Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) on plasma concentrations of thyroid hormones, and effects of ACTH and dexamethasone on plasma concentrations of cortisol, were studied in adult male ferrets. Thirteen ferrets were randomly assigned to test or control groups of eight and five animals, respectively. Combined (test + control groups) mean basal plasma thyroxine (T4) values were different between the TRH (1.81 +/- 0.41 micrograms/dl, mean +/- SD) and TSH (2.69 +/- 0.87 micrograms/dl) experiments, which were performed 2 months apart. Plasma T4 values significantly (P less than 0.05) increased as early as 2 hours (3.37 +/- 1.10 micrograms/dl) and remained high until 6 hours (3.45 +/- 0.86 micrograms/dl) after IV injection of 1 IU of TSH/ferret. In contrast, IV injection of 500 micrograms of TRH/ferret did not induce a significant increase until 6 hours (2.75 +/- 0.79) after injection, and induced side effects of hyperventilation, salivation, vomiting, and sedation. There was no significant increase in triiodothyronine (T3) values following TSH or TRH administration. Combined mean basal plasma cortisol values were not significantly different between ACTH stimulation (1.29 +/- 0.84 micrograms/dl) and dexamethasone suppression test (0.74 +/- 0.56 micrograms/dl) experiments. Intravenous injection of 0.5 IU of ACTH/ferret induced a significant increase in plasma cortisol concentrations by 30 minutes (5.26 +/- 1.21 micrograms/dl), which persisted until 60 minutes (5.17 +/- 1.99 micrograms/dl) after injection. Plasma cortisol values significantly decreased as early as 1 hour (0.41 +/- 0.13 micrograms/dl), and had further decreased by 5 hours (0.26 +/- 0.15 micrograms/dl) following IV injection of 0.2 mg of dexamethasone/ferret.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Thyroid and adrenal function tests in adult male ferrets. 215 47

Effects of thyrotropin-releasing hormone (TRH) on serum concentrations of thyroid hormones were studied in 36 mixed-bred dogs. Dogs were randomly assigned to 7 groups. Significant increases (P less than 0.05) of serum thyroxine (T4) values occurred as early as 2 hours and reached a peak at 6 to 8 hours after IV injection of 300 to 1,100 micrograms of TRH. Thyroxine concentrations in response to a TRH dose greater than 500 micrograms were similar to those observed with the 300-micrograms dose. Transient coughing, vomiting, salivation, and defecation after large doses (900 and 1,100 micrograms) were observed. Mean serum T4 concentration decreased from 2.1 micrograms/dl to 0.9 micrograms/dl within 1 day of thyroidectomy. Clinical signs of hypothyroidism, including lethargy, dry coats, and diffuse alopecia, were present in 2 dogs at a month after surgical operation. Thyroxine concentrations were detectable for greater than 2 months. Injection (IV) of 700 micrograms of TRH 6 weeks after surgical operation had no effect on serum concentration of T4 in thyroidectomized dogs. In 5 T4-treated dogs, TRH (700 micrograms, IV) significantly increased the serum T4 value, indicating that pituitary thyrotropes were responsive to TRH, in spite of daily medication of 0.8 mg of T4. Four dogs were treated orally with 200 mg of propylthiouracil/day for 5 weeks. Intravenous injection of 700 micrograms of TRH in propylthiouracil-treated dogs had no effect on the serum T4 concentration, indicating that TRH had no effect on serum T4 values in these dogs during the experimental period. These results indicate that TRH can replace bovine thyrotropin for the canine thyroid function test.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of thyrotropin-releasing hormone on serum concentrations of thyroxine and triiodothyronine in healthy, thyroidectomized, thyroxine-treated, and propylthiouracil-treated dogs. 308 Sep 28

Serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) were studied in 47 women with anorexia nervosa (AN) (group I) and in 11 bulimic patients of normal weight (group II). In group I, TSH responses were low in nine patients, delayed in 32 and normal in six. Patients with a normal TSH response had a lesser degree of anorexia than those with a delayed TSH response. Bulimia and vomiting were more frequently observed in the low response group. The maximum increase in TSH concentrations following TRH administration in the group I patients with vomiting (4.0 +/- 0.90 microU/ml, mean +/- S.E.) was significantly lower than that in the group I patients without vomiting or in normal controls (11.2 +/- 0.82 microU/ml and 11.1 +/- 2.34 microU/ml, respectively). Twenty-five patients with abnormal TSH responses in group I were retested after weight gain. Initially, TSH responses were low in six and delayed in 19. Following weight recovery, responses continued to be abnormal in five of the six and in eight of the 19, respectively. The symptoms of eating disorders continued in all patients with abnormal TSH responses even after weight recovery, whereas patients with normal responses after weight gain recovered from all symptoms. Of 11 patients in group II, six had abnormal TSH responses to TRH; the responses were delayed in four and low in two. Patients with normal responses had a lesser degree of eating disorder, compared with abnormal responders. These observations suggest that abnormal TSH responses in patients with AN were not necessarily due to weight loss alone; rather, they may be related to the eating disorder itself.
 ...
PMID:Serum thyrotropin (TSH) responses to thyrotropin-releasing hormone (TRH) in patients with anorexia nervosa and bulimia: influence of changes in body weight and eating disorders. 310 19

The addition of thyrotropin-releasing hormone (TRH) to antenatal glucocorticoid treatment of women at risk of preterm delivery has been reported to lower the risk of respiratory distress syndrome (RDS) in the infant. We have assessed the efficacy of 200 micrograms TRH in a multicentre randomised trial. 1234 women at 24 weeks to 31 weeks 6 days of gestation with a singleton or twin pregnancy and at risk of preterm delivery were randomly allocated to groups receiving 200 micrograms TRH or placebo intravenously every 12 h up to a maximum of four doses. Randomisation was stratified by duration of gestation and centre. All women received glucocorticoids. Clinical outcome is known for 1231 women and their 1397 infants. The frequencies of the main prespecified study outcomes RDS (relative risk 1.17 [95% CI 1.00-1.36], p = 0.05) and need for ventilation (1.15 [1.01-1.31], p = 0.04) were higher in TRH-group infants than in control infants. The excess risk in the TRH group was greater in infants who were born more than 10 days after treatment. Multivariate analysis adjusting for duration of gestation at randomisation, time from randomisation to delivery, parity, history of perinatal death, and infant's sex did not affect the risk estimates. TRH administration was associated with increased risks of maternal nausea, vomiting, lightheadedness, and a rise in blood pressure to 140/90 mm Hg or higher. Antenatal TRH given with glucocorticoids to women at high risk of preterm delivery is associated with maternal and perinatal risks and cannot be recommended for widespread clinical use.
 ...
PMID:Australian collaborative trial of antenatal thyrotropin-releasing hormone (ACTOBAT) for prevention of neonatal respiratory disease. 779 58

Gastric hypomotility, loss of appetite, nausea, and vomiting frequently accompany critical infectious illness, radiation sickness, and carcinogenesis. The present studies examined the possibility that the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), may be responsible for provoking some of these autonomic signs associated with illness. Gastric motility of urethane-anesthetized rats was prestimulated with intracisternal applications of thyrotropin-releasing hormone (TRH), a peptide known to activate parasympathetic vagal excitatory pathways to the stomach. Microinjection of TNF-alpha (as low as 0.02 fmol) directly into the dorsal vagal comples (DVC) suppressed TRH-stimulated gastric motility for prolonged periods of time. Duration of suppression ranged from 5 min to more than an hour, dependent on both the dose of TNF-alpha and accuracy of placement of the microinjection within the DVC. This suppression demonstrated a dose-dependent effect of TNF-alpha that required an intact vagal pathway. These studies indicate that TNF-alpha may represent a unique cytokine 'afferent' signal which directly regulates the excitability of vago-vagal reflex circuits resulting in altered gastric motility during disease states.
 ...
PMID:Tumor necrosis factor-alpha in the dorsal vagal complex suppresses gastric motility. 852 Nov 42

The acute toxicity studies of taltirelin tetrahydrate (TA-0910), a new thyrotropin-releasing hormone (TRH) analogue, were performed in Slc:ddY mice, Slc:Wistar rats and beagle dogs of both sexes. The drug was administered to mice and rats by oral (p.o.), intravenous (i.v.) and subcutaneous (s.c.) routes, and to dogs by the p.o. and i.v. routes. LD50 values were more than 5,000 mg/kg in mice and rats of both sexes by the p.o. and s.c. routes. Some mice and rats died immediately after i.v. injection, the LD50 values were more than 2,000 mg/kg in mice of both sexes and calculated as 799 and 946 mg/kg in male and female rats, respectively. The minimum lethal doses were more than 2000 mg/kg in dogs of both sexes by the p.o. route. Though all dogs treated intravenously with 1000 mg/kg could survive during the observation period, a female dog with 500 mg/kg died on the day after administration. In general condition, hyperactivity, tremor and straub tail, that reflected central stimulatory effects of TA-0910, were observed in mice and rats, and also wet dog shaking in only rats. Vomiting and hyperactivity were seen in dogs by the p.o. route, and exaltation (during the dosing) and sedation by the i.v. route. In addition, salivation and transient tachycardia were observed in the both routes. In blood chemical examination, the transient changes of glucose, protein, lipid and/or serum enzyme were shown. In autopsy, no notable changes were seen in mice, rats and dogs.
 ...
PMID:[Acute toxicity studies of taltirelin tetrahydrate in mice, rats, and dogs]. 943 92

Taltirelin tetrahydrate (TA-0910), novel thyrotropin-releasing hormone (TRH) analogue, was orally administered to dogs as dose levels 0.5, 5, and 50 mg/kg for 13 weeks and 0.15, 1.5 and 15 mg/kg for 52 weeks. Blood concentrations of test substance measured in 52-week study revealed that absorption of TA-0910 was with dose-dependent manner and not changed through the treatment period. These toxicokinetics suggested that there were no alterations on metabolism of TA-0910 with repeated treatment. The animals receiving 5 or 50 mg/kg showed decrease in body weight or suppression of body weight gain, and decrease in food intake (13-week study). As an abnormality in general conditions, vomiting and salivation (5 mg/kg or more, both in 13- and 52-week studies), increase in behavior as water intake (5 mg/kg or more, 13-week study), and hyperlocomotion (50 mg/kg) were observed. Elevating GPT values were noted temporally in the animals treated with 5 mg/kg or more (both in 13- and 52-week studies) without abnormal findings in histopathology. The thyroid weights were increased in treated animals receiving 5 or 50 mg/kg in 13-week study, but no histopathological changes were noted. Electron microscopy revealed dilatation of granular endoplasmic reticulums in follicular cells of thyroid from 50 mg/kg group in 13-week study. It was concluded that no-effect levels of 13- and 52-week studies were 0.5 mg/kg and 1.5 mg/kg, respectively.
 ...
PMID:[Repeated dose toxicity studies of taltirelin tetrahydrate (TA-0910) with oral administration to dogs]. 943 94

Unfortunately, surfactant therapy is not routinely available to infants in some parts of the world because of its cost. It is the hypothesis of this article that in situations where surfactant is not available, there may be a role for antenatal thyrotropin-releasing hormone (TRH) plus glucocorticoid therapy. Data from randomized clinical trials, which compared therapy with antenatal glucocorticoid plus TRH to that with glucocorticoid alone were extracted and subjected to meta-analysis. The trials that incorporated surfactant therapy were analyzed separately from those in which surfactant was not used. In addition, because surfactant therapy was only available to some patients in the Australian ACTOBAT trial, each group analysis was performed with and without the ACTOBAT data. A characteristic of the earlier presurfactant trials is that few were designed for "intention to treat" analysis. In most of these studies, it was decided a priori to include babies who delivered within a specified time period after hormone therapy. The addition of TRH did not decrease respiratory distress syndrome in those trials in which surfactant therapy was used. In the presurfactant trials, respiratory distress syndrome was significantly decreased when "intention to treat" data were examined, as well as in those infants who delivered between 1 and 10 days after maternal therapy. There was also a significant decrease in oxygen dependency at 28 days after birth, and in oxygen dependency or death at this time, in those infants who delivered 1 to 10 days after treatment. Antenatal TRH had no significant effect of on neonatal complications such as air leak, intraventricular hemmorhage, patent ductus arteriosus, retinopathy of prematurity, or necrotizing enterocolitis. However, TRH did produce transient suppression of the pituitary thyroid axis. There were also a variety of transient complications in the mothers, including nausea, vomiting or flushing, light-headed feeling, and increased blood pressure. The authors conclude that the implementation of appropriate antenatal glucocorticoid treatment is the first priority. Once this has been established, the data presented here suggest that addition of antenatal TRH should be considered in those situations where surfactant is not available.
 ...
PMID:Is there a role for antenatal TRH therapy for the prevention of neonatal lung disease? 1177 11

Our previous studies suggested that the cytokine tumor necrosis factor-alpha (TNF-alpha) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function, such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF-alpha is capable of affecting gastric function via the DVC circuitry has been impeded by the lack of an antagonist for TNF-alpha. The present studies used localized central nervous system applications of the TNF-adsorbant construct (TNFR:Fc; TNF-receptor linked to the Fc portion of the human immunoglobulin IgG1) to attempt to neutralize the suppressive effects of endogenously produced TNF-alpha. Gastric motility of thiobutabarbital-anesthetized rats was monitored after systemic administration of lipopolysaccharide (LPS) to induce TNF-alpha production. Continuous perfusion of the floor of the fourth ventricle with TNFR:Fc reversed the potent gastroinhibition induced by LPS, i.e., central thyrotropin-releasing hormone-induced increases in motility were not inhibited. This disinhibition of gastric stasis was not seen after intravenous administration of similar doses of TNFR:Fc nor ventricular application of the Fc fragment of human immunoglobulin. These results validate our previous studies that suggest that circulating TNF-alpha may act directly within the DVC to affect gastric function in a variety of pathophysiological states.
 ...
PMID:LPS-induced suppression of gastric motility relieved by TNFR:Fc construct in dorsal vagal complex. 1218 Nov 77