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Stem cells derived from adult tissues may serve as cell therapy to enhance the healing process in skin wounds. This study was designed to evaluate the use of autologous muscle-derived stem cells in an experimental skin wound model in terms of their efficiency at promoting tissue repair/regeneration. Muscle-derived cells obtained from the dorsal muscle of New Zealand rabbits were cultured in vitro for 2 weeks. The cell population was identified using the satellite markers CD34, m-cadherin and Myf5, and the proliferative capacity of the adult stem cells was determined. The population was then fluorescently labeled with PKH26 and seeded onto a circular 2 cm diameter defect created on the dorsal side of the ear of the rabbit from which the cells had been harvested. Similar defects on the contra lateral ears were left untreated to form the control group. Fourteen days later, specimens were taken for light, transmission, and scanning electron microscopy, as well as for immunolabeling with antibodies against vimentin, α-actin, desmin, myosin, fibronectin, and cytokeratin 14. Areas of wound contraction and reepithelialization were determined by image analysis. Wound contraction was significantly greater in the control than the treatment group ( p<0.05); control specimens also showed more myosin expression. Reepithelialized areas were significantly greater in the treatment group ( p<0.05). Control wounds showed nonepithelialized areas and inflammatory granulation tissue. Reepithelialization occurred as epidermal tongues of fusiform cells. Our findings indicate that the use of autologous stem cells on skin wounds expedites and improves the organism's natural healing process. [ABSTRACT FROM AUTHOR]

This study evaluates possible changes in the synthesis/degradation of elastic components of the vein wall in an attempt to explain the development of varicosis. Healthy and varicose saphenous veins were subjected to immunohistochemical analysis using anti-elastin, anti-fibrillin-1, anti-elastase, anti-transforming growth factor (TGF)-β and anti-latent TGFβ binding protein (LTBP)-2 monoclonal antibodies. In situ hybridization was performed using specific probes for tropoelastin and fibrillin-1. In healthy veins, elastin and fibrillin-1 showed even, overlapping distribution patterns indicating their particular abundance in the adventitia and at the intima/media interface. The expression of tropoelastin and fibrillin-1 was high in smooth muscle cells bordering the elastic laminae. Elastin, fibrillin-1, and cells expressing fibrillin-1 and tropoelastin mRNA showed a patchy disorganized pattern, particularly in the proximal varicose segments of patients under 50 years of age. Enhanced elastase activity was noted in both control and varicose specimens from elderly subjects. Varicose veins specimens showed greater LTBP-2 and TGF expression. Both molecules were detected in the subendothelium and the media, particularly in areas of marked injury. Our findings suggest that the development of the varicose condition involves a restructuring of the elastic component of the vein wall, perhaps as a consequence of changes in the transcription mechanisms of muscle layer cells. [ABSTRACT FROM AUTHOR]

Intercellular contacts formed between endothelial cells (EC) permit the formation of a confluent monolayer and play a major role in the recruitment and the migration of leukocytes in the inflammatory response. It is currently accepted that cytokines are responsible for the signals involved in the induction of such endothelial alterations. The platelet EC adhesion molecule (PECAM-1), a specific component of EC junctions, is one of many molecules which participate in the regulation of EC interaction with blood components. Given that the regulatory mechanisms which affect the expression of this adhesion molecule are only partially understood, the aim of the present study was to compare the effects of two antagonistic inflammatory cytokines, interferon (IFN)-γ and interleukin (IL)-10, on the expression of PECAM-1. Human umbilical vein EC grown to subconfluence were stimulated with IL-10 (10 ng/ml) and/or IFNγ (100 U/ml) for 24 h. PECAM-1 expression was determined by FACScan and immunofluorescence. Morphological analysis of the cell cultures was performed by optical and scanning electron microscopy. In the presence of IL-10, no changes in cell growth and morphology or in the intensity of PECAM-1 expression were observed. However, when the cultures were treated with IFNγ, the EC acquired a fibroblast-like appearance, growth was disorganized and PECAM-1 disappeared from cell junctions. The mean intensity expression and the percentage of EC expression of this antigen were analyzed by flow cytometry and significantly decreased after culture in the presence of IFNγ. The simultaneous addition of IFNγ and IL-10 to the EC cultures induced modifications similar to those observed in the presence of IFNγ alone. Regulation of the expression of PECAM-1 with the subsequent functional implications seems to be dependent upon the IFNγ signal and it is unaffected by IL-10. The different effects shown by IL-10 and IFNγ on the expression of PECAM-1 in EC could reflect opposite regulatory actions of the inflammatory response induced by these cytokines. [ABSTRACT FROM AUTHOR]

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43− and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic. [ABSTRACT FROM AUTHOR]

Normal arterial aging processes involve vascular cell dysfunction associated with wall stiffening, the latter being due to progressive elastin and elastic fiber degradation, and elastin and collagen cross-linking by advanced glycation end products (AGEs). These processes progressively lead to cardiovascular dysfunction during aging. Elastin is only synthesized during late gestation and childhood, and further degradation occurring throughout adulthood cannot be physiologically compensated by replacement of altered material. However, the ATP-dependent K+ channel opener minoxidil has been shown to stimulate elastin expression in vitro and in vivo in the aorta of young adult rats. Therefore, we have studied the effect of a 10-week chronic oral treatment with minoxidil (120 mg/L in drinking water) on the aortic structure and function in aged 24-month-old mice. Minoxidil treatment increased tropoelastin, fibulin-5, and lysyl-oxidase messenger RNA levels, reinduced a moderate expression of elastin, and lowered the levels of AGE-related molecules. This was accompanied by the formation of newly synthesized elastic fibers, which had diverse orientations in the wall. A decrease in the glycation capacity of aortic elastin was also produced by minoxidil treatment. The ascending aorta also underwent a minoxidil-induced increase in diameter and decrease in wall thickness, which partly reversed the age-associated thickening and returned the wall thickness value and strain-stress relation closer to those of younger adult animals. In conclusion, our results suggest that minoxidil presents an interesting potential for arterial remodeling in an antiaging perspective, even when treating already aged animals. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVeD) is a rising medical condition characterized by a broad spectrum of disorders in the venous system. Varicose veins (VVs) represent a frequent clinical manifestation of CVeD, particularly in the lower limbs. Prior histopathological studies have defined a set of alterations observed in the venous wall of patients with VVs, affecting their structure and behavior. Metabolic changes in the veins appear to be a critical biological mechanism aiding our understanding of the pathogenesis of CVeD. In this sense, previous studies have identified a potential role of a glycolytic phenotype in the development of different vascular disorders; however, its precise role in CVeD remains to be fully explored. Thus, the aim of the present study was to analyze the gene and protein expression of glucose transporter 1 (GLUT-1) and the glycolytic enzymes PGK-1, ALD, GA3PDH and LDH in the VVs of patients with CVeD (n = 35) in comparison to those expressed in healthy subjects. Our results display enhanced gene and protein expression of GLUT-1, PGK-1, ALD, GA3PDH and LDH in patients with CVeD, suggesting a glycolytic switch of the venous tissue. Greater understanding of the impact of this glycolytic switch in patients with CVeD is required to define a possible pathophysiological role or therapeutic implications of these changes. [ABSTRACT FROM AUTHOR]

Penile carcinoma is a rare urological neoplasia in men compared to other more common tumors, such as prostate, kidney, or bladder tumors. However, this neoplasm continues to affect a large number of patients worldwide, with developing countries presenting the highest incidence and mortality rates. Important risk factors such as the human papilloma virus, a factor affecting a large number of patients, have been described; however, few studies have evaluated screening programs in populations at risk for this disease, which severely affects the quality of life of older men. The management of these patients is usually complex, requiring surgical interventions that are not without risk and that have a great impact on the functionality of the male reproductive system. In addition, in cases of disseminated disease or with significant locoregional involvement, patients are evaluated by multidisciplinary oncological committees that can adjust the application of aggressive neoadjuvant or adjuvant chemotherapy on numerous occasions without clear improvement in survival. Chemotherapy regimens are usually aggressive, and unlike in other urological neoplasms, few advances have been made in the use of immunotherapy in these patients. The study of serological and histological biomarkers may help to better understand the underlying pathophysiology of these tumors and select patients who have a higher risk of metastatic progression. Similarly, the analysis of molecular markers will improve the availability of targeted therapies for the management of patients with disseminated disease that would benefit prognosis. Therefore, the purpose of this article is to summarize the main advances that have occurred in the development of serological and histological markers and their therapeutic implications in patients diagnosed with penile carcinoma, explaining the limitations that have been observed and analyzing future perspectives in the management of this disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is one of the most heterogeneous and aggressive tumours that exist. The median survival of diagnosed patients is limited. For all these reasons, it is necessary to develop new disease markers that allow guidelines for clinical action to improve the average survival of patients with pancreatic cancer. The incidence and prevalence of pancreatic adenocarcinoma have increased in recent years. Pancreatic cancer is the seventh leading cause of cancer death, but it is projected to become the second leading cause of cancer-related mortality by 2040. Most patients are diagnosed in an advanced stage of the disease, with very limited 5-year survival. The discovery of different tissue markers has elucidated the underlying pathophysiology of pancreatic adenocarcinoma and allowed stratification of patient risk at different stages and assessment of tumour recurrence. Due to the invasive capacity of this tumour and the absence of screening markers, new immunohistochemical and serological markers may be used as prognostic markers for recurrence and in the study of possible new therapeutic targets because the survival of these patients is low in most cases. The present article reviews the currently used main histopathological and serological markers and discusses the main characteristics of markers under development. [ABSTRACT FROM AUTHOR]

Pancreatic cancer will be positioned by the year 2030 as the second cause of oncological death after lung cancer. The pathophysiology of the most common variety, which involves the adenocarcinoma of the pancreas, represents one of the main challenges for current oncology to explain its tumorigenesis and create a targeted treatment. The tumor microenvironment, metastatic capacity, and lack of early diagnosis lead patients to present advanced stages at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcomes and with respect to the improved survival of these patients. For this reason, in recent years, numerous diagnostic tests, treatments, and possible approaches in the fields of radiotherapy, chemotherapy, immunotherapy, and surgery have been developed to find a combination of methods that improves life expectancy in patients diagnosed with this disease. On the other hand, the scientific community has made numerous advances in the molecular bases of pancreatic cancer since several oncogenetic pathways have been described and the markers expressed by the tumor have proven to be useful in the prognosis of pancreatic adenocarcinoma. These molecular alterations allow the study of possible therapeutic targets that improve the prognosis of these patients, but even numerous tumor cell-individual interactions must be explained to understand the underlying pathophysiology causing the high mortality. Therefore, the purpose of our study is to examine the expression of markers such as EGFR, Cyclin D1, andCDK4 in order to find a relationship with the possible long-term prognostic factors of patients affected by pancreatic ductal adenocarcinoma. Our results show that there is a prognostic role for ErbB2, EGFR, beta catenin, cyclin D1, and CDK4. Of these, we highlight the clinical importance of ErbB2 in the survival rates of patients who overexpress this component. [ABSTRACT FROM AUTHOR]

Mesenchymal cells (MSCs) are considered to be cellular populations of common embryological origin. For clinical research applications, MSCs are expanded and increased with cells obtained from a primary culture. By extracting cells from tissue and encouraging them to reproduce, the stem cell population ends up dominating the culture due to a high proliferation rate and self-renewal. The first subcultures between the third and sixth are chosen in order to obtain the maximum number of cells with optimal differentiation capacity. However, few studies have reported long-term cultivation of MSCs. The objective of this study was to advance the knowledge on the characteristics of MSCs by assessing their capacity for self-renewal and phenotypic maintenance beyond 50 cell subcultures, which is defined as the normal limit for cellular survival. Rat subcutaneous adipose tissue was the source of mesenchymal adipose stem cells (MASCs) cultured over 175 subcultures. Early 1 to 5 and late 25 to 30 subcultures were used to induce cellular differentiation to become adipogenic, chondrogenic and osteogenic connective tissue cells. MASCs characteristics were studied using flow cytometry, transmission electron microscopy (TEM), and immunohistochemical and reverse transcription polymerase chain reaction (RT-qPCR) assays. The MASCs maintained cell differentiation capacity for more than 30 subcultures but lost potentiality starting at 60 up to 175 subcultures. MASCs showed the embryonic phenotypes OCT3/4 and Nanog indefinitely, and developed compensatory mechanisms, such as autophagy, to achieve cell survival over a long time period. Therefore, long-term subcultures showed that MASCs could maintain their potential for clinical research use. [ABSTRACT FROM AUTHOR]

The wear rate on Total Hip Arthroplasty (THA) entails a heavy burden for patients. This becomes more relevant with increased wear risk and its consequences such as osteolysis. In addition, osteolysis has been described in cemented and uncemented acetabular implants, and nowadays, controversy remains as to whether or not to cement the acetabular component. A personalized theoretical study was carried out to investigate which parameters have an influence on wear risk and to determine the best fixation method. Liner wear risk was assessed for two different types of fixation (cemented vs uncemented) through Finite Elements Analysis (FEA). The intraoperative variables used to determine the wear risk (cervical-diaphyseal angle, Center of Rotation positioning -COR-, head material, head size, and liner thickness) are vital parameters in surgical planning. Two types of tridimensional liner models of Ultra High Molecular Weight Polyethene (UHMWPE) were simulated through finite element analysis (FEA—over 216 cases were the core of this research). A significant relationship was found between the cervical-diaphyseal angle and wear risk (p < 0.0001), especially in valgus morphology. The acetabular fixation technique (p < 0.0001) and liner thickness (p < 0.0001) showed a significant relationship with wear risk. According to our study, using a cemented fixation with a thick liner in the right center of rotation appears to be the proper stratagy for preventing polyethylene liner wear. [ABSTRACT FROM AUTHOR]

Background: This study was designed to establish whether the spatial structure of a prosthesis conditions its behavior at the peritoneal level.Methods: Abdominal defects comprising all the wall (except skin) were created in rabbits and repaired with a laminar (DM) or reticular (CV-4) ePTFE-prosthesis. Fourteen days postimplant, specimens were obtained for scanning electron and light microscopy. Peritoneal adhesions, resistance to traction, and neoperitoneum thickness were quantified.Results: Adhesions to CV-4 were firm and integrated within surrounding tissue; only scarce adhesion formation was observed for DM. Adhesion area was significantly greater (P <0.01) in the CV-4 than in DM (7.00 ± 2.6; 0.15 ± 0.08 cm2). The neoperitoneum was organized for DM and disorganized for CV-4. This layer was significantly thicker (P <0.05) in DM than CV-4 (455 ± 3.4; 70 ± 3.1 μm). The CV-4 showed a greater resistance to traction than the DM (26.75 ± 3.71; 14.11 ± 3.71 N; P <0.05).Conclusions: The structure of a biomaterial, rather than its chemical composition, modulates behavior at the peritoneal interface. [Copyright &y& Elsevier]

An experimental study of platelet aggregation was performed in 22 male Landrace × Large-White crossbred pigs treated with propofol at different doses, to compare the results of optical aggregometry with those of the PFA-100™ (Dade Int., Miami, FL, USA), a new platelet function analyzer. Platelet aggregation was analyzed in basal blood samples by both methods, after which the pigs were divided into three groups: G1, anaesthetic induction with propofol (2 mg/kg intravenously (i.v.)); G2, anaesthetic induction with propofol (2 mg/kg i.v.), followed by a second dose of 1.5 mg/kg; and G3, anaesthetic induction with propofol (2 mg/kg i.v.), followed by 1 h of continuous i.v. infusion at 13 mg/kg/h. Four minutes after propofol injection, blood samples were again taken from each group and studied by both methods. In groups G2 and G3, both methods showed reduced platelet aggregation, while in group G1 neither evidenced an anti-aggregating effect of propofol. Under our experimental conditions: (1) the propofol effect on platelet aggregation depends on the plasma concentration; (2) the results obtained with the two methods are comparable; (3) PFA-100™ may provide an alternative to optical aggregometry for detecting the effects of anaesthetic agents ex vivo. [ABSTRACT FROM AUTHOR]

Immunodeficient mouse models with human skin xenografts have been developed in the past decades to study different conditions of the skin. Features such as follow-up period and size of the graft are of different relevance depending on the purpose of an investigation. The aim of this study is to analyze the different mouse models grafted with human skin. A systematic review of the literature was performed in line with the PRISMA statement using MEDLINE/PubMed databases from January 1970 to June 2020. Articles describing human skin grafted onto mice were included. Animal models other than mice, skin substitutes, bioengineered skin, postmortem or fetal skin, and duplicated studies were excluded. The mouse strain, origin of human skin, graft dimensions, follow-up of the skin graft, and goals of the study were analyzed. Ninety-one models were included in the final review. Five different applications were found: physiology of the skin (25 models, mean human skin graft size 1.43 cm2 and follow-up 72.92 days), immunology and graft rejection (17 models, mean human skin graft size 1.34 cm2 and follow-up 86 days), carcinogenesis (9 models, mean human skin graft size 1.98 cm2 and follow-up 253 days), skin diseases (25 models, mean human skin graft size 1.55 cm2 and follow-up 86.48 days), and would healing/scars (15 models, mean human skin graft size 2.54 cm2 and follow-up 129 days). The follow-up period was longer in carcinogenesis models (253 ± 233.73 days), and the skin graft size was bigger in wound healing applications (2.54 ± 3.08 cm2). Depending on the research application, different models are suggested. Careful consideration regarding graft size, follow-up, immunosuppression, and costs should be analyzed and compared before choosing any of these mouse models. To our knowledge, this is the first systematic review of mouse models with human skin transplantation. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVeD) has a remarkable prevalence, with an estimated annual incidence of 2%. It has been demonstrated how the loss of homeostatic mechanisms in the vein wall can take part in the physiopathology of CVeD. In this regard, it has been described how different axis, such as IGF-1/PAPP-A/STC-2 axis, may play an essential role in tissue homeostasis. The aim of this research is to study both genetic and protein expressions of the IGF-1/PAPP-A/STC-2 axis in CVeD patients. It is a cross-sectional study in which genetic (RT-qPCR) and protein (immunohistochemistry) expression analysis techniques were accomplished in saphenous veins from CVeD patients (n = 35) in comparison to individuals without vascular pathology (HV). Results show a significant increase in both genetic and protein expressions of PAPP-A and IGF-1, and a decrement STC-2 expression at the same time in CVeD patients. Our study is a pioneer for demonstrating that the expression of the different components of the IGF-1/PAPP-A/STC-2 axis is altered in CVeD patients. This fact can be a part of the loss of homeostatic mechanisms of the venous tissue. Further research should be destined to deepen into alterations of this axis, as well as to evaluate the usage of these components as therapeutic targets for CVeD. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVeD) has a remarkable prevalence, with an estimated annual incidence of 2%. It has been demonstrated how the loss of homeostatic mechanisms in the vein wall can take part in the physiopathology of CVeD. In this regard, it has been described how different axis, such as IGF-1/PAPP-A/STC-2 axis, may play an essential role in tissue homeostasis. The aim of this research is to study both genetic and protein expressions of the IGF-1/PAPP-A/STC-2 axis in CVeD patients. It is a cross-sectional study in which genetic (RT-qPCR) and protein (immunohistochemistry) expression analysis techniques were accomplished in saphenous veins from CVeD patients (n = 35) in comparison to individuals without vascular pathology (HV). Results show a significant increase in both genetic and protein expressions of PAPP-A and IGF-1, and a decrement STC-2 expression at the same time in CVeD patients. Our study is a pioneer for demonstrating that the expression of the different components of the IGF-1/PAPP-A/STC-2 axis is altered in CVeD patients. This fact can be a part of the loss of homeostatic mechanisms of the venous tissue. Further research should be destined to deepen into alterations of this axis, as well as to evaluate the usage of these components as therapeutic targets for CVeD. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is the final treatment for knee osteoarthritis, and 15–30% of patients show little or no improvement. This high percentage is related to aspects of the surgical technique, the selected implant, and specific patient characteristics. The aim of this study was to analyze whether there are differences in quality of life (QoL) and functional capacity among patients undergoing TKA with conventional implants compared to those treated with hypoallergenic oxinium implants. A pragmatic clinical study was carried out that included patients who underwent TKA between January 2013 and December 2015. During this period, 245 knees in 228 patients were treated. Eleven patients were excluded, leaving a sample of 161 conventionally treated knees, 72 knees treated with hypoallergenic implants, and one patient who received both implant types. In all patients, QoL and functional capacity were measured with the WOMAC index, the SF-12 questionnaire, and the Euro-Qol-5D L-VAS. We also assessed the psychological distress of each patient and related the findings to the functional results. The differences in QoL were tested using ANCOVA and propensity score matching (PSM) models adjusted for sex, age, weight, psychiatric history and associated complications. Patients who underwent TKA using conventional prostheses had significantly better scores on the total WOMAC index and in the pain domain (p < 0.05) than those who received hypoallergenic prostheses, but no significant differences were observed for the other domains in the ANCOVA. In contrast, with the PSM, we also found statistically significant differences in the difficulty domain of the WOMAC. Significant differences were found for the SF-12 mental health questionnaire results (p = 0.038), but the same did not occur for the physical health domain in the ANCOVA and PSM. We also found statistically significant differences in the Euro-Qol-5D index results (p = 0.041), but not in the VAS scale scores for the same questionnaire in the ANCOVA, and we did not find significant differences in either with the PSM. Patients with metal allergies and those who present psychological distress had WOMAC, SF-12, and Euro-Qol-5D results that were statistically significantly worse than those of patients who received conventional implants. Patients who underwent hypoallergic TKA had lower scores on the QoL and functional capacity scales than patients who received conventional Cr–Co implants. Additionally, patients with psychological distress had worse results on the questionnaires, and those with a metal allergy had even lower scores; the differences were statistically significant. [ABSTRACT FROM AUTHOR]

Breast cancer is the cancer with the highest prevalence in women and is the number-one cause of cancer mortality worldwide. Cell transduction is a fundamental process in the development and progression of cancer. Modifications in various cell signalling pathways promote tumour cell proliferation, progression, and survival. The PI3K/Akt/mTOR pathway is an example of that, and it is involved in growth, proliferation, survival, motility, metabolism, and immune response regulation. Activation of this pathway is one of the main causes of cancer cell resistance to antitumour therapies. This makes PI3K/Akt/mTOR signalling a crucial object of study for understanding the development and progression of this disease. Thus, this pathway may have a role as a potential therapeutic target, as well as prognostic and diagnostic value, in patients with breast cancer. Despite the existence of selective PI3K/Akt/mTOR pathway inhibitors and current clinical trials, the cellular mechanisms are not yet known. The present review aims to understand the current state of this important disease and the paths that must be forged. [ABSTRACT FROM AUTHOR]

Pregnancy is a period in a woman's life in which changes can occur that affect different physiological processes. Common conditions during this period include vascular changes, such as lower extremity venous insufficiency (VI). This is an observational, analytical, and prospective cohort study in which 114 pregnant women were analyzed, of which 62 were clinically diagnosed with VI. In parallel, 52 control patients without VI (HC) were studied. The aim of this study was to observe changes in angiogenesis and inflammation markers as well as the presence of calcium deposits. The expression of vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and pigment epithelium-derived factor (PEDF) was analyzed by immunohistochemistry and RT-qPCR. The presence of calcium deposits was revealed using the von Kossa method. In the placentas of mothers with VI, gene expression of VEGF (34.575 [32.380–36.720] VI vs 32.965 [30.580–36.320] HC) and PEDF (25.417 [24.459–27.675] VI vs 24.400 [23.102–30.223] HC) significantly increased, as was protein expression in the placental villi. An increase in calcium deposits was observed in the placentas of women with VI (72.58% VI/53.84% HC). This study revealed the existence of cellular damage in the placental villi of mothers with VI with tissue implications such as increased calcification. [ABSTRACT FROM AUTHOR]

Chronic venous disorder (CVeD), is a disorder in which there is a modification in the conditions of blood return to the heart. The disorder may arise from incompetent valves and the resultant venous reflux (chronic venous insufficiency, CVI). The economic burden of CVeD on health systems is high, and research efforts have sought to elucidate the mechanisms involved as possible therapeutic targets. The mitogen-activated protein kinase (MAPK) enzymes mediate a wide array of physiopathological processes in human tissues. In this family of proteins, extracellular signal-regulated kinase (ERK)1/2 plays a direct role in the cell homeostasis that determines the viability of mammalian tissues. This study sought to examine whether ERK1/2 plays a role in venous reflux. This was a prospective study performed on 56 participants including 11 healthy controls. Of the CVeD patients, 23 had venous reflux with CVI (CVI-R) and 22 had no reflux (NR). Distribution by age was: controls <50 years (n = 4) and ≥50 years (n = 7); NR <50 years (n = 9) and ≥50 years (n = 13); CVI-R <50 years (n = 11) and ≥50 years (n = 12). Great saphenous vein specimens were subjected to gene (real-time polymerase chain reaction, RT-qPCR) and protein (immunohistochemistry, IHC) expression techniques to identify ERK1/2. Data was compared between groups using the Mann Whitney U test. Patients with CVI showed significant gene activation of ERK1/2 protein, and, in those with venous reflux, the expression of this gene was significantly greater. The CVI-R group <50 years showed significantly greater ERK1/2 gene expression than their age-matched controls. Expression patterns were consistent with IHC findings. Our studies suggest that ERK1/2 expression is involved in venous vascular disease. [ABSTRACT FROM AUTHOR]

In this work, we evaluate the tissue response and tolerance to a designed 3D porous scaffold composed of nanocrystalline carbonate-hydroxyapatite and agarose as a preliminary step in bone repair and regeneration. These scaffolds were subcutaneously implanted into rats, which were sacrificed at different times. CD4+, CD8+ and ED1+ cells were evaluated as measurements of inflammatory reaction and tolerance. We observed some inflammatory response early after subcutaneous implantation. The 3D interconnected porosity increased scaffold integration via the formation of granulation tissue and the generation of a fibrous capsule around the scaffold. The capsule is initially formed by collagen which progressively invades the scaffold, creating a network that supports the settlement of connective tissue and generating a compact structure. The timing of the appearance of CD4+ and CD8+ cell populations is in agreement with the resolved inflammatory response. The appearance of macrophage activity evidences a slow and gradual degradation activity. Degradation started with the agarose component of the scaffold, but the nano-apatite was kept intact for up to 30 days. Therefore, this apatite/agarose scaffold showed a high capacity for integration by a connective network that stabilizes the scaffold and results in slow nano-apatite degradation. The fundamental properties of the scaffold would provide mechanical support and facilitate bone mobilization, which is of great importance in the masticatory system or large bones. [ABSTRACT FROM AUTHOR]

Varicose veins are a disease with high incidence and prevalence. In the venous wall, the smooth muscle cells (SMCs) act in the vascular homeostasis that secretes multiple substances in response to stimuli. Any alteration of these cells can modify the function and structure of the other venous layers such as the endothelium, resulting in increases in endothelial permeability and release of substances. Therefore, knowing the cellular and molecular mechanisms of varicose veins is imperative. The aims of this study are to understand how SMCs of patients with varicose veins subjected to saphenectomy of the great saphenous vein react under hypoxic cell conditions and to determine the role of vascular endothelial growth factor (VEGF) in this process. We obtained SMCs from human saphenous vein segments from patients with varicose veins (n=10) and from organ donors (n=6) undergoing surgery. Once expanded, the cells were subjected to hypoxic conditions in specific chambers, and expansion was examined through analyzing morphology and the expression of α-actin. Further gene expression studies of HIF-1α, EGLN3, VEGF, TGF-β1, eNOS, and Tie-2 were performed using RT-qPCR. This study reveals the reaction of venous cells to sustained hypoxia. As significant differential gene expression was observed, we were able to determine how venous cells are sensitive to hypoxia. We hypothesize that venous insufficiency leads to cellular hypoxia with homeostatic imbalance. VEGF plays a differential role that can be related to the cellular quiescence markers in varicose veins, which are possible therapeutic targets. Our results show how SMCs are sensitive to hypoxia with a different gene expression. Therefore, we can assume that the condition of venous insufficiency leads to a situation of sustained cellular hypoxia. This situation may explain the cellular response that occurs in the venous wall as a compensatory mechanism. [ABSTRACT FROM AUTHOR]

Chronic wounds are a serious healthcare problem. As non-healing wounds involve continuous pathologic inflammatory stage, research is focused on anti-inflammatory treatments. Our objective was to analyze the effect of S42909, a potent NADPH oxidase inhibitor activity, with vascular anti-inflammatory properties. An ischemic rabbit ear ulcer model (24 New Zealand white rabbits) was used to evaluate the reepithelialization/contraction areas, anti-/pro-inflammatory cytokines mRNA (TGF-β1/IL-10/IFN-γ/VEGF) by qRT-PCR, collagen I/III deposition, and neovascularization (TGF-β1/VEGF) by morphological and immunohistochemical analyses. Three different doses were administered by gavage for 2 weeks: 10 and 30 mg/kg/d in self-microemulsion drug delivery system (SMEDDS) and 100 mg/kg/d in arabic gum. Each vehicle was used as control. No signs of infection or necrosis were found. Reepithelialization was almost complete whatever the groups reaching 95% at the dose of 100 mg/kg. Wound contraction was significantly reduced in all S42909-treated groups. A significant increase in anti-inflammatory cytokines TGF-β1 mRNA and IL-10 mRNA was observed at the dose of 100 and 30 mg/kg/d, respectively. No changes were observed in pro-inflammatory factors INF-γ and VEGF mRNA. Ischemic skin wound areas had scarce expression of collagen I/III and showed rich glycosaminoglycans content. Treatment increased the collagen deposition and TGF-β1 protein expression and decreased glycosaminoglycan content dose dependently; however, no effect in VEGF was appreciated. Therefore, our results indicate that S42909 improved healing process by dampening excessive inflammation and facilitating collagen deposition without wound contraction phenomena. S42909 might be a promising therapy to treat chronic wounds as venous leg ulcers. [ABSTRACT FROM AUTHOR]

Introduction: Pressure ulcers are a prevalent health problem in today's society. The shortage of suitable animal models limits our understanding and our ability to develop new therapies. This study aims to report on the development of a novel and reproducible human skin pressure ulcer model in mice. Material and Methods: Male non-obese, diabetic, severe combined immunodeficiency mice (n = 22) were engrafted with human skin. A full-thickness skin graft was placed onto 4×3 cm wounds created on the dorsal skin of the mice. Two groups with permanent grafts were studied after 60 days. The control group (n = 6) was focused on the process of engraftment. Evaluations were conducted with photographic assessment, histological analysis and fluorescence in situ hybridization (FISH) techniques. The pressure ulcer group (n = 12) was created using a compression device. A pressure of 150 mmHg for 8 h, with a total of three cycles of compression-release was exerted. Evaluations were conducted with photographic assessment and histological analysis. Results: Skin grafts in the control group took successfully, as shown by visual assessment, FISH techniques and histological analysis. Pressure ulcers in the second group showed full-thickness skin loss with damage and necrosis of all the epidermal and dermal layers (ulcer stage III) in all cases. Complete repair occurred after 40 days. Conclusions: An inexpensive, reproducible human skin pressure ulcer model has been developed. This novel model will facilitate the development of new clinically relevant therapeutic strategies that can be tested directly on human skin. [ABSTRACT FROM AUTHOR]

Chronic infections are one of the most serious adverse outcomes of prosthetic surgery. Prosthetic revision surgery using a bone cement loaded with antibiotics between the two stages of the surgery is commonly performed. However, this method often fails to reach the minimum inhibitory concentration and promotes antibiotic resistance, thus emphasizing the need for improving the current available therapies. Materials and methods: In this study, we performed a study of the in vivo response of a polymer-based construct of poly (lactic-co-glycolic acid) (PLGA) in the solid phase of Palacos R® in combination with vancomycin, daptomycin, and/or linezolid. To test its effectiveness, we applied an in vivo model, using both histological and immunohistochemical analyses to study the bone tissue. Results: The presence of PLGA in the combination of vancomycin with daptomycin showed the most promising results regarding the preservation of bone cytoarchitecture and S. aureus elimination. Conversely, the combination of vancomycin plus linezolid was associated with a loss of bone cytoarchitecture, probably related to an increased macrophage response and inefficient antimicrobial activity. Conclusions: The modification of Palacos R® bone cement with PLGA microspheres and its doping with the antibiotic daptomycin in combination with vancomycin improve the tissue response to bone infection. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) is a multifactorial vascular disorder frequently manifested in lower limbs in the form of varicose veins (VVs). Women are a vulnerable population for suffering from CVD, especially during pregnancy, when a plethora of changes occur in their cardiovascular system. Previous studies have indicated a worrisome association between CVD in pregnancy with the placental structure and function. Findings include an altered cellular behavior and extracellular matrix (ECM) composition. Integrin-linked kinase (ILK) is a critical molecule involved in multiple physiological and pathological conditions, and together with cadherins, is essential to mediate cell to ECM and cell to cell interplay, respectively. Thus, the aim of this study was to evaluate the implication of ILK and a set of cadherins (e-cadherin, cadherin-6 and cadherin-17) in placentas of women with CVD in order to unravel the possible pathophysiological role of these components. Gene expression (RT-qPCR) and protein expression (immunohistochemistry) studies were performed. Our results show a significant increase in the gene and protein expression of ILK, cadherin-6 and cadherin-17 and a decrease of e-cadherin in the placenta of women with CVD. Overall, this work shows that an abnormal expression of ILK, e-cadherin, cadherin-6 and cadherin-17 may be implicated in the pathological changes occurring in the placental tissue. Further studies should be conducted to determine the possible associations of these changes with maternal and fetal well-being. [ABSTRACT FROM AUTHOR]

Abstract: Background: Adhesions commonly appear in patients after abdominal surgery, with considerable individual variation in adhesion composition and severity of the repair process. Here, we address the influence of transforming growth factor (TGF)-β3 and betaglycan in this response, in relation to TGF-β1, in an adhesiogenic rabbit model. Materials and methods: Omental adhesions were recovered 3, 7, 14, and 90 d after the implantation of a polypropylene mesh on the parietal peritoneum in New Zealand White rabbits. Omentum from nonoperated animals served as control. Tissue specimens were examined for TGF-β3 and TGF-β1 (Western blotting, reverse transcription-polymerase chain reaction), and TGF-β1:TGF-β3 messenger RNA and protein expression ratios were analyzed. Immunohistochemical detection of TGF-β3 and betaglycan was performed. Results: Injury to the omentum led to mobilization of TGF-β3 and betaglycan-expressing cells from milky spots. Fibrous zones in adhesions were simultaneous to the presence of TGF-β1 and the membrane-bound form of betaglycan (7-d adhesions), whereas soluble betaglycan appeared in TGF-β1–positive areas showing limited fibrosis (3-d adhesions). The elevated expression of TGF-β3 concurrent with the presence of membrane-bound form of betaglycan was observed in zones of adipose regeneration (14-d adhesions), whereas zones of fibrous consistency were negative for TGF-β3. Conclusions: Milky spots on the omentum contain inflammatory/immune cells positive for TGF-β3, TGF-β1, and betaglycan, playing a role in the damaged omentum repair. Our observations support the contribution of TGF-β3 to tissue repair through adipose tissue regeneration and the profibrotic role of TGF-β1 and suggest that these effects on the local wound repair response could be driven by the expression of betaglycan in its soluble or membrane-bound form. [Copyright &y& Elsevier]

Pterygium is a benign fibrovascular lesion of the bulbar conjunctiva with frequent involvement of the corneal limbus. Its pathogenesis has been mainly attributed to sun exposure to ultraviolet-B radiation. Obtained evidence has shown that it is a complex and multifactorial process which involves multiple mechanisms such as oxidative stress, dysregulation of cell cycle checkpoints, induction of inflammatory mediators and growth factors, angiogenic stimulation, extracellular matrix (ECM) disorders, and, most likely, viruses and hereditary changes. In this review, we aim to collect all authors' experiences and our own, with respect to the study of fibroelastic ECM of pterygium. Collagen and elastin are intrinsic indicators of physiological and pathological states. Here, we focus on an in-depth analysis of collagen (types I and III), as well as the main constituents of elastic fibers (tropoelastin (TE), fibrillins (FBNs), and fibulins (FBLNs)) and the enzymes (lysyl oxidases (LOXs)) that carry out their assembly or crosslinking. All the studies established that changes in the fibroelastic ECM occur in pterygium, based on the following facts: An increase in the synthesis and deposition of an immature form of collagen type III, which showed the process of tissue remodeling. An increase in protein levels in most of the constituents necessary for the development of elastic fibers, except FBLN4, whose biological roles are critical in the binding of the enzyme LOX, as well as FBN1 for the development of stable elastin. There was gene overexpression of TE, FBN1, FBLN5, and LOXL1, while the expression of LOX and FBLN2 and -4 remained stable. In conclusion, collagen and elastin, as well as several constituents involved in elastic fiber assembly are overexpressed in human pterygium, thus, supporting the hypothesis that there is dysregulation in the synthesis and crosslinking of the fibroelastic component, constituting an important pathogenetic mechanism for the development of the disease. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has a dire prognosis and will represent the second leading cause of cancer death in the next 10 years. The multifactorial approach represents one of the main issues in controlling the extension of this neoplasm. In recent years, the characteristics of the tumor microenvironment, metastasis mechanisms and the relationship between immune system and neoplastic cells have been described, which has made it possible to understand the pathophysiology of pancreatic adenocarcinoma. Currently, there is a failure to provide an effective preventive method or early detection, so patients present with an advanced stage at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcome and in improving survival in long term. Therefore, in the recent years, diverse diagnostic tests, treatments and possible approaches have been developed in the fields of radiotherapy, chemotherapy and surgery to find a combination of them that improves life expectancy in patients diagnosed with pancreatic cancer. At the moment, numerous clinical trials are being conducted to evaluate preventive diagnostic procedures such as serological markers or perfecting available imaging tests. On the other hand, implementation of immunotherapy is being studied in a neoplasm that has lagged in the application of this procedure since present possible treatments do not substantially improve quality of life. Therefore, the purpose of our study is to summarize the main progresses that have been made in the diagnosis, treatment and screening of this disease, explaining the limitations that have been observed and analyzing future prospects in the management of this illness. [ABSTRACT FROM AUTHOR]

Background: When repairing an abdominal wall defect, sometimes a prosthetic mesh needs to be placed directly on the parietal peritoneum. Although the standard mesh for this purpose is the laminar implant expanded polytetrafluoroethylene (PTFE), it is gradually being replaced by the laminar collagen-based meshes. This study was designed to assess the intraperitoneal behavior of three of these biomeshes, mainly in terms of their susceptibility to adhesion formation. Methods: Two 3-cm × 3-cm fragments of prosthetic material were placed on the parietal peritoneum in male New Zealand White rabbits in the following combinations: PTFE and CollaMend, PTFE and Permacol, or PTFE and Surgisis. The meshes were fixed at the four corners with individual 4/0 polypropylene sutures. Adhesion formation was quantified by sequential laparoscopy and image analysis performed at 3, 7, 14, and 90 days postimplant. All animals were killed at 90 days and the mesh specimens were subjected to microscopy and immunohistochemistry. Results: Intensely vascularized adhesions to all the implants were observed, although Surgisis showed the lowest percentage of adhesions at each follow-up time. Adhesions had stabilized by 7-14 days. The PTFE meshes were enveloped by a layer of macrophages and connective tissue, bounded by a monolayer of mesothelial cells. Permacol and CollaMend showed similar histological behavior, including cell ingrowth through their fenestrations with no signs of degradation detected at 90 days. In contrast, the Surgisis mesh at 90 days was practically replaced with neoformed tissue. Conclusions: No difference in susceptibility to adhesion formation was noted in the crosslinked collagen meshes compared to PTFE meshes. The noncrosslinked collagen mesh Surgisis showed the best behavior in that it induced fewer adhesions. Ninety days after implant, a more intense macrophage response was observed in CollaMend and Permacol than in PTFE or Surgisis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate possible changes in the collagen and elastic components of the subepithelial connective tissue of human pterygium. Design: Immunohistochemical study. Methods: Immunohistochemical staining using antitropoelastin, anti-fibulin-2, and anti-fibulin-3 antibodies was performed in 10 normal conjunctival and 20 pterygium specimens. Masson trichome staining also was performed to study subepithelial connective tissue. Sirius red staining was used to identify collagen type I and III components. Tropoelastin, fibulin-2, and fibulin-3 messenger ribonucleic acid (mRNA) expressions were analyzed in 9 conjunctival and 12 pterygium specimens by quantitative real-time polymerase chain reaction assay. Results: The subepithelial connective tissue and vessels were more predominant in pterygium compared with the normal conjunctival tissue. Amorphous subepithelial zones were observed in the areas of the pterygium tissue, but not in normal conjunctiva. Increased tropoelastin staining was seen in the pterygium tissue with areas of degenerative changes or immature formation of elastic fibers, as well an increase in tropoelastin mRNA, in contrast with fibulin-2 and fibulin-3 messenger levels. Fibulin-2 and fibulin-3 expression was colocalized in the subepithelial connective tissue and was distributed along blood and lymphatic vessels. Collagen type III, an immature form of collagen, was increased in the pathologic samples in association with a tissue remodeling process. Conclusions: Elastin metabolism is dysregulated in the pathogenesis of human pterygium with tropoelastin, fibulin-2, and fibulin-3 overexpression in the subepithelial connective tissue. [ABSTRACT FROM AUTHOR]

Background Prior studies suggest impaired collagen metabolism involving the whole abdominal wall including the skin in patients with abdominal hernia. We compared expression patterns of matrix metalloproteinase-2 (MMP-2) and its modulators membrane type-1-matrix metalloproteinase (MT-1 MMP) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the skin of patients with and without primary inguinal hernia. Materials and methods Skin biopsy specimens from abdominal wall incisions were obtained during surgery from patients with direct inguinal hernia, indirect inguinal hernia or without hernia (controls). MMP-2, MT-1 MMP and TIMP-2 expression were determined using immunocytochemistry and immunoblotting in intact tissue and in cultured fibroblasts isolated from the biopsies. The degradation activity of MMP-2 was semiquantitatively determined using zymography. Results Significantly greater active MMP-2 expression was observed in skin fibroblasts obtained from patients with direct hernia compared with controls. MT1-MMP expression was directly correlated with MMP-2 expression with most intense staining produced in patients with direct or indirect inguinal hernia. TIMP-2, was maximally expressed in the control group, with significantly diminished expression levels recorded in the hernia groups. Conclusions Our findings indicate active MMP-2 upregulation in the abdominal skin of patients with direct inguinal hernia. This metalloproteinase plays a role in matrix degradation, weakening the abdominal wall. Skin disorders and previously described transversalis fascia defects in these patients could point to a systemic collagen metabolism abnormality as a risk factor for direct hernia. [ABSTRACT FROM AUTHOR]

Abstract: Parathyroid hormone-related protein (PTHrP) is an important regulator of bone formation and remodeling. Our recent findings demonstrate that PTHrP (107–111) (osteostatin) loaded onto silica-based ordered mesoporous SBA15 materials exhibit osteogenic features in osteoblastic cell cultures. We aimed here to elucidate whether these peptide-coated materials might be suitable for promoting bone repair following a cavitary defect in the rabbit femur. Histological examination revealed the absence of significant inflammation or bone resorption within the time of study (4 and 8 weeks) after implantation. At 8 weeks, the peptide-unloaded materials were still separated from the bone marrow by a fibrous cap, which was greatly diminished by the presence of the PTHrP peptide. By using μCT analysis, new bone formation was evident at different distances from the implants, mainly for the latter peptide-loaded biomaterials. This was confirmed by performing immunostaining for different osteoblast markers. Our findings demonstrate that these PTHrP (107–111)-loaded bioceramics significantly improve local bone induction, as compared to that observed with the unloaded material. [ABSTRACT FROM AUTHOR]

Human Wharton's jelly stem cells (HWJSC) emerged as a potential source of viable cells for use in tissue engineering. In this work, we have analyzed the transdifferentiation capabilities of HWJSC towards transdifferentiated endothelial-like cells (Tr-ELC) in order to establish the potential usefulness of these cells in vascular tissue engineering. Our results show that Tr-ELC became more polygonal and less proliferative than HWJSC, resembling the structure and proliferation rate of the endothelial cells. In addition, the markers of mesenchymal undifferentiation CD9, E-cad, PODXL, and SSEA-4 are downregulated in Tr-ELC, suggesting that these cells can be in the process of adult differentiation. Besides, RT-PCR and microarray analyses revealed that some genes with a role in defining the endothelial phenotype and structure are upregulated (VEGF-R1, EDF1, AAMP, CD31, CD34, CDH5, and ICAM2) or downregulated (VEGF) in Tr-ELC, although a number of genes related to relevant endothelial cell functions (CD36, ECE2, VWF, THBD, PGI2, ECE1, and ACE) did not change or were only partially induced. All this implies that HWJSC are able to efficiently transdifferentiate towards Tr-ELC at the phenotypical level following a hierarchical pattern of gene activation, with an earlier induction of morphological and phenotypical genes. J. Cell. Physiol. 223:640–647, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Although it has been established that postoperative adhesions in the peritoneal cavity are the consequence of injury to the peritoneum, there is much controversy over the nature of the cells giving rise to this neotissue. Here, we establish a novel adhesiogenic model in the rabbit to analyze the phenotype and proliferation in vitro of cells comprising adhesion tissue seven days postsurgery. Adhesion-free omentum tissue was used as control. Cells derived from adhesions and from the control omentum were subcultured and characterized through immunofluorescence and Western blotting procedures to determine markers of cell differentiation and pluripotential, and viability and proliferation assays. Our findings indicate the existence of a mesenchymal population in the omentum revealed by markers of pluripotent cells with high angiogenic capacity. This population seems to be responsible for the adhesions formed in response to mesothelial damage. Depending on the local environment, mesenchymal cells are capable of in vivo differentiation towards at least two different cell phenotypes rendering two types of adhesions with clearly differentiated characteristics. One type of adhesion shows a highly vascularized adipose morphology containing cells differentiating into a vascular lineage. The other adhesions are fibrous with large amounts of collagen and comprised mainly of myofibroblasts conferring less compliance to this tissue. [ABSTRACT FROM AUTHOR]

Background. Over the years, reticular prostheses have undergone changes in their structure and composition to give rise to today's partially absorbable lightweight meshes. This study was designed to assess the biological and biomechanical behavior of these prostheses to establish whether they offer any advantages over nonabsorbable lightweight polypropylene prostheses. Materials and Methods. 7 × 5 cm defects were created in the anterior abdominal wall of New Zealand White rabbits and repaired by securing different prostheses to the edges of the defect with a running 4/0 polypropylene suture. The lightweight biomaterials compared were two nonabsorbable meshes: Parietene® and Optilene elastic® , and two partially absorbable prostheses: Vypro II® and Ultrapro®. At 14 and 90 days postimplant, tissue/prosthesis specimens were subjected to histological, immunohistochemical, shrinkage, and biomechanical analyses. Results. Adhesion formation on the peritoneum-facing surface of the meshes was significantly less extensive in the meshes with absorbable components at 90 days postimplant. The newly formed tissue around the prosthetic filaments was comprised of collagen fibers, fibroblasts, blood vessels, and macrophages. The partially absorbable meshes showed higher macrophage proportions (due to remnants of absorbable material and their structure) than the nonabsorbable meshes at 90 days, although differences were not significant. At 90 days postimplant, similar tensile strengths were recorded for all the implants. Conclusions. All the prosthetic materials induced good host tissue ingrowth, with no significant differences in tensile strength observed. Our findings suggest that partially absorbable lightweight prostheses could offer advantages over nonabsorbable lightweight meshes since less foreign material persists in the recipient, improving abdominal wall compliance. [ABSTRACT FROM AUTHOR]

Chronic venous disease (CVD) is the response to a series of hemodynamic changes in the venous system and the onset of this disease is often triggered by pregnancy. Placental tissue is particularly sensitive to the characteristic changes which occurs in venous hypertension. In this regard, changes in the extracellular matrix (ECM), that occur to adapt to this situation, are fundamental to controlling elastogenesis. Therefore, the aim of the present study was to analyze the changes that occur in the mRNA and protein expression level of proteins related to elastogenesis in the placental villi of women diagnosed with CVD, in the third trimester of pregnancy. An observational, analytical and prospective cohort study was conducted, in which the placenta from 62 women with CVD were compared with that in placenta from 52 women without a diagnosis of CVD. Gene and protein expression levels were analyzed using reverse transcription-quantitative PCR and immunohistochemistry, respectively. The results showed a significant decrease in the gene and protein expression level of EGFL7 in the placental villi of women with CVD. By contrast, significant increases in the gene and protein expression level of ECM-related proteins, such as tropoelastin, fibulin 4, fibrillin 1 and members of the lysyl oxidase family (LOX and LOXL-1) were also found in the placental villi of women with CVD. To the best of our knowledge, the results from the present study showed for the first time that CVD during pregnancy was associated with changes in the mRNA and protein expression level in essential components of the EGFL7-modulated elastogenesis process in placental villi. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the main risk factors associated with third and fourth degree postpartum perineal tears in women attended to in our obstetrics service. Methods: An observational, retrospective, hospital cohort study was carried out in women whose deliveries were attended to in the obstetrics service of the Hospital General Universitario Gregorio Marañón de Madrid (HGUGM), during the period from January 2010 to April 2017. Results: During the study period, a total of 33,026 patients were included in the study. For maternal variables, the associated increased risk of severe perineal tearing in nulliparous women is OR = 3.48, for induced labor OR = 1.29, and for instrumental delivery by forceps OR = 4.52 or spatulas OR = 4.35; for the obstetric variable of episiotomy, it is OR = 3.41. For the neonatal variables, the weight of the newborns has a directly proportional relationship with the risk of severe tears, and for birth weights of 3000 g (OR = 2.41), 3500 g (OR = 1.97), and 4000 g (OR = 2.17), statistically significant differences were found in each of the groups (p < 0.05). Conclusion: Primiparity, induction of labor, episiotomy, instrumental delivery with forceps or spatula, and a birth weight of 3000 g or more are significantly associated with an increased risk of third and fourth degree perineal tears. [ABSTRACT FROM AUTHOR]

Abstract: Background: The aim of this study was to establish whether new prosthetic materials with absorbable components, designed to reduce the amount of foreign material in abdominal wall repair, offer advantages over the conventional polypropylene meshes. Methods: Seven × 5 cm defects created in the anterior abdominal wall of New Zealand white rabbits were repaired by using a nonabsorbable polypropylene prosthesis (Surgipro; Tyco, Barcelona, Spain) or 1 of 2 partially absorbable prostheses available on the market (Vypro II and Ultrapro; Johnson & Johnson, St. Stevens-Woluwe, Belgium). At 14 and 90 days after surgery, tissue/prosthesis specimens were subjected to histological studies, biomechanical strength tests, and shrinkage evaluation. Results: At 90 days, the absorbable filaments of Vypro II had been completely reabsorbed, whereas Ultrapro only showed signs of biodegradation in a few zones. Host tissue infiltration and collagen I deposition in the 3 reticular meshes was optimal. Macrophage counts, mesh shrinkage, and biomechanical resistance values were similar. Conclusions: Partially absorbable prostheses perform as well as the standard polypropylene mesh and have the benefit that less foreign material remains in the recipient, without compromising mechanical resistance. [Copyright &y& Elsevier]

Background: Although the etiology of venous insufficiency is not well understood, immune response and aging are beginning to emerge as contributing factors. Factors involved in tissue remodeling such as TGF-β1 also seem to play an important role in extracellular matrix production. The aim of this study was to explore the relationship between chronic venous insufficiency and TGF-β1 examining the latent/mature form of TGF-β1 and the presence of mast cells. Effects of age were also evaluated. Methods: Saphenous veins were obtained from patients subjected to aortocoronary bypass (controls) and undergoing varicose vein surgery. These were immunolabeled using anti-LAP TGF-β1/anti-TGF-β1 antibodies and subjected to Western blot. Mast cell population was identified by metachromatic staining.Results:Latent TGF-β1 was significantly reduced in varicose veins from older subjects. In contrast, smooth muscle cells obtained from the varicosities showed intense levels. Mature TGF-β1 significantly differed between healthy and varicose veins. No mature TGF-β1 was detected in the cell cultures. Mast cell number and degranulation were increased with aging and varicose disease, colocalizing with the mature form of TGF-β1. Conclusion: Aging and varicose pathology induce dysregulation of TGF-β1 that could play an important role in the fibrous process, representing the final stages of venous insufficiency. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The prosthetic materials currently used to repair abdominal wall defects sometimes have to be placed in contact with the visceral peritoneum. This interface is often a site of complications such as intestinal obstruction or fistulas due to adhesions. The aim of this study was to follow the process of adhesion formation in several prosthetic materials by sequential laparoscopy. Material and Methods: Defects (7 × 5 cm) were created in the abdominal wall of 30 New Zealand White rabbits and repaired using Surgipro polypropylene mesh (PP), Ultrapro monocryl-prolene mesh (UP), Dual Mesh expanded polytetrafluoroethylene (ePTFE), Composix (PP-ePTFE), Parietex Composite (polyester with collagen-polyethylene glycol-glycerol coating [PO-gl]), or PL-PU99 (PP-polyurethane) patches fixed to the edges of the defect by running polypropylene suture. Adhesions to the implants were laparoscopically determined at 3, 7, and 14 days after surgery. Results: Percentage adhesion scores were significantly lower for ePTFE, PP-ePTFE, PO-gl, and PP-PU, compared to PP or UP. No differences were observed in adhesion scores recorded at 3, 7, and 14 days postimplant. Reticular prostheses were infiltrated by disorganized scar tissue with fibers concentric to the mesh filaments. In contrast, ePTFE implants were encapsulated by organized tissue, with fibers running parallel to the surface of biomaterial. All three composites achieved good recipient tissue integration and a homogeneous, organized, and well-vascularized neoperitoneum. Conclusion: At 14 days postimplant, laminar prostheses and composites showed similar results in terms of adhesion formation and integration within host tissue. Our findings suggest that both the composite prostheses and the laminar ePTFE performed very well in terms of reduced adhesion formation at the peritoneal interface. [ABSTRACT FROM AUTHOR]

Background: Despite intense research efforts, incisional hernias continue to be a problem in patients who undergo laparotomy. This study was designed to reinforce the midline laparotomy closure by including a new prosthetic design between the edges of the surgical wound. Study design: A midline incision was made in New Zealand white rabbits and closed by inserting a polypropylene strip, T-shaped in cross-section, between the incisional borders. The T was placed upside down such that the horizontal arm of the T, whose surface is coated with extra-low pore size expanded polytetrafluoroethylene, made contact with the visceral peritoneum. The mesh was secured by a mass polypropylene 3/0 running suture. Surgery outcomes in these animals were compared with those in which the surgical wound was closed by simple suture and with control, nonoperated animals. Results: The T-mesh induced an increased amount of scar tissue at the midline, where neoformed recipient tissue appeared around the polypropylene mesh filaments. The expanded polytetrafluoroethylene lamina became appropriately mesothelialized. Compared with the simple suture, the T-mesh provided a significant gain in biomechanical strength at postoperative week 6 (43.99±4.17 Newtons and 56.96±10.94 Newtons, respectively, p < 0.05). At 6 months, the strength of the reinforced wound even surpassed, although not significantly, that of the control intact abdominal wall (82.25±7.60 Newtons versus 79.55±11.46 Newtons). Data were expressed as mean ± standard deviation. Conclusions: The use of a nonabsorbable biomaterial for midline laparotomy closure significantly improves its biomechanical resistance. Used in high-risk patients or even prophylactically, this technique could reduce the incidence of incisional hernia. [Copyright &y& Elsevier]

Abstract: The use of arterial homografts in clinical practice is becoming increasingly common, yet there is an urgent need to address one of the most well-established problems associated with their use: the loss of integrity of the endothelium following cryopreservation. The partial lack of endothelium causes contact between the extracellular matrix and blood flow, which, in turn, often gives rise to thrombosis and/or restenosis. Our objective was first to attempt to replace the arterial endothelial cells lost during the cryopreservation process by seeding autologous venous endothelial cells, and to evaluate the behaviour of venous and arterial endothelial cells in co-culture. The idea was to establish whether venous endothelial cells would be accepted by arterial endothelial cells and could therefore be used to restore the endothelial lining for the subsequent use of these vessels in in vivo grafting procedures. For the co-culture experiments, endothelial cells were obtained from the jugular vein and both iliac arteries of the minipig by treatment with 0.1% type I collagenase. The venous endothelial cells were fluorescently labelled with the membrane intercalating dye PKH26. Equal numbers of venous and arterial endothelial cells were mixed and co-cultured for 24h, 48h or 4 days. Cell viability, determined by 2% trypan blue staining and the TUNEL method, was established before and after fluorescence labelling. Cellular activity was determined by estimating PGI2 levels in the cultures. The proliferation index was established by [H3]thymidine (1μCi/ml) in the cell culture medium. For the in vivo tests, 5cm length segments of minipig iliac artery were used to establish the groups: control (n =6), fresh arterial segments; group I (n =16), cryopreserved arterial segments and group II (n =16), cryopreserved arterial segments seeded with autologous venous endothelial cells. The cryopreserved vessels in group II were seeded by flooding with a labelled venous endothelial cell suspension. Once seeded, the arterial segments were included in an in vitro flow circuit. All the specimens were processed for fluorescence and light microscopy, and scanning electron microscopy. The denuded endothelial surface was determined in each group. Cell death was evaluated by the TUNEL method. We confirmed the existence of intercellular PECAM1-type junctions between venous (PKH26+) and arterial cells in co-culture and the functional activity of the cells. The cryopreserved arterial segments showed a well-preserved wall structure. However, different size areas of marked endothelial denudation were detected. After seeding with labelled cells (PKH26+), these denuded areas of the cryopreserved artery were entirely covered by fluorescent cells. After seeding, a drop in the proportion of damaged endothelial cells was recorded. Despite some loss of seeded cells after inclusion in the in vitro flow circuit, the endothelial cell count was not significantly different to those recorded for control, non-cryopreserved specimens. In conclusion arterial and venous endothelial cells growing in co-culture modify their behaviour to form multilayers. The two cell populations form normal PECAM1 junctions and preserve their functional properties. Seeding autologous venous endothelial cells on the luminal surface of cryopreserved arterial segments serves to restore the integrity of the endothelial layer. [Copyright &y& Elsevier]

Background: Temporary abdominal wound closure is sometimes desirable when tension-free approximation of the wound edges is impractical or when reexploration is planned.Methods: The behavior of a composite prosthesis (PL-PU99) designed by our group was evaluated as a method of temporary abdominal closure in white New Zealand rabbits. After a 7 cm long midline laparotomy, a spindle-shaped 4 cm (maximum width) by 7 cm (length) fragment of PL-PU99 was sutured to the edges of the peritoneal, muscular, and fascial abdominal tissues, so that the biomaterial remained in contact with the exterior. The PL-PU99 composite is composed of a polypropylene mesh adhered to a sheet of polyurethane with an acrylic cement. At 7 and 14 days after implant, animals were sacrificed and specimens taken for morphological, ultrastructural, morphometry of the neoperitoneum, and immunohistochemical (macrophage reaction, RAM-11) analysis.Results: No death or signs of infection or rejection of the prostheses were recorded. No adhesions could be macroscopically observed between the composite and the intestinal loops. The biomaterial achieved a good seal, no leakage of fluids being detected. Fourteen days after implant, the neoperitoneum formed on the prosthesis was of an even structure and was made up of organized, vascularized connective tissue covered by an uninterrupted mesothelium.Conclusions: The PL-PU99 prosthesis shows optimal behavior at the prosthesis/visceral peritoneum interface, making it ideal for its use in the temporary closure of the abdomen. The implanted composite may also prove useful for the permanent repair of the abdominal wall. [Copyright &y& Elsevier]

ABSTRACT We designed a composite-structure (laminar-reticular) prosthesis using expanded polytetrafluoroethylene (ePTFE) as the biomaterial in an attempt to improve the biomechanical resistance of the same biomaterial in the form of a single lamina. Defects (7 × 5 cm) were created in the abdominal wall of male white New Zealand rabbits (n = 24). The defects, which comprised all the wall layers except the skin, were then repaired with one of two types of ePTFE prosthesis. One was a latest generation laminar prosthesis (DualMesh, or Gore-Tex) and the other was a composite of in-house design (CV-4 mesh composite) made by suturing a mesh woven out of ePTFE thread to an ePTFE lamina. After sacrificing the animals at 14 or 90 days after surgery, implant specimens were subjected to morphologic analysis (light microscopy and scanning electron microscopy); and adhesion formation, neoperitoneal thickness, and biomechanical strength were evaluated. No significant differences were recorded between the two prosthesis regarding the consistency of adhesions or the area occupied by adhesions (DM 0.17 ± 0.06; CV-4 mesh composite 0.18 ± 0.08 cm2) (p > 0.05). Notably, improved tissue integration was achieved using the composite prosthesis; its reticular side became infiltrated by dense connective tissue that enveloped the mesh filaments. In contrast, the DM prosthesis became encapsulated by host tissue. The neoperitoneum induced by both prostheses was homogeneous and orderly, with a layer of typical mesothelial cells lining its inner surface. The thickness of the neoperitoneum was similar (p > 0.05) for the two implants (385.0 ± 3.4 vs. 390 ± 3.1 μm), although significantly higher (p < 0.05) mechanical resistance values were recorded for the composite prosthesis (26.75 ± 3.71 vs. 14.11 ± 3.71 N). Our findings suggest that the use of a reticular and a laminar ePTFE layer in the same prosthesis leads to better repair and biomechanical behavior compared to the use of a single-structure laminar implant. [ABSTRACT FROM AUTHOR]

The endothelial loss provoked by the methods of vascular cryopreservation used at most human vessel banks is one of the main factors leading to the failure of grafting procedures performed using cryopreserved vessel substitutes. This study evaluates the effects of the storage temperature and thawing protocol on the endothelial cell loss suffered by cryopreserved vessels, and optimises the thawing temperature and protocol for cryopreserving arterial grafts in terms of that producing least endothelial loss. Segments of the common iliac artery of the minipig (n=20) were frozen at a temperature reduction rate of 1 °C/min in a biological freezer. After storing the arterial fragments for 30 days, study groups were established according to the storage temperature (−80, −145 or −196 °C) and subsequent thawing procedure (slow or rapid thawing). Fresh vessel segments served as the control group. Once thawed, the specimens were examined by light, transmission, and scanning electron microscopy. The covered endothelial surface was determined by image analysis. Data for the different groups were compared by one way ANOVA. When cryopreservation at each of the storage temperatures was followed by slow thawing, the endothelial cells showed improved morphological features and viability over those of specimens subjected to rapid thawing. Rapidly thawed endothelial cells showed irreversible ultrastructural damage such as mitochondrial dilation and rupture, reticular fragmentation, and peripheral nuclear condensation. In contrast, slow thawing gave rise to changes compatible with reversible damage in a large proportion of the endothelial cells: general swelling, reticular dilation, mitochondrial swelling, and nuclear chromatin condensation. Gradually thawed cryopreserved arteries showed a lower proportion of damaged cells identified by the TUNEL method compared to the corresponding rapidly thawed specimens (p<0.05, for all temperatures). In all the groups in which vessels underwent rapid thawing (except at −145 °C), significant differences (p<0.05) in endothelial cover values were recorded with respect to control groups. Storage of cryopreserved vessels at −80 °C followed by rapid thawing led to greatest endothelial cell loss (61.36 ± 9.06% covered endothelial surface), while a temperature of −145 °C followed by slow thawing was best at preserving the endothelium of the vessel wall (89.38 ± 16.67% surface cover). In conclusion, storage at a temperature of −145 °C in nitrogen vapour followed by gradual automated thawing seems to be the best way of preserving the endothelial surface of the arterial cryograft. This method gives rise to best endothelial cell viability and cover values, with obvious benefits for subsequent grafting. [Copyright &y& Elsevier]

Objective: To compare the behaviour of two composite biomaterials in rabbit peritoneum. Design: Animal study. Setting: Faculty of Medicine, University of Alcalá, Spain. Animals: 14 white New Zealand white rabbits divided into 2 groups of 7 each. Interventions: Defects (7 × 5 cm) involving all the layers of the abdominal wall were created and repaired using Parietex Composite[sup ®] or Vypro[sup ®] prostheses. Fourteen days after implantation, prosthetic specimens were examined by microscopy, and morphometric and biomechanical analysis. Main outcome measures: Infection, healing, development of adhesions, and histological appearance of the interface. Results: Firm adhesions were detected after the implant of Vypro while adhesion were loose in the Parietex group. The mean (SD) prosthetic surface area covered by adhesions was significantly greater in the Vypro group 22.3 (2.8) compared with 0.2 (0.02), p < 0.01). The neoperitoneum formed after the implant of Parietex was well-organised and homogeneous and covered by a typical mesothelium, while in the Vypro it was disorganised, with a rough texture composed of prosthetic filaments and nodes. The neoperitonum was thicker in the Parietex group 154.0 (5.4) compared with 50.8 (2.3), p < 0.05) while higher biomechanical resistance values were recorded in the Vypro group 30.4 (1.9) compared with 15.0 (2.73), p < 0.05). Conclusions: While both biomaterials integrated well with tissue, Parietex behaved better at the peritoneal interface. [ABSTRACT FROM AUTHOR]

Objective: To compare pelvic floor disorders between vaginal delivery (VD) and cesarean delivery (CD). Methods: For this study, a PUBMED database search was used, utilizing a combination of relevant medical subjects' headings (MeSH) terms, with the following keywords: "Pelvic floor disorders" or "Pelvic floor morbidity" and "Delivery". Search limits were articles in English or Spanish, about women, published from December 2009 to December 2019. The STATA 16 package was used for meta-analysis and data heterogeneity assessment. Results: Thirteen studies meeting eligibility criteria were identified comprising 1,597,303 participants. Abstract: Pelvic floor morbidity prevalence was Urinary Incontinence (UI) 27.9% (5411 patients in 7 studies with reported cases), Pelvic Organ Prolapse (POP) 14.2% (6019 patients in 8 studies with reported cases), and Anal Incontinence (AI) 0.4% (1,589,740 patients in 5 studies with reported cases). Our meta-analyses revealed significantly higher rates of all three morbidities and overall morbidity in the VD versus CD group: UI OR = 2.17, 95% CI 1.64–2.87, p for heterogeneity ≤ 0.0001, I2 = 84%; POP OR = 3.28, 95% CI 1.91–5.63, p for heterogenicity ≤ 0.043, I2 = 63%; AI OR = 1.53, 95% CI 1.32–1.77; p for heterogeneity ≤ 0.291, I2 = 20%; and overall morbidity (OR = 2.17, 95% CI 1.64–2.87; p for heterogeneity ≤ 0.0001, I2 = 84%). Conclusion: Vaginal delivery is directly related to the appearance of pelvic floor disorders, mainly UI, POP, and AI. The risk of POP should be taken into higher consideration after vaginal delivery and postpartum follow-up should be performed, to identify and/or treat it at the earliest stages. [ABSTRACT FROM AUTHOR]

Simple Summary: During the recent years, the field of exercise and physical activity have expanded prominently, not only for the prevention but also for the management of different pathologies, including breast cancer. A broad range of studies have been conducted to analyze this relationship, in aim to find the best routines and use of exercise in breast cancer management. Although many works provide contradictory results in these terms, there is less doubt regarding the role of physical activity as a central support for breast cancer patients, due to the systemic benefits of exercise in these women, therefore decreasing the risk of breast cancer-related complications and increasing their quality of life and survival. Future research should be established in order to individualize the physical activity performed by these women based on the available scientific evidence in a multidisciplinary context to maximize the success of breast cancer management. Breast cancer (BC) is the most common malignancy and the second cause of cancer-related death among women. It is estimated that 9 in 10 cases of BC are due to non-genetic factors, and approximately 25% to 30% of total breast cancer cases should be preventable only by lifestyle interventions. In this context, physical activity represents an excellent and accessible approach not only for the prevention, but also for being a potential support in the management of breast cancer. The present review will collect the current knowledge of physical activity in the background of breast cancer, exploring its systemic and molecular effects, considering important variables in the training of these women and the evidence regarding the benefits of exercise on breast cancer survival and prognosis. We will also summarize the various effects of physical activity as a co-adjuvant therapy in women receiving different treatments to deal with its adverse effects. Finally, we will reveal the impact of physical activity in the enhancement of quality of life of these patients, to conclude the central role that exercise must occupy in breast cancer management, in an adequate context of a healthy lifestyle. [ABSTRACT FROM AUTHOR]

Infectious diseases are one of the main global public health risks, predominantly caused by viruses, bacteria, fungi, and parasites. The control of infections is founded on three main pillars: prevention, treatment, and diagnosis. However, the appearance of microbial resistance has challenged traditional strategies and demands new approaches. Dendrimers are a type of polymeric nanoparticles whose nanometric size, multivalency, biocompatibility, and structural perfection offer boundless possibilities in multiple biomedical applications. This review provides the reader a general overview about the uses of dendrimers and dendritic materials in the treatment, prevention, and diagnosis of highly prevalent infectious diseases, and their advantages compared to traditional approaches. Examples of dendrimers as antimicrobial agents per se, as nanocarriers of antimicrobial drugs, as well as their uses in gene transfection, in vaccines or as contrast agents in imaging assays are presented. Despite the need to address some challenges in order to be used in the clinic, dendritic materials appear as an innovative tool with a brilliant future ahead in the clinical management of infectious diseases and many other health issues. [ABSTRACT FROM AUTHOR]