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Modular Procedure for Wide open Partial Side to side Laryngectomy: Step-by-Step Anatomic Dissection.
In contrast, inappropriate use was observed in 41% (95% CI 34-48%; 82/200) and unclear/other use was observed in 20% (95% CI 15-26%; 40/200). CONCLUSIONS and Relevance Reporting guidelines of health research studies are frequently used inappropriately. Authors may require further education around appropriate use of reporting guidelines in research reporting. AIM The enzyme 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with cardiac and pathological remodeling and ion channel function regulation. However, whether it regulates hyperpolarization-activated cyclic nucleotide-modulated channels (HCNs) remains unclear. MAIN METHODS In the atrial myocytes of heart-specific PDK1 "knockout" mouse model and neonatal mice, protein kinase B (AKT)-related inhibitors or agonists as well as knockdown or overexpression plasmids were used to study the relationship between PDK1 and HCNs. KEY FINDINGS HCN1 expression and AKT phosphorylation at the Thr308 site were significantly decreased in atrial myocytes after PDK1 knockout or inhibition; in contrast, HCN2 and HCN4 levels were significantly increased. Also, a similar trend of HCNs expression has been observed in cultured atrial myocytes after PDK1 inhibition, as further demonstrated via immunofluorescence and patch-clamp experiments. Moreover, these results of PDK1 overexpression indicate an opposite trend compared with the previous experimental results. However, the results of PDK1 inhibition or overexpression could be reversed by activating or inhibiting AKT, respectively. SIGNIFICANCE These results indicate that the PDK1-AKT signaling pathway is involved in the regulation of HCN mRNA transcription, protein expression, HCN current density, and cell membrane location. Diabetic neuropathy (DN) is a common complication of diabetes mellitus (DM). Pathophysiology of DN includes inflammation and changes in expression and function of voltage-gated sodium channels (Nav) in peripheral nerves; and central reduction of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) expression. AIM This study explored the effect of ranolazine (RN) versus pioglitazone (PIO) in DN induced in rats. The role of sciatic interleukin (IL)-1β, tumor necrosis factor-alpha (TNF)-α, Nav1.7, and spinal PPAR-γ expressions were determined. MATERIALS AND METHODS For induction of Type-2 DM, 40 high fat diet-fed rats were challenged by a single dose of intraperitoneal streptozotocin (30 mg/kg). One week later, oral PIO (10 mg/kg; once daily) or RN (20, 50 and 100 mg/kg; twice daily) were administered for six weeks. Weekly body weight and fasting blood sugar (FBS) were measured. Rats were tested for thermal hyperalgesia and mechanical allodynia. At the end of the experiment, sciatic nerves homogenates were examined for TNF-α and IL-1B levels, and Nav1.7 channel expression. Segments of spinal cords were investigated for the PPAR-γ gene expression. Evaluation of histopathology of sciatic nerves and spinal cords were done. KEY FINDINGS In diabetic rats, PIO and RN individually improved evoked-pain behaviors, reduced sciatic TNF-α and 1L-1B levels; downregulated expressional levels of Nav1.7 channels; and increased the spinal PPAR-γ gene expression. RN in the dose of 100 mg/kg/day showed the most advantageous effects. SIGNIFICANCE RN has neuroprotective effects in Type-2 diabetes-induced DN. Further studies of combined RN-PIO treatment are recommended, especially in diabetic patients with cardiovascular co-morbidity. BACKGROUND Mental stress (MS) is related to endothelial dysfunction in overweight/obese men. It is believed that the pro-oxidant profile, associated with an imbalance in the vascular remodeling process, may contribute to deleterious effects of MS on endothelial function. However, it is unknown whether administration of ascorbic acid (AA), a potent antioxidant, can prevent oxidative and remodeling dysfunction during MS in these subjects. METHODS Fourteen overweight/obese grade I men (27 ± 7 years; 29.7 ± 2.6 kg·m-2) underwent the Stroop Color Word Test for 5 min to induce MS after AA (3 g) or placebo (PL, 0.9% NaCl) intravenous infusions. Venous blood samples were collected at baseline and the last minute of MS to measure nitrite concentration (chemiluminescence), protein carbonylation, thiobarbituric acid reactive substances (TBARS) and catalase activity (colorimetric assays), superoxide dismutase (SOD; immunoenzymatic assay), activities of active/inactive (pro) forms of metalloproteinases-9 and -2 (MMP; zymography) and its respective tissue inhibitors concentration (TIMP-1 and TIMP-2; immunoenzymatic assays). click here RESULTS At baseline, MMP-9 activity (p less then 0.01), the MMP-9/proMMP-9 ratio (p = 0.02) and TIMP-1 concentration (p = 0.05) were reduced, whereas proMPP-9 activity was increased (p = 0.02) after AA compared to PL infusion. After PL infusion, MS increased protein carbonylation (p less then 0.01), catalase (p less then 0.01), and the MMP-9/proMMP-9 ratio (p = 0.04) when compared to baseline. AA infusion reduced protein carbonylation (p = 0.02), MMP-9 activity (p less then 0.01), and MMP-9/pro-MMP-9 ratio (p less then 0.01), while SOD (p = 0.04 vs baseline), proMPP-9 (p less then 0.01 vs PL), MMP-2 (p less then 0.01 vs PL) and TIMP-2 (p = 0.02 vs baseline) remained elevated during MS. CONCLUSIONS AA appears to minimize the oxidative imbalance and vascular remodeling induced by MS. Increased levels of endocannabinoids, 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA) have a pathophysiological role in the setting of cardiometabolic diseases. This systematic review was carried out to appraise the effect of omega-3 on cardiometabolic risk factors by highlighting the mediating effect of endocannabinoids. SCOPUS, PubMed, Embase, Google Scholar and ProQuest databases were searched until January 2020. All published English-language animal studies and clinical trials that evaluated the effects of omega-3 on cardiometabolic diseases with a focus on endocannabinoids were included. Of 1407 studies, 16 animal studies and three clinical trials were included for analysis. Eleven animal studies and two human studies showed a marked reduction in 2-AG and AEA levels following intake of omega-3 which correlated with decreased adiposity, weight gain and improved glucose homeostasis. Moreover, endocannabinoids were elevated in three studies that replaced omega-3 with omega-6. Omega-3 showed anti-inflammatory properties due to reduced levels of inflammatory cytokines, regulation of T-cells function and increased levels of eicosapentaenoyl ethanolamide, docosahexaenoyl ethanolamide and oxylipins; however, a limited number of studies examined a correlation between inflammatory cytokines and endocannabinoids following omega-3 administration.
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