Bone mineral density in Japanese prostate cancer patients under androgen-deprivation therapy

Androgen-deprivation therapy (ADT) of patients with prostate cancer (PCa) is known to reduce bone mineral density (BMD). However, the most studies examined Caucasian or black patients and the effects of ADT on the bone metabolism of East Asians are unclear. Therefore, we performed a cross-sectional study to elucidate the influence of ADT on bone metabolism in Japanese patients. In total, 101 native Japanese patients with PCa were enrolled. They consisted of 58 ADT-treated and 43 hormone-naive patients. The BMD in the lumbar spine, total hip, and femoral neck was measured by dual energy X-ray absorptiometry and expressed in s.d. units relative to young adult men (T-score) or age-matched men (Z-score). Serum levels of bone metabolism markers were also measured. The BMDs at the three sites revealed that 2.3% (1/43) and 8.6% (5/58) of the hormone-naive and ADT-treated PCa patients had osteoporosis respectively, but this difference failed to achieve statistical significance (P=0.294). The two groups also did not differ significantly in their Z-scores of the three sites, and univariate and multivariate analyses indicated that ADT was not a significant risk factor for decreased BMD. In addition, a significant correlation between the duration of ADT and BMD was not observed for all three sites measured. However, the ADT-treated patients had significantly higher serum levels of N-terminal telopeptide of type I collagen (NTx) than the hormone-naive patients (P=0.017). To our knowledge, this is the first study to demonstrate the low prevalence of osteoporosis in both ADT-treated and hormone-naive Japanese PCa patients. Moreover, ADT did not significantly increase the prevalence of osteoporosis in this Japanese population.     

Effect of sex hormone status on chloroform nephrotoxicity and renal mixed function oxidases in mice

In mice, only makes are susceptible to chloroform (CHCl₃) nephrotoxicity and the susceptibility appears to be related to renal mixed function oxidase activity. There were sex-related differences of renal cytochrome P-450 and b₅ concentrations and of ethoxycoumarin O-deethylase activity in mouse kidneys; in all cases activity was higher in males. Castration of male mice eliminated susceptibility to ChCl₃ nephrotoxicity and reduced renal mixed function oxidases to concentrations observed in female mice. Treatment of male and female mice with testosterone increased the susceptibility to ChCl₃ nephrotoxicity and increased renal mixed function oxidases to similar activities in both sexes. Previous data have suggested that CHCl₃ is metabolized in situ by the kidney, possibly by a mechanism similar to that occurring in the liver. The data from this investigation are consistent with the concept that CHCl₃ is metabolized by a cytochrome P-450-dependent mechanism in the kidney.     

A new vitamin E (alpha-tocomonoenol) from eggs of the Pacific salmon Oncorhynchus keta

A novel alpha-tocomonoenol 3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyl-12-tridecenyl )-2H-1- benzopyran-6-ol[ having an unusual methylene unsaturation at the isoprenoid-chain terminus of alpha-tocopherol was isolated from the lipophilic fraction of chum salmon eggs. The structure of this marine-derived tocopherol (MDT) was established by spectral analyses. The peroxyl radical-trapping activities of MDT and alpha-tocopherol were compared in aqueous phosphatidylcholine liposomal suspension and in methanolic solution at 37 degrees C. The antioxidant activity of MDT was found to be identical to that of alpha-tocopherol under the experimental conditions of measurement.     

Spliceosome discards intermediates via the DEAH box ATPase Prp43p

To promote fidelity in nuclear pre-mRNA splicing, the spliceosome rejects and discards suboptimal substrates that have engaged the spliceosome. Whereas DExD/H box ATPases have been implicated in rejecting suboptimal substrates, the mechanism for discarding suboptimal substrates has remained obscure. Corroborating evidence that suboptimal, mutated lariat intermediates can be exported to the cytoplasm for turnover, we have found that the ribosome can translate mutated lariat intermediates. By glycerol gradient analysis, we have found that the spliceosome can dissociate mutated lariat intermediates in vivo in a manner that requires the DEAH box ATPase Prp43p. Through an in vitro assay, we demonstrate that Prp43p promotes the discard of suboptimal and optimal 5′ exon and lariat intermediates indiscriminately. Finally, we demonstrate a requirement for Prp43p in repressing splicing at a cryptic splice site. We propose a model for the fidelity of exon ligation in which the DEAH box ATPase Prp22p slows the flow of suboptimal intermediates through exon ligation and Prp43p generally promotes discard of intermediates, thereby establishing a pathway for turnover of stalled intermediates. Because Prp43p also promotes spliceosome disassembly after exon ligation, this work establishes a parallel between the discard of suboptimal intermediates and the dissociation of a genuine excised intron product.     

Matrix metalloproteinase-9 and vascular endothelial growth factor: a possible link in adult T-cell leukaemia cell invasion

Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL, 39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering ATL, two patients) and 20 healthy controls was analysed for the presence of type IV gelatinase activity with clinical features. A significant elevation of plasma matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients, particularly in the patients with malignant cell infiltration. MMP-9 was found to be secreted into the conditioned medium from all ATL cell lines examined. Moreover, the corresponding mRNA was detectable both in all ATL cell lines examined and in the majority of primary acute ATL cells, indicating that ATL cells are capable of synthesizing and secreting MMP-9. We previously demonstrated that a high incidence of ATL cell infiltration was closely related to a high plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells themselves. This present study showed that the presence of increased plasma MMP-9 was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we showed that both increased plasma MMP-9 and VEGF were significantly related to high ATL cell infiltration. All these findings strongly suggest that MMP-9 and VEGF act co-operatively in the process of ATL cell invasion.     

Effects of aminoglycosides on glomerular ultrastructure

Effects of the aminoglycosides, gentamicin, netilmicin and tobramycin (30 mg/kg/day X 7, i.p.), on glomerular ultrastructure were determined in male Wistar rats. Glomerular ultrastructure was studied by scanning and transmission electron microscopy. The average number of capillary endothelial fenestrae per 5 microns of capillary wall decreased from a control value of 10.8 to 8.2 and 8.1 in gentamicin- and tobramycin-treated rats, respectively, as shown by transmission electron microscopy (TEM). Scanning electron microscopy (SEM) showed that the density of endothelial fenestrae decreased to about 80% of control in gentamicin- and tobramycin-treated rats. In addition, gentamicin and tobramycin produced a marked reduction in the number of granulated myoepithelioid++ cells of the juxtaglomerular apparatus. Netilmicin appeared to have no effect on glomerular ultrastructure. Both TEM and SEM, indicate that the nephrotoxic aminoglycosides gentamicin and tobramycin alter the ultrastructure of the fenestrated endothelia of the glomerular capillaries. These ultrastructural changes appear to be correlated to the impairment of the glomerular permeability for different compounds.