ВИВЧЕННЯ МОРФОЛОГО-АНАТОМІЧНОЇ БУДОВИ БРУНЬОК ВІЛЬХИ КЛЕЙКОЇ ALNUS GLUTINOSA (L.) Gaertn.

The aim of the work. Research of the morphological and anatomical structure of black alder buds. Materials and methods. The pharmacopoeial methods of analysis investigated the morphological and anatomical structure of 5 series of buds of black alder of ordinary domestic harvest. Morphological features were studied at no less than 15 samples of raw materials of each series. The anatomical structure was studied at no less than 15 samples of raw materials of each series. Results and Discussion. The measurements of the buds and covering margins (morphometric parameters) made it possible to set the boundaries of the length and diameter of the bud and the length and width of the covering margins. The morphological description of black alder buds with the definition of diagnostic features is made (the size, shape and color of the buds and the covering bracts). The anatomical structure of the black alder buds was investigated. The main diagnostic features were identified: the shape of the cells of the epidermis of the bracts and the porosity of their shells, the types and topography of the thrichoms of the bracts, the presence of essential oil glands. Conclusions. Features of the morphological and anatomical structure of 5 series of adhesive alder buds of various harvesting regions have been established. Morphometric indices were determined, limits for the length and diameter of the buds and ophthalmic bracts were established. The criteria for the morphological description were selected and a morphological description of the sticky alder buds was created with the definition of diagnostic signs. The study of the anatomical structure of sticky alder buds made it possible to identify the diagnostic features of raw materials. The obtained results can become the basis for the development of the sections “Identification A” and “Identification B” of the draft monograph on the sticky alder buds as a promising type of medicinal plant material.Мета роботи – дослідити морфолого-анатомічну будову бруньок вільхи клейкої Аlnus glutinosa (L.) Gaertn. Матеріали і методи. За допомогою фармакопейних методів аналізу дослідили морфологічну та анатомічну будову 5 серій бруньок вільхи клейкої вітчизняних регіонів заготівлі. Морфологічні особливості вивчали не менш ніж на 15 зразках сировини кожної серії. Для дослідження анатомічної будови, виготовляли не менш ніж 15 препаратів сировини кожної серії. Результати й обговорення. Проведені виміри бруньок та криючих брактей (морфометричні показники) дозволили встановити граничні межі довжини та діаметру власне бруньки та довжини і ширини криючих брактей. Складений морфологічний опис бруньок вільхи клейкої з визначенням діагностичних ознак (форма, колір, характер поверхні криючих брактей). Дослідили анатомічну будову бруньок вільхи клейкої. Виділили основні діагностичні риси: форма клітин епідерми брактей та пористість їхніх оболонок, типи та топографія трихом брактей, наявність ефіроолійних залозок. Висновки. Встановлено особливості морфолого-анатомічної будови 5 серій бруньок вільхи клейкої різних регіонів заготівлі. Визначено морфометричні показники, встановлено граничні межі довжини та діаметру бруньки та криючих брактей. Обрано критерії морфологічного опису та створено морфологічний опис бруньок вільхи клейкої із визначенням діагностичних ознак. Дослідження анатомічної будови бруньок вільхи клейкої дозволило виділити діагностичні риси сировини. Отриманні результати можуть стати основою для розробки розділів «Ідентифікація А» та «Ідентифікація В» проекту монографії на бруньки вільхи клейкої як перспективного виду лікарської рослинної сировини

The impact of terahertz radiation on an extremophilic archaean Halorubrum saccharovorum proteome

Nonthermal effects of terahertz radiation on living objects are currently intensely studied, as more sources of this radiation type and devices employing it are being constructed. Terahertz radiation is increasingly used in security and inspection systems, medical and scientific appliances due to its low quant energy, which does not cause severe effects on organisms as other radiation types with higher quant energies do. The aim of this study was the identification of protein complexes participating in the response of the archaea Halorubrum saccharovorum H3 isolated from an extreme natural environment to terahertz radiation. We developed a microfluidic system for irradiation of bacterial and archaeal cultures with terahertz radiation and performed a 5-hour-long exposure of H. saccharovorum to terahertz radiation at a wavelength of 130 μm and a power density of 0.8 Wt per cm2 for 5 h. We identified under- or overexpressed proteins in response to terahertz radiation using 2D electrophoresis with subsequent MALDI-TOF mass spectrometry. A total of 16 differentially expressed protein fractions with at least 1.5-fold changes in expression level were detected. The obtained data suggest that Halorubrum cells respond to exposure to terahertz radiation by expression changes in gene products involved in translation regulation

The HIV Envelope but Not VSV Glycoprotein Is Capable of Mediating HIV Latent Infection of Resting CD4 T Cells

HIV fusion and entry into CD4 T cells are mediated by two receptors, CD4 and CXCR4. This receptor requirement can be abrogated by pseudotyping the virion with the vesicular stomatitis virus glycoprotein (VSV-G) that mediates viral entry through endocytosis. The VSV-G-pseudotyped HIV is highly infectious for transformed cells, although the virus circumvents the viral receptors and the actin cortex. In HIV infection, gp120 binding to the receptors also transduces signals. Recently, we demonstrated a unique requirement for CXCR4 signaling in HIV latent infection of blood resting CD4 T cells. Thus, we performed parallel studies in which the VSV-G-pseudotyped HIV was used to infect both transformed and resting T cells in the absence of coreceptor signaling. Our results indicate that in transformed T cells, the VSV-G-pseudotyping results in lower viral DNA synthesis but a higher rate of nuclear migration. However, in resting CD4 T cells, only the HIV envelope-mediated entry, but not the VSV-G-mediated endocytosis, can lead to viral DNA synthesis and nuclear migration. The viral particles entering through the endocytotic pathway were destroyed within 1–2 days. These results indicate that the VSV-G-mediated endocytotic pathway, although active in transformed cells, is defective and is not a pathway that can establish HIV latent infection of primary resting T cells. Our results highlight the importance of the genuine HIV envelope and its signaling capacity in the latent infection of blood resting T cells. These results also call for caution on the endocytotic entry model of HIV-1, and on data interpretation where the VSV-G-pseudotyped HIV was used for identifying HIV restriction factors in resting T cells

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Macrophage signaling in HIV-1 infection

The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection

Host hindrance to HIV-1 replication in monocytes and macrophages

Monocytes and macrophages are targets of HIV-1 infection and play critical roles in multiple aspects of viral pathogenesis. HIV-1 can replicate in blood monocytes, although only a minor proportion of circulating monocytes harbor viral DNA. Resident macrophages in tissues can be infected and function as viral reservoirs. However, their susceptibility to infection, and their capacity to actively replicate the virus, varies greatly depending on the tissue localization and cytokine environment. The susceptibility of monocytes to HIV-1 infection in vitro depends on their differentiation status. Monocytes are refractory to infection and become permissive upon differentiation into macrophages. In addition, the capacity of monocyte-derived macrophages to sustain viral replication varies between individuals. Host determinants regulate HIV-1 replication in monocytes and macrophages, limiting several steps of the viral life-cycle, from viral entry to virus release. Some host factors responsible for HIV-1 restriction are shared with T lymphocytes, but several anti-viral mechanisms are specific to either monocytes or macrophages. Whilst a number of these mechanisms have been identified in monocytes or in monocyte-derived macrophages in vitro, some of them have also been implicated in the regulation of HIV-1 infection in vivo, in particular in the brain and the lung where macrophages are the main cell type infected by HIV-1. This review focuses on cellular factors that have been reported to interfere with HIV-1 infection in monocytes and macrophages, and examines the evidences supporting their role in vivo, highlighting unique aspects of HIV-1 restriction in these two cell types

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered