Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An experiment on intake of toxic doses of drugs (TDD) was conducted in Russia on 27 mature white rats divided into 3 groups. The 1st group was given intramuscular injections of synestrol (10-15 mg/kg), pituitrin (5 mg/kg), pachycarpine (40-50 mg/kg) and quinine (200 mg/kg) outside the pregnancy phase. The 3rd group was in the pregnancy phase and given the same doses of these drugs. The 2nd group was in the pregnancy phase and not given these preparations. The control group consisted of 4 rats injected with a physiological solution in the amount of 2 mg/kg. The preparations were given over a 5-day period. After decapitation, the anterior and posterior sections of the hypothalamus and cerebral cortex were analyzed. It showed that structural and metabolic changes in the rats of the 1st group were represented equally both in the cerebral cortex and in the hypothalamic area. In the 3rd group, these changes were considerably greater in hypothalamic area than in the cerebral cortex. In the 2nd group, only minor metabolic changes were observed in the hypothalamic area, apparently caused by the pregnancy itself. All this proves that injection of TDD during pregnancy primarily affects the hypothalamic area. Twenty-five women with affection of the hypothalamic area, developing as a result of TDD intake (synestrol, pituitrin, pachycarpine and quinine) to terminate pregnancy. Duration of intake was 2-5 days. Clinical investigations, EEG's, cranial x-rays, and examination of the fundus of the eye and conditions of the autonomic nervous system were conducted on all the women. An autonomic-vascular form of hypothalamic syndrome was noted in all the patients, in all cases combined with minor neuroendocrine and thermoregulation disturbances. There also were observed innervation impairment of cranial nerves, changes in muscle tone, and asymmetry of deep reflexes. Hypertension syndrome was also determined in a number of cases. The emotional disorders which are typical of patients suffering from primary affection of the hypothalamic area should also be noted. Hypothalamic syndrome in the women did not develop immediately after taking TDD, but 2 weeks to 2 months later. There is reason to believe that during the pregnancy there is a heightened "vulnerability" of the hypothalamus as a result of changes in its functional state and activities. Intake of TDD to interrupt a pregnancy disturbs the activities of the hypothalamus and also the limbic system as a whole. The activities of the gestational integrative functional system are especially important during pregnancy. Intake of TDD results in structural and functional failure of the gestational functional system and its principal performance organ--the hypothalamus.
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PMID:[Hypothalamic syndromes after the administration of toxic doses of drugs for terminating pregnancy]. 243 55

Hypothalamic dysfunction has emerged as an important mechanism involved in the development of obesity and its comorbidities, as well as in the process of ageing and age-related diseases, such as type 2 diabetes mellitus, hypertension and Alzheimer disease. In both obesity and ageing, inflammatory signalling is thought to coordinate many of the cellular events that lead to hypothalamic neuronal dysfunction. This process is triggered by the activation of signalling via the toll-like receptor 4 pathway and endoplasmic reticulum stress, which in turn results in intracellular inflammatory signalling. However, the process that connects inflammation with neuronal dysfunction is complex and includes several regulatory mechanisms that ultimately control the homeostasis of intracellular proteins and organelles (also known as 'proteostasis'). This Review discusses the evidence for the key role of proteostasis in the control of hypothalamic neurons and the involvement of this process in regulating whole-body energy homeostasis and lifespan.
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PMID:The pathophysiology of defective proteostasis in the hypothalamus - from obesity to ageing. 2738 87