Accumulating evidence shows that metformin is an insulin-sensitizing antidiabetic drug widely used in the treatment of type 2 diabetes mellitus (T2DM), which can exert favorable effects on cardiovascular risk and may be safely used in patients with heart failure (HF), and even able to reduce the incidence of HF and to reduce HF mortality. In failing hearts, metformin improves myocardial energy metabolic status through the activation of AMP (adenosine monophosphate)-activated protein kinase (AMPK) and the regulation of lipid and glucose metabolism. By increasing nitric oxide (NO) bioavailability, limiting interstitial fibrosis, reducing the deposition of advanced glycation end-products (AGEs), and inhibiting myocardial cell apoptosis metformin reduces cardiac remodeling and hypertrophy, and thereby preserves left ventricular systolic and diastolic functions. While a lot of preclinical and clinical studies showed the cardiovascular safety of metformin therapy in diabetic patients and HF, to confirm observed benefits, the specific large-scale trials configured for HF development in diabetic patients as a primary endpoints are necessary.
To date, it remains unclear whether mild form of acute pancreatitis (AP) may cause myocardial damage which may be asymptomatic for a long time. Pathogenesis of AP-related cardiac injury may be attributed in part to ROS/RNS overproduction. The aim of the present study was to evaluate the oxidative stress changes in both the pancreas and the heart and to estimate the protective effects of 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine (tempol) at the early phase of AP. Cerulein-induced AP led to the development of acute edematous pancreatitis with a significant decrease in the level of sulfhydryl (–SH) groups (oxidation marker) both in heart and in pancreatic tissues as well as a substantial increase in plasma creatine kinase isoenzyme (CK-MB) activity (marker of the heart muscle lesion) which confirmed the role of oxidative stress in the pathogenesis of cardiac damage. The tempol treatment significantly reduced the intensity of inflammation and oxidative damage and decreased the morphological evidence of pancreas injury at early AP stages. Moreover, it markedly attenuated AP-induced cardiac damage revealed by normalization of the –SH group levels and CK-MB activity. On the basis of these studies, it is possible to conclude that tempol has a profound protective effect against cardiac and pancreatic damage induced by AP.
Previously, we have demonstrated that leptin increases blood pressure (BP) in the rats through two oxidative stress-dependent mechanisms: stimulation of extracellular signal-regulated kinases (ERK) by H(2)O(2) and scavenging of nitric oxide (NO) by superoxide (O(2-.)). Herein, we examined if renal glutathione system and antioxidant enzymes determine the mechanism of prohypertensive effect of leptin. Leptin administered at 0.5 mg/kg/day for 4 or 8 days increased BP and renal Na(+),K(+)-ATPase activity and reduced fractional sodium excretion; these effects were prevented by NADPH oxidase inhibitor, apocynin. Superoxide scavenger, tempol, abolished the effect of leptin on BP and renal Na(+) pump in rats receiving leptin for 8 days, whereas ERK inhibitor, PD98059, was effective in animals treated with leptin for 4 days. Leptin administered for 4 days decreased glutathione (GSH) and increased glutathione disulfide (GSSG) in the kidney. In animals receiving leptin for 8 days GSH returned to normal level, which was accompanied by up-regulation of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of the GSH biosynthetic pathway. In addition, superoxide dismutase (SOD) activity was decreased, whereas glutathione peroxidase (GPx) was increased in rats receiving leptin for 8 days. Cotreatment with gamma-GCS inhibitor, buthionine sulfoximine (BSO), accelerated, whereas GSH precursor, N-acetylcysteine (NAC), attenuated leptin-induced changes in gamma-GCS, SOD, and GPx. In addition, coadministration of BSO changed the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent in animals receiving leptin for 4 days, whereas NAC had the opposite effect in rats treated with leptin for 8 days. These results suggest that initial change in GSH redox status induces decrease in SOD/GPx ratio, which results in greater amount of (O)2-.)) versus H(2)O(2) in later phase of leptin treatment, thus shifting the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent.
The infection of a vascular prosthesis is potentially fatal, and its effective treatment still remains the greatest challenge for vascular surgeons. We present our initial experience using bovine pericardial vascular prostheses to replace infected aortoiliac vascular grafts. Six consecutive patients with infection of the graft were prospec-
hyperhomocysteinemia (hhcy) is a well-known risk factor of cardiovascular diseases, however, the mechanism of its detrimental effect is incompletely understood. some studies suggest that, paradoxically, hhcy may promote traditional risk factors such as hyperlipidemia. We examined the effect of experimental hhcy on plasma lipid profile, glucose and insulin concentrations as well as on high-density lipoprotein (hDl)-associated antiatherosclerotic enzyme, paraoxonase 1 (pOn1). hyperhomocysteinemia was induced by feeding male Wistar rats with diet enriched with methionine or diet enriched in methionine and deficient in folate, vitamin b 6 and b 12 for 8 weeks. These diets resulted in the 3.3-and 9.6-fold elevation of plasma hcy, respectively. plasma total and hDl-cholesterol, triglycerides and apolipoprotein a-I were similar in all groups. highmethionine diets had no effect on fasting plasma glucose but significantly increased fasting plasma insulin concentration indicating impaired ability of insulin to suppress hepatic glucose output. pOn1 activity was unchanged in high methionine vitamin bsufficient diet-fed rats, but was decreased by 30-40% toward various substrates in high methionine vitamin b-deficient diet-fed animals. The results indicate that hhcy has no effect on lipid metabolism, however, induces insulin resistance and, above certain hcy level, pOn1 deficiency. Impaired insulin signaling and reduced pOn1 activity may contribute to detrimental effects of hhcy. Adipobiology 2012; 4: 77-84
2Kierownik: dr hab. r. BraczkowskiCommon use of venipuncture on upper and lower limbs for diagnostic purposes (such as coronarography or arteriography), and also during the course of treatment (angioplasty), very often bares a complication in the form of pseudoaneurysms. According to various reports, the incidence of pseudoaneurysms ranges from 0.005% to 0.5% of all vascular procedures requiring arterial cannulation (Common Femoral Artery, Brachial Artery, Radial Artery). The use of Bio Trombina® 400 in the embolization of pseudoaneurysms allows minimally invasive and effective treatment. the aim of the study was to evaluate the efficacy of pseudoaneurysm embolization with the use of Trombina 400, authors' own experience. material and methods. In the years 2011 -2013, the authors of this study performed 38 vascular interventional procedures involving pseudoaneurysms as complications of venipuncture in upper and lower limbs for diagnostic and treatment purposes. All procedures involved the direct injection of thrombin into the chamber of the pseudoaneurysm under the guidance of USG Doppler (6.2 MHz linear head). 34 cases presented single chamber pseudoaneurysms while 4 cases involved multi-chamber pseudoaneurysms, which required several thrombin reinjections (Bio Trombina® 400) into each of the chambers. Pseudoaneurysm maximum size of 4 cm was set as an inclusion criterion for the embolization procedure. Furthermore, all pseudoaneurysms with a significantly wide tract in transverse dimensions were treated as an exclusion criterion because of high risk of the peripheral arteries embolization. Results. Initial success was observed in 36 patients (94.73%) in the first day after the procedure, 1 patient (2.63%) underwent thrombin reinjection procedure in the second day after the first embolization. Another patient (2.63%) underwent an open procedure in which the Common Femoral Artery was accessed, the clot evacuated, and CFA was sutured with continuous suture Prolene 6-0. conclusions. 1. Embolization of pseudoaneurysms with USG Doppler-guided thrombin injection is an effective course of treatment for complications of cannulation. 2. The safety of pseudoaneurysm embolization depends on a surgeon's experience. It is also crucial to keep in mind the inclusion and exclusion criteria for this type of procedure (the size of a pseudoaneurysm, the width of its base). 3. Furthermore, its cost effectiveness and short hospitalization period make pseudoaneurysm embolization an effective and valuable alternative to the classic approach.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.