СТАН НАДАННЯ ПОСЛУГ АРТ ВІЛ-ІНФІКОВАНИМ ОСОБАМ І ХВОРИМ НА СНІД У ТЕРНОПІЛЬСЬКІЙ ОБЛАСТІ

Сounteracting HIV/AIDS is one of the key areas of the state policy in the healthcare sector.The aim – to assess the efficiency of implementation of ART services in Ternopil region for making recommendations for the development of national and regional HIV/AIDS control programs for 2019-2023. The ART coverage of PLHIV is not sufficient to have a positive impact on the HIV epidemic situation.Materials and methods. To determine of epidemiological indicators, was analiesed a routine epidemiological surveillance data and epidemic prognosis of the HIV / AIDS in the SPECTRUM program for 2009-2016.Results and conclusions. The mortality of disease caused by HIV tends to increase. There is progress in the coverage of ART services by regional population, but the part of people in need, but not receiving ART, is increasing. Treatment is prescribed in accordance with patients quotas. The network of ART sites needs to expand in the region. Only one NGO provides these services and covers exclusively the residents of the regional center. Commercial sex workers and men who have sex with men are not covered by care and support services.Питання протидії ВІЛ-інфекції/СНІДу є одним із пріоритетних напрямів державної політики у сфері охорони здоров’я. Мета роботи − оцінити результативність впровадження послуг антиретровірусної терапії (АРТ) у Тернопільській області для формування рекомендацій з розробки національної та регіональної програм протидії ВІЛ-інфекції/СНІД на 2019-2023 роки. Матеріали і методи. Для визначення тенденцій епідеміологічних показників проведений аналіз та синтез даних рутинного епідеміологічного нагляду, прогнозування епідемії ВІЛ-інфекції/СНІДу у програмі SPECTRUM за 2009-2016 роки.Результати досліджень і висновки. Рівень охоплення людей, що живуть з ВІЛ (ЛЖВ), АРТ недостатній для здійснення позитивного впливу на епідемічну ситуацію з ВІЛ-інфекції. Показник смертності населення від хвороб, зумовлених ВІЛ, має тенденцію до зростання. Існує прогрес в охопленні послугами АРТ населення області, проте зростає і частка осіб, які потребують, але не отримують АРТ. Лікування призначається відповідно до встановленої квоти набору пацієнтів. Мережа сайтів АРТ в області потребує розширення. Лише одна неурядова організація (НУО) надає ці послуги і ними охоплені винятково жителі обласного центру. Послугами з догляду та підтримки не охоплені працівники комерційного сексу та чоловіки, які практикують секс з чоловіками

Following autophagy step by step

Autophagy is an evolutionarily conserved lysosomal degradation route for soluble components of the cytosol and organelles. There is great interest in identifying compounds that modulate autophagy because they may have applications in the treatment of major diseases including cancer and neurodegenerative disease. Hundeshagen and colleagues describe this month in BMC Biology a screening assay based on flow cytometry that makes it possible to track distinct steps in the autophagic process and thereby identify novel modulators of autophagy

ПЕРФОРАЦІЯ ТОНКОЇ КИШКИ У ВІЛ-ІНФІКОВАНОЇ ХВОРОЇ З ПОЗАЛЕГЕНЕВИМ ТУБЕРКУЛЬОЗОМ

SUMMARY. Perforation of the small intestine in HIV-infected disease with extrapulmonary tuberculosis was describe as clinical case. Pay attention of the difficult clinical course of disease and diagnostic terms. According to the authors, available in Ukraine regulations aimed mainly at protecting the personal rights of HIV-positive people and do not protect other members of society.Key words: small intestine, perforation, HIV, tuberculosis.Наведено клінічний випадок перфорації тонкої кишки у ВІЛ-інфікованої хворої з позалегеневим туберкульозом. Звертається увага на різноманітність клінічного перебігу і складність в діагностичному плані. На думку авторів, наявні в Україні нормативно-правові акти направлені в основному на захист особистих прав ВІЛ-інфікованих осіб і не захищають інших членів суспільства.Ключові слова: тонка кишка, перфорація, ВІЛ-інфекція, туберкульоз.

Autophagy mediates degradation of nuclear lamina

Z.D. is supported by a fellow award from the Leukemia & Lymphoma Society. B.C.C. is supported by career development awards from the Dermatology Foundation, Melanoma Research Foundation, and American Skin Association. S.L.B., P.D.A. and R.M. are supported by NIA P01 grant (P01AG031862). S.L.B. is also supported by NIH R01 CA078831. R.D.G. is supported by R01 GM106023 and the Progeria Research Foundation

Disruption of Neuronal Autophagy by Infected Microglia Results in Neurodegeneration

There is compelling evidence to support the idea that autophagy has a protective function in neurons and its disruption results in neurodegenerative disorders. Neuronal damage is well-documented in the brains of HIV-infected individuals, and evidence of inflammation, oxidative stress, damage to synaptic and dendritic structures, and neuronal loss are present in the brains of those with HIV-associated dementia. We investigated the role of autophagy in microglia-induced neurotoxicity in primary rodent neurons, primate and human models. We demonstrate here that products of simian immunodeficiency virus (SIV)-infected microglia inhibit neuronal autophagy, resulting in decreased neuronal survival. Quantitative analysis of autophagy vacuole numbers in rat primary neurons revealed a striking loss from the processes. Assessment of multiple biochemical markers of autophagic activity confirmed the inhibition of autophagy in neurons. Importantly, autophagy could be induced in neurons through rapamycin treatment, and such treatment conferred significant protection to neurons. Two major mediators of HIV-induced neurotoxicity, tumor necrosis factor-α and glutamate, had similar effects on reducing autophagy in neurons. The mRNA level of p62 was increased in the brain in SIV encephalitis and as well as in brains from individuals with HIV dementia, and abnormal neuronal p62 dot structures immunoreactivity was present and had a similar pattern with abnormal ubiquitinylated proteins. Taken together, these results identify that induction of deficits in autophagy is a significant mechanism for neurodegenerative processes that arise from glial, as opposed to neuronal, sources, and that the maintenance of autophagy may have a pivotal role in neuroprotection in the setting of HIV infection

PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk

Autophagy, a process in which cellular components are engulfed and degraded within double-membrane vesicles termed autophagosomes, has an important role in the response to oxidative damage. Here we identify a novel cascade of phosphorylation events, involving a network of protein and lipid kinases, as crucial components of the signaling pathways that regulate the induction of autophagy under oxidative stress. Our findings show that both the tumor-suppressor death-associated protein kinase (DAPk) and protein kinase D (PKD), which we previously showed to be phosphorylated and consequently activated by DAPk, mediate the induction of autophagy in response to oxidative damage. Furthermore, we map the position of PKD within the autophagic network to Vps34, a lipid kinase whose function is indispensable for autophagy, and demonstrate that PKD is found in the same molecular complex with Vps34. PKD phosphorylates Vps34, leading to activation of Vps34, phosphatydilinositol-3-phosphate (PI(3)P) formation, and autophagosome formation. Consistent with its identification as a novel inducer of the autophagic machinery, we show that PKD is recruited to LC3-positive autophagosomes, where it localizes specifically to the autophagosomal membranes. Taken together, our results describe PKD as a novel Vps34 kinase that functions as an effecter of autophagy under oxidative stress

Autophagy fights disease through cellular self-digestion

Autophagy, or cellular self-digestion, is a cellular pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. For example, autophagic dysfunction is associated with cancer, neurodegeneration, microbial infection and ageing. Paradoxically, although autophagy is primarily a protective process for the cell, it can also play a role in cell death. Understanding autophagy may ultimately allow scientists and clinicians to harness this process for the purpose of improving human health.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62766/1/nature06639.pd

β-Hydroxy-β-Methylbutyrate (HMB) Normalizes Dexamethasone-Induced Autophagy-Lysosomal Pathway in Skeletal Muscle

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.This project has been funded by Abbott Nutrition R&D

Curvature of Double-Membrane Organelles Generated by Changes in Membrane Size and Composition

Transient double-membrane organelles are key players in cellular processes such as autophagy, reproduction, and viral infection. These organelles are formed by the bending and closure of flat, double-membrane sheets. Proteins are believed to be important in these morphological transitions but the underlying mechanism of curvature generation is poorly understood. Here, we describe a novel mechanism for this curvature generation which depends primarily on three membrane properties: the lateral size of the double-membrane sheets, the molecular composition of their highly curved rims, and a possible asymmetry between the two flat faces of the sheets. This mechanism is evolutionary advantageous since it does not require active processes and is readily available even when resources within the cell are restricted as during starvation, which can induce autophagy and sporulation. We identify pathways for protein-assisted regulation of curvature generation, organelle size, direction of bending, and morphology. Our theory also provides a mechanism for the stabilization of large double-membrane sheet-like structures found in the endoplasmic reticulum and in the Golgi cisternae

Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20

Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However, it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation induces selective autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin-editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes, including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting ‘autophagy receptors’ in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly, only under the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)-induced proinflammatory gene expression. Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF–TRAF6. Furthermore, although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on TLR signaling