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Optimization of a previously disclosed sorbitol dehydrogenase inhibitor (SDI, II) for potency and duration of action was achieved by replacing the metabolically labile N,N-dimethylsulfamoyl group with a variety of heterocycles. Specifically, this effort led to a series of novel, in vitro potent SDIs with longer serum half-lives and acceptable in vivo activity in acutely diabetic rats (e.g., 62, 67, and 69). However, the desired in vivo potency in chronically diabetic rats, ED90 less than or equal to 5 mg/kg/day, was achieved only through further modification of the piperazine linker. Several members of this family, including 86, showed better than the targeted potency with ED90 values of 1-2 mg/kg/day. Compound 86 was further profiled and found to be a selective inhibitor of sorbitol dehydrogenase, with excellent pharmacodynamic/pharmacokinetic properties, demonstrating normalization of sciatic nerve fructose in a chronically diabetic rat model for approximately 17 h, when administered orally at a single dose of 2 mg/kg/day.  相似文献   
73.
Smith  TP; Cragg  AH; Berbaum  KS 《Radiology》1989,170(3):941
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74.
Background  Alopecia areata is a complex genetic disease with still many unknown aspects, and many studies have been tried to find some clues about it.
Objective  We aimed to investigate the demographic and clinical characteristics of alopecia areata in Turkish patients.
Methods  Demographic data, localization, attack number in addition to some parameters such as disease duration, severity, age of onset, family history and ophiasis pattern were evaluated in 539 alopecia areata patients.
Results  The male to female ratio was 1.6 : 1. Occipital and beard-moustache areas were mostly affected. Positive family history was noticed in 24.1% of the patients. The age of onset was earlier in women than in men ( P =  0.04). Severe forms showed more persistent (≥ 1 year) disease duration ( P =  0.00). Ophiasis was more common in severe, long duration (≥ 1 year) and early onset (≤ 18 years) disease ( P =  0.00 for all parameters). Childhood alopecia areata (≤ 18 years) was also associated with long duration of the disease ( P =  0.016) and positive family history ( P =  0.008) when compared with adult onset (> 18 years) alopecia areata.  相似文献   
75.
Vascular endoprostheses made of knitted tantalum wire and expanded over angioplasty balloons were placed into aortas or iliac arteries of 14 normal dogs. Twelve stents were placed into the infrarenal abdominal aorta and two stents in the left common iliac arteries by the left carotid artery approach. To firmly expand the stent against the vascular wall, nominal stent sizes 0.5-1.0 mm larger than the measured arterial diameter were required. Arteriography performed at specified follow-up intervals showed no evidence of thrombi or emboli; all side branches (lumbar arteries) covered by the stents remained patent. Vascular diameter decreased minimally at 8 and 26 weeks, associated with histopathologic evidence of neointimal buildup. This buildup was highest at 8 weeks (mean, 313 microns) and was slightly less at 26 weeks (mean, 223 microns). Almost complete coverage by endothelium was seen as early as 3 weeks. It is concluded that the flexible tantalum wire stents are well tolerated by the arterial wall and become quickly endothelialized. No excessive neointimal buildup was observed during the 6-month study.  相似文献   
76.
The radiographic findings in five pediatric patients in whom unregulated B-cell lymphoproliferative disorders developed following bone marrow transplantation are described. Four patients received T-cell-depleted bone marrow from mismatched donors and one received nondepleted marrow from a matched sibling donor. These disorders are similar to B-cell lymphoproliferative disorders that have been described in other immunosuppressed hosts. They are associated with Epstein-Barr virus and range from polyclonal proliferation without cytogenetic abnormalities to monoclonal lymphoma with clonal cytogenetic changes. Unlike other postallograft lymphoproliferative processes, B-cell lymphoproliferative disorders in these patients have not responded to antiviral therapy, immunologic therapy, or chemotherapy. The radiographic patterns of disease include diffuse or focal hepatic involvement; gallbladder wall thickening; and pulmonary, soft-tissue, and basal-ganglion masses. These radiologic findings are not specific and evaluation of tissue histology is required for diagnosis.  相似文献   
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78.

Background  

DNA fingerprinting of Mycobacterium tuberculosis isolates offers better opportunities to study links between tuberculosis (TB) cases and can highlight relevant issues in urban TB control in low-endemic countries.  相似文献   
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