Manageable droplet infections in the Dobrich region - past, present and future

Въведение: В края на ХІХ и началото на ХХ век главната причина за смъртността в света са инфекциозните болести. Научните постижения в борбата с инфекциозните заболявания доведоха до ликвидиране на вариолата през 1980 година и изпълнение на международни програми за ликвидиране на други - морбили, епидемичен паротит, вродена рубеола и други. Това са ваксино-предотвратими инфекции, наречени управляеми, за които са въвеждани обективни критерии за епидемиологичен надзор, които дават възможност за своевременни корекции в имунизационните програми и повлияване на заболеваемостта от тях.Цел и задачи: Проучване на регистрираната обща инфекциозна и управляемата въздушно капкова заболяемост в Добричка област за периода 1995- 2012 год.Материали и методи: Отчети, анализи на РЗИ, МЗ, НЦЗПБ, епидемиологично проучване, епидемиологичен анализ, статистически методи.Резултати: Основните показатели на епидемиологичния анализ, които включват заболяемост, смъртност, леталитет, заболяемост по възрастови групи, разглеждаме за продължителен период (1995-2012 г.), тъй като влиянието на имунопрофилактиката при въздушно-капковите инфекции е бавен процес, свързан както с възрастта, така и с държавната политика в областта на имунизационното дело.Изводи: Общата заразна заболяемост в област Добрич за проучвания 18-годишен период (1995- 2012 г.) е около или под средните стойности за страната с изключение на няколко години (1996 г., 2001 г., 2002 г., 2003 г., 2004 г.). Управляемите въздушно-капкови инфекции - морбили, епидемичен паротит, и рубеола са с ниска заболяемост до липсваща такава.Introduction: In the late nineteenth and early twentieth century the main cause of mortality in the world was infectious diseases. Scientific advances in the fight against infectious diseases led to the eradication of smallpox in 1980 and implementation of international programs for the eradication of others - measles, mumps, congenital rubella and others. These are vaccine-preventable infections (the socalled manageable infections), for which objective criteria for epidemiological surveillance have been introduced, that allow for timely adjustments in immunization programs and to influence their morbidity.Purpose and tasks: To investigate the registered total infectious and manageable droplet morbidity in the Dobrich region for the 1995-2012 period.Materials and Methods: Reports, analysis of RHI (Regional Health Inspectorate), MH (Ministry of Health), NCIPD (National Center of Infectious and Parasitic Diseases), epidemiological study, epidemiological analysis, statistical methods.Results: We observed the main indicators of epidemiological analysis, which include morbidity, mortality, lethality and incidence by age groups, for a long period (years 1995-2012), since the impact of immunotherapy in droplet infections is a slow process, related to age as well as to government immunization policies.Conclusions: The total infectious morbidity in Dobrich for the studied 18 years period (1995- 2012) was around or below the national average with exception of a few years (1996, 2001, 2002, 2003 and 2004). The manageable droplet infections - measles, mumps, and rubella have low or no morbidit

Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy

Histone deacetylase (HDAC)-inhibitors (HDACis) are well characterized anti-cancer agents with promising results in clinical trials. However, mechanistically little is known regarding their selectivity in killing malignant cells while sparing normal cells. Gene expression-based chemical genomics identified HDACis as being particularly potent against Down syndrome associated myeloid leukemia (DS-AMKL) blasts. Investigating the anti-leukemic function of HDACis revealed their transcriptional and posttranslational regulation of key autophagic proteins, including ATG7. This leads to suppression of autophagy, a lysosomal degradation process that can protect cells against damaged or unnecessary organelles and protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mTOR activation. Consequently, HDAC inhibition repressed autophagy below a critical threshold, which resulted in accumulation of mitochondria, production of reactive oxygen species, DNA-damage and apoptosis. Those HDACi-mediated effects could be reverted upon autophagy activation or aggravated upon further pharmacological or genetic inhibition. Our findings were further extended to other major acute myeloid leukemia subgroups with low basal level autophagy. The constitutive suppression of autophagy due to mTOR activation represents an inherent difference between cancer and normal cells. Thus, via autophagy suppression, HDACis deprive cells of an essential pro-survival mechanism, which translates into an attractive strategy to specifically target cancer cells

RIPping the Skin Apart : Necroptosis Signaling in Toxic Epidermal Necrolysis

Toxic epidermal necrolysis (TEN) is a rare but potentially fatal drug hypersensitivity reaction. Although a number of pathophysiological hints have been identified over the past decade, details of the effector mechanisms within the skin remain obscure. A novel study by Kim et al. now sheds light on its pathophysiology. The investigators demonstrate convincingly that receptor-interacting kinase 3 (RIPK3) levels are upregulated substantially in the lesional skin of patients with TEN and that this is followed by the generation of reactive oxygen species, activation of mixed lineage kinase-like protein, and subsequent necroptotic cell death of keratinocytes. These data suggest that therapies that interfere with RIPK3 activation and necroptosis induction could benefit patients with TEN