No abstract

Based on this short pilot study, topical dexamethasone-cyclodextrin eye drops are well tolerated, decrease central macular thickness, and improve visual acuity in DME. The results encourage comparative studies between dexamethasone cyclodextrin microparticle eye drops and other treatments for DME. (http://www.umin.ac.jp/ctr number, UMIN000001790.).

Docetaxel (DTX) is a useful chemotherapeutic drug for the treatment of hormone-refractory prostate cancer. However, emergence of DTX resistance has been a therapeutic hurdle. In this study, we investigated the effect of combining DTX with Bcl-2 family inhibitors using human prostate cancer cell lines (PC3, LNCaP, and DU145 cells). PC3 cells were less sensitive to DTX than were the other two cell lines. In contrast to ABT-199, which inhibits Bcl-2 and Bcl-w, both ABT-263 and ABT-737, which inhibit Bcl-2, Bcl-xL, and Bcl-w, significantly augmented the antitumor effect of DTX on PC3 cells. ABT-263 also enhanced the antitumor effect of DTX on a DTX-resistant PC3 variant cell line. The antitumor effect of ABT-263 was due mainly to its inhibitory effect on Bcl-xL. In a xenograft mouse model, DTX and ABT-737 combination therapy significantly inhibited PC3 tumor growth. Interestingly, although ABT-263 activated caspase-9 in PC3 cells, inhibition of caspase-9 unexpectedly promoted ABT-263-induced apoptosis in a caspase- 8-dependent manner. This augmented apoptosis was also observed in LNCaP cells. These findings indicate that Bcl-xL inhibition can sensitize DTX-resistant prostate cancer cells to DTX, and they reveal a unique apoptotic pathway in which antagonism of Bcl-2 family members in caspase-9-inhibited prostate cancer cells triggers caspase-8-dependent apoptosis.

SUMMARYA seroprevalence survey on measles, mumps, rubella and varicella was conducted on healthcare workers (HCWs) at Shimane University Hospital, Japan utilizing an enzyme immunoassay. Of 1811 HCWs tested, 91·8% were seropositive to measles, 92·1% to mumps, 89·5% to rubella and 96·3% to varicella. Sex-related differences in seroprevalence were found in rubella (males vs. females: 84·7 vs. 92·2%, P < 0·001). Moreover, males aged 30–39 years were most susceptible to rubella (22·4%), which may be attributed to the design of childhood immunization programmes in Japan. Individuals aged ⩽29 years were more susceptible to measles (14·3%) and mumps (10·9%), compared to other age groups. There were no significant sex- and age-related differences in varicella seroprevalence. The physician occupational group was more susceptible to rubella, but no significant occupational-related difference was observed in the other diseases. Susceptible subjects, with negative or equivocal serological results were given a vaccine which induced seroconversion in most vaccinees. Seroconversion occurred more frequently in the equivocal group than in the negative group. These findings provide a new insight for the seroprevalence survey of vaccine-preventable diseases in Japanese HCWs with special reference to vaccine efficacy.

Endothelial modulation of norepinephrine (NE)-induced constriction of the isolated rat aorta was studied at normal (PCO2, 41 +/- 0 mmHg) and high CO2 tensions (PCO2, 91 +/- 1 mmHg). In preparations with intact endothelium, increased CO2 tension resulted in rightward shift of the NE dose-response curve with attenuation of maximal contraction. This effect of CO2 was not modified by indomethacin. Treatment with hemoglobin or rubbing of the endothelium meant that increased CO2 tension still resulted in rightward shift of the NE dose-response curve but without altering the maximal contractile response. The basal guanosine 3',5'-cyclic monophosphate (cGMP) levels in control and NE-treated aortic preparations were not affected by increasing the CO2 tension. Thus the inhibitory action of CO2 on NE-induced contraction in the presence of endothelium may not be derived from facilitation of endothelium-derived relaxation factor (EDRF)-induced cGMP synthesis. Increasing the CO2 tension attenuated the sustained contraction induced by the addition of NE and Ca2+ (2.5 mM) to intact endothelium preparations previously bathed in Ca2(+)-free solution. Further addition of Ca2+ (total 5.0 mM) did not increase the contraction. These findings suggest that the intrinsic activity of NE is greatly modified by endothelium at a high CO2 tension. Vasodilation during hypercapnia may be induced at least in part by synergistic actions of EDRF and CO2 on smooth muscle cells.