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641.
Radiation chemistry can contribute to drug design by quantifying redox properties of drugs (useful parameters in quantitative structure-activity relationships), and where free radicals are suspected intermediates in drug action, radiation can be used to generate these putative species and help characterize relevant reactions. Steady radiolysis produces radicals at a readily-varied but quantified rate; pulse radiolysis with fast spectrophotometric and/or conductimetric detection enables the kinetic properties of radicals to be monitored directly. Using these methods, radical intermediates from drugs with specific cytotoxicity towards hypoxic cells have been shown to react rapidly with oxygen, a reaction probably responsible for the therapeutic differential. Radical oxidants from activated neutrophils include superoxide and hydroxyl radicals, and radiation-chemical methods have an important role to play in rational drug design to exploit such oxidative chemistry. Antioxidants can also be evaluated quantitatively by radiolysis methods; the conjugation reactions of thiyl radicals with thiolate and oxygen are now recognised to be major contributions of pulse radiolysis to thiol biochemistry.  相似文献   
642.
A cross-sectional study was undertaken to assess the haematological condition of the San (Bushmen) relocated from Namibia to South Africa. We studied 238 subjects--145 men and 93 women; none of the women was pregnant. We performed full blood counts and estimations of serum vitamin B12, folate, ferritin and erythrocyte folate concentrations. The mean haemoglobin concentration among the men was 14.7 g/dl and 19 (13%) were anaemic; among the women it was 13.8 g/dl and 18 (19%) were anaemic. Thirteen (9%) of the men and 22 (24%) of the women had low concentrations of serum ferritin, and 38 (26%) of the men and 22 (24%) of the women had erythrocyte folate concentrations of less than 270 nmol/l. Three (2%) men and 4 (4%) women had serum vitamin B12 concentrations of less than 120 pmol/l. Eighty-one (56%) of the men and 76 (82%) of the women had eosinophilia, probably because of parasitic infections. It would appear from this and previous studies that prolonged exposure of these hunter-gatherers to a Western lifestyle has resulted in a high prevalence of anaemia, caused by low iron and folate intakes, complicated by alcohol consumption.  相似文献   
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644.
This study investigated the relationships between renal allograft interstitial fibrosis, renal function and graft survival. A total of 107 consecutive renal transplant recipients immunosuppressed with cyclosporin were studied. Needle core transplant biopsies were performed before operation and at 1, 6 and 12 months after transplantation. Allograft fibrosis was assessed by histomorphometric analysis of graft interstitial volume fraction. Renal function was measured by isotopic glomerular filtration rate (GFR) measurement at the same time points. Interstitial volume fraction was already high in preperfusion biopsies, significantly increased with time but stabilized at 6 months after transplantation. GFR correlated negatively with interstitial volume fraction at 6 months (P = 0.05). Interstitial volume fraction at 1 month was not a useful predictor of subsequent graft survival but for allografts surviving to 6 months an interstitial volume fraction above 25 per cent predicted significantly poorer survival (P = 0.04). It provides an objective measure of chronic allograft damage and may prove to be a useful surrogate endpoint in the study of therapeutic intervention.  相似文献   
645.
Out of 162 workers exposed to chemicals in the manufacture of construction plastics an outpatient and inpatient examination revealed gastrointestinal problems in 84.3%, vegetative nervous disorders in 62.6% of the examinees. In a random sample of 47 workers high acid production occurred in 63.3% and erosions, ulcers, cicatrices in the stomach and duodenum in 45.2% of them. No HLA genetic predisposition to duodenal ulcer was reported. Histological findings on gastroduodenal mucosa biopsies were indicative of the dystrophy in the chief and lining cells of the gastric glands, epithelium and stroma with formation of the dark cells. The authors insist on consideration of the above facts in examination and treatment of workers exposed to chemicals at construction plastics plants.  相似文献   
646.
Infusion of the serine and thiol protease inhibitor, leupeptin, is known to cause a reduction of fast axoplasmic transport, and accumulation of lysosomal dense bodies in neuronal perikarya. We have found these dense bodies in hippocampal and cerebellar neurons contain ubiquitin conjugated proteins. We now demonstrate that these accumulated neuronal lysosomes are labeled by antisera to the cytoplasmic, transmembrane and extracellular domains of beta-amyloid precursor protein (APP) and also that lysosomal APP is fragmented. This in vivo model confirms that neurons can process APP via a lysosomal pathway and that neuronal lysosomes in vivo contain both N-terminal and potentially amyloidogenic C-terminal fragments of APP. We also show that increased APP immunoreactivity after leupeptin treatment is seen first in neurons and later in astrocytes. On recovery from infusion, APP N-terminal immunoreactivity diminishes whilst C-terminal reactivity remains in neurons. These findings are consistent with production in whole brain of potentially amyloidogenic fragments of APP within neuronal lysosomes in perikarya and dendrites implying that neurons may play a role in forming the beta-amyloid of plaques.  相似文献   
647.
Since a number of 2-hydroxy(alkoxy)-2-phenyl-4(5,6)-(tri)alkyl-morpholines presented antioxidant and interesting biologic activity which may implicate free radical processes, some 2-hydroxy(alkoxy)-2-biphenyl-4-methyl-morpholine derivatives were prepared in an attempt to synthesize more potent antioxidants with interesting biologic action. The 2-hydroxy-2-biphenyl-4-methyl-morpholine was prepared by reacting the N-methyl-ethanolamine with the p-phenyl-phenacylbromide, the 2-hydroxy-derivative formed after spontaneous cyclisation gave the 2-alkoxy-2-biphenyl-4-methyl morpholines by an acid catalyzed ketal formation. The lipophilicity of the synthesized compounds was determined by the reversed phase TLC technique as RM values. The synthesized 2-biphenyl substituted morpholines were evaluated for their antioxidant activity on hepatic microsomal lipid peroxidation and on hydroxyl radical mediated oxidation of dimethylsulfoxide. The synthesized compounds were found to possess potent antioxidant activity. A possible mechanism was proposed for the antioxidant properties while lipophilicity was found not to be an important determinant of this property.  相似文献   
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649.
Target cell proliferation was investigated throughout the development of esophageal cancer induced by N-nitroso-methylbenzylamine (NMBA) in weanling rats maintained on zinc-deficient or sufficient diets. Deficient rats were fed ad libitum, while zinc-sufficient rats were either pair-fed to the deficient animals or fed ad libitum. After 5 weeks, half of the animals in each dietary group were given six intragastric doses of NMBA (2 mg/kg; twice weekly). The remaining rats were untreated by carcinogen. At weeks 1, 2, 3, 4, 5, 7, 9 and 11 post first dose, esophageal cell proliferation was assessed in rats from each group by in vivo bromodeoxyuridine (BrDU) labeling followed by immunohistochemical detection of cells in S-phase. At 11 weeks, the tumor incidence was 100, 23 and 6%, respectively, in the zinc-deficient, zinc-sufficient, ad libitum and pair-fed groups. In vivo BrDU labeling revealed that in the NMBA-untreated groups, the labeling index (LI), the number of labeled cells, and the total number of cells per cross section of entire esophagi were significantly increased by zinc deficiency at all time points; LI was lowest in zinc-sufficient, pair-fed rats. During NMBA treatment (weeks 6, 7 and 8), increased cell proliferation occurred in both groups of zinc-sufficient esophagi but only during week 6 in the deficient ones. In the weeks following the cessation of NMBA treatment, zinc-deficient esophagi showed significantly increased LI and greater number of labeled cells than the carcinogen treated, zinc-sufficient pair-fed or ad libitum fed groups. On the other hand, NMBA-treated zinc-sufficient pair-fed rats showed lower LI and smaller number of labeled cells than their zinc-sufficient ad libitum counterparts. Most importantly, esophageal papillomas were found in two zinc-deficient animals that had received no NMBA treatment, after 10-11 weeks of experimental diet. These data support a direct relationship between cell proliferation and tumor incidence, and also provide evidence that zinc deficiency and its associated cell proliferation could be carcinogenic.  相似文献   
650.
Silicon - To overcome the fabrication complexity and achieve a better switching ratio is a major grave concern for applications in semiconductor devices. In this regards, a novel stack gate-oxide...  相似文献   
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