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  • 1
    ISSN: 1432-0428
    Keywords: Ciglitazone ; C57BL/6J-ob/ob mice ; C57BL/KsJ-db/db mice ; β-cell granulation ; electron microscopy ; rough endoplasmic reticulum ; Golgi apparatus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Pancreases of treated and control male C57BL/6J-ob/ob and C57BL/KsJ-db/db mice were evaluated by qualitative and morphometric microscopic techniques to determine the effects of chronic ciglitazone treatment on the morphology of β cells and surface area and number of pancreatic islets. The β cells of treated ob/ob and db/db mice displayed moderate to heavy granulation whereas most β cells of untreated obese and diabetic mice were extensively degranulated. Although moderate proliferation of the rough endoplasmic reticulum and Golgi apparatus was evident in some β cells of treated db/db mice, both groups of treated ob/ob and db/db mice displayed an improved pattern of insulin synthesis and storage. In contrast, the β cells of untreated ob/ob and db/db mice were in a severe state of stress which was indicated by extensive hypertrophy of the rough endoplasmic reticulum, Golgi apparatus and mitochondria. Some β cells of untreated db/ db mice also displayed lysosome aggregates indicative of early stages of necrosis. Morphometric analysis revealed that the surface area of islets of treated ob/ob mice was significantly smaller in comparison with that of untreated ob/ob mice. Since the surface area of islets of treated C57BL/6J-+/? mice (lean littermates of ob/ob mice) was less than that of treated ob/ob mice, the progression of islet hypertrophy in the obese mice was probably arrested or attenuated but not to the level of the treated +/? mice. The number of pancreatic islets was significantly greater in treated than in untreated db/ db mice. A majority of the islets of untreated db/db mice were atrophie and consisted of acinar and endocrine cells whereas most of the islets of treated db/db mice appeared to be intact and unremarkable. The results of this study suggest that ciglitazone is an effective hypoglycaemic agent which may directly or indirectly promote β-cell regranulation and an improved pattern of insulin synthesis and storage in ob/ob and db/db mice. However, in treated db/db mice, there still was some evidence of stress in the β cells. Overall, the prolonged treatment with ciglitazone also seemed to inhibit the hypertrophy of islets in ob/ob mice and protect the structural integrity and viability of islets in db/db mice.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Ciglitazone ; C57BL/6J-ob/ob mice and their lean littermates ; glucose turnover rate in vivo ; gluconeogenesis in vivo ; Cori cycle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ciglitazone is orally active in preventing and reversing the hyperglycaemic syndrome in C57BL/6J-ob/ob mice and it is only mildly and transiently hypoglycaemic in lean littermates (C57BL/6J- +/?). Its effect on glucose disposal in vivo was estimated by injecting glucose-6-3H/14C and following the specific activity of radiolabelled glucose at 15, 30, 45, and 60 min after injection. The rate constants of glucose turnover were calculated to be as follows in decreasing order: treated obese (0.046/min), treated lean (0.032/min), control lean (0.026/min), and control obese (0.022/min). The obese mice showed less futile Cori cycle activity than the lean mice and ciglitazone had negligible effect on glucose recycling. The control obese mice incorporated more radiolabels in hepatic lipids, glycogen, and proteins than the control lean mice and ciglitazone further enhanced the incorporations. Ciglitazone also increased hepatic accumulations of radiolabels in the glycogen and lipid fractions in the lean littermates. Using lactate-14C as precursor, gluconeogenesis in vivo was measured in control and treated obese and lean mice. Ciglitazone significantly lowered the rate of conversion of lactate-14C to glucose-14C in the obese mice but not in the lean littermates.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 44 (1999), S. S26 
    ISSN: 1432-0843
    Keywords: Keywords Ifosfamide ; Carboplatin ; Etoposide ; Metastatic breast cancer ; Salvage therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Twenty-five patients with metastatic breast cancer were treated with ICE after failure of previous chemotherapy. Their median age was 50 years (range 36–73). All but 1 patient had multiple sites of metastases. Nineteen (76%) patients had undergone two or more chemotherapy regimens for metastatic disease prior to ICE. The performance status (PS) of the patients was Eastern Cooperative Oncology Group (ECOG) 0:6; 1:12; 2:5; 3:2. Ifosfamide 1.25 g/m2 over 3 h D1-3 along with mesna, etoposide 80 mg/m2 D1-3 and carboplatin 300 mg/m2 D1 were given every 3 weeks. We observed a partial response in 10 patients (40%, 95% confidence interval 21–62%). The response duration ranged from 1 to 15 months with a median duration of 4.5 months. The survival of all 25 patients ranged from 10 days to 25 months, with a median of 9 months. All 25 patients were evaluable for toxicity. Thirteen patients (52%) experienced grade 4 hematological toxicity, which improved after growth factor support. Four patients had leukopenic fever, 1 had gram-negative sepsis, while 2 had Clostridium difficile enterocolitis and another had herpes zoster reactivation. Four patients (16%) experienced grade 3–4 gastrointestinal (G-I) toxicity. No hepatic or renal toxicity was observed (1 patient had microscopic hematuria). One patient died of G-I bleed, and another patient died at home of undetermined cause. We conclude that ICE is an effective salvage regimen in metastatic and refractory breast cancer, even in heavily pretreated patients, and is a tolerable treatment when used with growth factor.
    Type of Medium: Electronic Resource
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