331 research outputs found
L-arginine deprivation impairs Leishmania major-specific T-cell responses.
No full textThe amino acid L-arginine plays a crucial role in the regulation of immune responses. We have recently shown that uncontrolled replication of Leishmania parasites at the site of pathology correlates with high levels of arginase activity in nonhealing leishmaniasis and that this elevated arginase activity causes local depletion of L-arginine. To further our understanding of the impact of L-arginine deprivation in experimental leishmaniasis, here we characterize in detail the effects of L-arginine deprivation on antigen-specific T cells and MPhi. The results of our study show that decrease of L-arginine levels in the extracellular milieu affects the biological activities of Leishmania major-specific T cells, both at the level of the magnitude and the quality of their responses. L. major-specific CD4(+) T cells rendered hyporesponsive by L-arginine deprivation can be partially rescued by addition of exogenous L-arginine to produce IL-4 and IL-10, but not to produce IFN-gamma. Furthermore, our results show that L-arginine deprivation also greatly impacts parasite growth in activated macrophages. In summary, our results suggest that L-arginine levels affect both Th cell responses and parasite replication
Combination of Psychological Intervention and Phosphodiesterase-5 Inhibitors for Erectile Dysfunction: A Narrative Review and Meta-Analysis
No full textINTRODUCTION
Erectile dysfunction (ED) is an increasing health problem that demands effective treatment. There is evidence that phosphodiesterase-5 inhibitors (PDE5-Is) and psychological intervention (PI) are effective treatment options; however, little is known about their comparative efficacy and the efficacy of combined treatments.
AIM
The aim of this systematic review and meta-analysis is to evaluate the comparative efficacy of PI, PDE5-Is, and their combination in the treatment of ED.
MAIN OUTCOME MEASURES
Primary outcome was ED symptoms, and secondary outcome was sexual satisfaction of the patient.
METHODS
A systematic literature search was conducted in order to identify relevant articles published between 1998 and 2012. We included randomized controlled trials and controlled trials comparing PI with PDE5-I treatment or one of them against a combination of both.
RESULTS
Eight studies with a total number of 562 patients were included in the meta-analysis. The results of the included studies are inconclusive, though they show a trend towards a larger effect of combined treatment compared with PI or PDE5-I treatment alone. The meta-analysis found that, overall, combined treatment was more efficacious for ED symptoms than PDE5-I treatment or PI alone. Combined treatment was more efficacious than PDE5-I use alone on sexual satisfaction. No differences were found between PDE5-Is and PI as stand-alone treatments. None of the moderators (treatment duration, methodological quality, or researcher allegiance) altered the effects.
CONCLUSIONS
The combination of PI and PDE5-Is is a promising strategy for a favorable outcome in ED and can be considered as a first-choice option for ED patients. Stronger RCTs are required to confirm this initial finding. Schmidt HM, Munder T, Gerger H, Frühauf S, and Barth J. Combination of psychological intervention and phosphodiesterase-5 inhibitors for erectile dysfunction: A narrative review and meta-analysis. J Sex Med **;**:**-**
It's time for action (there's no option): about feminism
No full textAccompanies an exhibition featuring work exploring issues relating to gender and feminism by women artists from different generations, including Anat Ben-David (b. 1970), Patty Chang (b. 1972), Mary Beth Edelson (b. 1933), Cosey Fanni Tutti (b. 1951), Manon (b. 1946), Yoko Ono (b. 1933), Pipilotti Rist (b. 1962), Katharina Sieverding (b. 1944), Annie Sprinkle (b. 1954) and Mathilde ter Heijne (b. 1969). Features video, actions, wall collage, drawings, assemblage, video projections, slide-show installations and photography. Contains essays by Katy Deepwell, Mercedes Bunz, Maria Elena Buszek and Amelia Jones
Differential impact of L-arginine deprivation on the activation and effector functions of T cells and macrophages.
No full textThe metabolism of the amino acid L-arginine is emerging as a crucial mechanism for the regulation of immune responses. Here, we characterized the impact of L-arginine deprivation on T cell and macrophage (MPhi) effector functions: We show that whereas L-arginine is required unconditionally for T cell activation, MPhi can up-regulate activation markers and produce cytokines and chemokines in the absence of L-arginine. Furthermore, we show that L-arginine deprivation does not affect the capacity of activated MPhi to up-regulate L-arginine-metabolizing enzymes such as inducible NO synthase and arginase 1. Thus, our results show that to exert their effector functions, T cells and MPhi have different requirements for L-arginine
Munder, Hugo (Death, 1881-10-27)
No full textAddress: 139 Wade St.Age at death: 18Pg 21/1881/428/M W S/Dr. Bigney/Selen/Walnut HillsOriginal record filed in drawer labeled 'MULLER-MURPHY, F'
Aryl Halides as Potential Components for O-Aryl-N-(9\u27-acridinyl)-hydroxylamines Antitumor Agents
No full textAcridine derivatives such as m-amsacrine (m-AMSA) are known to intercalate deoxyribonucleic acid (DNA). Their action targets the growth, function, and replication of cancer cells. Because of this, they are primarily used as anticancer and antimalaria drugs. Unfortunately, due to the low half-life m-AMSA possesses because of the ease of hydrolysis of the carbon 9-nitrogen bond (C9-N bond), large concentrations of the drug are needed to be pharmaceutically effective. This results in a large concentration of toxic aniline byproducts. To reduce the rate of hydrolysis but still maintain the binding to DNA, a modification to the m-AMSA structure was made. A series of m-AMSA derivatives with a hydroxylamine linkage between the acridine nucleus and the C9-pendant was prepared via a linear three-step synthesis. Commercially available aryl bromides were coupled with hydroxylamine using catalytic palladium. Once the resulting O-substituted hydroxylamine was hydrolyzed, the product could be coupled with 9-chloroacridine to form the target compounds. Spectroscopic methods such as Proton nuclear magnetic resonance spectroscopy (1H NMR), Carbon-13 nuclear magnetic resonance spectroscopy (13C-NMR), 1H Correlation Spectroscopy (COSY), and heteronuclear single-quantum coherence (HSQC) were used to determine the purity and structure of each target derivative. The target derivatives will be analyzed and evaluated for their ability to bind DNA through thermal denaturation. A trial with DNA in a phosphate buffer through thermal denaturation was conducted to make a baseline for the thermal denaturation. The baseline showed that the melting point of calf-thymus DNA in the specific phosphate buffer system ranged between 68-71°C
Encompassing a global mental health perspective into psychotherapy research: a critique of approaches to measuring the efficacy of psychotherapy for depression
No full textCommentary paper on: Munder T, Flückiger C, Leichsenring F Abbass A Hilsenroth M Luyten P, Rabung S, Steinert C and Wampold B. Is psychotherapy effective? A re-analysis of treatments for depression. Epidemiol Psychiatr Sci . 2018 Jul 30:1 – 7. doi: 10.1017/S204579601800035
Local increase of arginase activity in lesions of patients with cutaneous leishmaniasis in Ethiopia.
No full textBACKGROUND: Cutaneous leishmaniasis is a vector-borne disease that is in Ethiopia mainly caused by the parasite Leishmania aethiopica. This neglected tropical disease is common in rural areas and causes serious morbidity. Persistent nonhealing cutaneous leishmaniasis has been associated with poor T cell mediated responses; however, the underlying mechanisms are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We have recently shown in an experimental model of cutaneous leishmaniasis that arginase-induced L-arginine metabolism suppresses antigen-specific T cell responses at the site of pathology, but not in the periphery. To test whether these results translate to human disease, we recruited patients presenting with localized lesions of cutaneous leishmaniasis and assessed the levels of arginase activity in cells isolated from peripheral blood and from skin biopsies. Arginase activity was similar in peripheral blood mononuclear cells (PBMCs) from patients and healthy controls. In sharp contrast, arginase activity was significantly increased in lesion biopsies of patients with localized cutaneous leishmaniasis as compared with controls. Furthermore, we found that the expression levels of CD3ζ, CD4 and CD8 molecules were considerably lower at the site of pathology as compared to those observed in paired PBMCs. CONCLUSION: Our results suggest that increased arginase in lesions of patients with cutaneous leishmaniasis might play a role in the pathogenesis of the disease by impairing T cell effector functions
TH1/TH2 dichotomy of murine CD4 T-cells is reflected in two alternate metabolic states of murine macrophages characterized by NO-synthase versus arginase induction
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