Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen produces both beneficial and adverse effects on cardiovascular health via mechanisms that remain unclear. Stroke-prone spontaneously hypertensive rats (SHRSP) maintained on Stroke-Prone Rodent Diet and 1% NaCl drinking water (starting at 8 wk of age) rapidly develop stroke and malignant nephrosclerosis that can be prevented, despite continued hypertension, by drugs targeting angiotensin II and aldosterone actions. This study evaluated estrogen's effects in the SHRSP model. Female SHRSP that were sham operated (SHAM), ovariectomized (OVX) at 4 wk of age, or OVX and treated with estradiol benzoate (E2,30 microg x kg-1 x wk-1) were studied. In a survival protocol, OVX rats lived significantly longer (15.1 +/- 0.3 wk) compared with SHAM (13.6 +/- 0.2 wk) or OVX+E2 rats (12.4 +/- 0.2 wk). In a protocol in which animals were matched for age, at 11.5 wk, terminal systolic blood pressure and urine protein excretion were elevated in SHAM and OVX+E2 rats compared with OVX rats; blood urea nitrogen, renal microvascular and glomerular lesions, and plasma renin concentration were elevated in OVX+E2 relative to SHAM or OVX rats. In a survival protocol using intact female SHRSP, treatment with an antiestrogen (tamoxifen, 7 mg.kg-1.wk-1) prolonged survival by >2 wk compared with controls (P < 0.01). The data indicate that estrogen promotes microangiopathy in the kidney and stroke in saline-drinking SHRSP.
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PMID:Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats. 1267 Aug 33

We are studying a Turkish family with autosomal-dominant hypertension and brachydactyly; affected persons die of stroke before 50 years of age. With interphase fluorescence in situ hybridization, we found a chromosome 12p deletion, reinsertion, and inversion in affected persons. This finding suggested that the hypertension could be caused by one or more of 3 genes, the ATP-dependent potassium channel Kir6.1, its regulator the sulfonyl urea receptor SUR2, and the phosphodiesterase PDE3A. We further studied 6 affected and 4 nonaffected persons. Buttocks biopsies were done, small vessels were tested on a myograph, and mRNA was extracted. We performed forearm blood flow studies with intrabrachial artery diazoxide, isoproterenol, and milrinone infusions. Systemic pharmacological testing was done with intravenous diazoxide, nitroprusside, and isoproterenol. PDE3A mRNA was high in vessels from 3 affected subjects, but not high in 3 others. The vessels responded similarly to forskolin, with or without glibenclamide, and to cromakalim. However, there was a suggestion that the dilatation after milrinone might be exaggerated. The forearm infusion studies showed no differences in the responses to diazoxide, isoproterenol, or milrinone. Systemically, affected persons showed a greater blood pressure response to diazoxide and nitroprusside, and a greater heart rate response to isoproterenol than nonaffected persons. The results shed doubt on Kir6.1 and SUR2. The differences in PDE3A expression and responses may be the result of hypertension rather than the cause. Although our 3 candidate genes are no longer likely, the rearrangement we describe greatly enhances the perspectives of this project.
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PMID:Autosomal-dominant hypertension with type E brachydactyly is caused by rearrangement on the short arm of chromosome 12. 1470 63

Inlet and outlet blood urea concentrations (Cin and Cout) can be used to directly measure dialyzer performance if simultaneous blood flow measurements (Qb) are available. Dialyzer clearance, for example, is the product of the urea extraction ratio [ER = (Cin - Cout)/Cin] and Qb. Urea concentrations are measured routinely in all hemodialysis clinics, but Qb is usually reported as the product of the pump rotational speed and pump segment stroke volume, which can be inaccurate at high flow rates. Dialyzer urea extraction is also a function of Qb, dialysate flow (Qd), and the membrane permeability-area coefficient (K0A) for urea. To determine true in vivo values for Qb and K0A in the absence of direct flow measurements, we developed a model based on an existing mathematical equation for hemodialyzer ER under conditions of countercurrent flow. Qb, K0A, and other variables were adjusted to fit the modeled ER to ER measured in 1,285 patients treated with Qb that ranged from 200 to 450 ml/min during the HEMO Study. Fitting was performed by least squares nonlinear regression using parametric and nonparametric methods for estimating true flow. As Qb rose above 250 ml/min, both methods for estimating actual Qb showed increasing deviations from the flow reported by the blood pump meter. Modeled values for K0A differed significantly among dialyzer models, ranging from 71% to 96% of the in vitro values. The previously described 14% increase in K0A, as Qd increased in vitro from 500 to 800 ml/min, was much less in vivo, averaging only 5.5 +/- 1.5% higher. Dialyzer reprocessing was associated with a 6.3 +/- 1.0% reduction in K0A and an approximate 2% fall in urea clearance per 10 reuses (p < 0.001). Multiple regression analysis showed a small but significant dialysis center effect on ER but no independent effects of other variables, including the ultrafiltration rate, diabetic status, race, ethnicity, sex, method of reuse, treatment time, access recirculation, and use of central venous accesses. The new algorithm allowed a more accurate determination of true Qb and in vivo K0A in the absence of direct flow measurements in a large population treated with a wide range of blood flow rates. Application of this technique for more than 1000 patients in the HEMO Study confirmed that in vitro measurements using simple crystalloid solutions cannot readily substitute for in vivo measurements of dialyzer function, and permitted a more accurate calculation of each patient's prescribed dialysis dose and urea volume.
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PMID:Dialyzer performance in the HEMO Study: in vivo K0A and true blood flow determined from a model of cross-dialyzer urea extraction. 1476 97

We examined whether amiloride, an agent that possesses epithelial sodium channel (ENaC)- and sodium/hydrogen exchange (NHE)-inhibitory activities, would exhibit renal vascular protection in saline-drinking, stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP received amiloride (1.0 mg.kg(-1).day(-1), n = 6) or deionized water (3 mg.kg(-1).day(-1), n = 6) for 5 wk starting at 61 days of age. Systolic blood pressure (SBP) did not differ among the groups, and there was no difference in the average daily urine output, sodium excretion, or potassium excretion. Terminal urinary protein excretion, blood urea nitrogen, and renal thrombotic microangiopathic lesions were markedly reduced in the amiloride group with no difference in plasma renin activity (PRA). In a survival protocol, SHRSP infused subcutaneously with benzamil (0.7 mg.kg(-1).day(-1), n = 8), a selective ENaC inhibitor, dimethylamiloride (0.7 mg.kg(-1).day(-1), n = 8), a selective NHE inhibitor, or vehicle (n = 7) had comparable SBP. Dimethylamiloride nonetheless prolonged survival of SHRSP (P < 0.005 vs. vehicle), and benzamil-treated SHRSP lived even longer (P < 0.0001 vs. vehicle; P < 0.05 vs. dimethylamiloride). In a separate series, plasma potassium concentration was elevated by dimethylamiloride (3.4 +/- 0.1 meq/l, n = 8) and benzamil (3.3 +/- 0.1 meq/l, n = 8) relative to vehicle (3.0 +/- 0.1 meq/l, n = 8) at 4 but not at 24 h after dosing. These findings suggest the involvement of a sodium transport mechanism in the development of thrombotic microangiopathy in SHRSP, unrelated to marked changes in arterial pressure, PRA, plasma potassium, or urinary water and electrolyte excretion.
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PMID:Sodium transport antagonism reduces thrombotic microangiopathy in stroke-prone spontaneously hypertensive rats. 1498 15

Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under conditions associated with cystic fibrosis and liver injury. In the present study, we evaluated the neuroprotective effect of 4-PBA on cerebral ischemic injury. Pre- or post-treatment with 4-PBA at therapeutic doses attenuated infarction volume, hemispheric swelling, and apoptosis and improved neurological status in a mouse model of hypoxia-ischemia. Moreover, 4-PBA suppressed ER-mediated apoptosis by inhibiting eukaryotic initiation factor 2alpha phosphorylation, CCAAT/enhancer-binding protein homologous protein induction, and caspase-12 activation. In neuroblastoma neuro2a cells, 4-PBA reduced caspase-12 activation, DNA fragmentation, and cell death induced by hypoxia/reoxygenation. It protected against ER stress-induced but not mitochondria-mediated cell death. Additionally, 4-PBA inhibited the expression of inducible nitric-oxide synthase and tumor necrosis factor-alpha in primary cultured glial cells under hypoxia/reoxygenation. These results indicate that 4-PBA could protect against cerebral ischemia through inhibition of ER stress-mediated apoptosis and inflammation. Therefore, the multiple actions of 4-PBA may provide a strong effect in treatment of cerebral ischemia, and its use as a chemical chaperone would provide a novel approach for the treatment of stroke.
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PMID:Sodium 4-phenylbutyrate protects against cerebral ischemic injury. 1522 15

Female CFY rats (21 months old) and male spontaneously hypertensive, stroke-prone (SHRsp) rats (3 months old), in conventional housing conditions, received placebo (5% gum arabic solution) or 50 mg/kg bw/day idebenone suspended in 5% gum arabic, through a gastric tube for 5 weeks; then their brains were elaborated as follows: (1) Total proteins as well as water-soluble and water-insoluble proteins (WSP and WIP, respectively) were separated from the brain homogenate by centrifugation at 500 X g. The WIP fractions were tested also in vitro by heat denaturation at 64 degrees C (10 min) and by 3 M urea treatment. In the placebo group of CFY rats the total protein content was 113.9 mg per g fresh weight. WIP amounted to 27.2% of the total proteins. Idebenone-treatment did not alter the protein composition in these old rats. In the SHRsp rats the total protein content of the brain cortex was almost identical with that of the normal, Wistar-derived CFY rats of much more advanced age (about 2 years). The idebenone-treatment did not alter the protein content of the brain cortex, although the WIP content and the heat-resistant fraction of it increased significantly in this strain. (2) The osmotic potential of brain tissue was determined by measuring swelling or shrinkage velocities in Ringer solution, the osmotic concentration of which was rendered hypo- or hyperosmotic by dilution or addition of polythylene glycol (PEG 6000), respectively. Idebenone treatment exerted no effect on the osmometric properties of the brain tissue in either the normal old or the SHRsp rats.
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PMID:The effect of idebenone on the total content and solubility characteristics of proteins and osmometric behavior of the intracellular mass in brain of CFY and SHRsp rats. 1537 76

Helicobacter pylori (H. pylori) have been associated both epidemiologically and pathogenetically with coronary atherosclerosis, but data on the relationship between chronic H. pylori infection and stroke are lacking. Therefore, we investigated the relationship between H. pylori infection and acute ischemic stroke in 62 patients with their first stroke and 143 controls. The stroke patients were all admitted to Harasanshin General Hospital (Fukuoka, Japan) and the controls were asymptomatic age-matched outpatients with hyperlipidemia who did not have cardiac disease or infections. All patients underwent cranial CT scanning and/or brain magnetic resonance imaging, duplex ultrasonography of the extracranial carotid arteries, and transthoracic echocardiography. H. pylori infection was diagnosed by detection of anti-H. pylori IgG antibodies, the 13C-urea breath test, and histology. Conditional logistic regression analysis was performed to analyze the data. The 62 stroke patients and 143 controls were aged from 41 to 92 years. Chronic H. pylori infection was associated with a higher risk of stroke due to small artery occlusion (odds ratio: 9.68; 95% CI: 3.56-33.08, P <0.001) and a lower risk of cardioembolic stroke (odds ratio: 0.27; 95% CI: 0.03-1.53). Chronic H. pylori infection still showed an overall association with ischemic stroke (odds ratio for all subtypes combined: 2.57; 95% CI: 1.09-6.08) after adjusting for major cardiovascular risk factors. These results suggest that chronic H. pylori infection may be a triggering factor that increases the risk of acute ischemic stroke.
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PMID:Association between chronic Helicobacter pylori infection and acute ischemic stroke: Fukuoka Harasanshin Atherosclerosis Trial (FHAT). 1569 38

A 73-year-old woman was presented with altered mental status and disorientation. She was diabetic and hypertensive, and she had experienced an ischemic cerebrovascular accident 3 years ago. Physical examination revealed the findings of chronic obstructive pulmonary disease, cor pulmonale and congestive heart failure. Hepatomegaly, splenomegaly and ascites were found and might be associated with postsinusoidal portal hypertension secondary to congestive heart failure. Laboratory tests showed uremia, lymphocytosis and thrombocytopenia. Neurologic findings were related with uremia and hypoxia. Multiple pathologic lymphadenopathies were seen in abdominal ultrasonography and thoracic computed tomography. Bone marrow histology indicated chronic lymphocytic leukaemia (CLL). The reason for acute renal failure was leukaemic infiltration of the kidneys due to CLL that was shown with renal biopsy. Blood urea nitrogen (BUN) and serum creatinine responded well to cyclophosphamide and methyl prednisolone treatment. In CLL, direct renal involvement is frequently seen in autopsy studies especially in advanced disease, however, renal failure due to leukaemic infiltration is extremely rare.
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PMID:Acute renal failure due to leukaemic infiltration in chronic lymphocytic leukaemia: case report. 1587 23

Helicobacter pylori (H. pylori) is the commonest bacterial pathogen found worldwide and more than half the world population aged 40 years and above is colonized with it. The infection rate is >95 % in some African countries. In 1994, the International Agency for Research on cancer classified H. pylori as a class I carcinogen in humans. It causes chronic active gastritis, duodenal and gastric ulcer and gastric malignancy, and is thought to be associated with coronary artery disease, cerebral stroke, vitamin B12 and iron-deficiency anaemia, etc. Therefore, non-invasive test-and-treatment strategies are widely recommended in primary care settings. Conventionally, H. pylori infection can be diagnosed by invasive techniques using an upper gastrointestinal endoscope for obtaining multiple biopsies from different sites of the stomach for RUT, culture, histological examination, polymerase chain reaction (PCR), etc. and by non-invasive tests such as Urea breath test (UBT), stool antigen test and blood serology. At present, 13/14C-UBT is considered the test of choice for confirmation of H. pylori infection. The UBT is based on the principle, that isotopically labelled urea ingested by an H. pylori--infected patient is rapidly hydrolysed by the microbial urease. The released 13/14CO2 is absorbed across the mucous layer to the gastric mucosa and hence, excreted via the systemic circulation in the breath which is collected and measured. The non-hydrolysed urea is excreted completely in the urine within 3-4 days. 13C-UBT being non-radioactive, 13C-UBT can be used in pregnant women and children, and a user's license is not required. There is still no standard protocol accepted and followed internationally for this test. Although the methods are almost similar, various laboratories/clinics use variable tracer doses, test meals, timings and methods for breath collection, and different cut-off values, which make formal validation studies necessary. This review describes the present status of the UBT and its application in the detection of H. pylori infection.
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PMID:Urea breath test for Helicobacter pylori detection: present status. 1591 72

1. There is evidence that the induction of inducible nitric oxide synthase (iNOS) and peroxynitrite by ischaemia/reperfusion may lead to renal cell injury. Herein, we investigated whether Sheng mai san (SMS), a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke by reducing iNOS-dependent nitric oxide (NO) and peroxynitrite formation. 2. Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 43 degrees C) to induce heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and renal blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, both colonic temperature and renal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma NO, creatinine and blood urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and peroxynitrite, were significantly higher in heat stroke rats compared with their normothermic controls. 3. Pretreatment with SMS (1.2 g/day per rat for 7 consecutive days before the initiation of heat stress) significantly attenuated the heat stroke-induced arterial hypotension, hyperthermia, renal ischaemia and damage, the increased renal immunoreactivity of iNOS and peroxynitrite and the increased plasma levels of NO, creatinine and BUN. Pretreatment with SMS resulted in a prolongation of survival time in heat stroke. 4. The results of the present study suggest that SMS protects against renal ischaemic damage by reducing iNOS-dependent NO and peroxynitrite production during heat stroke.
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PMID:Sheng mai san, a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke in the rat. 1617 31


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