Toxische Kombinationseffekte bei herzwirksamen Reinglykosiden

Ohne Zusammenfassung

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Toxic effects of combinations of pure cardiac-active glycosides

     

Clinical experience with docetaxel for Chinese breast cancer patients: Hematological toxicity profiles

BACKGROUND: Asians are generally regarded to tolerate cytotoxic drugs less well than their Caucasian counterpart. A substantial proportion of patients receive suboptimal doses of chemotherapy for fear of severe toxicity. This retrospective study aims to evaluate the adverse events, especially hematological, of docetaxel in Chinese patients with breast cancer. PATIENTS AND METHODS: Fifty-nine patients, age ranged from 33 to 70 (median=47) years, were assigned to receive 3 to 6 (median=4) cycles of Docetaxel 100 mg/m2 every 21 days as neoadjuvant (n=3), adjuvant (n=26), neoadjuvant plus adjuvant (n=3), or active therapy for metastatic or relapsed breast cancer (n=27). RESULTS: A total of 56 (95%) patients completed the assigned whole regimen and only 3 (5%) patients discontinued due to either poor tolerance to the drug's side effects or worsening of disease leading to death. On average, the received dose intensity (RDI) was 0.86 for docetaxel 100 mg/m2 in this study. Among all the clinical adverse events, hematological toxicities were not excessively higher. Of the total 59 patients, major adverse events of all grades were leukopenia (22%), neutropenia (20%), fever (19%), and febrile neutropenia (14%). Only 12% and 14% of patients experienced grade 3 or 4 leukopenia and neutropenia, respectively. CONCLUSION: In view of the increasing breast cancer incidence and the acceptable toxicity profile of docetaxel among Chinese patients, a dosage of 100 mg/m2 can be recommended for use among Asians.     

放线瑞香宁碱的解热镇痛作用

从青藤科植物黑吹风(Illigera sp)总生物碱中分离出一个单体,经化学鉴定命名为放线瑞香宁碱(actinodapbnine简称Ac)。分子式C_(18)H_(17)NO_4,为10-甲氧基-1,2-(次甲二氧基)-6-去甲阿朴菲-9-醇(图1)。动物实验表明,Ac具有解痉、镇痛、局麻及降低小鼠体温等作用,并证明其镇痛作用系非中枢性。本文进一步研究其镇痛作用和对不同动物正常     

Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation

Background

Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans -10, cis -12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays.

Results

Inclusion of CLA or CLA enriched with its trans -10, cis -12 isomer in the diet of female genetically obese (lep ^ob /lep ^ob ) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans -10, cis -12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans -10, cis -12 isomer, but not with its cis -9, trans -11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity.

Conclusions

CLA initially decreased but subsequently increased insulin sensitivity in lep ^ob /lep ^ob mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans -10, cis -12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity.     

World experience after more than a decade of clinical hand transplantation: update from the Louisville hand transplant program

In the last 12 years, the Louisville CTA program has screened more than 600 interested hand transplant candidates and has transplanted 6 patients with 7 hand allografts. The program is a collaborative effort between the surgeons and staff of Kleinert, Kutz and Associates, Jewish Hospital and St. Mary's Healthcare, the Christine M. Kleinert Institute, and the University of Louisville. The functional outcome and long-term results of clinical hand transplantation have exceeded initial expectations both within the program and in the community at large. This report summarizes the successes and challenges of the Louisville CTA experience in composite tissue allotransplantation.     

Sodium/myo‐inositol cotransporter 1 and myo‐inositol are essential for osteogenesis and bone formation

myo‐Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1^?/?) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1^?/? embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1^?/? mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1^?/? mice and strengthened bone structure in SMIT1^+/+ mice. Although MI content was much lower in SMIT1^?/? mesenchymal cells (MSCs), the I(1,4,5)P₃ signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3‐E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP‐2)–induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. © 2011 American Society for Bone and Mineral Research.