In Vitro and In Vivo Evaluation of Chitosan/HPMC/Insulin Hydrogel for Wound Healing Applications.

Treatment of chronic wounds is challenging, and the development of different formulations based on insulin has shown efficacy due to their ability to regulate oxidative stress and inflammatory reactions. The formulation of insulin with polysaccharides in biohybrid hydrogel systems has the advantage of synergistically combining the bioactivity of the protein with the biocompatibility and hydrogel properties of polysaccharides. In this study, a hydrogel formulation containing insulin, chitosan, and hydroxypropyl methyl cellulose (Chi/HPMC/Ins) was prepared and characterized by FTIR, thermogravimetric, and gel point analyses. The in vitro cell viability and cell migration potential of the Chi/HPMC/Ins hydrogel were evaluated in human keratinocyte cells (HaCat) by MTT and wound scratch assay. The hydrogel was applied to excisional full-thickness wounds in diabetic mice for twenty days for in vivo studies. Cell viability studies indicated no cytotoxicity of the Chi/HPMC/Ins hydrogel. Moreover, the Chi/HPMC/Ins hydrogel promoted faster gap closure in the scratch assay. In vivo, the wounds treated with the Chi/HPMC/Ins hydrogel resulted in faster wound closure, formation of a more organized granulation tissue, and hair follicle regeneration. These results suggest that Chi/HPMC/Ins hydrogels might promote wound healing in vitro and in vivo and could be a new potential dressing for wound healing.

Photobiomodulation with Blue Light on Wound Healing: A Scoping Review.

BACKGROUND: Photobiomodulation consists of inducing healing by irradiating light. This scoping review investigates the effect of blue light on the healing process. METHODS: The MEDLINE, Web of Science, Scopus, and CINAHL databases were searched. Two reviewers independently examined the search results and extracted data from the included studies. A descriptive analysis was performed. RESULTS: Twenty-two articles were included. Studies were categorized as in vitro/mixed, preclinical, and clinical. The power density used was 10-680 mW/cm2 in most of the in vitro/preclinical studies, the irradiation time ranged from 5 s to 10 min, and different wavelengths and energy densities were used. In clinical studies, the wavelength ranged from 405 to 470 nm, and the energy density varied from 1.5 to 30 J/cm2. CONCLUSIONS: A low energy density (<20 J/cm2) was able to stimulate the different cell types and proteins involved in healing, while a high energy density, 20.6-50 J/cm2, significantly reduced cell proliferation, migration, and metabolism. There is a great variety of device parameters among studies, and this makes it difficult to conclude what the best technical specifications are. Thus, further studies should be performed in order to define the appropriate parameters of light to be used.

An older diabetes-induced mice model for studying skin wound healing.

Advances in wound treatment depend on the availability of animal models that reflect key aspects of human wound healing physiology. To this date, the accepted mouse models do not reflect defects in the healing process for chronic wounds that are associated with type two diabetic skin ulcers. The long term, systemic physiologic stress that occurs in middle aged or older Type 2 diabetes patients is difficult to simulate in preclinical animal model. We have strived to incorporate the essential elements of this stress in a manageable mouse model: long term metabolic stress from obesity to include the effects of middle age and thereafter onset of diabetes. At six-weeks age, male C57BL/6 mice were separated into groups fed a chow and High-Fat Diet for 0.5, 3, and 6 months. Treatment groups included long term, obesity stressed mice with induction of diabetes by streptozotocin at 5 months, and further physiologic evaluation at 8 months old. We show that this model results in a severe metabolic phenotype with insulin resistance and glucose intolerance associated with obesity and, more importantly, skin changes. The phenotype of this older age mouse model included a transcriptional signature of gene expression in skin that overlapped that observed with elderly patients who develop diabetic foot ulcers. We believe this unique old age phenotype contrasts with current mice models with induced diabetes.

Exogenous succinate impacts mouse brown adipose tissue mitochondrial proteome and potentiates body mass reduction induced by liraglutide.

Obesity is one of the leading noncommunicable diseases in the world. Despite intense efforts to develop strategies to prevent and treat obesity, its prevalence continues to rise worldwide. A recent study has shown that the tricarboxylic acid intermediate succinate increases body energy expenditure by promoting brown adipose tissue thermogenesis through the activation of uncoupling protein-1; this has generated interest surrounding its potential usefulness as an approach to treat obesity. It is currently unknown how succinate impacts brown adipose tissue protein expression, and how exogenous succinate impacts body mass reduction promoted by a drug approved to treat human obesity, the glucagon-like-1 receptor agonist, liraglutide. In the first part of this study, we used bottom-up shotgun proteomics to determine the acute impact of exogenous succinate on the brown adipose tissue. We show that succinate rapidly affects the expression of 177 brown adipose tissue proteins, which are mostly associated with mitochondrial structure and function. In the second part of this study, we performed a short-term preclinical pharmacological intervention, treating diet-induced obese mice with a combination of exogenous succinate and liraglutide. We show that the combination was more efficient than liraglutide alone in promoting body mass reduction, food energy efficiency reduction, food intake reduction, and an increase in body temperature. Using serum metabolomics analysis, we showed that succinate, but not liraglutide, promoted a significant increase in the blood levels of several medium and long-chain fatty acids. In conclusion, exogenous succinate promotes rapid changes in brown adipose tissue mitochondrial proteins, and when used in association with liraglutide, increases body mass reduction.NEW & NOTEWORTHY Exogenous succinate induces major changes in brown adipose tissue protein expression affecting particularly mitochondrial respiration and structural proteins. When given exogenously in drinking water, succinate mitigates body mass gain in a rodent model of diet-induced obesity; in addition, when given in association with the glucagon-like peptide-1 receptor agonist, liraglutide, succinate increases body mass reduction promoted by liraglutide alone.

A Free Fatty Acid Synthetic Agonist Accelerates Wound Healing and Improves Scar Quality in Mice.

BACKGROUND: Impaired wound healing is a health problem around the world, and the search for a novel product to repair wounded skin is a major topic in the field. GW9508 is a synthetic molecule described as a selective agonist of free fatty acid receptors (FFARs) 1 and 4, and there is evidence of its anti-inflammatory effects on several organs of the body. PURPOSE: Here, we aimed to evaluate the effects of topical GW9508 on wound healing in mice. RESEARCH DESIGN: First, we used bioinformatic methods to determine the expression of FFAR1 and FFAR4 mRNA in the skin from a human cell atlas assembled with single-cell transcriptomes. Next, we employed 6-week-old C57BL6J mice with 2 wounds inflicted in the back. The mice were randomly divided into 2 groups, a control group, which received topical vehicle, and a treatment group, which received GW9508, for 12 days. The wound was monitored by photographic documentation every 2 days, and samples were collected at day 6 and 12 post injury for RT-PCR, western blot and histology analyses. RESULTS: FFAR1 and FFAR4 mRNA are expressed in skin cells in similar amounts to those in other tissues. Topical GW9508 accelerated wound healing and decreased gene expression of IL-10 and metalloproteinase 9 on days 6 and 12 post injury. It increased the quantity of Collagen I and improved the organization of collagen fibres. Conclusions: Our results show that GW9508 could be an attractive drug treatment for wounded skin. Future studies need to be performed to assess the impact of GW9508 in chronic wound models.

Oxaliplatin versus Irinotecan no câncer colorretal avançado / Oxaliplatin versus Irinotecan in advanced colorectal cancer

O câncer colorretal é uma neoplasia com alta prevalência e letalidade. A razão desse elevado número de mortes é a detecção da doença em estágios metastáticos, de difícil cura e que necessitam de terapia quimioterápica adjuvante ou paliativa. Na atualidade, o principal tratamento quimioterápico dessa neoplasia tem como base as drogas Oxaliplatina ou Irinotecano, isolados ou combinados com outros medicamentos. O objetivo desta revisão sistemática é avaliar se há superioridade do esquema quimioterápico com Irinotecano sobre o regime com Oxaliplatina. Foi realizada a análise de ensaios clínicos randomizados, fase II ou III, nas bases de dados eletrônicas Central e PubMed. Critérios de inclusão: ensaios clínicos randomizados comparando regimes à base de irinotecano ou oxaliplatina como tratamentos de primeira linha para câncer colorretal metastático. O desfecho primário analisado foi a superioridade entre os quimioterápicos sobre a sobrevida global. Os desfechos secundários incluíram sobrevida livre de progressão, taxa de resposta e efeitos colaterais. Registro na PROSPERO: CRD42019130339. Não houve diferença significativa nos 13 estudos sobre a sobrevida dos pacientes. Sobre os efeitos colaterais dos medicamentos, os regimes baseados em irinotecano foram associados a uma alta incidência de neutropenia e diarreia grave. Já os associados com oxaliplatin cursaram com alta incidência de neuropatia sensitiva. Não houve diferença estatisticamente significativa sobre a sobrevida global, sobrevivência livre de progressão e na taxa de resposta quando comparamos os pacientes que receberam oxaliplatina e irinotecano (AU)

Colorectal cancer is a highly prevalent and lethal neoplasm. The reason for this high number of deaths is the detection of the disease in metastatic stages, which are difficult to cure and require adjuvant or palliative chemotherapy therapy. Currently, the main chemotherapeutic treatment of this neoplasm is based on the drugs Oxaliplatin or Irinotecan, alone or combined with other drugs. The objective of this systematic review is to evaluate whether there is superiority of the chemotherapy regimen with Irinotecan over that with Oxaliplatin. Analysis of randomized clinical trials, phase II or III, was performed in the electronic databases Central and PubMed. Inclusion criteria: randomized clinical trials comparing irinotecan- or oxaliplatin-based regimens as first-line treatments for metastatic colorectal cancer. The primary endpoint analyzed was the superiority between chemotherapies on overall survival. Secondary endpoints included progression-free survival, response rate, and side effects. PROSPERO registration: CRD42019130339. There was no significant difference in the 13 studies on patient survival. On drug side effects, irinotecan-based regimens were associated with a high incidence of neutropenia and severe diarrhea. Those associated with oxaliplatin were associated with a high incidence of sensory neuropathy. There was no statistically significant difference in overall survival, progression-free survival, and response rate when comparing patients receiving oxaliplatin and irinotecan (AU)

Accelerative action of topical piperonylic acid on mice full thickness wound by modulating inflammation and collagen deposition.

Epidermal growth factor (EGF) promotes cell growth, proliferation, and survival in numerous tissues. Piperonylic acid, a metabolite present in peppers (Piper nigrum L. and Piper longum L.), can bind to the epidermal growth factor receptor (EGFR) and induce an intracellular signaling cascade leading to the transcription of genes responsible for these actions, especially in keratinocytes. These cells are fundamental in maintaining cutaneous homeostasis and are the first to be damaged in the case of a wound. Thus, we hypothesized that piperonylic acid improves wound healing. C57BL6/J male mice were submitted to dorsal skin wounds caused by a 6 mm punch and treated topically with piperonylic acid or vehicle. The wounds were evaluated macro- and microscopically, and tissue samples were collected for immunofluorescence and real-time PCR analyses on days 6, 9 and 19 post-injury. Topical piperonylic acid improved wound healing from day 6 post-injury until closure. This phenomenon apparently occurred through EGFR activation. In addition, piperonylic acid modulated the gene expression of interleukin (Il)-6, il-1ß, tumor necrosis factor (Tnf)-α, il-10, monocyte chemoattractant protein (Mcp)-1 and insulin-like growth factor (Igf)-1, which are important for the healing process. By day 19 post-injury, the new tissue showed greater deposition of type I collagen and a morphology closer to intact skin, with more dermal papillae and hair follicles. We conclude that piperonylic acid may be a viable option for the treatment of skin wounds.

Interleukin-6 actions in the hypothalamus protects against obesity and is involved in the regulation of neurogenesis.

BACKGROUND: Interleukin-6 (IL6) produced in the context of exercise acts in the hypothalamus reducing obesity-associated inflammation and restoring the control of food intake and energy expenditure. In the hippocampus, some of the beneficial actions of IL6 are attributed to its neurogenesis-inducing properties. However, in the hypothalamus, the putative neurogenic actions of IL6 have never been explored, and its potential to balance energy intake can be an approach to prevent or attenuate obesity. METHODS: Wild-type (WT) and IL6 knockout (KO) mice were employed to study the capacity of IL6 to induce neurogenesis. We used cell labeling with Bromodeoxyuridine (BrdU), immunofluorescence, and real-time PCR to determine the expression of markers of neurogenesis and neurotransmitters. We prepared hypothalamic neuroprogenitor cells from KO that were treated with IL6 in order to provide an ex vivo model to further characterizing the neurogenic actions of IL6 through differentiation assays. In addition, we analyzed single-cell RNA sequencing data and determined the expression of IL6 and IL6 receptor in specific cell types of the murine hypothalamus. RESULTS: IL6 expression in the hypothalamus is low and restricted to microglia and tanycytes, whereas IL6 receptor is expressed in microglia, ependymocytes, endothelial cells, and astrocytes. Exogenous IL6 reduces diet-induced obesity. In outbred mice, obesity-resistance is accompanied by increased expression of IL6 in the hypothalamus. IL6 induces neurogenesis-related gene expression in the hypothalamus and in neuroprogenitor cells, both from WT as well as from KO mice. CONCLUSION: IL6 induces neurogenesis-related gene expression in the hypothalamus of WT mice. In KO mice, the neurogenic actions of IL6 are preserved; however, the appearance of new fully differentiated proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons is either delayed or disturbed.

A Smartphone App for Individual Xylazine/Ketamine Calculation Decreased Anesthesia-Related Mortality in Mice.

Currently, experimental animals are widely used in biological and medical research. However, the scientific community has raised several bioethical concerns, such as the number of animals required to achieve reproducible and statistically relevant results. These concerns involve aspects related to pain, discomfort, and unwanted animal loss. Retrospectively, we compare two different approaches for anesthesia dosage: a mobile app for dose calculation and a standard dose calculation. A total of 939 C57BL/6J and Swiss mice were analyzed. We collected data on intraoperative and anesthesia-related mortality as described in electronic or physical handwritten records. Our results showed that the mobile app approach significantly reduces anesthetic-related deaths upon using doses of ketamine and xylazine. The results suggest that anesthesia-related mortality can be minimized even more using information technology approaches, helping to solve an old but transversal challenge for researchers working with experimental mice. The mobile app is a free and open code which could be implemented worldwide as an essential requirement for all anesthetic procedures in mice using xylazine and ketamine combination. As an open code app, the Labinsane initiative could also represent the starting point to unify and validate other anesthetic procedures in different species and strains.

Presença de sintomas de fobia social, transtorno do pânico e ansiedade de separação em estudantes de 11 a 17 anos, em uma escola da rede pública de ensino de Salvador / Presence of symptoms of social phobia, panic and separation anxiety in students aged 11 to 17 years from a school of th public system of Salvador

Introdução: crianças e adolescentes, não raro, apresentam sintomas de fobia social, transtorno do pânico e ansiedade de separação, que podem causar comprometimento nas habilidades sociais e dificultar as relações de forma incapacitante. Objetivo: Este estudo tem como objetivo verificar a presença de sintomas fóbicos sociais, transtorno de pânico e ansiedade de separação em adolescentes, com idade entre 11 e 17 anos, de uma escola pública da cidade de Salvador. Metodologia: este é um estudo observacional, transversal, que integra outro mais amplo, realizado em escola pública de Salvador, entre março e dezembro de 2015. A escala Revised Children's Anxiety and Depression foi aplicada em uma amostra de 674 alunos. Resultados: os alunos apresentaram sintomas de fobia social, transtorno do pânico e ansiedade de separação, em escala crescente, de acordo com a idade.

Introduction:children and adolescents often present symptoms of social phobia, panic disorder and separation anxiety disorder, which can cause social impairments and hinder relationships in a disabling way. Objective: this study aims to investigate the presence of social phobia, panic disorder and separation anxiety symptoms in adolescents aged between 11 and 17 years from a public school in the city of Salvador. Methodology: the present study is an observational cross-sectional research, which is part of a broader study conducted in a public school in Salvador, between March and December 2015. The Revised Children's Anxiety and Depression Scale (RCADS) was used in a sample of 674 students. Results: the students presented symptoms of social phobia, panic disorder and separation anxiety on an increasing scale proportional to age.

Fatores associados à remoção do dispositivo de acesso vascular periférico em pacientes pediátricos / Factors associated to the withdrawal of peripheral vascular access device in pediatric patients

Objetivo: identificar fatores relacionados à retirada do cateter venoso periférico em crianças hospitalizadas em uma Unidade de Internação Pediátrica. Métodos: Coorte prospectiva realizada com crianças com cateter venoso periférico, internadas em uma Unidade de Internação Pediátrica. A amostra foi consecutiva, não probabilística, os dados foram coletados, por um período de 90 dias. Na análise estatística foram utilizados os testes Qui-quadrado, Mann-Whitney e modelos de riscos proporcionais de Cox. Considerou-se nível de significância igual a 5%. Resultados: Amostra composta por 134 crianças, com média de idade de 4,27 anos (DP 3,45). Os motivos de retirada dos cateteres venosos periféricos foram causas planejadas em aproximadamente 56% dos casos, como alta hospitalar, término da terapia intravenosa e transferência. Em 44% dos cateteres venosos periféricos retirados, as causas foram não planejadas, com predomínio de infiltração/extravasamento (16,42%) e flebite (11,94%). O uso de anti-infecciosos (OR=7,03; p=0,0001), punções venosas em membros inferiores (OR=5,12; p=0,0070), punções anteriores (OR=3,24; p=0,0014) e sexo masculino (OR= 2,70; p=0,0092) aumentaram o risco de retirada dos cateteres venosos periféricos por causas não planejadas. Conclusão: os resultados sugerem, principalmente, revisão dos locais para punção venosa em Pediatria, bem como, diluição e infusão criteriosa de anti-infecciosos. (AU)

Objective: To identify factors related to the withdrawal of peripheral venous catheter in hospitalized children in a Pediatric Inpatient Unit. Methods: Prospective cohort study conducted with children with peripheral venous catheter admitted to a Pediatric Inpatient Unit. The sample was consecutive, non-probability, data were collected for a period of 90 days. Statistical analysis Chi-square, Mann-Whitney and models of Cox proportional hazards were used. A significance level of 5% was considered. Results: A sample was composed of 134 children, mean age of 4.27 years (SD 3.45). The reasons for withdrawal peripheral venous catheters were planned causes approximately 56% of cases, such as hospital discharge, end of the intravenous therapy and transfer. At 44% of the removed peripheral venous catheters, the causes were not planned, with infiltration / extravasation (16.42%) and phlebitis (11.94%) predominating. The use of anti-infectives (OR = 7.03; p = 0.0001), venous punctures in the lower limbs (OR = 5.12; p = 0.0070), anterior punctures (OR = 3.24; p = 0.0014) and male gender (OR = 2.70; p = 0.0092) increased the risk of catheters withdrawal for unplanned causes. Conclusion: The results suggest, principally, reviewing sites for venipuncture in pediatrics, as well as dilution and judicious infusion of anti-infective. (AU)

Objetivo: Identificar los factores relacionados con la perdida del catéter venoso periférico en niños hospitalizados en una unidad de hospitalización pediátrica. Métodos: Estudio de corte prospectiva realizada con niños con catéter venoso periférico, hospitalizadas en una unidad de hospitalización pediátrica. La muestra fue consecutiva, no probabilística, los datos se recopilaron durante un período de 90 días. En el análisis estadístico, se realizaron las pruebas de chi-cuadrados, Mann-Whitney y modelos de riesgo de Cox. El nivel de significancia fue 5%. Resultados: Muestra que consta de 134 niños, con una edad media de 4.27 años (DE 3.45). Entre las razones del retiro de los catéteres venosos periféricos están: planificados en aproximadamente el 56% de los casos, como al momento del alta hospitalaria, termino de la terapia intravenosa y la transferencia. En el 44% de los catéteres venosos periféricos perdidos, las causas no se planificaron, con predominio de infiltración / extravasación (16,42%) y flebitis (11.94%). El uso de terapia anti-infecciosa (OR = 7,03, p = 0,0001), punciones venosas en las extremidades inferiores (OR = 5,12, p = 0.0070), punciones anteriores (OR = 3.24; p = 0.0014) y género masculino (OR = 2.70, p = 0.0092) aumentó el riesgo de retiro de los catéteres venosos periféricos mediante causas no planificadas. Conclusión: Los resultados sugieren que, principalmente, una revisión de sitios de punción venosa en pediatría, así como dilución e infusión criteriosa de terapias anti-infecciosas. (AU)

Novel fibrin-fibronectin matrix accelerates mice skin wound healing.

Plasma fibrinogen (F1) and fibronectin (pFN) polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing. About 90% of plasma F1 has a homodimeric pair of γ chains (γγF1), and 10% has a heterodimeric pair of γ and more acidic γ' chains (γγ'F1). We have synthesized a novel fibrin matrix exclusively from a 1:1 (molar ratio) complex of γγ'F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII (rFXIIIa). In this matrix, the fibrin nanofibers were decorated with pFN nanoclusters (termed γγ'F1:pFN fibrin). In contrast, fibrin made from 1:1 mixture of γγF1 and pFN formed a sporadic distribution of "pFN droplets" (termed γγF1+pFN fibrin). The γγ'F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells (HUVECs) relative to the γγF1+FN fibrin. Three dimensional (3D) culturing showed that the γγ'F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts. HUVECs in the 3D γγ'F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in the γγF1+pFN fibrin. Relative to γγF1+pFN fibrin, mouse dermal wounds that were sealed by γγ'F1:pFN fibrin exhibited accelerated and enhanced healing. This study suggests that a 3D pFN presentation on a fibrin matrix promotes wound healing.

Bioactive Fatty Acids in the Resolution of Chronic Inflammation in Skin Wounds.

Significance: Optimal skin wound healing is crucial for maintaining tissue homeostasis, particularly in response to an injury. The skin immune system is under regulation of mediators such as bioactive lipids and cytokines that can initiate an immune response with controlled inflammation, followed by efficient resolution. However, nutritional deficiency impacts wound healing by hindering fibroblast proliferation, collagen synthesis, and epithelialization, among other crucial functions. In this way, the correct nutritional support of bioactive lipids and of other essential nutrients plays an important role in the outcome of the wound healing process. Recent Advances and Critical Issues: Several studies have revealed the potential role of lipids as a treatment for the healing of skin wounds. Unsaturated fatty acids such as linoleic acid, α-linolenic acid, oleic acid, and most of their bioactive products have shown an effective role as a topical treatment of chronic skin wounds. Their effect, when the treatment starts at day 0, has been observed mainly in the inflammatory phase of the wound healing process. Moreover, some of them were associated with different dressings and were tested for clinical purposes, including pluronic gel, nanocapsules, collagen films and matrices, and polymeric bandages. Therefore, future research is still needed to evaluate these dressing technologies in association with different bioactive fatty acids in a wound healing context. Future Directions: This review summarizes the main results of the available clinical trials and basic research studies and provides evidence-based conclusions. Together, current data encourage the use of bioactive fatty acids for an optimal wound healing resolution.

Sublethal effects of spirodiclofen on biological and demographic parameters of the citrus leprosis mite Brevipalpus yothersi (Acari: Tenuipalpidae).

BACKGROUND: Brevipalpus yothersi Baker is one of the main vectors of citrus leprosis. Knowing the biology of this mite species when under chemical control is extremely important to understand its population dynamics, and then to solve problems of management of this pest. Therefore, we assessed the effects of one sublethal dose of spirodiclofen (0.48 ppm) on biological and demographic parameters of B. yothersi under laboratory and greenhouse conditions, comparing them with non-exposed mite population. RESULTS: Under laboratory conditions, where citrus fruits were used as a substrate, the duration of developmental stages (pre-egg-laying and egg-laying) and mite longevity showed no differences between treatments. However, the number of laid eggs increased in acaricide-treated fruits. In the greenhouse experiment, where citrus plants were used as a substrate, the instantaneous growth rate (ri) of mites was positive in all untreated plots. In contrast, in treated plants, ri was negative in 12 experimental units, and mite populations were suppressed in five of them. Moreover, mite population dynamics had a positive ri in three treated plants. CONCLUSIONS: Spirodiclofen sublethal dose had no negative effect on the offspring of B. yothersi females. However, it is not safe for citrus leprosis mite since it may increase egg number per female in some conditions. Biological and demographic differences could influence mite population dynamics in the field, requiring appropriate management strategies to improve citrus leprosis control. © 2019 Society of Chemical Industry.

Topical Topiramate Improves Wound Healing in an Animal Model of Hyperglycemia.

Wound healing is severely affected in hyperglycemia and other metabolic conditions. Finding new therapeutic approaches that accelerate wound healing and improve the quality of the scar may reduce the morbidity commonly associated with skin lesions in diabetes. This study evaluated the effect of topical topiramate (TPM) on wound healing in C57 mice. Streptozotocin-induced hyperglycemic mice were subjected to a wound on the back and randomly allocated for treatment with either vehicle or topical TPM cream (2%) once a day for 14 days. Polymerase chain reaction, Western blotting, and microscopy were performed for the analysis. TPM improved wound healing (complete resolution at Day 10, 98% ± 5 for TPM vs. 81% ± 28 for vehicle), increased organization and deposition of collagen Type I, and enhanced the quality of the scars as determined by microscopy. In addition, TPM modulated the expression of cytokines and proteins of the insulin-signaling pathway: In early wound-healing stages, expression of interleukin-10, an anti-inflammatory marker, increased, whereas at the late phase, the pro-inflammatory markers tumor necrosis factor-α and monocyte chemoattractant protein-1 increased and there was increased expression of a vascular endothelial growth factor. Proteins of the insulin-signaling pathway were stimulated in the late wound-healing phase. Topical TPM improves the quality of wound healing in an animal model of hyperglycemia. The effect of TPM is accompanied by modulation of inflammatory and growth factors and proteins of the insulin-signaling pathway. Therefore, topical TPM presents as a potential therapeutic agent in skin wounds in patients with hyperglycemia.

Prognostic value of coronary computed tomography in patients with non-significant perfusion defects by myocardial perfusion SPECT.

AIMS: Myocardial perfusion scintigraphy (MPS) is an important diagnostic tool in the management of patients with suspected coronary artery disease (CAD). However, the presence of mild-moderate perfusion defects can be challenging and may lead to unnecessary cardiac catheterization. Coronary computed tomography angiography (CCTA) is a method with excellent accuracy in the evaluation of CAD, but its role in this setting of patients has not been fully defined. This study aims to assess the potential of CCTA in the prediction of cardiac adverse events in patients with suspected CAD with non-significant perfusion defects by MPS. METHODS AND RESULTS: We conducted a cohort study in 292 patients presenting with non-significant perfusion defects by MPS undergoing a CCTA. The patients were followed for a mean of 34 months for occurrence of major cardiac adverse events - MACE. The majority of the patients (64.7%) were male, with a mean age of 57.9 ± 12.6 years. During the follow-up there were 37 MACE. In multivariate Cox proportional hazards model, hypertension and CCTA were independent predictors of MACE. The patients who presented a significant coronary obstruction by CCTA had a high risk of MACE (HR 15.3; 95% CI 4.06 to 57.90; P < 0.001). Kaplan-Meier curve showed a significant difference (log-rank χ²; P < 0.001) using CCTA in predicting MACE. CONCLUSION: CCTA carries a powerful prognostic value in predicting adverse events in patients with suspected CAD and MPS with mild-moderate perfusion defects and may be useful in risk stratification of these patients.

Perception of parents of children with and without disabilities about teething disturbances and practices adopted

Aim: To evaluate and compare the perception of parents of children with and without disabilitiesabout the occurrence of local and systemic manifestations during the eruption of primary teeth and toinvestigate the parents’ practices used to alleviate teething disturbances. Methods: A cross-sectionalstudy was conducted in a sample of parents of children without disabilities (GI) and parents of childrenwith disabilities (GII) treated at a University Pediatric Dentistry Clinic. Data from GI and GII werecollected using a structured questionnaire applied during an interview with the parents, and wereanalyzed using descriptive statistics. Mann-Whitney and Wilcoxon tests were employed and the levelof significance was set at p<0.05. Results: The questionnaires were filled out by 86 parents, being45 in GI and 41 in GII. For GI, the most frequent local manifestations were edema around the tooth(84.44%) and increased suction (75.56%); and for GII were edema and erythema around the tooth(78.05% and 70.73%, respectively). The most frequent systemic manifestations, according to parentsof both groups, were irritability and fever. There was no statistically significant difference betweengroups (p<0.05). It was observed that 46.66% and 68.3% of parents of GI and GII, respectively,adopted different practices to alleviate teething disturbances. Conclusions: During primary teetheruption, local and systemic manifestations may occur and different practices were adopted by theInterviewed parents, mainly those with children with disabilities.