Platinum-based anticancer drugs, represented by cisplatin, play important roles in present cancer chemotherapy. Although three or five platinum-based drugs have been approved for clinical use worldwide or in Japan, many active researches are still ongoing to seek next generation platinum-based drugs with less side effect and higher efficacy. Tetrazolato-bridged dinuclear platinum(II) complexes (tetrazolato-bridged complex) are distinctively different from existing platinum-based drugs in cytotoxicity spectra, DNA interactions, and cellular uptake profiles, probably due to their unique structures. Tetrazolato-bridged complexes provide high in vivo antitumor activity toward pancreatic cancer which is difficult to cure. In this review, we introduce the recent drug development researches on platinum-based drugs and update the latest findings of tetrazolato-bridged complex.
The aim of this study was to examine whether a high protein diet promotes zinc deficiency in rats compared with an adequate protein diet. Rats were given free access to either a 20% protein (adequate protein) diet or a 40% protein (high protein) diet under a zinc-deficient condition (≦0.5 mg/kg Zn). There was no difference in the survival time of zinc-deficient rats fed either the 20% or the 40% protein diet. Similar results were also obtained for serum zinc enzyme activity, zinc concentrations of the serum and femur and zinc/protein ratio of zinc-deficient rats. The serum zinc enzyme activity, zinc concentration, and zinc/protein ratio of rats were analyzed as parameters of zinc status in the body similar to survival time. These results revealed that the zinc status of zinc-deficient rats fed the 20% or 40% protein diet did not differ. Moreover, the zinc status did not further deteriorate when zinc-deficient rats were switched from a 20% to a 40% protein diet.
In our previous study, we described how L-carnosine and its zinc complex polaprezinc could be promising novel agents for the oral treatment of pressure ulcers (PUs). For its potency, polaprezinc did not differ significantly from L-carnosine in comparison between treatment groups. Thus, the key question of whether additional zinc confers a benefit was not answered. For patients previously treated with L-carnosine for 4 weeks, in the present study we replaced L-carnosine with polaprezinc to examine the extent to which polaprezinc differs from L-carnosine. Patients received 150 mg/day polaprezinc (containing 116 mg L-carnosine and 34 mg zinc) orally for ≤8 weeks. PU severity was measured weekly using the Pressure Ulcer Scale for Healing (PUSH) score. Ten patients (61.0±11.2 years) orally ingesting standard diets were enrolled. PU stages were III (eight patients) and IV (two). Mean weekly improvement in PUSH score (MWIP) was 1.8±0.9, which was numerically, but not significantly, greater compared with during L-carnosine treatment (P=0.156, 1.3±0.6). Increased MWIP was found in five patients, unchanged MWIP in three, and decreased MWIP in two. One patient dropped out (week 4; pneumonia) and the PUs of the remaining nine patients healed within 8 weeks. Serum level of zinc was 65.3±4.6μg/dL at baseline and increased significantly from week 1 (P<0.01). The switching treatment from L-carnosine to polaprezinc indicated that orally-administered additional zinc tended to improve PU healing, although statistic power was limited. Further study is needed to test for larger sample sizes as well as for subjects with poorer zinc status, especially those with eating difficulty.
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