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)

Thrombospondin (TSP)-2 is a matricellular protein that participates in the processes of tissue repair and the foreign body response. In addition, TSP2 has been shown to influence synaptogenesis and recovery of the brain following stroke. In the present study we investigated the response following the implantation of polyvinyl alcohol (PVA) sponges in the brain. PVA sponges were implanted into the brain cortex of wild type and TSP2-null mice for a period of 4 and 8 weeks and the response was analyzed by histochemistry and quantitative immunohistochemistry. TSP2 expression was detected in the interstices of the sponge and co-localized with the extracellular matrix and astrocytes. PVA sponge invasion in TSP2-null mice was characterized by dense deposition of extracellular matrix and increased invasion of reactive astrocytes and macrophages/microglia. Furthermore, the angiogenic response was elevated and the detection of mouse serum albumin (MSA) in the brain cortex indicated excessive vessel leakage, suggesting that TSP2 plays a role in the repair/maintenance of the blood brain barrier. Finally, immunostaining demonstrated an increase in the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Taken together, our observations support a role for TSP2 as critical determinant of the brain response to biomaterials.
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PMID:Thrombospondin 2-null mice display an altered brain foreign body response to polyvinyl alcohol sponge implants. 1902 Mar 42

Understanding and improving drug release kinetics from dendrimer-drug conjugates are key steps to improve their in vivo efficacy. N-Acetyl cysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. There is a need for delivery of NAC which can enhance its efficacy, reduce dosage and prevent it from binding plasma proteins. For this purpose, a poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. The results indicate that the prepared conjugate can deliver approximately 60% of its NAC payload within 1h at intracellular GSH concentrations at physiological pH, whereas the conjugate did not release any drug at plasma GSH levels. The stability of the conjugate in the presence of bovine serum albumin at plasma concentrations was also demonstrated. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells (target cells in vivo) using the reactive oxygen species (ROS) assay. The conjugates showed an order of magnitude increase in antioxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.
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PMID:Poly(amidoamine) dendrimer-drug conjugates with disulfide linkages for intracellular drug delivery. 1917 76

In a retrospective study, acute renal failure (ARF) was found in 10 (3.3%) among 304 hospitalized adults with dengue hemorrhagic fever (DHF), and 6 (60%) of the 10 patients with ARF died, whereas all 294 patients without ARF (controls) survived (P < 0.001). Compared with the controls, DHF patients with ARF were found to be significantly older (P = 0.002) and male predominant (P < 0.001) and to have higher frequency of previous stroke (P = 0.005), chronic renal insufficiency (P = 0.046), dengue shock syndrome (DSS; P < 0.001), gastrointestinal bleeding (P < 0.001), and concurrent bacteremia (P = 0.009), lower hemoglobin (P = 0.003) and serum albumin levels (P = 0.003), and higher incidences of prolonged prothrombin time (P < 0.001), elevated aspartate aminotransferase (P < 0.001), and alanine aminotransferase levels (P < 0.001). Multivariate analysis showed DSS (odd ratio = 220.0; P < 0.001) was an independent risk factor for development of ARF in DHF patients. The high fatality rate in DHF patients complicated with ARF in our series underscore the importance of clinicians' alertness to this potentially fatal complication so that initiation of timely appropriate treatment is possible.
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PMID:Clinical characteristics, risk factors, and outcomes in adults experiencing dengue hemorrhagic fever complicated with acute renal failure. 1934 94

The demographic and laboratory predictors of long-stay patients with ischemic stroke were sought in this retrospective hospital-based study. In the univariate and multivariate analysis, advanced age, male gender, leukocytosis, elevated creatinine, low-serum albumin, elevated alkaline transaminases, and lactate dehydrogenase were identified as independent predictors of "long" stayers. At an optimal probability cut-offs, the receiver operating curve incorporating these variables was 0.70, sensitivity 68%, specificity 80%, positive-predictive value 39% and negative-predictive value 95%. Application of this information may assist physicians to triage patients at risk of severe stroke for early therapy and care.
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PMID:Can demographic and admission laboratory variables be useful to identify long-stay patients with acute ischemic stroke? A hospital-based cohort study in Singapore. 1938 44

1. Studies have documented the proliferative effects of epidermal growth factor (EGF) on neural progenitor cells in the normal or injured brain. The effect of EGF on post-stroke cerebral expression of nestin, a marker of neural progenitor cells, has not been examined in hypertensive rats. 2. In the present study, adult renovascular hypertensive Sprague-Dawley rats underwent either real or sham middle cerebral artery occlusion (MCAO). Intracerebroventricular injections of either 1 microg EGF or vehicle (0.01 mol/L phosphate-buffered saline containing 0.1 mg/mL rat serum albumin) were made 24 and 48 h after MCAO. Then, 1, 2, 3 and 4 weeks after MCAO, the postural reflex was evaluated in a blinded fashion before rat brains were processed to determine the infarct volume plus immunoreactivity for nestin and/or glial fibrillary acidic protein (GFAP). Another group of rats was used to quantify nestin expression using western blot analysis. 3. Middle cerebral artery occlusion resulted in a focal infarct that was largest at 1 week and diminished gradually over the time. The impaired postural reflex followed a similar time-course. In addition, MCAO induced a marked increase in nestin expression in both hemispheres, with a higher expression in the right hemisphere; this change was maximal at 1 week and largely subsided at 3 or 4 weeks. Within the right hemisphere, nestin expression was most pronounced in the subventricular and peri-infarct zones. Most nestin-immunoreactive cells were also positive for GFAP. 4. Thus, EGF treatment significantly increases nestin expression, reduces infarct volume and ameliorates postural reflex impairment in adult hypertensive rats.
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PMID:Intracerebroventricular injection of epidermal growth factor reduces neurological deficit and infarct volume and enhances nestin expression following focal cerebral infarction in adult hypertensive rats. 1967 37

This study examined the neuroprotective ability of tetrapeptide L-Asp-Ala-His-Lys (DAHK) in permanent middle cerebral artery occlusion in rats. One DAHK dose (16 mg/kg) or saline solution were i.v. administered 30 min after occlusion and neurological deficit was evaluated at 2, 24, 48, 72 and 96 h using Longa scoring scale. The striatum infarction area was evaluated until 96 h after occlusion in both groups after staining with hematoxylin-eosin. DAHK-treated group showed a significant (P < 0.05) protection of 70% of neurological deficit at 96 h after occlusion, in comparison with the control-group that showed permanent neurological deficit. The DAHK-treated group showed a significant (P < 0.05) reduction of 52% infarction area in the striatum, as compared to control values. Results presented here support the possible therapeutic application of DAHK as a neuroprotective agent in human patients with stroke, as the peptide is part of human serum albumin, already being tested in clinical trials.
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PMID:Neuroprotective effect of DAHK peptide in an occlusive model of permanent focal ischemia in rats. 1977 46

The incidence of ischemic stroke increases with age, and it has a great impact on patients' functional independence. The aim of this study was to analyze the clinical features, laboratory findings, and stroke subtypes in different age subgroups and identify the predictive factors for functional independence 6 months after stroke. A total of 533 patients with first-ever ischemic stroke were enrolled in this study. They were divided into two subgroups: more than 80 years old (n = 108) and less than 80 years old (n = 425). Patients aged 80 years or over had higher frequencies of heart disease and atrial fibrillation, and lower frequencies of dyslipidemia, alcohol drinking, and a family history of ischemic stroke. Significantly lower body mass index, serum albumin levels, and lipid profiles, including total cholesterol, low-density lipoprotein, and triglyceride levels, but higher severity of initial neurologic deficit, and higher rates of mortality and complications during hospitalization were noted in patients aged over 80 years. The multivariate logistic regression analysis showed that higher serum total cholesterol level, less severity of neurologic deficit at admission, and absence of a history of diabetes mellitus were predictive of functional independence 6 months after stroke.
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PMID:First-ever ischemic stroke in Taiwanese elderly patients: predicting functional independence after a 6-month follow-up. 2000 22

Vascular endothelial growth factor (VEGF) is known to be an important stroke-related pathogenic factor for the formation of brain edema. We examined the therapeutic effect of human serum albumin on VEGF expression in acute ischemic stroke. Adult male Sprague-Dawley (SD) rats were subjected to Middle Cerebral Artery Occlusion (MCAO), the suture was withdrawn 2 h later, and 25% albumin (1.25 g/kg) or saline (5 ml/kg) was administered intravenously after reperfusion. The model was evaluated by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining, neurological deficits and brain water content. Serum albumin level was determined. VEGF expression was studied by enzyme linked immunosorbent assay (ELISA), quantitative real-time PCR and immunohistochemistry. We demonstrated that albumin administration maintained the serum albumin at a higher level than the sham group at 6 h, 1 d, 2 d and 3 d after MCAO, and significantly improved the neurological deficits and decreased the brain water content. In addition, the strong up-regulation of VEGF expression at 6 h and 1d after MCAO can be attenuated by albumin administration. However, albumin administration had no significant depressing effect on VEGF expression at 2 d, 3 d and 5 d after MCAO in the cortex and hippocampus. Strong up-regulation of VEGF immunoreactivity was noted in the saline group in the blood-brain barrier (BBB), and in neurons surrounding the peri-infarct area and periventricular area at 24 h after MCAO. The expression of VEGF in the albumin group was much weaker. Furthermore, there were high correlations between the brain water content with the serum albumin level, with serum VEGF protein level, and with brain VEGF mRNA expression at 24 h after MCAO. In conclusion, maintaining the serum albumin at a higher level, and attenuating endogenous VEGF expression at 6 h and 1d, but not 2 d, 3 d, or 5 d after MCAO, may partially contribute to the protective effects of albumin on reduction of brain edema in the early stage of ischemia.
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PMID:Protective effect of albumin on VEGF and brain edema in acute ischemia in rats. 2013 68

Sub-Saharan Africans face an increasing burden of hypertension. Although controversial, recent experimental evidence strongly suggests that serum calcium contributes to elevated blood pressure through increased vascular resistance. We investigated the associations of 24-h blood pressure and cardiovascular reactivity with serum calcium in African men stratified by age. The study consisted of 50 younger (median age: 38 years) and 49 older (median age: 49 years) participants. We measured 24-h ambulatory blood pressure with a mean successful inflation rate of 72.6%. Total peripheral resistance and stroke volume reactivity were obtained using a Finometer device during application of the Stroop color and word conflict test. Total serum calcium was adjusted for serum albumin. Results showed that serum calcium levels were similar between the younger and older groups. However, in the younger group, 24-h systolic blood pressure, 24-h diastolic blood pressure and total peripheral resistance reactivity correlated positively, whereas stroke volume reactivity correlated negatively with serum calcium in single and multiple regression analyses (systolic blood pressure: B=34.99, P=0.017; diastolic blood pressure: B=34.93, P<0.001; total peripheral resistance reactivity: B=65.44, P=0.048; stroke volume reactivity: B=-45.40, P=0.017). No associations were evident in the older African men. In conclusion, 24-h ambulatory systolic and diastolic blood pressures are positively associated with serum calcium in African men younger than 43 years. The blood pressure-serum calcium relationship seems to be mediated through increased vascular resistance during stress.
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PMID:Serum calcium revisited: associations with 24-h ambulatory blood pressure and cardiovascular reactivity in Africans. 2044 35

The primary objective of this prospective dose-finding pilot study is to demonstrate the tolerability and safety of four dosages of 25% human albumin in patients with subarachnoid hemorrhage (SAH). For each dosage group, the study will enroll 20 patients who meet the eligibility criteria. The enrolled patients will undergo follow-up for 90 days post-treatment. The primary tolerability hypothesis is that intravenous 25% human albumin can be given without precipitating treatment related serious adverse events beyond expectations. The study will determine the maximum tolerated dosage of 25% human albumin therapy based on the rate of treatment related serious adverse events during treatment: severe or life-threatening heart failure. The secondary objectives are to obtain preliminary estimates of the albumin treatment effect using the incidence of neurological deterioration within 15 days after symptom onset. In addition, the incidence of rebleeding, hydrocephalus, seizures, delayed cerebral ischemia and the incidence of vasospasm (both symptomatic and by transcranial Doppler ultrasound criteria) within 15 days after symptom onset will be evaluated. Furthermore, the serum osmolality and serum albumin concentrations, serum magnesium concentration, blood pressure and heart rate within 15 days of symptom onset will also be observed. The Glasgow Outcome Scale, Barthel Index, modified Rankin Scale, NIH Stroke Scale, and Stroke Impact Scale will be performed 3 months after the onset of symptoms to assess residual neurological deficits.
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PMID:Treatment of subarachnoid hemorrhage with human albumin: ALISAH study. Rationale and design. 2053 87


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