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Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.
Assuntos
Neoplasias Pancreáticas , Receptores de Antígenos Quiméricos , Feminino , Humanos , Linhagem Celular Tumoral , Proteínas Ligadas por GPI/metabolismo , Mesotelina , Neoplasias Pancreáticas/tratamento farmacológico , Linfócitos T/metabolismoRESUMO
The study of plasma in liquid jets represents a significant area of research encompassing plasma science, dynamics, and properties. This paper presents experimental studies on plasma formation processes in liquid jets of water, ethanol, and isopropyl based on the dynamics of the third harmonic (TH) reflection from the induced plasma. Through time-resolved experiments, and theoretical estimations using the Keldysh theory, plasma properties including density and frequency for all three media are evaluated. Isopropyl demonstrates the highest values of the characteristics mentioned. These findings hold significant potential for advancing our understanding of plasma-based radiation sources, e.g., terahertz generation.
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Aim To study platelet adhesion mediated by von Willebrand factor (VWF) in patients with premature ischemic heart disease (IHD).Material and methods This study enrolled 58 patients with stable IHD, including 45 men younger than 55 years with the first manifestation of IHD at the age of <50 years and 13 women younger than 65 years with the first manifestation of IHD at the age of <60 years. The control group consisted of 33 patients, 13 men younger than 55 years and 20 women younger than 65 years without IHD. Platelet adhesion to the collagen surface at the shear rate of 1300 s-1 was studied by evaluating the intensity of scattered laser light from the collagen-coated optical substrate in a flow chamber of a microfluidic device after 15-min circulation of whole blood in the chamber. Decreases in platelet adhesion after addition to the blood of monoclonal antibodies (mAb) to platelet receptors glycoproteins Ib (GPIb) to inhibit the receptor interaction with VWF were compared for patients of both groups. Results In patients with premature IHD, the decrease in platelet adhesion following the platelet GPIb receptor inhibition was significantly less than in patients of the control group (74.8â% (55.6; 82.7) vs. 28.9â% (-9.8; 50,5), p <0.001). For the entire sample, the median decrease in platelet adhesion following the GPIb receptor inhibition was 62.8â% (52.2; 71.2). With an adjustment for traditional risk factors of IHD, a decrease in platelet adhesion of >62.8% after blocking GPIb receptors increased the likelihood of premature IHD (OR=9.84, 95â% CI: 2.80-34.59; p <0.001).Conclusion Blocking the interaction of GPIb receptors with VWF in patients with premature IHD and increased shear rate induced a greater decrease in platelet adhesion than in patients without this disease. This suggested that an excessive interaction of VWF with platelets might contribute to the pathogenesis of premature IHD.
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Doença da Artéria Coronariana , Fator de von Willebrand , Humanos , Feminino , Pessoa de Meia-Idade , Fator de von Willebrand/farmacologia , Fator de von Willebrand/fisiologia , Doença da Artéria Coronariana/diagnóstico , Adesividade Plaquetária/fisiologia , Plaquetas , Complexo Glicoproteico GPIb-IX de Plaquetas , ColágenoRESUMO
The differential diagnosis of neoplasms of various localizations is the primary task in clinical practice of all physicians. We present a description of the case of invasion with Dirofilaria repens in the lung of a 68-year-old patient. In 2016 the patient was diagnosed with cancer of the left kidney and underwent a left-sided nephrectomy. During the dynamic observation in 2019, a lump was found in the left lung, which was regarded as a metastasis. An atypical SIX resection of the left lung was performed. Microscopy of the removed lump revealed the presence of a nematode of the genus Dirofilaria, presumably D. repens. The species identity of D. repens was confirmed by polymerase chain reaction using species-specific primers. It is known that the morphological identification of parasites up to the species in the surgical material presents certain difficulties and requires high professional training of the researcher. Therefore, the diagnosis of dirofilariasis in atypical localizations of nematodes in the human body is of great importance in the differentiation of malignant and benign formations, and the use of the polymerase chain reaction method can significantly increase the accuracy in establishing the final diagnosis.
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Dirofilaria repens , Dirofilariose , Animais , Humanos , Idoso , Dirofilariose/diagnóstico , Dirofilariose/cirurgia , Dirofilaria repens/genética , Reação em Cadeia da Polimerase , Pulmão/patologia , Diagnóstico DiferencialRESUMO
Aim To study the relationship between monomeric C-reactive protein (mCRP) and the progression of asymptomatic carotid atherosclerosis in patients with a moderate risk for cardiovascular diseases (CVD) as assessed with the SCORE model.Material and methods The study included 80 men and women aged 53.1±5.8 years assigned to the category of a moderate risk for CVDs by the SCORE model with a low-density lipoprotein cholesterol (LDL-C) level of 2.7-4.8 mmol/l and asymptomatic, hemodynamically insignificant (<50% luminal narrowing) carotid atherosclerosis according to ultrasonic data. All patients were prescribed atorvastatin to achieve a LDL-C level <2.6âmmol/l. After 7 years of follow-up, ultrasonic examination of carotid arteries was performed, and concentrations of high-sensitivity C-reactive protein (hsCRP) and mCRP were measured.Results A concentration of LDL-C <2.6 mmol/l was achieved in all patients. The progression of atherosclerosis as determined by an increased number of atherosclerotic plaques (ASPs), was observed in 45 (56â%) patients. At 7 months of follow-up, concentrations of cCRP were higher in the group of patients with progressive carotid atherosclerosis, while the levels of hsCRP did not differ between the groups. Increased mCRP concentrations were associated with changes in variables of the "atherosclerotic load", including the number of ASPs, total ASP height, and the intima-media thickness (IMT). In patients with a median mCRP concentration of 5.2 [3.3; 7.1] µg/l and more, the increases in mean ACP number and total ASP height were considerably higher than in patients with mCRP concentrations lower than the median (3.9 and 2.7 times, respectively), whereas the odds ratio for the progression of asymptomatic carotid atherosclerosis was 5.5 (95â% confidence interval, CI: 2.1-14.6; p=0.001). ROC analysis showed that the concentration of hsCRP had no predictive value for prognosis of asymptomatic carotid atherosclerosis (p=0.16), while the area under the ROC curve (AUC) for mCRP was 0.75±0.056 (95â% CI: 0.64-0.86; p=0.001).Conclusion According to the results of 7-year follow-up, the plasma concentration of mCRP was significantly higher in patients with an increased number of ASPs than in patients without this increase. An increased level of mCRP may indicate a higher inflammatory risk of CVD.
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Aterosclerose , Proteína C-Reativa , Doenças Cardiovasculares , Doenças das Artérias Carótidas , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Biomarcadores , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/metabolismo , Espessura Intima-Media Carotídea , LDL-Colesterol , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The non-adiabatic electronic matrix elements, LΠΣ(R), that arise from the spin-conserving electron-rotational interactions between all mΣ+ and mΠ states, where multiplicity m = 1, 3, converging to the lowest three dissociation limits of Li-containing alkali diatomics, LiM (M = Na, K, Rb), were calculated ab initio up to large internuclear distances, R. The required electronic wavefunctions were obtained within the framework of the multi-reference configuration interaction treatment of the two-valence-electron problem constructed using small-core scalar-relativistic effective core potentials and l-independent core-polarization potentials. A least squares analysis of the ab initio functions at large internuclear distances in conjunction with long-range perturbation theory (LRPT) revealed three different asymptotic behaviors of the LΠΣ(R â +∞)-functions: const. + ß[n]/Rn, characterized by n = -1, 3 and 6. The asymptotic coefficients ß[n], extracted from the point-wise ab initio data, were found to be in agreement with their LRPT counterparts, which were evaluated analytically using the relevant atomic parameters. The mass dependence of the LΠΣ matrix elements was investigated analytically and numerically. To confirm the reliability of the LΠΣ(R)-functions and interatomic potentials at small and intermediate distances, the empirical q-factors available for the D1Π-states of all LiM molecules studied were compared with their theoretical counterparts derived from the present ab initio data.
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The spin-orbit (SO) interactions in low-lying electronic states of the LiM (M = Na, K, Rb, Cs) molecular series are studied through ab initio calculations of potential energy curves and SO coupling matrix elements as functions of the interatomic distance, R. Two different approaches are employed: (a) the Fock-space relativistic coupled-cluster calculations (FS-RCC) which directly yield full relativistic energies, Urel(R); the SO coupling functions, ξso(R), are extracted a posteriori through projecting scalar-relativistic wave functions onto the subspaces spanned by their full-relativistic counterparts; (b) the evaluation of the scalar-relativistic electronic energies, Usr(R), and relevant ξso(R) functions using the configuration interaction method with core-valence correlation accounted for using core polarization potentials (CI-CPP). The SO-free potentials and SO coupling functions obtained within the framework of both approaches are in good agreement with each other and their prior theoretical and empirical counterparts.
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The ion channel TRPV1, which is one of the most important integrators of pain and inflammatory stimuli, is considered a promising therapeutic target in the treatment of pain conditions. In this work, we performed a comparative study of the analgesic effect in the "hot plate" test of recombinant analogues of Kunitz-type peptides from the sea anemone Heteractis crispa venom: APHC1-modulator of TRPV1 and HCRG21-a full blocker of TRPV1. As a result of biological tests, it was shown that the full blocker HCRG21, despite the higher value of 50% effective concentration of TRPV1 inhibition, had an equal analgesic ability with the APHC1 upon intramuscular administration and retained it for 13 h of observation. The analgesic effect of APHC1 at a dose of 0.1 mg/kg when administered intramuscularly developed very quickly in 5 min but lasted 3 h. The differences in the pharmacodynamic profile of the peptides are in good agreement with different mechanisms of binding to TRPV1.
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Analgésicos/farmacologia , Venenos de Cnidários/farmacologia , Dor/tratamento farmacológico , Peptídeos/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Sequência de Aminoácidos , Analgésicos/administração & dosagem , Animais , Venenos de Cnidários/administração & dosagem , Modelos Animais de Doenças , Temperatura Alta , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos ICR , Dor/metabolismo , Peptídeos/administração & dosagem , Anêmonas-do-Mar , Homologia de SequênciaRESUMO
The article presents the results of a multicenter study of the etiology, antibiotic sensitivity and pharmacoepidemiology of infective endocarditis in the Russian Federation. The purpose of this study is to analyze the current practice of management of patients with infective endocarditis in conditions of low frequency of etiologically significant pathogens in the Russian Federation. The study included patients of both sexes of all age groups with definite and probable infective endocarditis. 406 cases of infectious endocarditis (240 in retrospect and 166 in the prospective part) were analyzed. Etiologically significant pathogen was isolated in 144 cases (35.5%). The structure of pathogens was dominated by gram (+) cocci (90.3%), most often - Staphylococcus aureus (46.5% of all isolated pathogens). Aminoglycosides (22.8%), parenteral cephalosporins of the III generation (22.1%) and glycopeptides (14.5%) were most frequently used in the course of starting antimicrobial therapy. When changing the mode of antimicrobial therapy, glycopeptides (18.6%), aminoglycosides (15.3%), fluoroquinolones (11.2%) and parenteral cephalosporins of generation III (9.5%) were most often prescribed.
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Antibacterianos/uso terapêutico , Endocardite Bacteriana/tratamento farmacológico , Cocos Gram-Positivos/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Cefalosporinas , Resistência a Medicamentos , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/microbiologia , Feminino , Cocos Gram-Positivos/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Farmacoepidemiologia , Estudos Prospectivos , Federação Russa/epidemiologia , Staphylococcus aureus/isolamento & purificação , Staphylococcus aureus/patogenicidadeRESUMO
In quality of life research, it is very important to understand the concept and methodology of its implementation. The quality of life study should be organized in accordance with standard generally accepted requirements. In order to obtain comparable data and to apply it in clinical practice, standard quality of life assessment tools should be implemented. The questionnaires are common as the tools assessing quality of life. In the United States and Europe, as well as in Russia, special centers are organized to develop such questionnaires. There are General questionnaires that can be used to assess quality of life in case of various diseases and special questionnaires targeted to specific group of diseases. Currently, more than 400 special questionnaires are used in practice. In Russia, due to urgency of increasing propagation of socially significant non-communicable diseases, especially in elderly population, particular attention is focused on research in the area of quality of life in field of palliative medicine, assigned to alleviate suffering of incurable patient. Its main goal is to maintain optimal quality of life of patient.
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Medicina Paliativa , Qualidade de Vida , Idoso , Europa (Continente) , Humanos , Cuidados Paliativos , Federação Russa , Inquéritos e Questionários , Estados UnidosRESUMO
TRPA1 is a cation channel located on the plasma membrane of many types of human and animal cells, including skin sensory neurons and epithelial cells of the intestine, lungs, urinary bladder, etc. TRPA1 is the major chemosensor that also responds to thermal and mechanical stimuli. Substances that activate TRPA1, e.g., allyl isothiocyanates (pungent components of mustard, horseradish, and wasabi), cinnamaldehyde from cinnamon, organosulfur compounds from garlic and onion, tear gas, acrolein and crotonaldehyde from cigarette smoke, etc., cause burning, mechanical and thermal hypersensitivity, cough, eye irritation, sneezing, mucus secretion, and neurogenic inflammation. An increased activity of TRPA1 leads to the emergence of chronic pruritus and allergic dermatitis and is associated with episodic pain syndrome, a hereditary disease characterized by episodes of debilitating pain triggered by stress. TRPA1 is now considered as one of the targets for developing new anti-inflammatory and analgesic drugs. This review summarizes information on the structure, function, and physiological role of this channel, as well as describes known TRPA1 ligands and their significance as therapeutic agents in the treatment of inflammation-associated pain.
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Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Inflamação Neurogênica/tratamento farmacológico , Dor/tratamento farmacológico , Canal de Cátion TRPA1/antagonistas & inibidores , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/química , Humanos , Ligantes , Estrutura Molecular , Inflamação Neurogênica/metabolismo , Dor/metabolismo , Canal de Cátion TRPA1/química , Canal de Cátion TRPA1/metabolismoRESUMO
AIM: The purpose of this study was to evaluate the diagnostic accuracy of Ñoronary Ñomputed tomography angiography (CCTA) in the diagnosis of stable coronary artery disease (CAD) in patients aged ≥70 years. MATERIALS AND METHODS: The study included 390 patients aged ≥70 years with symptoms suggested stable CAD which underwent elective coronary artery angiography (CAG). Initially the prevalence of angiographically significant CAD was estimated according to the gender and chest pain character, and identifications of patients in whom CCTA was appropriate. After that diagnostic accuracy and Ñost-efficiency of CCTA in the diagnosis of stable CAD in 82 patients with atypical angina and non-anginal chest pain were evaluated. RESULTS: The prevalence of obstructive CAD in patients with typical angina was very high and they were excluded from the final analysis. Among 82 patients with atypical angina and non-anginal pain which underwent CCTA 48 (59%) patients had obstructive CAD. CСTA data matched with results of CAG in all cases. Among 34 patients that had non-obstructive CAD the results of CCTA and CAG matched in 88% cases. CCTA has sensitivity, specificity, positive predictive value, negative predictive value of 100%, 88%, 92% and 100% respectively. The likelihood ratio for positive result was 8.3, likelihood ratio for negative result was 0.3. Positive result increased post-test probability of obstructive CAD from 42% to 86%, negative result reduced post-test probability of obstructive CAD to 0%. CONCLUSION: negative CCTA result in patients aged 70 years and older with atypical angina and non-anginal pain allows to exclude the presence of obstructive CAD. The likelihood ratio for positive result indicates a moderately difference between the pre-test and post-test probability of the presence of obstructive CAD. In patients aged ≥70 years with atypical angina or non-anginal chest pain which have inconclusive results of functional testing or unable undergo functional testing CCTA allows to increase diagnostic yield of CAG and reduce the frequency of minor complications and diagnostic evaluation costs.
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Doença da Artéria Coronariana , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris , Dor no Peito , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Humanos , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios XRESUMO
AIM: to compare diagnostic accuracy of exercise treadmill testing and stress echocardiography in the diagnosis of stable coronary artery disease (CAD) in patients aged >70 years. MATERIALS AND METHODS: The study included 390 patients aged >70 years with suspected stable ischemic heart disease, who underwent elective coronary artery angiography (CAG). Exercise treadmill testing (ETT) according to the modified Bruce protocol was carried out in 189 patients (48 %), bicycle stress echocardiography - in 179 patients (46 %). Initially we determined the prevalence of angiographically significant CAD according to the gender and chest pain character, and identified persons in whom stress testing was appropriate. After that diagnostic accuracy of both tests was evaluated in patients with atypical angina and non-anginal chest pain. RESULTS: Among 72 patients with atypical angina and non-anginal pain who underwent ETT and had unequivocal results, 38 (53 %) had obstructive CAD. ETT for detection of obstructive CAD had sensitivity 79 %, specificity 82 %, positive likelihood ratio (LR+) 4.4, and negative likelihood ratio (LR-) 0.3. Positive result increased probability of obstructive CAD from 53 % to 83 %, negative result reduced probability of obstructive CAD to 25 %. Among 111 patients with atypical angina and non-anginal pain who underwent stress echocardiography and had unequivocal results, 69 (62 %) had obstructive CAD. Sensitivity, specificity, LR+, and LR- of stress echocardiography were equal to 89 %, 95 %, 17.8, and 0.1, respectively. Positive result increased probability of obstructive CAD from 62 % to 95 %, negative result reduced probability of obstructive CAD to 16 %. CONCLUSION: bicycle stress echocardiography was found to be more accurate than ETT to rule in or rule out obstructive CAD in patients aged ≥ 70 years with atypical angina and non-anginal pain.
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Doença da Artéria Coronariana , Ecocardiografia sob Estresse , Idoso , Angina Pectoris , Angiografia Coronária , Teste de Esforço , HumanosRESUMO
CP is a copper-containing ferroxidase of blood plasma, which acts as an acute phase reactant during inflammation. The effect of oxidative modification of CP induced by oxidants produced by MPO, such as HOCl, HOBr, and HOSCN, on its spectral, enzymatic, and anti-inflammatory properties was studied. We monitored the chemiluminescence of lucigenin and luminol along with fluorescence of hydroethidine and scopoletin to assay the inhibition by CP of the neutrophilic respiratory burst induced by PMA or fMLP. Superoxide dismutase activity of CP and its capacity to reduce the production of oxidants in respiratory burst of neutrophils remained virtually unchanged upon modifications caused by HOCl, HOBr, and HOSCN. Meanwhile, the absorption of type I copper ions at 610 nm became reduced, along with a drop in the ferroxidase and amino oxidase activities of CP. Likewise, its inhibitory effect on the halogenating activity of MPO was diminished. Sera of either healthy donors or patients with Wilson disease were co-incubated with neutrophils from healthy volunteers. In these experiments, we observed an inverse relationship between the content of CP in sera and the rate of H2O2 production by activated neutrophils. In conclusion, CP is likely to play a role of an anti-inflammatory factor tempering the neutrophil respiratory burst in the bloodstream despite the MPO-mediated oxidative modifications.
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Ceruloplasmina/farmacologia , Neutrófilos/efeitos dos fármacos , Peroxidase/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Ceruloplasmina/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Neutrófilos/metabolismo , Oxirredução/efeitos dos fármacos , Peroxidase/metabolismoRESUMO
The ab initio electronic transition dipole moments (ETDMs) of heteronuclear dimers XY (X, Y = Li, Na, K, Rb) were calculated between the ground and excited states converging to the lowest three dissociation limits. The spin-allowed ETDMs were evaluated in a wide range of interatomic distances, R, by means of the quasi-relativistic electronic wave functions obtained by the multi-reference configuration interaction method. The inner-shell electrons (2 electrons for Li and Na atoms, and 10 and 28 for K and Rb, respectively) were described using the non-empirical shape-consistent effective core potentials. The l-independent core polarization potentials of each atom were used to take core-polarization and core-valence correlation effects into account. The long-range behavior of both singlet-singlet X1Σ+-(2,3)1Σ+;(1,2)1Π and triplet-triplet a3Σ+-(2,3)3Σ+;(1,2)3Π transition moments is perfectly fitted at large R-distance by the asymptotic formula of X. Chu and A. Dalgarno, Phys. Rev. A: At., Mol., Opt. Phys., 2002, 66, 024701: , where the coefficient ß is equal to 2 and -1 for the Σ-Σ and Σ-Π transitions, respectively. The n2S-n2P transition moments, dA, and dynamic polarizabilites, αB, of the alkali atoms in the n2S state extracted from the present molecular calculations coincide with their empirical and ab initio counterparts to within a few percent.
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The study was aimed at assessing the dynamics of asymptomatic atherosclerosis of carotid arteries (CA) depending upon the achieved level of low-density lipoprotein cholesterol (LDLC) in patients with moderate total risk by the SCORE scale. We followed up a total of eighty-two 40-to-65-year-old patients with the LDLC level above 2.6 mmol/l, being at moderate total risk by the SCORE scale and having symptom-free atherosclerosis of the extracranial portion of brachiocephalic arteries (up to 50% narrowing of their lumen) as diagnosed by duplex scanning. The patients were randomly divided into two groups. Group One patients (n=41) received therapy with atorvastatin in order to achieve the LDLC level less than 1.8 mmol/l. Group Two patients (n=41) were treated in order to achieve the LDLC level below 2.6 mmol/l. At 12 months of follow up we compared the dynamics of carotid atherosclerosis (change in the number, total height, structure, echogenicity, as well as the state of the surface of atherosclerotic plaques, alteration of the thickness of the CA intima-media complex). Group Two patients were found to have an increase in the number and average sum of the heights of atherosclerotic plaques. An increase of the maximum thickness of the intima-media complex of the wall of the right and left CA was more pronounced as compared with that in Group One patients. Aggressive hypolipidemic therapy aimed at achieving the LDLC level below 1.8 mmol/l turned out to be more effective in slowing down the progression of asymptomatic carotid atherosclerosis in patients with moderate cardiovascular risk than therapy targeted at achieving the LDLC level below 2.6 mmol/l.
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Atorvastatina/administração & dosagem , Tronco Braquiocefálico , Doenças das Artérias Carótidas , LDL-Colesterol/análise , Adulto , Anticolesterolemiantes/administração & dosagem , Doenças Assintomáticas , Tronco Braquiocefálico/diagnóstico por imagem , Tronco Braquiocefálico/patologia , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/tratamento farmacológico , Doenças das Artérias Carótidas/fisiopatologia , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Medição de Risco/métodos , Resultado do Tratamento , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/efeitos dos fármacos , Ultrassonografia Doppler Dupla/métodosRESUMO
The purpose of study is to investigate significance of detection of number of CD45-positive thrombocytes and ratio neutrophils/lymphocytes in evaluation of risk of development of re-stenosis after implantation of drug-eluting stents in patients with chronic ischemic heart disease and diabetes mellitus type II. The examination was applied to 126 patients with chronic forms of ischemic heart disease who passed through repeat coronary angiography during first year after implantation of drug-eluting stents. The patients were separated on two groups depending on availability of diabetes mellitus type II. In both groups, the patients passed through comparing of angiography and clinical characteristics. Also, a logistic model was developed prognosticating development of re-stenosis. The re-stenosis developed more often in patients with diabetes mellitus type II (54.5%) than in patients without diabetes mellitus type II (32.4%; p=0.01). The comparative analysis of more than 35 characteristics permitted to establish risk factors of development of re-stenosis with the highest prognosticating capacity among patients with diabetes mellitus type II. These risk factors were CD45-positive thrombocytes and ratio neutrophils/lymphocytes. To prognosticate development of re-stenosis a logistic regression model was developed comprising number of circulating CD45-positive thrombocytes, ratio neutrophils/lymphocytes and availability of diabetes mellitus type II. The model demonstrated high prognosticating value as regards development of re-stenosis: OR = 15.1 (95% CI 4.81-31, p < 0.001). The square under ROC-curve: AUC = 0.83 (95% CI 0,72-0,92; Ñ < 0,001). The increasing of number of circulating CD45-positive thrombocytes and ratio neutrophils/lymphocytes can be considered as a valuable risk factors of development of re-stenosis in case of diabetes mellitus type II.
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Plaquetas/citologia , Reestenose Coronária/sangue , Diabetes Mellitus Tipo 2/complicações , Linfócitos/citologia , Isquemia Miocárdica/complicações , Neutrófilos/citologia , Constrição Patológica , Angiografia Coronária , Diabetes Mellitus Tipo 2/sangue , Stents Farmacológicos , Humanos , Antígenos Comuns de Leucócito , Isquemia Miocárdica/sangue , Fatores de Risco , Resultado do TratamentoRESUMO
The study was carried out in 126 patients with stable angina pectoris, who underwent elective coronary artery stenting with drug-eluting stents and follow-up angiography within 6-12 months thereafter. Five significant risk factors of restenosis were identified by binary comparisons of different variables. The logistic regression equation that included the level of CD45-positive platelets, diabetes, small vessel stenting, number of simultaneously implanted stents in one patient, and lesion length demonstrates the highest level of prediction of in-stent restenosis (OR=22.8; p<0.001). ROC-analysis demonstrated high prognostic value of the logit model (area under ROC curve 0.87, p<0.001). The data suggest that a close relationship exists between the development of restenosis and the level of circulating CD45+ platelets.
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Angina Pectoris/patologia , Plaquetas/patologia , Constrição Patológica/patologia , Doença das Coronárias/patologia , Stents Farmacológicos/efeitos adversos , Adulto , Idoso , Angina Pectoris/metabolismo , Angina Pectoris/cirurgia , Plaquetas/metabolismo , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Angiografia Coronária , Doença das Coronárias/metabolismo , Doença das Coronárias/cirurgia , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Vasos Coronários/cirurgia , Diabetes Mellitus/fisiopatologia , Feminino , Expressão Gênica , Humanos , Antígenos Comuns de Leucócito/genética , Antígenos Comuns de Leucócito/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de RiscoRESUMO
The authors overview data on the prevalence of Zika fever with reference to biological properties of the causative agent, epidemiological process, pathogenesis, and clinical symptoms of the disease. Special attention is given to the identification of the virus in pregnant women, microcephaly in the babies born by Zika-infected women, algorithm of laboratory diagnostics, and measures needed to prevent and control mosquitoes that spread viruses.
Assuntos
Transmissão de Doença Infecciosa/prevenção & controle , Microcefalia , Complicações Infecciosas na Gravidez/diagnóstico , Infecção por Zika virus , Zika virus , Algoritmos , Feminino , Humanos , Recém-Nascido , Microcefalia/epidemiologia , Microcefalia/etiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Prevalência , Zika virus/imunologia , Zika virus/isolamento & purificação , Zika virus/patogenicidade , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/terapia , Infecção por Zika virus/virologiaRESUMO
A quantum key distribution system based on the subcarrier wave modulation method has been demonstrated which employs the BB84 protocol with a strong reference to generate secure bits at a rate of 16.5 kbit/s with an error of 0.5% over an optical channel of 10 dB loss, and 18 bits/s with an error of 0.75% over 25 dB of channel loss. To the best of our knowledge, these results represent the highest channel loss reported for secure quantum key distribution using the subcarrier wave approach. A passive unidirectional scheme has been used to compensate for the polarization dependence of the phase modulators in the receiver module, which resulted in a high visibility of 98.8%. The system is thus fully insensitive to polarization fluctuations and robust to environmental changes, making the approach promising for use in optical telecommunication networks. Further improvements in secure key rate and transmission distance can be achieved by implementing the decoy states protocol or by optimizing the mean photon number used in line with experimental parameters.