香兰酸异丙胺盐的降压作用

香兰酸异丙胺盐iv 5mg/kg、10mg/kg,对麻醉大鼠有显著的降压作用,且呈剂量依赖关系,在降压的同时伴有心率减慢。 对毁脊髓大鼠标本,结果与哌唑嗪不同,不能使苯福林的量效曲线平行右移,对兔主动脉条也无直接扩张作用。但可使大鼠右房异丙肾上腺素的剂量—频率反应曲线平行右移,最大反应不变,其pA_2值为3.9,明显弱于普萘洛尔。     

小唐松草碱的降压作用

小唐松草碱(ocoteine)1～10 mg/kg iv对麻醉、清醒的正常血压大鼠和肾性高血压大鼠均有迅速而持久的降压作用,脑室内注射给药也有明显的降压作用。切断双侧迷走神经合用阿托品,及用苯海拉明不影响 ocoteine的降压作用。在毁脊髓大鼠,ocoteinc 1～3mg/kg使甲氧明的量效曲线平行右移,而不影响B-HT920的量效曲线。结果提示ocoteine选择性阻断血管性平滑肌突触后α_1受体,并可能具有中枢性降压作用;其降压作用不是通过迷走神经或释放组胺。     

布诺洛尔和普萘洛尔对β肾上腺素受体阻断作用的比较

布诺洛尔(10~(-3),10~(-7),10~(-6)mol/L)能使离体兔右心房肌和豚鼠气管条对Iso所致正性变时性和负性变力性作用的量—效曲线平行右移,pA_2为9.3和9.1。布诺洛尔对心脏β_1受体阻断作用比普荼洛尔强约5倍,对气管β_2受体阻断作用比普荼洛尔强约2.6倍,对心脏β_1受体阻断作用比对气管β_2受体阻断作用略强(约1.6倍)。布诺洛尔(1mg/kg)能完全阻断肾上腺素(10μg/kg)所致大鼠降压反应,对利血平化动物血压及心率无明显影响。     

异钩藤碱的降压及血流动力学作用(英文)

在清醒正常血压大鼠,iv Isorhy2.5 mg/kg对BP及HR均无明显影响,iv5 mg/kg则使DAP和HR降低,但SAP无变化,剂量加大至10 mg/kg时,上述各项指标均明显降低。经十二指肠内给Isorhy10 mg/kg后20 min出现BP及HR降低,而20mg/kg剂量组于10 min开始出现BP及HR的进一步下降.Isorhy(10mg/kg和2 mg/kg,iv)亦能分别降低肾性高血压清醒大鼠和麻醉犬的BP。icv表明中枢不是降压作用的主要部位,在体条件下无α-受体和神经节阻断作用。Isorhy使清醒大鼠和麻醉犬的LVSP,dP/dt_(max),V_(max)等左室收缩性能指标短暂下降,而BP呈持久性降低。在麻醉犬给药后CO,CI,HR及LVWI下降的同时SV和SI不变,TPVR降低,反映心肌氧耗的TTI明显减少.结果提示Isorhy具有肯定的降压作用,其持续降压与扩张血管及减慢心率导致CO下降有关,而其负性肌力作用亦可能参与了早期的降压机理.Isorhy能减少心肌氧耗对高血压心肌劳损可能有保护意义。     

1-(对羟苄基)-N-甲基-6-甲氧基-7-羟基异喹啉对α肾上腺素受体的作用

在大鼠输精管上,BMIQ 10μmol/L和YHB 1μmol/L都能使CLN的量效曲线平行右移,最大反应不变,表明二者均能竞争性地阻断突触前α_2受体,其pA_2值分别为6.69和7.8.大鼠肛尾肌实验表明,BMIQ亦有竞争性拮抗突触后α_1受体作用,pA_2值为5.14。其α_2/α_1阻断作用之比率为35.5,说明BMIQ对α_2受体的选择性大于α_1受体.BMIQ和YHB在毁脊髓大鼠标本上,均能使B—HT920升高舒张血压的量效曲线平行右移,最大反应不变.二者的剂量比率分别为2.7和14.8,且BMIQ抗突触后膜α_2受体作用仅为YHB的1/5.5。     

苄基四氢巴马汀对α和β等受体的影响

苄基四氢巴马汀(BTHP)使苯福林对大鼠肛尾肌和兔主动脉条作用的累积量效曲线平行右移,最大反应不压低,pA_2值分别为5.86和5.8,但对甲氧明和B-HT920升高DP作用的量效曲线无明显影响。BTHP可使异丙肾上腺素和组胺正性频率作用的量效曲线非平行右移,最大反应压低。BTHP还能明显缩短大鼠再灌流所致心律失常的持续时间。结果提示,BTHP对α_1受体的阻断及对β和H_2受体的非竞争性拮抗作用可能与该药抗心律失常作用有部分关系但并非其主要机理。     

小檗碱的负性变时作用

小檗碱(Ber)4mg/kg ⅳ使正常大鼠的血压(BP)降低,心率(HR)不变;迷走神经切断大鼠的BP降低,HR减慢;毁脊髓大鼠的HR减慢,BP不变。在离体豚鼠右心房,Ber产生负性变时作用,且不被阿托品对抗。Ber使异丙肾上腺素、组胺和CaCl_2正性变时作用的量效曲线非平行性右移,最大反应压低,呈非竞争性拮抗作用,其pD_2分别为4.82,4.51和4.68。结果表明Ber对正常大鼠的负性变时作用,可因其降压所致的反射性HR加快而抵消。Ber的负性变时作用可能与心肌M,β和H_2受体无关,也不是选择性阻滞Ca~(2+)内流所致。     

甲基莲心碱降低血压及松弛血管作用的分析

甲基莲心碱(neferine,Nef)对自发性高血压大鼠有明显的降压作用,ig给药降压作用可维持3h以上。对由高钾去极化引起的兔主动脉环收缩的抑制作用为维拉帕米(verapamil,Ver)的1/792,使CaCl_2及甲氧明(methoxamine,Met)的量效曲线平行右移,最大反应前者压低、后者不变,pD_2及pA_2值分别为5.4及6.3。还抑制由去甲肾上腺素(norepinephrine,NE)引起的依内钙收缩反应,提示Nef对α_1肾上腺素受体有阻断作用及较弱的钙拮抗作用。     

内皮素受体拮抗剂抑制异丙肾上腺素诱导大鼠心肌细胞搏动加速及凋亡

观察内皮素受体拮抗剂CPU0213能否阻断异丙肾上腺素(isoprenaline,ISO)所致大鼠心肌细胞搏动加速及凋亡。分离大鼠心肌细胞。给ISO(10-7M)的同时给CPU0213(10-7、10-6、10-5M),并以普萘洛尔(10-6M)作为阳性药对照,观察各组心肌细胞的搏动次数。采用吖啶橙/碘化丙啶(AO/PI)染色法检测成年大鼠心肌细胞凋亡率的变化。普萘洛尔明显抑制ISO效应(P<0.001)。内皮素受体拮抗剂CPU0213明显抑制ISO所致的心肌细胞搏动和细胞凋亡,且呈浓度依赖性。大剂量CPU0213对ISO生物效应的阻断作用(P<0.001)与普萘洛尔相仿。内皮素受体拮抗剂CPU0213阻断ISO所致的心肌细胞搏动加速和增加细胞凋亡率等生物学效应,提示内皮素介导β-受体效应。     

左旋四氢巴马汀对5-羟色胺所致血管收缩作用的影响

在毁脊髓大鼠,5-羟色胺iv引起舒张压升高。左旋四氢巴马汀预先ia对此升压效应具有剂量相关的明显抑制作用,其ID_(50)为27mg/kg。以兔离休肺动脉环标本测定5-HT,NE,KCl引起的收缩反应。左旋四氢巴马汀使5-HT量效曲线平行右移,PA_2值为4.64。对NE,KCl所致收缩也有拮抗作用。提示左旋四氢巴马汀具有一定的抗5-HT作用,但专一性较低。     

盐酸普萘洛尔在角质层内的吸附与经皮渗透

用离体的大鼠腹部皮肤研究盐酸普萘洛尔的经皮渗透过程,并分离出角质层进行吸附实验。结果表明,盐酸普萘洛尔在角质层内的吸附符合Langmuir吸附等温式,通过全皮的渗透系数和时滞随浓度提高而减小,而通过剥离角质层的活性皮肤渗透系数和时滞不受浓度影响。根据吸附扩散理论,提出了药物在角质层内渗透系数与浓度的关系式,讨论了浓度与时滞的关系。     

Review of the Association Between Treatment for Substance Misuse and Reductions in Intimate Partner Violence

A substantial body of research supports a strong cross-sectional and longitudinal association between substance misuse and perpetration of intimate partner violence (IPV). This article briefly addresses the theoretical connection between substance use and intimate partner violence and research on the association between substance misuse and IPV. Studies examining the effect of individual and couples-based addiction treatments on IPV are reviewed. The implications of this work and future directions for research are discussed.     

The association between alcohol use and intimate partner violence: linear effect, threshold effect, or both?

The present study examined whether the association between alcohol and male-to-female intimate partner violence (IPV) is most meaningfully described as a linear relationship, a threshold effect, or both. Men in two nationally representative samples, the National Family Violence Survey (NFVS) and the National Survey of Families and Households (NSFH), were divided into similar drinking groups based on quantity and frequency of alcohol consumption. Analyses of the association between IPV and drinking category revealed that although linear associations between drinking classification and IPV were significant in both samples, the associated effect sizes were very small. Further, only heavy drinkers and binge drinkers were major contributors to the significant chi-squares. Overall, the results revealed both linear and threshold effects, and suggest that distinctions among drinking patterns may be more important than incremental increases in quantity or frequency in conceptualizing alcohol as a risk factor for IPV.     

Intimate partner violence outcomes in women with PTSD and substance use: A secondary analysis of NIDA Clinical Trials Network “Women and Trauma” Multi-site Study

Studies have shown strong associations between intimate partner violence (IPV) and both posttraumatic stress disorder (PTSD) and substance use disorders (SUD). Despite these linkages, research on the dual diagnosis of PTSD–SUD and its relationship to IPV is in an early stage, and little is known about how PTSD–SUD treatment might influence IPV outcomes. The current study is a secondary analysis of a larger NIDA Clinical Trials Network study exploring the effectiveness of two behavioral interventions for women with comorbid PTSD–SUD. Participants (n = 288) were randomly assigned to Seeking Safety (SS), a cognitive-behavioral treatment that focuses on trauma and substance abuse symptoms, or to Women's Health Education, a psychoeducational group. Logistic regressions were used to examine how treatment condition, identified risk factors and their interactions were related to IPV. Results showed that participants who were abstinent at baseline were significantly less likely to experience IPV over the 12-month follow-up period, whereas participants living with someone with an alcohol problem were significantly more likely to experience IPV over follow-up. Findings also showed that at a trend level participants with recent interpersonal trauma at baseline and higher total of lifetime trauma exposures were more likely to report IPV during follow-up. Although there was no main effect for treatment condition, a significant interaction between treatment condition and baseline abstinence was found. Participants who were abstinent at baseline and in the SS condition were significantly less likely to report IPV over follow-up. These findings indicate that an integrated treatment for PTSD and SUD was associated with significantly better IPV outcomes for a subset of individuals. The possibility that women with PTSD–SUD may differentially benefit from SS has important clinical implications. Further research examining the intersection of PTSD, SUD and IPV, and the impact of treatment on a range of outcomes is needed.     

Evaluating Barriers to Bioavailability in Vivo: Validation of a Technique for Separately Assessing Gastrointestinal Absorption and Hepatic Extraction

PURPOSE: The purpose of this study was to develop and validate a method for separately evaluating the roles of gastrointestinal absorption and hepatic extraction as barriers to oral bioavailability (BA). The method was validated using five reference compounds known to have different absorption and hepatic extraction properties. Dose-dependence was also investigated for one reference compound. METHODS: Five reference compounds, amoxicillin, antipyrine, atenolol, propranolol, and testosterone, were administered as a cassette intravenouly (IV), via the hepatoportal vein (IPV), intraduodenally (ID), and intracolonically (IC) to male Sprague-Dawley rats. Blood samples were taken at nine time points, and the compounds were extracted from plasma using solid phase extraction. Plasma concentrations of each compound were determined using Liquid Chromatography Tandem Mass Spectrometry (LC/MS/MS). Pharmacokinetic parameters including bioavailability were calculated for each compound for each route of administration. RESULTS: Testosterone BA was less than 10% by ID, IC, and IPV routes, due to high hepatic extraction, consistent with its high systemic clearance (63 ml x min(-1) x kg(-1)) and short terminal plasma half-life (23 min). The IPV BA of amoxicillin was 95%+/-6% indicating the absence of hepatic extraction in the rat, but with an ID BA of approximately 39% suggesting incomplete GI absorption to be the main barrier to bioavailability. Absorption was poor from the colon, demonstrating site-dependence consistent with literature reports of site-dependent absorption. Low oral BA of propranolol was due in part to first-pass hepatic extraction (IPV BA of 36%). The IPV BA of propranolol was dose-dependent, most likely due to saturation of the P450 enzymes. Atenolol was incompletely bioavailable due to incomplete intestinal absorption, with no contribution of hepatic first-pass metabolism. Antipyrine was highly bioavailable by all routes. CONCLUSIONS: This in vivo rat model is demonstrated to be useful for identifying and quantifying the causes of incomplete bioavailabilty. It separately evaluates intestinal absorption, hepatic extraction, and site-dependent absorption. Concentration-dependence of saturable processes can also be examined.     

脊髓灰质炎灭活疫苗抗原含量检测方法的研究进展

脊髓灰质炎灭活疫苗(inactived poliovirus vaccine ,IPV)的问世使全球范围内消灭脊髓灰质炎成为可能,而且IPV在全球致力于消灭脊髓灰质炎中的作用日益增强.通过IPV D抗原检测可以检测IPV效力,因此IPV D抗原的快速定量检测成为亟待解决的关键问题.目前,最常用的体外检测法是ELISA法,然而,尚无国际公认的标准IPV效力检测法.此文就IPV抗原含量检测方法的研究进展加以综述.     

Risk Factors for Recent Intimate Partner Violence among Methamphetamine-Using Men and Women

The Substance Abuse, Violence, and HIV/AIDS (SAVA) syndemic model describes how the confluence of the three epidemics of substance abuse, violence, and HIV risk work synergistically to create excess burden among populations. We sought to identify risk factors associated with recent intimate partner violence (IPV) victimization among heterosexual methamphetamine (meth)-using men (n = 108) and women (n = 122) enrolled in FASTLANE-II, an HIV behavioral intervention in San Diego, CA. Women and men reported high rates of physical-only (women: 20%; men: 18%) and sexual (women: 25%; men: 23%) IPV. Multinomial regression analysis revealed that individuals who reported lower social support and individuals who reported a greater likelihood of engaging in risky sexual behaviors while high on meth were more likely to report IPV versus no IPV. Women who reported a greater likelihood of engaging in risky sexual behaviors while high on meth were 1.58 times more likely to report physical-only IPV versus no IPV, while men who reported similar behaviors were 1.15 times more likely to report physical-only IPV versus no IPV. Our findings highlight the influence of interpersonal factors on IPV. This research supports further study on gender-specific risk/protective factors and the development of gender-specific interventions targeting the SAVA syndemic among meth users.     

脊髓灰质炎灭活疫苗和减毒活疫苗联合接种效果分析

目的：探讨脊髓灰质炎灭活疫苗（IPV）和减毒活疫苗（OPV）不同联合接种方式的临床效果。方法本研究为队列研究,将2009~2013年内收集的在管辖区域具备进行计划免疫4个部门的2400例新生儿进行随机分组,其中一组进行1剂IPV和2剂OPV序贯（I-O-O）（A组）,另一组2剂IPV和1剂OPV序贯（I-I-O）（B组）,并观察两组新生儿进行接种后的反应。结果这两种方式对于新生儿计划免疫无明显的差异。结论这两种方式对于新生儿进行脊髓灰质炎的计划免疫无不良反应。     

Psychosocial and substance-use risk factors for intimate partner violence

OBJECTIVE: Few emergency department (ED) studies have described the relationship between family violence and subsequent intimate partner violence (IPV) or accounted for partner alcohol use in IPV victimization. This study sought to identify family history and substance-use factors associated with IPV among women presenting to an urban emergency department. METHODS: Case-control study in which cases (women identified as having IPV concerns and an IPV history) and controls (women without IPV) were frequency-matched by age group and race/ethnicity. Logistic regression was performed to calculate adjusted odds ratios (AOR) for any IPV, physical IPV, and sexual IPV. RESULTS: The sample included 182 cases and 147 controls. Living with a partner (not married) and witnessing parental violence were independent risk factors for any IPV (AOR 2.55 and AOR 2.21, respectively). Partner's alcohol use (AOR 1.22 for every five drinks consumed per week) and heavier drinking (AOR 5.07) were also significant risk factors, but not subject's substance-use. The pattern of risk factors varied only slightly for physical IPV and sexual IPV. CONCLUSION: This study suggests a substantial relationship between partner alcohol use and IPV among women beyond the woman's substance-use and confirms previous reports regarding the cycle of violence in women's lives.     

Legal factors associated with change in alcohol use and partner violence among offenders

Intimate partner violence (IPV) is a pervasive social concern that may be exacerbated by high rates of alcohol dependence among perpetrators. Society has attempted to combat IPV through various legal interventions, but the effects of specific legal factors on behavioral change and treatment compliance remain largely unexamined. The primary focus of the current study was to comprehensively evaluate the impact of various legal factors (i.e., judicial mandate, judicial monitoring, stage of change, and stake in conformity) on mandatory treatment compliance and behavioral change over a 12 week post-adjudication period among a high-risk sample of alcohol dependent IPV offenders (N = 60). Growth curve analyses revealed effects of judicial monitoring and stage of change such that participants reporting low perceived judicial monitoring and early stages of change reported higher initial levels and a more rapid reduction in IPV than those reporting high perceived judicial monitoring and late stages of change, who reported consistently low IPV. Although we found that legal factors were poor predictors of treatment compliance and alcohol use during treatment, the association between alcohol and IPV was moderated by the legal factors. Stake in conformity was negatively associated with IPV among low alcohol users and positively associated among high alcohol users whereas stage of change was negatively associated with IPV among high alcohol users. The current results suggest that pretreatment legal factors may represent an important consideration in reducing IPV among alcohol dependent offenders. Further research is required to determine the efficacy of legal factors in isolation of treatment as well as methods of manipulating these factors to optimally compliment a prescribed course of treatment.