Investigation of the effect of space environment on the contents of atropine and scopolamine in Datura metel by capillary zone electrophoresis

The seeds of Datura metel were carried aboard a retrievable satellite and exposed to space environment. The effects of space environment (weightlessness and ionizing radiation) on the contents of atropine and scopolamine in D. metel were investigated by using an effective capillary zone electrophoresis (CZE) method, which employed 50 mmol/l phosphate buffer (pH 8) containing 10% (v/v) tetrahydrofuran as the running buffer. The results showed that the contents of atropine and scopolamine varied to some extent, and the earth-control group has the lowest content of atropine. However, the variation of atropine and scopolamine contents in three groups was not obvious based on t-test. At the same time, the optimization of the separation was discussed in detail and the two compounds were completely separated within 10 min with satisfactory repeatability and calibration linearity.     

Novel Calbindin-D(9k) protein as a useful biomarker for environmental estrogenic compounds in the uterus of immature rats

The compounds that bind the estrogen receptors (ER) and induce or modulate an ER-mediated response can be defined as estrogenic endocrine disruptors (EDs). We demonstrated that environmental estrogens induced the uterine CaBP-9k mRNA in rats using Northern blot assay suggesting that CaBP-9k gene could be a biomarker for the estrogenicity of chemicals in the previous studies. In the present studies, we further collaborated this idea by investigating the regulation and localization of CaBP-9k protein in response to estrogenic compounds. Immature rats were injected with estrogenic chemicals, 4-tert-octylphenol (OP), nonylphenol (NP) and bisphenol A (BPA) or 17beta-estradiol (E2). After treatment with these estrogenic compounds, the effects on the accumulation of CaBP-9k protein and uterine localization were examined by Western blot analysis and immunohistochemical staining (IHC), respectively. A dose- and time-dependent increase in CaBP-9k protein was observed in the uterus of immature rats when treated with OP and NP. In addition, treatment with BPA resulted in a significant increase in CaBP-9k protein at dose of 500mg/kg BW/day. Taken together, CaBP-9k protein is strongly up-regulated by estrogenic compounds (OP, NP and BPA) and E2 itself in the uterus of immature rats. These results indicate that CaBP-9k protein can be a useful biomarker for detection of the estrogenicity of putative estrogenic compounds. Thus, regarding to risk assessment, we propose that CaBP-9k protein assay in the immature rat uterus can be a very sensitive and powerful tool to identify compounds with estrogenic activity when used in combination with classical assays.     

Ras transgene expression in TG-AC mice treated with benzo[a]pyrene

Transgene expression and skin tumorigenicity were investigated in transgenic TG-AC mice carrying the v-Ha-ras after treatment with benzo[a]pyrene (BP). Animals treated with 40 microg BP (x2/week/mouse) showed 100% tumor response after 25 weeks, as did 40% of the mice treated with 20 microg BP but 10 microg BP did not produce a tumor response. In the case of animals treated with 40 microg BP for 25 weeks, most of the tumors were proven to be carcinomas (80%, 4 out of 5 mice), and all tumors were shown to be positive in terms of transgene expression detected by in situ hybridization. These data suggest that BP was tumorigenic in a dose-dependent manner in TG-AC mice and that TG-AC mice were dependent on transgene expression during BP carcinogenesis.     

Hypotensive effect of butein via the inhibition of angiotensin converting enzyme

Butein (3,4,2',4'-tetrahydroxychalcone), a plant polyphenol, has been known to elucidate endothelium-dependent vasodilation. In the present study, the hypotensive effect of butein and its possible mechanism, especially an angiotensin converting enzyme (ACE) inhibitory effect, were investigated. Intravenous injection of butein lowered the arterial blood pressure of anesthetized rats in a dose-dependent manner. The plasma ACE activities were significantly inhibited by the addition of butein in a dose-dependent manner, the IC(50) value of which was 198 microg/ml (730 microM). Moreover, angiotensin I-induced contraction was markedly attenuated by prior exposure of endothelium-intact aortic rings to butein, but angiotensin II-induced contraction was not altered. These results suggest that butein has a hypotensive effect, at least in part, via the inhibition of angiotensin converting enzyme.     

Inhibitory effects of nardostachin on nitric oxide, prostaglandin E2, and tumor necrosis factor-alpha production in lipopolysaccharide activated macrophages

Nardostachin, which is an iridoid isolated from Patrinia saniculaefolia, was examined by assessing its effect on the production of tumor necrosis factor-alpha (TNF-alpha) and expression of 2 enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. This compound consistently inhibited the production of nitric oxide (NO) and TNF-alpha production in a dose-dependent manner, with respective IC(50) values of 12.3 and 16.2 microM. The decrease in quantity of NO products was accompanied by a decrease in the iNOS protein level, as assessed by Western blotting probed with specific anti-iNOS antibodies. In addition, this compound also reduced the COX-2 protein expression level and the attendant PGE(2) production in LPS-stimulated macrophages. These results suggest that nardostachin may be useful for inhibiting the production of inflammatory mediators such as TNF-alpha, NO and PGE(2) in inflammatory diseases.     

Neural responses to relative speed in the primary visual cortex of rhesus monkey

Relative motion information, especially relative speed between different input patterns, is required for solving many complex tasks of the visual system, such as depth perception by motion parallax and motion-induced figure/ground segmentation. However, little is known about the neural substrate for processing relative speed information. To explore the neural mechanisms for relative speed, we recorded single-unit responses to relative motion in the primary visual cortex (area VI) of rhesus monkeys while presenting sets of random-dot arrays moving at different speeds. We found that most VI neurons were sensitive to the existence of a discontinuity in speed, that is, they showed higher responses when relative motion was presented compared to homogenous field motion. Seventy percent of the neurons in our sample responded predominantly to relative rather than to absolute speed. Relative speed tuning curves were similar at different center-surround velocity combinations. These relative motion-sensitive neurons in macaque area VI probably contribute to figure/ground segmentation and motion discontinuity detection.     

The impact of financial incentives and a patient registry on preventive care quality: increasing provider adherence to evidence-based smoking cessation practice guidelines

BACKGROUND: This study tested the effects of two organizational support processes, the provision of financial incentives for superior clinical performance and the availability of a patient (smoker) registry and proactive telephone support system for smoking cessation, on provider adherence to accepted practice guidelines and associated patient outcomes. METHODS: Forty clinics of a large multispecialty medical group practice providing primary care services were randomly allocated to study conditions. Fifteen clinics each were assigned to the experimental conditions "control" (distribution of printed versions of smoking cessation guidelines) and "incentive" (financial incentive pay-out for reaching preset clinical performance targets). Ten clinics were randomized to receive financial incentives combined with access to a centralized patient registry and intervention system ("registry"). Main outcome measures were adherence to smoking cessation clinical practice guidelines and patients' smoking cessation behaviors. RESULTS: Patients' tobacco use status was statistically significant (P < 0.01) more frequently identified in clinics with the opportunity for incentives and access to a registry than in clinics in the control condition. Patients visiting registry clinics accessed counseling programs statistically significantly more often (P < 0.001) than patients receiving care in the control condition. Other endpoints did not statistically significantly differ between the experimental conditions. CONCLUSIONS: The impact of financial incentives and a patient registry/intervention system in improving smoking cessation clinical practices and patient behaviors was mixed. Additional research is needed to identify conditions under which such organizational support processes result in significant health care quality improvement and warrant the investment.     

<Emphasis Type="Italic">Scutellaria baicalensis</Emphasis> extract decreases cisplatin-induced pica in rats

Purpose Nausea/vomiting are significant side effects associated with the use of chemotherapy in cancer patients. Treatment of nausea/vomiting caused by cisplatin, a potent chemotherapeutic agent and one of the most emetogenic stimuli, requires a combination of different antiemetic drugs. In this study, we investigated the effects of Scutellaria baicalensis, an antioxidant herbal medicine, on cisplatin-induced nausea using a rat model.Methods Rats react to emetic/nausea-producing stimuli, such as cisplatin, with altered feeding habits, manifested by pica or increased consumption of kaolin (a type of clay). We measured pica in rats to quantify cisplatin-induced nausea, and to evaluate the antinausea effect of pretreatment with S. baicalensis extract (SbE) given intraperitoneally.Results Cisplatin at 3 mg/kg induced significant pica accompanied by reduced food intake, suggesting the presence of nausea. Hence, this cisplatin dose was selected for testing the antinausea activity of SbE. Cisplatin-induced pica decreased significantly when animals were pretreated with SbE at doses of 1 mg/kg and 3 mg/kg (P<0.01). At a higher SbE dose (10 mg/kg), kaolin consumption increased, rather than further decreased, and was significantly different from that in the groups treated with low SbE doses.Conclusions SbE pretreatment decreased cisplatin-induced kaolin intake in the rat model of simulated nausea, suggesting that SbE and its active constituent(s) may play a therapeutic role in chemotherapy-induced emesis. Absence of therapeutic effect at the highest tested SbE dose could have been a result of prooxidant activity often associated with excess antioxidant concentration.This work was supported in part by NIH grants R01 CA79042, P30 CA14599, and R21 AT00381.     

平喘冲剂治疗小儿哮喘临床观察

为观察平喘冲剂治疗小儿哮喘的临床疗效,将196例患儿随机分为治疗组100例口服中药平喘冲剂,对照组96例静脉滴注青霉素、氨茶碱,疗程1周,观察治疗前后喘憋、咳嗽、紫绀、哮鸣音、肺功能、肺阻抗血流的变化。结果：治疗组总有效率为98．00％,对照组总有效率为93．75％,各项检测指标治疗组均优于对照组。提示平喘冲剂具有平喘止咳、化痰通瘀的作用。     

Dihydropyridines as inhibitors of capacitative calcium entry in leukemic HL-60 cells

A series of 1,4-dihydropyridines (DHPs) were investigated as inhibitors of capacitative calcium influx through store-operated calcium (SOC) channels. Such channels activate after ATP-elicited release of inositol trisphosphate (IP(3))-sensitive calcium stores in leukemia HL-60 cells. The most potent DHPs were those containing a 4-phenyl group with an electron-withdrawing substituent, such as m- or p-nitro- or m-trifluoromethyl (IC(50) values: 3-6 microM). Benzyl esters, corresponding to the usual ethyl/methyl esters of the DHPs developed as L-type calcium channel blockers, retained potency at SOC channels, as did N-substituted DHPs. N-Methylation reduced by orders of magnitude the potency at L-type channels resulting in DHPs nearly equipotent at SOC and L-type channels. DHPs with N-ethyl, N-allyl, and N-propargyl groups also had similar potencies at SOC and L-type channels. Replacement of the usual 6-methyl group of DHPs with larger groups, such as cyclobutyl or phenyl, eliminated activity at the SOC channels; such DHPs instead elicited formation of inositol phosphates and release of IP(3)-sensitive calcium stores. Other DHPs also caused a release of calcium stores, but usually at significantly higher concentrations than those required for the inhibition of capacitative calcium influx. Certain DHPs appeared to cause an incomplete blockade of SOC channel-dependent elevations of calcium, suggesting the presence of more than one class of such channels in HL-60 cells. N-Methylnitrendipine (IC(50) 2.6 microM, MRS 1844) and N-propargylnifrendipine (IC(50) 1.7 microM, MRS 1845) represent possible lead compounds for the development of selective SOC channel inhibitors.