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

Using noninvasive imaging, we have previously demonstrated that myocardial efficiency is impaired in hypothyroidism and improves after establishing euthyroid conditions. Little is known about the effects of abnormally elevated thyroid hormone exposure on cardiac metabolic performance. We studied 10 patients without evidence of heart disease in mild hyperthyroidism, and after therapy under euthyroid conditions. Cardiac oxidative metabolism was quantified by positron emission tomography with [(11)C]acetate. Left ventricular geometry was determined by cine magnetic resonance imaging. Myocardial efficiency, defined by the relation between work and oxygen consumption, was estimated using the work metabolic index [WMI = stroke volume * systolic blood pressure * heart rate/(oxidative metabolism * ventricular mass)]. In hyperthyroidism, heart rate and cardiac output were expectedly higher. Peripheral vascular resistance was reduced. Differences of blood pressure, stroke volume, and ventricular mass were not observed. Oxidative metabolism was significantly higher, but WMI was not different from the euthyroid state. In summary, while improvement of efficiency through thyroid hormone substitution was observed previously in hypothyroidism, our data in mild hyperthyroidism suggest an increase of oxygen consumption, paralleled by an increase of work. Thus, moderately elevated thyroid hormone levels neither result in further increase nor in reduction of cardiac metabolic performance.
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PMID:Cardiac oxidative metabolism, function, and metabolic performance in mild hyperthyroidism: a noninvasive study using positron emission tomography and magnetic resonance imaging. 1285 14

This study investigated the expression of deiodinases of thyroid hormones in the rat brain after transient occlusion of the middle cerebral artery. The activity of type 2 deiodinase (D2), which catalyzes the deiodination of thyroxine into the more active thyroid hormone 3,5,3'-triiodothyronine, was strongly increased by cerebral ischemia at 6 and 24 hours in the striatum and at 24 hours in the cerebral cortex. The activity of type 3 deiodinase, which catalyzes the inactivation of thyroid hormones, was not affected by ischemia. In situ hybridization showed, as soon as 6 hours, an upregulation of the expression of D2 mRNA in the ipsilateral striatum, which disappeared at 24 hours. In the ipsilateral cortex, the induction of D2 mRNA started at 6 hours, was increased at 24 hours and finally declined at 72 hours. These results were confirmed by reverse transcription-PCR for D2 mRNA in the striatum and cerebral cortex. The upregulation of D2 mRNA after ischemia was mainly localized in astrocytic cell bodies. These results show that D2 is rapidly induced in astrocytes after ischemic stroke. Future work will include the exploration of the role of the upregulation of this enzyme, responsible for local 3,5,3'-triiodothyronine production as a neuroprotective mechanism in the brain.
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PMID:Induction of type 2 iodothyronine deiodinase in astrocytes after transient focal cerebral ischemia in the rat. 1567 35

Changes of the affective and cognitive function are usually associated with thyroid gland dysfunction. In autoimmune thyroid disease, these changes can be caused by thyroid dysfunction (hypo- or hyperthyroidism) or associated with the presence of antithyroid antibodies. Even a small change in thyroid hormone concentration is associated with change of cognitive function. In euthyroid older males, variation of total and free thyroxin accounts for about 10% of Wechsler adult intelligence test variance. In euthyroid females, lower cognitive function, measured by Mini Mental test, also correlates with blood thyroxin. Short-term (4 weeks) hypothyroidism induces clinically significant cognitivedysfunction, which is reversible by thyroid hormone substitution. Mild hypothyroidism (TSH less than 10) also induces reversible cognitive dysfunction. In hypothyroidism, PET scanning shows global reduction of brain blood flow and glucose metabolism. Hashimoto's encephalopathy is characterized by corticosteroid reversible encephalopathy associated with the presence of antithyroid antibodies. Encephalopathy can be manifested as multiple stroke-like episodes (vasculitis like), or as diffuse, progressive type characterized by dementia and psychiatric symptoms. In euthyroid patients with Hashimoto's thyroiditis and no evidence of neurological disease, SPECT showed brain perfusion abnormalities. Post mortem and brain biopsy findings can be normal or show perivascular lymphocytic infiltration. Recently, presence of antineuronal antibodies has been found in patients with Hashimoto's thyroiditis. Specific high reactivity against human alpha-enolase was high in patients with Hashimoto's encephalopathy, but absent in patients with other neurological disorders and healthy subjects. Specific antineural antibodies were found in another group of Hashimoto's encephalopathy patients. Furthermore, Ferracci et al, found antithyroid antibodies in the CSF of patients with Hashimoto's encephalopathy.
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PMID:[Autoimmune thyroid disease and brain]. 1640 64

The cardiocirculatory changes in hyperthyroidism seem to be an accommodation to the increased metabolic demands and lead to an increased perfusion of the peripheral tissues. Due to the influence of elevated thyroid hormone levels, contractility, stroke volume, resting heart rate, and contraction and relaxation velocity of the left ventricle increase. Caused by direct effect on the smooth vascular muscle, systemic vascular resistance is decreased with the consequence of a diminished afterload and an increased cardiac efficiency. The activation of the renin-angiotensin-aldosteron system and the increased production of erythropoietin additionally lead to an increased blood volume, which increases cardiac preload together with the increased venous backflow. Manifest hypothyroidism is characterized by bradycardia and diastolic dysfunction in rest and systolic dysfunction at stress. Despite a slight increase of diastolic blood pressure due to an increased systemic vascular resistance, blood pressure remains nearly stable because of diminished cardiac output. Hypercholesterinaemia and diastolic hypertension in hypothyroid patients can lead to the development of arteriosclerosis and coronary heart disease (CHD). Also subclinical hypothyroidism is associated with a significantly higher risk for arteriosclerosis and CHD, whereas subclinical hyperthyroidism seems to be associated with an increased mortality for all reasons, especially for cardiovascular diseases.
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PMID:[Thyroid and cardiovascular system]. 1642 99

Thyroid hormone has been studied in cardiovascular disease but rarely in cerebrovascular disease (CVD). Recently, hypothyroidism has been suggested to be related to risk factors such as atherosclerosis but not directly to CVD. We reported a 52-year-old woman with acute ischemic stroke, and greatly improved general conditions after thyroid hormone replacement. Hypothyroidism is reported to be one of the causes of hypertension or elevated cholesterol levels, the established risk factors of CVD. Further studies of the possible association of thyroid hormone and CVD are warranted. Thyroid hormone might need to be surveyed in CVD patients especially if there are symptoms and signs of thyroid disorders.
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PMID:Hypothyroidism and cerebral infarction: a case report and literature review. 1699

The members of the NOX/DUOX family of NADPH oxidases mediate such physiologic functions as host defense, cell signaling, and thyroid hormone biosynthesis through the generation of reactive oxygen species (ROS), including superoxide anion and hydrogen peroxide. Moreover, ROS are involved in a broad range of fundamental biochemical and cellular processes, and data accumulated in recent years indicate that the NOX enzymes comprise one of the most important biological sources of ROS. Given the high biochemical reactivity of ROS, it is not surprising that they have been implicated in a wide variety of pathologies and diseases. Prominent among the settings that feature ROS-mediated tissue injury are disorders associated with inflammation, aging, and progressive degenerative changes in cells and organ systems, and it appears that essentially no organ system is exempt. Among the disorders currently believed to be mediated at least in part by NOX-derived ROS are hypertension, aortic aneurysm, myocardial infarction (and other ischemia-reperfusion disorders), pulmonary fibrosis and hypertension, amyotropic lateral sclerosis, Alzheimer's disease, Parkinson's disease, ischemic stroke, diabetic nephropathy, and renal cell carcinoma. Several small-molecule and peptide inhibitors of the NOX enzymes have been useful in experimental studies, but issues of specificity, potency, and toxicity militate against any of the existing published compounds as candidates for drug development. Given the broad array of disease targets documented in recent work, the time is here for vigorous efforts to develop clinically useful inhibitors of the NOX enzymes. As most (though not all) NOX-related diseases appear to be mediated by a single member of the NOX family, agents with isoform specificity will be preferred, although broadly active NOX inhibitors may prove to be useful in some settings.
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PMID:NOX enzymes as novel targets for drug development. 1850 46

Hypothyroidism and subclinical hyperthyroidism have both been associated with cognitive impairment and dementia. The association between thyroid stimulating hormone (TSH), free thyroid hormone or thyroxine (FT4) levels and cognition was investigated at baseline and after a 2 year follow-up in 1047 participants over 64 years of age, without physical frailty or severe cognitive impairment at baseline. Results indicated that high log transformed TSH levels were associated with lower MMSE performance (B=-0.24 (S.E.=0.09), 95% CI=-0.41 to -0.07) at baseline, independent of FT4, age, sex, education and mood, and, in separate analyses, cardiovascular (risk) factors. Importantly, half of all hypothyroid cases were untreated and unaware of having this disorder. In analyses which excluded cases with thyroid disorders, stroke and those suspected of possible dementia/cognitive impairment (MMSE less than 25) or psychiatric mood disorders at baseline, high-normal FT4 levels were associated with worse MMSE performance and a greater risk for a drop of at least 4 points on the MMSE after 2 years (per pmol/l O.R.=1.13, 95% C.I.=1.03-1.22). In conclusion, elderly patients with cognitive impairment should always be assessed for hypothyroidism. It is unclear why high normal FT4 levels were independently associated with accelerated cognitive decline in those without overt thyroid disease. Other studies found that thyroxine can generate oxidative stress and damage neurons. Treatment with thyroxine in those without thyroid disease (as is sometimes done in anti-ageing clinics) is thus not recommended on the basis of these data and the optimal therapeutic level in the elderly may be lower than is assumed.
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PMID:Thyroid function and cognitive decline in the MRC Cognitive Function and Ageing Study. 1864 Jul 83

The objective of this study was to investigate the clinical features, diagnosis, treatment and outcomes of subclinical pituitary adenoma apoplexy (SPAA) in 185 consecutive patients between January 1990 and May 2007. Of the 185 patients, 133 (71.89%) underwent transsphenoidal tumor decompression and the remaining 52 patients (28.11%) underwent transcranial surgery. Preoperative and postoperative endocrinological hormone concentrations were measured in all patients. Pituitary imaging was obtained by CT scans or MRI. Follow-up outcomes were obtained from the records of outpatient visits and by telephone interviews. Visual disturbance, headache and pituitary function impairment improved significantly in all patients. Prolactinoma was the most frequent type of pituitary adenoma in our series (51.89%). SPAA usually occurred in patients with large or giant adenomas (85.95%). Postoperative follow-up ranged from 1 year to 17 years with a mean of 7.4+/-1.6 years. The tumor recurred in 23 patients, 18 of whom were treated with postoperative radiotherapy for either residual tumors (n=8) or recurrence (n=10). Long-term thyroid hormone replacement was necessary in eight patients and steroid hormone replacement in six patients. The incidence of SPAA is relatively high compared with that of acute pituitary apoplexy. The exact pathogenic mechanism of SPAA remains unknown. MRI is significantly better than CT scans for detection of SPAA. Transsphenoidal decompression is safe and effective. Surgical decompression should be performed as early as possible.
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PMID:Manifestation, management and outcome of subclinical pituitary adenoma apoplexy. 1957 75

Whole-brain irradiation (WBI) represents the primary mode of treatment for brain metastases; about 200 000 patients receive WBI each year in the USA. Up to 50% of adult and 100% of pediatric brain cancer patients who survive >6 months post-WBI will suffer from a progressive, cognitive impairment. At present, there are no proven long-term treatments or preventive strategies for this significant radiation-induced late effect. Recent studies suggest that the pathogenesis of radiation-induced brain injury involves WBI-mediated increases in oxidative stress and/or inflammatory responses in the brain. Therefore, anti-inflammatory strategies can be employed to modulate radiation-induced brain injury. Peroxisomal proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the steroid/thyroid hormone nuclear receptor superfamily. Although traditionally known to play a role in metabolism, increasing evidence suggests a role for PPARs in regulating the response to inflammation and oxidative injury. PPAR agonists have been shown to cross the blood-brain barrier and confer neuroprotection in animal models of CNS disorders such as stroke, multiple sclerosis and Parkinson's disease. However, the role of PPARs in radiation-induced brain injury is unclear. In this manuscript, we review the current knowledge and the emerging insights about the role of PPARs in modulating radiation-induced brain injury.
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PMID:Role of PPARs in Radiation-Induced Brain Injury. 1978 38

Excessive thyroid hormone induces cardiac hypertrophy and promotes heart failure in patients with hyperthyroidism, but the mechanism remains elusive. Rats were orally administered with levothyroxine (100 microg/kg, T(4)) for 4 weeks to induce hyperthyroidism. The calculated stroke volume decreased and the shortening amplitude-frequency relationship in unloaded contraction of isolated cardiomyocytes was negative in T(4)-treated rats. Apoptotic rates increased and DNA laddering was also detectable in T(4)-treated rat hearts. By contrast, in primary cultured cardiomyocytes, T(3) induced dose-dependent hypertrophy but did not affect the apoptotic rate. Angiotensin II further increased the apoptotic rate of T(3)-induced hypertrophied cardiomyocytes. The apoptotic rate was dependent on the extent of cardiomyocyte hypertrophy. These results suggest that cardiac contractility is enhanced during the early stage of hyperthyroidism, but decreased during the late stage of hyperthyroidism. The hypertrophied cardiomyocytes were also susceptible to apoptotic stimulation by angiotensin II. Depressed cardiac contractility and enhanced apoptosis may lead to heart failure in hypertrophied myocardium.
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PMID:Excessive thyroxine enhances susceptibility to apoptosis and decreases contractility of cardiomyocytes. 2012 86


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