Suppression of Plasmodium chabaudi parasitemia is independent of the action of reactive oxygen intermediates and/or nitric oxide

The killing of blood-stage malaria parasites in vivo has been attributed to reactive intermediates of oxygen (ROI) and of nitrogen (RNI). However, in the case of the latter, this contention is challenged by recent observations that parasitemia was not exacerbated in nitric oxide synthase (NOS) knockout (KO) (NOS2-/- or NOS3-/-) mice or in mice treated with NOS inhibitors. We now report that the time course shows that Plasmodium chabaudi parasitemia in NADPH oxidase KO (p47phox-/-) mice also was not exacerbated, suggesting a minimal role for ROI-mediated killing of blood-stage parasites. It is possible that the production of protective antibodies during malaria may mask the function of ROI and/or RNI. However, parasitemia in B-cell-deficient JH-/- x NOS2-/- or JH-/- x p47phox-/- mice was not exacerbated. In contrast, the magnitude of peak parasitemia was significantly enhanced in p47phox-/- mice treated with the xanthine oxidase inhibitor allopurinol, but the duration of patent parasitemia was not prolonged. Whereas the time course of parasitemia in NOS2-/- x p47phox-/- mice was nearly identical to that seen in normal control mice, allopurinol treatment of these double-KO mice also enhanced the magnitude of peak parasitemia. Thus, ROI generated via the xanthine oxidase pathway contribute to the control of ascending P. chabaudi parasitemia during acute malaria but alone are insufficient to suppress parasitemia to subpatent levels. Together, these results indicate that ROI or RNI can contribute to, but are not essential for, the suppression of parasitemia during blood-stage malaria.     

What’s important when caring for a loved one? Population-based preference weights for the Adult Social Care Outcomes Toolkit for informal carers (ASCOT-Carer) for Austria

Quality of Life Research - The Adult Social Care Outcomes Toolkit for informal carers (ASCOT-Carer) can be used to assess long-term care-related quality of life (LTC-QoL) of adult informal carers...     

Disassociation of the plasma insulin response from the blood glucose concentration during glucose infusions in normal dogs

Twenty-two anesthetized dogs were given a constant glucose infusion (14 mg/kg/min) for 360 min, while blood glucose concentration was continuously monitored. Plasma insulin concentration was measured every 30 min. The blood glucose peaked at 60 min and then steadily fell (mean fall, $\text{56}\text{mg}\text{100}\text{ml}$), while plasma insulin continuously rose (mean rise, 65 μU/ml). This suggests that blood glucose concentratiion was not the primary stimulus for insulin secretion. In a second series of experiments, five dogs received glucose infusions as described above. One week later, each dog was reinfused with a larger total glucose load, regulated by continuous blood glucose monitoring to exactly reproduce the blood glucose response observed during the first infusion. Plasma insulin concentrations during the high load infusions were significantly higher than during the low load infusions. Thus, changes in glucose load produced changes in plasma insulin concentration, even though blood glucose levels were held constant. Thus, using two different approaches, we have demonstrated that plasma insulin levels can be dissociated from the coexisting blood glucose concentration. These results suggest that the level of blood glucose may not be the primary determinant of the insulin response to glucose during the chronic phase of insulin secretion.     

Venlafaxine in the treatment of dysthymia: an open-label study

BACKGROUND: Numerous studies have demonstrated the effectiveness of antidepressant medications in the treatment of dysthymia, or chronic mild depression. Venlafaxine blocks reuptake of both serotonin and norepinephrine and may produce a more complete antidepressant response than do single-mechanism selective serotonin reuptake inhibitors. The purpose of this open-label study was to provide preliminary data on the tolerability and effectiveness of venlafaxine for patients with dysthymia. METHOD: Twenty-two dysthymic subjects (DSM-III-R criteria) were enrolled in this 10-week, open-label trial, and 5 dropped out prior to their second visit. Seventeen subjects (77.3%) received more than 1 week of medication. RESULTS: Of these 17 subjects, 13 (76.5%) were treatment responders. Results of paired sample t tests were highly significant, indicating that, on average, there was significant improvement on all measures of symptomatology and functioning, with mean +/- SD scores on the Hamilton Rating Scale for Depression decreasing from 20.95 +/- 6.50 at baseline to 6.06 +/- 5.49 at week 10. The mean +/- SD final dose was 178.68 +/- 70.80 mg/day. Side effects were reported by 17 (85%) of the 20 subjects for whom tolerability was assessed (the most common were fatigue, dry mouth, and nausea); 5 (22.7%) of 22 patients discontinued treatment because of side effects, primarily nausea (N = 3). CONCLUSION: These findings suggest the benefit of venlafaxine in the treatment of chronic depression and the need for more rigorous studies.     

Statistical methods for characterizing similarities and differences between semantic structures

This paper describes a variety of statistical methods for obtaining precise quantitative estimates of the similarities and differences in the structures of semantic domains in different languages. The methods include comparing mean correlations within and between groups, principal components analysis of interspeaker correlations, and analysis of variance of speaker by question data. Methods for graphical displays of the results are also presented. The methods give convergent results that are mutually supportive and equivalent under suitable interpretation. The methods are illustrated on the semantic domain of emotion terms in a comparison of the semantic structures of native English and native Japanese speaking subjects. We suggest that, in comparative studies concerning the extent to which semantic structures are universally shared or culture-specific, both similarities and differences should be measured and compared rather than placing total emphasis on one or the other polar position.     

Citalopram in the treatment of dysthymic disorder

This study aimed to provide preliminary data on the tolerability and effectiveness of citalopram for patients with dysthymic disorder. Twenty-one adult subjects meeting DSM-IV criteria for dysthymic disorder were enrolled in this 12-week open-label study, of whom 15 had pure dysthymia (e.g. no major depression in the past 2 years). Citalopram was initiated at 20 mg/day, and increased to a maximum of 60 mg/day. Response was defined as 50% or greater drop in score on the Hamilton Depression Rating Scale (HDRS) and a Clinical Global Impressions-I score of 1 ('very much improved') or 2 ('much improved'). Of these 15 pure dysthymic disorder subjects, all completed the trial, and 11 (73.3%) were treatment responders. All paired sample t-tests were highly significant, demonstrating significant average improvement on all measures of symptomatology and functioning. Scores on the 24-item HDRS decreased from 22.3+/-4.3 at baseline to 9.1+/-7.8 at week 12 [t(14)=6.1, P<0.001]. In addition, improvement was noted in self-reported measures of temperament and social functioning. The average final dose of citalopram was 39 mg/day. Side-effects were reported by nine of 15 subjects (60%), most frequently gastrointestinal symptoms (n=5), dry mouth (n=5) and sexual side-effects (n=3). These findings suggest the effectiveness and tolerability of citalopram in treating dysthymic disorder. Double-blind prospective studies are needed comparing citalopram both to placebo and to other medications, assessing both initial and sustained response to treatment.     

In vitro transdermal delivery of the major catechins and caffeine from extract of Camellia sinensis

The aim of this study was to investigate the feasibility of the transdermal delivery of catechins and caffeine from green tea extract. Drug-in-adhesive patches containing 1.35, 1.03, 0.68, and 0.32 mg cm(-2) green tea extract were formulated and the dissolution of (-)-epigallocatechin gallate (EGCg), (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) from these was determined. Transdermal delivery was determined across full thickness pig ear skin from saturated solutions of green tea extract in pH 5.5 citrate-phosphate buffer, polyethylene glycol 400 and a 50:50 mixture of the citrate phosphate buffer and polyethylene glycol in addition to patches containing 1.35 mg cm(-2) green tea extract. Dissolution experiments indicated first order release which was dose dependent in respect of the loading level, although the amounts permeated were not always proportional to the amounts in the formulation. The highest percentage permeation of EGCg was found to be from the patch formulation. EGCg, EGC and EC were all successfully delivered transdermally from saturated solutions and adhesive patches containing green tea extract in this study. There was some evidence for the dermal metabolism of EGCg, but after 24 h 0.1% permeated from the patches containing 1.35 mg cm(-2) green tea extract. This was equivalent to the percentage absorbed after intragastric administration of green tea extract in rats. In addition, the concentration of EGCg in the Franz cell receptor chamber after 24 h permeation from the 0.9 cm diameter patch containing 1.35 mg cm(-2) was within the range of Cmax plasma levels achieved after oral dosing of 2.2-4.2 gm(-2) green tea extract. Caffeine was also delivered at concentrations above those previously reported.     

Rating dysthymia: an assessment of the construct and content validity of the Cornell Dysthymia Rating Scale

BACKGROUND: Mason et al. developed the Cornell Dysthymia Rating Scale (CDRS), a 20-item clinician-rated inventory, and hypothesized that it may be superior to the commonly-used Hamilton Depression Rating Scale (HDRS) in assessing the symptoms of dysthymia, a form of chronic depression. The purpose of this study was to compare these instruments in an outpatient sample of dysthymic patients. METHOD: The CDRS and the HDRS and other inventories (including the Hopkins Symptom Check List (SCL)) were administered to 110 patients meeting DSM-IIIR diagnosis of dysthymia. RESULTS: There was a significant correlation between the CDRS and the HDRS at baseline and termination, indicating concurrent validity. Distributional statistics were compared for baseline and termination severity scores, showing that the CDRS has greater severity range scores than the HDRS. Furthermore, results of the DSM-IV Mood Disorders Field Trial suggest that the CDRS has better content validity than the HDRS when it comes to the dysthymic population. LIMITATIONS: The results are limited by the use of a homogeneous sample, the absence of observer ratings of divergent symptoms, and less than excellent validity of self-report divergent symptoms. CONCLUSIONS: Our results support the value of the CDRS in assessing symptoms of dysthymia.     

Age and Year of HIV Diagnosis are Associated with Perceptions of Discrimination and Internalized Stigma Among Sexual Minority Men Who Use Substances

Discrimination and internalized stigma are barriers to engagement in HIV self-care among men who have sex with men (MSM) living with HIV. However, differences in perceptions of discrimination and internalized stigmas by age, year of HIV-diagnosis, and race are poorly understood. We assessed differences in reported discrimination related to HIV, race, sexual orientation, and substance use and internalized stigmas among 202 MSM living with HIV who use substances. Younger participants reported higher levels of all types of discrimination and internalized stigmas (p-values < 0.001–0.030). Those diagnosed after the advent of antiretrovirals reported higher levels of discrimination related to HIV, sexual orientation, and substance use, as well as internalized stigma related to HIV and substance use (p-values 0.001–0.049). We explored perceived community HIV stigma, which accounted for associations involving age and year of diagnosis. Age, year of diagnosis, and race should be considered when assessing and intervening with stigma.

     

Psychological and behavioral moderators of the relationship between trauma severity and HIV transmission risk behavior among MSM with a history of childhood sexual abuse

Childhood sexual abuse (CSA) is associated with post-traumatic stress disorder (PTSD), which can be associated with condomless sex among men who have sex with men (MSM). However, the impact of moderating factors on the relationship between PTSD symptom severity and condomless sex is poorly understood. We examined whether PTSD symptom severity was associated with condomless sex among MSM with CSA histories, and whether substance dependence, self-esteem, and distress tolerance moderated that relationship (n = 288). Notably, no direct relationship between PTSD symptom severity and condomless sex was found. Adjusted models indicated that condomless sex was differentially impacted by PTSD symptom severity among those without substance dependence (ΔR² = 0.03, p = 0.034) and, counterintuitively, those with high self-esteem (ΔR² = 0.07, p = 0.005). PTSD symptom severity was associated with condomless sex across levels of distress tolerance. Findings indicate that substance use, self-esteem, and distress tolerance should be targeted in high-risk MSM with CSA even if they do not have PTSD.