A differential diagnosis for a postpartum headache.

Headache is a common finding in the postpartum period. A wide variety of factors can contribute for its appearance and the causes include primary as well as secondary headache disorders. The postdural puncture is one of the most common headache causes in this context, but not the only one, which is why a differential diagnosis of postpartum headache is essential. We describe a patient with a headache in the immediate postpartum period. It was initially diagnosed as a common postdural puncture headache, but was later discovered to be a cervical hematoma.

Measurement properties and factor analysis of the Diabetic Foot Ulcer Scale-short form (DFS-SF).

The purpose of this paper is to provide measurement properties evaluation and factor analysis of the Brazilian version of the diabetic foot ulcer scale-short form (DFS-SF). This methodological study evaluated the measurement properties of the DFS-SF by ceiling and floor effect reliability, responsiveness, and structural construct validity. The study included 290 people with diabetic foot under regular follow-up in a specialised outpatient clinic in inland São Paulo. Reliability was assessed by internal consistency using Cronbach's alpha and composite reliability. Ceiling and floor effects were assessed by the percentage of participants who scored the 15% worst (floor) and 15% best (ceiling) possible scale results. Validity was tested by correlating the instrument values with the domains of the Brazilian version of the Short Form Health Survey (SF-36). Responsiveness (n = 34) was accessed through the wound area obtained by photography and evaluated by the Image J Features program and the DFS-SF score at two moments, with a 4-week interval between them. The instrument had good evidence of reliability, shown by adequate internal consistency (Cronbach's alpha in domains >0.70) and compound reliability (0.84 > CC > 0.92); and of convergent validity, by significant positive correlations of moderate to strong magnitude with SF-36. Structural construct validity was examined by applying the DFS-SF confirmatory factor analysis, which indicated that the Brazilian version of the instrument is properly fitted to the original dimensional structure. The ceiling and floor effect analysis showed no ceiling or floor effects. Responsiveness was observed in the wound area, but not in the DFS-SF scores in the times. The Brazilian version of the DFS-SF presented evidence of validity and reliability, suggesting that this instrument is a valid tool for assessing the quality of life of people with diabetic foot in the Brazilian population.

Assessment of the use of Unna boot in the treatment of chronic venous leg ulcers in adults: systematic review protocol.

INTRODUCTION: Chronic venous insufficiency (CVI) is an anomaly of the normal functioning of the venous system caused by valvular incompetence with or without the obstruction of venous flow. This condition can affect either or both of the superficial and the deep venous systems. Venous dysfunction can even result in congenital or acquired disorders, and its complications include venous leg ulcers (VLUs). The objective of this systematic review is to determine the effectiveness of Unna boot in the treatment of wound healing of VLU by assessing the quality of the available evidence. METHODS AND ANALYSIS: A literature search in PubMed, CINAHL, Scopus, Web of Science, Cochrane Library, BVS/BIREME, Embase, ProQuest, BDTD, Thesis and Dissertation Catalog, Sao Paulo Research Foundation/Thesis and dissertation, OPEN THESIS, A service of the US National Institute of Health, Center for Reviews and Dissemination-University of New York and SciElo published in the last 10 years, the period from January 1999 to March 2019. The review will include primary studies (original), and Controlled Trials or Observational studies (cross-sectional, case-control or longitudinal studies) with VLU. The exclusion will include leg ulceration due to different causes, such as pressure, arterial, diabetic or mixed-aetiology leg ulcers. Data synthesis will be performed using a narrative summary and quantitative analysis. ETHICS AND DISSEMINATION: This systematic review does not require approval by the ethics committee, as individual patient data will not be collected. Dissemination of findings will be through publications in peer-reviewed journals and/or via conference presentations. PROSPERO REGISTRATION NUMBER: CRD42019127947.

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.

Effects of topical topiramate in wound healing in mice.

Recent studies have indicated that systemic topiramate can induce an improvement on the aesthetic appearance of skin scars. Here, we evaluated topical topiramate as an agent to improve wound healing in C57/BL6 mice. Mice were inflicted with a 6.0 mm punch to create two wounds in the skin of the dorsal region. Thereafter, mice were randomly assigned to either vehicle or topical topiramate (20 µl of 2% cream) once a day for 14 days, beginning on the same day as wound generation. We analyzed the wound samples over real-time PCR, Western blotting, and microscopy. There was no effect of the topiramate treatment on the time for complete reepithelization of the wound. However, on microscopic analysis, topiramate treatment resulted in increased granulation tissue, thicker epidermal repair, and improved deposition of type I collagen fibers. During wound healing, there were increased expressions of anti-inflammatory markers, such as IL-10, TGF-ß1, and reduced expression of the active form of JNK. In addition, topiramate treatment increased the expression of active forms of two intermediaries in the insulin-signaling pathway, IRS-1 and Akt. Finally, at the end of the wound-healing process, topiramate treatment resulted in increased expression of SOX-2, a transcription factor that is essential to maintain cell self-renewal of undifferentiated embryonic stem cells. We conclude that topical topiramate can improve the overall quality of wound healing in the healthy skin of mice. This improvement is accompanied by reduced expression of markers involved in inflammation and increased expression of proteins of the insulin-signaling pathway.

Topical Docosahexaenoic Acid (DHA) Accelerates Skin Wound Healing in Rats and Activates GPR120.

BACKGROUND: The development of methods for improving skin wound healing may have an impact on the outcomes of a number of medical conditions. The topical use of polyunsaturated fatty acids (PUFAs) can accelerate skin wound healing through mechanisms that involve, at least in part, the modulation of inflammatory activity. PURPOSE: We evaluated whether G-protein-coupled receptor 120 (GPR120), a recently identified receptor for docosahexaenoic acid (DHA) with anti-inflammatory activity, is expressed in the skin and responds to topical DHA. METHOD: Male Wistar rats were submitted to an 8.0-mm wound on the back and were immediately administered a topical treatment of a solution containing 30 µM of DHA once a day. The healing process was photodocumented, and tissues were collected on Days 5, 9, and 15 for protein and RNA analyses and histological evaluation. RESULTS: GPR120 was expressed in the intact skin and in the wound. Keratinocytes expressed the most skin GPR120, while virtually no expression was detected in fibroblasts. Upon DHA topical treatment, wound healing was significantly accelerated and was accompanied by the molecular activation of GPR120, as determined by its association with ß-arrestin-2. In addition, DHA promoted a reduction in the expression of interleukin (IL) 1ß and an increase in the expression of IL-6. Furthermore, there was a significant increase in expression of transforming growth factor ß (TGF-ß) and the keratinocyte marker involucrin. DISCUSSION: Topical DHA improved skin wound healing. The activation of GPR120 is potentially involved in this process.

Topical 5-azacytidine accelerates skin wound healing in rats.

The development of new methods to improve skin wound healing may affect the outcomes of a number of medical conditions. Here, we evaluate the molecular and clinical effects of topical 5-azacytidine on wound healing in rats. 5-Azacytidine decreases the expression of follistatin-1, which negatively regulates activins. Activins, in turn, promote cell growth in different tissues, including the skin. Eight-week-old male Wistar rats were submitted to 8.0-mm punch-wounding in the dorsal region. After 3 days, rats were randomly assigned to receive either a control treatment or the topical application of a solution containing 5-azacytidine (10 mM) once per day. Photo documentation and sample collection were performed on days 5, 9, and 15. Overall, 5-azacytidine promoted a significant acceleration of complete wound healing (99.7% ± 0.7.0 vs. 71.2% ± 2.8 on day 15; n = 10; p < 0.01), accompanied by up to threefold reduction in follistatin expression. Histological examination of the skin revealed efficient reepithelization and cell proliferation, as evaluated by the BrdU incorporation method. 5-Azacytidine treatment also resulted in increased gene expression of transforming growth factor-beta and the keratinocyte markers involucrin and cytokeratin, as well as decreased expression of cytokines such as tumor necrosis factor-alpha and interleukin-10. Lastly, when recombinant follistatin was applied to the skin in parallel with topical 5-azacytidine, most of the beneficial effects of the drug were lost. Thus, 5-azacytidine acts, at least in part through the follistatin/activin pathway, to improve skin wound healing in rodents.

Topical insulin accelerates wound healing in diabetes by enhancing the AKT and ERK pathways: a double-blind placebo-controlled clinical trial.

BACKGROUND: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. OBJECTIVE: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. RESEARCH DESIGN AND METHODS: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing. RESULTS AND CONCLUSIONS: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1α in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01295177.

Up-regulation of the phosphatidylinositol 3-kinase/protein kinase B pathway in the ovary of rats by chronic treatment with hCG and insulin.

Polycystic ovary syndrome (PCOS) manifests as chronic anovulation, ovarian hyperandrogenism, and follicular cysts, which are amplified by insulin as well as the inability of the hormone to stimulate glucose uptake in classic target tissues such as muscle and fat. In the present study, we evaluated the regulation of the insulin-signaling pathways by using immunoprecipitation and immunoblotting in whole extracts of ovaries from non-pregnant human chorionic gonadotropin (hCG)-treated rats, hyperinsulinemic-induced rats and hyperinsulinemic-induced rats, treated with hCG for 22 consecutive days. There were increased associations of insulin receptor substrate (IRS)-1 and IRS-2 with phosphatidylinositol (PI) 3-kinase, followed by enhanced protein kinase B (Akt) serine and threonine phosphorylation, in the ovaries of rats that were treated with hCG, either alone or with insulin. In contrast, the skeletal muscle demonstrated a reduced IRS-1/PI 3-kinase/Akt pathway in hyperinsulinemic-induced rats. These intracellular modifications were accompanied by follicular cysts, detected by optical microscopy, and increased androstenedione serum levels. In summary, our data show that chronic treatment with hCG or hCG plus insulin can induce changes in ovaries that simulate PCOS. In these situations, an increase in the insulin-induced IRS/PI 3-kinase/Akt pathway occurs in the ovary, suggesting that the activation of this pathway may have a role in the development of PCOS.

Novel signal transduction pathway for luteinizing hormone and its interaction with insulin: activation of Janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/Akt pathways.

The actions of LH are mediated through a single class of cell surface LH/human chorionic gonadotropin receptor, which is a member of the G protein-coupled receptor family. In the present study we showed that LH induced rapid tyrosine phosphorylation and activation of the Janus kinase 2 (JAK2) in rat ovary. Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. In addition, LH induced IRS-1/phosphoinositol 3-kinase and Shc /growth factor receptor-binding protein 2 (Grb2) associations and downstream AKT (protein kinase B, homologous to v-AKT) serine phosphorylation and ERK tyrosine phosphorylation, respectively. The simultaneous infusion of insulin and LH induced higher phosphorylation levels of JAK2, STAT5b, IRS-1, and AKT compared with each hormone alone in the whole ovary of normal rats. By immunohistochemistry we demonstrated that these late events take place in follicular cells and both external and internal theca. These results indicate a new signal transduction pathway for LH and show that there is positive cross-talk between the insulin and LH signaling pathways at the level of phosphoinositol 3-kinase/AKT pathway in this tissue.

Modulation of growth hormone signal transduction in kidneys of streptozotocin-induced diabetic animals: effect of a growth hormone receptor antagonist.

Growth hormone (GH) and IGFs have a long distinguished history in diabetes, with possible participation in the development of renal complications. The implicated effect of GH in diabetic end-stage organ damage may be mediated by growth hormone receptor (GHR) or postreceptor events in GH signal transduction. The present study investigates the effects of diabetes induced by streptozotocin (STZ) on renal GH signaling. Our results demonstrate that JAK2, insulin receptor substrate (IRS)-1, Shc, ERKs, and Akt are widely distributed in the kidney, and after GH treatment, there is a significant increase in phosphorylation of these proteins in STZ-induced diabetic rats compared with controls. Moreover, the GH-induced association of IRS-1/phosphatidylinositol 3-kinase, IRS-1/growth factor receptor bound 2 (Grb2), and Shc/Grb2 are increased in diabetic rats as well. Immunohistochemical studies show that GH-induced p-Akt and p-ERK activation is apparently more pronounced in the kidneys of diabetic rats. Administration of G120K-PEG, a GH antagonist, in diabetic mice shows inhibitory effects on diabetic renal enlargement and reverses the alterations in GH signal transduction observed in diabetic animals. The present study demonstrates a role for GH signaling in the pathogenesis of early diabetic renal changes and suggests that specific GHR blockade may present a new concept in the treatment of diabetic kidney disease.