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We studied the production of short-chain fatty acids (SCFA) by the intestinal microbiota in mice with obesity caused by a diet and a genetic defect in the leptin receptor gene. In mice, intestinal contents were examined and SCFA were quantitatively assayed by gas chromatography. SCFA concentration in the intestinal contents of mice with alimentary obesity model was significantly lower in the first phase of the experiment (day 14), and the change in their production in dynamics was fundamentally different from this process in the control group (standard diet). The dynamics of the concentration of these metabolites in the model of genetic obesity was similar to that in the control, but the production of SCFA was significantly reduced in mice with leptin resistance in the middle phase (day 60) of the experiment. These findings indicate that the production of SCFA is more influenced by the diet than by leptin resistance.
Assuntos
Leptina , Obesidade , Animais , Camundongos , Leptina/genética , Obesidade/metabolismo , Intestinos , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , DietaRESUMO
BACKGROUND: Pulmonary hemorrhage (PH) is occasionally seen in premature infants after surfactant treatment for respiratory distress syndrome (RDS). These infants receive frequent chest radiographs (CXR) during and after hospitalization enabling long-term radiographic-clinical correlation. OBJECTIVE: To chart the natural evolution of CXR findings of PH in RDS and correlate radiographic patterns to supplemental oxygen requirement. MATERIALS AND METHODS: Retrospective review of clinical notes for gestational age (GA), birth weight (BW), intraventricular hemorrhage (IVH) and oxygen requirement were performed. CXRs were reviewed at 4 time-points; during PH, 28 days postnatal age, 36 weeks and at farthest available clinical follow-up. RESULTS: 18 infants born (2003-2016), GA (24-30 weeks); BW (482-1590 grams) were included. Mean onset of PH was 1.94 (0-5) days. 9/18 (50%) had IVH. 3 died during PH; all had IVH. During PH, CXR showed whiteout 9/18 (50%); patchy opacities 5/18 (27%); diffuse haziness 1/18 (6%) and no change 3/18 (17%). At 28 days postnatal age, CXR showed fine-interstitial (FI) markings 14/15 (93%) and whiteout 1/15 (7%). At 36 weeks,12/14 (85%) had FI and 2/14 (15%) developed cystic-interstitial changes. At farthest follow-up, FI 3/13 (23%); coarse-interstitial 4/13 (30%); peri-bronchial cuffing 5/13 (38%); normal 1/13 (9%) and the majority had hyperinflation 9/13 (69%). At discharge, 9/14 (64%) required home-oxygen and 5/14 (36%) were on room-air. At farthest follow-up, 6/14 (42%) required home-oxygen and 8/14 (58%) were on room-air. CONCLUSION: Premature infants that survive PH may later develop chronic lung disease of prematurity with an evolving interstitial pattern on CXR that clears overtime as they outgrow the need for supplemental oxygen.
Assuntos
Displasia Broncopulmonar/epidemiologia , Hemorragia/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Administração Tópica , Displasia Broncopulmonar/prevenção & controle , Hemorragia Cerebral Intraventricular/epidemiologia , Criança , Pré-Escolar , Comorbidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Surfactantes Pulmonares/uso terapêutico , Radiografia Torácica , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Despite platelets properties varies during storage, transfused platelets are included in blood clot in the same way as well as native. We assume that after transfusion the prevalence of platelets with changed activity lead to worse quality of blood clot in vivo. AIM: The aim was the in vitro study of platelet-dependent clot properties that are formed from some stored platelet concentrates (PCs). MATERIALS AND METHODS: Twenty-six PCs in autologous plasma and 24 PCs in platelet additive solution SSP+ (MacoPharma, France) (70vol.%) were analized by thromboelastography with and without platelets activation, and by standard aggregometry. The testing were carried out at the day of proceeding, after 24 hours, and at 3rd and 5th days of storage. We used Trima Accel (Terumo BCT, USA) for the proceeding of platelets apheresis. RESULTS: We found that clot demonstrated gradual reduction of elasticity and deformability starting from second day to fifth day in stored PCs suspended in autologous plasma. From the third storage day platelets lost their meaning for clot properties. The platelets apheresis with next re-suspending in SSP+ solution leads to the depression for platelets aggregability. Actived platelets had no impact to clot properties during full storage time. Total decline of clot quality including low elasticity and impaired deformability were found starting from 3rd storage day compared to the day of proceeding. CONCLUSIONS: We assume that such properties of clot as both elasticity and deformability are forming in PCs at the day of proceeding. Further clot changes observed in PCs does not depend directly from platelets aggregability because clot forming are under other influences. The last are determined mainly by the coagulation what was no included in this study. Also obtained results confirms the 5th-days storage as a benefit independent from PCs proceeding method.
RESUMO
INTRODUCTION: In today's antithrombotic prevention we forget that hemorheologic abnormalities are part of Virchow's triad. Isn't this one of reasons that venous thromboembolism (VTE) including catheter-related thrombosis (CRT) retain high frequency despite of modern antithrombotic therapy? AIM: The aim was to investigate rheological behavior of blood in patients with some myeloproliferative neoplasms. MATERIALS AND METHODS: The study included 16 adults with Polycythemia Vera (PV), 42 young with acute lymphoblastic leukemia (ALL), and 67 healthy donors as control group. Of patients 38% had thrombosis. We measured plasma viscosity, and whole blood viscosity (WBV) by shear rate from 300 to 5 s-1. Then indices were calculated for erythrocyte aggregation, and deformability, and non-Newtonian behavior of blood. Hematocrit, erythrocytes count, erythrocyte indices, leukocyte count, fibrinogen and B-type natriuretic peptide (BNP) were analyzed simultaneously. RESULTS: Increased WBV revealed totally in PV-patients but not by all shear rates in ALL-patients. Unlike donor, in patients WBV values had no equivalence under sequential one sample measurements with a decrease and then an increase of shear rates. We speculated this difference becomes diagnostic meaning like one and by its size. WBV dependent on leukocytes count, on MCH and mainly on MCV. Forty percent of patients had elevated BNP assuming subclinical cardiac dysfunction. The latter explains discoordinated changes in shear stress values required for fully reversible erythrocyte aggregation. As a result, residual units like "erythrocyte-erythrocyte" and/or "erythrocyte-leukocyte" interferes blood stream and violates mechanically blood flow in small vessels. Moreover in PV-patients but not in ALL-patients we found loss of non-Newtonian behavior of blood later than in control group. Both myeloproliferative neoplasms lead to increased erythrocyte aggregation but not impair deformability of red blood cells. In total these facts explains chronic hypoxia in these patients. CONCLUSIONS: Patients with some myeloproliferative neoplasms has abnormal blood flow properties. Revealed hemorheologic disturbances could be as a trigger to start of VTE or to growth of blood clot in the area of permanent venous catheter. These non-hemocoagulation conditions leaded for thrombus formation makes hemorheologic therapy looking attractive for antithrombotic management. The choice of targeted methods requires to continue this study.
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The catalytic activity of the c-Abl tyrosine kinase is tightly regulated by its Src homology 3 (SH3) domain through a complex mechanism that may involve intramolecular binding to Pro242 in the linker region between the SH2 and catalytic domains as well as interactions with a trans-inhibitor. We analysed the effect of mutation or replacement of SH3 on c-Abl tyrosine kinase activity and transformation. Random mutagenesis of SH3 identified several novel point mutations that dysregulated c-Abl kinase activity in vivo, but the RT loop was insensitive to mutational activation. Activating SH3 mutations abolished binding of proline-rich SH3 ligands in vitro, while mutations at Ser140 in the connector between the SH3 and SH2 domains activated Abl kinase activity in vivo and in vitro but did not impair SH3 ligand-binding. Abl was regulated efficiently when its SH3 domain was replaced with a heterologous SH3 from c-Src that binds a different spectrum of proline-rich ligands, but not by substitution of a modular WW domain with similar ligand-binding specificity. These results suggest that the SH3 domain regulates Abl principally by binding to the atypical intramolecular ligand Pro242 rather than a canonical PxxP ligand. Coordination between the SH3 and SH2 domains mediated by the connector region may be required for regulation of Abl even in the absence of SH2 ligand binding.
Assuntos
Mutagênese/genética , Mutação Puntual/genética , Proteínas Proto-Oncogênicas c-abl/química , Proteínas Proto-Oncogênicas c-abl/metabolismo , Domínios de Homologia de src/genética , Sequência de Aminoácidos , Animais , Far-Western Blotting , Caenorhabditis elegans , Catálise , Linhagem Celular , Transformação Celular Neoplásica , Ativação Enzimática , Cinética , Ligantes , Ligação Proteica , Estrutura Terciária de Proteína/genética , Proteínas Proto-Oncogênicas c-abl/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Especificidade por SubstratoRESUMO
The effect of mutations in the Src homology 2 (SH2) domain of the BCR/ABL oncogene on leukemogenesis was tested in a quantitative murine bone marrow transduction/transplantation assay that accurately models human Philadelphia-positive B-lymphoid leukemia and chronic myeloid leukemia (CML). The SH2 domain was not required for induction of B-lymphoid leukemia in mice by BCR/ABL. Under conditions where the p190 and p210 forms of BCR/ABL induce fatal CML-like myeloproliferative disease within 4 weeks, p210 SH2 mutants induced CML-like disease in some mice only after a significant delay, with other recipients succumbing to B-lymphoid leukemia instead. In contrast, p190 BCR/ABL SH2 point and deletion mutants rapidly induced CML-like disease. These results provide the first direct evidence of significant differences in cell signaling by the Bcr/Abl tyrosine kinase between these distinct leukemias. Contrary to previous observations, high levels of phosphatidylinositol 3-kinase (PI 3-kinase) activity in primary malignant lymphoblasts and myeloid cells from recipients of marrow transduced with the BCR/ABL SH2 mutants were found. Hence, the decreased induction of CML-like disease by the p210 BCR/ABL SH2 mutants is not due to impaired activation of PI 3-kinase.