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Background: Intra-abdominal hypertension and abdominal compartment syndrome are common with clinically significant consequences. We investigated the pathophysiological effects of raised IAP as part of a more extensive exploratory animal study. The study design included both pneumoperitoneum and mechanical intestinal obstruction models. Methods: Forty-nine female swine were divided into six groups: a control group (Cr; n = 5), three pneumoperitoneum groups with IAPs of 20mmHg (Pn20; n = 10), 30mmHg (Pn30; n = 10), 40mmHg (Pn40; n = 10), and two mechanical intestinal occlusion groups with IAPs of 20mmHg (MIO20; n = 9) and 30mmHg (MIO30; n = 5). Results: There were significant changes (p<0.05) noted in all organ systems, most notably systolic blood pressure (SBP) (p<0.001), cardiac index (CI) (p = 0.003), stroke volume index (SVI) (p<0.001), mean pulmonary airway pressure (MPP) (p<0.001), compliance (p<0.001), pO2 (p = 0.003), bicarbonate (p = 0.041), hemoglobin (p = 0.012), lipase (p = 0.041), total bilirubin (p = 0.041), gastric pH (p<0.001), calculated glomerular filtration rate (GFR) (p<0.001), and urine output (p<0.001). SVV increased progressively as the IAP increased with no obvious changes in intravascular volume status. There were no significant differences between the models regarding their impact on cardiovascular, respiratory, renal and gastrointestinal systems. However, significant differences were noted between the two models at 30mmHg, with MIO30 showing worse metabolic and hematological parameters, and Pn30 and Pn40 showing a more rapid rise in creatinine. Conclusions: This study identified and quantified the impact of intra-abdominal hypertension at different pressures on several organ systems and highlighted the significance of even short-lived elevations. Two models of intra-abdominal pressure were used, with a mechanical obstruction model showing more rapid changes in metabolic and haematological changes. These may represent different underlying cellular and vascular pathophysiological processes, but this remains unclear. [ABSTRACT FROM AUTHOR]

The main contribution of this paper is the assets of the current and voltage ripples in a buck converter with an LED load. The results indicate that the ripples are different and that it is possible to reduce the passive filter concerning the model of the LED as a simple resistance. The paper presents the design and simulation of a buck converter as a power supply for an LED lamp. Modeling the LED as a resistor and a voltage source (SVRM), the equations to calculate the components of the circuit using the SVRM model are presented, where the Fourier series and phasors are used to calculate the output filter. The equations are validated with SPICE simulations. The results indicate that the SVRM model for the LED load affects the calculation of the output filter of the buck converter as well as the voltage and current ripples, making it a more precise design alternative to the proposed development. [ABSTRACT FROM AUTHOR]

Surgical site occurrences pose a threat to patient health, potentially resulting in significant increases in health care spending caused by using additional resources. The objective of this study was to reach a consensus among a group of experts in incisional negative pressure wound therapy to determine the indications for using this type of treatment prophylactically and to analyze the associated risk factors of surgical site occurrences in abdominal surgery. A group of experts in incisional negative pressure wound therapy from Spain and Portugal was formed among general surgery specialists who frequently perform colorectal, esophagogastric, or abdominal wall surgery. The Coordinating Committee performed a bibliographic search to identify the most relevant publications and to create a summary table to serve as a decision-making protocol regarding the use of prophylactic incisional negative pressure wound therapy based on factors related to the patient and type of procedure. The patient risk factors associated with surgical site occurrence development such as age, immunosuppression, anticoagulation, hypoalbuminemia, smoking, American Society of Anesthesiologists classification, diabetes, obesity, and malnutrition were analyzed. For surgical procedure factors, surgical time, repeated surgeries, organ transplantation, need for blood transfusion, complex abdominal wall reconstruction, surgery at a contaminated site, open abdomen closure, emergency surgery, and hyperthermic intraperitoneal chemotherapy were analyzed. In our experience, this consensus has been achieved on a tailored set of recommendations on patient and surgical aspects that should be considered to reduce the risk of surgical site occurrences with the use of prophylactic incisional negative pressure wound therapy, particularly in areas where the evidence base is controversial or lacking. [Display omitted] [ABSTRACT FROM AUTHOR]

Unsuccessful wound closure in chronic wounds can be linked to altered keratinocyte activation and their inability to re-epithelize. Suggested mechanisms driving this impairment involve unbalanced cytokine signaling. However, the molecular events leading to these aberrant responses are poorly understood. Among cytokines affecting keratinocyte responses, Transforming Growth Factor-β (TFG-β) is thought to have a great impact. In this study, we have used a previously characterized skin epidermal in vitro model, HaCaT cells continuously exposed to TGF-β1, to study the wound recovery capabilities of chronified/senescent keratinocytes. In this setting, chronified keratinocytes show decreased migration and reduced activation in response to injury. Amniotic membrane (AM) has been used successfully to manage unresponsive complicated wounds. In our in vitro setting, AM treatment of chronified keratinocytes re-enabled migration in the early stages of wound healing, also promoting proliferation at later stages. Interestingly, when checking the gene expression of markers known to be altered in TGF-β chronified cells and involved in cell cycle regulation, early migratory responses, senescence, and chronic inflammation, we discovered that AM treatment seemed to reset back to keratinocyte status. The analysis of the evolution of both the levels of keratinocyte activation marker cytokeratin 17 and the spatial-temporal expression pattern of the proliferation marker Ki-67 in human in vivo biopsy samples suggests that responses to AM recorded in TGF-β chronified HaCaT cells would be homologous to those of resident keratinocytes in chronic wounds. All these results provide further evidence that sustained TGF-β might play a key role in wound chronification and postulate the validity of our TGF-β chronified HaCaT in vitro model for the study of chronic wound physiology. [ABSTRACT FROM AUTHOR]

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Cell therapy is a progressively growing field that is rapidly moving from preclinical model development to clinical application. Outcomes obtained from clinical trials reveal the therapeutic potential of stem cell-based therapy to deal with unmet medical treatment needs for several disorders with no therapeutic options. Among adult stem cells, mesenchymal stem cells (MSCs) are the leading cell type used in advanced therapies for the treatment of autoimmune, inflammatory and vascular diseases. To date, the safety and feasibility of autologous MSC-based therapy has been established; however, their indiscriminate use has resulted in mixed outcomes in preclinical and clinical studies. While MSCs derived from diverse tissues share common properties depending on the type of clinical application, they markedly differ within clinical trials in terms of efficacy, resulting in many unanswered questions regarding the application of MSCs. Additionally, our experience in clinical trials related to critical limb ischemia pathology (CLI) shows that the therapeutic efficacy of these cells in different animal models has only been partially reproduced in humans through clinical trials. Therefore, it is crucial to develop new research to identify pitfalls, to optimize procedures and to clarify the repair mechanisms used by these cells, as well as to be able to offer a next generation of stem cell that can be routinely used in a cost-effective and safe manner in stem cell-based therapies targeting CLI. [ABSTRACT FROM AUTHOR]

Objective: The amniotic membrane (AM) is a tissue with low immunogenity and high therapeutic potential due to its anti-inflammatory, anti-fibrotic and antimicrobial effects. This paper describes the use of cryopreserved amniotic membrane allografts to treat diabetic foot ulcers (DFUs) in patients with diabetes. Method: In this case series, AM was processed to obtain a final medicinal product: cryopreserved amniotic membrane. cryopreserved AM was applied every 7–10 days until total epithelialisation of the DFUs. Results: A total of 14 patients with DFUs (median size: 12.30cm, (range: 0.52–42.5cm2) were treated and followed up until complete closure (median time: 20 weeks, range: 7–56 weeks). Patients received 4–40 AM applications. All patients in this study achieved complete epithelialisation of the wound. No adverse events were observed. Conclusion: AM is a feasible and safe treatment in complex DFUs. Furthermore, the treatment is successful in achieving epithelialisation of long-evolution, unhealed wounds resistant to conventional therapies. [ABSTRACT FROM AUTHOR]

Background: A mechanical intestinal obstruction (MIO) can generate intraabdominal hypertension (IAH) that is life threatening. The intestines are very sensitive to IAH since the low splanchnic perfusion causes intestinal hypoxia, local acidosis and bacterial translocations. This may lead to acute intestinal distress syndrome (AIDS). The identification of intestinal injuries during IAH and its correlation with clinical parameters as the abdominal perfusion pressure (APP), the gastric intramucosal pH (pHi) and lactic acid (Lc) are still unknown. This study aimed to evaluate the sequence of intestinal histopathological findings in an MIO model and to analyze potential relationships with parameters currently used in clinical practice (APP, pHi and Lc). Material and methods: Twenty pigs were divided into three groups: a control group (n = 5) and two experimental groups with 20 mmHg (G1, n = 10) and 30 mmHg (G2, n = 5) of IAH by MIO. The pressures were maintained for 3 hours, except in 5 animals in G1 where it was maintained for 5 hours. The APP, pHi and LA were recorded and biopsies of the terminal ileum were taken every 30 minutes in all groups. The intestinal damage was graded according to the Park Score. Results: Intestinal injuries were found in 42.9% of pigs in the experimental groups. The lesions were independent of the level and duration of IAH. Although APP and pHi were slightly lower in injured animals (I +) of G1 and G2, there were no significant differences among those uninjured (I-). Lc was significantly increased in all I+ pigs from the onset of IAH. Conclusion: The IAH by MIO causes intestinal lesions from the first 30 minutes with concurrent decreases in APP and pHi and increases in Lc. Lc could be the best clinical parameter related to intestinal damages with a clear difference between I + and I- animals. [ABSTRACT FROM AUTHOR]

Background: Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation in deep traumatic wounds. Methods and Findings: To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21) and CDK2B (p15). The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border. Conclusions: The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation. [ABSTRACT FROM AUTHOR]

Epithelial and mesenchymal cells isolated from the amniotic membrane (AM) possess stem cell characteristics, differentiation potential toward lineages of different germ layers, and immunomodulatory properties. While their expansion and differentiation potential have been well studied and characterized, knowledge about their immunomodulatory properties and the mechanisms involved is still incomplete. These mechanisms have been evaluated on various target cells of the innate and the adaptive system and in animal models of different inflammatory diseases. Some results have evidenced that the immunomodulatory effect of AM-derived cells is dependent on cell-cell contact, but many of them have demonstrated that these properties are mediated through the secretion of suppressive molecules. In this review, we present an update on the described immunomodulatory properties of the derived amniotic cells and some of the proposed involved mechanisms. Furthermore, we describe some assays in animal models of different inflammatory diseases which reveal the potential use of these cells to treat such diseases. [ABSTRACT FROM AUTHOR]

Large-surface or deep wounds often become senescent in the inflammatory or proliferation stages and cannot progress to reepithelialization. This failure makes intervention necessary to provide the final sealing epithelial layer. The best current treatment is autologous skin graft, although there are other choices such as allogenic or autologous skin substitutes and synthetic dressings. Amniotic membrane (AM) is a tissue of interest as a biological dressing due to its biological properties and immunologic characteristics. It has low immunogenicity and beneficial reepithelialization effects, with antiinflammatory, antifibrotic, antimicrobial, and nontumorigenic properties. These properties are related to its capacity to synthesize and release cytokines and growth factors. We report the use of AM as a wound dressing in two patients with large and deep traumatic wounds. Negative pressure wound therapy followed by AM application was capable of restoring skin integrity avoiding the need for skin graft reconstruction. AM induced the formation of a well-structured epidermis. To understand this effect, we designed some assays on human keratinocyte-derived HaCaT cells. AM treatment of HaCaT induced ERK1/2 and SAP/JNK kinases phosphorylation and c-jun expression, a gene critical for keratinocytes migration; however, it did not affect cell cycle distribution. These data suggest that AM substantially modifies the behavior of keratinocytes in chronic wounds, thereby allowing effective reepithelialization. [ABSTRACT FROM AUTHOR]