Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smoking should be stopped and hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism treated in elderly patients with peripheral arterial disease (PAD) of the lower extremities. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in patients with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, angiotensin-converting enzyme inhibitors, and statins should be given to all elderly patients with PAD without contraindications to these drugs. Beta blockers should be given if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery are (1) incapacitating claudication in patients interfering with work or lifestyle; (2) limb salvage in patients with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and (3) vasculogenic impotence.
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PMID:Peripheral arterial disease in the elderly. 1822 66

Thyroid hormones are closely related to cardiac structure and function. We have been studying their effects for over 15 years in various experimental models:--Daily triidothyronin (T3) administration to rats for 14 days improves the ability of the isolated heart to tolerate ischemia, without abolishing the capacity for ischemic preconditioning (IP).--When hypothyroidism is induced in rats by administering propylthiouracil for 21 days, the isolated heart is markedly more tolerant of 30 min of global ischemia but can no longer undergo IP.--After myocardial infarction induced in rats by left coronary artery ligation, the post--infarct heart is protected against global ischemia but its contractility is reduced. T3 administration for 2 and 13 weeks significantly improves contractility and reduces both remodeling and the sphericity index.--TNF exposure delays cultured neonatal rat myocyte elongation (maturation), and this effect is prevented by concomitant T3 administration.--Thus, thyroid hormones offer valuable insights into cardiac structure and function and may have therapeutic potential in patients with cardiovascular disease.
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PMID:[Thyroid hormones and their action on the myocardium]. 1971 90

Peripheral arterial disease (PAD) is chronic arterial occlusive disease of the lower extremities caused by atherosclerosis whose prevalence increases with age. Only one-half of women with PAD are symptomatic. Symptomatic and asymptomatic women with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from coronary artery disease. Modifiable risk factors that predispose women to PAD include active cigarette smoking, passive smoking, diabetes mellitus, hypertension, dyslipidemia, increased plasma homocysteine levels and hypothyroidism. With regard to management, women who smoke should be encouraged to quit and referred to a smoking cessation program. Hypertension, diabetes mellitus, dyslipidemia, and hypothyroidism require treatment. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in women with PAD and hypercholesterolemia. Anti-platelet drugs such as aspirin or especially clopidogrel, angiotensin-converting enzyme inhibitors and statins should be given to all women with PAD. Beta blockers are recommended if coronary artery disease is present. Exercise rehabilitation programs and cilostazol increase exercise time until intermittent claudication develops. Chelation therapy should be avoided as it is ineffective. Indications for lower extremity percutaneous transluminal angioplasty or bypass surgery in women are (1) incapacitating claudication interfering with work or lifestyle; and (2) limb salvage in women with limb-threatening ischemia as manifested by rest pain, non-healing ulcers, and/or infection or gangrene. Future research includes investigation of mechanisms underlying why women have a higher risk of graft failure and major amputation.
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PMID:Peripheral arterial disease in women. 1985 89

A hallmark of cardiac metabolism before birth is the predominance of carbohydrate use for energy provision. After birth, energy substrate metabolism rapidly switches to the oxidation of fatty acids. This switch accompanies the expression of "adult" isoforms of metabolic enzymes and other proteins. However, in a variety of pathophysiologic conditions, including hypoxia, ischemia, hypertrophy, atrophy, diabetes, and hypothyroidism, the postnatal heart returns to the "fetal" gene program. These adaptive mechanisms are also a feature of the failing heart muscle, where at a certain point this fetal-like reprogramming no longer suffices to support cardiac structure and function. We advance the hypothesis that in the postnatal heart, metabolic remodeling triggers the process through glycosylation of transcription factors, potentially protecting the stressed heart from irreversible functional impairment and programmed cell death. In other words, we propose a metabolic link to gene expression in the heart.
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PMID:Return to the fetal gene program: a suggested metabolic link to gene expression in the heart. 2020 3

Hypothyroidism in humans is characterized by severe neurological consequences that are often irreversible, highlighting the critical role of thyroid hormone (TH) in the brain. Despite this, not much is known about the signaling pathways that control TH action in the brain. What is known is that the prohormone thyroxine (T4) is converted to the active hormone triiodothyronine (T3) by type 2 deiodinase (D2) and that this occurs in astrocytes, while TH receptors and type 3 deiodinase (D3), which inactivates T3, are found in adjacent neurons. Here, we modeled TH action in the brain using an in vitro coculture system of D2-expressing H4 human glioma cells and D3-expressing SK-N-AS human neuroblastoma cells. We found that glial cell D2 activity resulted in increased T3 production, which acted in a paracrine fashion to induce T3-responsive genes, including ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), in the cocultured neurons. D3 activity in the neurons modulated these effects. Furthermore, this paracrine pathway was regulated by signals such as hypoxia, hedgehog signaling, and LPS-induced inflammation, as evidenced both in the in vitro coculture system and in in vivo rat models of brain ischemia and mouse models of inflammation. This study therefore presents what we believe to be the first direct evidence for a paracrine loop linking glial D2 activity to TH receptors in neurons, thereby identifying deiodinases as potential control points for the regulation of TH signaling in the brain during health and disease.
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PMID:Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. 2045 38

We investigated protective effects of hypothyroidism on delayed neuronal death, gliosis, lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) in the gerbil hippocampal CA1 region (CA1) after 5 min of transient cerebral ischemia. The hypothyroidism was induced by 0.025% methimazole treatment. Free triiodothyronine and thyroxine levels were markedly decreased in the hypothyroid group. Four days after ischemia/reperfusion, only a few NeuN-immunoreactive (+) neurons were detected in the CA1 of euthyroid-ischemia (eu-ischemia) group; however, at this time point, the number of NeuN(+) neurons was significantly higher in the hypothyroid-ischemia (hypo-ischemia) group than in the eu-ischemia group. At 5 days postischemia, NeuN(+) neurons were significantly decreased in the hypo-ischemia group: The number of NeuN(+) neurons in this group was similar to that in the eu-ischemia group. Activations of GFAP(+) astrocytes and Iba-1(+) microglia in the CA1 were higher in the eu-ischemia group 3 and 4 days after ischemia/reperfusion. At 5 days postischemia, the activations of both the glial cells in the CA1 were similar between the two groups. 4-Hydroxy-2-nonenal (HNE), a marker for lipid peroxidation, immunoreactivity in the eu-ischemia group was higher than in the hypo-ischemia group; at 5 days postischemia, the immunoreactivity was similar between the two groups. In contrast, SOD1 level was lower in the CA1 of the eu-ischemia group. These results suggest that hypothyroid state does not protect against delayed neuronal death but only delays the neuronal death in the hippocampal CA1 region after transient cerebral ischemia by reducing lipid peroxidation and increasing SOD1.
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PMID:Hypothyroid state does not protect but delays neuronal death in the hippocampal CA1 region following transient cerebral ischemia: focus on oxidative stress and gliosis. 2054 24

Hypothyroidism induces several metabolic changes that allow understanding some physiopathological mechanisms. Under experimental hypothyroid conditions in rats, heart and kidney are protected against oxidative damage induced by ischemia reperfusion. An increased resistance to opening of the permeability transition pore seems to be at the basis of such protection. Moreover, glomerular filtration rate of hypothyroid kidney is low as a result of adenosine receptors-induced renal vasoconstriction. The vascular tone of aorta is also regulated by adenosine in hypothyroid conditions. In other context, thyroid hormones regulate lipoprotein metabolism. High plasma level of LDL cholesterol is a common feature in hypothyroidism, due to a low expression of the hepatic LDL receptor. In contrast, HDL-cholesterol plasma levels are variable in hypothyroidism; several proteins involved in HDL metabolism and structure are expressed at lower levels in experimental hypothyroidism. Based on the positive influence of thyroid hormones on lipoprotein metabolism, thyromimetic drugs are promising for the treatment of dyslipidemias. In summary, hypothyroid status has been useful to understand molecular mechanisms involved in ischemia reperfusion, regulation of vascular function and intravascular metabolism of lipoproteins.
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PMID:Pleiotropic effects of thyroid hormones: learning from hypothyroidism. 2176 Sep 77

In systemic sclerosis, the frequency of thyroid derangements (clinical and subclinical hypothyroidism) is 43 and 73% respectively; in its pathogenesis participate structural, autoimmune and genetic mechanisms. It is important to run thyroid function test and to investigate the manifestation of clinical and subclinical hypothyroidism and to initiate treatment with levothyroxine. The frequency of hyperprolactinemia in SS goes from 13 to 59% and the implied mechanisms are the hypothalamic dysfunction and prolactinomas. The frequency of prolactinomas runs up to 66%. The frequency of osteopenia and osteoporosis is from 3 to 35 and from 35 to 44% respectively. The osteoporosis in escleroderma is multifactorial (ischemia, immobilization, intestinal malabsorption syndrome, steroids, menopause, hyperprolactinemia, among other). It is important to erform bone densitometry in these patients and to identify the cases of osteoporosis and to start opportune treatment.
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PMID:[Endocrinological alterations in systemic sclerosis]. 2179 86

Ogilvie's syndrome [acute colonic pseudo-obstruction (ACPO)] presents as massive colonic dilatation without a mechanical cause, usually in critically ill patients due to imbalanced sympathetic and parasympathetic activity. The initial therapy remains conservative with supportive measures (correction of metabolic, infectious or pharmacologic factors) followed by neostigmine and decompressive colonoscopy. Surgery is reserved for patients with clinical deterioration or with evidence of colonic ischemia or perforation. A 60-year-old lady presented with fever, altered sensorium, obstipation, bradycardia and abdominal distension. Investigation revealed hyponatremia and acute colonic pseudo-obstruction. Supportive measures and decompressive colonoscopy were not of great benefit. Thyroid profile was suggestive of primary hypothyroidism. Colonic motility was restored only on starting thyroxin. The case is illustrative of the need to consider hypothyroidism, a common endocrine disorder, in the differential diagnosis of Ogilvie's.
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PMID:Ogilvie's syndrome in a case of myxedema coma. 2262 18

In neurons, the type 3 deiodinase (D3) inactivates thyroid hormone and reduces oxygen consumption, thus creating a state of cell-specific hypothyroidism. Here we show that hypoxia leads to nuclear import of D3 in neurons, without which thyroid hormone signaling and metabolism cannot be reduced. After unilateral hypoxia in the rat brain, D3 protein level is increased predominantly in the nucleus of the neurons in the pyramidal and granular ipsilateral layers, as well as in the hilus of the dentate gyrus of the hippocampal formation. In hippocampal neurons in culture as well as in a human neuroblastoma cell line (SK-N-AS), a 24 h hypoxia period redirects active D3 from the endoplasmic reticulum to the nucleus via the cochaperone Hsp40 pathway. Preventing nuclear D3 import by Hsp40 knockdown resulted an almost doubling in the thyroid hormone-dependent glycolytic rate and quadrupling the transcription of thyroid hormone target gene ENPP2. In contrast, Hsp40 overexpression increased nuclear import of D3 and minimized thyroid hormone effects in cell metabolism. In conclusion, ischemia/hypoxia induces an Hsp40-mediated translocation of D3 to the nucleus, facilitating thyroid hormone inactivation proximal to the thyroid hormone receptors. This adaptation decreases thyroid hormone signaling and may function to reduce ischemia-induced hypoxic brain damage.
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PMID:Neuronal hypoxia induces Hsp40-mediated nuclear import of type 3 deiodinase as an adaptive mechanism to reduce cellular metabolism. 2272 89


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