Electric currents of 448 kHz upregulate anti-senescence pathways in human dermal fibroblasts.

BACKGROUND: Currently, finding new therapeutic strategies that reduce skin aging is a challenge for dermatologists and aesthetic doctors. In recent years, physical therapies have been included in the options for antiaging treatments; however, the biological bases of such treatments have scarcely been studied. One of these physical therapies is capacitive-resistive electric transfer (CRET) therapy. Previous studies have shown that subthermal treatment with CRET promotes the proliferation and migration of various cell types involved in skin regeneration, such as human ADSC (stem cells), fibroblasts, or keratinocytes. OBJECTIVE: This study investigates the effects of in vitro treatment with CRET-Std (standard, non-modulated signal) or CRET-Mod (modulated signal) on cell proliferation and migration, markers of aging, and extracellular matrix production. METHODS: Three types of human dermal fibroblasts were used: neonatal fibroblasts (HFn), replicative senescent fibroblasts (HFs), and adult fibroblasts (HFa). The effects of electric stimulation on cell proliferation and migration were studied through XTT and wound closure assays, respectively. The expression of the aging marker ß-galactosidase was assessed using a colorimetric assay, whereas immunoblot, immunofluorescence, and ELISAs were carried out to analyze the expression levels of migration, aging, and extracellular matrix proteins. RESULTS: The treatment with CRET-Std increased HFn and HFa proliferation, as well as migration in the three types of fibroblasts studied compared to those of the controls. Conversely, CRET-Mod did not modify either of these two processes with respect to the controls. Additionally, CRET-Std also reduced the cellular senescence markers ß-gal, vimentin, p53, and p21 in all three types of human skin fibroblasts. In addition, the application of CRET-Std also induced fibronectin production in HFn and was able to stimulate ECM neocollagenesis. CONCLUSION: CRET treatment improves a number of functions related to migration and proliferation, and it reduces age-related cellular changes in human dermal fibroblasts. Therefore, the use of this CRET therapy to reduce the signs of dermal aging and to promote tissue regeneration could be of interest.

Anti-Fibrotic Effects of RF Electric Currents.

Hypertrophic scars and keloids are two different manifestations of excessive dermal fibrosis and are caused by an alteration in the normal wound-healing process. Treatment with radiofrequency (RF)-based therapies has proven to be useful in reducing hypertrophic scars. In this study, the effect of one of these radiofrequency therapies, Capacitive Resistive Electrical Transfer Therapy (CRET) on biomarkers of skin fibrosis was investigated. For this, in cultures of human myofibroblasts treated with CRET therapy or sham-treated, proliferation (XTT Assay), apoptosis (TUNEL Assay), and cell migration (Wound Closure Assay) were analyzed. Furthermore, in these cultures the expression and/or localization of extracellular matrix proteins such as α-SMA, Col I, Col III (immunofluorescence), metalloproteinases MMP1 and MMP9, MAP kinase ERK1/2, and the transcription factor NFκB were also investigated (immunoblot). The results have revealed that CRET decreases the expression of extracellular matrix proteins, modifies the expression of the metalloproteinase MMP9, and reduces the activation of NFκB with respect to controls, suggesting that this therapy could be useful for the treatment of fibrotic pathologies.

Sudden Death Due to Thrombosis Associated with Implantable Cardioverter-Defibrillator Electrodes.

Thrombosis associated with pacemaker leads is extremely rare, although the literature on this subject is scarce. A clinical case is reported, describing this condition and its clinical presentation, the complementary tests for establishing the diagnosis and the available therapeutic options. LEARNING POINTS: Thrombosis associated with pacemaker leads is extremely rare.The different causes that contribute to thrombosis all have Virchow's triad (blood stasis, endothelial injury/dysfunction and hypercoagulability) in common.Transthoracic and/or transoesophageal Doppler echocardiography is the gold standard for establishing the diagnosis, while the treatment options are anticoagulation, thrombolysis and surgical or endovascular embolectomy.

Constitutional Syndrome, Ascites and Duodenal Thickening Presenting as Groove Pancreatitis.

Groove pancreatitis (GP) is a very infrequent subtype of chronic pancreatitis affecting the pancreatic-duodenal junction. It usually manifests in middle-aged men with a history of chronic alcoholism, though it has also been described in women and in individuals who do not consume alcohol[1]. Even though the underlying etiology is unclear, chronic alcohol consumption is known to increase the viscosity of the pancreatic juice and exacerbate the inflammatory process[2]. We present a case of GP that posed diagnostic difficulties because it manifested as ascites and duodenal thickening, with pancreatic imaging findings initially normal. LEARNING POINTS: Groove pancreatitis typically manifests as upper hemiabdominal pain, postprandial vomiting and weight loss.It is important to establish a differential diagnosis with carcinoma of the head of the pancreas and duodenal neoplasms.Presentation of the disease in the form of ascites is exceptional but a possibility that must be taken into account.

Lower free thyroxin associates with a less favorable metabolic phenotype in healthy pregnant women.

CONTEXT: A lower free T(4) (fT4), within the euthyroid range, has been shown in adults to associate with an adverse metabolic phenotype. Thyroid physiology changes significantly during gestation and affects maternal and fetal well-being. OBJECTIVE: The aim of the study was to test the hypothesis that a lower serum fT4 in healthy euthyroid pregnant women is related to a less favorable metabolic phenotype and to fetal or placental weight. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: We examined associations of thyroid function tests (TSH and fT4) and the free T(3) (fT3)-to-fT4 ratio (as a proxy of deiodinase activity) with a metabolic profile [preload and postload glucose, glycosylated hemoglobin (HbA1c), high molecular-weight (HMW)-adiponectin, homeostasis model of assessment for insulin resistance (HOMA-IR), and serum lipids] in 321 healthy pregnant women. All women were euthyroid and had negative anti-thyroid peroxidase antibodies. None received thyroid hormone replacement. Blood tests were performed in women between 24 and 28 wk gestation. Placentas and newborns were weighed at birth. RESULTS: Circulating TSH did not relate to metabolic parameters, but decreasing fT4 and increasing fT3-to-fT4 ratio associated with a less favorable metabolic phenotype, as judged by higher postload glucose, HbA1c, fasting insulin, HOMA-IR, and triglycerides, and by a lower HMW-adiponectinemia (all P ≤ 0.005). In multiple regression analyses, fT4 was independently associated with HbA1c (ß = -0.135; P = 0.038), HMW-adiponectin (ß = 0.218; P < 0.001), and placental weight (ß = -0.185; P < 0.005), whereas the fT3-to-fT4 ratio was independently associated with maternal body mass index (ß = 0.265; P < 0.001), HMW-adiponectinemia (ß = -0.237; P < 0.002), HOMA-IR (ß = 0.194; P = 0.014), and placental weight (ß = 0.174; P = 0.020). CONCLUSION: In pregnant women without a history of thyroid dysfunction, lower concentrations of fT4 and a higher conversion of fT4 to fT3, as inferred by changes in the fT3-to-fT4 ratio, were found to be associated with a less favorable metabolic phenotype and with more placental growth.