72 research outputs found
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 (65β74 %), MRSA (22,7β35 %) is stably high and. especially quota of producers of different Ξ²-lactamases among other Enterobacteriaceae pathogens (3,2β65 %) increased that caused, significant expenses for antibiotic therapy by carbapenems (22,7β40 %), glycopeptides (2,7β10 %). 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
ΠΡΠ±ΠΎΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΠ»Π΅ΠΊΡΡΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΏΠΎΡΠΎΡΠΊΠΎΠ² ΡΠΈΠ½ΠΊΠ° Π΄Π»Ρ ΠΌΠ΅ΡΠ°Π»Π»Π½Π°ΠΏΠΎΠ»Π½Π΅Π½Π½ΡΡ ΠΊΠΎΠΌΠΏΠΎΠ·ΠΈΡΠΈΠΉ
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.Π ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ ΡΠΏΠΎΡΠΎΠ± ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ Π²ΡΡΠΎΠΊΠΎΠ΄ΠΈΡΠΏΠ΅ΡΡΠ½ΡΡ
ΠΏΠΎΡΠΎΡΠΊΠΎΠ² ΡΠΈΠ½ΠΊΠ° ΡΠ»Π΅ΠΊΡΡΠΎΠ»ΠΈΠ·ΠΎΠΌ ΠΈ ΡΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠΈΠ½ΠΊΠ½Π°ΠΏΠΎΠ»Π½Π΅Π½Π½ΡΡ
ΠΊΠΎΠΌΠΏΠΎΠ·ΠΈΡΠΈΠΉ, ΠΏΡΠΈΠ³ΠΎΡΠΎΠ²Π»Π΅Π½Π½ΡΡ
Ρ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΠΈΠ³ΠΌΠ΅Π½ΡΠ° ΡΠΈΠ½ΠΊΠΎΠ²ΡΡ
ΠΏΠΎΡΠΎΡΠΊΠΎΠ², ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΡΠ°Π·Π½ΡΠΌΠΈ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΡΠ΅ ΠΈΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΡΠ΄Π΅Π»ΡΠ½Π°Ρ ΡΠ»Π΅ΠΊΡΡΠΎΠΏΡΠΎΠ²ΠΎΠ΄Π½ΠΎΡΡΡ ΡΠΈΠ½ΠΊΠ½Π°ΠΏΠΎΠ»Π½Π΅Π½Π½ΡΡ
ΠΏΠΎΠΊΡΡΡΠΈΠΉ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ
ΡΠ»Π΅ΠΊΡΡΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΏΠΎΡΠΎΡΠΎΠΊ ΡΠΈΠ½ΠΊΠ°, Π½Π΅ ΡΡΡΡΠΏΠ°Π΅Ρ ΠΏΠΎ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠΌΠΎΡΡΠΈ ΠΏΠ»Π΅Π½ΠΊΠ°ΠΌ Ρ ΠΏΠΎΡΠΎΡΠΊΠΎΠΌ ΠΠ¦ΠΠ-0, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈΡΠΏΠ°ΡΠ΅Π½ΠΈΡ-ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ, Π½Π΅ΡΠΌΠΎΡΡΡ Π½Π° ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎΠ΅ ΡΠ°Π·Π»ΠΈΡΠΈΠ΅ Π² ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅ ΡΠΈΠ½ΠΊΠΎΠ²ΠΎΠ³ΠΎ ΠΏΠΈΠ³ΠΌΠ΅Π½ΡΠ°. ΠΠ° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
Π΄Π°Π½Π½ΡΡ
ΠΌΠΎΠΆΠ½ΠΎ ΡΠ΄Π΅Π»Π°ΡΡ Π²ΡΠ²ΠΎΠ΄, ΡΡΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ»Π΅ΠΊΡΡΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΠΎΡΠΎΡΠΊΠ° ΡΠΈΠ½ΠΊΠ° Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΠΈΠ³ΠΌΠ΅Π½ΡΠ° ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎ ΡΠΊΠΎΠ½ΠΎΠΌΠΈΡΡ ΡΠΈΠ½ΠΊ.This work was supported by RFBR, project number 11-03-00226.Π Π°Π±ΠΎΡΠ° Π²ΡΠΏΠΎΠ»Π½Π΅Π½Π° ΠΏΡΠΈ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠ΅ Π Π€Π€Π, ΠΏΡΠΎΠ΅ΠΊΡ β 11-03-00226
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 womenβs gestational dominants in the Chelyabinsk region, an interrelation of the type of a psychological component of a gestational dominant with medicobiologic factors and babiesβ 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 babiesβ 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.Π ΡΡΠ°ΡΡΠ΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΎΡΠ΅Π½ΠΊΠΈ Π³Π΅ΡΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ Π΄ΠΎΠΌΠΈΠ½Π°Π½ΡΡ Ρ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΡΡ
ΠΆΠ΅Π½ΡΠΈΠ½ Π§Π΅Π»ΡΠ±ΠΈΠ½ΡΠΊΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ, ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π° Π²Π·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Ρ ΡΠΈΠΏΠ° ΠΏΡΠΈΡ
ΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ° Π³Π΅ΡΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ Π΄ΠΎΠΌΠΈΠ½Π°Π½ΡΡ Ρ ΠΌΠ΅Π΄ΠΈΠΊΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠ°ΠΊΡΠΎΡΠ°ΠΌΠΈ ΠΈ ΡΠΎΡΡΠΎΡΠ½ΠΈΠ΅ΠΌ Π·Π΄ΠΎΡΠΎΠ²ΡΡ Π΄Π΅ΡΠ΅ΠΉ, ΠΎΡΠ΅Π½Π΅Π½Π° ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΈΡ
ΠΎΠΊΠΎΡΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ Ρ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΡΠΌΠΈ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ 45,8% ΠΆΠ΅Π½ΡΠΈΠ½ ΡΠΎΡΡΠ°Π²Π»ΡΡΡ Π³ΡΡΠΏΠΏΡ ΡΠΈΡΠΊΠ° ΠΏΠΎ ΡΠ°Π½Π½Π΅ΠΌΡ ΠΎΡΠΊΠ°Π·Ρ ΠΎΡ Π³ΡΡΠ΄Π½ΠΎΠ³ΠΎ Π²ΡΠΊΠ°ΡΠΌΠ»ΠΈΠ²Π°Π½ΠΈΡ ΠΈ ΡΡΠ΅Π±ΡΡΡ ΡΠΈΡΡΠ΅ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠΈΡ
ΠΎΠΊΠΎΡΡΠ΅ΠΊΡΠΈΠΎΠ½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΡ Π΅ΡΠ΅ Π½Π° ΡΡΠ°ΠΏΠ΅ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΡΡΠΈ Π΄Π»Ρ ΡΡΠΏΠ΅ΡΠ½ΠΎΠ³ΠΎ Π³ΡΡΠ΄Π½ΠΎΠ³ΠΎ Π²ΡΠΊΠ°ΡΠΌΠ»ΠΈΠ²Π°Π½ΠΈΡ. Π£ ΠΆΠ΅Π½ΡΠΈΠ½ Ρ Π±Π»Π°Π³ΠΎΠΏΠΎΠ»ΡΡΠ½ΡΠΌ ΡΠΈΠΏΠΎΠΌ ΠΠΠΠ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎ ΡΠ΅ΠΆΠ΅ ΡΠ΅Π³ΠΈΡΡΡΠΈΡΠΎΠ²Π°Π»ΠΈΡΡ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΡ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΡΡΠΈ ΠΈ ΡΠΎΠ΄ΠΎΠ², ΠΎΡΠΌΠ΅ΡΠ°Π»ΠΈΡΡ ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΡΠ΅ ΡΡΠΎΠΊΠΈ ΠΏΠ΅ΡΠ²ΠΎΠ³ΠΎ ΠΏΡΠΈΠΊΠ»Π°Π΄ΡΠ²Π°Π½ΠΈΡ Π½ΠΎΠ²ΠΎΡΠΎΠΆΠ΄Π΅Π½Π½ΠΎΠ³ΠΎ ΠΊ Π³ΡΡΠ΄ΠΈ ΠΈ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ Π³ΡΡΠ΄Π½ΠΎΠ³ΠΎ Π²ΡΠΊΠ°ΡΠΌΠ»ΠΈΠ²Π°Π½ΠΈΡ, ΠΎΠΏΡΠΈΠΌΠ°Π»ΡΠ½ΡΠ΅ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΠΈ Π·Π΄ΠΎΡΠΎΠ²ΡΡ Π΄Π΅ΡΠ΅ΠΉ. Π£ ΠΆΠ΅Π½ΡΠΈΠ½, ΠΏΠΎΠ»ΡΡΠΈΠ²ΡΠΈΡ
ΠΏΡΠΈΡ
ΠΎΠΊΠΎΡΡΠ΅ΠΊΡΠΈΡ, ΡΠ°ΡΠ΅ ΠΎΡΠΌΠ΅ΡΠ°Π΅ΡΡΡ Π³Π»Π°Π΄ΠΊΠΎΠ΅ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΡΡΠΈ, Π±Π»Π°Π³ΠΎΠΏΡΠΈΡΡΠ½ΡΠΉ ΠΈΡΡ
ΠΎΠ΄ ΡΠΎΠ΄ΠΎΠ², ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ Π³ΡΡΠ΄Π½ΠΎΠ³ΠΎ Π²ΡΠΊΠ°ΡΠΌΠ»ΠΈΠ²Π°Π½ΠΈΡ, ΡΡΠΏΠ΅ΡΠ½Π°Ρ Π°Π΄Π°ΠΏΡΠ°ΡΠΈΡ Π΄Π΅ΡΠ΅ΠΉ Π² ΠΏΠΎΡΡΠ½Π°ΡΠ°Π»ΡΠ½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅
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
ΠΠΠΠΠΠΠ‘Π’ΠΠ§ΠΠ ΠΠΠΠ§ΠΠΠΠ― ΠΠΠΠΠ ΠΠ’ΠΠ ΠΠΠ₯ ΠΠΠΠΠΠΠΠΠΠ ΠΠΠΠΠΠΠΠΠΠ ΠΠΠ’ΠΠΠ‘ΠΠΠΠ¦ΠΠ ΠΠ Π ΠΠΠΠΠ‘ΠΠΠ’ΠΠΠ¬ΠΠΠ ΠΠΠΠΠΠΠΠΠ
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.ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅. Π‘ΠΈΠ½Π΄ΡΠΎΠΌ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΠΎΠΉ ΠΈΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΠΈΠΈ (EI) Π² Π½Π°ΡΡΠΎΡΡΠ΅Π΅ Π²ΡΠ΅ΠΌΡ ΠΎΡΡΠ°Π΅ΡΡΡ Π²Π΅Π΄ΡΡΠΈΠΌ Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½Π΅ Π²Π½Π΅Π±ΠΎΠ»ΡΠ½ΠΈΡΠ½ΠΎΠΉ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΠΈΠΈ (ΠΠ), Π΅Π³ΠΎ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΡΡΡ ΡΠΎΠΎΡΠ½ΠΎΡΠΈΡΡΡ Ρ ΡΡΠΆΠ΅ΡΡΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. ΠΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½Ρ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΠΈΠΈ, Π²ΡΡΠΎΠΊΠ°Ρ ΡΠ°ΡΡΠΎΡΠ° Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΡ Π΅Π΅ Π°ΡΠΈΠΏΠΈΡΠ½ΡΡ
ΡΠΎΡΠΌ, Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΉ ΡΡΠΎΠ²Π΅Π½Ρ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΠΈ ΠΎΠ±ΡΡΠ»ΠΎΠ²Π»ΠΈΠ²Π°ΡΡ Π½Π΅ΠΎΠ±Ρ
ΠΎΠ΄ΠΈΠΌΠΎΡΡΡ Π²ΡΡΡΠ½Π΅Π½ΠΈΡ ΡΠ΅ΡΠΊΠΈΡ
ΠΊΡΠΈΡΠ΅ΡΠΈΠ΅Π² ΠΎΡΠ΅Π½ΠΊΠΈ ΡΡΠΆΠ΅ΡΡΠΈ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ°. Π ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΡΠ°ΠΊΠΈΡ
ΠΊΡΠΈΡΠ΅ΡΠΈΠ΅Π² ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Ρ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΠ΅ ΠΌΠ°ΡΠΊΠ΅ΡΡ ΠΠ, Π½ΠΎ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΈΡ
Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π·Π½Π°ΡΠ΅Π½ΠΈΡ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ°Π΅ΡΡΡ.Π¦Π΅Π»ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ°Π»ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ
ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΠΠ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ Π² Π·Π°Π²ΠΈΡΠΈΠΌΠΎΡΡΠΈ ΠΎΡ ΡΡΠΆΠ΅ΡΡΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΎ 175 Π±ΠΎΠ»ΡΠ½ΡΡ
ΠΠ, ΠΊΠΎΡΠΎΡΡΡ
ΡΠ°Π·Π΄Π΅Π»ΠΈΠ»ΠΈ Π½Π° 3 Π³ΡΡΠΏΠΏΡ ΠΏΠΎ ΡΡΠΆΠ΅ΡΡΠΈ ΡΠ΅ΡΠ΅Π½ΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΡΠΎΠ³Π»Π°ΡΠ½ΠΎ ΡΠΊΠ°Π»Ρ Pneumonia PORT. Π ΡΠ°Π·Π³Π°Ρ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ»ΠΈ ΡΠ»Π΅Π΄ΡΡΡΠΈΠ΅ ΠΌΠ°ΡΠΊΠ΅ΡΡ ΠΠ: ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ ΡΡΠ΅Π΄Π½Π΅ΠΉ ΠΌΠ°ΡΡΡ ΡΡΠ²ΠΎΡΠΎΡΠΊΠΈ ΠΊΡΠΎΠ²ΠΈ ΡΡΠ°ΠΊΡΠΈΠΉ MΠ‘M254 ΠΈ MΠ‘M280, Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°ΡΠ½ΡΠΉ ΠΈΠ½Π΄Π΅ΠΊΡ ΠΈΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΠΈΠΈ, ΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ ΡΡΠ²ΠΎΡΠΎΡΠΊΠΈ ΠΊΡΠΎΠ²ΠΈ ΠΈ ΠΈΠ½ΡΠ΅ΡΡΡΠΈΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΆΠΈΠ΄ΠΊΠΎΡΡΠΈ Ρ ΡΠ΅ΠΌΠ΅Π½Π½ΡΠΌ ΡΠ΅ΡΡΠΎΠΌ.Π Π΅Π·ΡΠ»ΡΡΠ°Ρ ΠΈ ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅. Π Π³ΡΡΠΏΠΏΠ°Ρ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠ II ΠΈ III ΠΊΠ»Π°ΡΡΠΎΠ² ΠΏΠΎ ΡΠΊΠ°Π»Π΅ Pneumonia PORT Π±ΡΠ»ΠΎ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ Π²ΠΎΡΠΏΠ°Π»Π΅Π½ΠΈΡ Π² Π»Π΅Π³ΠΊΠΈΡ
ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°Π΅ΡΡΡ ΡΠΎΠΊΡΠ΅ΠΌΠΈΠ΅ΠΉ: Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ² Π² Π³ΡΡΠΏΠΏΠ°Ρ
ΠΎΠ±ΡΠ»Π΅Π΄ΡΠ΅ΠΌΡΡ
ΡΠΎΡΠ»ΠΈ ΠΏΡΠΎΠΏΠΎΡΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎ ΡΡΠΆΠ΅ΡΡΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ. Π’ΡΠΆΠ΅Π»ΠΎΠ΅ ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΠΈΠΈ (IV ΠΊΠ»Π°ΡΡ) ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°Π»ΡΡ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΡΠΌ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ΠΌ ΡΠΎΠΊΡΠΈΠ½ΠΎΠ² Π² ΠΈΠ½ΡΠ΅ΡΡΡΠΈΡΠΈΠΈ, Π·Π°ΠΌΠ΅ΡΠ½ΡΠΌ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ΠΌ ΠΠ‘Π280, Π° Ρ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ
ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² - ΠΏΠ°ΡΠ°Π΄ΠΎΠΊΡΠ°Π»ΡΠ½ΡΠΌ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ΠΌ Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°ΡΠ½ΠΎΠ³ΠΎ ΠΈΠ½Π΄Π΅ΠΊΡΠ° ΠΈΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΠΈΠΈ. ΠΡΠΈ Π΄Π°Π½Π½ΡΠ΅ ΡΠΊΠ°Π·ΡΠ²Π°ΡΡ Π½Π° ΠΏΠ΅ΡΠ΅Π½Π°ΠΏΡΡΠΆΠ΅Π½ΠΈΠ΅ ΡΠΈΡΡΠ΅ΠΌ Π΄Π΅ΡΠΎΠΊΡΠΈΠΊΠ°ΡΠΈΠΈ, ΠΊΠΎΡΠΎΡΡΠ΅ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½Ρ Π΄Π»Ρ ΡΠ½Π΄ΠΎΡΠΎΠΊΡΠΈΠΊΠΎΠ·Π°.ΠΡΠ²ΠΎΠ΄. ΠΠ°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΠ΅ ΠΌΠ°ΡΠΊΠ΅ΡΡ ΡΠ½Π΄ΠΎΠ³Π΅Π½Π½ΠΎΠΉ ΠΈΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½Ρ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΊΡΠΈΡΠ΅ΡΠΈΠ΅Π² ΡΡΠΆΠ΅ΡΡΠΈ Π²Π½Π΅Π±ΠΎΠ»ΡΠ½ΠΈΡΠ½ΠΎΠΉ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΠΈΠΈ, Π½ΠΎ ΠΈΡ
ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π΄ΠΎΠ»ΠΆΠ½ΠΎ Π±ΡΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΡΠΌ, ΡΡΠΎΠ±Ρ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°ΡΡ ΠΊΠ°ΠΊ ΡΠΎΠΊΡΠ΅ΠΌΠΈΠΈ, ΡΠ°ΠΊ ΠΈ Π΅Π½Π΄ΠΎΡΠΎΠΊΡΠΈΠΊΠΎΠ·.ΠΡΡΡΠΏ. Π‘ΠΈΠ½Π΄ΡΠΎΠΌ Π΅Π½Π΄ΠΎΠ³Π΅Π½Π½ΠΎΡ ΡΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΡΡ (EI) Π½Π° ΡΡΠΎΠ³ΠΎΠ΄Π½Ρ Π·Π°Π»ΠΈΡΠ°ΡΡΡΡΡ ΠΏΡΠΎΠ²ΡΠ΄Π½ΠΈΠΌ Ρ ΠΊΠ»ΡΠ½ΡΡΠ½ΡΠΉ ΠΊΠ°ΡΡΠΈΠ½Ρ Π½Π΅Π³ΠΎΡΠΏΡΡΠ°Π»ΡΠ½ΠΎΡ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΡΡ (ΠΠ), ΠΉΠΎΠ³ΠΎ Π²ΠΈΡΠ°ΠΆΠ΅Π½ΡΡΡΡ ΡΠΏΡΠ²Π²ΡΠ΄Π½ΠΎΡΠΈΡΡΡΡ Π· ΡΡΠΆΠΊΡΡΡΡ Π·Π°Ρ
Π²ΠΎΡΡΠ²Π°Π½Π½Ρ. ΠΠΌΡΠ½Π° ΠΊΠ»ΡΠ½ΡΡΠ½ΠΎΡ ΠΊΠ°ΡΡΠΈΠ½ΠΈ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΡΡ, Π²ΠΈΡΠΎΠΊΠ° ΡΠ°ΡΡΠΎΡΠ° Π²ΠΈΠ½ΠΈΠΊΠ½Π΅Π½Π½Ρ ΡΡ Π°ΡΠΈΠΏΠΎΠ²ΠΈΡ
ΡΠΎΡΠΌ, Π·Π½Π°ΡΠ½ΠΈΠΉ ΡΡΠ²Π΅Π½Ρ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΡ Π·ΡΠΌΠΎΠ²Π»ΡΡΡΡ Π½Π΅ΠΎΠ±Ρ
ΡΠ΄Π½ΡΡΡΡ Π²ΠΈΡΠ²Π»Π΅Π½Π½Ρ ΡΡΡΠΊΠΈΡ
ΠΊΡΠΈΡΠ΅ΡΡΡΠ² ΠΎΡΡΠ½ΠΊΠΈ ΡΡΠΆΠΊΠΎΡΡΡ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡ. Π ΡΠΊΠΎΡΡΡ ΡΠ°ΠΊΠΈΡ
ΠΊΡΠΈΡΠ΅ΡΡΡΠ² ΠΌΠΎΠΆΡΡΡ Π±ΡΡΠΈ Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Ρ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½Ρ ΠΌΠ°ΡΠΊΠ΅ΡΠΈ ΠΠ, Π°Π»Π΅ Π²ΠΈΠ²ΡΠ΅Π½Π½Ρ ΡΡ
Π΄ΡΠ°Π³Π½ΠΎΡΡΠΈΡΠ½ΠΎΠ³ΠΎ Π·Π½Π°ΡΠ΅Π½Π½Ρ ΡΡΠΈΠ²Π°Ρ.ΠΠ΅ΡΠΎΡ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ ΡΡΠ°Π»ΠΎ Π²ΠΈΠ·Π½Π°ΡΠ΅Π½Π½Ρ Π·ΠΌΡΠ½ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΠΈΡ
ΠΏΠΎΠΊΠ°Π·Π½ΠΈΠΊΡΠ² ΠΠ Ρ Ρ
Π²ΠΎΡΠΈΡ
Π½Π° ΠΠ Π·Π°Π»Π΅ΠΆΠ½ΠΎ Π²ΡΠ΄ ΡΡΠΆΠΊΠΎΡΡΡ Π·Π°Ρ
Π²ΠΎΡΡΠ²Π°Π½Π½Ρ.ΠΠ°ΡΠ΅ΡΡΠ°Π» Ρ ΠΌΠ΅ΡΠΎΠ΄ΠΈ. ΠΠ±ΡΡΠ΅ΠΆΠ΅Π½ΠΎ 175 Ρ
Π²ΠΎΡΠΈΡ
Π½Π° ΠΠ, ΡΠΊΠΈΡ
ΠΏΠΎΠ΄ΡΠ»ΠΈΠ»ΠΈ Π½Π° 3 Π³ΡΡΠΏΠΈ Π·Π° ΡΡΠΆΠΊΡΡΡΡ ΠΏΠ΅ΡΠ΅Π±ΡΠ³Ρ Π·Π°Ρ
Π²ΠΎΡΡΠ²Π°Π½Π½Ρ Π·Π³ΡΠ΄Π½ΠΎ Π·Ρ ΡΠΊΠ°Π»ΠΎΡ PneumoniaΒ PORT. Π£ ΡΠΎΠ·ΠΏΠ°Π» Π·Π°Ρ
Π²ΠΎΡΡΠ²Π°Π½Π½Ρ Π²ΠΈΠ·Π½Π°ΡΠ°Π»ΠΈ Π½Π°ΡΡΡΠΏΠ½Ρ ΠΌΠ°ΡΠΊΠ΅ΡΠΈ ΠΠ: ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΠΈ ΡΠ΅ΡΠ΅Π΄Π½ΡΠΎΡ ΠΌΠ°ΡΠΈ ΡΠΈΡΠΎΠ²Π°ΡΠΊΠΈ ΠΊΡΠΎΠ²Ρ ΡΡΠ°ΠΊΡΡΠΉ MΠ‘M254 ΡΠ° MΠ‘M280, Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°ΡΠ½ΠΈΠΉ ΡΠ½Π΄Π΅ΠΊΡ ΡΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΡΡ, ΡΠΎΠΊΡΠΈΡΠ½ΡΡΡΡ ΡΠΈΡΠΎΠ²Π°ΡΠΊΠΈ ΠΊΡΠΎΠ²Ρ ΡΠ° ΡΠ½ΡΠ΅ΡΡΡΠΈΡΡΠ°Π»ΡΠ½ΠΎΡ ΡΡΠ΄ΠΈΠ½ΠΈ Π·Π° ΡΡΠΌβΡΠ½ΠΈΠΌ ΡΠ΅ΡΡΠΎΠΌ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ. Π£ Π³ΡΡΠΏΠ°Ρ
ΠΏΠ°ΡΡΡΠ½ΡΡΠ² Π· ΠΠ II Ρ III ΠΊΠ»Π°ΡΡΠ² Π·Π° ΡΠΊΠ°Π»ΠΎΡ PneumoniaΒ PORT Π±ΡΠ»ΠΎ Π²ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΠΎ ΡΠΎΠ·Π²ΠΈΡΠΎΠΊ Π·Π°ΠΏΠ°Π»Π΅Π½Π½Ρ Π² Π»Π΅Π³Π΅Π½ΡΡ
ΡΡΠΏΡΠΎΠ²ΠΎΠ΄ΠΆΡΡΡΡΡΡ ΡΠΎΠΊΡΠ΅ΠΌΡΡΡ: Π·Π½Π°ΡΠ΅Π½Π½Ρ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΡΠ²Π°Π½ΠΈΡ
ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΡΠ² Ρ Π³ΡΡΠΏΠ°Ρ
ΠΎΠ±ΡΡΠ΅ΠΆΡΠ²Π°Π½ΠΈΡ
Π·ΡΠΎΡΡΠ°Π»ΠΈ ΠΏΡΠΎΠΏΠΎΡΡΡΠΉΠ½ΠΎ Π΄ΠΎ ΡΡΠΆΠΊΠΎΡΡΡ Π·Π°Ρ
Π²ΠΎΡΡΠ²Π°Π½Π½Ρ. Π’ΡΠΆΠΊΠΈΠΉ ΠΏΠ΅ΡΠ΅Π±ΡΠ³ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΡΡ (IVΒ ΠΊΠ»Π°Ρ) ΡΡΠΏΡΠΎΠ²ΠΎΠ΄ΠΆΡΠ²Π°Π²ΡΡ Π·Π½Π°ΡΠ½ΠΈΠΌ Π½Π°ΠΊΠΎΠΏΠΈΡΠ΅Π½Π½ΡΠΌ ΡΠΎΠΊΡΠΈΠ½ΡΠ² Π² ΡΠ½ΡΠ΅ΡΡΡΠΈΡΡΡ, ΠΏΠΎΠΌΡΡΠ½ΠΈΠΌ ΠΏΡΠ΄Π²ΠΈΡΠ΅Π½Π½ΡΠΌ ΠΠ‘Π280, Π° Ρ Π΄Π΅ΡΠΊΠΈΡ
ΠΏΠ°ΡΡΡΠ½ΡΡΠ² β ΠΏΠ°ΡΠ°Π΄ΠΎΠΊΡΠ°Π»ΡΠ½ΠΈΠΌ Π·Π½ΠΈΠΆΠ΅Π½Π½ΡΠΌ Π»Π΅ΠΉΠΊΠΎΡΠΈΡΠ°ΡΠ½ΠΎΠ³ΠΎ ΡΠ½Π΄Π΅ΠΊΡΡ ΡΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΡΡ. Π¦Ρ Π΄Π°Π½Ρ Π²ΠΊΠ°Π·ΡΡΡΡ Π½Π° ΠΏΠ΅ΡΠ΅Π½Π°ΠΏΡΡΠΆΠ΅Π½Π½Ρ ΡΠΈΡΡΠ΅ΠΌ Π΄Π΅ΡΠΎΠΊΡΠΈΠΊΠ°ΡΡΡ, ΡΠΊΡ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½Ρ Π΄Π»Ρ Π΅Π½Π΄ΠΎΡΠΎΠΊΡΠΈΠΊΠΎΠ·Ρ.ΠΠΈΡΠ½ΠΎΠ²ΠΎΠΊ. ΠΠ°Π±ΠΎΡΠ°ΡΠΎΡΠ½Ρ ΠΌΠ°ΡΠΊΠ΅ΡΠΈ Π΅Π½Π΄ΠΎΠ³Π΅Π½Π½ΠΎΡ ΡΠ½ΡΠΎΠΊΡΠΈΠΊΠ°ΡΡΡ ΠΌΠΎΠΆΡΡΡ Π±ΡΡΠΈ Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Ρ ΡΠΊ ΠΊΡΠΈΡΠ΅ΡΡΡ ΡΡΠΆΠΊΠΎΡΡΡ Π½Π΅Π³ΠΎΡΠΏΡΡΠ°Π»ΡΠ½ΠΎΡ ΠΏΠ½Π΅Π²ΠΌΠΎΠ½ΡΡ, Π°Π»Π΅ ΡΡ
Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Π½Ρ ΠΌΠ°Ρ Π±ΡΡΠΈ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΈΠΌ, ΡΠΎΠ± Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΠ²Π°ΡΠΈ ΡΠΊ ΡΠΎΠΊΡΠ΅ΠΌΡΡ, ΡΠ°ΠΊ Ρ Π΅Π½Π΄ΠΎΡΠΎΠΊΡΠΈΠΊΠΎΠ·
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>)<sup>cy18</sup> displays severely obese phenotypes at the adult stage. In Tg(<em>krt4:Hsa.myrAkt1</em>)<sup>cy18</sup>, the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3Ξ±/Ξ², 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>)<sup>cy18</sup> 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>)<sup>cy18</sup>. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)<sup>cy18</sup>, 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
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