A role of RGS proteins in drug addiction

The diverse family of Regulators of G protein signaling (RGS) proteins are widely distributed proteins with multiple functions, including GAP activity for heterotrimeric G protein alpha subunits. Three members of the RGS family, RGS9-2, RGS4 and RGSz, have been shown to play an essential modulatory role in psychostimulant and opiate drug actions. Interestingly, these proteins show distinct structure, distribution pattern and cellular localization. In addition, each of these proteins is differentially regulated by drugs of abuse in particular brain networks and appears to modulate distinct signal transduction events. The striatal enriched RGS9 plays a prominent role in opiate and psychostimulant drug reward; RGS4 appears to modulate opiate dependence via actions in the locus coeruleus, whereas RGSz modulates analgesia via activation of the PKC pathway.     

A sex-specific evaluation of predicted lean and fat mass composition and cardiovascular disease onset and progression: A combined analysis of the ATTICA and GREECS prospective epidemiological studies

ObjectivesTo evaluate the association of predicted lean and fat mass on 10-year first and recurrent CVD incidence separately for men and women.MethodsTwo prospective studies, ATTICA (2002-2012, n = 3042 subjects free-of-CVD, n = 1514 men (46 ± 13 years) and n = 1528 women (45 ± 14 years)) and GREECS (2004-2014, n = 2172 subjects with acute coronary syndrome (ACS), n = 1649 men (65 ± 13 years) and n = 523 women (62 ± 11 years)) were used. Lean mass index (LMI) and fat mass index (FMI) were created through total body lean and fat mass (indirectly calculated through population formulas based on body weight, height and waist circumference) divided by height squared. Follow-up was performed in n = 2020 of ATTICA (n = 317 first CVD events) and in n = 2172 patients of GREECS (n = 811 recurrent CVD events).ResultsIn ATTICA study, CVD rate from 1st to 3rd FMI tertile was 9.4%, 16.1% and 19.9% while in GREECS 36.2%, 37.0%, 38.3%. The LMI-related rates were 17.1%, 15.0% and 11.9% vs. 38.8%, 35.8% and 36.7%. Multiadjusted analysis revealed U-shape trend between LMI and CVD recurrence with 2nd LMI tertile having the best prognosis; this observation was more evident in women. In apparently healthy subjects, LMI-cardioprotective association was revealed only in 3rd tertile (HR = 0.91 95%CI (0.74, 0.95)); this was more evident in men. The FMI aggravating association (3rd tertile) was retained significant only in healthy women and ACS men.ConclusionThis work expands previous findings regarding body composition and cardiac health, implying that the association of lean and fat mass on long-term CVD incidence varies according to sex and prevention stage.     

A case-control study of coronary heart disease in Athens, Greece.

A case-control study of coronary heart disease (CHD) was conducted in Athens, Greece. The case series consisted of 329 patients with electrocardiographically confirmed coronary infarct or a diagnostic coronary arteriogram, or both, who were admitted during a 16-month period to a major teaching hospital. Controls were 570 patients admitted to the same hospital just before or after the CHD cases for minor surgery; eye, ear, nose or minor urological problems; or chest problems definitely shown to be unrelated to CHD. All cases and controls were interviewed in the hospital wards and selected laboratory data were abstracted. The main analysis was done by modelling through multiple logistic regression, controlling for demographic variables as well as for the mutual confounding effects of the investigated risk factors. Obesity, hypertension, diabetes mellitus, elevated blood cholesterol and excessive coffee intake were significant (P < 0.02) independent risk factors with relative risk estimates in the 2- to 3-fold range. Non-significant positive associations were found with respect to tobacco smoking and modest coffee consumption, whereas non-significant negative associations were noted with respect to alcohol intake and regular exercise. A negative association with duration of afternoon siesta was of borderline statistical significance.     

Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results

Ex vivo cultured limbal epithelial stem cells have been used successfully to treat corneal limbal stem cell deficiency. We identified 17 reports of the application of this novel cell-based therapy in humans. In addition we identified four reports of the use of culture oral mucosal epithelial cells to treat limbal stem cell deficiency. We examined these reports to discern the success rate, complication rate, visual outcome, whether there is an optimal technique and which patients are the most likely to benefit. We also discuss the different culture methods employed and the regulations governing cell banks that are providing this service. We found that the techniques used to cultivate and transplant cells varied, but that no individual method was clearly superior. The reported success rate is similar across all studies for both allografts and autografts. The clinical indications for this treatment are not clearly defined as indicated by the variety of disorders treated. Follow-up is limited and the long-term success rate is yet to be established. Nonetheless, we conclude that there is sufficient evidence to support the continued use and refinement of this procedure as a treatment for corneal stem cell deficiency.     

Biallelic interferon regulatory factor 8 mutation: A complex immunodeficiency syndrome with dendritic cell deficiency,monocytopenia, and immune dysregulation

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