Influence of Grip Strength on Metacarpal Bone Mineral Density in Postmenopausal Japanese Women: A Cross-Sectional Study

Most published studies on the role of muscle strength in the maintenance of bone mineral density (BMD) focused on the relationship between specific muscle groups and adjacent bones, mostly in young and premenopausal women. This study examined the influence of grip strength on BMD of the metacarpal index in postmenopausal Japanese women. Subjects included 1168 postmenopausal women aged 40–70 years. BMD measurement was done with computed X-ray densitometry (CXD) by analyzing X-ray films of the right second metacarpal index. Grip strength was measured in both the dominant and nondominant hands using a squeeze dynamometer. Grip strength (r = 0.2474; P= 0.0001) and age (r =−0.5443; P= 0.0001) significantly correlated positively and negatively, respectively, with BMD. Physical activity (r = 0.1318; P= 0.0001) also correlated positively with BMD. Breastfeeding (r =−0.1658; P= 0.0001), however, correlated negatively with BMD. Subjects with a history of regular physical activity had higher grip strengths and BMD, than those with no physical activity. Adjustment for age, physical activity, calcium intake, BMI, breastfeeding, testing site, and menopausal type indicated a significant (P for trend = 0.0013) positive association of grip strength with BMD. Subjects with stronger grip strengths had a decreased risk for low BMD. Received: 24 February 1998 / Accepted: 7 August 1998     

Rapid pulse injection of indocyanine green angiography for evaluation of choroidal venous circulation]

PURPOSE: To investigate the influence of the injection duration on the early phase of indocyanine green fundus angiography, we performed indocyanine green fundus angiography using a rapid pulse injection method, and compared early-phase findings with those obtained using a previous injection method. METHODS: Rabbit eyes were used. Normal eyes (10), eyes with chorioretinal atrophy (5), and eyes with occlusion of vortex veins (5) were examined. RESULTS: In normal eyes, rapid pulse injection resulted in visualization of some small bright fluorescent boluses from 6 to 12 seconds after injection, whereas with the previous method they were unclear. In eyes with occlusion of vortex veins, rapid pulse injection resulted in visualization of delayed hyperfluorescence of choroidal veins against the background, and the region of delayed venous filling could easily be determined. In eyes with chorioretinal atrophy, only the rapid pulse injection clearly revealed delayed filling of choroidal veins. CONCLUSIONS: The rapid pulse injection method enabled detection of lesions which were not clearly visible using the previous injection method, and is useful for study of choroidal circulation.     

In vitro schedule-dependent interaction between paclitaxel and SN-38 (the active metabolite of irinotecan) in human carcinoma cell lines

Paclitaxel and irinotecan are important new anticancer agents. The combination of these two agents has been considered for use against a variety of advanced solid tumors. Since the schedule-dependent effects of this combination may be crucial to its use, we studied the interaction of paclitaxel and SN-38 (the active metabolite of irinotecan) in various schedules in four human cancer cell lines in culture. Cell growth inhibition after 5 days was determined using an MTT assay. The effects of drug combinations at the IC₈₀ level were analyzed by the isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h produced antagonistic (subadditive and protective) effects in the human lung cancer cell line A549, the breast cancer cell line MCF7, and the colon cancer cell line WiDr, and produced additive effects in the ovarian cancer cell line PA1. Sequential exposure to paclitaxel for 24 h followed by SN-38 for 24 h, and the reverse sequence, produced additive effects in all four cell lines. These findings suggest that sequential administration, not simultaneous administration, may be the appropriate schedule for the therapeutic combination of paclitaxel and irinotecan. Continued preclinical and clinical studies should provide further insights and assist in determining the optimal schedule for this combination in clinical use. Received: 25 February 1997 / Accepted: 6 November 1997     

Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma

PURPOSE: To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells. MATERIALS AND METHODS: Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed. RESULTS: The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium. CONCLUSIONS: Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions.     

中药对大鼠自发性慢性胰腺炎的干预作用及其方证病态基础

目的探讨桂枝汤、柴胡桂枝汤、小柴胡汤和卡莫司他对大鼠自发性慢性胰腺炎的干预作用及其方证病态基础。方法57只雄性4周龄WBN/Kob大鼠随机分为5组模型组、桂枝汤组、柴胡桂枝汤组、小柴胡汤组和卡莫司他组,每组大鼠均予以相应药物干预,共12周。每4周取大鼠胰腺组织观察胰腺湿重;HE染色观察胰腺组织病理学改变;RT-PCR技术检测大鼠胰腺胰腺炎相关蛋白(pancreatitis-associatedprotein,PAP)mRNA的表达水平;免疫组织化学方法检测胰腺PAP蛋白的表达。结果模型组自12周龄起胰腺组织发生胰腺炎病理学改变;桂枝汤组未观察到胰腺炎病理学改变;小柴胡汤组和卡莫司他组在16周龄时,胰腺组织均发生明显的胰腺炎病理学改变。桂枝汤组抑制PAPmRNA表达的作用大于其他各中药干预组。桂枝汤组和柴胡桂枝汤组在12周龄时,未发现胰腺PAP的表达。结论桂枝汤、柴胡桂枝汤、小柴胡汤和卡莫司他对大鼠自发性慢性胰腺炎具有不同程度的防治作用,其中以桂枝汤的作用最为明显。“太阳表证”可能是大鼠自发性慢性胰腺炎的中医基本证候病机,PAP的表达可能是其证候病机的病态基础之一。     

Intraoperative hemodilutional autotransfusion using a closed circuit for patients of Jehovah's Witness

We conducted hemodilutional autotransfusion using a closed circuit combined with a cell washing reinfusing system (Cell Saver) for two surgical patients of Jehovah's Witness. One was a 12 yr-old boy for extirpation of the teratoma in the anterior mediastinum and another was a 44 yr-old woman for left total hip replacement. The patients and their relatives had consented to the use of blood substitutes, hemodilutional autotransfusion using a closed circuit and Cell Saver. We devised a closed circuit system for hemodilutional autotransfusion combined with Cell Saver, in which two pumps for blood transfusion were used; one was for drawing blood from the femoral or the internal jugular vein and the other for returning blood to the peripheral vein. Blood volume in a bag interposed in the closed circuit was easily controlled by adjusting the speed of each pump. Blood collected from the surgical field by Cell Saver was also led to the bag. Acid citrate dextrose solution was infused into the closed circuit from the site close to the blood drawing. Both of our surgical patients were safely managed without homologus blood transfusion, although there remained some problems concerning the use of anticoagulants.     

Mechanistic Study of the Oxidative Degradation of the Triazole Antifungal Agent CS-758 in an Amorphous Form

In this study, the degradates generated from a pharmaceutical solid were characterized, and a mechanistic pathway underlying their formation was proposed. The chemical stability of a novel triazole antifungal drug, CS‐758, deteriorated significantly when the crystal was disordered, and characteristic degradates were generated. A total of eight degradates in solution and nine degradates in a solid state were isolated by preparative liquid chromatography. Degradates were characterized using high‐performance liquid chromatography–photodiode array, mass spectrometry, and nuclear magnetic resonance. Radical‐mediated oxidation is proposed as the main degradation pathway in the solid state. The initiation step of this pathway is hydrogen atom abstraction from a methine carbon that is adjacent to a dien moiety and the formation of a delocalized vinylic radical intermediate. Molecular oxygen is then added to the radical position to form hydroperoxides. There are three potential oxidation routes based on the proposed autoxidation pathway that lead to the generation of the dioxane ring‐opening hydroxyl form, the 9,10‐epoxide form, or the 11,12‐epoxide form, depending on the substituted position of the added molecular oxygen. The epimer compound generated via the vinylic radical intermediate and sulfoxides was characterized. This degradation mechanism provides the scientific foundation for an oxidative stressing system currently under investigation.     

A Flexible Urban Health Index for Small Area Disparities

Available urban health metrics focus primarily on large area rankings. Less has been done to develop an index that provides information about level of health and health disparities for small geographic areas. Adopting a method used by the Human Development Index, we standardized indicators for small area units on a (0, 1) interval and combined them using their geometric mean to form an Urban Health Index (UHI). Disparities were assessed using the ratio of the highest to lowest decile and measurement of the slope of the eight middle deciles (middle; 80 %) of the data. We examined the sensitivity of the measure to weighting, to changes in the method, to correlation among indicators, and to substitution of indicators. Using seven health determinants and applying these methods to the 128 census tracts in the city of Atlanta, USA, we found a disparity ratio of 5.92 and a disparity slope of 0.54, suggesting substantial inequality and heterogeneity of risk. The component indicators were highly correlated; their systematic removal had a small effect on the results. Except in extreme cases, weighting had a little effect on the rankings. A map of Atlanta census tracts exposed a swath of high disparity. UHI rankings, ratio, and slope were resistant to alteration in composition and to non-extreme weighting schemes. This empirical evaluation was limited to a single realization, but suggests that a flexible tool, whose method rather than content is standardized, may be of use for local evaluation, for decision making, and for area comparison.     

Enhanced Percolation and Gene Expression in Tumor Hypoxia by PEGylated Polyplex Micelles

In regard to gene vectors for cancer gene therapy, their percolation into the tumor tissue should be essential for successful outcome. Here, we studied the tumor penetrability of nonviral vectors (polyplexes) after incubation with the multicellular tumor spheroid (MCTS) models and intratumoral (i.t.) injection into subcutaneous tumors. As a result, polyethylene glycolated (PEGylated), core–shell type polyplexes (polyplex micelles) showed facilitated percolation and improved transfection inside the tumor tissue, whereas conventional polyplexes from cationic polymers exhibited limited percolation and localized transfection. Furthermore, the transfection of hypoxia-responsive plasmid demonstrated that polyplex micelles allowed the transfection to the hypoxic region of the tumor tissue in both in vitro and in vivo experiments. To the best of our knowledge, our results demonstrated for the first time that polyplex micelles might show improved tumor penetrability over cationic polyplexes, thereby achieving transfection into the inside of the tumor tissue.