified a novel znuA homolog (vpa1307) that belongs to a novel subfamily of ZnuA, a bacterial zinc transporter. The vpa1307 gene is located upstream of the V. parahaemolyticus pathogenicity island (Vp-PAIs) in both tdh-positive and trh-positive V. parahaemolyticus strains. Phylogenetic analysis revealed the exogenous origin of vpa1307 with 40% of V. parahaemolyticus clinical isolates possessing this gene. The expression of vpa1307 gene in V. parahaemolyticus clinical strain VP3218 is induced under zinc limitation condition. Gene deletion and complementation assays confirmed that vpa1307 contributes to the growth of VP3218 under zinc depletion condition and that conserved histidine residues of Vpa1307 contribute to its activity. Importantly, vpa1307 contributes to the cytotoxicity of VP3218 in HeLa cells and a certain degree of virulence in murine model. These results suggest that the horizontally acquired znuA subfamily gene, vpa1307, contributes to the fitness and virulence of Vibrio species. PMID:24133656

Characterization of a novel zinc transporter ZnuA acquired by Vibrio parahaemolyticus through horizontal gene transfer.

PubMed

Liu, Ming; Yan, Meiying; Liu, Lizhang; Chen, Sheng

2013-01-01

Vibrio parahaemolyticus is a clinically important foodborne pathogen that causes acute gastroenteritis worldwide. It has been shown that horizontal gene transfer (HGT) contributes significantly to virulence development of V. parahaemolyticus. In this study, we identified a novel znuA homolog (vpa1307) that belongs to a novel subfamily of ZnuA, a bacterial zinc transporter. The vpa1307 gene is located upstream of the V. parahaemolyticus pathogenicity island (Vp-PAIs) in both tdh-positive and trh-positive V. parahaemolyticus strains. Phylogenetic analysis revealed the exogenous origin of vpa1307 with 40% of V. parahaemolyticus clinical isolates possessing this gene. The expression of vpa1307 gene in V. parahaemolyticus clinical strain VP3218 is induced under zinc limitation condition. Gene deletion and complementation assays confirmed that vpa1307 contributes to the growth of VP3218 under zinc depletion condition and that conserved histidine residues of Vpa1307 contribute to its activity. Importantly, vpa1307 contributes to the cytotoxicity of VP3218 in HeLa cells and a certain degree of virulence in murine model. These results suggest that the horizontally acquired znuA subfamily gene, vpa1307, contributes to the fitness and virulence of Vibrio species.

Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mai, Leemin; Pan, Jenntser

1990-01-01

The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 {mu}g/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 {mu}g/rat in stimulating PRL release, whilemore » consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 {mu}g/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective.« less

A Japanese Family with Central Hypothyroidism Caused by a Novel IGSF1 Mutation.

PubMed

Nishigaki, Satsuki; Hamazaki, Takashi; Fujita, Keinosuke; Morikawa, Shuntaro; Tajima, Toshihiro; Shintaku, Haruo

2016-12-01

Hemizygous mutations in the immunoglobulin superfamily member 1 (IGSF1) gene have been demonstrated to cause congenital central hypothyroidism in males. This study reports a family with a novel mutation in the IGSF1 gene located on the long arm of the X chromosome. A two-month-old boy was diagnosed with central hypothyroidism because of prolonged jaundice. A thyrotropin-releasing hormone (TRH) stimulation test indicated dysfunction in both the hypothalamus and the pituitary gland, and prompted the IGSF1 gene to be analyzed. The patient had a novel nonsense variant, c.2713C>T (p.Q905X), in exon 14 of the IGSF1 gene. Studies of the family revealed that the patient's sister and mother were heterozygous carriers of the IGSF1 mutation. The patient's maternal uncle carried the same mutation as the proband but had no overt symptoms. The mother and uncle started levothyroxine supplementation because of subclinical hypothyroidism. A novel mutation (c.2713C>T, p.Q905X) of the IGSF1 gene was identified that causes congenital central hypothyroidism in a Japanese family. The findings further expand the clinical heterogeneity of this entity.

Theoretical Estimate of Maximum Possible Nuclear Explosion

DOE R&D Accomplishments Database

Bethe, H. A.

1950-01-31

The maximum nuclear accident which could occur in a Na-cooled, Be moderated, Pu and power producing reactor is estimated theoretically. (T.R.H.) 2O82 Results of nuclear calculations for a variety of compositions of fast, heterogeneous, sodium-cooled, U-235-fueled, plutonium- and power-producing reactors are reported. Core compositions typical of plate-, pin-, or wire-type fuel elements and with uranium as metal, alloy, and oxide were considered. These compositions included atom ratios in the following range: U-23B to U-235 from 2 to 8; sodium to U-235 from 1.5 to 12; iron to U-235 from 5 to 18; and vanadium to U-235 from 11 to 33. Calculations were performed to determine the effect of lead and iron reflectors between the core and blanket. Both natural and depleted uranium were evaluated as the blanket fertile material. Reactors were compared on a basis of conversion ratio, specific power, and the product of both. The calculated results are in general agreement with the experimental results from fast reactor assemblies. An analysis of the effect of new cross-section values as they became available is included. (auth)

Prevalence and antimicrobial susceptibility of Vibrio parahaemolyticus isolated from oysters in Korea.

PubMed

Kang, Chang-Ho; Shin, YuJin; Kim, WooRi; Kim, YongGyeong; Song, KiCheol; Oh, Eun-Gyoung; Kim, SuKyung; Yu, HongSik; So, Jae-Seong

2016-01-01

Vibrio parahaemolyticus is the most prevalent gastroenteritis-causing pathogen in Korea and in some other Asian countries. It is frequently found in oysters and other seafood. This study monitored changes in the prevalence of V. parahaemolyticus and environmental parameters in oyster aquaculture environments in Korea. From June to October 2014, we tested oysters (Crassostrea gigas) from shellfish-harvesting areas off the west coast of Korea. These 71 isolates were the sum of 16 (22.5%), 19 (26.8%), 23 (32.4%), and 13 (18.3%) isolates collected in July, August, September, and October, respectively. These 71 isolates had the following profiles of resistance against 16 antibiotics: all isolates were resistant to ampicillin and vancomycin, and 52.2, 50.7, and 50.7% of isolates exhibited resistance to cephalothin, rifampin, and streptomycin, respectively. PCR analysis for the presence of the species-specific toxR gene confirmed that 38 (53.5%) of the total 71 isolated strains were positive for V. parahaemolyticus. In PCR analysis for virulence of V. parahaemolyticus, of the 71 isolates tested in the present study, only 38 (53.5%) were positive for the trh virulence gene and 71 (100%) was negative for the tdh virulence gene.

Establishment and Validation of RNA-Based Predictive Models for Understanding Survival of Vibrio parahaemolyticus in Oysters Stored at Low Temperatures

PubMed Central

Liao, Chao; Zhao, Yong

2017-01-01

ABSTRACT This study developed RNA-based predictive models describing the survival of Vibrio parahaemolyticus in Eastern oysters (Crassostrea virginica) during storage at 0, 4, and 10°C. Postharvested oysters were inoculated with a cocktail of five V. parahaemolyticus strains and were then stored at 0, 4, and 10°C for 21 or 11 days. A real-time reverse transcription-PCR (RT-PCR) assay targeting expression of the tlh gene was used to evaluate the number of surviving V. parahaemolyticus cells, which was then used to establish primary molecular models (MMs). Before construction of the MMs, consistent expression levels of the tlh gene at 0, 4, and 10°C were confirmed, and this gene was used to monitor the survival of the total V. parahaemolyticus cells. In addition, the tdh and trh genes were used for monitoring the survival of virulent V. parahaemolyticus. Traditional models (TMs) were built based on data collected using a plate counting method. From the MMs, V. parahaemolyticus populations had decreased 0.493, 0.362, and 0.238 log10 CFU/g by the end of storage at 0, 4, and 10°C, respectively. Rates of reduction of V. parahaemolyticus shown in the TMs were 2.109, 1.579, and 0.894 log10 CFU/g for storage at 0, 4, and 10°C, respectively. Bacterial inactivation rates (IRs) estimated with the TMs (−0.245, −0.152, and −0.121 log10 CFU/day, respectively) were higher than those estimated with the MMs (−0.134, −0.0887, and −0.0732 log10 CFU/day, respectively) for storage at 0, 4, and 10°C. Higher viable V. parahaemolyticus numbers were predicted using the MMs than using the TMs. On the basis of this study, RNA-based predictive MMs are the more accurate and reliable models and can prevent false-negative results compared to TMs. IMPORTANCE One important method for validating postharvest techniques and for monitoring the behavior of V. parahaemolyticus is to establish predictive models. Unfortunately, previous predictive models established based on plate counting methods or on DNA-based PCR can underestimate or overestimate the number of surviving cells. This study developed and validated RNA-based molecular predictive models to describe the survival of V. parahaemolyticus in oysters during low-temperature storage (0, 4, and 10°C). The RNA-based predictive models show the advantage of being able to count all of the culturable, nonculturable, and stressed cells. By using primers targeting the tlh gene and pathogenesis-associated genes (tdh and trh), real-time RT-PCR can evaluate the total surviving V. parahaemolyticus population as well as differentiate the pathogenic ones from the total population. Reliable and accurate predictive models are very important for conducting risk assessment and management of pathogens in food. PMID:28087532

Establishment and Validation of RNA-Based Predictive Models for Understanding Survival of Vibrio parahaemolyticus in Oysters Stored at Low Temperatures.

PubMed

Liao, Chao; Zhao, Yong; Wang, Luxin

2017-03-15

This study developed RNA-based predictive models describing the survival of Vibrio parahaemolyticus in Eastern oysters ( Crassostrea virginica ) during storage at 0, 4, and 10°C. Postharvested oysters were inoculated with a cocktail of five V. parahaemolyticus strains and were then stored at 0, 4, and 10°C for 21 or 11 days. A real-time reverse transcription-PCR (RT-PCR) assay targeting expression of the tlh gene was used to evaluate the number of surviving V. parahaemolyticus cells, which was then used to establish primary molecular models (MMs). Before construction of the MMs, consistent expression levels of the tlh gene at 0, 4, and 10°C were confirmed, and this gene was used to monitor the survival of the total V. parahaemolyticus cells. In addition, the tdh and trh genes were used for monitoring the survival of virulent V. parahaemolyticus Traditional models (TMs) were built based on data collected using a plate counting method. From the MMs, V. parahaemolyticus populations had decreased 0.493, 0.362, and 0.238 log 10 CFU/g by the end of storage at 0, 4, and 10°C, respectively. Rates of reduction of V. parahaemolyticus shown in the TMs were 2.109, 1.579, and 0.894 log 10 CFU/g for storage at 0, 4, and 10°C, respectively. Bacterial inactivation rates (IRs) estimated with the TMs (-0.245, -0.152, and -0.121 log 10 CFU/day, respectively) were higher than those estimated with the MMs (-0.134, -0.0887, and -0.0732 log 10 CFU/day, respectively) for storage at 0, 4, and 10°C. Higher viable V. parahaemolyticus numbers were predicted using the MMs than using the TMs. On the basis of this study, RNA-based predictive MMs are the more accurate and reliable models and can prevent false-negative results compared to TMs. IMPORTANCE One important method for validating postharvest techniques and for monitoring the behavior of V. parahaemolyticus is to establish predictive models. Unfortunately, previous predictive models established based on plate counting methods or on DNA-based PCR can underestimate or overestimate the number of surviving cells. This study developed and validated RNA-based molecular predictive models to describe the survival of V. parahaemolyticus in oysters during low-temperature storage (0, 4, and 10°C). The RNA-based predictive models show the advantage of being able to count all of the culturable, nonculturable, and stressed cells. By using primers targeting the tlh gene and pathogenesis-associated genes ( tdh and trh ), real-time RT-PCR can evaluate the total surviving V. parahaemolyticus population as well as differentiate the pathogenic ones from the total population. Reliable and accurate predictive models are very important for conducting risk assessment and management of pathogens in food. Copyright © 2017 American Society for Microbiology.

A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche?

PubMed

Iwatani, N; Kodama, M; Seto, H

1992-06-01

We describe a female child with pituitary gigantism and precocious adrenarche. From two years of age she showed unusual overgrowth, and at 5 years old she was 133.5 cm (+ 5.5 SD) tall and weighed 40.5 kg. Her precocious manifestations were public hair, acne vulgaris, hirsutism, and advanced bone age. Endocrinological examination revealed markedly increased serum growth hormone (GH) and prolactin (PRL), which responded paradoxically to a TRH test. In addition, the concentrations of serum dehydroepiandrosterone (DHA) and its sulfate (DHAS) were increased to adult levels, moving in accordance with changes in ACTH, which suggested that these androgens were secreted from the adrenal glands functionally. These androgens seemed to be responsible for her partial precocity. Prior reports have suggested that GH and/or PRL overproduction might have played a role in the induction of adrenarche. Also, in previous reports of 9 gigantism patients under 10 years old, the manifestation of precocious adrenarche was suggested in 8. Further investigation of the influence of GH and PRL on adrenal androgen production in children with pituitary gigantism is required. On the other hand, in short children with normal GH secretion, attention should be paid to whether or not the GH therapy in early childhood induces precocious adrenarche.

Ternary lithium stannides Li xT 3Sn 7-x ( T=Rh, Ir)

NASA Astrophysics Data System (ADS)

Sreeraj, Puravankara; Kurowski, Daniel; Hoffmann, Rolf-Dieter; Wu, Zhiyun; Pöttgen, Rainer

2005-11-01

The ternary stannides Li xRh 3Sn 7-x ( x=0.45, 0.64, 0.80) and Li xIr 3Sn 7-x ( x=0.62 and 0.66) were synthesized from the elements in sealed tantalum tubes in a water-cooled sample chamber of an induction furnace. The samples were characterized by X-ray diffraction on powders and single crystals. The stannides adopt the cubic Ir 3Ge 7-type structure (space group Im3¯m, Z=4). In this structure type the tin atoms occupy the Wyckoff positions 12 d and 16 f and form two interpenetrating frameworks consisting of cubes and square antiprisms. The rhodium and iridium atoms center the square antiprisms and are arranged in pairs. With increasing lithium substitution the lattice parameter of Ir 3Sn 7 (936.7) decreases via 932.2 pm ( x=0.62) to 931.2 pm ( x=0.66), while the Ir-Ir distance remains almost the same (290 pm). A similar trend is observed for the rhodium compounds. The lithium atoms substitute Sn on both framework sites. However, the 16 f site shows a substantially larger preference for Li occupation. This is in contrast to the isotypic magnesium based compounds.

An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.

PubMed

Krashes, Michael J; Shah, Bhavik P; Madara, Joseph C; Olson, David P; Strochlic, David E; Garfield, Alastair S; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen D; Lowell, Bradford B

2014-03-13

Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.

Comparison of the Effects of Environmental Parameters on the Growth Variability of Vibrio parahaemolyticus Coupled with Strain Sources and Genotypes Analyses

PubMed Central

Liu, Bingxuan; Liu, Haiquan; Pan, Yingjie; Xie, Jing; Zhao, Yong

2016-01-01

Microbial growth variability plays an important role on food safety risk assessment. In this study, the growth kinetic characteristics corresponding to maximum specific growth rate (μmax) of 50 V. parahaemolyticus isolates from different sources and genotypes were evaluated at different temperatures (10, 20, 30, and 37°C) and salinity (0.5, 3, 5, 7, and 9%) using the automated turbidimetric system Bioscreen C. The results demonstrated that strain growth variability increased as the growth conditions became more stressful both in terms of temperature and salinity. The coefficient of variation (CV) of μmax for temperature was larger than that for salinity, indicating that the impact of temperature on strain growth variability was greater than that of salinity. The strains isolated from freshwater aquatic products had more conspicuous growth variations than those from seawater. Moreover, the strains with tlh+/tdh+/trh− exhibited higher growth variability than tlh+/tdh−/trh− or tlh+/tdh−/trh+, revealing that gene heterogeneity might have possible relations with the growth variability. This research illustrates that the growth environments, strain sources as well as genotypes have impacts on strain growth variability of V. parahaemolyticus, which can be helpful for incorporating strain variability in predictive microbiology and microbial risk assessment. PMID:27446034

Strategies for enhancing catecholamine-mediated neurotransmission

NASA Technical Reports Server (NTRS)

Wurtman, Richard J.

1992-01-01

Major findings made during this project period included the following observations: changes in tyrosine availability do affect brain dopamine release, as assessed by in vivo microdialysis, but that neuronal feedback mechanisms limit the durations of this effect except when dopaminergic neurotransmission has been deficient; the circulating hormone TRH markedly stimulates brain dopamine release, an effect probably mediated by its diketopiperazine metabolite; the amount of circulating L-dopa which enters the brain is both enhanced by carbohydrate consumption and suppressed by protein intake (both nutritional effects can be damaging, inasmuch as a sudden rush of L-dopa into the brain can facilitate dyskinesias, while the inhibition of brain L-dopa uptake by proteins suppresses its conversion to brain dopamine; an appropriate mixture of dietary proteins and carbohydrates can obviate both effects); serotonin release from superfused hypothalamic slices is a linear function of available tryptophan levels throughout the normal dynamic range; the daily rhythm in plasma melatonin levels is abnormal both in the sudden infant death syndrome and in women with secondary amenorrhea; tyrosine can potentiate the anorectic effects of widely-used sympathomimetic drugs; newly-described COMT inhibitors can enhance brain dopamine release in vivo; and a cell culture system, based on Y-79 (retinoblast) cells, exists in which melatonin reliably suppresses dopamine release.

Molecular cloning, molecular evolution and gene expression of cDNAs encoding thyrotropin-releasing hormone receptor subtypes in a teleost, the sockeye salmon (Oncorhynchus nerka).

PubMed

Saito, Yuichi; Mekuchi, Miyuki; Kobayashi, Noriaki; Kimura, Makoto; Aoki, Yasuhiro; Masuda, Tomohiro; Azuma, Teruo; Fukami, Motohiro; Iigo, Masayuki; Yanagisawa, Tadashi

2011-11-01

Molecular cloning of thyrotropin-releasing hormone receptors (TRHR) was performed in a teleost, the sockeye salmon (Oncorhynchus nerka). Four different TRHR cDNAs were cloned and named TRHR1, TRHR2a, TRHR2b and TRHR3 based on their similarity to known TRHR subtypes in vertebrates. Important residues for TRH binding were conserved in deduced amino acid sequences of the three TRHR subtypes except for the TRHR2b. Seven transmembrane domains were predicted for TRHR1, TRHR2a and TRHR3 proteins but only five for TRHR2b which appears to be truncated. In silico database analysis identified putative TRHR sequences including invertebrate TRHR and reptilian, avian and mammalian TRHR3. Phylogenetic analyses predicted the molecular evolution of TRHR in vertebrates: from the common ancestral TRHR (i.e. invertebrate TRHR), the TRHR2 subtype diverged first and then TRHR1 and TRHR3 diverged. Reverse transcription-polymerase chain reaction analyses revealed TRHR1 transcripts in the brain (hypothalamus), retina, pituitary gland and large intestine; TRHR2a in the brain (telencephalon and hypothalamus); and TRHR3 in the brain (olfactory bulbs) and retina. Copyright © 2011 Elsevier Inc. All rights reserved.

Investigation of Reference Genes in Vibrio parahaemolyticus for Gene Expression Analysis Using Quantitative RT-PCR.

PubMed

Ma, Yue-Jiao; Sun, Xiao-Hong; Xu, Xiao-Yan; Zhao, Yong; Pan, Ying-Jie; Hwang, Cheng-An; Wu, Vivian C H

2015-01-01

Vibrio parahaemolyticus is a significant human pathogen capable of causing foodborne gastroenteritis associated with the consumption of contaminated raw or undercooked seafood. Quantitative RT-PCR (qRT-PCR) is a useful tool for studying gene expression in V. parahaemolyticus to characterize its virulence factors and understand the effect of environmental conditions on its pathogenicity. However, there is not a stable gene in V. parahaemolyticus that has been identified for use as a reference gene for qRT-PCR. This study evaluated the stability of 6 reference genes (16S rRNA, recA, rpoS, pvsA, pvuA, and gapdh) in 5 V. parahaemolyticus strains (O3:K6-clinical strain-tdh+, ATCC33846-tdh+, ATCC33847-tdh+, ATCC17802-trh+, and F13-environmental strain-tdh+) cultured at 4 different temperatures (15, 25, 37 and 42°C). Stability values were calculated using GeNorm, NormFinder, BestKeeper, and Delta CT algorithms. The results indicated that recA was the most stably expressed gene in the V. parahaemolyticus strains cultured at different temperatures. This study examined multiple V. parahaemolyticus strains and growth temperatures, hence the finding provided stronger evidence that recA can be used as a reference gene for gene expression studies in V. parahaemolyticus.

A functional thyrotropin- and growth hormone-secreting pituitary adenoma with a ultrastructurally monomorphic feature: a case study.

PubMed

Ozawa, Y; Kameya, T; Kasuga, A; Naritaka, H; Kanda, N; Maruyama, H; Saruta, T

1998-04-01

A 38-yr-old female with a TSH- and GH-secreting pituitary adenoma is described, who had both overt symptoms, hyperthyroidism and acromegaly. Her serum TSH was not suppressed despite high concentrations of free T3 and free T4, and her alpha-subunit/TSH molar ratio was high. Her serum GH was consistently high, and was not suppressed by an oral glucose tolerance test. Preoperative testing revealed that, although the TSH response was impaired, TSH, alpha-subunit and GH were increased by TRH injection, and that these hormones were reduced by bromocriptine or somatostatin analog. Although she did not have hyperprolactinemia, the in vitro culture and immunohistochemical studies revealed that the adenoma cells produced and released PRL, in addition to TSH, alpha-subunit and GH. Immunohistochemical studies showed the presence of GH in the cytoplasm of many adenoma cells. TSH beta-positive adenoma cells were less frequently seen than GH-positive adenoma cells. No cells showed the coexistence of GH and TSH beta, and a few cells were positive for PRL. By electron microscopy, the adenoma was found to be composed of a single cell type resembling thyrotrophs, and did not have any characteristics of somatotrophs. This case was considered to be of interest, because the adenoma was ultrastructurally monomorphous, but immunohistochemically polymorphous.

Material Processing with High Power CO2-Lasers

NASA Astrophysics Data System (ADS)

Bakowsky, Lothar

1986-10-01

After a period of research and development lasertechnique now is regarded as an important instrument for flexible, economic and fully automatic manufacturing. Especially cutting of flat metal sheets with high power C02-lasers and CNC controlled two or three axes handling systems is a wide spread. application. Three dimensional laser cutting, laser-welding and -heat treatment are just at the be ginning of industrial use in production lines. The main. advantages of laser technology. are - high. accuracy - high, processing velocity - law thermal distortion. - no tool abrasion. The market for laser material processing systems had 1985 a volume of 300 Mio S with growth rates between, 20 % and 30 %. The topic of this lecture are hiTrh. power CO2-lasers. Besides this systems two others are used as machining tools, Nd-YAG- and Eximer lasers. All applications of high. power CO2-lasers to industrial material processing show that high processing velocity and quality are only guaranteed in case of a stable intensity. profile on the workpiece. This is only achieved by laser systems without any power and mode fluctuations and by handling systems of high accuracy. Two applications in the automotive industry are described, below as examples for laser cutting and laser welding of special cylindrical motor parts.

Highly diverse recombining populations of Vibrio cholerae and Vibrio parahaemolyticus in French Mediterranean coastal lagoons

PubMed Central

Esteves, Kévin; Mosser, Thomas; Aujoulat, Fabien; Hervio-Heath, Dominique; Monfort, Patrick; Jumas-Bilak, Estelle

2015-01-01

Vibrio parahaemolyticus and Vibrio cholerae are ubiquitous to estuarine and marine environments. These two species found in Mediterranean coastal systems can induce infections in humans. Environmental isolates of V. cholerae (n = 109) and V. parahaemolyticus (n = 89) sampled at different dates, stations and water salinities were investigated for virulence genes and by a multilocus sequence-based analysis (MLSA). V. cholerae isolates were all ctxA negative and only one isolate of V. parahaemolyticus displayed trh2 gene. Most Sequence Types (ST) corresponded to unique ST isolated at one date or one station. Frequent recombination events were detected among different pathogenic species, V. parahaemolyticus, V. cholerae, Vibrio mimicus, and Vibrio metoecus. Recombination had a major impact on the diversification of lineages. The genetic diversity assessed by the number of ST/strain was higher in low salinity condition for V. parahaemolyticus and V. cholerae whereas the frequency of recombination events in V. cholerae was lower in low salinity condition. Mediterranean coastal lagoon systems housed V. cholerae and V. parahaemolyticus with genetic diversities equivalent to the worldwide diversity described so far. The presence of STs found in human infections as well as the frequency of recombination events in environmental vibrios populations could predict a potential epidemiological risk. PMID:26236294

Pituitary function in patients with hereditary haemochromatosis.

PubMed

Uitz, P M; Hartleb, S; Schaefer, S; Al-Fakhri, N; Kann, P H

2013-01-01

Haemochromatosis may impair the function of endocrine organs, amongst others the pituitary gland. It was the aim of this study to determine pituitary function in adult patients with genetically defined hereditary haemochromatosis in a prospective diagnostic study using a standardised stimulation test. Therefore, 22 patients (7 females, 15 males; age at diagnosis of haemochromatosis 48.1 ± 7.9 years; age at study inclusion 50.7 ± 7.7 years) with genetically defined hereditary haemochromatosis were investigated by a combined pituitary stimulation test (CRH, GHRH/arginine, GnRH, TRH). In 11 patients (50% of the study population; 2 females, 9 males), pituitary insufficiencies were detected [isolated corticotrophic insufficiency (peak cortisol < 181.25 μg/l/500 nmol/l) n=10 (2 females, 8 males); combined corticotrophic and borderline gonadotrophic insufficiency (basal testosterone 2.4-3.0 μg/l without basal LH-elevation) in 1 male]. Somatotrophic pituitary insufficiencies were not found. IFG-1 concentrations below -2 standard deviations in 7 patients (32%) may be attributed to impaired hepatic IGF-1 synthesis. Hypopituitarism, particularly corticotrophic insufficiency, seems to be prevalent in a considerable number of middle-aged patients with hereditary haemochromatosis. Despite normal somatotrophic function, low IGF-1 serum concentrations may be found in a subgroup of haemochromatosis patients. © Georg Thieme Verlag KG Stuttgart · New York.

Detection and molecular characterization of Vibrio parahaemolyticus isolated from seafood harvested along the southwest coast of India.

PubMed

Raghunath, Pendru; Acharya, Sadananda; Bhanumathi, Amarbahadur; Karunasagar, Iddya; Karunasagar, Indrani

2008-09-01

The levels of total and tdh(+)Vibrio parahaemolyticus were estimated in 83 seafood samples from southwest coast of India by colony hybridization. Conventional enrichment and isolation technique was also used to study the prevalence. Polymerase chain reaction (PCR) was performed on bacterial cell lyates for detection of total and pathogenic V. parahaemolyticus by amplification of specific genes. Of 83 samples tested, V. parahaemolyticus could be detected in 74 (89.2%) samples and tdh(+)V. parahaemolyticus in 5 (6.0%) samples by colony hybridization. V. parahaemolyticus was detected in 68 (81.9%) of 83 samples after 18 h of enrichment by PCR, and isolated from 63 (75.9%) of 83 samples by conventional isolation. The virulence genes tdh and trh could be detected in 8.4% and 25.3%, respectively, in the sample enrichment broths by PCR. Use of colony hybridization following enrichment to achieve sensitive detection of tdh(+)V. parahaemolyticus in seafood was evaluated using another set of 58 seafood samples. Thirty pathogenic V. parahaemolyticus strains isolated during the study were screened by PCR for genetic markers to be specific for the detection of the pandemic clone. Results of this study suggest that the GS-PCR may serve as a reliable genetic marker for the pandemic clone of V. parahaemolyticus.

The hot oyster: levels of virulent Vibrio parahaemolyticus strains in individual oysters.

PubMed

Klein, Savannah L; Lovell, Charles R

2017-02-01

Vibrio parahaemolyticus is the leading cause of seafood-associated gastroenteritis and is most commonly transmitted by raw oysters. Consequently, detection of virulent strains of this organism in oysters is a primary concern for seafood safety. Vibrio parahaemolyticus levels were determined in 110 individual oysters harvested from two sampling sites in SC, USA. The majority of oysters (98%) contained low levels of presumptive V. parahaemolyticus However, two healthy oysters contained presumptive V. parahaemolyticus numbers that were unusually high. These two 'hot' oysters contained levels of presumptive V. parahaemolyticus within the gills that were ∼100-fold higher than the average for other oysters collected at the same date and location. Current V. parahaemolyticus detection practices require homogenizing a dozen oysters pooled together to determine V. parahaemolyticus numbers, a procedure that would dilute out V. parahaemolyticus in these 'hot' oysters. This study demonstrates the variability of V. parahaemolyticus densities taken from healthy, neighboring individual oysters in the environment. Additionally, environmental V parahaemolyticus isolates were screened for the virulence-related genes, tdh and trh, using improved polymerase chain reaction primers and protocols. We detected these genes, previously thought to be rare in environmental isolates, in approximately half of the oyster isolates. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Subclinical and manifested hypothyroidism as a consequence of thyroid autoimmune disease].

PubMed

Milosević, Dragoslav P; Djurica, Snezana; Davidović, Mladen; Stević, Radmila; Rajić, Miodrag; Marković, Natasa

2005-10-01

Chronic thyroiditis (Hashimoto's disease) is a slowly developing persistent inflamation of the thyroid gland, which frequently leads to hypothyroidism. Some of the up-to-date knowledge about hypothyroidism, both subclinical and manifested, caused by autoimmune disease, was presented. Autoimmune thyroid gland disease can occur at any age, but predominantly affects women after periods of high emotional and physical stress or accidents, as well as during periods of hormonal changes. It can also develop in families, and having an autoimmune disease slightly increases the risk of developing another. This paper showed an increasing incidence of subclinical hypothyroidism (4.17%) in elderly, and, at the same time, the incidence of primary hypothyroidism accounting for 1%. It is very usefull to estimate the stimulated thyrotropin (TSH) response, as well as the value of fast, short time thyroid gland reserves, analyzed by T3 and T4 serum level at 60th minute after TRH stimulation. Treatment of choice for HT (hypothyroidism of any cause) is thyroid hormone replacement. Drug of choice is orally administered levothyroxine sodium, usually for life-time. The standard dose is 1.6-1.8 mcg/kg body weight per day, but is in most cases patient dependent. Elderly patients usually require smaller replacement dose of levothyroxine, sometimes less than 1 mcg/kg body weight per day with coronary dilatator at the same time.

[Characterization of haemolysis of the Vibrio parahaemolyticus no.93].

PubMed

Su, S C; Lee, C Y

1997-02-01

Vibrio parahaemolyticus is a causative bacterium of food poisoning, and the haemolysin produced by this organism has been considered as one of the important virulence factors. In order to understand the pathogenic mechanism of this bacterium, the characteristics of haemolysin from Vibrio parahaemolyticus isolated from Taiwan were studied. One of the clinical strains, V. parahaemolyticus No.93, presents a weak hemolytic zone on 7% NaCl-Wagatsuma medium. The DNA hybridization results show that V. parahemolyticus has neither tdh nor trh gene. V. parahaemolyticus No.93 shows obviously hemolytic zone on 3%-NaCl Wagatsuma medium (human blood). The crude extracellular protein of V. parahaemolyticus No. 93 was evaluated for its heat tolerance and enzyme activities by media assay. The results show that this crude extracellular protein is thermolabile. The crude extracellular protein of V. parahaemolyticus No.93 was analyzed on 10% SDS-PAGE and an apparent band of 64 kDa protein was observed. Furthermore, the crude extracellular protein was analyzed by running gelatin-SDS-PAGE and hemoglobin-SDS-PAGE, and three clear zones on 62 kDa, 52 kDa and 41 kDa were observed on both SDS-PAGEs. Thus we propose that the crude extracellular protein of the V. parahaemolyticus No.93 can degrade gelatin as well as hemoglobin. Whether these protease being the virulence factors of Vibrio parahaemolyticus No.93 needs to be further studied.

Progesterone and norgestrel alter transcriptional expression of genes along the hypothalamic-pituitary-thyroid axis in zebrafish embryos-larvae.

PubMed

Liang, Yan-Qiu; Huang, Guo-Yong; Ying, Guang-Guo; Liu, Shuang-Shuang; Jiang, Yu-Xia; Liu, Shan

2015-01-01

The aim of this study was to investigate the effects of progestins on the hypothalamic-pituitary-thyroid (HPT) axis in the early stage of zebrafish. Zebrafish embryos were exposed to progesterone (P4) or norgestrel (NGT) at 5, 50 and 100 ng L(-1) for 144 h post fertilization (hpf), and the transcriptional levels of target genes along the hypothalamic-pituitary-thyroid axis were determined daily. The results showed that P4 had only minor effects on the mRNA expression of thyroglobulin (Tg), iodothyronine deiodinase type Ι (Dio1) and thyroid hormone receptor β (Thrb) genes. Similarly, the effects of NGT on transcripts of thyrotropin-releasing hormone (Trh), Dio1, iodothyronine deiodinase type II (Dio2) and thyroid hormone receptor α (Thra) genes were generally low. In addition, NGT resulted in some alterations of Tg and Thrb transcripts at different time points. However, a strong induction of Nis mRNA by P4 and NGT was observed in zebrafish embryos-larvae. The overall results showed that besides Nis no effects on the hypothalamic-pituitary-thyroid (HPT) axis are observed following exposure to P4 and NGT, which imply that both P4 and NGT have potential effects on the thyroid endocrine system by inducing transcript of Nis gene during the early stage of zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypothyroidism Compromises Hypothalamic Leptin Signaling in Mice

PubMed Central

Groba, Claudia; Mayerl, Steffen; van Mullem, Alies A.; Visser, Theo J.; Darras, Veerle M.; Habenicht, Andreas J.

2013-01-01

The impact of thyroid hormone (TH) on metabolism and energy expenditure is well established, but the role of TH in regulating nutritional sensing, particularly in the central nervous system, is only poorly defined. Here, we studied the consequences of hypothyroidism on leptin production as well as leptin sensing in congenital hypothyroid TRH receptor 1 knockout (Trhr1 ko) mice and euthyroid control animals. Hypothyroid mice exhibited decreased circulating leptin levels due to a decrease in fat mass and reduced leptin expression in white adipose tissue. In neurons of the hypothalamic arcuate nucleus, hypothyroid mice showed increased leptin receptor Ob-R expression and decreased suppressor of cytokine signaling 3 transcript levels. In order to monitor putative changes in central leptin sensing, we generated hypothyroid and leptin-deficient animals by crossing hypothyroid Trhr1 ko mice with the leptin-deficient ob/ob mice. Hypothyroid Trhr1/ob double knockout mice showed a blunted response to leptin treatment with respect to body weight and food intake and exhibited a decreased activation of phospho-signal transducer and activator of transcription 3 as well as a up-regulation of suppressor of cytokine signaling 3 upon leptin treatment, particularly in the arcuate nucleus. These data indicate alterations in the intracellular processing of the leptin signal under hypothyroid conditions and thereby unravel a novel mode of action by which TH affects energy metabolism. PMID:23518925

Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.).

PubMed

Geven, Edwin J W; Verkaar, Folkert; Flik, Gert; Klaren, Peter H M

2006-12-01

The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

[Dwarfism due to familial panhypopituitarism].

PubMed

Cos Welsh, J; Espinosa de los Monteros, A; de la Luz Ajuria, M; Morillo Almao, E

1977-01-01

Three sisters of 27 7/12, 13 8/12 and 9 1/12 years of age, respectively, with proportionate dwarfism, high pitched voice and lack of sexual development are described. All the patients had very low serum levels of immunoreactive growth hormone (GH), as well as of LH and FSH. Hypoglycemia induced by insulin and arginine infusion failed to increase GH levels, and the administration of the hypothalamic LH-FSH releasing hormone (LH-RH) did not elicit any response in the secretion of gonadotropins. The oldest sister developed hypothyroidism in recent years, since the I131 thyroid uptake was normal ten years before; her serum TSH was low and did not change with TRH stimulation. In addition, a low pituitary ACTH reserve was demonstrated by the hypoglycemia and metirapone tests. Case 2 showed partial pituitary TSH and ACTH reserve, whereas the youngest child only had low TSH pituitary reserve. These patients had all the clinical and laboratory characteristics of familial panhypopituitarism, with normal sella turcica. Genetic transmission in this cases is consistent with the autosomal recessive form, which is the most frequent type of inheritance of this entity. Consanguinity can not be ruled out. The results of the hypothalamic-pituitary functional tests apparently suggest that the primary defect could be located at the pituitary level. It is also possible that the pathological process may have a progressive evolution.

Prevalence and Antimicrobial Resistance of Vibrio spp. in Retail and Farm Shrimps in Ecuador.

PubMed

Sperling, L; Alter, T; Huehn, S

2015-11-01

The aim of this study was to investigate the prevalence of Vibrio spp. in shrimp at retail and in shrimp farms in Ecuador and to determine the antimicrobial agent resistance patterns of farm isolates. The presence of genes linked to early mortality syndrome (EMS) or acute hepatopancreatic necrosis disease (AHPND) also was evaluated. Vibrio spp. were isolated from retail shrimps in Cuenca, Ecuador, and farm shrimps originating from provinces El Oro and Guayas, Ecuador. A total of 229 shrimp samples were collected, of which 71 originated from retail markets in Cuenca and 158 came from shrimp farms. Overall, 219 (95.6%) samples tested positive for Vibrio spp. Vibrio parahaemolyticus (80.8%) was the most common species detected, followed by Vibrio alginolyticus (50.2%), Vibrio cholerae (11.3%), and Vibrio vulnificus (3.5%). None of the V. parahaemolyticus isolates carried the virulence-associated tdh and trh genes. In V. parahaemolyticus shrimp farm isolates, high resistance was found to ampicillin (92.2%), and intermediate resistance was found to tetracycline (51.3%) and amikacin (22.1%). Of the V. parahaemolyticus strains, 68 were resistant to at least three antimicrobial agents, and 2 were resistant to seven antimicrobial agents simultaneously. Up to 18 resistant isolates were found for V. alginolyticus, whereas V. vulnificus and V. cholerae isolates were more susceptible. None of the V. parahaemolyticus isolates carried the EMS-AHPND plasmid. The results of this study revealed the ubiquitous occurrence of Vibrio spp. in shrimps at retail and on shrimp farms in Ecuador.

Experimental evaluation of the impact of maternal consumption of aqueous leaf extract of Hybanthus enneaspermus on pregnancy in Sprague Dawley rats.

PubMed

Olubajo, Awobajo Funmileyi; Adefunke, Adegoke Olufeyisipe; Olubusola, Iranloye Bolanle; Ibilola, Olatunji-Bello Ibiyemi

2013-01-01

The impact of aqueous leaf extract of Hybanthus enneaspermus (HEaq) on pregnancy factors and litter survival was investigated in Sprague Dawley (SD) rat. Control group received distilled water while the test group received 2g/kg body weight of HEaq orally. Blood samples were collected on days one and twenty of pregnancy for total blood count, serum thyroid hormone, thyroid stimulating hormone (TSH) and thyrotropin releasing hormone (TRH) assay. Half the number of rats in each group was sacrificed on day nineteen of pregnancy and the placenta and foetus were removed and weighed. The second half carried their pregnancy to term. Number and weights of litter were recorded at birth and the litter were also subjected to righting reflex test. Post-natal survival rate was determined for each group while effect of HEaq was also examined in-vivo on the activities of pregnant myometrial muscle. HEaq significantly decreased (p<0.05) foetal weight, placenta weight, foetal growth and survival, number and weights of litter at birth, maternal serum triiodotyroxine T3 and TSH level. Mean corpuscular haemoglobin, white blood cell count, platelet count and lipid profile were significantly increased (P<0.05). HEaq increased the frequency and percentage contraction of gravid myometrial muscle in a dose dependent manner. Maternal consumption of aqueous leaf extract of Hybanthus enneaspermus adversely affected pregnancy and development of the foetus, as it precipitated resorption of developing foetus and reduced size and weight of litter at term.

Different abundance and correlational patterns exist between total and presumed pathogenic Vibrio vulnificus and V. parahaemolyticus in shellfish and waters along the North Carolina coast.

PubMed

Williams, Tiffany C; Froelich, Brett A; Phippen, Britney; Fowler, Patricia; Noble, Rachel T; Oliver, James D

2017-06-01

Monitoring of Vibrio vulnificus and V. parahaemolyticus abundance is pertinent due to the ability of these species to cause disease in humans through aquatic vectors. Previously, we performed a multiyear investigation tracking Vibrio spp. levels in five sites along the southeastern North Carolina coast. From February 2013 to October 2015, total V. vulnificus and V. parahaemolyticus abundance was measured in water, oysters and clams. In the current study, pathogenic subpopulations were identified in these isolates using molecular markers, revealing that 5.3% of V. vulnificus isolates possessed the virulence-correlated gene (vcgC), and 1.9% of V. parahaemolyticus isolates harbored one or both of the virulence-associated hemolysin genes (tdh and trh). Total V. parahaemolyticus abundance was not sufficient to predict the abundance of pathogenic subpopulations. Specifically, pathogenic V. parahaemolyticus isolates were more often isolated in cooler waters and were sometimes isolated when no other V. parahaemolyticus strains were detectable. Vibrio vulnificus clinical (C-) genotypes correlated with total V. vulnificus; however, salinity, water depth and total suspended solids influenced C- and E-genotypes differently. Lastly, we documented individual oysters harboring significantly higher V. vulnificus levels for which there was no ecological explanation, a phenomenon that deserves closer attention due to the potentially elevated health hazard associated with these 'hot' shellfish. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ecology of Vibrio parahaemolyticus and Vibrio vulnificus in the Coastal and Estuarine Waters of Louisiana, Maryland, Mississippi, and Washington (United States)

PubMed Central

Bowers, John C.; Griffitt, Kimberly J.; Molina, Vanessa; Clostio, Rachel W.; Pei, Shaofeng; Laws, Edward; Paranjpye, Rohinee N.; Strom, Mark S.; Chen, Arlene; Hasan, Nur A.; Huq, Anwar; Noriea, Nicholas F.; Grimes, D. Jay; Colwell, Rita R.

2012-01-01

Vibrio parahaemolyticus and Vibrio vulnificus, which are native to estuaries globally, are agents of seafood-borne or wound infections, both potentially fatal. Like all vibrios autochthonous to coastal regions, their abundance varies with changes in environmental parameters. Sea surface temperature (SST), sea surface height (SSH), and chlorophyll have been shown to be predictors of zooplankton and thus factors linked to vibrio populations. The contribution of salinity, conductivity, turbidity, and dissolved organic carbon to the incidence and distribution of Vibrio spp. has also been reported. Here, a multicoastal, 21-month study was conducted to determine relationships between environmental parameters and V. parahaemolyticus and V. vulnificus populations in water, oysters, and sediment in three coastal areas of the United States. Because ecologically unique sites were included in the study, it was possible to analyze individual parameters over wide ranges. Molecular methods were used to detect genes for thermolabile hemolysin (tlh), thermostable direct hemolysin (tdh), and tdh-related hemolysin (trh) as indicators of V. parahaemolyticus and the hemolysin gene vvhA for V. vulnificus. SST and suspended particulate matter were found to be strong predictors of total and potentially pathogenic V. parahaemolyticus and V. vulnificus. Other predictors included chlorophyll a, salinity, and dissolved organic carbon. For the ecologically unique sites included in the study, SST was confirmed as an effective predictor of annual variation in vibrio abundance, with other parameters explaining a portion of the variation not attributable to SST. PMID:22865080

The role of limited proteolysis of thyrotropin-releasing hormone in thermoregulation. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prasad, C.

1982-01-01

Cyclo (His-Pro) is a biologiclly active cyclic dipeptide derived from thyrotropin-releasing hormone by its limited proteolysis. We have developed a specific radioimmunoassay for this cyclic peptide and shown its presence throughout rat and monkey brains. The normal rat brain concentration of cyclo (His-Pro) ranged from 35-61 pmols/brain. The elution profiles of rat brain cyclo (His-Pro)-like immunoreactivity and synthetic radioactive cyclo (His-Pro) following gel filtration, ion-exchange chromatography and high pressure liquid chromatography were similar. An analysis of the regional distribution of cyclo (His-Pro) and TRH in rat and monkey brains exhibited no apparent precursor-product relationship. Studies on the neuroanatomic sites formore » the thermoregulatory effects of cyclo (His-Pro) suggested that the neural loci responsible for cyclo (His-Pro)-induced hypothermia resides within POA/AHA. The endogenous levels of brain cyclo (His-Pro) were elevated when rats were made either hypothyroid by surgical thyroidectomy or forced to drink alcohol for six weeks. These studies demonstrate that cyclo (His-Pro) is present throughout the central nervous system in physiologically relevant concentrations which can be modified by appropriate physiological and pharamacological manipulations. These data in conjunction with earlier reports of multiple biological activities of exogenous cyclo (His-Pro), suggest that endogenous cyclo (His-Pro) is a biological active peptide and it may play a neurotransmitter or neuromodulator role in the central nervous system.« less

Complete genome sequence of Vibrio parahaemolyticus strain FORC_008, a foodborne pathogen from a flounder fish in South Korea.

PubMed

Kim, Suyeon; Chung, Han Young; Lee, Dong-Hoon; Lim, Jong Gyu; Kim, Se Keun; Ku, Hye-Jin; Kim, You-Tae; Kim, Heebal; Ryu, Sangryeol; Lee, Ju-Hoon; Choi, Sang Ho

2016-07-01

Vibrio parahaemolyticus is a Gram-negative, motile, nonspore-forming pathogen that causes foodborne illness associated with the consumption of contaminated seafoods. Although many cases of foodborne outbreaks caused by V. parahaemolyticus have been reported, the genomes of only five strains have been completely sequenced and analyzed using bioinformatics. In order to characterize overall virulence factors and pathogenesis of V. parahaemolyticus associated with foodborne outbreak in South Korea, a new strain FORC_008 was isolated from flounder fish and its genome was completely sequenced. The genomic analysis revealed that the genome of FORC_008 consists of two circular DNA chromosomes of 3266 132 bp (chromosome I) and 1772 036 bp (chromosome II) with a GC content of 45.36% and 45.53%, respectively. The entire genome contains 4494 predicted open reading frames, 129 tRNAs and 31 rRNA genes. While the strain FORC_008 does not have genes encoding thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH), its genome encodes many other virulence factors including hemolysins, pathogenesis-associated secretion systems and iron acquisition systems, suggesting that it may be a potential pathogen. This report provides an extended understanding on V. parahaemolyticus in genomic level and would be helpful for rapid detection, epidemiological investigation and prevention of foodborne outbreak in South Korea. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Genetic diversity of Vibrio parahaemolyticus strains isolated from farmed Pacific white shrimp and ambient pond water affected by acute hepatopancreatic necrosis disease outbreak in Thailand.

PubMed

Chonsin, Kaknokrat; Matsuda, Shigeaki; Theethakaew, Chonchanok; Kodama, Toshio; Junjhon, Jiraphan; Suzuki, Yasuhiko; Suthienkul, Orasa; Iida, Tetsuya

2016-01-01

Acute hepatopancreatic necrosis disease (AHPND) is an emerging shrimp disease that causes massive die-offs in farmed shrimps. Recent outbreaks of AHPND in Asia have been causing great losses for shrimp culture and have become a serious socioeconomic problem. The causative agent of AHPND is Vibrio parahaemolyticus, which is typically known to cause food-borne gastroenteritis in humans. However, there have been few reports of the epidemiology of V. parahaemolyticus AHPND strains, and the genetic relationship among AHPND strains is unclear. Here, we report the genetic characterization of V. parahaemolyticus strains isolated from AHPND outbreaks in Thailand. We found eight isolates from AHPND-suspected shrimps and pond water that were positive for AHPND markers AP1 and AP2. PCR analysis confirmed that none of these eight AP-positive AHPND strains possesses the genes for the conventional virulence factors affecting to humans, such as thermostable direct hemolysin (TDH), TDH-related hemolysin (TRH) and type III secretion system 2. Phylogenetic analysis by multilocus sequence typing showed that the AHPND strains are genetically diverse, suggesting that AHPND strains were not derived from a single genetic lineage. Our study represents the first report of molecular epidemiology of AHPND-causing V. parahaemolyticus strains using multilocus sequence typing, and provides an insight into their evolutionary mechanisms. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Endocrine abnormalities in a patient with borderline personality disorder--case 8/2014].

PubMed

Gassenmaier, Christoph; Schittenhelm, Jens; Selo, Nadja; Schnauder, Günter

2014-12-01

We report on a 44-year-old woman who was treated for borderline personality disorder in the Department of Psychiatry. In addition, symptoms of hyperthyroidism (anxiety, weight loss, hyperdefecation) were noticeable. Thyroid stimulating hormone (TSH) was marginally elevated, free triiodothyronine (T3) and free thyroxine (T4) were clearly elevated. Hence, the patient was transferred to the Department of Endocrinology. Thyroid ultrasound revealed a diffuse goiter with a total volume of 24,8 ml. Antibody screening did not show elevated titers. The thyrotropin releasing hormone (TRH) test depicted a blunted TSH response. Serum levels of free glycoprotein hormone alpha-subunit, prolactin and insulin-like growth factor 1 were increased. In cranial magnetic resonance imaging (MRI), a hypointense lesion on the left side of the anterior pituitary gland was detected indicating a thyrotropin-secreting microadenoma with concomitant secretion of prolactin and possible secretion of human growth hormone (HGH). A thyreostatic therapy was initiated aiming at euthyreosis. For symptom control, betablockers were administered. Subsequently, the patient underwent an uncomplicated transsphenoidal resection. Histological examination confirmed the diagnosis of a pituitary adenoma with expression of TSH, prolactin and HGH. As expected, thyroid hormones declined afterwards. TSHoma is rare. Diagnosis is confirmed by endocrinological testing and cranial imaging. Therapeutic options comprise transsphenoidal adenomectomy, drug therapy (somatostatin analogues, dopaminergic agonists) and irradiation. Resistance to thyroid hormones should be included in the differential diagnosis. © Georg Thieme Verlag KG Stuttgart · New York.

Iodine excess exposure during pregnancy and lactation impairs maternal thyroid function in rats

PubMed Central

Salgueiro, Rafael Barrera; Vitzel, Kaio Fernando; Pantaleão, Thiago; Corrêa da Costa, Vânia Maria

2017-01-01

Adequate maternal iodine consumption during pregnancy and lactation guarantees normal thyroid hormones (TH) production, which is crucial to the development of the fetus. Indeed, iodine deficiency is clearly related to maternal hypothyroidism and deleterious effects in the fetal development. Conversely, the effects of iodine excess (IE) consumption on maternal thyroid function are still controversial. Therefore, this study aimed to investigate the impact of IE exposure during pregnancy and lactation periods on maternal hypothalamus–pituitary–thyroid axis. IE-exposed dams presented reduced serum TH concentration and increased serum thyrotropin (TSH) levels. Moreover, maternal IE exposure increased the hypothalamic expression of Trh and the pituitary expression of Trhr, Dio2, Tsha and Tshb mRNA, while reduced the Gh mRNA content. Additionally, IE-exposed dams presented thyroid morphological alterations, increased thyroid oxidative stress and decreased expression of thyroid genes/proteins involved in TH synthesis, secretion and metabolism. Furthermore, Dio1 mRNA expression and D1 activity were reduced in the liver and the kidney of IE-treated animals. Finally, the mRNA expression of Slc5a5 and Slc26a4 were reduced in the mammary gland of IE-exposed rats. The latter results are in accordance with the reduction of prolactin expression and serum levels in IE-treated dams. In summary, our study indicates that the exposure to IE during pregnancy and lactation induces primary hypothyroidism in rat dams and impairs iodide transfer to the milk. PMID:28814477

[131I therapy in hyperthyroidism. Results of treatment from 1960-1974].

PubMed

Heinze, H G; Schenk, F

1977-02-01

488 PATIENTS WITH Graves' disease were treated by 131Iodine between 1960 and 1974. 427 (87,5%) of these patients were reexamined several times (clinically, 131I-uptake, PB127I, T4 (CPB-A), T3-uptake, and since 1973 TRH-test). The 131I was given as an individually calculated single dose treatment, using 7 000 -- 10 000 rd before 1965 and 6 000 rd thereafter. Two thirds of the patients became euthyroid after a single 131I-dose. In 20% the treatment had to be repeated. These patients show evidently a different biological behaviour of their disease, since multiple treatments revealed a higher rate of failure (33--35%). There is no principal difference between the out-come after 131I-therapy and surgery concerning the rate of failure, respectively relapse (3--4%) and hypothyroidism. Early incidence of hypothyrodism is dose--dependent, as could be shown in patients treated with higher doses before 1965. The reduction of the irradiation dose to 6 000 rd was followed by a drop of hypothyroidism from 18% to 7%. The reasons of late incidence of hypothyroidism are discussed. The incidence of hypothroidism was calculated by three different methods (over-all incidence, incidence within the observed interval after therapy, life-table method). All three methods revealed different results. This has to be taken into account comparing results after radioiodine as well as after surgery. Radioiodine therapy for hyperthyroidism offers a true alternative to surgery.

An Improved Multiplex Real-Time SYBR Green PCR Assay for Analysis of 24 Target Genes from 16 Bacterial Species in Fecal DNA Samples from Patients with Foodborne Illnesses.

PubMed

Kawase, Jun; Etoh, Yoshiki; Ikeda, Tetsuya; Yamaguchi, Keiji; Watahiki, Masanori; Shima, Tomoko; Kameyama, Mitsuhiro; Horikawa, Kazumi; Fukushima, Hiroshi; Goto, Ryoichi; Shirabe, Komei

2016-05-20

Here, we developed a new version of our original screening system (Rapid Foodborne Bacterial Screening 24; RFBS24), which can simultaneously detect 24 genes of foodborne pathogens in fecal DNA samples. This new version (RFBS24 ver. 5) detected all known stx2 subtypes, enterotoxigenic Escherichia coli (STh genotype), and Vibrio parahaemolyticus (trh2), which were not detected by the original RFBS24 assay. The detection limits of RFBS24 ver. 5 were approximately 5.6 × 10(-2)-5.6 × 10(-5) (ng DNA)/reaction, significantly lower (10- to 100-fold) than those of the original RFBS24 for the 22 target genes analyzed here. We also tested the new assay on fecal DNA samples from patients infected with Salmonella, Campylobacter, or enterohemorrhagic E. coli. The number of bacterial target genes detected by RFBS24 ver. 5 was greater than that detected by RFBS24. RFBS24 ver. 5 combined with an Ultra Clean Fecal DNA Isolation Kit showed adequate performance (sensitivity and specificity 89% and 100%, respectively, for Salmonella spp. and 100% and 83%, respectively, for Campylobacter jejuni) in terms of rapid detection of a causative pathogen during foodborne-illness outbreaks. Thus, RFBS24 ver. 5 is more useful than the previous assay system for detection of foodborne pathogens and offers quick simultaneous analysis of many targets and thus facilitates rapid dissemination of information to public health officials.

Inherited tertiary hypothyroidism in Sprague-Dawley rats.

PubMed

Stoica, George; Lungu, Gina; Xie, Xueyi; Abbott, Louise C; Stoica, Heidi M; Jaques, John T

2007-05-07

Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.

[Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study].

PubMed

Milewicz, A; Gejdel, E; Sworen, H; Sienkiewicz, K; Jedrzejak, J; Teucher, T; Schmitz, H

1993-07-01

The efficacy of a Vitex agnus castus preparation (Strotan capsules) was investigated in a randomized double blind study vs. placebo. This clinical study involved 52 women with luteal phase defects due to latent hyperprolactinaemia. The daily dose was one capsule (20 mg) Vitex agnus castus preparation and placebo, respectively. Aim of the study was to prove whether the elevated pituitary prolactin reserve can be reduced and deficits in luteal phase length and luteal phase progesterone synthesis be normalized. Blood for hormonal analysis was taken at days 5-8 and day 20 of the menstrual cycle before and after three month of therapy. Latent hyperprolactinaemia was analysed by monitoring the prolactin release 15 and 30 min after i.v. injection of 200 micrograms TRH. 37 complete case reports (placebo: n = 20, verum: n = 17) after 3 month of therapy were statistically evaluated. The prolactin release was reduced after 3 months, shortened luteal phases were normalised and deficits in the luteal progesterone synthesis were eliminated. These changes were significant and occurred only in the verum group. All other hormonal parameters did not change with the exception of 17 beta-estradiol which rouse up in the luteal phase in patients receiving verum. Side effects were not seen, two women treated with the Vitex agnus castus preparation got pregnant. The tested preparation is thought to be an efficient medication in the treatment of luteal phase defects due to latent hyperprolactinaemia.

Genomic analysis of two emergent Vibrio parahaemolyticus ecotypes

NASA Astrophysics Data System (ADS)

Moreno, E.; Parks, M. C.; Pinnell, L. J.; Turner, J.

2016-02-01

Vibrio parahaemolyticus [Vp] is a Gram-negative bacterium indigenous to marine coastal waters. Vp is also the causative agent of a mild to severe gastroenteritis associated with the consumption of raw or undercooked seafood. The majority of infections are caused by a genetically distinct ecotype commonly referred to as the pandemic clonal complex. However, localized outbreaks associated with non-pandemic ecotypes are frequently reported. In the East Pacific, two such ecotypes, identified as ST65 and ST417 by multilocus sequence typing, have been associated with outbreaks in Peru, Chile and the United States. In this study, we sequenced and assembled draft genomes from 4 clinical isolates (ST65: 3328, 3355; ST417: 3646, 3631) that were positive for both the thermostable direct hemolysin (tdh) and thermostable direct-related hemolysin (trh). When compared with the pandemic type strain (V. parahaemolyticus RIMD2210633), each of these isolates harbored more than 400 Kb of novel genetic material. Proteins encoded by this novel genetic material include CcdA-CcdB toxin-antitoxin systems, an efflux pump belonging to the multidrug and toxic efflux (MATE) family, and a repeats-in-toxin (RTX) gene cluster. These features share significant homology and synteny with virulence-associated features found in clinical V. vulnificus and Escherichia coli strains. We hypothesize that these features contribute to a pathogenic phenotype. The identification and characterization of multiple clinical ecotypes could improve efforts aimed at preventing V. parahaemolyticus infections. Further, a greater understanding of the species' biogeography may lead to a more effective public health response.

Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue.

PubMed

Miao, Yifei; Wu, Wanfu; Dai, Yubing; Maneix, Laure; Huang, Bo; Warner, Margaret; Gustafsson, Jan-Åke

2015-11-10

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

Thyroid axis dysfunction in patients with Prader-Willi syndrome during the first 2 years of life.

PubMed

Vaiani, Elisa; Herzovich, Viviana; Chaler, Eduardo; Chertkoff, Lilien; Rivarola, Marco A; Torrado, Maria; Belgorosky, Alicia

2010-10-01

Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11-13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism has been documented in 20-30% of patients with PWS, thyroid function during the first 2 years of life has not been clearly defined. To evaluate hypothalamic-pituitary-thyroid function in infant PWS patients. Eighteen patients with PWS, aged 0.16-2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and thyroid-stimulating hormone (TSH) were evaluated in the patients with PWS included in the study. Serum hormone values were compared to those of a large reference population of the same age. In 13 of 18 patients with PWS (72.2%), serum TT4 and/or FT4 levels were below the 2.5th percentile of the reference population, while in only one PWS patient serum T3 was below this cut-off. The results of this study suggest that transient or definitive thyrotropin-releasing hormone (TRH)-TSH thyroid axis dysfunction may frequently be present in infant PWS patients. Paediatricians should be aware of this dysfunction in this critical period of thyroid hormone action on neurological development. © 2010 Blackwell Publishing Ltd.

Childhood thyromegaly: recent developments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reiter, E.O.; Root, A.W.; Rettig, K.

1981-10-01

Evaluation of a child with goiter includes historical review, physical examination, and measurement of serum concentrations of PBI, T4 and T3RU, TSH, and titers of antithyroglobulin and antithyroid microsomal antibodies. If there are no indications for more intensive evaluation such as history of cervical irradiation, a palpable abnormality of the thyroid gland or unusual laboratory findings (e.g., a significant PBI-thyroxine iodine discrepancy in the absence of a positive antithyroid antibody titer), a trial of TSH-suppressive therapy with thyroxine is undertake, even if the cause of thyromegaly has not been identified. If thyroid size diminishes in the ensuing six to 12more » months, treatment is maintained for approximately two years and then discontinued. If the goiter recurs, or if there is impaired thyroid function, treatment is resumed. Periodically, antithyroid antibody titers and indices of thyroid function are determined. If the goiter does not diminish after a reasonable trial of suppressive therapy with adequate amounts of thyroxine (i.e., those quantities which will inhibit TRH-induced secretion of TSH), subtotal thyroidectomy is recommended to be certain that an underlying neoplasm has not been overlooked. A biopsy of the thyroid is not performed routinely in such children prior to operative therapy. Almost invariably, examination of the surgical specimen reveals CLT. Postoperatively, suppressive doses of thyroxine are maintained indefinitely. Inasmuch as thyroxine suppression of TSH secretion is essential in the management of patients with thyroid neoplasms, a limited medical trial, as described, does not place the patient at undue risk.« less

Central Hypothyroidism in Miniature Schnauzers.

PubMed

Voorbij, Annemarie M W Y; Leegwater, Peter A J; Buijtels, Jenny J C W M; Daminet, Sylvie; Kooistra, Hans S

2016-01-01

Primary hypothyroidism is a common endocrinopathy in dogs. In contrast, central hypothyroidism is rare in this species. The objective of this article is to describe the occurrence and clinical presentation of central hypothyroidism in Miniature Schnauzers. Additionally, the possible role of the thyroid-stimulating hormone (TSH)-releasing hormone receptor (TRHR) gene and the TSHβ (TSHB) gene was investigated. Miniature Schnauzers with proven central hypothyroidism, based on scintigraphy, and the results of a 3-day-TSH-stimulation test, or a TSH-releasing hormone (TRH)-stimulation test or both, presented to the Department of Clinical Sciences of Companion Animals at Utrecht University or the Department of Medicine and Clinical Biology of Small Animals at Ghent University from 2008 to 2012. Retrospective study. Pituitary function tests, thyroid scintigraphy, and computed tomography (CT) of the pituitary area were performed. Gene fragments of affected dogs and controls were amplified by polymerase chain reaction (PCR). Subsequently, the deoxyribonucleic acid (DNA) sequences of the products were analyzed. Central hypothyroidism was diagnosed in 7 Miniature Schnauzers. Three dogs had disproportionate dwarfism and at least one of them had a combined deficiency of TSH and prolactin. No disease-causing mutations were found in the TSHB gene and the exons of the TRHR gene of these Schnauzers. Central hypothyroidism could be underdiagnosed in Miniature Schnauzers with hypothyroidism, especially in those of normal stature. The fact that this rare disorder occurred in 7 dogs from the same breed suggests that central hypothyroidism could have a genetic background in Miniature Schnauzers. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

The effect of lead intoxication on endocrine functions.

PubMed

Doumouchtsis, K K; Doumouchtsis, S K; Doumouchtsis, E K; Perrea, D N

2009-02-01

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

Transplacental effects of 3,5-dimethyl-3'-isopropyl-L-thyronine on fetal hypothyroidism in primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachrach, L.K.; Dibattista, D.; Burrow, G.N.

1983-06-01

Pregnant Rhesus monkeys treated with 131I at midgestation become hypothyroid and produce fetuses without demonstrable thyroid tissue. In an effort to prevent both maternal and fetal hypothyroidism, we treated 131I-treated pregnant monkeys with 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT), a thyroid hormone analog with structural changes which facilitate placental transfer. Five pregnant monkeys were treated with 131I (mCi/kg) at 83-87 days of gestation. One week later, three monkeys were started on treatment with DIMIT (10 micrograms kg-1 day-1, im) and two on im L-T4 (2 micrograms kg-1 day-1). Treatment was continued until delivery by Caesarian section at 152-157 days of gestation. None of themore » DIMIT-treated mothers became clinically hypothyroid, nor did they have elevated serum TSH concentrations despite low serum levels of T3 and T4. T4-treated mothers were also maintained clinically and biochemically euthyroid. At delivery, infants of DIMIT-treated mothers had normal respiratory function and skeletal maturation. Basal and TRH-stimulated TSH concentrations were suppressed in two of the three infants. By contrast, both T4-treated infants resembled untreated cretinous newborns and died soon after delivery from respiratory failure. Serum TSH concentrations were elevated and skeletal maturation was markedly delayed in these animals. We conclude that DIMIT administration to 131I-treated monkeys prevents clinical and biochemical hypothyroidism in the mother and prevents the major clinical manifestations of cretinism in the fetus.« less

Genetic Analysis of Vibrio parahaemolyticus O3:K6 Strains That Have Been Isolated in Mexico Since 1998

PubMed Central

Licea-Navarro, Alexei Fedorovish; Revilla-Castellanos, Valeria Jeanette; Wong-Chang, Irma; González-Sánchez, Ricardo

2017-01-01

Vibrio parahaemolyticus is an important human pathogen that has been isolated worldwide from clinical cases, most of which have been associated with seafood consumption. Environmental and clinical toxigenic strains of V. parahaemolyticus that were isolated in Mexico from 1998 to 2012, including those from the only outbreak that has been reported in this country, were characterized genetically to assess the presence of the O3:K6 pandemic clone, and their genetic relationship to strains that are related to the pandemic clonal complex (CC3). Pathogenic tdh+ and tdh+/trh+ strains were analyzed by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Also, the entire genome of a Mexican O3:K6 strain was sequenced. Most of the strains were tdh/ORF8-positive and corresponded to the O3:K6 serotype. By PFGE and MLST, there was very close genetic relationship between ORF8/O3:K6 strains, and very high genetic diversities from non-pandemic strains. The genetic relationship is very close among O3:K6 strains that were isolated in Mexico and sequences that were available for strains in the CC3, based on the PubMLST database. The whole-genome sequence of CICESE-170 strain had high similarity with that of the reference RIMD 2210633 strain, and harbored 7 pathogenicity islands, including the 4 that denote O3:K6 pandemic strains. These results indicate that pandemic strains that have been isolated in Mexico show very close genetic relationship among them and with those isolated worldwide. PMID:28099500

Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats.

PubMed

Tekin, Suat; Erden, Yavuz; Ozyalin, Fatma; Onalan, Ebru Etem; Cigremis, Yilmaz; Colak, Cemil; Tekedereli, Ibrahim; Sandal, Suleyman

2018-05-01

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Distribution and dynamics of epidemic and pandemic Vibrio parahaemolyticus virulence factors

PubMed Central

Ceccarelli, Daniela; Hasan, Nur A.; Huq, Anwar; Colwell, Rita R.

2013-01-01

Vibrio parahaemolyticus, autochthonous to estuarine, marine, and coastal environments throughout the world, is the causative agent of food-borne gastroenteritis. More than 80 serotypes have been described worldwide, based on antigenic properties of the somatic (O) and capsular (K) antigens. Serovar O3:K6 emerged in India in 1996 and subsequently was isolated worldwide, leading to the conclusion that the first V. parahaemolyticus pandemic had taken place. Most strains of V. parahaemolyticus isolated from the environment or seafood, in contrast to clinical strains, do not produce a thermostable direct hemolysin (TDH) and/or a TDH-related hemolysin (TRH). Type 3 secretion systems (T3SSs), needle-like apparatuses able to deliver bacterial effectors into host cytoplasm, were identified as triggering cytotoxicity and enterotoxicity. Type 6 secretion systems (T6SS) predicted to be involved in intracellular trafficking and vesicular transport appear to play a role in V. parahaemolyticus virulence. Recent advances in V. parahaemolyticus genomics identified several pathogenicity islands (VpaIs) located on either chromosome in both epidemic and pandemic strains and comprising additional colonization factors, such as restriction-modification complexes, chemotaxis proteins, classical bacterial surface virulence factors, and putative colicins. Furthermore, studies indicate strains lacking toxins and genomic regions associated with pathogenicity may also be pathogenic, suggesting other important virulence factors remain to be identified. The unique repertoire of virulence factors identified to date, their occurrence and distribution in both epidemic and pandemic strains worldwide are described, with the aim of highlighting the complexity of V. parahaemolyticus pathogenicity as well as its dynamic genome. PMID:24377090

Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea.

PubMed

De Leo, V; la Marca, A; Lanzetta, D; Morgante, G

2000-05-01

To investigate the hypothalamo-pituitary-ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of L-thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Gynecological Endocrinology Research Center, University of Siena (Italy). 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Administration of 50 microgram GnRH and 200 microgram TRH. The women with functional hypothalamic amenorrhea were divided into groups A (n=8) and B (n=8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone (L-thyroxine) for 3 months. Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Administration of clomiphene and clomiphene plus L-thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5+/-1.2 ng/ml in group A and 5.1+/-1.3 ngl/ml in group B. Administration of L-thyroxine with clomiphene does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.

GHRH excess and blockade in X-LAG syndrome.

PubMed

Daly, Adrian F; Lysy, Philippe A; Desfilles, Céline; Rostomyan, Liliya; Mohamed, Amira; Caberg, Jean-Hubert; Raverot, Veronique; Castermans, Emilie; Marbaix, Etienne; Maiter, Dominique; Brunelle, Chloe; Trivellin, Giampaolo; Stratakis, Constantine A; Bours, Vincent; Raftopoulos, Christian; Beauloye, Veronique; Barlier, Anne; Beckers, Albert

2016-03-01

X-linked acrogigantism (X-LAG) syndrome is a newly described form of inheritable pituitary gigantism that begins in early childhood and is usually associated with markedly elevated GH and prolactin secretion by mixed pituitary adenomas/hyperplasia. Microduplications on chromosome Xq26.3 including the GPR101 gene cause X-LAG syndrome. In individual cases random GHRH levels have been elevated. We performed a series of hormonal profiles in a young female sporadic X-LAG syndrome patient and subsequently undertook in vitro studies of primary pituitary tumor culture following neurosurgical resection. The patient demonstrated consistently elevated circulating GHRH levels throughout preoperative testing, which was accompanied by marked GH and prolactin hypersecretion; GH demonstrated a paradoxical increase following TRH administration. In vitro, the pituitary cells showed baseline GH and prolactin release that was further stimulated by GHRH administration. Co-incubation with GHRH and the GHRH receptor antagonist, acetyl-(d-Arg(2))-GHRH (1-29) amide, blocked the GHRH-induced GH stimulation; the GHRH receptor antagonist alone significantly reduced GH release. Pasireotide, but not octreotide, inhibited GH secretion. A ghrelin receptor agonist and an inverse agonist led to modest, statistically significant increases and decreases in GH secretion, respectively. GHRH hypersecretion can accompany the pituitary abnormalities seen in X-LAG syndrome. These data suggest that the pathology of X-LAG syndrome may include hypothalamic dysregulation of GHRH secretion, which is in keeping with localization of GPR101 in the hypothalamus. Therapeutic blockade of GHRH secretion could represent a way to target the marked hormonal hypersecretion and overgrowth that characterizes X-LAG syndrome. © 2016 Society for Endocrinology.

Direct detection of various pathogens by loop-mediated isothermal amplification assays on bacterial culture and bacterial colony.

PubMed

Yan, Muxia; Li, Weidong; Zhou, Zhenwen; Peng, Hongxia; Luo, Ziyan; Xu, Ling

2017-01-01

In this work, loop-mediated isothermal amplification based detection assay using bacterial culture and bacterial colony for various common pathogens direct detection had been established, evaluated and further applied. A total of five species of common pathogens and nine detection targets (tlh, tdh and trh for V. Parahaemolyticus, rfbE, stx1 and stx2 for E. coli, oprI for P. aeruginosa, invA for Salmonella and hylA for L. monocytogenes) were performed on bacterial culture and bacterial colony LAMP. To evaluate and optimize this assay, a total of 116 standard strains were included. Then, for each detected targets, 20 random selected strains were applied. Results were determined through both visual observation of the changed color by naked eye and electrophoresis, which increased the accuracy of survey. The minimum adding quantity of each primer had been confirmed, and the optimal amplification was obtained under 65 °C for 45 min with 25 μl reaction volume. The detection limit of bacterial culture LAMP and PCR assay were determined to be 10 2 and 10 4 or 10 5  CFU/reaction, respectively. No false positive amplification was observed when subjecting the bacterial -LAMP assay to 116 reference strains. This was the first report of colony-LAMP and culture-LAMP assay, which had been demonstrated to be a fast, reliable, cost-effective and simple method on detection of various common pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

Central congenital hypothyroidism due to gestational hyperthyroidism: detection where prevention failed.

PubMed

Kempers, Marlies J E; van Tijn, David A; van Trotsenburg, A S Paul; de Vijlder, Jan J M; Wiedijk, Brenda M; Vulsma, Thomas

2003-12-01

Much worldwide attention is given to the adverse effects of maternal Graves' disease on the fetal and neonatal thyroid and its function. However, reports concerning the adverse effects of maternal Graves' disease on the pituitary function, illustrated by the development of central congenital hypothyroidism (CCH) in the offspring of these mothers, are scarce. We studied thyroid hormone determinants of 18 children with CCH born to mothers with Graves' disease. Nine mothers were diagnosed after pregnancy, the majority after their children were detected with CCH by neonatal screening. Four mothers were diagnosed during pregnancy and treated with antithyroid drugs since diagnosis. Another four mothers were diagnosed before pregnancy, but they used antithyroid drugs irregularly; free T(4) concentrations less than 1.7 ng/dl (<22 pmol/liter) were not encountered during pregnancy. All neonates had decreased plasma free T(4) concentrations (range 0.3-0.9 ng/dl, 3.9-11.5 pmol/liter); plasma TSH ranged between 0.1 and 6.6 mU/liter. TRH tests showed pituitary dysfunction. Seventeen children needed T(4) supplementation. Because all mothers were insufficiently treated during pregnancy, it is hypothesized that a hyperthyroid fetal environment impaired maturation of the fetal hypothalamic-pituitary-thyroid system. The frequent occurrence of this type of CCH (estimated incidence 1:35000) warrants early detection and treatment to minimize the risk of cerebral damage. A T(4)-based screening program appears useful in detecting this type of CCH. However, the preferential and presumably best strategy to prevent CCH caused by maternal Graves' disease is preserving euthyroidism throughout pregnancy.

KCNQ channels determine serotonergic modulation of ventral surface chemoreceptors and respiratory drive

PubMed Central

Hawryluk, Joanna M.; Moreira, Thiago S.; Takakura, Ana C.; Wenker, Ian C.; Tzingounis, Anastasios V.; Mulkey, Daniel K.

2012-01-01

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes. Their activity is also sensitive to neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of respiratory control. However, molecular mechanisms that control their activity and susceptibility to neuromodulation are unknown. Here, we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In particular, we find that pharmacological block of KCNQ channels (XE991, 10 μM) increased basal activity and CO2-responsivness of RTN neurons in rat brain slices; whereas KCNQ channel activation (retigabine 2–40 μM) silenced these neurons. Interestingly, we also find that KCNQ and apamin sensitive SK channels act synergistically to regulate firing rate of RTN chemoreceptors; simultaneous blockade of both channels led to a increase in CO2-responsivness. Furthermore, we also show that KCNQ channels but not SK channels are downstream effectors of serotonin modulation of RTN activity in vitro. In contrast, inhibition of KCNQ channel did not prevent modulation of RTN activity by Substance P or TRH; previously identified neuromodulators of RTN chemoreception. Importantly, we also show that KCNQ channels are critical for RTN activity in vivo. Inhibition of KCNQ channels lowered the CO2 threshold for phrenic nerve discharge in anesthetized rats and decreased the ventilatory response to serotonin in awake and anesthetized animals. Given that serotonergic dysfunction may contribute to respiratory failure, our findings suggest KCNQ channels as a new therapeutic avenue for respiratory complications associated with multiple neurological disorders. PMID:23175845

Risk of Vibrio transmission linked to the consumption of crustaceans in coastal towns of Côte d'Ivoire.

PubMed

Traoré, S G; Bonfoh, B; Krabi, R; Odermatt, P; Utzinger, J; Rose, K-N; Tanner, M; Frey, J; Quilici, M-L; Koussémon, M

2012-06-01

The purpose of this study was to assess the risk of Vibrio spp. transmission from crustaceans to humans in two coastal towns of Côte d'Ivoire. Bacteriologic analysis was performed on 322 crustacean samples obtained from six markets in Abidjan and one in Dabou. Suspected Vibrio colonies were identified by morphological, cultural, biochemical, and molecular tests and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. PCR assays were used to further characterize Vibrio strains. A survey on consumption of crustaceans was conducted among 120 randomly selected households in Abidjan. Overall, Vibrio spp. were isolated from 7.8% of the crustacean samples studied, at levels as high as 6.3 log CFU/g. Of the Vibrio strains identified, 40% were V. alginolyticus, 36% were V. parahaemolyticus, and 24% were nontoxigenic V. cholerae; the latter two species can cause mild to severe forms of seafood-associated gastroenteritis. Among interviewed households, 11.7% reported daily consumption of crustaceans, confirming the high probability of exposure of human population to Vibrio spp., and 7.5% reported symptoms of food poisoning after consumption of crustaceans. The absence of genes encoding major virulence factors in the studied strains, i.e., cholera toxin (ctxA and ctxB) in V. cholerae and thermostable direct hemolysin (tdh) and thermostable direct hemolysin-related hemolysin (trh) in V. parahaemolyticus, does not exclude the possibility of exposure to pathogenic strains. However, human infections are not common because most households (96.7%) boil crustaceans, usually for at least 45 min (85.9% of households) before consumption.

Population Relationship of Vibrio parahaemolyticus Isolates Derived from Aquaculture Ponds, a Seafood Market, Restaurants, and Clinical Samples.

PubMed

Gao, Lei; Deng, Yi Qin; Chen, Chang; Ke, Chang Wen; Li, Bo Sheng; Long, Yun Ying; Liu, Zhu Hong; Wei, Lu

2016-06-01

To study the relationship between environmental and clinical populations of Vibrio parahaemolyticus, we collected in total 86 isolates from Southern China during one and a half years. Sixty-eight isolates were recovered from aquaculture ponds, a seafood market, and restaurants, and 18 isolates were recovered from clinical samples. Virulence gene analysis revealed that 25 isolates (14 clinical and 11 environmental) tested positive for tdh, but only 4 carried trh. Interestingly, none of the tdh(+) environmental isolates was recovered from ponds. Both environmental and clinical tdh(+) isolates, except for one clinical isolate, harbor type III secretion system 2α (T3SS2α) and T3SS2β-related genes, including vopB2α, which was previously suggested to be absent from environmental strains. More than 70% of clinical isolates carried the pandemic marker of new toxRS (GS-PCR(+)), which was not present in the environmental isolates. Pulsed-field gel electrophoresis and multilocus sequence typing analysis showed a high degree of genetic diversity within the environmental isolates. In contrast, the clinical population formed a tight cluster that differed from the environmental isolates. These findings suggest that the pandemic strains of V. parahaemolyticus may not directly originate from marine animals. Rather the environments where they are maintained could serve as reservoirs for toxigenic, but not pandemic strains. These environments provide an ideal place for generation of new toxigenic strains through DNA exchange, which was revealed by extensive recombination events in recA sequences of the environmental isolates.

Rapid effects of deep brain stimulation reactivation on symptoms and neuroendocrine parameters in obsessive-compulsive disorder

PubMed Central

de Koning, P P; Figee, M; Endert, E; van den Munckhof, P; Schuurman, P R; Storosum, J G; Denys, D; Fliers, E

2016-01-01

Improvement of obsessions and compulsions by deep brain stimulation (DBS) for obsessive-compulsive disorder (OCD) is often preceded by a rapid and transient mood elevation (hypomania). In a previous study we showed that improvement of mood by DBS for OCD is associated with a decreased activity of the hypothalamus–pituitary adrenal axis. The aim of our present study was to evaluate the time course of rapid clinical changes following DBS reactivation in more detail and to assess their association with additional neuroendocrine parameters. We included therapy-refractory OCD patients treated with DBS (>1 year) and performed a baseline assessment of symptoms, as well as plasma concentrations of thyroid-stimulating hormone (TSH), prolactin, growth hormone, copeptin and homovanillic acid. This was repeated after a 1-week DBS OFF condition. Next, we assessed the rapid effects of DBS reactivation by measuring psychiatric symptom changes using visual analog scales as well as repeated neuroendocrine measures after 30 min, 2 h and 6 h. OCD, anxiety and depressive symptoms markedly increased during the 1-week OFF condition and decreased again to a similar extent already 2 h after DBS reactivation. We found lower plasma prolactin (41% decrease, P=0.003) and TSH (39% decrease, P=0.003) levels during DBS OFF, which increased significantly already 30 min after DBS reactivation. The rapid and simultaneous increase in TSH and prolactin is likely to result from stimulation of hypothalamic thyrotropin-releasing hormone (TRH), which may underlie the commonly observed transient mood elevation following DBS. PMID:26812043

Extreme obesity is associated with variation in genes related to the circadian rhythm of food intake and hypothalamic signaling.

PubMed

Mariman, Edwin C M; Bouwman, Freek G; Aller, Erik E J G; van Baak, Marleen A; Wang, Ping

2015-06-01

The hypothalamus is important for regulation of energy intake. Mutations in genes involved in the function of the hypothalamus can lead to early-onset severe obesity. To look further into this, we have followed a strategy that allowed us to identify rare and common gene variants as candidates for the background of extreme obesity from a relatively small cohort. For that we focused on subjects with a well-selected phenotype and on a defined gene set and used a rich source of genetic data with stringent cut-off values. A list of 166 genes functionally related to the hypothalamus was generated. In those genes complete exome sequence data from 30 extreme obese subjects (60 genomes) were screened for novel rare indel, nonsense, and missense variants with a predicted negative impact on protein function. In addition, (moderately) common variants in those genes were analyzed for allelic association using the general population as reference (false discovery rate<0.05). Six novel rare deleterious missense variants were found in the genes for BAIAP3, NBEA, PRRC2A, RYR1, SIM1, and TRH, and a novel indel variant in LEPR. Common variants in the six genes for MBOAT4, NPC1, NPW, NUCB2, PER1, and PRRC2A showed significant allelic association with extreme obesity. Our findings underscore the complexity of the genetic background of extreme obesity involving rare and common variants of genes from defined metabolic and physiologic processes, in particular regulation of the circadian rhythm of food intake and hypothalamic signaling. Copyright © 2015 the American Physiological Society.

Cytokine profiles of HeLa and human diploid cells induced by different fractions of Vibrio parahaemolyticus cultures exposed to stress conditions.

PubMed

Chifiriuc, Mariana Carmen; Bleotu, Coralia; Pîrcălăbioru, Gratiela; Israil, Anca Michaela; Dinu, Sorin; Rută, Simona Maria; Grancea, Camelia; Lazăr, Veronica

2010-01-01

Vibrio (V.) parahaemolyticus is an aquatic halophilic bacteria which produces gastroenteritis and in rare cases septicaemia after the consumption of raw or under-cooked contaminated seafood.The severity of diarrheal illness caused by this bacterium is closely related to the presence of two types of hemolysins (the thermostable direct hemolysin-TDH and TDH related hemolysin-TRH) and also of type III secretion system (TTSS) proteins. The TTSS type 1 induces a wide array of effects on infected HeLa cells such as autophagy, oncosis, cell rounding and lysis. Previous studies have shown that heat shock proteins have the ability to stimulate the production of interleukins in different cellular cultures. In our studies we have stimulated two cellular lines (HeLa and human diploid cells) with different V. parahaemolyticus culture fractions in order to observe the effect on cytokines production. Thus, the purpose of this study was to analyze the expression of IL-1, IL-2, IL-4, IL-6, IL-10 and TNF-alpha induced by the cell treatment with total cellular lysate, periplasmic fractions and culture supernatants extracted from V. parahaemolyticus exposed to normal and also to stress conditions. The ELISA assay of the cytokine profile of the HeLa and HDC cell lines stimulated with different bacterial fractions revealed that in the V. parahemolyticus cultures submitted to osmotic and heat shock stress are accumulating factors (probably heat shock proteins) which are exhibiting immunomodulatory activity, responsible for the induction of a pro-inflammatory response associated with increased levels of IL-6 and TNF-alpha expression, however balanced by the stimulation of the anti-inflammatory cytokine IL-4 synthesis.

Association of Pandemic Vibrio parahaemolyticus O3:K6 Present in the Coastal Environment of Northwest Mexico with Cases of Recurrent Diarrhea between 2004 and 2010

PubMed Central

Velazquez-Roman, Jorge; León-Sicairos, Nidia; Flores-Villaseñor, Héctor; Villafaña-Rauda, Santiago

2012-01-01

In 2004, more than 1,230 cases of gastroenteritis due to pandemic O3:K6 strains of Vibrio parahaemolyticus were reported in southern Sinaloa, a state in Northwestern Mexico. Recurrent sporadic cases arose from 2004 to 2010, spreading from the south to the north. In the present study, Vibrio parahaemolyticus was detected in both environmental samples and clinical cases along the Pacific coast of Sinaloa during 2004 to 2010. An evaluation was made of the serotypes, distribution of virulence genes, and presence of pandemic O3:K6 strains. A total of 144 strains were isolated from environmental samples (from sediment, seawater, and shrimp), and 154 clinical strains were isolated. A total of 10 O serogroups and 30 serovars were identified in the strains. Environmental strains (n = 144) belonged to 10 O serogroups and 28 serovars, while clinical strains (n = 154) belonged to 8 O serogroups and 14 serovars. Ten serovars were shared by both environmental and clinical strains. Among 144 environmental isolates, 4.1% (6/144) belonged to the pandemic clone, with 83.3% containing the orf8 gene and with O3:K6 accounting for 67%. On the other hand, pathogenic strains (tdh and/or trh) accounted for 52% (75/144) of the environmental isolates. Interestingly, among 154 clinical isolates, 80.5% (124/154) were pandemic strains, with O3:K6 (tdh, toxRSnew, and orf8) representing the predominant serovar (99.2%, 123/124). Overall, our results indicate that in spite of a high serodiversity and prevalence of pathogenic Vibrio parahaemolyticus in the environment, the pandemic strain O3:K6 caused >79% of reported cases between 2004 and 2010 in Sinaloa, Mexico. PMID:22247160

Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine

PubMed Central

Werneck de Castro, Joao Pedro; Fonseca, Tatiana L.; Ueta, Cintia B.; McAninch, Elizabeth A.; Abdalla, Sherine; Wittmann, Gabor; Lechan, Ronald M.; Gereben, Balazs; Bianco, Antonio C.

2015-01-01

The current treatment for patients with hypothyroidism is levothyroxine (L-T4) along with normalization of serum thyroid-stimulating hormone (TSH). However, normalization of serum TSH with L-T4 monotherapy results in relatively low serum 3,5,3′-triiodothyronine (T3) and high serum thyroxine/T3 (T4/T3) ratio. In the hypothalamus-pituitary dyad as well as the rest of the brain, the majority of T3 present is generated locally by T4 deiodination via the type 2 deiodinase (D2); this pathway is self-limited by ubiquitination of D2 by the ubiquitin ligase WSB-1. Here, we determined that tissue-specific differences in D2 ubiquitination account for the high T4/T3 serum ratio in adult thyroidectomized (Tx) rats chronically implanted with subcutaneous L-T4 pellets. While L-T4 administration decreased whole-body D2-dependent T4 conversion to T3, D2 activity in the hypothalamus was only minimally affected by L-T4. In vivo studies in mice harboring an astrocyte-specific Wsb1 deletion as well as in vitro analysis of D2 ubiquitination driven by different tissue extracts indicated that D2 ubiquitination in the hypothalamus is relatively less. As a result, in contrast to other D2-expressing tissues, the hypothalamus is wired to have increased sensitivity to T4. These studies reveal that tissue-specific differences in D2 ubiquitination are an inherent property of the TRH/TSH feedback mechanism and indicate that only constant delivery of L-T4 and L-T3 fully normalizes T3-dependent metabolic markers and gene expression profiles in Tx rats. PMID:25555216

Serum concentrations of pituitary and adrenal hormones in female pigs exposed to two photoperiods.

PubMed

Kraeling, R R; Rampacek, G B; Mabry, J W; Cunningham, F L; Pinkert, C A

1983-11-01

Serum concentrations of pituitary and adrenal hormones were determined in lactating sows and ovariectomized (OVX) gilts exposed to 8 h (8L:16D) or 16 h of light (16L:8D). In addition serum prolactin (PRL) concentrations were determined after a thyrotropin releasing hormone (TRH) challenge. At 103 +/- 2 d of gestation or 3 wk after ovariectomy of nulliparous gilts on d 7 to 9 of the estrous cycle (d - 10), blood samples were collected from jugular vein cannulae at 30-min intervals for 8 h beginning at 0800 h. Immediately after the last sample, 13 sows and five OVX gilts were assigned to 8L:16D and 14 sows and five OVX gilts were assigned to 16L:8D/d and placed in two identical chambers in the farrowing house. Blood sampling was repeated on d 7, 14 and 21 of lactation in the sows and on d 7, 14, 21 and 28 in the OVX gilts. In Exp. 1, serum cortisol (C) concentrations were similar for sows exposed to 8L:16D (n = 7) and 16L:8D (n = 6) treatments, whereas in Exp. 2, serum C concentrations for sows exposed to 8L:16D (n = 6) were lower than those exposed to 16L:8D (n = 6) on d 7, 14 and 21. Photoperiod failed to influence serum concentrations of PRL, luteinizing hormone (LH) and growth hormone in the lactating sows or PRL in the OVX gilts. Photoperiod also failed to affect mean basal serum concentrations, peak height and peak frequency for PRL and LH in the lactating sows or for PRL in the OVX gilts.(ABSTRACT TRUNCATED AT 250 WORDS)

Temporal and spatial variability in culturable pathogenic Vibrio spp. in Lake Pontchartrain, Louisiana, following hurricanes Katrina and Rita.

PubMed

Nigro, Olivia D; Hou, Aixin; Vithanage, Gayatri; Fujioka, Roger S; Steward, Grieg F

2011-08-01

We investigated the abundance, distribution, and virulence gene content of Vibrio cholerae, V. parahaemolyticus, and V. vulnificus in the waters of southern Lake Pontchartrain in Louisiana on four occasions from October 2005 to September 2006, using selective cultivation and molecular assays. The three targeted pathogenic vibrios were generally below the detection level in January 2006, when the water was cold (13°C), and most abundant in September 2006, when the lake water was warmest (30°C). The maximum values for these species were higher than reported previously for the lake by severalfold to orders of magnitude. The only variable consistently correlated with total vibrio abundance within a single sampling was distance from shore (P = 0.000). Multiple linear regression of the entire data set revealed that distance from shore, temperature, and turbidity together explained 82.1% of the variability in total vibrio CFU. The log-transformed mean abundance of V. vulnificus CFU in the lake was significantly correlated with temperature (P = 0.014), but not salinity (P = 0.625). Virulence-associated genes of V. cholerae (ctx) and V. parahaemolyticus (trh and tdh) were not detected in any isolates of these species (n = 128 and n = 20, respectively). In contrast, 16S rRNA typing of V. vulnificus (n = 298) revealed the presence of both environmental (type A) and clinical (type B) strains. The percentage of the B-type V. vulnificus was significantly higher in the lake in October 2005 (35.8% of the total) than at other sampling times (P ≤ 0.004), consistent with the view that these strains represent distinct ecotypes.

Detection of pathogenic Vibrio spp. in shellfish by using multiplex PCR and DNA microarrays.

PubMed

Panicker, Gitika; Call, Douglas R; Krug, Melissa J; Bej, Asim K

2004-12-01

This study describes the development of a gene-specific DNA microarray coupled with multiplex PCR for the comprehensive detection of pathogenic vibrios that are natural inhabitants of warm coastal waters and shellfish. Multiplex PCR with vvh and viuB for Vibrio vulnificus, with ompU, toxR, tcpI, and hlyA for V. cholerae, and with tlh, tdh, trh, and open reading frame 8 for V. parahaemolyticus helped to ensure that total and pathogenic strains, including subtypes of the three Vibrio spp., could be detected and discriminated. For DNA microarrays, oligonucleotide probes for these targeted genes were deposited onto epoxysilane-derivatized, 12-well, Teflon-masked slides by using a MicroGrid II arrayer. Amplified PCR products were hybridized to arrays at 50 degrees C and detected by using tyramide signal amplification with Alexa Fluor 546 fluorescent dye. Slides were imaged by using an arrayWoRx scanner. The detection sensitivity for pure cultures without enrichment was 10(2) to 10(3) CFU/ml, and the specificity was 100%. However, 5 h of sample enrichment followed by DNA extraction with Instagene matrix and multiplex PCR with microarray hybridization resulted in the detection of 1 CFU in 1 g of oyster tissue homogenate. Thus, enrichment of the bacterial pathogens permitted higher sensitivity in compliance with the Interstate Shellfish Sanitation Conference guideline. Application of the DNA microarray methodology to natural oysters revealed the presence of V. vulnificus (100%) and V. parahaemolyticus (83%). However, V. cholerae was not detected in natural oysters. An assay involving a combination of multiplex PCR and DNA microarray hybridization would help to ensure rapid and accurate detection of pathogenic vibrios in shellfish, thereby improving the microbiological safety of shellfish for consumers.

Detection of Pathogenic Vibrio spp. in Shellfish by Using Multiplex PCR and DNA Microarrays

PubMed Central

Panicker, Gitika; Call, Douglas R.; Krug, Melissa J.; Bej, Asim K.

2004-01-01

This study describes the development of a gene-specific DNA microarray coupled with multiplex PCR for the comprehensive detection of pathogenic vibrios that are natural inhabitants of warm coastal waters and shellfish. Multiplex PCR with vvh and viuB for Vibrio vulnificus, with ompU, toxR, tcpI, and hlyA for V. cholerae, and with tlh, tdh, trh, and open reading frame 8 for V. parahaemolyticus helped to ensure that total and pathogenic strains, including subtypes of the three Vibrio spp., could be detected and discriminated. For DNA microarrays, oligonucleotide probes for these targeted genes were deposited onto epoxysilane-derivatized, 12-well, Teflon-masked slides by using a MicroGrid II arrayer. Amplified PCR products were hybridized to arrays at 50°C and detected by using tyramide signal amplification with Alexa Fluor 546 fluorescent dye. Slides were imaged by using an arrayWoRx scanner. The detection sensitivity for pure cultures without enrichment was 102 to 103 CFU/ml, and the specificity was 100%. However, 5 h of sample enrichment followed by DNA extraction with Instagene matrix and multiplex PCR with microarray hybridization resulted in the detection of 1 CFU in 1 g of oyster tissue homogenate. Thus, enrichment of the bacterial pathogens permitted higher sensitivity in compliance with the Interstate Shellfish Sanitation Conference guideline. Application of the DNA microarray methodology to natural oysters revealed the presence of V. vulnificus (100%) and V. parahaemolyticus (83%). However, V. cholerae was not detected in natural oysters. An assay involving a combination of multiplex PCR and DNA microarray hybridization would help to ensure rapid and accurate detection of pathogenic vibrios in shellfish, thereby improving the microbiological safety of shellfish for consumers. PMID:15574946

Field and experimental evidence of Vibrio parahaemolyticus as the causative agent of acute hepatopancreatic necrosis disease of cultured shrimp (Litopenaeus vannamei) in Northwestern Mexico.

PubMed

Soto-Rodriguez, Sonia A; Gomez-Gil, Bruno; Lozano-Olvera, Rodolfo; Betancourt-Lozano, Miguel; Morales-Covarrubias, Maria Soledad

2015-03-01

Moribund shrimp affected by acute hepatopancreatic necrosis disease (AHPND) from farms in northwestern Mexico were sampled for bacteriological and histological analysis. Bacterial isolates were molecularly identified as Vibrio parahaemolyticus by the presence of the tlh gene. The tdh-negative, trh-negative, and tlh-positive V. parahaemolyticus strains were further characterized by repetitive extragenic palindromic element-PCR (rep-PCR), and primers AP1, AP2, AP3, and AP and an ems2 IQ2000 detection kit (GeneReach, Taiwan) were used in the diagnostic tests for AHPND. The V. parahaemolyticus strains were used in immersion challenges with shrimp, and farmed and challenged shrimp presented the same clinical and pathological symptoms: lethargy, empty gut, pale and aqueous hepatopancreas, and expanded chromatophores. Using histological analysis and bacterial density count, three stages of AHNPD (initial, acute, and terminal) were identified in the affected shrimp. The pathognomonic lesions indicating severe desquamation of tubular epithelial cells of the hepatopancreas were observed in both challenged and pond-infected shrimp. The results showed that different V. parahaemolyticus strains have different virulences; some of the less virulent strains do not induce 100% mortality, and mortality rates also rise more slowly than they do for the more virulent strains. The virulence of V. parahaemolyticus strains was dose dependent, where the threshold infective density was 10(4) CFU ml(-1); below that density, no mortality was observed. The AP3 primer set had the best sensitivity and specificity. Field and experimental results showed that the V. parahaemolyticus strain that causes AHPND acts as a primary pathogen for shrimp in Mexico compared with the V. parahaemolyticus strains reported to date. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Antibiotic and heavy-metal resistance of Vibrio parahaemolyticus isolated from fresh shrimps in Shanghai fish markets, China.

PubMed

He, Yu; Jin, Lanlan; Sun, Fengjiao; Hu, Qiongxia; Chen, Lanming

2016-08-01

Vibrio parahaemolyticus is a causative agent of human serious seafood-borne gastroenteritis disease and even death. Shrimps, often eaten raw or undercooked, are an important reservoir of the bacterium. In this study, we isolated and characterized a total of 400 V. parahaemolyticus strains from commonly consumed fresh shrimps (Litopenaeus vannamei, Macrobrachium rosenbergii, Penaeus monodon, and Exopalaemon carinicauda) in Shanghai fish markets, China in 2013-2014. The results revealed an extremely low occurrence of pathogenic V. parahaemolyticus carrying two major toxic genes (tdh and trh, 0.0 and 0.5 %). However, high incidences of antibiotic resistance were observed among the strains against ampicillin (99 %), streptomycin (45.25 %), rifampicin (38.25 %), and spectinomycin (25.50 %). Approximately 24 % of the strains derived from the P. monodon sample displayed multidrug resistant (MDR) phenotypes, followed by 19, 12, and 6 % from the E. carinicauda, L. vannamei, and M. rosenbergii samples, respectively. Moreover, tolerance to heavy metals of Cr(3+) and Zn(2+) was observed in 90 antibiotic resistant strains, the majority of which also displayed resistance to Cu(2+) (93.3 %), Pb(2+) (87.8 %), and Cd(2+)(73.3 %). The pulsed-field gel electrophoresis (PFGE)-based genotyping of these strains revealed a total of 71 distinct pulsotypes, demonstrating a large degree of genomic variation among the isolates. The wide distribution of MDR and heavy-metal resistance isolates in the PFGE clusters suggested the co-existence of a number of resistant determinants in V. parahaemolyticus population in the detected samples. This study provided data in support of aquatic animal health management and food safety risk assessment in aquaculture industry.

Catching Galactic open clusters in advanced stages of dynamical evolution

NASA Astrophysics Data System (ADS)

Angelo, M. S.; Piatti, A. E.; Dias, W. S.; Maia, F. F. S.

2018-04-01

During their dynamical evolution, Galactic open clusters (OCs) gradually lose their stellar content mainly because of internal relaxation and tidal forces. In this context, the study of dynamically evolved OCs is necessary to properly understand such processes. We present a comprehensive Washington CT1 photometric analysis of six sparse OCs, namely: ESO 518-3, Ruprecht 121, ESO 134-12, NGC 6573, ESO 260-7 and ESO 065-7. We employed Markov chain Monte-Carlo simulations to robustly determine the central coordinates and the structural parameters and T1 × (C - T1) colour-magnitude diagrams (CMDs) cleaned from field contamination were used to derive the fundamental parameters. ESO 518-03, Ruprecht 121, ESO 134-12 and NGC 6573 resulted to be of nearly the same young age (8.2 ≤log(t yr-1) ≤ 8.3); ESO 260-7 and ESO065-7 are of intermediate age (9.2 ≤log(t yr-1) ≤ 9.4). All studied OCs are located at similar Galactocentric distances (RG ˜ 6 - 6.9 kpc), considering uncertainties, except for ESO 260-7 (RG = 8.9 kpc). These OCs are in a tidally filled regime and are dynamically evolved, since they are much older than their half-mass relaxation times (t/trh ≳ 30) and present signals of low-mass star depletion. We distinguished two groups: those dynamically evolving towards final disruptions and those in an advanced dynamical evolutionary stage. Although we do not rule out that the Milky Way potential could have made differentially faster their dynamical evolutions, we speculate here with the possibility that they have been mainly driven by initial formation conditions.

Vibrio parahaemolyticus Strains of Pandemic Serotypes Identified from Clinical and Environmental Samples from Jiangsu, China

PubMed Central

Li, Jingjiao; Xue, Feng; Yang, Zhenquan; Zhang, Xiaoping; Zeng, Dexin; Chao, Guoxiang; Jiang, Yuan; Li, Baoguang

2016-01-01

Vibrio parahaemolyticus has emerged as a major foodborne pathogen in China, Japan, Thailand, and other Asian countries. In this study, 72 strains of V. parahaemolyticus were isolated from clinical and environmental samples between 2006 and 2014 in Jiangsu, China. The serotypes and six virulence genes including thermostable direct hemolysin (TDR) and TDR-related hemolysin (TRH) genes were assessed among the isolates. Twenty five serotypes were identified and O3:K6 was one of the dominant serotypes. The genetic diversity was assessed by multilocus sequence typing (MLST) analysis, and 48 sequence types (STs) were found, suggesting this V. parahaemolyticus group is widely dispersed and undergoing rapid evolution. A total of 25 strains of pandemic serotypes such as O3:K6, O5:K17, and O1:KUT were identified. It is worth noting that the pandemic serotypes were not exclusively identified from clinical samples, rather, nine strains were also isolated from environmental samples; and some of these strains harbored several virulence genes, which may render those strains pathogenicity potential. Therefore, the emergence of these “environmental” pandemic V. parahaemolyticus strains may poses a new threat to the public health in China. Furthermore, six novel serotypes and 34 novel STs were identified among the 72 isolates, indicating that V. parahaemolyticus were widely distributed and fast evolving in the environment in Jiangsu, China. The findings of this study provide new insight into the phylogenic relationship between V. parahaemolyticus strains of pandemic serotypes from clinical and environmental sources and enhance the MLST database; and our proposed possible O- and K- antigen evolving paths of V. parahaemolyticus may help understand how the serotypes of this dispersed bacterial population evolve. PMID:27303379

[Primary hypothyroidism associated with empty sella turcica and hypopituitarism].

PubMed

Milosević, Maja; Stojanović, Milos; Nesović, Milica

2005-01-01

Empty sella syndrome is a rather frequent neuroradiological finding in the general population and can be associated with hypopituitarism. Examinations reveal low pituitary hormone levels and lack of response to stimuli. Most patients suffer from central hypothyroidism as part of pituitary insufficiency. Primary hypothyroidism is a rare finding in these patients. We present 3 patients: one female and two male, suffering from complete hypopituitarism, as part of the empty sella syndrome diagnosed due to low concentrations of all pituitary hormones, elevated TSH and low thyroid hormones. TRH, LHRH, ACTH and ITT tests, as well as IGF1 have confirmed hypopituitarism and primary hypothyroidism. CT and NMR in all three patients showed empty sella without a tumor in it. The diagnosis of primary hypothyrodism in the first patient was made before hypopituitarism has taken place, or at the same time in the second patient, whereas in the third patient it was diagnosed twenty years later. In two patients anti-TPO and anti-Tg antibody levels were high, and in the third patient they were not elevated. It can be assumed that the etiology of primary hypothyrodism in all three patients was of autoimmune origin, which caused thyroid hypofunction. High level of TSH in all three patients and especially in the patient whose hypopituitarism was diagnosed twenty years later, showed presence of thyrotrophic cells in the pituitary. Evaluation of the hypothalamic-pituitary-thyroid axis was carried out during the complete substitution therapy of hypopituitarism. Diagnosing primary hypothyroidism associated with hypopituitarism helps improving the knowledge on empty sella syndrome and points to different clinical syndromes characterized by lack of mixoedema, although approach to therapy is the same for both primary and central hypothyroidism.

A survey of oysters (Crassostrea gigas) in New Zealand for Vibrio parahaemolyticus and Vibrio vulnificus.

PubMed

Kirs, M; Depaola, A; Fyfe, R; Jones, J L; Krantz, J; Van Laanen, A; Cotton, D; Castle, M

2011-05-27

A microbiological survey was conducted to determine the levels of total and pathogenic Vibrio parahaemolyticus (Vp) and Vibrio vulnificus (Vv) in Pacific oysters (Crassostrea gigas) collected from commercial growing areas in the North Island, New Zealand. The survey was intended to be geographically representative of commercial growing areas of Pacific oysters in New Zealand, while selecting the time frame most likely to coincide with the increased abundance of pathogenic vibrio species. Vp was detected in 94.8% of oyster samples examined (n=58) with a geometric mean concentration of 99.3 MPN/g, while Vv was detected in 17.2% of oyster samples examined with a geometric mean concentration of 7.4 MPN/g. The frequency of Vp positive samples was 1.7 fold greater than reported in a study conducted three decades ago in New Zealand. Potentially virulent (tdh positive) Vp was detected in two samples (3.4%, n=58) while no trh (another virulence marker) positive samples were detected. 16S rRNA genotype could be assigned only to 58.8% of Vv isolates (8:1:1 A:B:AB ratio, n=10). There was a good agreement [98.2% of Vp (n=280) and 94.4% of Vv (n=18) isolates] between molecular tests and cultivation based techniques used to identify Vibrio isolates and there was a significant (R(2)=0.95, P<0.001, n=18) linear relationship between the MPN estimates by real-time PCR and cultivation. There was no significant correlation between any of the environmental parameters tested and Vp or Vv concentrations. Copyright © 2011 Elsevier B.V. All rights reserved.

Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

PubMed

Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

2015-03-01

In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of hypothalamic Sirt1 in body weight and energy balance regulation is debated. The first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague-Dawley rats. Central inhibition of Sirt1 decreased body weight and food intake as a result of a forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which in turn increased phosphorylated FoxO1 via improved insulin/phosphorylated AKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-melanocyte-stimulating hormone (α-MSH) maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (triiodothyronine, thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

PubMed

Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

2014-07-01

In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of Sirt1 in the brain, particularly the hypothalamus, in body weight and energy balance regulation is debated. Among the first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague Dawley rats. In that study, central inhibition of Sirt1 decreased body weight and food intake as a result of a Forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which, in turn, increased phosphorylated FoxO1 via improved insulin/pAKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-MSH maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

TrhOnt: building an ontology to assist rehabilitation processes.

PubMed

Berges, Idoia; Antón, David; Bermúdez, Jesús; Goñi, Alfredo; Illarramendi, Arantza

2016-10-04

One of the current research efforts in the area of biomedicine is the representation of knowledge in a structured way so that reasoning can be performed on it. More precisely, in the field of physiotherapy, information such as the physiotherapy record of a patient or treatment protocols for specific disorders must be adequately modeled, because they play a relevant role in the management of the evolutionary recovery process of a patient. In this scenario, we introduce TRHONT, an application ontology that can assist physiotherapists in the management of the patients' evolution via reasoning supported by semantic technology. The ontology was developed following the NeOn Methodology. It integrates knowledge from ontological (e.g. FMA ontology) and non-ontological resources (e.g. a database of movements, exercises and treatment protocols) as well as additional physiotherapy-related knowledge. We demonstrate how the ontology fulfills the purpose of providing a reference model for the representation of the physiotherapy-related information that is needed for the whole physiotherapy treatment of patients, since they step for the first time into the physiotherapist's office, until they are discharged. More specifically, we present the results for each of the intended uses of the ontology listed in the document that specifies its requirements, and show how TRHONT can answer the competency questions defined within that document. Moreover, we detail the main steps of the process followed to build the TRHONT ontology in order to facilitate its reproducibility in a similar context. Finally, we show an evaluation of the ontology from different perspectives. TRHONT has achieved the purpose of allowing for a reasoning process that changes over time according to the patient's state and performance.

Biological markers of melancholia and reclassification of depressive disorders.

PubMed

Greden, J F

1982-01-01

Pathophysiological markers of melancholia are being developed in four major areas: 1) neuroendocrine; 2) sleep; 3) psychomotor and 4) biochemical. Neuroendocrine markers include a failure of suppress plasma cortisol secretion in the dexamethasone suppression test (DST), diminished thyrotrophin (TSH) response to thyrotrophin releasing hormone (TRH stimulation test), and blunted growth hormone response to a variety of stimulating agents such as d-amphetamine, methylamphetamine, clonidine, L-dopa and insulin (growth hormone test). Of these, the DST is the best standardized. It is a highly specific laboratory marker with documented value in diagnosis, assessing prognosis and monitoring treatment progress. Sleep EEG abnormalities include reduced REM latency, increased REM density, reduction in delta sleep and impaired sleep efficiency. Sleep EEGs are pragmatically difficult, but results are quite specific. Elongated speech pause time (SPT) during "automatic speech" is a promising marker of psychomotor regulation. This simple, non-invasive measure may have special value in reducing clinical subjectivity and in monitoring treatment progress. Biochemical markers include: 1) platelet monoamine oxidase (MAO) activity; 2) in vitro lithium RBC transport and 3) urinary MHPG levels. Standardizations of biochemical tests are still lacking. Most biological tests for melancholia operate by indirectly "marking" CNS limbic system dysfunction. For wide acceptance, a test must be safe, moderately sensitive, highly specific, practical, relatively inexpensive and not significantly altered by common anti-depressant treatments. The DST best meets these criteria at this time. Proper utilization of test results requires knowledge of baseline prevalence rates and of the concepts of sensitivity (true-positive rate), specificity (true negative rate) and positive and negative predictive values (diagnostic confidence). No single marker will meet all clinical needs. Combinations or serial use of tests will hopefully enhance their already considerable usefulness.

Catching Galactic open clusters in advanced stages of dynamical evolution

NASA Astrophysics Data System (ADS)

Angelo, M. S.; Piatti, A. E.; Dias, W. S.; Maia, F. F. S.

2018-07-01

During their dynamical evolution, Galactic open clusters (OCs) gradually lose their stellar content mainly because of internal relaxation and tidal forces. In this context, the study of dynamically evolved OCs is necessary to properly understand such processes. We present a comprehensive Washington CT1 photometric analysis of six sparse OCs, namely ESO 518-3, Ruprecht 121, ESO 134-12, NGC 6573, ESO 260-7, and ESO 065-7. We employed Markov chain Monte Carlo simulations to robustly determine the central coordinates and the structural parameters and T1 × (C - T1) colour-magnitude diagrams cleaned from field contamination were used to derive the fundamental parameters. ESO 518-03, Ruprecht 121, ESO 134-12, and NGC 6573 resulted to be of nearly the same young age [8.2 ≤log(t yr-1) ≤ 8.3]; ESO 260-7 and ESO065-7 are of intermediate age [9.2 ≤log(t yr-1) ≤ 9.4]. All studied OCs are located at similar Galactocentric distances (RG ˜6-6.9 kpc), considering uncertainties, except for ESO 260-7 (RG = 8.9 kpc). These OCs are in a tidally filled regime and are dynamically evolved, since they are much older than their half-mass relaxation times (t/trh ≳ 30) and present signals of low-mass star depletion. We distinguished two groups: those dynamically evolving towards final disruptions and those in an advanced dynamical evolutionary stage. Although we do not rule out that the Milky Way potential could have made differentially faster their dynamical evolutions, we speculate here with the possibility that they have been mainly driven by initial formation conditions.

Hormones in the immune system and their possible role. A critical review.

PubMed

Csaba, György

2014-09-01

Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.

Prevalence of Vibrio parahaemolyticus in oyster and clam culturing environments in Taiwan.

PubMed

Yu, Wei-Ting; Jong, Koa-Jen; Lin, Yu-Ren; Tsai, Shing-en; Tey, Yao Hsien; Wong, Hin-chung

2013-01-01

Vibrio parahaemolyticus is the most prevalent gastroenteritis pathogen in Taiwan and some other Asian countries, and it frequently occurs in oysters and other seafood. This study monitors changes in the density of V. parahaemolyticus and environmental parameters in oyster and hard clam aquacultural environments in Taiwan. Water, sediment and shellfish samples were collected from five sampling sites in 2008-2010, and analyzed for environmental physiochemical parameters, numbers of indicator bacteria (total aerobic counts, total coliforms and fecal coliforms), Vibrio and V. parahaemolyticus present. The results for open oyster farms and hard clam ponds did not differ significantly. V. parahaemolyticus was detected in 77.5, 77.5, 70.8 and 68.8% of the water, sediment, oyster and clam samples, respectively. The densities of V. parahaemolyticus were significantly higher in shellfish than in sediment or water samples, with mean values of 1.33, 1.04 and -0.02 Log CFU/g, respectively. Among these five sampling sites, Shengang and Fangyuan yielded significantly different data from those obtained at the other three sites. As determined by linear multiple regression, V. parahaemolyticus density in water samples depended significantly on the precipitation and Vibrio count, while the V. parahaemolyticus density in the sediment or shellfish samples depended significantly on the salinity of the seawater. Among 1076 isolates examined, a total of three putative pathogenic isolates were identified from 2.5% of the examined samples, and these isolates exhibited hemolytic or urease activities and the presence of gene markers for tdh, trh, type III secretion system (T3SS) 1 (vcrD1) or T3SS2α (vcrD2). The results herein may facilitate the assessment of risk associated with this pathogen in Taiwan and other geographically similar regions. Copyright © 2012 Elsevier B.V. All rights reserved.

Pathologic hyperprolactinemia.

PubMed

Molitch, M E

1992-12-01

Unlike other pituitary hormones, PRL is under tonic inhibition by the hypothalamus by way of the PRL inhibitory factor, dopamine. GAP and GABA may also be inhibitory. PRL-releasing factors include TRH and VIP and possibly others. Circulating PRL is predominantly monomeric, although some patients with hyperprolactinemia appear to have increased quantities of the less biologically active polymeric forms. PRL is secreted episodically, with an increase in the amplitude of the secretory pulses with sleep. A transitory increase also occurs in response to the protein component of meals. Basal PRL levels increase in response to the hormonal milieu of pregnancy, and suckling postpartum triggers PRL release. Pathologic increases of PRL owing to hypothalamic dysregulation occur with a variety of medications, including the neuroleptics, metoclopramide, antidepressants, methyldopa, reserpine and verapamil, abuse of opiates and cocaine, renal insufficiency, cirrhosis, hypothyroidism, adrenal insufficiency, neurogenic stimulation, and idiopathically. Hyperprolactinemia also may occur from structural lesions of the stalk and hypothalamus, which cause disinhibition with or without maintenance of PRF activity, ectopic neoplasm production, and, most commonly, from prolactinomas. Diagnostic testing consists of routine chemistry and thyroid testing and imaging with MRI or CT. Dopamine agonists are the treatment of choice of prolactinomas of all sizes. Transsphenoidal surgery is an alternative for the patient who does not respond to medical therapy or who wishes definitive tumor removal, realizing that long-term cure is achieved in only 50% to 60% of patients with microadenomas and a much lower number in those with macroadenomas. Radiotherapy is reserved for patients who do respond to either medical or surgical treatment. Patients wishing to become pregnant usually are treated with bromocriptine, although prepregnancy surgical debulking may be advisable for those with large macroadenomas to reduce problems with tumor enlargement.

Temporal and Spatial Variability in Culturable Pathogenic Vibrio spp. in Lake Pontchartrain, Louisiana, following Hurricanes Katrina and Rita ▿ †

PubMed Central

Nigro, Olivia D.; Hou, Aixin; Vithanage, Gayatri; Fujioka, Roger S.; Steward, Grieg F.

2011-01-01

We investigated the abundance, distribution, and virulence gene content of Vibrio cholerae, V. parahaemolyticus, and V. vulnificus in the waters of southern Lake Pontchartrain in Louisiana on four occasions from October 2005 to September 2006, using selective cultivation and molecular assays. The three targeted pathogenic vibrios were generally below the detection level in January 2006, when the water was cold (13°C), and most abundant in September 2006, when the lake water was warmest (30°C). The maximum values for these species were higher than reported previously for the lake by severalfold to orders of magnitude. The only variable consistently correlated with total vibrio abundance within a single sampling was distance from shore (P = 0.000). Multiple linear regression of the entire data set revealed that distance from shore, temperature, and turbidity together explained 82.1% of the variability in total vibrio CFU. The log-transformed mean abundance of V. vulnificus CFU in the lake was significantly correlated with temperature (P = 0.014), but not salinity (P = 0.625). Virulence-associated genes of V. cholerae (ctx) and V. parahaemolyticus (trh and tdh) were not detected in any isolates of these species (n = 128 and n = 20, respectively). In contrast, 16S rRNA typing of V. vulnificus (n = 298) revealed the presence of both environmental (type A) and clinical (type B) strains. The percentage of the B-type V. vulnificus was significantly higher in the lake in October 2005 (35.8% of the total) than at other sampling times (P ≤ 0.004), consistent with the view that these strains represent distinct ecotypes. PMID:21642406

Bovine brain pyroglutamyl aminopeptidase (type-1): purification and characterisation of a neuropeptide-inactivating peptidase.

PubMed

Cummins, P M; O'Connor, B

1996-08-01

Pyroglutamyl aminopeptidase type-1 (PAP-I) is reported to be a soluble, broad specificity aminopeptidase, capable of removing the pyroglutamic acid (pGlu) residue from the amino terminus of pGlu-peptides (e.g. TRH, LHRH, neurotensin and bombesin). The central aim of this study was to undertake, for the first time, the complete purification and characterisation of a PAP activity observed within the cytosolic fraction of bovine whole brain and to compare the properties of the enzyme with previous findings. A series of chromatographic steps (DEAE-Sepharose, Sephacryl S-200 and Activated Thiol Sepharose 4B) generated a soluble PAP activity purified to near homogeneity with a total active yield of 6.6% The enzyme displayed a native molecular mass of approximately 23,700 Da, which compares well with that value obtained under denaturing conditions via SDS-PAGE (24,000 Da), suggesting that the enzyme exists as a monomer. The expression of PAP activity displayed an absolute requirement for the presence of a disulphide bond-reducing agent such as DTT, whilst optimum activity was observed at pH 8.5. strong inhibition of PAP activity was observed with a number of different agents, including transition metal ions, sulphydryl-blocking agents and 2-pyrrolidone (a pGlu analog). A broad pyroglutamyl substrate specificity, which excludes substrates commencing with the pGlu-Pro bond, was also demonstrated for the bovine brain enzyme. Based on a comparison of these findings with those reported for PAP-I in other mammalian tissues, the soluble PAP activity observed in bovine whole brain can tentatively be classified as a pyroglutamyl aminopeptidase type-1 (EC 3.4.19.3).

Resolution of G(s)alpha and G(q)alpha/G(11)alpha proteins in membrane domains by two-dimensional electrophoresis: the effect of long-term agonist stimulation.

PubMed

Matousek, P; Novotný, J; Svoboda, P

2004-01-01

Low-density membrane-domain fractions were prepared from S49 lymphoma cells and clone e2m11 of HEK293 cells expressing a large number of thyrotropin-releasing hormone receptor (TRH-R) and G(11)alpha by flotation on sucrose density gradients. The intact cell structure was broken by detergent-extraction, alkaline-treatment or drastic homogenization. Three types of low-density membranes were resolved by two-dimensional electrophoresis and analyzed for G(s)alpha (S49) or G(q)alpha/G11) (e2m11) content. Four individual immunoblot signals of Gsalpha protein were identified in S49 lymphoma cells indicating complete resolution of the long G(s)alpha L+/-ser and short G(s)alpha S+/-ser variants of G(s)alpha. All these were diminished by prolonged agonist (isoprenaline) stimulation. In e2m11-HEK cells, five different immunoblot signals were detected indicating post-translational modification of G proteins of G(q)alpha/G(11)alpha family. The two major spots corresponding to exogenously (over)expressed G(11)alpha and endogenous G(q)alpha were reduced; the minor spots diminished by hormonal stimulation. Parallel analysis by silver staining of the total protein content indicated that no major changes in protein composition occurred under these conditions. Our data thus indicate that agonist-stimulation of target cells results in down-regulation of all different members of G(s) and G(q)/G(11) families. This agonist-specific effect may be demonstrated in crude membrane as well as domain/raft preparations and it is not accompanied by changes in overall protein composition.

HYPERTHYROIDISM AND HYPERPROLACTINEMIA: IS THERE ANY ASSOCIATION?

PubMed

Sanjari, Mojgan; Safi, Zohreh; Tahroodi, Khatereh Mohammadi

2016-12-01

To compare the serum prolactin level in hyperthyroid and normal control females. Hyperthyroidism is a common disease. Although a direct association has been demonstrated between hypothyroidism and increased prolactin levels, this association has not been established for hyperthyroidism. Cross-sectional study in cases and control groups. Control subjects were chosen from those participating in the Kerman Coronary Artery Disease Risk Factors study. To select the cases, all women referred to the laboratories of Kerman with a thyroid-stimulating hormone (TSH) level ≤0.5 mIU/L who met the inclusion criteria were entered in the study. A total of 231 women aged 15 to 50 years were enrolled. The case group included 71 hyperthyroid women, and the control group included 160 women with normal thyroid function matched by age. The mean (SD) serum level of prolactin was 16.56 (0.97) ng/mL (95% confidence interval [CI], 15.41 ng/mL to 15.71 ng/mL) in the controls and 23.07 (1.49) ng/mL (95% CI, 22.7 ng/mL to 23.4 ng/mL) in the case subjects. Hyperprolactinemia was more common in the hyperthyroid group (16.5 [0.97] ng/mL versus 23.07 [1.49] ng/mL; P<.001). The prolactin level decreased with age. Hyperthyroidism and estradiol increased the prolactin level. After adjusting for age and estradiol, hyperthyroidism increased the serum prolactin level (P<.001). The results of this study revealed that hyperprolactinemia is more frequent in hyperthyroid females. Serum prolactin level can be increased in hyperthyroidism. PRL = prolactin T4 = thyroxine TRH = thyrotropin-releasing hormone TSH = thyroid-stimulating hormone.

In vitro pituitary and thyroid cell proliferation assays and their relevance as alternatives to animal testing.

PubMed

Jomaa, Barae; Aarts, Jac M M J G; de Haan, Laura H J; Peijnenburg, Ad A C M; Bovee, Toine F H; Murk, Albertinka J; Rietjens, Ivonne M C M

2013-01-01

This study investigates the in vitro effect of eleven thyroid-active compounds known to affect pituitary and/or thyroid weights in vivo, using the proliferation of GH3 rat pituitary cells in the so-called "T-screen," and of FRTL-5 rat thyroid cells in a newly developed test denoted "TSH-screen" to gain insight into the relative value of these in vitro proliferation tests for an integrated testing strategy (ITS) for thyroid activity. Pituitary cell proliferation in the T-screen was stimulated by three out of eleven tested compounds, namely thyrotropin releasing hormone (TRH), triiodothyronine (T3) and thyroxine (T4). Of these three compounds, only T4 causes an increase in relative pituitary weight, and thus T4 was the only compound for which the effect in the in vitro assay correlated with a reported in vivo effect. As to the newly developed TSH-screen, two compounds had an effect, namely, thyroid-stimulating hormone (TSH) induced and T4 antagonized FRTL-5 cell proliferation. These effects correlated with in vivo changes induced by these compounds on thyroid weight. Altogether, the results indicate that most of the selected compounds affect pituitary and thyroid weights by modes of action different from a direct thyroid hormone receptor (THR) or TSH receptor (TSHR)-mediated effect, and point to the need for additional in vitro tests for an ITS. Additional analysis of the T-screen revealed a positive correlation between the THR-mediated effects of the tested compounds in vitro and their effects on relative heart weight in vivo, suggesting that the T-screen may directly predict this THR-mediated in vivo adverse effect.

Abundance of Vibrio cholerae, V. vulnificus, and V. parahaemolyticus in oysters (Crassostrea virginica) and clams (Mercenaria mercenaria) from Long Island sound.

PubMed

Jones, Jessica L; Lüdeke, Catharina H M; Bowers, John C; DeRosia-Banick, Kristin; Carey, David H; Hastback, William

2014-12-01

Vibriosis is a leading cause of seafood-associated morbidity and mortality in the United States. Typically associated with consumption of raw or undercooked oysters, vibriosis associated with clam consumption is increasingly being reported. However, little is known about the prevalence of Vibrio spp. in clams. The objective of this study was to compare the levels of Vibrio cholerae, Vibrio vulnificus, and Vibrio parahaemolyticus in oysters and clams harvested concurrently from Long Island Sound (LIS). Most probable number (MPN)-real-time PCR methods were used for enumeration of total V. cholerae, V. vulnificus, V. parahaemolyticus, and pathogenic (tdh(+) and/or trh(+)) V. parahaemolyticus. V. cholerae was detected in 8.8% and 3.3% of oyster (n = 68) and clam (n = 30) samples, with levels up to 1.48 and 0.48 log MPN/g in oysters and clams, respectively. V. vulnificus was detected in 97% and 90% of oyster and clam samples, with median levels of 0.97 and -0.08 log MPN/g, respectively. V. parahaemolyticus was detected in all samples, with median levels of 1.88 and 1.07 log MPN/g for oysters and clams, respectively. The differences between V. vulnificus and total and pathogenic V. parahaemolyticus levels in the two shellfish species were statistically significant (P < 0.001). These data indicate that V. vulnificus and total and pathogenic V. parahaemolyticus are more prevalent and are present at higher levels in oysters than in hard clams. Additionally, the data suggest differences in vibrio populations between shellfish harvested from different growing area waters within LIS. These results can be used to evaluate and refine illness mitigation strategies employed by risk managers and shellfish control authorities. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

First Multi-Year Retrospective Study on Vibrio Parhaemolyticus and Vibrio Vulnificus Prevalence in Ruditapes Philippinarum Harvested in Sacca Di Goro, Italy.

PubMed

Serratore, Patrizia; Ostanello, Fabio; Passalacqua, Pier Luca; Zavatta, Emanuele; Bignami, Giorgia; Serraino, Andrea; Giacometti, Federica

2016-09-20

The present work describes a retrospective study aiming to verify a possible correlation between the environmental conditions (temperature, salinity and dissolved oxygen), the abundance of Vibrio spp., and the prevalence of V. parahaemolyticus and V. vulnificus in the Manila clam R. philippinarum harvested in Sacca di Goro, Emilia-Romagna Region, Northern Italy. On the whole, 104 samples, collected in the period 2007-2015 and submitted to microbiological analyses (isolation and genotyping), have been reconsidered for Vibrio spp. load, V. parahaemolyticus prevalence (total, gene marker toxRP; potentially pathogenic, gene markers tdh and/or trh) and V. vulnificus prevalence (total, gene markers vvh A and hsp) together with environmental data obtained from the monitoring activity of the Emilia-Romagna Regional Agency for the Prevention, the Environment and the Energy. Environmental data have been processed to calculate the median of each, assessing the seasonal range of seawater temperature (warmer months: April-October, T°C >16.45°C; cooler months November-March, T°C <16.45°C), salinity (27 psu), and dissolved oxygen (< or >8.2 mg/L). Total V. vulnificus , total and potentially pathogenic V. parahaemolyticus were present respectively in the 11.5, 29.8 and 6.7% of the samples. The Vibrio spp. load (mean value of 4.69±0.65 log 10 colony forming unit g -1 ) and the prevalence of potentially pathogenic V. parahaemolyticus , were not significantly correlated to the environmental conditions (P>0.05), whereas the prevalence of both total V. vulnificus and total V. parahaemolyticus was significantly higher in the warmer period (P<0.05), without correlation with salinity and dissolved oxygen values (P>0.05).

Use of Whole-Genome Phylogeny and Comparisons for Development of a Multiplex PCR Assay To Identify Sequence Type 36 Vibrio parahaemolyticus.

PubMed

Whistler, Cheryl A; Hall, Jeffrey A; Xu, Feng; Ilyas, Saba; Siwakoti, Puskar; Cooper, Vaughn S; Jones, Stephen H

2015-06-01

Vibrio parahaemolyticus sequence type 36 (ST36) strains that are native to the Pacific Ocean have recently caused multistate outbreaks of gastroenteritis linked to shellfish harvested from the Atlantic Ocean. Whole-genome comparisons of 295 genomes of V. parahaemolyticus, including several traced to northeastern U.S. sources, were used to identify diagnostic loci, one putatively encoding an endonuclease (prp), and two others potentially conferring O-antigenic properties (cps and flp). The combination of all three loci was present in only one clade of closely related strains of ST36, ST59, and one additional unknown sequence type. However, each locus was also identified outside this clade, with prp and flp occurring in only two nonclade isolates and cps in four. Based on the distribution of these loci in sequenced genomes, prp identified clade strains with >99% accuracy, but the addition of one more locus increased accuracy to 100%. Oligonucleotide primers targeting prp and cps were combined in a multiplex PCR method that defines species using the tlh locus and determines the presence of both the tdh and trh hemolysin-encoding genes, which are also present in ST36. Application of the method in vitro to a collection of 94 clinical isolates collected over a 4-year period in three northeastern U.S. states and 87 environmental isolates revealed that the prp and cps amplicons were detected only in clinical isolates identified as belonging to the ST36 clade and in no environmental isolates from the region. The assay should improve detection and surveillance, thereby reducing infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Prevalence and molecular characteristics of Vibrio spp. isolated from preharvest shrimp of the North Western Province of Sri Lanka.

PubMed

Koralage, Madura Sanjeevani Gonsal; Alter, Thomas; Pichpol, Duangporn; Strauch, Eckhard; Zessin, Karl-Hans; Huehn, Stephan

2012-10-01

This study investigated the prevalence and molecular characteristics of Vibrio spp. in farmed shrimp (Penaeus monodon) in Sri Lanka. A total of 170 shrimp samples (100 g of whole shrimp each) taken from individual ponds from 54 farms were collected 1 week prior to harvest from the North Western Province of Sri Lanka. Overall, 98.1% of the farms and 95.1% of the ponds were positive for Vibrio spp. in shrimp; at the pond level, V. parahaemolyticus (91.2%) was most common, followed by V. alginolyticus (18.8%), V. cholerae non-O1/non-O139 (4.1%), and V. vulnificus (2.4%). Multiple Vibrio spp. were detected in 20.6% of the ponds. None of the V. parahaemolyticus isolates (n = 419) were positive for the virulence-associated tdh (thermostable direct hemolysin) and trh (TDH-related hemolysin) genes. V. cholerae was confirmed by the presence of ompW, and all isolates (n = 8) were negative for the cholera toxin (ctxA) gene. V. cholerae isolates were serogrouped by PCR and identified as V. cholerae non-O1/non-O139. All four V. vulnificus strains, isolated from different ponds of two geographical regions, showed pathogenic potential; they belonged to vcgC sequence type, type B 16S rRNA genotype and contained a pilF polymorphism associated with human pathogenicity. The results of this study revealed the ubiquitous nature of vibrios in farmed shrimp. To minimize the potential risk of Vibrio infections due to handling or consumption of raw or undercooked seafood products, good manufacturing practices as well as proper handling and processing should be addressed.

Altered respiratory response to substance P in capsaicin-treated rats.

PubMed

Towle, A C; Mueller, R A; Breese, G R; Lauder, J

1985-01-01

The present investigation sought to examine the importance of substance P in the altered respiratory activity after neonatal capsaicin administration. Halothane-anesthetized adult rats given capsaicin neonatally exhibit a decreased basal minute ventilation with PaCO2 equal to and PaO2 greater than vehicle injected controls. In addition, the minute ventilation-PaCO2 curve was displaced to the right. Acute bilateral cervical vagotomy severely blunted the minute ventilation response to PaCO2 and abolished the differences in ventilation between capsaicin treated and control rats. Neonatal capsaicin significantly reduced pons-medulla substance P content but not TRH, serotonin or 5-hydroxyindole acetic acid. Immunohistochemical studies revealed that substance P fibers of the trigeminal spinal nucleus were the most severely affected in the brain stem and that substance P fibers in the lung were totally absent. The intracerebroventricular administration of substance P increased minute ventilation similarly in both control and capsaicin treated rats, largely as a result of increases in tidal volume. The minute ventilation-PaCO2 curve was similar in both groups after substance P administration. Simultaneous administration of the peptidase inhibitor captopril with substance P increased the respiratory response to substance P in normal rats. Administration of captopril to capsaicin treated rats restored the ventilation-PaCO2 curve to the position observed in normal rats. The hypotensive response to intracerebroventricular captopril alone in control rats was less profound in rats given neonatal capsaicin. These results are consistent with the thesis that respiratory depression after capsaicin treatment is at least in part due to the loss of substance P primary afferent nerve terminals in the brain stem, suggesting that substance P fibers in the brain stem may participate in the normal modulation of respiratory activity.

Field and Experimental Evidence of Vibrio parahaemolyticus as the Causative Agent of Acute Hepatopancreatic Necrosis Disease of Cultured Shrimp (Litopenaeus vannamei) in Northwestern Mexico

PubMed Central

Gomez-Gil, Bruno; Lozano-Olvera, Rodolfo; Betancourt-Lozano, Miguel; Morales-Covarrubias, Maria Soledad

2014-01-01

Moribund shrimp affected by acute hepatopancreatic necrosis disease (AHPND) from farms in northwestern Mexico were sampled for bacteriological and histological analysis. Bacterial isolates were molecularly identified as Vibrio parahaemolyticus by the presence of the tlh gene. The tdh-negative, trh-negative, and tlh-positive V. parahaemolyticus strains were further characterized by repetitive extragenic palindromic element-PCR (rep-PCR), and primers AP1, AP2, AP3, and AP and an ems2 IQ2000 detection kit (GeneReach, Taiwan) were used in the diagnostic tests for AHPND. The V. parahaemolyticus strains were used in immersion challenges with shrimp, and farmed and challenged shrimp presented the same clinical and pathological symptoms: lethargy, empty gut, pale and aqueous hepatopancreas, and expanded chromatophores. Using histological analysis and bacterial density count, three stages of AHNPD (initial, acute, and terminal) were identified in the affected shrimp. The pathognomonic lesions indicating severe desquamation of tubular epithelial cells of the hepatopancreas were observed in both challenged and pond-infected shrimp. The results showed that different V. parahaemolyticus strains have different virulences; some of the less virulent strains do not induce 100% mortality, and mortality rates also rise more slowly than they do for the more virulent strains. The virulence of V. parahaemolyticus strains was dose dependent, where the threshold infective density was 104 CFU ml−1; below that density, no mortality was observed. The AP3 primer set had the best sensitivity and specificity. Field and experimental results showed that the V. parahaemolyticus strain that causes AHPND acts as a primary pathogen for shrimp in Mexico compared with the V. parahaemolyticus strains reported to date. PMID:25548045

Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer.

PubMed

Pujol, P; Daures, J P; Nsakala, N; Baldet, L; Bringer, J; Jaffiol, C

1996-12-01

We investigate whether the prognosis of patients with differentiated thyroid cancer is improved by maintaining a greater level of TSH suppression. One hundred and forty-one patients who underwent hormone therapy after thyroidectomy were followed up from 1970 to 1993 (mean, 95 months). Patients received levothyroxine (L-T4; mean dose, 2.6 micrograms/kg-day). TSH suppression was evaluated by TRH stimulation test until 1986 and thereafter by a second generation immunoradiometric assay. As TSH underwent fluctuation over time in most patients, we focused on subgroups of patients with relatively constant TSH levels during the follow-up. The relapse-free survival (RFS) was longer in the group with constantly suppressed TSH (all TSH values, < or = 0.05 mU/L; n = 18) than in the group with nonsuppressed TSH (all TSH values, > or = 1 mU/L; n = 15; P < 0.01). Age, sex, tumor node metastasis stage, and initial therapy were not different between the suppressed and nonsuppressed TSH groups. In the overall population, we analyzed the level of TSH suppression by studying the percentage of undetectable TSH values (< or = 0.05 mU/L) during the follow-up. The patients with a greater degree of TSH suppression (> 90% of undetectable TSH values; n = 19) had a trend toward a longer RFS than the remaining population (n = 102; P = 0.14). The patients with a lesser degree of TSH suppression (< 10% of undetectable TSH values; n = 27) had a shorter RFS than the remaining patients (n = 94; P < 0.01). In multivariate analysis that included TSH suppression, age, sex, histology, and tumor node metastasis stage, the degree of TSH suppression predicted RFS independently of other factors (P = 0.02). This study shows that a lesser degree of TSH suppression is associated with an increased incidence of relapse, supporting the hypothesis that a high level of TSH suppression is required for the endocrine management of thyroid cancer.

Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials.

PubMed

van Die, M Diana; Burger, Henry G; Teede, Helena J; Bone, Kerry M

2013-05-01

Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.Eight databases were searched using Latin and common names for Vitex and phytotherapeutic preparations of the herb as a sole agent, together with filters for randomised, controlled trials or clinical trials. Methodological quality was assessed according to the Cochrane risk of bias and Jadad scales, as well as the proposed elaboration of CONSORT for reporting trials on herbal interventions.Thirteen randomised, controlled trials were identified and twelve are included in this review, of which eight investigated premenstrual syndrome, two premenstrual dysphoric disorder, and two latent hyperprolactinaemia. For premenstrual syndrome, seven of eight trials found Vitex extracts to be superior to placebo (5 of 6 studies), pyridoxine (1), and magnesium oxide (1). In premenstrual dysphoric disorder, one study reported Vitex to be equivalent to fluoxetine, while in the other, fluoxetine outperformed Vitex. In latent hyperprolactinaemia, one trial reported it to be superior to placebo for reducing TRH-stimulated prolactin secretion, normalising a shortened luteal phase, increasing mid-luteal progesterone and 17β-oestradiol levels, while the other found Vitex comparable to bromocriptine for reducing serum prolactin levels and ameliorating cyclic mastalgia. Adverse events with Vitex were mild and generally infrequent. The methodological quality of the included studies varied, but was generally moderate-to-high. Limitations include small sample sizes in some studies, heterogeneity of conditions being treated, and a range of reference treatments.Despite some methodological limitations, the results from randomised, controlled trials to date suggest benefits for Vitex extracts in the treatment of premenstrual syndrome, premenstrual dysphoric disorder and latent hyperprolactinaemia. Further research is recommended, and greater transparency in reporting for future trials. Georg Thieme Verlag KG Stuttgart · New York.

Temperature dependence of the control of energy homeostasis requires CART signaling.

PubMed

Lau, Jackie; Shi, Yan-Chuan; Herzog, Herbert

2016-10-01

Cocaine- and amphetamine-regulated transcript (CART) is a key neuropeptide with predominant expression in the hypothalamus central to the regulation of diverse biological processes, including food intake and energy expenditure. While there is considerable information on CART's role in the control of feeding, little is known about its thermoregulatory potential. Here we show the consequences of lack of CART signaling on major parameters of energy homeostasis in CART -/- mice under standard ambient housing (RT, 22°C), which is considered a mild cold exposure for mice, and thermoneutral conditions (TN, 30°C). WT mice kept at RT showed an increase in food intake, energy expenditure, BAT UCP-1 expression, and physical activity compared with TN condition, reflecting the augmented energy demand for thermogenesis at RT. On the molecular level, RT housing led to upregulated mRNA expression of TH, CRH, and TRH at the PVN, while NPY, AgRP and CART mRNA levels in the Arc were downregulated. CART -/- mice displayed elevated adiposity and diminished lean mass across both RT and TN. At RT, CART -/- mice showed unchanged food consumption yet greater body weight gain. In addition, an increase in energy expenditure and heightened BAT thermogenesis marked by UCP-1 protein expression was observed in the CART -/- mice. In contrast, TN-housed CART -/- mice exhibited lower weight gain than WT mice accompanied with pronounced reduction in basal feeding. These findings were correlated with reduced BAT temperature, but unchanged energy expenditure and UCP-1 levels. Interestingly, the respiratory exchange ratio for CART -/- mice, which shifted from lower at RT to higher at TN with respect to WT controls, indicates a transition of relative fuel source preference from fat to carbohydrate in the absence of CART signaling. Taken together, these results demonstrate that CART is a critical regulator of energy expenditure, energy partitioning and utilization dependent on the thermal environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Holoprosencephaly: ZIC2 mutation in a case with panhypopituitarism.

PubMed

Tasdemir, Sener; Sahin, Ibrahim; Cayır, Atilla; Doneray, Hakan; Solomon, Benjamin D; Muenke, Maximilian; Yuce, Ihsan; Tatar, Abdulgani

2014-07-01

Holoprosencephaly (HPE), the most common malformation of the brain, results from failed or incomplete separation of the embryonic forebrain (prosencephalon). HPE occurs in approximately 1 in 250 embryos and in about 1 in 10,000 births. It is etiologically heterogeneous, and may be caused by cytogenetic anomalies and teratogenic influences; it occurs as part of a syndrome, or due to heterozygous mutations in 1 of over 10 HPE-associated genes. ZIC2 mutations are the second-most common cause of non-syndromic non-chromosomal HPE (after sonic hedgehog) and occur de novo in 74% of the affected probands. The objective of the study was to describe the first case of ZIC2-related HPE with both anterior and posterior pituitary insufficiencies. We report about a 2-year-8-month-old boy who was born as a second child in a non-consanguineous healthy Turkish family. He has the characteristic ZIC2 phenotype: bitemporal narrowing, upslanting palpebral fissures, large ears, short nose with anteverted nares and broad and deep philtrum. Magnetic resonance imaging revealed alobar HPE. During laboratory investigation, his blood sodium level was 158 mmol/L and the specific gravity of his urine was 1.002. Serum osmolarity was 336 mOsm/L and urine osmolality was 135 mOsm/kg. His FT4 was 0.8 ng/dL and TSH was 0.79 mLU/mL. Response to vasopressin confirmed the diagnosis of central diabetes insipidus and TRH-stimulating test supported the central hypothyroidism. A frameshift mutation (NM_007129.2:c1091_1092 del, p.Gln364Leufs*2) in the ZIC2 gene was detected. Pituitary insufficiency other than isolated diabetes insipidus is a rare finding of HPE, and occurs most frequently in patients with GLI2 mutations (the phenotype of which typically does not include frank neuroanatomic anomalies such as HPE); ours is the only described patient with a ZIC2 mutation and both anterior and posterior pituitary dysfunction.

Preterm birth

PubMed Central

2010-01-01

Introduction Preterm birth occurs in about 5% to 10% of all births in resource-rich countries, but in recent years the incidence seems to have increased in some countries, particularly in the USA. We found little reliable evidence for incidence in resource-poor countries. The rate in northwestern Ethiopia has been reported to vary from 11% to 22%, depending on the age group of mothers studied, and is highest in teenage mothers. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in women at high risk of preterm delivery? What are the effects of interventions to improve neonatal outcome after preterm rupture of membranes? What are the effects of treatments to stop contractions in preterm labour? What are the effects of elective compared with selective caesarean delivery for women in preterm labour? What are the effects of interventions to improve neonatal outcome in preterm delivery? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amnioinfusion for preterm rupture of membranes; antenatal corticosteroids; antibiotic treatment; bed rest; beta mimetics; calcium-channel blockers; elective caesarean; enhanced antenatal care programmes; magnesium sulphate; oxytocin receptor antagonists (atosiban); progesterone; prophylactic cervical cerclage; prostaglandin inhibitors (e.g., indometacin); selective caesarean; and thyrotropin-releasing hormone (TRH) (plus corticosteroids).

Preterm birth

PubMed Central

2011-01-01

Introduction Preterm birth occurs in about 5% to 10% of all births in resource-rich countries, but in recent years the incidence seems to have increased in some countries, particularly in the USA. We found little reliable evidence for incidence in resource-poor countries. The rate in northwestern Ethiopia has been reported to vary from 11% to 22%, depending on the age group of mothers studied, and is highest in teenage mothers. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of preventive interventions in women at high risk of preterm delivery? What are the effects of interventions to improve neonatal outcome after preterm rupture of membranes? What are the effects of treatments to stop contractions in preterm labour? What are the effects of elective compared with selective caesarean delivery for women in preterm labour? What are the effects of interventions to improve neonatal outcome in preterm delivery? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 58 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: amnioinfusion for preterm rupture of membranes, antenatal corticosteroids, antibiotic treatment, bed rest, beta-mimetics, calcium channel blockers, elective caesarean, enhanced antenatal care programmes, magnesium sulphate, oxytocin receptor antagonists (atosiban), progesterone, prophylactic cervical cerclage, prostaglandin inhibitors (e.g., indometacin), selective caesarean, and thyrotropin-releasing hormone (TRH) (plus corticosteroids). PMID:21463540

Factors for consideration in the interpretation of the adverse effects of elevated environmental temperatures on reproduction in the male rat

NASA Astrophysics Data System (ADS)

Bedrak, E.; Chap, Z.; Fried, K.

1980-06-01

Continuous exposure of male rats to an elevated environmental temperature (33 35° C) for 3 weeks led to heat-acclimatized (HA) rats whose serum testosterone concentratrion was significantly lower (P<0.01) than that of control (C) rats (20 22° C). The decrease in the androgen level was independent of major changes in serum FSH and LH concentrations, as well as hypothalamic content of thyrotropin-releasing hormone (THR), gonadotropin-releasing hormone (GnRH) and prostaglandin E2 (PGE2). However, the prostaglandin F2α(PGF2α) content of the hypothalamus of HA rats was significantly lower (P < 0.05) than that of C. The number of receptors for human chorionic gonadotropin (hCG) was significantly lower in testicular tissue of HA rats as compared to C males. Histological examination of the testis disclosed that exposure to heat adversely affected the sperm production and integrity of the Sertoli cells. Activity of enzymes associated with testosterone biosynthesis in testicular tissue of rats incubated at temperatures similar to those prevailing in the scrotum of HA rats resembled the activity of these enzymes observed in HA animals. Catabolism of testosterone was enhanced when kidney and liver of C rats were incubated at temperatures similar to the deep-body temperatures of HA rats, supporting the thesis that acclimatization to heat is coupled, inter alin, with increase androgen catabolism and excretion. It is suggested that the lower reproductive performance of HA rats is associated with several phenomena: a low number of receptors for hCG in the testes, decreased testoster one production rate by the Leydig cells, increased cata bolism and excretion of androgen, and partial atrophy of seminiferous tubules and Sertoli cells. These changes appear to be independent of either alteration in serum gonadotropin concentration or hypothalamic contents of TRH, GnR H and PGE2. The physiological significance in the response of PGF2α awaits further clarification.

Serology, virulence, antimicrobial susceptibility and molecular characteristics of clinical Vibrio parahaemolyticus strains circulating in southeastern China from 2009 to 2013.

PubMed

Chen, Y; Chen, X; Yu, F; Wu, M; Wang, R; Zheng, S; Han, D; Yang, Q; Kong, H; Zhou, F; Zhu, J; Yao, H; Zhou, W; Li, L

2016-03-01

Vibrio parahaemolyticus is a leading cause of food-borne diarrhoea in coastal countries. Although V. parahaemolyticus cases have been reported since 1950, they have been poorly documented. From July 2009 to June 2013, we collected 6951 faecal specimens for pathogen detection; V. parahaemolyticus strains were isolated from 563 specimens (8.1%). We then analysed the characteristics of the 501 V. parahaemolyticus strains that were isolated as the sole pathogen. Twenty-one serotypes were identified among these strains; O3:K6 was the most common serotype (65.1%), followed by O4:K8, O4:K68 and O1:K36. One strain of the O4:K18 serotype was isolated from clinical patients for the first time. Pandemic O3:K6 clones were predominant and accounted for 69.1% of all of the pandemic strains. This is the first report of one strain expressing the O3:K8 serotype with a pandemic genotype. The presence of the haemolysin gene tdh (93.0%) was the key characteristic of the virulent strains; however, a few strains carried the trh gene. We also confirmed the presence of the type III secretion system 2 (T3SS2) genes in all of the pathogenic strains. Subsequent multilocus sequence typing split the isolates into 16 sequence types (STs), with ST3 and ST88 as the most prevalent in southeastern China. Most isolates were sensitive to common antimicrobial agents, apart from ampicillin. However, the resistance rate to ampicillin has apparently increased in this area. In conclusion, our results indicate that pandemic O3:K6 V. parahaemolyticus isolates are predominant in southeastern China, and additional surveillance should be conducted to facilitate control of the transmission of this pathogen. Copyright © 2016. Published by Elsevier Ltd.

Serogroup, virulence, and molecular traits of Vibrio parahaemolyticus isolated from clinical and cockle sources in northeastern Thailand.

PubMed

Mala, Wanida; Alam, Munirul; Angkititrakul, Sunpetch; Wongwajana, Suwin; Lulitanond, Viraphong; Huttayananont, Sriwanna; Kaewkes, Wanlop; Faksri, Kiatichai; Chomvarin, Chariya

2016-04-01

Vibrio parahaemolyticus is responsible for seafood-borne gastroenteritis worldwide. Isolates of V. parahaemolyticus from clinical samples (n=74) and cockles (Anadara granosa) (n=74) in Thailand were analyzed by serotyping, determination of virulence and related marker genes present, response to antimicrobial agents, and genetic relatedness. Serological analysis revealed 31 different serotypes, 10 of which occurred among both clinical and cockle samples. The clinical isolates commonly included the pandemic serogroup O3:K6, while a few of the cockle isolates exhibited likely pandemic serovariants such as O3:KUT and O4:KUT, but not O3:K6. The pandemic (orf8 gene-positive) strains were more frequently found among clinical isolates (78.4%) than cockle isolates (28.4%) (p<0.001). Likewise, the virulence and related marker genes were more commonly detected among clinical than cockle isolates; i.e., tdh gene (93.2% versus 29.7%), vcrD2 (97.3% versus 23.0%), vopB2 (89.2% versus 13.5%), vopT (98.6% versus 36.5%) (all p<0.001) and trh (10.8% versus 1.4%) (p<0.05). Pulsed-field gel electrophoresis of NotI-digested genomic DNA of 41 randomly selected V. parahaemolyticus isolates representing different serotypes produced 33 pulsotypes that formed 5 different clusters (clonal complexes) (A-E) in a dendrogram. Vibrio parahaemolyticus O3:K6 and likely related pandemic serotypes were especially common among the numerous clinical isolates in cluster C, suggesting a close clonal link among many of these isolates. Most clinical and cockle isolates were resistant to ampicillin. This study indicates that O3:K6 and its likely serovariants based on the PFGE clusters, are causative agents. Seafoods such as cockles potentially serve as a source of virulent V. parahaemolyticus, but further work is required to identify possible additional sources. Copyright © 2016. Published by Elsevier B.V.

Ecological fitness and virulence features of Vibrio parahaemolyticus in estuarine environments.

PubMed

Lovell, Charles R

2017-03-01

Vibrio parahaemolyticus is a commonly encountered and highly successful organism in marine ecosystems. It is a fast-growing, extremely versatile copiotroph that is active over a very broad range of conditions. It frequently occurs suspended in the water column (often attached to particles or zooplankton), and is a proficient colonist of submerged surfaces. This organism is an important pathogen of animals ranging from microcrustaceans to humans and is a causative agent of seafood-associated food poisoning. This review examines specific ecological adaptations of V. parahaemolyticus, including its broad tolerances to temperature and salinity, its utilization of a wide variety of organic carbon and energy sources, and its pervasive colonization of suspended and stationary materials that contribute to its success and ubiquity in temperate and tropical estuarine ecosystems. Several virulence-related features are examined, in particular the thermostable direct hemolysin (TDH), the TDH-related hemolysin (TRH), and the type 3 secretion system, and the possible importance of these features in V. parahaemolyticus pathogenicity is explored. The impact of new and much more effective PCR primers on V. parahaemolyticus detection and our views of virulent strain abundance are also described. It is clear that strains carrying the canonical virulence genes are far more common than previously thought, which opens questions regarding the role of these genes in pathogenesis. It is also clear that virulence is an evolving feature of V. parahaemolyticus and that novel combinations of virulence factors can lead to emergent virulence in which a strain that is markedly more pathogenic evolves and propagates to produce an outbreak. The effects of global climate change on the frequency of epidemic disease, the geographic distribution of outbreaks, and the human impacts of V. parahaemolyticus are increasing and this review provides information on why this ubiquitous human pathogen has increased its footprint and its significance so dramatically.

[Inhibition analysis of resveratrol against Vibrio parahaemolyticus biofilm based on RNA-Seq technology].

PubMed

Zhang, Fang; Zhu, Junli; Feng, Lifang

2016-05-04

Food phytochemicals as biofilm inhibitor of pathogens have been highlighted. Our study aimed to investigate the effects of resveratrol on biofilm formation of an aquatic pathogen Vibrio parahaemolyticus, and to elucidate the important regulatory genes. In the subinhibitory concentrations, the inhibition of resveratrol aganist biofilm and exopolysaccharides of V. parahaemolyticus was detected, and the differentially expressed genes were analyzed based on RNA-Seq. Four genes involved in biofilm formation was validated by qRT-PCR. The minimum inhibitory concentration of resveratrol against V. parahaemolyticus was 20 μg/mL. Resveratrol at the subinhibitory concentration of 5 μg/mL and 10 μg/mL significantly decreased the biofilm development and exopolysaccharides production in V. parahaemolyticus (P < 0.05). Scanning electron microscopy micrographs showed a significant reduction of adherence and extracellular polymeric substances. RNA-Seq analysis revealed that 22.6% up-regulated and 77.4% down-regulated gene (P < 0.05) after treatment by 10 μg/mL resveratrol among 106 differential gene expressions. These differential genes in V. parahaemolyticu focused on 7 metabolic pathways, and 14 genes involved in biofilm formation were down-regulated by resveratrol, such as outer membrane protein (W, YedS, OmpK), quorum sensing (LuxS), flagellin (FlaA), fimbrial assembly protein (PilQ), hemolysin secreted protein. qRT-PCR confirmed that the expressions of luxS, trh, tlh and flaA, was significantly repressed in the presence of resveratrol, which was consistent with transcriptomics data. Inhibitory activity of resveratrol on biofilm formation was assicated with multiple genes and diverse cellular processes in V. parahaemolyticus. These findings suggest that resveratrol would disturb various metabolic pathways, particularly quorum sensing system, adhesion process and membrane proteins secretion, resulting in inhibition of attachment and biofilm development. The present work provided valuable information to explore molecular mechanism of resveratrol as an novel anti-biofilm compound.

Experimentally determined standard thermodynamic properties of synthetic MgSO(4)·4H(2)O (Starkeyite) and MgSO(4)·3H(2)O: a revised internally consistent thermodynamic data set for magnesium sulfate hydrates.

PubMed

Grevel, Klaus-Dieter; Majzlan, Juraj; Benisek, Artur; Dachs, Edgar; Steiger, Michael; Fortes, A Dominic; Marler, Bernd

2012-11-01

The enthalpies of formation of synthetic MgSO(4)·4H(2)O (starkeyite) and MgSO(4)·3H(2)O were obtained by solution calorimetry at T=298.15 K. The resulting enthalpies of formation from the elements are [Formula: see text] (starkeyite)=-2498.7±1.1 kJ·mol(-1) and [Formula: see text] (MgSO(4)·3H(2)O)=-2210.3±1.3 kJ·mol(-1). The standard entropy of starkeyite was derived from low-temperature heat capacity measurements acquired with a physical property measurement system (PPMS) in the temperature range 5 K

Exposure to PFDoA causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae.

PubMed

Zhang, Shengnan; Guo, Xiaochun; Lu, Shaoyong; Sang, Nan; Li, Guangyu; Xie, Ping; Liu, Chunsheng; Zhang, Liguo; Xing, Yi

2018-04-01

Perfluorododecanoic acid (PFDoA), a kind of perfluorinated carboxylic acid (PFCA) with 12 carbon atoms, has an extensive industrial utilization and is widespread in both wildlife and the water environment, and was reported to have the potential to cause a disruption in the thyroid hormone system homeostasis. In this study, zebrafish embryos/larvae were exposed to different concentrations of PFDoA (0, 0.24, 1.2, 6 mg/L) for 96 h post-fertilization (hpf). PFDoA exposure caused obvious growth restriction connected with the reduced thyroid hormones (THs) contents in zebrafish larvae, strengthening the interference effect on the growth of fish larvae. The transcriptional level of genes within the hypothalamic-pituitary-thyroid (HPT) axis was analyzed. The gene expression levels of thyrotropin-releasing hormone (trh) and corticotrophin-releasing hormone (crh) were upregulated upon exposure to 6 mg/L of PFDoA, and iodothyronine deiodinases (dio2) was upregulated in the 1.2 mg/L PFDoA group. The transcription of thyroglobulin (tg) and thyroid receptor (trβ) were significantly downregulated upon exposure to 1.2 mg/L and 6 mg/L of PFDoA. PFDoA could also decrease the levels of sodium/iodide symporter (nis) and transthyretin (ttr) gene expression in a concentration-dependent manner after exposure. A significant decrease in thyroid-stimulating hormoneβ (tshβ), uridinediphosphate-glucuronosyltransferase (ugt1ab) and thyroid receptor (trα) gene expression were observed at 6 mg/L PFDoA exposure. Upregulation and downregulation of iodothyronine deiodinases (dio1) gene expression were observed upon the treatment of 1.2 mg/L and 6 mg/L PFDoA, respectively. All the data demonstrated that gene expression in the HPT axis altered after different PFDoA treatment and the potential mechanisms of the disruption of thyroid status could occur at several steps in the process of synthesis, regulation, and action of thyroid hormones. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

PubMed

Tian, Ying; Arai, Eri; Gotoh, Masahiro; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Kanai, Yae

2014-10-20

The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes. DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort. Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs. The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.

Ablation of Sim1 Neurons Causes Obesity through Hyperphagia and Reduced Energy Expenditure

PubMed Central

Xi, Dong; Gandhi, Nilay; Lai, Meizan; Kublaoui, Bassil M.

2012-01-01

Single-minded 1 (Sim1) is a transcription factor necessary for development of the paraventricular nucleus of the hypothalamus (PVH). This nucleus is a critical regulator of appetite, energy expenditure and body weight. Previously we showed that Sim1+/− mice and conditional postnatal Sim1−/− mice exhibit hyperphagia, obesity, increased linear growth and susceptibility to diet-induced obesity, but no decrease in energy expenditure. Bilateral ablation of the PVH causes obesity due to hyperphagia and reduced energy expenditure. It remains unknown whether Sim1 neurons regulate energy expenditure. In this study, Sim1cre mice were bred to homozygous inducible diphtheria toxin receptor (iDTR) mice to generate mice expressing the simian DTR in Sim1 cells. In these mice, Sim1 neuron ablation was performed by intracerebroventricular (ICV) injection of diphtheria toxin. Compared to controls, mice with Sim1 neuron ablation became obese (with increased fat mass) on a chow diet due to increased food intake and reduced energy expenditure. In post-injection mice, we observed a strong inverse correlation between the degree of obesity and hypothalamic Sim1 expression. The reduction in baseline energy expenditure observed in these mice was accompanied by a reduction in activity. This reduction in activity did not fully account for the reduced energy expenditure as these mice exhibited decreased resting energy expenditure, decreased body temperature, decreased brown adipose tissue temperature, and decreased UCP1 expression suggesting an impairment of thermogenesis. In injected mice, hypothalamic gene expression of Sim1, oxytocin (OXT) and thyrotropin releasing hormone (TRH) was reduced by about 50%. These results demonstrate that Sim1 neurons in adult mice regulate both food intake and energy expenditure. Based on the body of work in the field, feeding regulation by Sim1 neurons likely occurs in both the PVH and medial amygdala, in contrast to energy expenditure regulation by Sim1 neurons, which likely is localized to the PVH. PMID:22558467

Ablation of Sim1 neurons causes obesity through hyperphagia and reduced energy expenditure.

PubMed

Xi, Dong; Gandhi, Nilay; Lai, Meizan; Kublaoui, Bassil M

2012-01-01

Single-minded 1 (Sim1) is a transcription factor necessary for development of the paraventricular nucleus of the hypothalamus (PVH). This nucleus is a critical regulator of appetite, energy expenditure and body weight. Previously we showed that Sim1(+/-) mice and conditional postnatal Sim1(-/-) mice exhibit hyperphagia, obesity, increased linear growth and susceptibility to diet-induced obesity, but no decrease in energy expenditure. Bilateral ablation of the PVH causes obesity due to hyperphagia and reduced energy expenditure. It remains unknown whether Sim1 neurons regulate energy expenditure. In this study, Sim1cre mice were bred to homozygous inducible diphtheria toxin receptor (iDTR) mice to generate mice expressing the simian DTR in Sim1 cells. In these mice, Sim1 neuron ablation was performed by intracerebroventricular (ICV) injection of diphtheria toxin. Compared to controls, mice with Sim1 neuron ablation became obese (with increased fat mass) on a chow diet due to increased food intake and reduced energy expenditure. In post-injection mice, we observed a strong inverse correlation between the degree of obesity and hypothalamic Sim1 expression. The reduction in baseline energy expenditure observed in these mice was accompanied by a reduction in activity. This reduction in activity did not fully account for the reduced energy expenditure as these mice exhibited decreased resting energy expenditure, decreased body temperature, decreased brown adipose tissue temperature, and decreased UCP1 expression suggesting an impairment of thermogenesis. In injected mice, hypothalamic gene expression of Sim1, oxytocin (OXT) and thyrotropin releasing hormone (TRH) was reduced by about 50%. These results demonstrate that Sim1 neurons in adult mice regulate both food intake and energy expenditure. Based on the body of work in the field, feeding regulation by Sim1 neurons likely occurs in both the PVH and medial amygdala, in contrast to energy expenditure regulation by Sim1 neurons, which likely is localized to the PVH.

Synaptic Activity in Serotonergic Neurons Is Required for Air-Puff Stimulated Flight in Drosophila melanogaster

PubMed Central

Sadaf, Sufia; Birman, Serge; Hasan, Gaiti

2012-01-01

Background Flight is an integral component of many complex behavioral patterns in insects. The giant fiber circuit has been well studied in several insects including Drosophila. However, components of the insect flight circuit that respond to an air-puff stimulus and comprise the flight central pattern generator are poorly defined. Aminergic neurons have been implicated in locust, moth and Drosophila flight. Here we have investigated the requirement of neuronal activity in serotonergic neurons, during development and in adults, on air-puff induced flight in Drosophila. Methodology/Principal Findings To target serotonergic neurons specifically, a Drosophila strain that contains regulatory regions from the TRH (Tryptophan Hydroxylase) gene linked to the yeast transcription factor GAL4 was used. By blocking synaptic transmission from serotonergic neurons with a tetanus toxin transgene or by hyperpolarisation with Kir2.1, close to 50% adults became flightless. Temporal expression of a temperature sensitive Dynamin mutant transgene (Shits) suggests that synaptic function in serotonergic neurons is required both during development and in adults. Depletion of IP3R in serotonergic neurons via RNAi did not affect flight. Interestingly, at all stages a partial requirement for synaptic activity in serotonergic neurons was observed. The status of serotonergic neurons was investigated in the central nervous system of larvae and adults expressing tetanus toxin. A small but significant reduction was observed in serotonergic cell number in adult second thoracic segments from flightless tetanus toxin expressing animals. Conclusions These studies show that loss of synaptic activity in serotonergic neurons causes a flight deficit. The temporal focus of the flight deficit is during pupal development and in adults. The cause of the flight deficit is likely to be loss of neurons and reduced synaptic function. Based on the partial phenotypes, serotonergic neurons appear to be modulatory, rather than an intrinsic part of the flight circuit. PMID:23029511

Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

PubMed

Harvey, S; Gineste, C; Gaylinn, B D

2014-08-01

Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor. Copyright © 2014 Elsevier Inc. All rights reserved.

Structural Health Monitoring of Composite Wound Pressure Vessels

NASA Technical Reports Server (NTRS)

Grant, Joseph; Kaul, Raj; Taylor, Scott; Jackson, Kurt; Myers, George; Sharma, A.

2002-01-01

The increasing use of advanced composite materials in the wide range of applications including Space Structures is a great impetus to the development of smart materials. Incorporating these FBG sensors for monitoring the integrity of structures during their life cycle will provide valuable information about viability of the usage of such material. The use of these sensors by surface bonding or embedding in this composite will measure internal strain and temperature, and hence the integrity of the assembled engineering structures. This paper focuses on such a structure, called a composite wound pressure vessel. This vessel was fabricated from the composite material: TRH50 (a Mitsubishi carbon fiber with a 710-ksi tensile strength and a 37 Msi modulus) impregnated with an epoxy resin from NEWPORT composites (WDE-3D-1). This epoxy resin in water dispersed system without any solvents and it cures in the 240-310 degrees F range. This is a toughened resin system specifically designed for pressure applications. These materials are a natural fit for fiber sensors since the polyimide outer buffer coating of fiber can be integrated into the polymer matrix of the composite material with negligible residual stress. The tank was wound with two helical patterns and 4 hoop wraps. The order of winding is: two hoops, two helical and two hoops. The wall thickness of the composite should be about 80 mil or less. The tank should burst near 3,000 psi or less. We can measure the actual wall thickness by ultrasonic or we can burst the tank and measure the pieces. Figure 1 shows a cylinder fabricated out of carbon-epoxy composite material. The strain in different directions is measured with a surface bonded fiber Bragg gratings and with embedded fiber Bragg gratings as the cylinder is pressurized to burst pressures. Figure 2 shows the strain as a function of pressure of carbon-epoxy cylinder as it is pressurized with water. Strain is measured in different directions by multiple gratings oriented in both axial and hoops directions.

Presence of brown adipose tissue in an adolescent with severe primary hypothyroidism.

PubMed

Kim, Mimi S; Hu, Houchun H; Aggabao, Patricia C; Geffner, Mitchell E; Gilsanz, Vicente

2014-09-01

Brown adipose tissue (BAT) generates heat during adaptive thermogenesis in response to cold temperature. Thyroid hormone (TH) receptors, type 2 deiodinase, and TSH receptors are present on brown adipocytes, indicating that the thyroid axis regulates BAT. It is unknown whether absent TH in humans would down-regulate development of BAT and its thermogenic function. The objective of the study was to examine BAT by magnetic resonance imaging (MRI) and infrared thermal imaging (IRT) in a pediatric patient with severe primary hypothyroidism before and after TH treatment. This study was a case report with longitudinal follow-up in a tertiary center. BAT fat fraction (FF) by MRI and skin temperature by IRT were measured. An 11.5-year-old female was severely hypothyroid (TSH, 989 μIU/mL; free T4, 0.10 ng/dL; low thyroglobulin, 3.0 ng/mL). Low MRI measures of FF (56.1% ± 3.7%) indicated that BAT was abundantly present in the supraclavicular fossa. IRT showed higher supraclavicular temperature (36.0°C ±0.16°C) than the suprasternal area (34.3°C ± 0.19°C). After 2 months of TH replacement, she was euthyroid (TSH, 4.3 μIU/mL; free T4, 1.49 ng/dL; T3, 102 ng/dL) at which time supraclavicular BAT decreased (increased FF 60.7% ± 3.8%). IRT showed a higher, more homogeneous skin temperature throughout the upper thorax (supraclavicular, 37.1°C ± 0.23°C; suprasternal, 36.4°C ± 0.13°C). The overall size of the supraclavicular fat depot decreased from 84.79 cm(3) to 41.21 cm(3). These findings document the presence of BAT and thermogenesis in profound hypothyroidism and suggest a role for TSH and/or TRH as a potential regulator of BAT.

Varying Success of Relaying To Reduce Vibrio parahaemolyticus Levels in Oysters ( Crassostrea virginica).

PubMed

Taylor, Michael A; Yu, Jong W; Howell, Thomas L; Jones, Stephen H

2018-04-01

Vibrio parahaemolyticus is the leading cause of seafood-borne human infections in the United States, and many of these illnesses are associated with consumption of raw molluscan shellfish. V. parahaemolyticus levels in shellfish vary temporally and spatially with environmental conditions in and around production areas. The objective of this study was to study the potential for reducing levels of V. parahaemolyticus in live oysters by relaying them during higher-risk warm weather to a site with elevated salinity and consistently low V. parahaemolyticus levels. The effectiveness of relaying was assessed by analyzing oyster samples collected on days 0, 2, 7, 10, and 14 for V. parahaemolyticus levels using a three-tube most-probable-number enrichment method in conjunction with genetic marker-based quantitative PCR. The salinity at the relay site was always higher than the salinity at the harvest site, with the difference between the two sites ranging from 3.4 to 19.1 ppt (average, 12 ppt) during 2011 to 2014. Oysters relayed during June, July, and August in 2011 and 2012 showed consistently reduced V. parahaemolyticus levels after 14 days, whereas relaying was less successful and V. parahaemolyticus populations changed to include trh-positive strains during 2013. When effective, relay required at least 10 days to reduce V. parahaemolyticus levels. A sample of oysters collected in August 2012, which was temperature abused to increase initial V. parahaemolyticus levels, showed a 4.5-log decrease in V. parahaemolyticus levels after 14 days of relay. These results suggest that relaying oysters to reduce V. parahaemolyticus levels holds promise, but that both microbial community and environmental conditions at relay sites can affect relay success. Further investigation to discover key factors that affect V. parahaemolyticus levels in relayed oysters may aid in developing a consistent approach for reducing V. parahaemolyticus in oysters to eliminate the risk of illness for oyster consumers.

Detection and quantification of Vibrio parahaemolyticus in shellfish from Italian production areas.

PubMed

Suffredini, Elisabetta; Mioni, Renzo; Mazzette, Rina; Bordin, Paola; Serratore, Patrizia; Fois, Federica; Piano, Annamaria; Cozzi, Loredana; Croci, Luciana

2014-08-01

Vibrio parahaemolyticus is a marine microorganism, recognized as an important cause of foodborne illness particularly in Asia, South America and United States. Outbreaks are rarely reported in Europe, but they can occur unexpectedly in relation, among other reasons, to the spread of highly virulent strains. It is known that the risk is proportional to exposure levels to pathogenic V. parahaemolyticus (i.e. carrying the tdh and/or the trh genes) but currently there is a lack of occurrence data for pathogenic V. parahaemolyticus in shellfish production areas of the Member States. In this study a total of 147 samples of bivalve molluscs, from harvesting areas of two Italian regions (Sardinia and Veneto) were analyzed for Escherichia coli and salmonella, according to Reg 2073/2005, and for detection and enumeration of total and toxigenic V. parahaemolyticus strains using a new DNA colony hybridization method. Environmental parameters (water temperature and salinity) were also recorded. Results of E. coli were consistently in agreement with the legislation limits for the harvesting class of origin and Salmonella was detected only in one sample. The average contamination levels for total V. parahaemolyticus were 84 and 73 CFU/g respectively for Sardinia and Veneto, with the highest value reaching 8.7 × 10(3)CFU/g. Nineteen samples (12.9%) resulted positive for the presence of potentially pathogenic V. parahaemolyticus strains, with levels ranging between 10 and 120 CFU/g and most of the positive samples (n=17) showing values equal or below 20 CFU/g. A significant correlation (r=0.41) was found between water temperature and V. parahaemolyticus levels, as well as with isolation frequency. The data provided in this study on contamination levels of total and potentially pathogenic V. parahaemolyticus, seasonal distribution and correlation with water temperature, will help in defining appropriate monitoring programs and post-harvest policies for this hazard, improving the management of the harvesting areas and the safety of bivalve molluscs. Copyright © 2014 Elsevier B.V. All rights reserved.

Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Šošić-Jurjević, Branka, E-mail: brankasj@ibiss.bg.ac.rs; Filipović, Branko; Wirth, Eva Katrin

We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10 mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh β, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T{sub 3}-activatedmore » genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T{sub 4} bound to Tg, determined thyroid T{sub 4} levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p < 0.05) correlated with immunohistochemical staining results, and together with decreased serum total T{sub 4} levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p < 0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p < 0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats. - Highlights: • We tested how genistein and daidzein interfere with thyroid hormone homeostasis. • Thyroid: decreased expression of Tg and TPO genes correlated with IHC results. • Serum: total T{sub 4} reduced and TSH increased. • Liver and kidney: expression of Spot 14 and liver Dio 1 activity increased. • Pituitary: expression of T{sub 3}-regulated genes and Dio 1 and 2 activities unchanged.« less

The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.

Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that ismore » neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor {alpha} and {beta}, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk assessments for AA.« less

A pandemic Vibrio parahaemolyticus O3:K6 clone causing most associated diarrhea cases in the Pacific Northwest coast of Mexico

PubMed Central

de Jesús Hernández-Díaz, Lucio; Leon-Sicairos, Nidia; Velazquez-Roman, Jorge; Flores-Villaseñor, Héctor; Guadron-Llanos, Alma M.; Martinez-Garcia, J. Javier; Vidal, Jorge E.; Canizalez-Roman, Adrián

2015-01-01

Between September and October of 2004, more than 1230 cases of gastroenteritis due to pandemic O3:K6 strains of Vibrio parahaemolyticus (V. parahaemolyticus) were reported in the relatively small geographical area of Southern Sinaloa, a state located in Northwest Mexico. Since then, V. parahaemolyticus-associated gastroenteritis cases have gradually increased in prevalence spreading from south to north. The present study conducted an epidemiological surveillance of V. parahaemolyticus strains in both environmental and clinical samples along the Pacific coast of Sinaloa from 2011 to 2013. The genetic relatedness, serotype dominance and antibiotic resistance of isolates were investigated. A total of 46 strains were isolated from environmental samples (e.g., sediment, seawater and shrimp), whereas 249 strains were obtained from stools of patients with gastroenteritis. Nine different O serogroups and 16 serovars were identified. Serovars O3:K6 and O6:K46 were identified in both environmental and clinical strains. Whereas most environmental isolates carried the tdh gene (71.74%, 33/46), only three (6.52%) belonged to pandemic clones (O3:K6, O3:KUT and OUT:KUT). In contrast, 81.1% (202/249) of clinical isolates belonged to pandemic serotypes, with O3:K6 (tdh, toxRS/new, and/or orf8) representing the predominant serovar (97%, 196/202). This prevalence of pathogenic (tdh and/or trh positive) and O3:K6 pandemic V. parahaemolyticus isolates in this study were similar to those found from 2004 to 2010. As investigated by REP-PCR, genetic lineages of selected O3:K6 strains isolated in this study and some isolated earlier were nearly identical. Antimicrobial susceptibility testing showed that most strains (93.8%) were resistant to ampicillin but sensitive to chloramphenicol (98.8%). Multidrug resistance significantly increased from 8.6% (2004–2010) to 22.93% (2011–2013; p < 0.05). Our data indicate that pandemic O3:K6 clone has endemically established in the Pacific Coast of Mexico. PMID:25852677

Prevalence, characterization, and antibiotic susceptibility of Vibrio parahaemolyticus isolated from retail aquatic products in North China.

PubMed

Xu, Xiaoke; Cheng, Jianheng; Wu, Qingping; Zhang, Jumei; Xie, Tengfei

2016-03-09

Vibrio parahaemolyticus is a major foodborne pathogen, particularly in Asian countries. Increased occurrence of outbreaks of V. parahaemolyticus gastroenteritis in China indicates the need to evaluation of the prevalence of this pathogenic species. V. parahaemolyticus distribution in shellfish from the eastern coast of China has been reported previously. However, to date, the prevalence of V. parahaemolyticus in retail aquatic products in North China has not been determined. To investigate the prevalence of V. parahaemolyticus in aquatic products in North China, 260 aquatic product samples were obtained from retail markets in 6 provinces of North China from November to December in 2012 and July to August in 2013. V. parahaemolyticus was detected in 94 (36.2%) of the samples by the most probable number method. The density of V. parahaemolyticus ranged from 1.50 to 1100 MPN/g. V. parahaemolyticus was detected at a rate of 50.0% and 22.7% in summer and in winter, respectively. The density of V. parahaemolyticus was significantly higher in summer than in winter, with mean levels of 16.5 MPN/g and 5.0 MPN/g, respectively. Among 145 V. parahaemolyticus isolates examined, none of the isolates possessed tdh and trh. In multiplex PCR-based O-antigen serotyping of these 145 isolates, all serotypes, other than O6, O7, and O9, were detected, and serotype O2 was found to be the most prevalent (detected in 54 isolates). The 145 isolates were grouped into 7 clusters by enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) at a similarity coefficient of 0.66. The antimicrobial resistance patterns of these 145 isolates to 12 antimicrobial agents revealed that most of the isolates were resistant to streptomycin (86.2%), while fewer were resistant to ampicillin (49.6%), cefazolin (43.5%), cephalothin (35.9%), and kanamycin (22.1%). All of the examined isolates were susceptible to azithromycin and chloramphenicol. The findings of this study will help in defining appropriate monitoring programs, understanding of the dissemination of antibiotic resistant strains, and providing information for the assessment of exposure to this microorganism at the consumption level.

Precipitation and Latent Heating Distributions from Satellite Passive Microwave Radiometry. Part 2; Evaluation of Estimates Using Independent Data

NASA Technical Reports Server (NTRS)

Yang, Song; Olson, William S.; Wang, Jian-Jian; Bell, Thomas L.; Smith, Eric A.; Kummerow, Christian D.

2004-01-01

Rainfall rate estimates from space-borne k&ents are generally accepted as reliable by a majority of the atmospheric science commu&y. One-of the Tropical Rainfall Measuring Mission (TRh4M) facility rain rate algorithms is based upon passive microwave observations fiom the TRMM Microwave Imager (TMI). Part I of this study describes improvements in the TMI algorithm that are required to introduce cloud latent heating and drying as additional algorithm products. Here, estimates of surface rain rate, convective proportion, and latent heating are evaluated using independent ground-based estimates and satellite products. Instantaneous, OP5resolution estimates of surface rain rate over ocean fiom the improved TMI algorithm are well correlated with independent radar estimates (r approx. 0.88 over the Tropics), but bias reduction is the most significant improvement over forerunning algorithms. The bias reduction is attributed to the greater breadth of cloud-resolving model simulations that support the improved algorithm, and the more consistent and specific convective/stratiform rain separation method utilized. The bias of monthly, 2.5 deg. -resolution estimates is similarly reduced, with comparable correlations to radar estimates. Although the amount of independent latent heating data are limited, TMI estimated latent heating profiles compare favorably with instantaneous estimates based upon dual-Doppler radar observations, and time series of surface rain rate and heating profiles are generally consistent with those derived from rawinsonde analyses. Still, some biases in profile shape are evident, and these may be resolved with: (a) additional contextual information brought to the estimation problem, and/or; (b) physically-consistent and representative databases supporting the algorithm. A model of the random error in instantaneous, 0.5 deg-resolution rain rate estimates appears to be consistent with the levels of error determined from TMI comparisons to collocated radar. Error model modifications for non-raining situations will be required, however. Sampling error appears to represent only a fraction of the total error in monthly, 2S0-resolution TMI estimates; the remaining error is attributed to physical inconsistency or non-representativeness of cloud-resolving model simulated profiles supporting the algorithm.

The effect of dermal benzophenone-2 administration on immune system activity, hypothalamic-pituitary-thyroid axis activity and hematological parameters in male Wistar rats.

PubMed

Broniowska, Żaneta; Ślusarczyk, Joanna; Starek-Świechowicz, Beata; Trojan, Ewa; Pomierny, Bartosz; Krzyżanowska, Weronika; Basta-Kaim, Agnieszka; Budziszewska, Bogusława

2018-04-13

Benzophenones used as UV filters, in addition to the effects on the skin, can be absorbed into the blood and affect the function of certain organs. So far, their effects on the sex hormone receptors and gonadal function have been studied, but not much is known about their potential action on other systems. The aim of the present study was to determine the effect of benzophenone-2 (BP-2) on immune system activity, hypothalamic-pituitary-thyroid (HPT) axis activity and hematological parameters. BP-2 was administered dermally, twice daily at a dose of 100 mg/kg for 4-weeks to male Wistar rats. Immunological and hematological parameters and HPT axis activity were assayed 24 h after the last administration. It was found that BP-2 did not change relative weights of the thymus and spleen and did not exert toxic effect on tymocytes and splenocytes. However, this compound increased proliferative activity of splenocytes, enhanced metabolic activity of splenocytes and thymocytes and nitric oxide production of these cells. In animals exposed to BP-2, the HPT axis activity was increased, as evidenced by reduction in the thyroid stimulating hormone (TRH) level and increase in free fraction of triiodothyronine (fT3) and thyroxin (fT4) in blood. BP-2 had no effect on leukocyte, erythrocyte and platelet counts or on morphology and hemoglobin content in erythrocytes. The conducted research showed that dermal, sub-chronic BP-2 administration evoked hyperthyroidism, increased activity or function of the immune cells but did not affect hematological parameters. We suggest that topical administration of BP-2 leading to a prolonged elevated BP-2 level in blood causes hyperthyroidism, which in turn may be responsible for the increased immune cell activity or function. However, only future research can explain the mechanism and functional importance of the changes in thyroid hormones and immunological parameters observed after exposure to BP-2. Copyright © 2018 Elsevier B.V. All rights reserved.

The crystal structure of ianthinite, [U 24+(UO 2) 4O 6(OH) 4(H 2O) 4](H 2O) 5: a possible phase for Pu 4+ incorporation during the oxidation of spent nuclear fuel

NASA Astrophysics Data System (ADS)

Burns, Peter C.; Finch, Robert J.; Hawthorne, Frank C.; Miller, Mark L.; Ewing, Rodney C.

1997-10-01

Ianthinite, [U 24+(UO 2) 4O 6(OH) 4(H 2O) 4](H 2O) 5, is the only known uranyl oxide hydrate mineral that contains U 4+, and it has been proposed that ianthinite may be an important Pu 4+-bearing phase during the oxidative dissolution of spent nuclear fuel. The crystal structure of ianthinite, orthorhombic, a = 0.7178(2), b = 1.1473(2), c = 3.039(1) nm, V = 2.5027 nm 3Z = 4, space group P2 1cn, has been solved by direct methods and refined by least-squares methods to an R index of 9.7% and a wR index of 12.6% using 888 unique observed [| F| ≥ 5 σ | F|] reflections. The structure contains both U 4+. The U 6+ cations are present as roughly linear (U 6+O 2) 2+ uranyl ion (Ur) that are in turn coordinated by five O 2- and OH - located at the equatorial positions of pentagonal bipyramids. The U 4+ cations are coordinated by O 2-, OH - and H 2O in a distorted octahedral arrangement. The Ur φ5and U 4+| 6 (φ: O 2-, OH -, H 2O) polyhedra l sharing edges to for two symmetrically distinct sheets at z ≈ 0.0 and z ≈ 0.25 that are parallel to (001). The sheets have the β-U 3O 8 sheet anion-topology. There are five symmetrically distinct H 2O groips located at z ≈ 0.125 between the sheets of U φn polyhedra, and the sheets of U φn polyhedra are linked together only by hydrogen bonding to the intersheet H 2O groups. The crystal-chemical requirements of U 4+ and Pu 4+ are very similar, suggesting that extensive Pu 4+ ↔ U 4+ substitution may occur within the sheets of U φn polyhedra in trh structure of ianthinine.

Implementing wireless sensor networks for architectural heritage conservation

NASA Astrophysics Data System (ADS)

Martínez-Garrido, M. I.; Aparicio, S.; Fort, R.; Izquierdo, M. A. G.; Anaya, J. J.

2012-04-01

Preventive conservation in architectural heritage is one of the most important aims for the development and implementation of new techniques to assess decay, lending to reduce damage before it has occurred and reducing costs in the long term. For that purpose, it is necessary to know all aspects influencing in decay evolution depending on the material under study and its internal and external conditions. Wireless sensor networks are an emerging technology and a minimally invasive technique. The use of these networks facilitates data acquisition and monitoring of a large number of variables that could provoke material damages, such as presence of harmful compounds like salts, dampness, etc. The current project presents different wireless sensors networks (WSN) and sensors used to fulfill the requirements for a complete analysis of main decay agents in a Renaissance church of the 16th century in Madrid (Spain). Current typologies and wireless technologies are studied establishing the most suitable system and the convenience of each one. Firstly, it is very important to consider that microclimate is in close correlation with material deterioration. Therefore a temperature(T) and relative humidity (RH)/moisture network has been developed, using ZigBee wireless communications protocols, and monitoring different points along the church surface. These points are recording RH/T differences depending on the height and the sensor location (inside the material or on the surface). On the other hand, T/RH button sensors have been used, minimizing aesthetical interferences, and concluding which is the most advisable way for monitoring these specific parameters. Due to the fact that microclimate is a complex phenomenon, it is necessary to examine spatial distribution and time evolution at the same time. This work shows both studies since the development expects a long term monitoring. A different wireless network has been deployed to study the effects of pollution caused by other active systems such as a forced-air heating system, the parishioners presence or feasts and other ventilation conditions. Finally weather conditions are registered through a weather station. Outside and inside conditions are compared to incorporate data to the network for a later decay modeling.

Prospects for Biocontrol of Vibrio parahaemolyticus Contamination in Blue Mussels (Mytilus edulus)—A Year-Long Study

PubMed Central

Onarinde, Bukola A.; Dixon, Ronald A.

2018-01-01

Vibrio parahaemolyticus is an environmental organism normally found in subtropical estuarine environments which can cause seafood-related human infections. Clinical disease is associated with diagnostic presence of tdh and/or trh virulence genes and identification of these genes in our preliminary isolates from retail shellfish prompted a year-long surveillance of isolates from a temperate estuary in the north of England. The microbial and environmental analysis of 117 samples of mussels, seawater or sediment showed the presence of V. parahaemolyticus from mussels (100%) at all time-points throughout the year including the colder months although they were only recovered from 94.9% of seawater and 92.3% of sediment samples. Throughout the surveillance, 96 isolates were subjected to specific PCR for virulence genes and none tested positive for either. The common understanding that consuming poorly cooked mussels only represents a risk of infection during summer vacations therefore is challenged. Further investigations with V. parahaemolyticus using RAPD-PCR cluster analysis showed a genetically diverse population. There was no distinct clustering for “environmental” or “clinical” reference strains although a wide variability and heterogeneity agreed with other reports. Continued surveillance of isolates to allay public health risks are justified since geographical distribution and composition of V. parahaemolyticus varies with Future Ocean warming and the potential of environmental strains to acquire virulence genes from pathogenic isolates. The prospects for intervention by phage-mediated biocontrol to reduce or eradicate V. parahaemolyticus in mussels was also investigated. Bacteriophages isolated from enriched samples collected from the river Humber were assessed for their ability to inhibit the growth of V. parahaemolyticus strains in-vitro and in-vivo (with live mussels). V. parahaemolyticus were significantly reduced in-vitro, by an average of 1 log−2 log units and in-vivo, significant reduction of the organisms in mussels occurred in three replicate experimental tank set ups with a “phage cocktail” containing 12 different phages. Our perspective biocontrol study suggests that a cocktail of specific phages targeted against strains of V. parahaemolyticus provides good evidence in an experimental setting of the valuable potential of phage as a decontamination agent in natural or industrial mussel processing (343w). PMID:29922246

Hypothyroidism Induces Hypophagia Associated with Alterations in Protein Expression of Neuropeptide Y and Proopiomelanocortin in the Arcuate Nucleus, Independently of Hypothalamic Nuclei-Specific Changes in Leptin Signaling.

PubMed

Calvino, Camila; Império, Güínever Eustáquio; Wilieman, Marianna; Costa-E-Sousa, Ricardo Henrique; Souza, Luana Lopes; Trevenzoli, Isis Hara; Pazos-Moura, Carmen Cabanelas

2016-01-01

Thyroid hormone and leptin are essential regulators of energy homeostasis. Both hormones stimulate energy expenditure but have opposite effects on appetite. The mechanisms behind food intake regulation in thyroid dysfunctions are poorly understood. It has been shown that hypothyroid rats exhibited impaired leptin anorexigenic effect and signaling in total hypothalamus, even though they were hypophagic. It was hypothesized that hypothyroidism modulates the expression of neuropeptides: orexigenic neuropeptide Y (NPY) and anorexigenic proopiomelanocortin (POMC), independently of inducing nuclei-specific changes in hypothalamic leptin signaling. Adult male rats were rendered hypothyroid by administration of 0.03% methimazole in the drinking water for 21 days. Protein content of NPY, POMC, and leptin signaling (the signal transducer and activator of transcription 3 [STAT3] pathway) were evaluated by Western blot, and mRNA levels by real time reverse transcription polymerase chain reaction in arcuate (ARC), ventromedial (VMN), and paraventricular (PVN) hypothalamic nuclei isolated from euthyroid (eu) and hypothyroid (hypo) rats. Leptin anorexigenic effect was tested by recording food intake for two hours after intracerebroventricular (i.c.v.) administration of leptin. Statistical differences were considered significant at p ≤ 0.05. Hypothyroidism was confirmed by decreased serum triiodothyronine, thyroxine, and increased thyrotropin, in addition to increased levels of pro-TRH mRNA in PVN and Dio2 mRNA in the ARC of hypo rats. Hypothyroidism decreased body weight and food intake associated with decreased protein content of NPY and increased content of POMC in the ARC. Conversely, hypothyroidism induced central resistance to the acute anorexigenic effect of leptin, since while euthyroid rats displayed reduced food intake after leptin i.c.v. injection, hypothyroid rats showed no response. Hypothyroid rats exhibited decreased leptin receptor (ObRb) protein content in ARC and VMN but not in PVN nucleus. ObRb protein changes were concomitant with decreased phosphorylated STAT3 in the ARC, and decreased total STAT3 in VMN and PVN. However, hypothyroidism did not affect mRNA levels of Lepr or Stat3 in the hypothalamic nuclei. Experimental hypothyroidism induced a negative energy balance accompanied by decreased NPY and increased POMC protein content in the ARC, resulting in predominance of anorexigenic pathways, despite central leptin resistance and impairment of the leptin signaling cascade in a nuclei-specific manner.

Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas.

PubMed

Selvais, P; Donckier, J; Buysschaert, M; Maiter, D

1998-02-01

Cushing's disease appears as a functionally heterogeneous disease, but criteria that are able to distinguish between different clinical forms remain elusive. We compared two subgroups of patients with proven Cushing's disease according to the size of the pituitary adenoma, evaluated by computed tomography or magnetic resonance imaging. Our series comprised 11 patients with a microadenoma and 10 with a macroadenoma (median volumes (range): 173 (13-270) and 3022 (500-10312) mm3 respectively; P < 0.0001). The clinical presentation was similar in the two groups, but the time elapsed before diagnosis was longer, and visual impairment was less frequent in the patients with a microadenoma (1.5+/-0.8 years and 0%) than in those with a macroadenoma (0.7+/-0.6 years and 40%; P < 0.05). Morning and evening peripheral concentrations of ACTH were greater in patients with macroadenoma (134+/-78 and 130+/-7 ng/l respectively) than in those with microadenoma (52+/-28 and 56+/-19 ng/l, P < 0.05). Hypokalaemia and lymphopenia were also more pronounced in patients with macroadenoma (3.4+/-0.3 mmol/l and 1273+/-401 lymphocytes/mm3) than in those with microadenoma (3.8+/-0.3 mmol/l and 1852+/-668 lymphocytes/mm3 P < 0.05), although morning and evening plasma cortisol concentrations were similar in both groups. In patients with macroadenoma, there was less relative nycthemeral variation of ACTH concentrations (28+/-24%, compared with 62+/-39% in those with microadenoma; P < 0.05), less suppression of plasma cortisol by high doses of dexamethasone (-30+/-14%, compared with -61+/-25%; P < 0.05), and a reduced concentration ratio of mean basal cortisol to ACTH (7+/-3, compared with 12+/-5; P < 0.05). Plasma IGF-I concentration and the TSH peak response to TRH were significantly lower in patients with macroadenoma than in those with microadenoma (0.4+/-0.2 x 10(3) IU/I and 2.3+/-1.8 mIU/I, compared with 1.8+/-0.6 x 10(3) IU/I and 5.2+/-1.6 mUI/l; P < 0.05). Thus, in comparison with microadenomas, corticotroph macroadenomas are characterized by a greater and more autonomous ACTH secretion, inducing more pronounced biological signs of hypercorticism, and are more often accompanied by visual field defects and impairment of other pituitary hormonal secretions.

Demographic, psychosocial, and genetic risk associated with smokeless tobacco use among Mexican heritage youth.

PubMed

Wilkinson, Anna V; Koehly, Laura M; Vandewater, Elizabeth A; Yu, Robert K; Fisher-Hoch, Susan P; Prokhorov, Alexander V; Kohl, Harold W; Spitz, Margaret R; Shete, Sanjay

2015-06-26

Despite well-established negative health consequences of smokeless tobacco use (STU), the number and variety of alternative non-combustible tobacco products on the market have increased tremendously over the last 10 years, as has the market share of these products relative to cigarettes. While STU among non-Hispanic white youth has decreased over the last 10 years, the prevalence has remained constant among Hispanic youth. Here we examine demographic, psychosocial, and genetic risk associated with STU among Mexican heritage youth. Participants (50.5 % girls) reported on psychosocial risk factors in 2008-09 (n = 1,087, mean age = 14.3 years), and smokeless tobacco use in 2010-11 (mean age = 16.7 years). Participants provided a saliva sample that was genotyped for genes in the dopamine, serotonin and opioid pathways. Overall 62 (5.7 %) participants reported lifetime STU. We identified five single nucleotide polymorphisms that increased the risk for lifetime use. Specifically, rs2023902 on SERGEF (OR = 1.93; 95 % CI: 1.05-3.53), rs16941667 on ALDH2 (OR = 3.14; 95 % CI: 1.65-5.94), and rs17721739 on TPH1 (OR = 1.71; 95 % CI: 1.00-2.91) in the dopamine pathway, rs514912 on TRH-DE (OR = 1.84; 95 % CI: 1.25-2.71) in the serotonin pathway, and rs42451417 on the serotonin transporter gene, SLC6A4 (OR = 3.53; 95 % CI: 1.56-7.97). After controlling for genetic risk, being male (OR = 1.86; 95 % CI: 1.02-3.41), obesity status (OR = 2.22; 95 % CI: 1.21-4.09), and both higher levels of anxiety (OR = 1.04; 95 % CI: 1.01-1.08) and social disinhibition (OR = 1.26; 95 % CI: 1.07-1.48) were associated with increased use. High subjective social status (OR = 0.78; 95 % CI: 0.64-0.93) was protective against use, while higher parental education (OR = 2.01; 95 % CI: 1.03-3.93) was associated with increased use. These data suggest that use of genetic risk, along with psychosocial, demographic, and behavioral risk factors may increase our ability to identify youth at increased risk for STU, which in turn may improve our ability to effectively target prevention messages to Mexican heritage youth.

Micromechanical Analyses of Sturzstroms

NASA Astrophysics Data System (ADS)

Imre, Bernd; Laue, Jan; Springman, Sarah M.

2010-05-01

Sturzstroms are very fast landslides of very large initial volume. As type features they display extreme run out, pared with intensive fragmentation of the involved blocks of rock within a collisional flow. The inherent danger to the growing communities in alpine valleys below future potential sites of sturzstroms must be examined and results of predictions of endangered zones allow to impact upon the planning processes in these areas. This calls for the ability to make Type A predictions, according to Lambe (1973), which are done before an event. But Type A predictions are only possible if sufficient understanding of the mechanisms involved in a process is available. The motivation of the doctoral thesis research project presented is therefore to reveal the mechanics of sturzstroms in more detail in order to contribute to the development of a Type A run out prediction model. It is obvious that a sturzstrom represents a highly dynamic collisional granular regime. Thus particles do not only collide but will eventually crush each other. Erismann and Abele (2001) describe this process as dynamic disintegration, where kinetic energy is the main driver for fragmenting the rock mass. In this case an approach combining the type features long run out and fragmentation within a single hypothesis is represented by the dynamic fragmentation-spreading model (Davies and McSaveney, 2009; McSaveney and Davies, 2009). Unfortunately, sturzstroms, and fragmentation within sturzstroms, can not be observed directly in a real event because of their long "reoccurrence time" and the obvious difficulties in placing measuring devices within such a rock flow. Therefore, rigorous modelling is required in particular of the transition from static to dynamic behaviour to achieve better knowledge of the mechanics of sturzstroms, and to provide empirical evidence to confirm the dynamic fragmentation-spreading model. Within this study fragmentation and their effects on the mobility of sturzstroms have been made observable and reproducible within a physical and a distinct element numerical modelling environment (DEM). As link between field evidence gained from the deposits of natural sturzstroms, the physical model within the ETH Geotechnical Drum Centrifuge (Springman et al., 2001) and the numerical model PFC-3D (Cundall and Strack, 1979; Itasca, 2005), serves a deterministic fractal analytical comminution model (Sammis et al., 1987; Steacy and Sammis, 1991). This approach allowed studying the effects of dynamic fragmentation within sturzstroms at true (macro) scale within the distinct element model, by allowing for a micro-mechanical, distinct particle based, and cyclic description of fragmentation at the same time, without losing significant computational efficiency. Theses experiments indicate rock mass and boundary conditions, which allow an alternating fragmenting and dilating dispersive regime to evolve and to be sustained long enough to replicate the spreading and run out of sturzstroms. The fragmenting spreading model supported here is able to explain the run out of a dry granular flow, beyond the travel distance predicted by a Coulomb frictional sliding model, without resorting to explanations by mechanics that can only be valid for certain, specific of the boundary conditions. The implications derived suggest that a sturzstrom, because of its strong relation to internal fractal fragmentation and other inertial effects, constitutes a landslide category of its own. Its mechanics differ significantly from all other gravity driven mass flows. This proposition does not exclude the possible appearance of frictionites, Toma hills or suspension flows etc., but it considers them as secondary features. The application of a fractal comminution model to describe natural and experimental sturzstrom deposits turned out to be a useful tool for sturzstrom research. Implemented within the DEM, it allows simulating the key features of sturzstrom successfully and consistent, based on standardised rock and rock mass properties. It also allows revealing the micro mechanical and energetically aspects of a sturzstrom, which suggests that the DEM, modified and developed in the frame of the research project is a promising tool for further research on sturzstroms. This study provides therefore good empirical evidences both to confirm the dynamic fragmentation-spreading model, and to provide a basis on which a successful Type A run out prediction model of sturzstrom may be developed. Cundall, P.A. and Strack, O.D.L., 1979. A discrete numerical model for granular assemblies. Géotechnique, 29(1): 47-65. Davies, T.R.H. and McSaveney, M.J., 2009. The role of rock fragmentation in the motion of large landslides. Engineering Geology, 109(1-2): 67-79. Erismann, T.H. and Abele, G., 2001. Dynamics of rockslides and rockfalls. Springer, Berlin, Heidelberg, Germany, 316 pp. Itasca, 2005. Particle Flow Code in 3 Dimensions. Itasca Consulting Group, Inc., Minneapolis, Minnesota. Lambe, T.W., 1973. The 13th Rankine Lecture, 1973: Predictions in soil engineering. Géotechnique, 23(2): 149-202. McSaveney, M.J. and Davies, T.R.H., 2009. Surface energy is not one of the energy losses in rock comminution. Engineering Geology, 109(1-2): 109-113. Sammis, C., King, G. and Biegel, R., 1987. The kinematics of gouge deformation. Pure and Applied Geophysics, 125(5): 777-812. Springman, S., Laue, J., Boyle, R., White, J. and Zweidler, A., 2001. The ETH Zurich Geotechnical Drum Centrifuge. International Journal of Physical Modelling in Geotechnics, 1(1): 59-70. Steacy, S.J. and Sammis, C.G., 1991. An automaton for fractal patterns of fragmentation. Nature, 353(6341): 250-252.

[Active etiological surveillance for foodborne diseases in Guangdong province, 2013-2014].

PubMed

Ke, B X; He, D M; Tan, H L; Zeng, H H; Yang, T; Li, B S; Liang, Y H; Lu, L L; Liang, J H; Huang, Q; Ke, C W

2016-10-10

Objective: To study the infection status, serotypes, drug resistance and molecular characteristics of Salmonella, Shigella, Vibrio parahemolyticus , enterotoxigenic Escherichia ( E. ) coli (ETEC), pathogenic E. coli (EPEC), Shiga Toxin producing E. coli (STEC) and Enteroinvasive E. coli (EIEC) collected from diarrhea patients in Guangdong. Methods: The strains of Salmonella, Shigella, V. parahemolyticus and 4 kinds of E. coli isolated from foodborne diseases surveillance during 2013-2014 were collected to conduct serotyping, drug resistance test and pulsed-field gel electrophoresis (PFGE). Results: A total of 3 372 stains of pathogens were isolated from 57 834 stool samples during 2013-2014, the overall positive rate was 5.83 % and the positive rate of Salmonella was highest, followed by that of V. parahemolyticus , 4 kinds of E. coli and Shigella . And 3 213 strains of Salmonella were divided into 143 serotypes. The most prevalent serotypes were Salmonella typhimurium , 4, 5, 12: i:-, Enteritidis , Stanley and Derby . Salmonella was sensitive to cephalosporin and fluoroquinolones, and showed significant differences in drug resistance rate among different serotypes. In top 10 common serotypes, S. enteritidis and S. derby were most resistant to cephalosporin and ciprofloxacin respectively. PFGE was performed for 2 289 strains of Salmonella , showing distribution diversity and significant fingerprint polymorphisms. The 85 strains of V. parahemolyticus were divided into 10 serotypes, O3∶K6 (61.18 % ) was the most common serotype, followed by O4∶K8. The results showed that the carrying rate of virulence genes tdh (81.18 % ) was high, while the carrying rate of trh was low (7.06 % ), and there were 10 strains carrying no the two kinds of virulence genes. The sensitive rate of V. parahemolyticus to imipenem, nalidixic acid, SMZ-TMP, chloramphenicol and tetracycline were more than 95 % . Thirteen strains of Shigella were detected, including 9 strains of Shigella sonnei , 3 strains of Shigella flexneri and 1 strains of Shigella bogdii . The strains all showed sensitivity to ceftazidime, ciprofloxacin and chloramphenicol (76.92 % ). There were 86 strains of E. coli detected, including 29 strains of ETEC (33.72 % ), 27 strains of EPEC (31.39 % ), 27 strains of STEC (31.39 % ) and 3 strains of EIEC (3.48 % ). Conclusions: In the active etiological surveillance for foodborne diseases in Guangdong during 2013-2014, the detection rate of Salmonella was highest (5.57 % ), followed by that of V. parahemolyticus , 4 kinds of E. coli and Shigella . Salmonella , V. parahemolyticus and Shigella were sensitive to cephalosporin and fluoroquinolones. Clustered cases of Salmonella infection were found in the surveillance, but no outbreaks occurred.

Gigantic landslides versus glacial deposits: on origin of large hummock deposits in Alai Valley, Northern Pamir

NASA Astrophysics Data System (ADS)

Reznichenko, Natalya

2015-04-01

As glaciers are sensitive to local climate, their moraines position and ages are used to infer past climates and glacier dynamics. These chronologies are only valid if all dated moraines are formed as the result of climatically driven advance and subsequent retreat. Hence, any accurate palaeoenvironmental reconstruction requires thorough identification of the landform genesis by complex approach including geomorphological, sedimentological and structural landform investigation. Here are presented the implication of such approach for the reconstruction of the mega-hummocky deposits formation both of glacial and landslide origin in the glaciated Alai Valley of the Northern Pamir with further discussion on these and similar deposits validity for palaeoclimatic reconstructions. The Tibetan Plateau valleys are the largest glaciated regions beyond the ice sheets with high potential to provide the best geological record of glacial chronologies and, however, with higher probabilities of the numerous rock avalanche deposits including those that were initially considered of glacial origin (Hewitt, 1999). The Alai Valley is the largest intermountain depression in the upper reaches of the Amudarja River basin that has captured numerous unidentified extensive hummocky deposits descending from the Zaalai Range of Northern Pamir, covering area in more than 800 km2. Such vast hummocky deposits are usually could be formed either: 1) glacially by rapid glacial retreat due to the climate signal or triggered a-climatically glacial changes, such as glacial surge or landslide impact, or 2) during the landslide emplacement. Combination of sediment tests on agglomerates forming only in rock avalanche material (Reznichenko et al., 2012) and detailed geomorphological and sedimentological descriptions of these deposits allowed reconstructing the glacial deposition in the Koman and Lenin glacial catchments with identification of two gigantic rock avalanches and their relation to this glacial deposits. Here are presented a new data on: parameters, extent and probable source for Lenin rock avalanche, travelled 24 km from the back wall of the Lenin Glacier over the glacial Achiktash hummock deposit covering more than 35 km2; updated data on Koman rock avalanche deposit, such as its extend and source; the first reconstruction of the Achiktash glacial material deposition with proposed landscape evolution during recent Quaternary in respect to the large landslide in the catchment. Hewitt, K., 1999. Quaternary moraines vs. catastrophic rock avalanches in the Karakoram Himalaya, Northern Pakistan. Quaternary Research, v. 51, p. 220-237. Reznichenko, N.V., Davies, T.R.H., Shulmeister, J. and Larsen S.H, 2012. A new technique for identifying rock-avalanche-sourced sediment in moraines and some paleoclimatic implications. Geology, v. 40, p. 319-322.

Selective expression of neuropeptides in the rat mammary gland: somatostatin gene is expressed during lactation.

PubMed

Chen, A; Laskar-Levy, O; Koch, Y

1999-12-01

The existence of numerous neuropeptides in milk, in concentrations that exceed those in maternal plasma, is well established. It is still unclear whether these neuropeptides are produced by the mammary gland or that the gland concentrates them from the general circulation. In this study, we have examined the possibility that the genes of these neuropeptides are expressed in the rat mammary gland. RNA was extracted from the mammary glands of female rats during different stages of reproduction as well as from other tissues such as hypothalami, pancreas, pineal glands, small intestine, and ovaries. Following RT reaction, the resulting cDNA were amplified by radioactive PCR using specific oligonucleotide primers. We have used specific primers for the following neuropeptides: galanin, somatostatin, vasoactive intestinal peptide, TRH, GH-releasing hormone, cholecystokinin, neurotensin, oxytocin, and relaxin. We have also used primers for serotonin N-acetyl-transferase, the enzyme that is involved in melatonin biosynthesis. The ribosomal protein S-16 served as an internal control. Among all the neuropeptides that have been examined, somatostatin was the only one that was found to be expressed in the mammary gland. Somatostatin was expressed in the mammary gland of lactating rats, but not of virgin rats. Expression of the somatostatin gene was confirmed by Southern blot analysis and by sequencing of the PCR products. Immunohistochemical studies demonstrated somatostatin immunoreactivity in the epithelial cells that compose the secretory alveoli and in the secretory material. In addition, we have found that the mammary glands of the lactating rat express the PC-1 proteinase gene that process prosomatostatin to generate somatostatin-14, but do not express furin, the enzyme that is responsible for somatostatin-28 production. This finding substantiates previous studies that demonstrated that only somatostatin-14 is present in milk. The finding that most of the neuropeptides, examined by RT-PCR, are not expressed by the mammary gland suggest that these neuropeptides are actively concentrated by the mammary glands from the general circulation. The GnRH gene has been previously demonstrated to be expressed in the mammary gland, and in this study somatostatin was the only neuropeptide that was found to be produced by the mammary gland. The observation that only a small portion of the neuropeptides that are present in milk are being produced by the lactating mammary gland suggest that these neuropeptides have important functions in the biology of the suckling neonate and probably also in the development and function of the breast.

Comparison of land surface humidity between observations and CMIP5 models

NASA Astrophysics Data System (ADS)

Dunn, Robert J. H.; Willett, Kate M.; Ciavarella, Andrew; Stott, Peter A.

2017-08-01

We compare the latest observational land surface humidity dataset, HadISDH, with the latest generation of climate models extracted from the CMIP5 archive and the ERA-Interim reanalysis over the period 1973 to present. The globally averaged behaviour of HadISDH and ERA-Interim are very similar in both humidity measures and air temperature, on decadal and interannual timescales. The global average relative humidity shows a gradual increase from 1973 to 2000, followed by a steep decline in recent years. The observed specific humidity shows a steady increase in the global average during the early period but in the later period it remains approximately constant. None of the CMIP5 models or experiments capture the observed behaviour of the relative or specific humidity over the entire study period. When using an atmosphere-only model, driven by observed sea surface temperatures and radiative forcing changes, the behaviour of regional average temperature and specific humidity are better captured, but there is little improvement in the relative humidity. Comparing the observed climatologies with those from historical model runs shows that the models are generally cooler everywhere, are drier and less saturated in the tropics and extra-tropics, and have comparable moisture levels but are more saturated in the high latitudes. The spatial pattern of linear trends is relatively similar between the models and HadISDH for temperature and specific humidity, but there are large differences for relative humidity, with less moistening shown in the models over the tropics and very little at high latitudes. The observed drying in mid-latitudes is present at a much lower magnitude in the CMIP5 models. Relationships between temperature and humidity anomalies (T-q and T-rh) show good agreement for specific humidity between models and observations, and between the models themselves, but much poorer for relative humidity. The T-q correlation from the models is more steeply positive than the observations in all regions, and this over-correlation may be due to missing processes in the models. The observed temporal behaviour appears to be a robust climate feature rather than observational error. It has been previously documented and is theoretically consistent with faster warming rates over land compared to oceans. Thus, the poor replication in the models, especially in the atmosphere-only model, leads to questions over future projections of impacts related to changes in surface relative humidity. It also precludes any formal detection and attribution assessment.

Experimentally Determined Standard Thermodynamic Properties of Synthetic MgSO4·4H2O (Starkeyite) and MgSO4·3H2O: A Revised Internally Consistent Thermodynamic Data Set for Magnesium Sulfate Hydrates

PubMed Central

Majzlan, Juraj; Benisek, Artur; Dachs, Edgar; Steiger, Michael; Fortes, A. Dominic; Marler, Bernd

2012-01-01

Abstract The enthalpies of formation of synthetic MgSO4·4H2O (starkeyite) and MgSO4·3H2O were obtained by solution calorimetry at T=298.15 K. The resulting enthalpies of formation from the elements are \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland, xspace}\\usepackage{amsmath, amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$$\\Delta_{ \\rm f}H^0_{298}$$\\end{document} (starkeyite)=−2498.7±1.1 kJ·mol−1 and \\documentclass{aastex}\\usepackage{amsbsy}\\usepackage{amsfonts}\\usepackage{amssymb}\\usepackage{bm}\\usepackage{mathrsfs}\\usepackage{pifont}\\usepackage{stmaryrd}\\usepackage{textcomp}\\usepackage{portland, xspace}\\usepackage{amsmath, amsxtra}\\pagestyle{empty}\\DeclareMathSizes{10}{9}{7}{6}\\begin{document}$$\\Delta_{ \\rm f}H^0_{298}$$\\end{document} (MgSO4·3H2O)=−2210.3±1.3 kJ·mol−1. The standard entropy of starkeyite was derived from low-temperature heat capacity measurements acquired with a physical property measurement system (PPMS) in the temperature range 5 K

Controls on Variations of Surface Energy, Water, and Carbon Budgets within Large-Scale Amazon Basin

NASA Technical Reports Server (NTRS)

Smith, Eric A.; Cooper, Harry J.; Grose, Andrew; Gu, Jiu-Jing; Norman, John; daRocha, Humberto R.; Dias, Pedro Silva

2002-01-01

A key research focus of the LBA Research Program is understanding the space-time variations in interlinked surface energy, water, and carbon budgets, the controls on these variations, and the implications of these controls on the carbon sequestering capacity of the large scale forest-pasture system that dominates the Amaz6nia landscape. Quantification of these variations and controls are investigated by a combination of in situ measurements, remotely sensed measurements from space, and a realistically forced hydrometeorological model coupled to a carbon assimilation model, capable of simulating details within the surface energy and water budgets along with the principle processes of photosynthesis and respiration. Herein we describe the results of an investigation concerning the space-time controls of carbon sources and sinks distributed over the large scale Amazon basin. The results are derived from a carbon-water-energy budget retrieval system for the large scale Amazon basin, which uses a coupled carbon assimilation-hydrometeorological model as an integrating system, forced by both in situ meteorological measurements and remotely sensed radiation and precipitation fluxes obtained from a combination of GOES, SSM/I, TOMS, and TRh4M satellite measurements. Results include validation of (a) retrieved surface radiation and precipitation fluxes based on 30-min averaged surface measurements taken at Ji-Parani in Rondania and Manaus in Amazonas, and (b) modeled sensible, latent, and C02 fluxes based on tower measurements taken at Reserva Jaru, Manaus and Fazenda Nossa Senhora. The space-time controls on carbon sequestration are partitioned into sets of factors classified by: (1) above canopy meteorology, (2) incoming surface radiation, (3) precipitation interception, and (4) indigenous stomatal processes varied over the different land covers of pristine rainforest, partially, and fully logged rainforests, and pasture lands. These are the principle meteorological, thermodynamical, hydrological, and biophysical control paths which perturb net carbon fluxes and sequestration, produce time-space switching of carbon sources and sinks, undergo modulation through atmospheric boundary layer feedbacks, and respond to any discontinuous intervention on the landscape itself such as produced by human intervention in converting rainforest to pasture or conducting selective/clearcut logging operations. The results demonstrate how relative carbon sequestration capacity of the Amazonian ecosystem responds to these controls, and how interpretation of space-time heterogeneities in carbon sequestration depends on a fairly exact quantification of the interacting non-linear properties of photosynthesis in response to incoming solar flux, air-canopy temperatures, and leaf water interception -- and soil respiration in response to upper layer soil temperature and water content. The results also show how the interpretation of the control processes is highly sensitive to the scales at which the surface fluxes are analyzed.

Urban effects on extreme heat in a mid-sized North American city

NASA Astrophysics Data System (ADS)

Schatz, J.; Kucharik, C. J.

2013-12-01

As climate change drives global temperatures higher, heat waves are projected to increase in frequency, intensity, and duration, particularly in cities where the urban heat island effect can further raise local temperatures. Cities contain 50% of the global population and 80% of the North American population, and these percentages are projected to reach 70% globally and 87% in North America by 2030. This creates a need to understand the nature of heat events not just globally but also within cities where local climate variation can be substantial. That local variation could prove highly consequential for heat adaptation in cities, making it important to understand the dynamics of extreme heat within urban landscapes. Our study addresses this need by characterizing 400m-resolution variation in air temperature and heat index during a historically hot year in Madison, Wisconsin. Madison is a mid-sized temperate city with a metropolitan area population of 568,593. It is surrounded by several large lakes and a complex rural landscape of agriculture, forests, wetlands, and grasslands. In 2012, Madison experienced its hottest year and third hottest summer on record, with the Madison airport reporting 39 days exceeding 90°F compared to an average of 9 days. In March 2012, we installed 135 Onset HOBO ProV2 T/RH sensors across the Madison area to record air temperature and relative humidity at 15 minute intervals. The data from this network provides a unique opportunity to study small-scale spatial variation in the magnitude and duration of hot conditions that are projected to become more common in the future. Our sensors recorded substantial variation in the magnitude and duration of high temperatures and heat indices during the summer of 2012. For temperature, the densest parts of the city experienced >200 hours ≥90°F compared to <100 hours in many rural areas. Temperatures ≥100°F occurred up to 22 hours in some parts of the city versus 0 hours in much of the rural surroundings. For heat index, the densest parts of Madison experienced >300 hours ≥90°F compared to <200 hours in most rural areas. Heat indices ≥100°F occurred >70 hours in dense urban areas compared to <50 hours in rural. The magnitude and duration of high temperatures were positively related to percent impervious surface coverage and negatively related to lake proximity, though lake proximity was not always significant. Heat index showed similar patterns with respect to impervious cover, but unlike temperature was negatively related to water body proximity due to the lakes providing a source of high humidity. Further results and analyses will be described and visualized, including a comparison with the relatively cool and wet summer of 2013. As climate change continues to raise heat related risks in cities across the world, these results have important implications for urban adaptation to high heat and its effects on human health, electric power demand, and the environment.

Rock avalanche deposits in Alai Valley, Central Asia: misinterpretation of glacial record

NASA Astrophysics Data System (ADS)

Reznichenko, Natalya; Davies, Tim; Robinson, Tom; De Pascale, Gregory

2013-04-01

The reconstruction of Quaternary glaciations has been restricted by conventional approaches with resulting contradictions in interpretation of the regional glacial record, that recently have been subjected to critical re-evaluation. Along with uncertainties in dating techniques and their applicability to particular landforms (Kirkbride and Winkler, 2012), it has recently been demonstrated that the presence of rock avalanche debris in a landform can be unequivocally detected; this allows for the first time definitive identification of and distinction between glacial moraines and landslide deposits. It also identifies moraines that have formed due to rock avalanche deposition on glaciers, possibly with no associated climatic signal (Reznichenko et al., 2012). Confusion between landslide deposits and moraines is evident for ranges in Central Asia (e.g., Hewitt, 1999) where the least-studied glacial record is selectively correlated with established glacial chronologies in Alpine ranges, which in turn masks the actual glacial extent and their responses to climate change, tectonics and landsliding activity. We describe examples in the glaciated Alai Valley, large intermountain depression between the Zaalay Range of the Northern Pamir and the Alay Range of the Southern Tien-Shan, showing that some large Quaternary deposits classically interpreted as moraines are of rock avalanche origin. Sediment from these deposits has been tested for the presence of agglomerates that are only produced under high stress conditions during rock avalanche motion, and are absent from glacial sediments (Reznichenko et al., 2012). This reveals that morphologically-similar deposits have radically different geneses: rock avalanche origin for a deposit in the Komansu river catchment and glacial origin for deposits in the Ashiktash and Kyzylart catchments. The enormous Komansu rock avalanche deposit, probably triggered by a rupture of the Main Pamir thrust, currently covers about 100 km2 with a minimum estimated volume more than 1 x 109 m3. Another smaller rock avalanche deposit rests on the Lenin Glacial sediment in the neighbour Ashiktash river catchment, which was previously suggested to originate from Mt. Lenin (7134 m). The revised origin of these deposits highlights the role of rock avalanches in glacial activity and in the resulting glacial record in this valley and other actively tectonic areas of Central Asia. Although further investigation is required to detail the geneses, magnitudes and ages for these and other landforms in the valley, this study contributes explicit evidence for contamination of palaeoclimate proxies with data from non-climatic events, and reinforces the urgent need for revised interpretation of the glacial chronologies. Hewitt, K., 1999. Quaternary moraines vs. catastrophic rock avalanches in the Karakoram Himalaya, Northern Pakistan. Quaternary Research, v. 51, p. 220-237. Kirkbride, M.P., and Winkler, S., 2012. Correlation of Late Quaternary moraines: impact of climate variability, glacier response, and chronological resolution: Quaternary Science Reviews, v. 46, p. 1-29. Reznichenko, N.V., Davies, T.R.H., Shulmeister, J. and Larsen S.H, 2012. A new technique for identifying rock-avalanche-sourced sediment in moraines and some paleoclimatic implications. Geology, v. 40, p. 319-322.

Deep-brain photoreceptors (DBPs) involved in the photoperiodic gonadal response in an avian species, Gallus gallus.

PubMed

Kang, Seong W; Kuenzel, Wayne J

2015-01-15

Three primitive photoreceptors [melanopsin (Opn4), neuropsin/opsin5 (Opn5) and vertebrate ancient opsin (VAOpn)] were reported as possible avian deep-brain photoreceptors (DBPs) involved in the perception of photoperiodic information affecting the onset and development of reproduction. The objective of this study was to determine the effect of long-day photostimulation and/or sulfamethazine treatment (SMZ, a compound known to advance light-induced testes development) on gene expression of DBPs and key hypothalamic and pituitary genes involved in avian reproductive function. Two-week old chicks were randomly selected into four experimental groups: short-day control (SC, LD8:16), short-day+SMZ (SS, LD8:16, 0.2% diet SMZ), long-day control (LC, LD16:8), and long-day+SMZ (LS, LD16:8, 0.2% diet SMZ). Birds were sampled on days 3, 7, and 28 after initiation of a long-day photoperiod and/or SMZ dietary treatments. Three brain regions [septal-preoptic, anterior hypothalamic (SepPre/Ant-Hypo) region, mid-hypothalamic (Mid-Hypo) region, posterior-hypothalamic (Post-Hypo) region], and anterior pituitary gland were dissected. Using quantitative real-time RT-PCR, we determined changes of expression levels of genes in distinct brain regions; Opn4 and Opn5 in SepPre/Ant-Hypo and Post-Hypo regions and, VAOpn in the Mid-Hypo region. Long-day treatment resulted in a significantly elevated testes weight on days 7 and 28 compared to controls, and SMZ augmented testes weight in both short- and long-day treatment after day 7 (P<0.05). Long-day photoperiodic treatment on the third day unexpectedly induced a large 8.4-fold increase of VAOpn expression in the Mid-Hypo region, a 15.4-fold increase of Opn4 and a 97.8-fold increase of Opn5 gene expression in the Post-Hypo region compared to SC birds (P<0.01). In contrast, on days 7 and 28, gene expression of the three DBPs was barely detectable. LC group showed a significant increase in GnRH-1 and TRH mRNA in the Mid-Hypo compared to SC on day 3. Pituitary LHβ and FSHβ mRNA were significantly elevated in LC and LS groups compared to SC on days 3 and 7 (P<0.05). On days 3 and 7, TSHβ mRNA level was significantly elevated by long-day treatment compared to the SC groups (P<0.05). Results suggest that long-day photoperiodic activation of DBPs is robust, transient, and temporally related with neuroendocrine genes involved in reproductive function. Additionally, results indicate that two subsets of GnRH-1 neurons exist based upon significantly different gene expression from long-day photostimulation and long-day plus SMZ administration. Taken together, the data indicate that within 3 days of a long-day photoperiod, an eminent activation of all three types of DBPs might be involved in priming the neuroendocrine system to activate reproductive function in birds. Copyright © 2014 Elsevier Inc. All rights reserved.

[Evaluation of selected endocrine complications in patients treated with auto- and allo-haematopoietic stem cell transplantation].

PubMed

Niedzielska, Ewa; Wójcik, Dorota; Barg, Ewa; Pietras, Wojciech; Sega-Pondel, Dorota; Doroszko, Adrian; Niedzielska, Małgorzata; Skarzyńska, Małgorzata; Chybicka, Alicja

2008-01-01

The aim of this study was to evaluate the endocrine complications, in particular disorders of growth and thyroid function and glucose metabolism dysfunctions in patients treated with allo- and auto-haematopoietic stem cell transplantation (HSCT). The investigated group consisted of: I. 16 patients after auto-HSCT (6 girls, 10 boys) aged 3-20 years (average 10,8+/-) because of acute myelogenous leukaemia (n=5), non Hodgkin lymphoma (n=3), neuroblastoma (n=3), embryonal cancer (n=2), medulloblastoma (n=1), Ewing's sarcoma/PNET (n=1), hyper eosinophilic syndrome (n=1). High dose chemiotherapy (HDC/T) included: BU/MEL (busulfan/melfalan) (n=7), BEAM (carmustine, eteposide, cytosine arabinose, melfalan) (n=3). II. 30 patients after allo-HSCT (20 girls, 10 boys) aged 3-17 years (average 9,56). Indication for HSCT was acute lymphoblastic leukaemia (n=11), acute myelogenous leukaemia (n=5), chronic myeloid leukaemia-CML (n=6), myelodysplastic syndromes (n=2), non Hodgkin lymphoma (n=1), juvenile myelomonocytic leukemia (n=1), severe aplastic anaemia (n=1), Blackfan-Diamond anaemia (n=1), severe combined immune deficiency (n=1), rhabdomyosarcoma (n=1). The patients underwent the following types of transplantation: HSCT of matched sibling donor (n=13), HSCT of matched unrelated donor (n=11) and HLA-mismatched related donor (n=6). The preparative regimens consisted of HDC/T usually BU/MEL (n=3); BU/CY/VP (busulfan, cyclophosphamide, etoposide) (6); BU/CY/ATG (anti-thymocyte globulin) (n=5), VP/ATG/TBI (total body irradiation) (n=3). 19 children received CI (cranial irradiation) prior to grafting: auto-HSCT (n=6) and allo-HSCT (n=13) and 6 patients underwent TBI. 18 children received high steroid doses at least 28 days before transplant, 4 patients in the auto-HSCT group, and in the allo-HSCT group 14 patients before and 20 after HSCT procedure. The analysis of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), hemoglobin A1c (HbA1c), prolactine (PRL), oral glucose tolerance test, growth hormone (GH test) and thyrotropin releasing hormone (TRH) test was performed in each case. Hypothyroidism was found in 5 patients (3 after allo-HSCT, 2 after auto-HSCT). Thyroid hormone substitution was applied. No case of hyperthyroidism was diagnosed. Growth deficit was found in 8 patients (6 girls, 2 boys) between 13 to 70 months after allo-transplantation (average 36 months). Three children from the above group received CI. Growth hormone substitution was applied in 1 girl (ALL, HLA MM REL, CI). An impaired excretion of GH after stimulation was diagnosed in 14 pts (10 after allo-HSCT, 4 after auto-HSCT). The growth process should still be observed in this subgroup. Glucose intolerance was found in 7 patients: in 4 treated with auto-HSCT and in 3 after allo-HSCT. Diabetes mellitus was diagnosed in none of them. An impaired glucose tolerance curve with increased excretion of insulin was diagnosed in 12 children. Early endocrinological care is necessary in patients treated both with auto-HSCT and allo-HSCT due to high risk of hormonal disorders.

Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes.

PubMed

Vogel, Adam P; Folker, Joanne; Poole, Matthew L

2014-10-28

Hereditary ataxia syndromes can result in significant speech impairment, a symptom thought to be responsive to treatment. The type of speech impairment most commonly reported in hereditary ataxias is dysarthria. Dysarthria is a collective term referring to a group of movement disorders affecting the muscular control of speech. Dysarthria affects the ability of individuals to communicate and to participate in society. This in turn reduces quality of life. Given the harmful impact of speech disorder on a person's functioning, treatment of speech impairment in these conditions is important and evidence-based interventions are needed. To assess the effects of interventions for speech disorder in adults and children with Friedreich ataxia and other hereditary ataxias. On 14 October 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, PsycINFO, Education Resources Information Center (ERIC), Linguistics and Language Behavior Abstracts (LLBA), Dissertation Abstracts and trials registries. We checked all references in the identified trials to identify any additional published data. We considered for inclusion randomised controlled trials (RCTs) or quasi-RCTs that compared treatments for hereditary ataxias with no treatment, placebo or another treatment or combination of treatments, where investigators measured speech production. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias of included studies using the standard methodological procedures expected by The Cochrane Collaboration. The review authors collected information on adverse effects from included studies. We did not conduct a meta-analysis as no two studies utilised the same assessment procedures within the same treatment. Fourteen clinical trials, involving 721 participants, met the criteria for inclusion in the review. Thirteen studies compared a pharmaceutical treatment with placebo (or a low dose of the intervention), in heterogenous groups of degenerative cerebellar ataxias. Three compounds were studied in two trials each: a levorotatory form of 5-hydroxytryptophan (L-5HT), idebenone and thyrotropin-releasing hormone tartrate (TRH-T); each of the other compounds (riluzole, varenicline, buspirone, betamethasone, coenzyme Q10 with vitamin E, α-tocopheryl quinone and erythropoietin) were studied in one trial. The 14th trial, involving a mixed group of participants with spinocerebellar ataxia, compared the effectiveness of nonspecific physiotherapy and occupational therapy within an inpatient hospital setting to no treatment. No studies utilised traditional speech therapies. We defined the primary outcome measure in this review as the percentage change (improvement) in overall speech production immediately following completion of the intervention or later, measured by any validated speech assessment tool. None of the trials included speech as a primary outcome or examined speech using any validated speech assessment tool. Eleven studies reported speech outcomes derived from a subscale embedded within disease rating scales. The remaining three studies used alternative assessments to measure speech, including mean time to produce a standard sentence, a subjective rating of speech on a 14-point analogue scale, patient-reported assessment of the impact of dysarthria on activities of daily living and acoustic measures of syllable length. One study measured speech both subjectively as part of a disease rating scale and with further measures of speech timing. Three studies utilised the Short Form-36 Health Survey (SF-36) and one used the Child Health Questionnaire as measures of general quality of life. A further study utilised the Functional Independence Measure to assess functional health.Five studies reported statistically significant improvement on an overall disease rating scale in which a speech subscale was included. Only three of those studies provided specific data on speech performance; all were comparisons with placebo. Improvements in overall disease severity were observed with α-tocopheryl quinone; however, no significant changes were found on the speech subscale in a group of individuals with Friedreich ataxia. A statistically significant improvement in speech according to a speech disorders subscale was observed with betamethasone. Riluzole was found to have a statistically significant effect on speech in a group of participants with mixed hereditary, sporadic and unknown origin ataxias. No significant differences were observed between treatment and placebo in any other pharmaceutical study. A statistically significant improvement in functional independence occurred at the end of the treatment period in the rehabilitation study compared to the delayed treatment group but these effects were not present 12 to 24 weeks after treatment. Of the four studies that assessed quality of life, none found a significant effect. A variety of minor adverse events were reported for the 13 pharmaceutical therapies, including gastrointestinal side effects and nausea. Serious adverse effects were reported in two participants in one of the L-5HT trials (participants discontinued due to gastrointestinal effects), and in four participants (three taking idebenone, one taking placebo) in the idebenone studies. Serious adverse events with idebenone were gastrointestinal side effects and, in people with a previous history of these events, chest pain and idiopathic thrombocytopenic purpura. The rehabilitation study did not report any adverse events.We considered six studies to be at high risk of bias in some respect. We suspected inadequate blinding of participants or assessors in four studies and poor randomisation in a further two studies. There was a high risk of reporting bias in two studies and attrition bias in four studies. Only one study had a low risk of bias across all criteria. Taken together with other limitations of the studies relating to the validity of the measurement scales used, we downgraded the quality of the evidence for many of the outcomes to low or very low. There is insufficient and low or very low quality evidence from either RCTs or observational studies to determine the effectiveness of any treatment for speech disorder in any of the hereditary ataxia syndromes.