Patterns of Childhood Trauma and Psychological Distress among Injecting Heroin Users in China

Background: Childhood trauma has been reported as a possible cause of future substance abuse in some countries. This study reports the prevalence of childhood trauma and examines its association with psychological distress among injecting drug users from mainland China. Methodology: The study was conducted in three government-operated drug rehabilitation facilities in Shanghai, China in 2007. The Early Trauma Inventory Self Report-Short Form (ETISR-SF) was used to evaluate 4 types (general, emotional, physical and sexual) and severity of childhood trauma, and the Symptom Checklist-90-Revised (SCL-90-R) to evaluate psychological distress. Principal Findings: Among 341 injecting drug users who completed the study, about 80 % reported one or more types o

IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH) on reducing blood pressure (BP) as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II.</p> <p>Methods</p> <p>We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP), MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP), or placebo (containing cellulose) for 4 weeks.</p> <p>Results</p> <p>In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080) and diastolic BP by 2.3 mm Hg (P = 0.0065) compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II.</p> <p>Conclusions</p> <p>MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT00471263</p

Berberine Chloride Mediates Its Anti-Leishmanial Activity via Differential Regulation of the Mitogen Activated Protein Kinase Pathway in Macrophages

BACKGROUND: A complex interplay between Leishmania and macrophages influences parasite survival and necessitates disruption of signaling molecules, eventually resulting in impairment of macrophage function. In this study, we demonstrate the immunomodulatory activity of Berberine chloride in Leishmania infected macrophages. PRINCIPAL FINDINGS: The IC(50) of Berberine chloride, a quaternary isoquinoline alkaloid was tested in an amastigote macrophage model and its safety index measured by a cell viability assay. It eliminated intracellular amastigotes, the IC(50) being 2.8 fold lower than its IC(50) in promastigotes (7.10 µM vs. 2.54 µM) and showed a safety index >16. Levels of intracellular and extracellular nitric oxide (NO) as measured by flow cytometry and Griess assay respectively showed that Berberine chloride in Leishmania infected macrophages increased production of NO. Measurement of the mRNA expression of iNOS, IL-12 and IL-10 by RT-PCR along with levels of IL-12p40 and IL-10 by ELISA showed that in infected macrophages, Berberine chloride enhanced expression of iNOS and IL-12p40, concomitant with a downregulation of IL-10. The phosphorylation status of extracellular signal related kinase (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK) was studied by western blotting. In infected macrophages, Berberine chloride caused a time dependent activation of p38 MAPK along with deactivation of ERK1/2; addition of a p38 MAPK inhibitor SB203580 inhibited the increased generation of NO and IL-12p40 by Berberine chloride as also prevented its decrease of IL-10. CONCLUSIONS: Berberine chloride modulated macrophage effector responses via the mitogen activated protein kinase (MAPK) pathway, highlighting the importance of MAPKs as an antiparasite target

NK Cells Promote Th-17 Mediated Corneal Barrier Disruption in Dry Eye

The conjunctiva contains a specialized population of lymphocytes that reside in the epithelium, named intraepithelial lymphocytes (IEL).Here we characterized the IEL population prior to and after experimental desiccating stress (DS) for 5 or 10 days (DS5, DS10) and evaluated the effect of NK depletion on DS. The frequency of IELs in normal murine conjunctiva was CD3(+)CD103(+) (~22%), CD3(+)γδ(+) (~9.6%), CD3(+)NK(+) (2%), CD3(-)NK(+) (~4.4%), CD3(+)CD8α (~0.9%), and CD4 (~0.6%). Systemic depletion of NK cells prior and during DS led to a decrease in the frequency of total and activated DCs, a decrease in T helper-17(+) cells in the cervical lymph nodes and generation of less pathogenic CD4(+)T cells. B6.nude recipient mice of adoptively transferred CD4(+)T cells isolated from NK-depleted DS5 donor mice showed significantly less corneal barrier disruption, lower levels of IL-17A, CCL20 and MMP-3 in the cornea epithelia compared to recipients of control CD4(+)T cells.Taken together, these results show that the NK IELs are involved in the acute immune response to desiccation-induced dry eye by activating DC, which in turn coordinate generation of the pathogenic Th-17 response

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin lightchain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed