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211.
212.
A new series of 3-(6-substituted-benzothiazol-2-yl)-6-phenyl-[1, 3]-oxazinane-2-thiones (4a-j) has been synthesised using an appropriate synthetic route (Scheme 1) and characterised by elemental analyses and spectral (IR, (1)HNMR, (13)C NMR, and EI MS) data. The anticonvulsant activity of all the title compounds (4a-j) was evaluated against Maximal Electroshock (MES) induced seizures and furthermore the most potent compounds were evaluated against subcutaneous pentylenetetrazole (sc PTZ) induced seizures model in mice. The neurotoxicity was assessed using the rotorod procedure. All the test compounds were administered intraperitoneally at various dose levels ranging from 30-200 mg/kg body wt and the median effective dose (ED(50)), median toxic dose (TD(50)), and protection index (PI) values were determined (Table 2). Among the compounds tested, the 3-(6-dimethylaminobenzothiazol-2-yl)-6-phenyl-[1, 3]-oxazinane-2-thiones (4j) was found to be the most potent (ED(50): 9.85 and 14.8 in MES model and 12 and 17 in scPTZ model at t = 0.5 h and 4 h, respectively, and TD(50) 42.8 and 44 at t = 0.5 h and 4 h, respectively, which has been found to be significant at p < 0.01 with respect to reference standard phenytoin) with protection index (PI) 4.85. 相似文献
213.
mdx muscle pathology is independent of nNOS perturbation 总被引:2,自引:0,他引:2
Crosbie RH; Straub V; Yun HY; Lee JC; Rafael JA; Chamberlain JS; Dawson VL; Dawson TM; Campbell KP 《Human molecular genetics》1998,7(5):823-829
In skeletal muscle, neuronal nitric oxide synthase (nNOS) is anchored to
the sarcolemma via the dystrophin-glycoprotein complex. When dystrophin is
absent, as in Duchenne muscular dystrophy patients and in mdx mice, nNOS is
mislocalized to the interior of the muscle fiber where it continues to
produce nitric oxide. This has led to the hypothesis that free radical
toxicity from mislocalized nNOS may contribute to mdx muscle pathology. To
test this hypothesis directly, we generated mice devoid of both nNOS and
dystrophin. Overall, the nNOS- dystrophin null mice maintained the
dystrophic characteristics of mdx mice. We evaluated the mice for several
features of the dystrophic phenotype, including membrane damage and muscle
morphology. Removal of nNOS did not alter the extent of sarcolemma damage,
which is a hallmark of the dystrophic phenotype. Furthermore, muscle from
nNOS-dystrophin null mice maintain the histological features of mdx
pathology. Our results demonstrate that relocalization of nNOS to the
cytosol does not contribute significantly to mdx pathogenesis.
相似文献
214.
Mutations in the sulonylurea receptor gene are associated with familial hyperinsulinism in Ashkenazi Jews 总被引:10,自引:1,他引:10
Nestorowicz A; Wilson BA; Schoor KP; Inoue H; Glaser B; Landau H; Stanley CA; Thornton PS; Clement JP th; Bryan J; Aguilar-Bryan L; Permutt MA 《Human molecular genetics》1996,5(11):1813-1822
Familial hyperinsulinism (HI) is a disorder of pancreatic beta-cell
function characterized by persistent hyperinsulinism despite severe
hypoglycemia. To define the molecular genetic basis of HI in Ashkenazi
Jews, 25 probands were screened for mutations in the sulfonylurea receptor
(SUR1) gene by single-strand conformation polymorphism (SSCP) analysis of
genomic DNA and subsequent nucleotide sequence analyses. Two common
mutations were identified: (I) a novel in-frame deletion of three
nucleotides (nt) in exon 34, resulting in deletion of the codon for F1388
(delta F1388) and (II) a previously described g-->a transition at
position-9 of the 3' splice site of intron 32 (designated 3992-9g-->a).
Together, these mutations are associated with 88% of the HI chromosomes of
the patients studied. 86Rb+ efflux measurements of COSm6 cells
co-expressing Kir6.2 and either wild-type or delta F1388 SUR1 revealed that
the F1388 mutation abolished ATP-sensitive potassium channel (KATP)
activity in intact cells. Extended haplotype analyses indicated that the
delta F1388 mutation was associated with a single specific haplotype
whereas the 3992-9g-->a mutation was primarily associated with a single
haplotype but also occurred in the context of several other different
haplotypes. These data suggest that HI in Ashkenazi Jews is predominantly
associated with mutations in the SUR1 gene and provide evidence for the
existence of at least two founder HI chromosomes in this population.
相似文献
215.
Intermittent ischaemic arrest and cardioplegia in coronary artery surgery: coming full circle? 总被引:1,自引:3,他引:1 下载免费PDF全文
D P Taggart S Bhusari J Hopper M Kemp P Magee J E Wright R Walesby 《Heart (British Cardiac Society)》1994,72(2):136-139
OBJECTIVE--To compare the cardioprotective efficacy of cold crystalloid cardioplegia and intermittent ischaemic arrest in patients undergoing elective coronary artery surgery. DESIGN--Prospective randomised trial. SETTING--London teaching hospital. SUBJECTS--20 patients with at least moderately good left ventricular function undergoing elective coronary artery surgery by one experienced surgeon and needing at least two bypass grafts. INTERVENTIONS--Patients were randomised to cold crystalloid cardioplegia or intermittent ischaemic arrest. MAIN OUTCOME MEASURES--The primary determinant of the efficacy of myocardial protection was serial measurement (before and at 1, 6, 24, and 72 hours after the end of cardiopulmonary bypass) of cardiac troponin T (cTnT), a highly sensitive and specific marker of myocardial damage. RESULTS--There was no significant difference in age, ejection fraction, number of grafts, bypass times, or cross clamp times between the two groups. One patient in the cardioplegia group had a perioperative infarct and was excluded from further study. In both groups there was a significant increase in cTnT, with peak concentrations being reached 6 hours after the end of cardiopulmonary bypass and remaining significantly high at 72 hours. At 6 hours the median (75% interquartile range) concentrations of cTnT were similar in both groups (1.8 (1.0-3.6) micrograms/l for cardioplegia v 1.9 (1.0-3.5) micrograms/l for intermittent ischaemic arrest). CONCLUSION--This trial shows that intermittent ischaemic arrest, even without systemic cooling or venting of the left ventricle, provides a similar level of myocardial protection to cardioplegia in patients with moderate left ventricular function and short ischaemic times. 相似文献
216.
The ability of an infusion of ex vivo expanded hematopoietic cells to ameliorate cytopenia following transplantation of hematopoietic stem cells (HSCs) is controversial. To address this issue, we measured the recovery of circulating leukocytes, erythrocytes, and platelets in lethally irradiated mice transplanted with 10(3) enriched HSCs, with or without their expanded equivalent (EE) generated after 7 days of culture in interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor and Steel Factor. Two HSC populations differing in their content of short-term repopulating progenitors were evaluated. Thy-1loLIN-Sca- 1+ (TLS) bone marrow (BM) is enriched in colony-forming cells (CFCs), day 8 and day 12 spleen colony-forming units (CFU-S) (435 +/- 19, 170 +/- 30, and 740 +/- 70 per 10(3) cells, respectively), and stem cells with competitive long-term repopulating potential (> or = 1 per 43 cells). Thy-1loSca-1+H-2Khl cells (TSHFU) isolated from BM 1 day after treatment of donor mice with 5-fluorouracil (5-FU) are also highly enriched in competitive repopulating units (CRU, > or = 1 per 55 cells), but are depleted of CFCs, day 8 and day 12 CFU-S (171 +/- 8, 0 and 15 +/- 4 per 10(3) cells, respectively). Recipients of 10(3) TLS cells transiently recovered leukocytes to > or = 2,000/microL in 12 days, but sustained engraftment required 25 days. Platelets recovered to > or = 200,000/microL in 15 days, and erythrocytes never decreased below 50% of normal. Mice transplanted with 10(3) TSHFU cells recovered leukocytes in 15 days, and platelets and erythrocytes in 18 days. Recipients of unseparated normal or 5-FU-treated BM cells (containing 10(3) TLS or TSHFU cells) recovered safe levels of blood cells in 9 to 12 days, suggesting that unseparated marrow contains early engrafting cells that were depleted by sorting. Upon ex vivo expansion, total cells, CFCs and day 12 CFU-S were amplified 2,062-,83- and 13-fold, respectively, from TLS cells; and 1,279-, 259- and 708-fold, respectively, from TSHFU cells. Expanded cells could regenerate the majority of lymphocytes and granulocytes in primary (17 weeks) and secondary (26 weeks) hosts and were only moderately impaired compared to fresh HSCs. The EE of TSHFU cells was more potent than that of TLS cells, suggesting that more highly enriched HSCs are more desirable starting populations for this application. When mice were transplanted with 10(3) TSHFU cells and their EE, the duration of thrombocytopenia was shortened from 18 to 12 days, and anemia was abolished. Leukocytes were also elevated on days 9 to 12, although sustained recovery was not accelerated. Anemia was also abrogated in recipients of 10(3) TLS cells and their EE. Early platelet counts were slightly higher than with TLS cells alone, but leukocyte recovery was not improved. These data confirm that TLS cells contribute to early and sustained hematopoiesis, and demonstrate a benefit of ex vivo expanded cells in accelerating engraftment of more primitive TSHFU stem cells depleted of progenitors. 相似文献
217.
Pradeep R Deshmukh Amol R Dongre KP Rajendran Suresh Kumar 《Indian Journal of Palliative Care》2015,21(1):39-44
Objective:
To find out the relationship of collective social, economic, and cultural properties of a population on the perceived quality of life (QOL) among old age people.Materials and Methods:
In a community-based cross-sectional study, we analyzed information on a representative sample of 900 old age (aged > 60 years) from 28 villages in Kollam district of Kerala. WHO-Quality of Life - BREF questionnaire was used. Ethical clearance from Institutional Ethics Committee was obtained. The mean scores for perceived QOL for domains such as physical health, psychological health, social relations, and control of environments were calculated. The three scales (social capital, cultural capital, and economic capital) were standardized using z-score transformation to make them comparable. Using multiple linear regression, we calculated the independent effect of economic capital, social capital, and cultural capital on perceived QOL among old people adjusted for age, sex, and the presence of chronic disease.Results:
For overall QOL, only cultural capital contributed significantly. An increase of one unit z-score cultural capital led to three units increase in overall QOL score (β = 3.362; 95% CI: 2.645-4.078). Social capital and cultural capital contributed significantly to the physical health domain of QOL. With one z-score increase in social capital and cultural capital, QOL score of physical health domain increased by 0.2 units (β = 0. 227; 95% CI: 0.020-0.434), and 0.5 (β = 0. 596; 95% CI: 0.384-0.808) units, respectively. Psychological health domain and environmental domain were affected by all three capitals significantly. But, the social relations domain was significantly affected only by cultural capital (β = 0. 576; 95% CI: 0.373-0.779).Conclusion:
Hence, the policies for old people should envision retaining our cultural and social norms along with the economic interventions for a better palliative care. 相似文献218.
Angiotensin-converting-enzyme inhibitors in the management of cardiac failure: are we ignoring the evidence? 总被引:2,自引:0,他引:2
Hillis GS; Trent RJ; Winton P; MacLeod AM; Jennings KP 《QJM : monthly journal of the Association of Physicians》1996,89(2):145-150
The benefits of angiotensin-converting enzyme (ACE) inhibition in the
management of cardiac failure have been extensively documented. However,
little is known about its impact upon the investigation and management of
this condition. We assessed how patients diagnosed as having cardiac
failure were investigated, which patients were treated with ACE inhibitors
and with what dosages. We reviewed the case notes of all 343 patients
discharged from Aberdeen Royal Infirmary 1 July-31 December 1992 with a
diagnosis of cardiac failure. In addition, a questionnaire was sent to the
general practitioners of the 166 patients still alive in October 1994. Only
40% of patients were discharged from hospital on ACE inhibitors. In 58.8%,
the diagnosis of cardiac failure was based purely on clinical or
radiological grounds. At discharge, 76.1% of patients were on lower doses
of ACE inhibitors than those used in the major survival studies; with 68.9%
receiving similar doses two years later. The majority of patients with
heart failure are under- investigated and under-treated.
相似文献
219.
Population based standards for pulmonary function in non-smoking adults in Singapore 总被引:1,自引:0,他引:1
Abstract Ethnic differences in lung function are well recognized, hence the use of normative data should therefore be based on reference equations that are derived specifically for different ethnic groups. We have collected data ( n =406) for population-based reference values of lung function from randomly selected samples of healthy non-smoking adults of both gender (aged 20–79 years) for each of the three major ethnic groups (Chinese, Malay and Indians) in Singapore. Lung function forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), FEV1 /FVC, diffusion capacity (transfer factor) for carbon monoxide (DLCO), total lung capacity (TLC), residual volume (RV), RV/TLC and functional residual capacity (FRC) was measured using standardization procedures and acceptability criteria recommended by the American Thoracic Society. Lung function values were predicted from age, height, weight, body mass index (BMI) and transformed variables of these anthropometric measures, using multiple regression techniques. Ethnic differences were demonstrated, with Chinese having the largest lung volumes and flow rates, and Indians the smallest. These prediction equations provide improved and additional (TLC, RV, RV/TLC, FRC) population-based reference values for assessment of pulmonary health and disease in Singapore 相似文献
220.