DYNAMICS OF ANTIBIOTIC RESISTANCE OF NOSOCOMIAL PATHOGENS AND STATE OF ANTIBIOTiC THERAPY IN MULTIFIELD CLINIC

We carried out comparative analysis of the results of microbiological researches and antibiotic resistance of main pathogens of nosocomial infections from 2005 to 2010 years. During this period quota of MRSE (65—74 %), MRSA (22,7—35 %) is stably high and. especially quota of producers of different β-lactamases among other Enterobacteriaceae pathogens (3,2—65 %) increased that caused, significant expenses for antibiotic therapy by carbapenems (22,7—40 %), glycopeptides (2,7—10 %). Monitoring of tendencies of resistance of the most important pathogens of hospital infections optimication of antimicrobial therapy and introduction, of the system of preventive measures allowed, to decrease economic expenses for antimicrobial means to 17,5 %

Mapping an atlas of tissue-specific drosophila melanogaster metabolomes by high resolution mass spectrometry

Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes

Выбор условий получения электролитических порошков цинка для металлнаполненных композиций

The paper presents a method of obtaining high-dispersed zinc powders by electrolysis and comparison of the properties of zinc-rich compositions prepared using as a pigment zinc powders obtained by different methods. Measurements have shown that the electrical conductivity of zinc-rich coatings containing electrolytic zinc powder, not inferior to the conductivity of the film with powder PZHD-0 obtained by the method of evaporation-condensation, despite the significant difference in the amount of zinc pigment. On the basis of the received data we can conclude that the use of electrolytic zinc powder as a pigment will significantly save zinc.В работе представлен способ получения высокодисперсных порошков цинка электролизом и сравнение свойств цинкнаполненных композиций, приготовленных с применением в качестве пигмента цинковых порошков, полученных разными методами. Проведенные измерения показали, что удельная электропроводность цинкнаполненных покрытий, содержащих электролитический порошок цинка, не уступает по проводимости пленкам с порошком ПЦВД-0, полученного методом испарения-конденсации, несмотря на существенное различие в количестве цинкового пигмента. На основании полученных данных можно сделать вывод, что использование электролитического порошка цинка в качестве пигмента позволит значительно экономить цинк.This work was supported by RFBR, project number 11-03-00226.Работа выполнена при поддержке РФФИ, проект № 11-03-00226

Safety and Tolerability of Implanted Subcutaneous Cardioverter-Defibrillator Systems

Aim. To study the safety and tolerability of the subcutaneous implantable cardioverter defibrillator (S-ICD) after implantation.Material and methods. The results of 33 patients with implanted S-ICD 6 months follow-up. The criteria for inclusion in the observational study were: age over 18 years, indications for primary or secondary prevention of sudden cardiac death. The exclusion criteria were indications for implantation of transvenous ICD (patients with sustained monomorphic ventricular tachycardia, the need for anti-bradycardia or resynchronization therapy), as well as patients with a QRS complex of more than 130 msec. All patients underwent a standard preoperative examination (routine blood tests, chest X-ray, transthoracic echocardiography), quality-of-life questionnaires and transesophageal echocardiography. At follow-up, patients were examined after 6 months after implantation, the device was interrogated and a quality-of-life questionnaire was completed. All episodes of shock therapy and complications were documented.Results. Male patients predominated (84%), with a mean age of 57 [43;62] years. Left ventricular ejection fraction was 30% [26;34]. The mean QRS duration was 100 [94;108] msec. According to the of 24-hour Holter ECG monitoring, episodes of unstable VT were recorded in 42.4% of patients. The most common indications for S-ICD implantation were dilated (33%) and ischemic cardiomyopathy (42%). Primary prevention was indicated in 97% of patients. At the end of the implantation of the S-ICD, the patients underwent a defibrillation test and device configuration. In 63.6% of cases, during automatic tuning, the device selected the primary perception vector. In 27.2% of patients, optimal recognition of the subcutaneous signal was observed in the secondary vector, and in 9.2% of patients, the alternative vector was favorable. All patients underwent two-zone programming. The conditional shock zone was programmed at an average rate of 192 beats/min (range 180-210 beats/min) and the shock zone was programmed at an average rate of 222 beats/min (range 220-240 beats/min). Perioperative complications occurred in two patients. During the follow-up period, no shocks were recorded in 27 patients. Adequate shocks for 6 months were recorded in two patients. During 6 months of observation, one lethal outcome was noted due to complications of viral pneumonia. During the observation period, there were no rehospitalizations for cardiovascular diseases.Conclusion. The use of S-ICD, even in patients with structural myocardial disease who do not require antibradycardia pacing, is effective in preventing SCD. The number of inadequate discharges and the number of complications in clinical practice is comparable to the data of multicenter studies. S-ICD implantation was not accompanied by a decrease in quality of life. Careful selection of candidates, along with state-of-the-art device programming, is an important parameter for the selection and success of S-ICD application

The estimation of efficiency of psychohygienic work with pregnant and feeding women of the Satkinskiy area of the Chelyabinsk region

The article represents the results of the estimation of pregnant women’s gestational dominants in the Chelyabinsk region, an interrelation of the type of a psychological component of a gestational dominant with medicobiologic factors and babies’ state of health, efficiency of psychocorrectional work with pregnant women is estimated. It is established that 45,8 % of women make a risk group of an early refusal from chest feeding and demand regular psychocorrectional work at a stage of pregnancy for successful chest feeding. Within the women of successful type of PCGD complications of pregnancy and childbirth were seldom registered, optimum terms of the first applying of the newborn to a breast and duration of chest feeding, optimum indicators of babies’ health were marked. Within the women who have received psychocorrection, smooth course of their pregnancy, a favorable result of childbirth, an increase of duration of chest feeding, successful adaptation of babies in postnatal period are more often marked.В статье представлены результаты оценки гестационной доминанты у беременных женщин Челябинской области, установлена взаимосвязь типа психологического компонента гестационной доминанты с медико-биологическими факторами и состоянием здоровья детей, оценена эффективность психокоррекционной работы с беременными. Установлено, что 45,8% женщин составляют группу риска по раннему отказу от грудного вскармливания и требуют систематической психокоррекционной работы еще на этапе беременности для успешного грудного вскармливания. У женщин с благополучным типом ПКГД достоверно реже регистрировались осложнения беременности и родов, отмечались оптимальные сроки первого прикладывания новорожденного к груди и продолжительности грудного вскармливания, оптимальные показатели здоровья детей. У женщин, получивших психокоррекцию, чаще отмечается гладкое течение беременности, благоприятный исход родов, увеличение продолжительности грудного вскармливания, успешная адаптация детей в постнатальном периоде

ДІАГНОСТИЧНЕ ЗНАЧЕННЯ ЛАБОРАТОРНИХ ПОКАЗНИКІВ ЕНДОГЕННОЇ ІНТОКСИКАЦІЇ ПРИ НЕГОСПІТАЛЬНІЙ ПНЕВМОНІЇ

Introduction. Syndrome of endogenous intoxication (EI) nowadays remains the leading place in manifestation of community-acquired pneumonia (CAP), and its expression correlates with the severity of the disease. Change of clinical manifestation of pneumonia, high accidence of its atypical forms as well as a significant level of mortality cause the need to find clear criteria for assessment of the pathological process severity. The laboratory markers of EI may be used as such criteria, but their diagnostic importance has been steel studied.The aim of study was to investigate changes in laboratory parameters of endogenous intoxication in patients with community-acquired pneumonia depending on the severity of the disease.Materials and methods. The study involved 175 patients with community-acquired pneumonia, which were divided into 3 groups according to Pneumonia PORT scale. In the midst of the disease the following laboratory markers of EI were investigated: the middle-mass molecules (fractions MMM254 and MMM280), leukocyte intoxication index, toxicity of blood serum and interstitial fluid according to spermatic test.Results and discussion. It was revealed that the development of inflammation in groups of patients with II and III class according to Pneumonia PORT scale was accompanied by toxemia: the value of the studied parameters in groups of surveyed was observed to be increased in proportion to the severity of the disease. In addition, severe course of pneumonia (IV class) was followed by significant accumulation of toxins in the interstitium, marked elevation of MMM280, paradoxic decrease of leukocyte index of intoxication in some patients. These findings indicate the overstrain of detoxification systems which is characteristic of endotoxicosis.Conclusion. Laboratory markers of endogenous intoxication can be used as criteria of severity of community-acquired pneumonia, but they need to be investigated in complex to characterize both toxemia and endotoxicosis.Введение. Синдром эндогенной интоксикации (EI) в настоящее время остается ведущим в клинической картине внебольничной пневмонии (НП), его выраженность соотносится с тяжестью заболевания. Изменение клинической картины пневмонии, высокая частота возникновения ее атипичных форм, значительный уровень смертности обусловливают необходимость выяснения четких критериев оценки тяжести патологического процесса. В качестве таких критериев могут быть использованы лабораторные маркеры ЭИ, но изучение их диагностического значения продолжается.Целью исследования стало определение изменений лабораторных показателей ЭИ у больных ВП в зависимости от тяжести заболевания.Материал и методы. Обследовано 175 больных ВП, которых разделили на 3 группы по тяжести течения заболевания согласно шкалы Pneumonia PORT. В разгар заболевания определяли следующие маркеры ЭИ: молекулы средней массы сыворотки крови фракций MСM254 и MСM280, лейкоцитарный индекс интоксикации, токсичность сыворотки крови и интерстициальной жидкости с семенным тестом.Результат и обсуждение. В группах пациентов с НП II и III классов по шкале Pneumonia PORT было установлено, что развитие воспаления в легких сопровождается токсемией: значение исследуемых параметров в группах обследуемых росли пропорционально тяжести заболевания. Тяжелое течение пневмонии (IV класс) сопровождался значительным накоплением токсинов в интерстиции, заметным повышением МСМ280, а у некоторых пациентов - парадоксальным снижением лейкоцитарного индекса интоксикации. Эти данные указывают на перенапряжение систем детоксикации, которые характерны для эндотоксикоза.Вывод. Лабораторные маркеры эндогенной интоксикации могут быть использованы в качестве критериев тяжести внебольничной пневмонии, но их исследование должно быть комплексным, чтобы характеризовать как токсемии, так и ендотоксикоз.Вступ. Синдром ендогенної інтоксикації (EI) на сьогодні залишається провідним у клінічній картині негоспітальної пневмонії (НП), його вираженість співвідноситься з тяжкістю захворювання. Зміна клінічної картини пневмонії, висока частота виникнення її атипових форм, значний рівень смертності зумовлюють необхідність виявлення чітких критеріїв оцінки тяжкості патологічного процесу. В якості таких критеріїв можуть бути використані лабораторні маркери ЕІ, але вивчення їх діагностичного значення триває.Метою дослідження стало визначення змін лабораторних показників ЕІ у хворих на НП залежно від тяжкості захворювання.Матеріал і методи. Обстежено 175 хворих на НП, яких поділили на 3 групи за тяжкістю перебігу захворювання згідно зі шкалою Pneumonia PORT. У розпал захворювання визначали наступні маркери ЕІ: молекули середньої маси сироватки крові фракцій MСM254 та MСM280, лейкоцитарний індекс інтоксикації, токсичність сироватки крові та інтерстиціальної рідини за сім’яним тестом.Результати. У групах пацієнтів з НП II і III класів за шкалою Pneumonia PORT було встановлено, що розвиток запалення в легенях супроводжується токсемією: значення досліджуваних параметрів у групах обстежуваних зростали пропорційно до тяжкості захворювання. Тяжкий перебіг пневмонії (IV клас) супроводжувався значним накопиченням токсинів в інтерстиції, помітним підвищенням МСМ280, а у деяких пацієнтів – парадоксальним зниженням лейкоцитарного індексу інтоксикації. Ці дані вказують на перенапруження систем детоксикації, які характерні для ендотоксикозу.Висновок. Лабораторні маркери ендогенної інтоксикації можуть бути використані як критерії тяжкості негоспітальної пневмонії, але їх дослідження має бути комплексним, щоб характеризувати як токсемію, так і ендотоксикоз

Proton-Assisted Amino Acid Transporter PAT1 Complexes with Rag GTPases and Activates TORC1 on Late Endosomal and Lysosomal Membranes

Mammalian Target of Rapamycin Complex 1 (mTORC1) is activated by growth factor-regulated phosphoinositide 3-kinase (PI3K)/Akt/Rheb signalling and extracellular amino acids (AAs) to promote growth and proliferation. These AAs induce translocation of mTOR to late endosomes and lysosomes (LELs), subsequent activation via mechanisms involving the presence of intralumenal AAs, and interaction between mTORC1 and a multiprotein assembly containing Rag GTPases and the heterotrimeric Ragulator complex. However, the mechanisms by which AAs control these different aspects of mTORC1 activation are not well understood. We have recently shown that intracellular Proton-assisted Amino acid Transporter 1 (PAT1)/SLC36A1 is an essential mediator of AA-dependent mTORC1 activation. Here we demonstrate in Human Embryonic Kidney (HEK-293) cells that PAT1 is primarily located on LELs, physically interacts with the Rag GTPases and is required for normal AA-dependent mTOR relocalisation. We also use the powerful in vivo genetic methodologies available in Drosophila to investigate the regulation of the PAT1/Rag/Ragulator complex. We show that GFP-tagged PATs reside at both the cell surface and LELs in vivo, mirroring PAT1 distribution in several normal mammalian cell types. Elevated PI3K/Akt/Rheb signalling increases intracellular levels of PATs and synergistically enhances PAT-induced growth via a mechanism requiring endocytosis. In light of the recent identification of the vacuolar H+-ATPase as another Rag-interacting component, we propose a model in which PATs function as part of an AA-sensing engine that drives mTORC1 activation from LEL compartments

Quantitative Analysis of Lipid Droplet Fusion: Inefficient Steady State Fusion but Rapid Stimulation by Chemical Fusogens

Lipid droplets (LDs) are dynamic cytoplasmic organelles containing neutral lipids and bounded by a phospholipid monolayer. Previous studies have suggested that LDs can undergo constitutive homotypic fusion, a process linked to the inhibitory effects of fatty acids on glucose transporter trafficking. Using strict quantitative criteria for LD fusion together with refined light microscopic methods and real-time analysis, we now show that LDs in diverse cell types show low constitutive fusogenic activity under normal growth conditions. To investigate the possible modulation of LD fusion, we screened for agents that can trigger fusion. A number of pharmacological agents caused homotypic fusion of lipid droplets in a variety of cell types. This provided a novel cell system to study rapid regulated fusion between homotypic phospholipid monolayers. LD fusion involved an initial step in which the two adjacent membranes became continuous (<10 s), followed by the slower merging (100 s) of the neutral lipid cores to produce a single spherical LD. These fusion events were accompanied by changes to the LD surface organization. Measurements of LDs undergoing homotypic fusion showed that fused LDs maintained their initial volume, with a corresponding decrease in surface area suggesting rapid removal of membrane from the fused LD. This study provides estimates for the level of constitutive LD fusion in cells and questions the role of LD fusion in vivo. In addition, it highlights the extent of LD restructuring which occurs when homotypic LD fusion is triggered in a variety of cell types

Overexpression of Akt1 Enhances Adipogenesis and Leads to Lipoma Formation in Zebrafish

<div><h3>Background</h3><p>Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the <em>Akt1</em> gene.</p> <h3>Methodology/Principal Findings</h3><p><em>Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1</em>)^cy18 displays severely obese phenotypes at the adult stage. In Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18, the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18 caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18, suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.</p> <h3>Conclusion/Significance</h3><p>Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.</p> </div