Computer simulation of cervical tissue response to a hydraulic dilator device

Background: Classical mechanical dilators for cervical dilation are associated with various complications, such as uterine perforation, cervical laceration, infections and intraperitoneal hemorrhage. A new medical device called continuous controllable balloon dilator (CCBD) was constructed to make a significant reduction in all of the side effects of traditional mechanical dilation. Method. In this study we investigated numerically the cervical canal tissue response for Hegar and CCBD using our poroelastic finite element model and in-house software development. Boundary conditions for pressure loading on the tissue for both dilators in vivo were measured experimentally. Material properties of the cervical tissue were fitted with experimental in vivo data of pressure and fluid volume or balloon size. Results: Obtained results for effective stresses inside the cervical tissue clearly showed higher stresses for Hegar dilator during dilation in comparison with our CCBD. Conclusion: This study opens a new avenue for the implementation of CCBD device instead of mechanical dilators to prevent cervical injury during cervical dilation. © 2013 Filipovic et al.; licensee BioMed Central Ltd

Increased severity of ulcerative colitis in the terminal phase of the metabolic syndrome

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro-and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome

Synthesis, Characterization, and Cytotoxicity of Binuclear Cooper(II)-Complexes with some S-Alkenyl Derivatives of Thiosalicyclic Acid

New complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid (alkenyl = propenyl-(L1), isobutenyl-(L2)) have been synthesized and characterized by microanalysis, infrared spectra, magnetic measurements, and by NMR spectra. The cytotoxic activity of two newly synthesized precursor S-alkenyl derivatives of thiosalicylic acid were tested using an MTT colorimetric technique on HCT-116 human colon carcinoma cells. The cytotoxic effect of the copper(II)- complexes were higher compared to the cytotoxicity of the corresponding ligand (for concentrations from 31.25 to 250 μM). Copper(II)-complexes showed a slightly lower cytotoxicity compared to cisplatin. Complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid (at concentrations from 250 to 1000 μM) had a cytotoxic effect on HCT-116 cells compared to cisplatin

Overexpression of Galectin 3 in Pancreatic β Cells Amplifies β-Cell Apoptosis and Islet Inflammation in Type-2 Diabetes in Mice

© Copyright © 2020 Petrovic, Pejnovic, Ljujic, Pavlovic, Miletic Kovacevic, Jeftic, Djukic, Draginic, Andjic, Arsenijevic, Lukic and Jovicic. Aims/Hypothesis: Galectin 3 appears to play a proinflammatory role in several inflammatory and autoimmune diseases. Also, there is evidence that galectin 3 plays a role in both type-1 and type-2 diabetes. During obesity, hematopoietic cell-derived galectin 3 induces insulin resistance. While the role of galectin 3 expressed in islet-invading immune cells in both type-1 and type-2 diabetes has been studied, the importance of the expression of this molecule on the target pancreatic β cells has not been defined. Methods: To clarify the role of galectin 3 expression in β cells during obesity-induced diabetogenesis, we developed transgenic mice selectively overexpressing galectin 3 in β cells and tested their susceptibility to obesity-induced type-2 diabetes. Obesity was induced with a 16-week high-fat diet regime. Pancreatic β cells were tested for susceptibility to apoptosis induced by non-esterified fatty acids and cytokines as well as parameters of oxidative stress. Results: Our results demonstrated that overexpression of galectin 3 increases β-cell apoptosis in HFD conditions and increases the percentage of proinflammatory F4/80+ macrophages in islets that express galectin 3 and TLR4. In isolated islets, we have shown that galectin 3 overexpression increases cytokine and palmitate-triggered β-cell apoptosis and also increases NO2−-induced oxidative stress of β cells. Also, in pancreatic lymph nodes, macrophages were shifted toward a proinflammatory TNF-α-producing phenotype. Conclusions/Interpretation: By complementary in vivo and in vitro approaches, we have shown that galectin 3-overexpression facilitates β-cell damage, enhances cytokine and palmitate-triggered β-cell apoptosis, and increases NO2−-induced oxidative stress in β cells. Further, the results suggest that increased expression of galectin 3 in the pancreatic β cells affects the metabolism of glucose and glycoregulation in mice on a high-fat diet, affecting both fasting glycemic values and glycemia after glucose loading

Molecular mechanisms underlying therapeutic potential of pericytes

Abstract Background Pericytes are multipotent cells present in every vascularized tissue in the body. Despite the fact that they are well-known for more than a century, pericytes are still representing cells with intriguing properties. This is mainly because of their heterogeneity in terms of definition, tissue distribution, origin, phenotype and multi-functional properties. The body of knowledge illustrates importance of pericytes in the regulation of homeostatic and healing processes in the body. Main body In this review, we summarized current knowledge regarding identification, isolation, ontogeny and functional characteristics of pericytes and described molecular mechanisms involved in the crosstalk between pericytes and endothelial or immune cells. We highlighted the role of pericytes in the pathogenesis of fibrosis, diabetes-related complications (retinopathy, nephropathy, neuropathy and erectile dysfunction), ischemic organ failure, pulmonary hypertension, Alzheimer disease, tumor growth and metastasis with the focus on their therapeutic potential in the regenerative medicine. The functions and capabilities of pericytes are impressive and, as yet, incompletely understood. Molecular mechanisms responsible for pericyte-mediated regulation of vascular stability, angiogenesis and blood flow are well described while their regenerative and immunomodulatory characteristics are still not completely revealed. Strong evidence for pericytes’ participation in physiological, as well as in pathological conditions reveals a broad potential for their therapeutic use. Recently published results obtained in animal studies showed that transplantation of pericytes could positively influence the healing of bone, muscle and skin and could support revascularization. However, the differences in their phenotype and function as well as the lack of standardized procedure for their isolation and characterization limit their use in clinical trials. Conclusion Critical to further progress in clinical application of pericytes will be identification of tissue specific pericyte phenotype and function, validation and standardization of the procedure for their isolation that will enable establishment of precise clinical settings in which pericyte-based therapy will be efficiently applied