Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight patients with amyotrophic lateral sclerosis received 500 mg TRH by IV infusion, at a progressive rate during 3 hours. Only 3 patients noted subjective improvement of strength. Clinical muscular testing and H response study failed to show any change. Moreover modifications of the prolactin, growth hormone, TSH and T3 serum levels raise a question concerning the tolerance with long term utilization of TRH.
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PMID:[Clinical, electrophysiologic and endocrine effects of the perfusion of high doses of TRH in amyotrophic lateral sclerosis]. 314 86

In recent years it has been established that patients with AD have a relatively specific loss of cerebral cortical and hippocampal cholinergic nerve terminals. This may be a reflection of degeneration of cholinergic neurons originating in the nucleus basalis of Meynert and septum which project to the cortex and hippocampus, respectively. In view of the long-standing association of cholinergic mechanisms with cognitive processes and the recognition of selective cholinergic deficits in AD, therapeutic attempts to enhance CNS cholinergic function have been undertaken in patients with AD. While only limited success with this strategy has been achieved to date, the use of TRH may offer a novel, yet rational, approach to treating AD. This assumption is predicated on the extensive literature documenting unique, facilitatory interactions of this peptide with cholinergic neurons throughout the neuraxis. Furthermore, the same rationale may account for the recently reported therapeutic benefit of TRH in patients with amyotrophic lateral sclerosis, which like AD, is a disease whose symptoms are manifested through a progressive degeneration of a subpopulation of CNS cholinergic neurons.
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PMID:The therapeutic potential of thyrotropin releasing hormone (TRH) in Alzheimer's disease (AD). 392 31

Very high intravenous doses (2-19 mg/min) of thyrotropin-releasing hormone (TRH, L-pyroglutamyl-L-histidyl-L-prolinamide) given to 12 patients with amyotrophic lateral sclerosis (ALS) produced a moderate to marked improvement of functions caused by deficiency of lower motor neurons (weakness) and upper motor neurons (spasticity). The improvement was sustained throughout the infusion and for about 1 h thereafter; sometimes a slight improvement was evident 20 h after infusion. At a given dose benefits and side-effects were more evident in men than in women. Whether TRH is replacing an ALS-associated deficiency or is simply a symptomatic treatment is unknown. The results of this study raise the possibility of a treatment for ALS, and may provide new insight into its pathogenesis. The potential response to TRH of spasticity and/or lower motor neuron involvement of other causes is proposed.
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PMID:Effect on weakness and spasticity in amyotrophic lateral sclerosis of thyrotropin-releasing hormone. 613 61

Concentrations of immunoreactive thyrotropin-releasing hormone (ir-TRH) were measured by specific radioimmunoassay in the spinal cord of six patients with amyotrophic lateral sclerosis (ALS) and seven with non-neurological diseases. Ir-TRH concentrations were the highest in the anterior horn, compared with other areas of the spinal cord, both in non-neurological diseases and ALS. Ir-TRH concentrations in the anterior horn of ALS were significantly lower than in non-neurological diseases, but were the same in both groups in other parts of the spinal cord (e.g. posterior horn, frontal part, lateral and central part, posterior part). Ir-TRH concentrations in rat spinal cords were stable for up to seven hours when spinal cord was stored after death at 4 degrees C or 22 degrees C. An elution profile of methanol-extracted human spinal cord on Sephandex G-10 column was identical to that of synthetic TRH. The cell population in the anterior horn in ALS was decreased markedly. The findings suggest that TRH is present in the human spinal cord and its decreased concentrations in the anterior horn of ALS may be due to a decrease in the cell population.
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PMID:Concentrations of immunoreactive thyrotropin-releasing hormone in spinal cord of patients with amyotrophic lateral sclerosis. 642 72

Motor neurone disease, or amyotrophic lateral sclerosis, is a serious progressive neurological disorder, characterized by loss of UMN and LMN. Pathological features include characteristic intracytoplasmic MN inclusion bodies and appearances on ubiquitin staining. The aetiopathogenesis of the disease remains unknown and there is, to date, no effective treatment. Several abnormalities have been demonstrated in neurotransmitter, neuropeptide and gene expression studies. Abnormalities in glutamate metabolism have led to the excitotoxin hypothesis of MN destruction. Other theories include deficits in MN trophic factors, trans-synaptic degeneration, impaired ability to detoxify putative toxic agents and impaired DNA/RNA metabolism. The existence of familial forms, some of which show linkage to markers in chromosome 21, allows a genetic approach to the mechanisms of disease. Recent studies suggest that mutations in the Cu/Zn SOD gene may be important in some of the familial forms. The atypical forms seen in the Western Pacific have stimulated a search for environmental agents. Agents undergoing therapeutic trials at present include CNTF, IGF1 glutamate antagonists, branched-chain amino acids and TRH analogue.
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PMID:Motor neurone disease. 792 18

F responses were recorded in 6 cases with SSP and in 22 normal controls. The present study confirmed that frequency, number of phases, F/M amplitude ratio and duration were significantly increased and CV of onset latencies was significantly reduced in cases with SSP. After intravenous injection of TRH (2 mg), all the parameters were altered toward normal sides. It was suggested that the hyperexcitability of motor neuron pool in SSP was stabilized by effects of TRH on injured pyramidal tracts and consequently abnormalities of F responses were improved. The Effect of TRH to correct the abnormal F responses in SSP might be consistent with effects of TRH to reduce spasticity in amyotrophic lateral sclerosis described previously.
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PMID:Abnormalities of F response in cases with spastic spinal paralysis and effects of TRH-T on them. 944 87

Post-traumatic stress-induced disorders are still the focus of interest and most recently discussions are under way whether stress-induced cortisol excess leads to atrophy of the brain. In investigation on carcinogenesis the first reports were published on the use of antisense-oligonucleotides during inhibition of the development of tumours by a humoral mechanism and on the gene-based neuroendocrine differentiation of the lungs, perhaps associated with the basis for the development of small cell carcinoma. The oncogenic action of superoxides has also humoral mediators. Interest in nitrogen oxide is focused on two areas: inflammations and hypertension. Intraluminal NO concentrations increase in asthma 2-10x, in cystitis 30-100x, in Crohn's disease 20-200x. Humoral mechanisms in asthma offer new drugs--inhibitors of the development or action of leucotrienes. The basal NO production is reduced in "essential" hypertension but it is not known whether it is the cause or consequence. IGF-I increases the formation of NO in the vascular wall and thus perhaps reduces vascular contractility. As far as IGF is concerned, it is obvious that if recombinant preparations will be available, they will be tested in amyotrophic lateral sclerosis, myotonic dystrophy, multiple sclerosis, catabolic conditions, osteoporosis, in renal failure and to promote wound healing. STH may also prove useful in cardiac failure, in particular in cardiac cachexia. That TRH has receptors in the gut is not surprising, it acts, however, even there via TSH. Thrombopoietin is being tested in clinical trials. Neocytolysis is a new phenomenon: when erythropoietin secretion declines new erythrocytes disappear and only old ones remain in the blood stream. Alpha-adducin is a renal tubular protein, regulating the sodium balance.
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PMID:[Endocrinology 1996-1997]. 965 Mar 40

Heart rate, respiratory rate, systolic and diastolic blood pressure, and oral and skin temperature changes following intravenous administration of TRH occur at lower infusion rates in patients with ALS and bulbar involvement than in patients with ALS without bulbar involvement. This autonomic sensitivity to TRH infusion is characteristic of a more advanced stage of ALS with difficulties in speaking and swallowing. Patients who will be receiving neuropeptides, such as TRH, must be carefully studied to determine whether subclinical bulbar involvement is present. Such patients may require a lower initial dose or dose rate adjustment as well as continual monitoring during neuropeptide administration.
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PMID:Intravenous thyrotropin releasing hormone in amyotrophic lateral sclerosis: autonomic effects. 1168 3

Patients in the Department of Neurology undergoing treatment for disorders such as cerebrovascular disease, dementia, metabolic disease, neuromuscular disease and intractable disease, are included as subjects requiring terminal care. Intractable diseases ware defined by the Ministry of Health and Welfare (Ministry of Health, Welfare and Labor) in 1972 as being of unknown etiology, untreatable, chronically progressive and sometimes worsened by the care provided when nursing these patients. Intractable diseases in the Department of Neurology rank with those seen in other departments. Amyotrophic lateral sclerosis is the most difficult to treat due to the lack of effective drugs. On the other hand, Parkinson disease is the most treatable among intractable diseases in the Department of Neurology with the appearance of several new effective drugs. TRH (thyrotropin releasing hormone) is effective for ataxic gait in some patients with spinocerebellar degeneration. In the terminal care of intractable diseases in the Department of Neurology, common problems such as disturbances of swallowing, respiration and speaking develop in almost all patients and measures must be taken to treat these disturbances. Artificial respiration must be considered for respiratory distress. Artificial feeding by intubation must be considered for swallowing disturbance. All kinds of communication aids must be considered for speaking difficulties. The medical and nursing care team needs to manage these problems with consideration of the quality of life of the patients and their families as well as the complication of the diseases.
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PMID:[Terminal care in the Department of Neurology]. 1499 9


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