Transforming growth factor β (TGF-β1) is a pleiotropic cytokine with many and complex effects in cell and tissue physiology. This is made possible by a very complex and interwoven signaling system, whose regulation continues to be the focus of a growing line of research. This complex regulation translates to a key role in cardiovascular physiology, hemostasis, and the blood–vessel interface. In accordance with this, the TGF-β1 pathway appears to be deregulated in related disorders, such as atherosclerotic vascular disease and myeloproliferative syndromes. It is expected that the growing amount of experimental and clinical research will yield medical advances in the applications of knowledge of the TGF-β1 pathway to diagnosis and therapeutics.
BackgroundTransforming growth factor beta (TGF-β1) is a pleiotropic cytokine, which is deregulated in atherosclerosis; however the role of age in this process is unknown. We aimed to assess whether TGF-β1 signaling is affected by age.MethodsVascular smooth muscle cells (VSMC) were obtained from patients undergoing abdominal surgery. Levels of TGF-β1 were measured by ELISA in sera from 169 patients undergoing coronary artery bypass grafting (CABG). The p27 expression was determined by Western blot from internal mammary arteries (IMA) obtained from CABG patients (n = 13). In VSMC from these patients undergoing abdominal surgery, secretion of TGF-β1 was determined by ELISA of cell-conditioned media.ResultsIn VSMC from aged patients we observed a lower TGF-β1 secretion, measured as TGF-β1 concentration in cell conditioned medium (p < 0.001). This effect was correlated to an age-dependent decrease of p27 expression in IMA from aged CABG patients. In a similar manner, there was an age-dependent decrease of serum TGF-β1 levels in CABG patients (p = 0.0195).ConclusionsVSMC from aged patients showed a higher degree of cellular senescence and it was associated to a lower TGF-β1 secretion and signaling.
Objective To evaluate whether the concentration of serum lactate during the diagnosis of postpartum hemorrhage (bleeding ≥500 mL during labor or ≥1000 mL during cesarean delivery) predicts severe hemorrhage (SPPH; blood loss ≥1500 mL at end of labor or in the following 24 h). Methods A prospective cohort pilot study was conducted of women with a vaginal or cesarean delivery from February 2018 to March 2019 who presented with bleeding ≥500 mL measured by the gravimetric method in a reference hospital in San Luis Potosi, Mexico. Venous blood samples were taken for analysis of serum lactate. A receiver operating characteristic curve determined the serum lactate threshold value for SPPH and χ2 test assessed the difference in serum lactate elevation between SPPH and non‐SPPH groups. Lastly, the prognostic capacity between the thresholds was compared. Results SPPH developed in 43.33% of the 30 women in the study group. The best prognostic threshold was 2.68 mmol/L of serum lactate (odds ratio [OR] 17.88, 95% confidence interval [CI] 2.7–16.8, P < 0.001); sensitivity was 0.85 (95% CI 0.55–0.98); specificity was 0.76 (95% CI 0.50–0.93). Conclusion Serum lactate may be a useful prognostic marker for SPPH, more studies are needed to validate these findings.
Dengue is a potentially letal mosquito-borne flavivirus disease with about 390 million worldwide infections per year. We have experienced recurrent dengue epidemics in Brazil and Paraguay. We aimed to determine the impact and clinical outcome of diabetes (DM) and hyperglycemia during hospital admission in hospitalized patients for dengue. A total of 294 patients were admitted to a single medical center. Of them,47 (16%) patients had the previous diagnosis of DM (age: 62±12 years, blood glucose [BG]: 238±116 mg/dl), 44 (14.9%) patients had hyperglycemia (BG ≥180 mg/dl) without a prior diagnosis of DM (49±18 years, BG; 165±34 mg/dl) and 214 (73%) had normoglycemia (49±19 years, BG: 110±18 mg/dl). Patients with diabetes and hyperglycemia were older and were more likely to present with severe or hemorrhagic dengue, hemodynamic shock, acute kidney injury (AKI) requiring admission to the ICU and blood transfusion, and longer length of stay. There was a single death in a non-DM patient. Compared to patients with normoglycemia, non-DM patients with hyperglycemia (≥180 mg/dl) had more severe form of dengue with AKI (9.1% vs. 20.7%, OR: 2.61), hemodynamic shock (3.4% vs. 33.3%, OR: 2.61), ICU admission (4.4% vs. 33%, p=0.03) and longer length of hospital stay (4.7 days and 7.1 days, p=0.01). Conclusion: Patients with DM and hyperglycemia were more likely to develop a more severe and hemorrhagic dengue compared to patients with normoglycemia. Because there is no specific dengue therapeutics, prevention is currently limited to vector control measures. A dengue vaccine program could represent a major advance in the control of the disease in patients with diabetes. Disclosure E.D. Bueno Colman: None. Y.A. Pozzo: None. G.E. Umpierrez: Research Support; Self; Sanofi US, Merck & Co., Inc., Novo Nordisk Inc., AstraZeneca. Advisory Panel; Self; Sanofi, Intarcia Therapeutics, Inc.. U.B. Medina: None. A. Benitez: None. S.N. Marin: None.
Background and objectives: Dipeptidyl-Peptidase 4 (DPP-4) is a protein expressed in numerous cells and tissues. Recently it has shown its involvement as a catalyst in the inflammatory response in various pulmonary, autoimmune, intestinal and other pathologies. The objective of this study was to compare the preoperative serum levels of DPP-4 in patients with and without surgical finding of perivesicular inflammation. Materials and methods: a cross-sectional analytical study nested in a prospective cohort, including patients scheduled for elective cholecystectomy, without surgical complications, that were 18–70 years of age, with low cardiovascular risk, without a history of peritonitis, pancreatitis, or jaundice and underwent ERCP protocol, type 2 diabetes mellitus, acute inflammatory (Protein C Reactive < 3 mg/L, leucocytes < 10 1000/mm3), neoplastic, nephrologic or liver disease, the use of anti-inflammatory drugs, steroids and/or antibiotics, the use of pacemakers or metallic implants and without major amputations and whom agreed to participate by providing their informed consent. Ethical and Research register: 45–16. Prior to surgery we compiled anthropometric data and a blood sample to determine the serum levels of DPP-4. The presence of perivesicular inflammation was determined in the surgery. The data was analyzed using the statistical program Rstudio. Results: High BMI values were observed (27.8 ± 6.4); waist circumference (94.7 ± 15.1) and percentage of fat mass (34.7 ± 11.7), showing a cumulative frequency of 65.9% for overweight/obesity. In 27.3% of the interventions, intraoperative perivesicular inflammation findings were reported. The serum levels of DPP-4 were lower in the group of patients with perivesicular inflammation (3947.6 ± 1659.5 vs. 3053.2 ± 1469.6, LC95% of the difference: 160.4–1628.3), being statistically significant (p = 0.018). Conclusions: In the subacute or chronic phases of cholecystitis, there appears to be a constant consumption of DPP-4, which would modulate a better immune response that could be related to the reduction of postoperative complications, so the use of Serum levels of DPP-4 as an early biomarker could improve the diagnostic accuracy of this pathology and the surgical approach.
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