Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

Self medication and health habits in the management of upper gastrointestinal symptoms

Upper gastrointestinal symptoms are a common complaint among the general population but only a small proportion of sufferers seek medical advice. The aim of this study was to examine what kind of perceptions persons using self medication have about the causes of their gastrointestinal symptoms, whether they have made any health-related lifestyle changes, and whether visits to a physician are related to lifestyle changes. A pharmacy-based survey was done in 10 pharmacies in the Helsinki area in 1995. The questionnaire was completed by 292 customers. The response rate was 53%. Respondents in a population-based health interview survey (n = 10,410) were used as a comparison group for poor health-behavior (consumption of tobacco, alcohol, coffee). The most common perceived causes of gastrointestinal symptoms were poor diet, coffee, and stress. Ignorance about possible causes of symptoms was especially common among less educated respondents and among those persons who had never visited a physician due to their symptoms. Respondents were significantly more often smokers and they had attempted to reduce their coffee and alcohol consumption more often than the general population. Those who had visited a physician during past year, less often had poor health-behavior and they had better knowledge about the possible causes of their symptoms. They had also made lifestyle changes more often, but after adjustment for background characteristics, physician visits were positively correlated only with coffee reduction. Counseling about healthy lifestyles, especially about smoking, should be increased in physician consultations and in pharmacies for all patients and customers having gastrointestinal problems.     

Treatment of major depressive disorder in the Finnish general population

Background : Few general population studies of the treatment of major depressive disorder (MDD) have included the whole spectrum of treatments. We estimated the rates of different treatments and the effect of individual and disorder characteristics plus provider type on treatment received. Methods : In the Health 2000 Study, a representative sample (n=6,005) from the adult Finnish population (≥30 years) were interviewed (CIDI) in 2000–2001 for the presence of DSM‐IV mental disorders during the past 12 months. Logistic regression models were used to examine factors influencing the type of treatment: either pharmacotherapies (antidepressants, anxiolytics, sedatives/hypnotics, antipsychotics) or psychological treatment. Results : Of the individuals with MDD (n=288), currently 24% used antidepressants, 11% anxiolytics, 16% sedatives/hypnotics, 5% antipsychotics, and 17% reported having received psychological treatment. Overall, 31% received antidepressants or psychological treatment or both; 18% received minimally adequate treatment. Of those 33% (n=94) using health care services for mental reasons, 76% received antidepressants or psychological treatment or both; 54% received minimal adequate treatment. In logistic regression models, the use of antidepressants was associated with female sex, being single, severe MDD, perceived disability, and comorbid dysthymic disorder; psychological treatment with being divorced, perceived disability, and comorbid anxiety disorder. Conclusions : Due to the low use of health services for mental reasons, only one‐third of subjects with MDD use antidepressants, and less than one‐fifth receives psychological treatment. The treatments provided are determined mostly by clinical factors such as severity and comorbidity, in part by sex and marital status, but not education or income. Depression and Anxiety 26:1049–1059, 2009. © 2009 Wiley‐Liss, Inc.     

Effects of Cardiomyoplasty on Cardiac Growth in Rats

A bstract Background and aim of the study : Cardiomyoplasty (CMP) has been proposed as a treatment for pediatric patients, but restriction of cardiac growth by the muscle wrap is a potential source of concern. This possibility was investigated in an immature animal model. Methods : Six-week-old rats (body weight 203.8 ± 5.4 g, mean ± SEM) underwent either left thoracotomy with CMP (group I, n = 7), or thoracotomy without CMP (group II, n = 8). A third group (group III, n = 7) served as untreated controls. Final measurements were made 20 weeks later after body weights had reached a plateau. Results : Preoperative body weights were not significantly different between the groups. At elective sacrifice, the body weights of animals that underwent surgery did not differ significantly (group I, 558.0 ± 21.5 g and group II, 617.3 ± 20.3 g), but were significantly less than those of control animals (727.6 ± 13.3 g, p < 0.001 and p < 0.01, respectively). Cardiac ventricular weights in the CMP group were significantly less than those of control animals (group I, 1.21 ± 0.06 g; group III 1.45 ± 0.04 g; p < 0.01), but were not statistically different from those of the sham thoracotomy group (group II, 1.36 ± 0.05 g). Mean left ventricular end-diastolic volumes were similar in all groups (group I, 0.67 ± 0.07 mL; group II, 0.66 ± 0.07 mL; and group III, 0.69 ± 0.10 mL; p = ns). Conclusions : A major surgical procedure impairs growth in juvenile rats. No evidence emerged from this study for additional restriction of cardiac development due to cardiac wrapping. However, studies that include stimulated muscle wraps are needed before CMP should be considered for the pediatric age group.     

Platelet membrane alterations induced by the local anesthetic dibucaine

Tertiary amine local anesthetics modify a variety of platelet membrane- related functions. The present study explored dibucaine (DB)-induced inhibition of platelet cohesion by examining structural and functional alterations of the human platelet membrane glycoprotein IIb-IIIa complex (GPIIb-IIIa) and platelet Ca2+ homeostasis. Complete inhibition of ADP-induced aggregation was achieved five minutes after platelet exposure to 0.10 to 0.25 mmol/L of DB when fibrinogen binding was reduced by 50%. At higher concentrations of DB (approximately 1 mmol/L), ADP-induced fibrinogen binding was completely blocked. Scatchard analysis revealed loss of high-affinity binding sites in addition to reduction in Bmax. In contrast, chymotrypsin-treated platelets sustained 50% inhibition of fibrinogen binding when incubated with 0.4 to 0.5 mmol/L DB, and kinetic analysis showed that the high- affinity platelet-fibrinogen interactions were reduced but not absent. Fibrinogen binding to chymotrypsin-treated platelets could not be completely inhibited even at high DB concentrations (1 mmol/L). The inhibition of fibrinogen binding to chymotrypsin-treated platelets correlated with changes in binding of a monoclonal antibody (10E5) specific for an epitope on the GPIIb-IIIa complex. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and radioelectroimmunoassay of DB-treated platelets, however, showed no evidence of a reduction or degradation of GP IIb or IIIa. Platelet incubation with DB (five minutes, 0.1 to 1.0 mmol/L) was also accompanied by: increased platelet membrane-associated Ca2+ involving low-affinity binding sites [Kd = 5 X 10(-5) mol/L-]; increased 45Ca2+ uptake which correlated with degradation of actin-binding protein (ABP) and digestion of GPIb as visualized on periodic-acid Schiff (PAS)- stained SDS gels and as inferred from decreased binding of a monoclonal antibody (6D1) directed against this glycoprotein; and enhanced Ca2+ exchange. Thus, exposure of platelets to DB results in membrane-related alterations that may contribute to inhibition of platelet cohesion: Decreased fibrinogen receptor exposure by traditional agonists and diminished accessibility of the GPIIb-IIIa complex to extracellular ligands correlate with DB-induced inhibition of platelet aggregation; and increased calcium uptake and exchange across the platelet membrane likely leads to activation of the calcium-dependent protease(s) which was previously shown to correlate with DB-induced inhibition of ristocetin-induced platelet agglutination.     

艾司洛尔联合胺碘酮治疗心室电风暴160例临床分析

目的：探讨和分析盐酸艾司洛尔与胺碘酮联合使用在治疗心室电风暴患者的效果。方法整群选取该院在2011年9月-2014年6月期间所收治的329例心室电风暴患者,遵照随机与知情自愿原则,分为观察组(160例)和对照组(169例)。给予药物胺碘酮治疗,对观察组患者采用盐酸艾司洛尔与胺碘酮联合治疗方案,疗程结束后,认真观察和对比两组患者所取得治疗的效果。结果观察组患者总有效率为95.0%,明显高于对照组的70.4%,该两组患者总有效率对比,差异有统计学意义(P<0.01);治疗后观察组患者收缩压与心率分别为(104.0±15.0)mmHg、(84.0±13.0)次/min全部低于对照组,该两组患者治疗后的收缩压与心率对比,差异有统计学意义(P<0.05)。结论采用盐酸艾司洛尔联合药物胺碘酮共同治疗心室电风暴患者的临床效果满意,能够提高心室风暴患者的治愈率,具有临床推广价值。     

Treatment of anxiety disorders in the Finnish general population

BACKGROUND: Treatments for anxiety disorders in the general population are not widely investigated. We determined the proportion, type and determinants of treatment in the Finnish general population. METHODS: Within the Health 2000 Study, a representative sample (n = 6005) of adults (age > 30 years) were interviewed in 2000-2001 with the Composite International Diagnostic Interview (M-CIDI) to assess the presence of DSM-IV mental disorders during the preceding 12 months. Logistic regression models were used to examine factors influencing the type of treatment (pharmacotherapy and/or psychological treatment) and also the types of pharmacotherapy (antidepressants, anxiolytics, or sedatives and hypnotics) used for anxiety disorders. RESULTS: For individuals with an anxiety disorder, 40% (95/229) currently used psychotropic medication, 23% (55/229) used antidepressants, 19% (44/229) anxiolytics and 17% (41/229) sedatives or hypnotics. Of those using health care services for mental health reasons (34%, 76/229), 80% (61/76) received pharmacotherapy. Only 45% (34/76) reported having psychological treatment, with few having more than 4 visits (27%, 20/76). Living in a semi-urban environment, retirement and high perceived disability increased the likelihood of pharmacotherapy-only treatment; higher education and comorbidity with mood disorders increased the likelihood of psychological treatment. General practitioners more often than psychiatrists provided pharmacotherapy treatment alone (67% vs. 34%, p < 0.05), particularly anxiolytics or sedatives. LIMITATIONS: Use of mental health services and psychological treatment were based on self-reports. No data on duration of pharmacotherapy was available. CONCLUSIONS: Anxiety disorders remain largely untreated in the general population. Among those seeking treatment, pharmacotherapy predominates, whereas even brief psychotherapies are rare. Contrary to clinical guidelines, anxiolytics and sedatives are commonly used instead of antidepressants.