Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease.

Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs), which accelerates their hemolysis. Normal RBC precursors eliminate their mitochondria during the terminal differentiation process. Strikingly, we observed an increased percentage of RBCs retaining mitochondria in SCD patient blood samples compared with healthy individuals. In addition, using an experimental SCD mouse model, we demonstrate that excessive levels of ROS in SCD are associated with this abnormal mitochondrial retention. Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Furthermore, gene expression analysis of SCD mice treated with RN-1 showed increased expression of mitophagy genes. Our findings suggest that reduction of mitochondria-retaining RBCs may provide a new therapeutic approach to preventing excessive ROS in SCD.

Prevalence of hidradenitis suppurativa: a population-based study in Olmsted County, Minnesota.

BACKGROUND: Hidradenitis suppurativa (HS) is a follicular occlusion disorder occurring in apocrine-rich regions of the skin. Estimates of the prevalence of this disorder have not been population-based. OBJECTIVE: We sought to provide population-based information on the prevalence of HS in Olmsted County, Minnesota, as of January 1, 2009. METHODS: The Rochester Epidemiology Project, a unique infrastructure that combines and makes accessible all medical records in Olmsted County since the 1960s, was used to collect population-based data on the prevalence of HS. RESULTS: We identified 178 confirmed cases of HS that included 135 females and 43 males, and estimated the total sex- and age-adjusted prevalence in Olmsted County to be 127.8 per 100,000 or 0.13%. The total prevalence was significantly higher among women than men. CONCLUSION: This study represents the first population-based investigation on the prevalence of HS. In this population-based cohort, HS was less prevalent than suggested by previous reports.

Effect of velocity on microdroplet fluorescence quantified by laser-induced fluorescence.

Microdroplets generated inside microfluidic devices have been widely used as miniaturized chemical and biological reactors allowing important reductions in experimental fluid volumes and making it possible to carry out high-throughput assays. Laser-induced fluorescence (LIF) is commonly used to detect and quantify the product, marker or cell content inside each individual droplet. In this work, we employed this technique to characterize the response of in-flow microdroplets filled with fluorescein dye at different laser powers and flow velocities. Using two parallel laser beams closely focused inside a microchannel we determined the microdroplet velocities and showed that the droplet fluorescence intensity decreases exponentially with reducing velocities because of the effects of photobleaching. In contrast, the fluorescence intensity increases linearly with laser power in the 4-10 mW range. When LIF is used for microdroplet measurements it is important to consider not just the fluorophore concentration but also the droplet velocity and laser power in the development of quantitative assays.

Incidence of hidradenitis suppurativa and associated factors: a population-based study of Olmsted County, Minnesota.

There are no population-based incidence studies of hidradenitis suppurativa (HS). Using the medical record linkage system of the Rochester Epidemiology Project, we sought to determine the incidence of the disease, as well as other associations and characteristics, among HS patients diagnosed in Olmsted County, Minnesota, between 1968 and 2008. Incidence was estimated using the decennial census data for the county. Logistic regression models were fit to evaluate associations between patient characteristics and disease severity. A total of 268 incident cases were identified, with an overall annual age- and sex-adjusted incidence of 6.0 per 100,000. Age-adjusted incidence was significantly higher in women compared with men (8.2 (95% confidence interval (CI), 7.0-9.3) vs. 3.8 (95% CI, 3.0-4.7). The highest incidence was among young women aged 20-29 years (18.4 per 100,000). The incidence has risen over the past four decades, particularly among women. Women were more likely to have axillary and upper anterior torso involvement, whereas men were more likely to have perineal or perianal disease. In addition, 54.9% (140/255) patients were obese; 70.2% were current or former smokers; 42.9% carried a diagnosis of depression; 36.2% carried a diagnosis of acne; and 6% had pilonidal disease. Smoking and gender were significantly associated with more severe disease.

Estudio multicéntrico abierto no comparativo de pefloxacina en dósis única de 800 mg en el tratamiento de uretrocistitis infecciosa, realizado en México / An open, multicentric, non-comparative study of Pefloxazyne in a single 800 mg dose, in the treatment of infectious urethrocystitis, performed in México

Se realizó un estudio multicéntrico abierto no comparaivo en el que participaron 18 reconocidos urólogos de la República Mexicana, de las ciudades de Monterey, Guadalajara, Toluca, León y el Distrito Federal. Se valoró la eficacia antimicrobiana y la tolerancia de pefloxacina en dosis única de dos comprimidos de 400 mg. en el tatamiento de uretrocistitits infecciosa, previa revisión del protocolo de investigación clínica por parte de los investigadores participantes con la finalidad de unificar criterior para su valoración posterior