Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice

Background: Sodium glucose co-transporter2 inhibitors reduce the incidence of cardiovascular events in patients with type 2 diabetes mellitus based on the results of recent cardiovascular outcome studies. Herein, we investigated the efects of long-term treatment with canaglifozin on biochemical and immunohistochemical markers related to atherosclerosis and atherosclerosis development in the aorta of apolipoprotein E knockout (Apo-E(−/−) ) mice. Methods: At the age of 5 weeks, mice were switched from normal to a high-fat diet. After 5 weeks, Apo-E(−/−) mice were divided into control-group (6 mice) treated with 0.5% hydroxypropyl methylcellulose and Cana-group (7 mice) treated with canaglifozin (10 mg/kg per day) per os. After 5 weeks of intervention, animals were sacrifced, and heart and aorta were removed. Sections stained with hematoxylin–eosin (H&E) were used for histomorphometry whereas Masson’s stained tissues were used to quantify the collagen content. Immunohistochemistry to assess MCP-1, CD68, a-smooth muscle actin, MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out and q-PCR experiments were performed to quantify mRNA expression. Results: Canaglifozin-group mice had lower total-cholesterol, triglycerides and glucose levels (P<0.01), while heart rate was signifcantly lower (P<0.05). Histomorphometry revealed that one in seven Cana-group mice versus four in six control mice developed atheromatosis, while aortic root plaque was signifcantly less, and collagen was 1.6 times more intense in canaglifozin-group suggesting increased plaque stability. Immunohistochemistry revealed that MCP-1 was signifcantly less expressed (P<0.05) in the aortic root of canaglifozin-group while reduced expression of a-actin and CD68 was not reaching signifcance (P=0.15). VCAM-1 and MCP-1 mRNA levels were lower (P=0.02 and P=0.07, respectively), while TIMP-1/MMP-2 ratio expression was higher in canaglifozin-group approaching statistical signifcance (P=0.07). Conclusions: Canaglifozin attenuates the progression of atherosclerosis, reducing (1) hyperlipidemia and hyper‑ glycemia, and (2) infammatory process, by lowering the expression of infammatory molecules such as MCP-1 and VCAM-1. Moreover, canaglifozin was found to increase the atherosclerotic plaque stability via increasing TIMP-1/ MMP-2 ratio expression

3,6-Dihydro-5<i>H</i>-pyrazolo [4′,3′:5,6]pyrano[3,4-<i>b</i>]indol-5-one

Pyrano [3,4-b]indol-1(9H)-ones and indolo [2,3-c]coumarins are important classes of heterocyclic compounds with versatile biological activities. Herein, we describe a straightforward and scalable synthesis of 3,6-dihydro-5H-pyrazolo [4′,3′:5,6]pyrano [3,4-b]indol-5-one, a pyrazolo-fused pyrano [3,4-b]indolone, via a three step approach including Fischer-indole synthesis and intramolecular esterification. The compound is fully characterized by means of 1H and 13C NMR spectra, using direct and long-range heteronuclear correlation experiments (HMBC and HMQC)

3,6-Dihydro-5H-pyrazolo [4&prime;,3&prime;:5,6]pyrano[3,4-b]indol-5-one

Pyrano [3,4-b]indol-1(9H)-ones and indolo [2,3-c]coumarins are important classes of heterocyclic compounds with versatile biological activities. Herein, we describe a straightforward and scalable synthesis of 3,6-dihydro-5H-pyrazolo [4&prime;,3&prime;:5,6]pyrano [3,4-b]indol-5-one, a pyrazolo-fused pyrano [3,4-b]indolone, via a three step approach including Fischer-indole synthesis and intramolecular esterification. The compound is fully characterized by means of 1H and 13C NMR spectra, using direct and long-range heteronuclear correlation experiments (HMBC and HMQC)

Case Report: Laparoscopic hepatectomy in an elderly patient with major comorbidities [version 2; referees: 2 approved]

Surgeons have been hesitant to proceed to hepatectomy in elderly patients, due to the higher rate of comorbidities and the reduced reserves. An 81-year-old male with hepatocellular carcinoma in the segment VI of the liver and several major cardiovascular, pulmonary and metabolic comorbid illnesses was referred to our department for treatment. He underwent transarterial chemoembolization of the liver tumor and afterwards he underwent laparoscopic resection of the hepatic segment VI, with an uneventful postoperative course. This case indicates that laparoscopic liver resections could be applied even to elderly patients with major comorbidities after optimization of their medical status

The Role of Calprotectin in Pediatric Disease

Calprotectin (CP) is a calcium- and zinc-binding protein of the S100 family expressed mainly by neutrophils with important extracellular activity. The aim of the current review is to summarize the latest findings concerning the role of CP in a diverse range of inflammatory and noninflammatory conditions among children. Increasing evidence suggests the implication of CP in the diagnosis, followup, assessment of relapses, and response to treatment in pediatric pathological conditions, such as inflammatory bowel disease, necrotizing enterocolitis, celiac disease, intestinal cystic fibrosis, acute appendicitis, juvenile idiopathic arthritis, Kawasaki disease, polymyositis-dermatomyositis, glomerulonephritis, IgA nephropathy, malaria, HIV infection, hyperzincemia and hypercalprotectinemia, and cancer. Further studies are required to provide insights into the actual role of CP in these pathological processes in pediatrics

The Role of Calprotectin in Pediatric Disease

Calprotectin (CP) is a calcium-and zinc-binding protein of the S100 family expressed mainly by neutrophils with important extracellular activity. The aim of the current review is to summarize the latest findings concerning the role of CP in a diverse range of inflammatory and noninflammatory conditions among children. Increasing evidence suggests the implication of CP in the diagnosis, followup, assessment of relapses, and response to treatment in pediatric pathological conditions, such as inflammatory bowel disease, necrotizing enterocolitis, celiac disease, intestinal cystic fibrosis, acute appendicitis, juvenile idiopathic arthritis, Kawasaki disease, polymyositis-dermatomyositis, glomerulonephritis, IgA nephropathy, malaria, HIV infection, hyperzincemia and hypercalprotectinemia, and cancer. Further studies are required to provide insights into the actual role of CP in these pathological processes in pediatrics

Laparoscopic hepatectomy in a morbidly obese patient with liver cirrhosis: A case report

Cirrhotic patients constitute a high-risk population, and present a major challenge for the performance of minimally invasive laparoscopic resections due to difficulties in parenchymal transection. The present study describes the case of a 71-year-old morbidly obese male patient who was referred to our department with a hepatic mass identified on routine abdominal ultrasound. Abdominal computer tomography and magnetic resonance imaging confirmed a mass in segments V-VI of the liver, highly suspicious for HCC. The patient&apos;s past medical history additionally included non-alcoholic steatohepatitis, diabetes mellitus and arterial hypertension and myocardial infarction. The patient&apos;s body mass index was 45 kg/m(2), and the American Society of Anesthesiologists&apos; classification of preoperative risk was 3. The patient underwent laparoscopic resection of segments V-VI and cholecystectomy. Two years postoperatively, the patient remains disease-free and in excellent condition. To the best of our knowledge, this is the first report on laparoscopic liver resection for such a morbidly obese patient in the context of advanced liver cirrhosis