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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electrophysiological actions of TRH were examined in the clonal pituitary cell line GH3 with the use of the perforated patch variation of the standard whole cell patch-clamp technique. The action of TRH on spontaneously spiking cells was to cause a brief hyperpolarization (first phase action), followed by a period during which action potential behavior was significantly modified (second phase action). The modifications during second phase action included a reduction in the slope of the up-stroke, a reduced peak potential, an increase in duration, and a depolarizing shift of the after-hyperpolarization. The modification of voltage- and calcium-dependent conductances that underlie these changes were investigated in voltage clamp experiments. During first phase action TRH was found to increase calcium-dependent potassium current. During second phase action TRH was found to significantly reduce the L-type calcium current (35%), with no alteration in the T-type calcium current. The second phase action of TRH on calcium-dependent potassium conductance was complex. First, a decrease was observed. This was followed by an increase that did not become fully manifest until after TRH was washed from the cell. TRH caused no change in voltage-dependent potassium current. These results indicate that the second phase action of TRH on action potential behavior in GH3 cells is mediated by a reduction in L-type calcium current and alterations in the behavior of calcium-dependent potassium currents, but not through changes in voltage-dependent potassium currents.
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PMID:Reevaluation of the electrophysiological actions of thyrotropin-releasing hormone in a rat pituitary cell line (GH3). 190 Jul 83

The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'-diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69-84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'-diphosphocholine infusions. The infusion of cytidine 5'-diphosphocholine induced a 4-fold (p less than 0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2-fold greater in the cytidine 5'-diphosphocholine treated group (706.85 +/- 185.1 vs 248.9 +/- 61.4 micrograms.l-1.(120 min)-1; p = 0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear.
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PMID:Effects of cytidine 5'-diphosphocholine administration on basal and growth hormone-releasing hormone-induced growth hormone secretion in elderly subjects. 202 9

The maximum walking speed, the stability of standing balance, and isokinetic strength for knee extension on the both sides were examined in 7 hemiparetic stroke patients before and 10-20 min after intravenous administration of 2-mg TRH. The maximum walking speed, the stability of standing balance and the strength of the affected side increased significantly with TRH but the strength of the non-affected side did not change. It seems that TRH enables functionally depressed areas to resume activity.
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PMID:Effect of thyrotropin-releasing hormone (TRH) on motor performance of hemiparetic stroke patients. 211 92

An ischemic cerebral lesion involves a progressive metabolic damage to neurons and neurotransmitter alterations. The consequent functional deficits give rise to the neurological and cognitive impairment seen in most stroke patients. As soon as neuronal loss brings synaptic activities to an end, a maximum release of neurotransmitters and peptides occurs, no longer balanced by effective synthesis activity. This unbalanced control of neurotransmitters causes the typical neurological and psychological disturbances of the post-stroke phase. In particular, the unbalance of the catecholaminergic and/or serotoninergic system seems to be related to emotional disturbances, whereas the cholinergic unbalance seems to be the cause of cognitive impairment (which is manifested in memory and learning capacity deficits). The recent demonstration that peptides also act as synaptic transmission modulators supplied the rationale to propose the use of neuropeptides as a substitutive therapy in many neurodegenerative pathologies and particularly in post-traumatic encephalopathies and stroke sequelae. Furthermore, one of these neuropeptides, protirelin, has been proved to have neurotransmitter and neuromodulator activities as well as being capable of inducing the functional maturity and regeneration of neurons and improving functional recovery and vigilance in cases of stroke sequelae. A double-blind multicenter trial versus placebo was therefore performed to evaluate the efficacy and tolerability of protirelin tartrate (TRH-T) in this pathology. The neuropsychological functions (attentiveness, learning capacity, memory) were evaluated in 136 patients with stroke sequelae, treated with TRH-T or with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Neuropsychologic and clinical effects of protirelin tartrate in patients with stroke sequelae]. 212 87

Clinical trial. The effects of protirelin tartrate (TRH-T) administration on chronic post-stroke spasticity were studied in a multicentre trial (study on the treatment of chronic post-stroke spasticity--11 centres involved). Patient evaluation included the quantification of muscular strength examined in proximal and distal areas, muscular tone according to the Ashworth scale, reflex intensities (using a 5 graded scale); daily autonomy was also considered according to the Parkside Behaviour Rating Scale (PBRS). Patients were administered 2 mg of TRH-T twice daily by intramuscular route. The most interesting finding emerging from the trial was that TRH-T administration elicited, at the same time, a reduction of spasticity, hypertonia and hyperreflexia together with an increase in muscular strength and improvement of daily activities. The therapeutic profile of TRH-T therefore seems to be based on its unusual capacity of acting simultaneously on deficiency symptoms (hyposthenia, loss of dexterity) and positive symptoms (hypertonia, hyperreflexia), both of which are present in cases of post-stroke spasticity. Electrophysiological findings. By means of coded electrophysiological tests it is possible to explore specific compartments of the motorial and spinal network and consequently obtain activity profiles for each single substance capable of modifying its reactivity. The H/M ratio, reciprocal Ia inhibition and the activities of the Renshaw circuit were not changed following TRH-T administration. Opposite findings were recorded with regard to the F wave according to whether the flector or extensor nucleus was explored; the consequent hypothesis of TRH-T activity at the interneuron level was supported by the inhibition of the short head biceps reflex following administration of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Use of TRH-T for the symptomatic treatment of the pathology of the upper motoneurons and electrophysiologic evaluation of its efficacy]. 212 88

Controlled clinical trials demonstrated protireline tartrate (TRH-T) efficacy, with its analeptic, analgesic and arousing effects, in the treatment of neurological and functional impairment due to cerebrovascular accidents and head injuries. While the efficacy profile has been extensively studied, there isn't yet a completely satisfactory evaluation on TRH-T tolerability profile. We decided to perform, in Italy, a phase IV clinical trial on the efficacy-safety ratio of TRH-T, involving more than 170 centers spread in the whole country. The trial was an open study, with no control group, enrolling 2359 patients (M = 1405; F = 930; n.d. = 24), most aged between 50 and 80 years. About 52% of them had stroke sequelae, about 15% head injury, 11% a TIA and another 11% cerebral hemorrhage. The patients received TRH-T (4 mg/die) for a cycle of 14 days, by either intramuscular or intravenous routes (slow infusion). Drug efficacy was declared good in about 45% and excellent in about 18% of the patients with stroke. Two hundred twenty eight adverse events were found in 153 patients (M = 92; F = 61), namely with an incidence of 6.49%; they were more frequently detected in elderly patients and in those affected by cerebral hemorrhage or TIA. The most frequent adverse events concerned mucocutaneous, gastrointestinal, cardiovascular and central nervous systems; they were mostly considered light or moderate, and only one third of them required suspension of treatment. Drug-event causal relationship was judged, referring to the "Lasagna algorithm", as definite in 23.7% of the adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Evaluation of the efficacy and tolerability of protirelin. Results of a multicenter study in Italy]. 212 89

Pituitary apoplexy is characterized by a wide spectrum of clinical features. A quite rare case of painless thyroiditis, hypopituitarism and central diabetes insipidus (DI) followed by pituitary apoplexy was presented. A 61-year-old woman was admitted to our hospital in May, 1986 because of marked general malaise, polydipsia and weight loss which became progressively worse. Four months earlier she had experienced episodes of abrupt onset of severe headache associated with nausea and blurring vision. Physical examinations revealed a fine tremor, dry skin and nervousness. The thyroid gland was not palpable. Visual fields were intact. Her blood pressure was 105/64 mmHg with variable tachycardia. The routine laboratory studies were normal or negative except for hypoalbuminemia, hypocholesterolemia and hypernatremia. Erythrocyte sedimentation rate was 12 mm/hr. An impairment in corticotropin secretion was suspected from the low plasma cortisol and the low urinary excretion of 17-OHCS and the sufficient response to ACTH. Basal levels of GH and gonadotropin were also low, and responses to the stimulation tests (Insulin-stress, L-DOPA, and LH-RH) were all blunted. Brain computed tomographic scan and magnetic resonance imaging demonstrated a suprasellar mass that, after infusion, developed peripheral ring-like enhancement and large hyperintense pituitary mass, respectively. A diagnosis of pituitary apoplexy with anterior pituitary failure was made. However, the initial levels of thyroid hormones showed elevated as follows: Free T3 7.6 pg/ml, Free T4 3.3 ng/dl and T3-resin uptake 41.1%. TSH responses to TRH were all suppressed. TSH receptor antibody (TBII) was negative. Both antithyroglobulin and antimicrosomal antibodies were repeatedly positive. A thyroid scan with 99mTc revealed no uptake in the thyroid area. These findings led us to the diagnosis of "painless autoimmune thyroiditis". She had become hypothyroid without any medication. At that time radioactive 99mTc and 123I uptakes increased significantly. When hydrocortisone was substituted, daily urine output abruptly increased to about 10 liters with low osmolality, and the presence of DI was suspected. This diagnosis was confirmed by water deprivation and hypertonic saline infusion tests and subsequent pitressin test. She is currently quite well on L-thyroxine, hydrocortisone and desmopressin (1988). This association with pituitary apoplexy must be a rare occurrence, as a literature search has failed to find a similar case. The pathogenetic trigger of "painless thyroiditis" in this case may be responsible for some immunological change due to secondary adrenal insufficiency after pituitary apoplexy.
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PMID:[An unusual association of transient resolving thyrotoxicosis due to painless thyroiditis, hypopituitarism and central diabetes insipidus associated with spontaneous pituitary apoplexy]. 230 57

The peptide, 7B2, originally isolated from pituitary, has been shown to be present in endocrine tumors of high concentrations in pancreatic islet tumors. Plasma from most of these patients showed very high 7B2 immunoreactivity (IR-7B2) though there is a lack of knowledge concerning physiological and pathological changes in plasma IR-7B2 levels in other conditions. To assess whether or not there is any alteration in circulating IR-7B2 levels due to age, sex or any specific condition, plasma levels of IR-7B2 were measured in the fasting state in 106 healthy subjects aged 3 months to 91 years, 101 diabetics, 28 patients with hyperthyroidism. 7 patients with primary hypothyroidism, 13 patients with liver cirrhosis, 43 patients with chronic renal failure, 35 patients with cerebral vascular accident, and 26 pregnant subjects. Twenty-four cord bloods were also included. The responses of circulating IR-7B2 to oral glucose, intravenous arginine infusion, volus thyrotropin (TRH) or volus luteinizing hormone-releasing hormone (LH-RH) injection were also evaluated. Particularly high IR-7B2 levels were found to exist in cord blood. Postnatally the concentrations decreased gradually with age to adult values (15.6 +/- 2.9pmol/liter (mean +/- SE) in 20's-60's), though plasma IR-7B2 levels again increased significantly in over 70's (37.1 +/- 3.2pmol/liter; P less than 0.01). There was no significant difference in plasma 7B2 levels in either sex. Among the pathological conditions studied, significantly high IR-7B2 levels were observed in patients with chronic renal failure (175.1 +/- 35.9pmol/liter). Some of the pregnant patients in their third trimester also showed high plasma IR-7B2 levels. A small but significant rise in plasma IR-7B2 was observed after a glucose load in control subjects and diabetics. Intravenous LH-RH exerted a rise in plasma 7B2 concentrations though arginine and TRH showed no significant effect on plasma IR-7B2 concentrations. Compared with the plasma concentrations, ten to fifty-fold high levels of IR-7B2 were observed in cerebrospinal fluid (CSF) from patients with cerebrovascular accidents or multiple sclerosis. These results suggested that the kidney plays a major role in 7B2 degradation and that LH-RH simulates IR-7B2 release from the pituitary gland. Whether reduced clearance or increased production was responsible for the IR-7B2 elevation in subjects under 10 years or over 70 years requires investigation. Furthermore, high levels of IR-7B2 in CSF might indicate its specific role for the central nervous system.
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PMID:[Immunoreactive 7B2 concentrations in plasma and cerebrospinal fluid in pathophysiological conditions and the responses to oral glucose load, intravenous LH-RH, TRH and arginine infusion]. 251 84

Opiate antagonists, including receptor antagonists and physiologic antagonists, have been shown to produce beneficial effects in a variety of models of CNS injury and in a variety of species. Opiate antagonists improve spinal cord blood flow, electrical conduction of the spinal cord, pathological changes, and motor recovery following traumatic spinal cord injury in cats. TRH appears to be superior to naloxone in this regard, although direct comparisons between receptor-selective opiate receptor antagonists and TRH have not been made. Similarly, opiate antagonists are effective in improving outcome and reducing pathological changes following ischemic spinal cord injury in rabbits. Beneficial effects for opiate receptor antagonists have also been observed after fluid percussion head injury in cats. Effects of opiate antagonists in the treatment of experimental stroke have been more controversial, although the weight of evidence supports a therapeutic effect in various models and species. Following spinal cord injury, best evidence suggests that pathophysiological responses produced by opioids may be mediated by the dynorphin opioid system and/or the kappa opiate receptor. This issue is of considerable importance, since it may lead to the development of more effective and specific forms of therapy. The role of specific opioid systems and specific opiate receptors in traumatic head injury or cerebral ischemia have not been adequately studied and should be the subject of future investigation. A number of controlled clinical studies are now either planned or under way to investigate the potential therapeutic effects of naloxone and TRH in CNS injury. Data from these studies should be available within the next several years.
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PMID:Role of thyrotropin-releasing hormone and opiate receptor antagonists in limiting central nervous system injury. 283 Jul 71

The effect of TRH (200 micrograms) on blood pressure, pulse rate, TSH and GH release was investigated in 10 acromegalics, four patients with non-GH secreting pituitary tumours, and seven normal controls. TRH produced a rapid-onset, short-lived pressor response in the acromegalic group (delta mean blood pressure 33 mmHg) compared to the two control groups (P less than 0.001). There was no response to the same volume of saline. The pressor response in the acromegalic group was not different in those who did or did not release GH. The pressor response to TRH was linearly related over the range 50-200 micrograms. Measurement of plasma noradrenaline and plasma renin activity during TRH testing in six acromegalics indicated that the pressor effect was neither mediated by adrenergic mechanisms, nor the renin-angiotensin system. Echocardiographic monitoring in five of these six patients showed that there was a significant increase in directly measured end systolic, end diastolic dimensions and heart rate (all P less than 0.02), and calculated stroke volume (P less than 0.001) and cardiac output (P less than 0.01) without changes in systemic vascular resistance. These data suggest that increase in preload, probably via venoconstriction, is the most likely factor producing the pressor response to TRH in acromegalics.
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PMID:Cardiovascular and hormonal responses to thyrotrophin releasing hormone in acromegalics. 311 46


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