The metabolic syndrome (MetS) is an obesity-associated disorder of pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered neural autonomic ...regulation, are important components and drivers of pathogenesis. Galantamine, an acetylcholinesterase inhibitor and a cholinergic drug that is clinically-approved (for Alzheimer's disease) has been implicated in neural cholinergic regulation of inflammation in several conditions characterized with immune and metabolic derangements. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.
The effects of galantamine treatment, 8 mg daily for 4 weeks or placebo, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (
= 22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.
Galantamine treatment significantly increased antioxidant enzyme activities, including SOD +1.65 USOD/mg protein, 95% CI 0.39-2.92,
= 0.004 and CAT +0.93 nmol/mg, 95% CI 0.34-1.51,
= 0.01, decreased lipid peroxidation thiobarbituric acid reactive substances log scale 0.72 pmol/mg, 95% CI 0.46-1.07,
= 0.05, and systemic nitrite levels log scale 0.83 μmol/mg protein, 95% CI 0.57-1.20,
= 0.04 compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.
Low-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates neural autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with the cholinergic drug galantamine to ameliorate MetS.
The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic ...stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3
and CD4
lymphocytes, and CD68
and CD206
macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4
lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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Currently, some techniques such as nerve stimulation have been used as a treatment to reduce inflammation levels in the organism. Inflammation is present in both metabolic syndrome and ...depression. In brain stimulation through the vagus nerve, the main neurotransmitter acetylcholine modulates the actions of various peptides, hypothalamic incretins and cholecystokinin, consequently modulating the actions of the Autonomic Nervous System. According to the World Health Organization, depression occurs in people of all genders and ages, affects 350 million people worldwide, is among the leading causes of disability. This study aimed to verify the impact of transcutaneous electrical stimulation of the vagus nerve on depressive symptoms in patients with metabolic syndrome. This is the analysis of patients with metabolic syndrome who underwent transcutaneous electrical stimulation in the left ear once a week for 30 minutes for a period of 8 weeks. Pre‐ and post‐Transcutaneous Electrical Stimulation analyzes were performed through interviews with the application of three psychometric depression assessment scales of Beck I (IDB), Hamilton (HAM‐D) and Montgomery‐Asberg (MADRS). Nine patients with Metabolic Syndrome from the city of São Paulo, Brazil, were interviewed. Of the 09 respondents, the study showed in the IDB Scale there are 06 (66.6%) with depression, HAM‐D 08 (88.8%) and MADRS all 08 (88.8%) with depression before Transcutaneous Electrical Stimulation. The results showed a significance level of 55.5% for depression scores after Transcutaneous Electrical Stimulation. A high prevalence of depressive symptoms was observed in the study sample. The research allowed us to reflect on the Transcutaneous Electrical Stimulation of the vagus nerve as an alternative treatment for individuals with Metabolic Syndrome and depressive symptoms aiming to prevent or mitigate the effects of these pathologies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
There is emerging evidence that the nervous system regulates immune and metabolic alterations mediating Metabolic syndrome (MetS) pathogenesis via the vagus nerve. This study evaluated the effects of ...transcutaneous auricular vagus nerve stimulation (TAVNS) on key cardiovascular and inflammatory components of MetS.
We conducted an open label, randomized (2:1), two-arm, parallel-group controlled trial in MetS patients. Subjects in the treatment group (n = 20) received 30 min of TAVNS with a NEMOS® device placed on the cymba conchae of the left ear, once weekly. Patients in the control group (n = 10) received no stimulation. Hemodynamic, heart rate variability (HRV), biochemical parameters, and monocytes, progenitor endothelial cells, circulating endothelial cells, and endothelial micro particles were evaluated at randomization, after the first TAVNS treatment, and again after 8 weeks of follow-up.
An improvement in sympathovagal balance (HRV analysis) was observed after the first TAVNS session. Only patients treated with TAVNS for 8 weeks had a significant decrease in office BP and HR, a further improvement in sympathovagal balance, with a shift of circulating monocytes towards an anti-inflammatory phenotype and endothelial cells to a reparative vascular profile.
These results are of interest for further study of TAVNS as treatment of MetS.
Combined oral contraceptives (COCs) may increase the risk for cardiovascular disease depending on the ethynyl estradiol (EE) dose and the androgenicity of the progestogens. Our objective was to ...evaluate the impact of a COC containing 20 mcg EE + 3 mg drospirenone on blood pressure (BP), renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women. Eighty-one healthy young women aged 30 ± 1 years (case group, n = 49, received COC; control group, n = 32, used no COC) were assessed twice, before and after the 6-month study. Statistical analysis employed the paired t-tests and expressed the data in mean and standard deviation. Results were as follows: no changes in BP or in BMI; a significant increase in aldosterone, plasma renin activity, triglycerides, and total cholesterol levels, but a non-significant increase in HDL and no significant changes in LDL levels (these parameters remained within normal ranges); a significant increase in the HOMA-IR index and a significant decrease in dehydroepiandrosterone sulfate (SDHEA), androstenedione, total testosterone, and free testosterone levels; no significant variations in the control group parameters. An oral contraceptive combination of a low EE dose and an anti-androgenic progestogen does not negatively influence the risk factors for a cardiovascular disease.
复方口服避孕药（COCs）由于含有不同的炔雌醇（EE）剂量和具有雄激素作用的孕激素而可能增加心血管疾病的风险。本研究的目的在于评估含20 mcg EE + 3mg屈螺酮的COC对健康年轻女性的血压（BP），肾素-血管紧张素-醛固酮系统，胰岛素抵抗的影响。81名年龄为30±1岁的健康年轻女性（实验组，n=49，给予COC；对照组，n=32，不使用COC）在实验前和6个月实验后分别评估两次。数据分析采用配对t检验，数据用均数±标准差表示。结果如下：BP或BMI无改变；醛固酮、血浆肾素活性、甘油三酯和总胆固醇水平显著增加，但HDL不显著增加和LDL水平无显著改变（这些参数仍在正常范围内）；HOMA-IR指数显著增加，脱氢表雄酮硫酸盐(SDHEA)、雄烯二酮、总睾酮和游离睾酮显著降低；对照组参数无明显改变。含低剂量EE和抗雄作用的孕激素的复方口服避孕药不对心血管疾病的风险产生负面影响。
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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