Visible Light and Triselenium Dicyanide (TSD): New Horizons in the Synthesis of Organic Selenocyanates.

Herein, we describe a new method for the synthesis of α-carbonyl selenocyanates by reacting triselenium dicyanide (TSD) and styrenes under blue light irradiation and O2 atmosphere. The reactions are triggered by the formation of Se-centered radical species, followed by the addition/oxidation of the styrene π-bond. α-Carbonyl selenocyanates and α-hydroxy selenocyanates were obtained in moderate to excellent yields from aryl- and alkyl-substituted alkenes, respectively. It was demonstrated that α-carbonyl selenocyanates could be used as a synthetic platform in a multicomponent reaction strategy to prepare 2-phenylimidazo[1,2-a]pyridine derivatives, which were evaluated for their photophysical properties. Overall, this new method provides a useful tool for synthesizing α-carbonyl selenocyanates, and demonstrates their potential for use in the synthesis of other compounds, thus giving new synthetic opportunities to construct organic selenocyanate compounds.

Insulin Modulates the Immune Cell Phenotype in Pulmonary Allergic Inflammation and Increases Pulmonary Resistance in Diabetic Mice.

Introduction: Reports have shown that the onset of diabetes mellitus (DM) in patients previously diagnosed with asthma decreases asthmatic symptoms, whereas insulin aggravates asthma. The present study evaluated the modulatory effect of insulin on the development of allergic airway inflammation in diabetic mice. Materials and Methods: To evaluate the effects of relative insulin deficiency, an experimental model of diabetes was induced by a single dose of alloxan (50 mg/kg, i.v.). After 10 days, the mice were sensitized with ovalbumin [OVA, 20 µg and 2 mg of Al(OH)3, i.p.]. A booster immunization was performed 6 days after the first sensitization [20 µg of OVA and 2 mg of Al(OH)3, i.p.]. The OVA challenge (1 mg/mL) was performed by daily nebulization for 7 days. Diabetic animals were treated with multiple doses of neutral protamine Hagedorn (NPH) before each challenge with OVA. The following parameters were measured 24 h after the last challenge: (a) the levels of p38 MAP kinase, ERK 1/2 MAP kinases, JNK, STAT 3, and STAT 6 in lung homogenates; (b) the serum profiles of immunoglobulins IgE and IgG1; (c) the concentrations of cytokines (IL-4, IL-5, IL-10, IL-13, TNF-α, VEGF, TGF-ß, and IFN-γ) in lung homogenates; (d) cells recovered from the bronchoalveolar lavage fluid (BALF); (e) the profiles of immune cells in the bone marrow, lung, thymus, and spleen; and (f) pulmonary mechanics using invasive (FlexiVent) and non-invasive (BUXCO) methods. Results: Compared to non-diabetic OVA-challenged mice, OVA-challenged diabetic animals showed decreases in ERK 1 (2-fold), ERK 2 (7-fold), JNK (phosphor-54) (3-fold), JNK/SAPK (9-fold), STAT3 (4-fold), the levels of immunoglobulins, including IgE (1-fold) and IgG1 (3-fold), cytokines, including Th2 profile cytokines such as IL-4 (2-fold), IL-5 (2-fold), IL-13 (4-fold), TNF-α (2-fold), VEGF (2-fold), and TGF-ß (2-fold), inflammatory infiltrates (14-fold), T cells, NK cells, B cells and eosinophils in the bone marrow, lung, thymus and spleen, and airway hyperreactivity. STAT6 was absent, and no eosinophilia was observed in BALF. Insulin treatment restored all parameters. Conclusion: The data suggested that insulin modulates immune cell phenotypes and bronchial hyperresponsiveness in the development of allergic airway inflammation in diabetic mice.

Cytokine and Adhesion Molecule Expression Induced by Different Strains of Staphylococcus aureus in Type 1 Diabetic Rats: Role of Insulin.

Introduction:Staphylococcus aureus may provoke peritonitis and death, especially in immunocompromized individuals such as diabetic patients. We evaluated the role of insulin in S. aureus-induced peritoneal infection in diabetic and non-diabetic rats. Materials/Methods: Alloxan-diabetic male Wistar rats and their respective controls received intraperitoneal injections of different strains of S. aureus or sterile phosphate-buffered saline. After 3 days of infection, the first set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of neutral protamine Hagedorn insulin and were analyzed 8 h later. The second set of diabetic and non-diabetic rats received 4 and 1 IU, respectively, of insulin 2 h before intraperitoneal infection and a half dose of insulin at 5 p.m. for the next 2 days and were analyzed 16 h later. The following measurements were performed: (a) number of cells in the peritoneal lavage fluid (PeLF), white blood cell count, and blood glucose; (b) serum insulin and corticosterone; (c) cytokine levels in the PeLF; (d) expression of adhesion molecules in the vascular endothelium; and (e) microbicidal activity. Results: Diabetic rats showed an increased number of polymorphonuclear leukocytes (PMNs) and increased concentrations of CINC-1, IL-4, and IFN-γ in the PeLF after infection with the ATCC 25923 or N315 αHL+ strain. The mesenteric expression of PECAM-1 was increased after infection with the N315 HLA+ strain. ICAM-1 expression was increased with ATCC infection. Treatment of diabetic rats with a single dose of insulin restored CINC-1 levels in the PeLF for both strains; however, PMN migration, IL-4, and IFN-γ were restored in rats infected with the ATCC strain, whereas the PeLF concentrations of CINC-2, IL-1ß, and IL-4 were increased in N315-infected animals. Insulin restored PMN migration and CINC-2 levels in the PeLF in ATCC-infected rats. After multiple treatments with insulin, the levels of IL-1ß, IL-6, and IFN-γ were increased in the PeLF of diabetic rats after infection with either strain, and CINC-2 levels were restored in N315-infected animals. Conclusion: These results suggest that insulin distinctively modulates cytokine production or release, PMN leukocyte migration, and adhesion molecule expression during the course of peritonitis induced by different strains of S. aureus.

Insulin Modulates Cytokine Release, Collagen and Mucus Secretion in Lung Remodeling of Allergic Diabetic Mice.

INTRODUCTION: The role of insulin in lung remodeling in a model of asthma in healthy and diabetic mice was evaluated. MATERIAL AND METHODS: Diabetic male BALB/c mice (alloxan, 50 mg/kg, intravenous) and controls were sensitized by subcutaneous (s.c.) injection of ovalbumin (OA, 20 µg) in aluminum hydroxide (Al(OH)3, 2 mg) 10 days after the alloxan injection and received the same dose 12 days later. Six days after the last sensitization, animals were nebulized with OA solution for 7 days. The first set of diabetic and control mice received 2 and 1 IU, respectively, of s.c. neutral protamine Hagedorn (NPH) insulin and were analyzed 8 h later. The second set of diabetic and control mice received 2 and 1 IU, respectively, of insulin 12 h before the OA challenge and half doses of insulin 2 h before each the seven OA challenges. Twenty-four hours after the last challenge, the following analyses were performed: (a) quantification of the cells in the bronchoalveolar lavage fluid (BALF), the white cell count, and blood glucose; (b) morphological analysis of lung tissues by hematoxylin and eosin staining; (c) quantification of collagen deposition in lung tissues and mucus by morphometric analysis of histological sections stained with Masson's trichrome and periodic acid-Schiff (PAS), respectively; and (d) quantification of the cytokine concentrations (IL-4, IL-5, and IL-13) in the BALF supernatant. RESULTS: Compared to controls, diabetic mice had significantly reduced inflammatory cells (81%) in the BALF, no eosinophils in the BALF and peripheral blood and reduced collagen deposition and mucus in the lungs. BALF concentrations of IL-4 (48%) and IL-5 (31%) decreased and IL-13 was absent. A single dose of insulin restored peripheral blood eosinophils and BALF mononuclear cells but not BALF eosinophils, collagen deposition, and mucus levels. However, multiple doses of insulin restored both total cells and eosinophils in the BALF and peripheral blood, BALF cytokines, and collagen deposition and mucus secretion into the lungs. CONCLUSION: The results suggest that insulin modulates the production/release of cytokines, cell migration, deposition of collagen, and mucus secretion in lung remodeling of a mouse model of asthma.

Vitamin D Modulates Hematological Parameters and Cell Migration into Peritoneal and Pulmonary Cavities in Alloxan-Diabetic Mice.

Background/Aims. The effects of cholecalciferol supplementation on the course of diabetes in humans and animals need to be better understood. Therefore, this study investigated the effect of short-term cholecalciferol supplementation on biochemical and hematological parameters in mice. Methods. Male diabetic (alloxan, 60 mg/kg i.v., 10 days) and nondiabetic mice were supplemented with cholecalciferol for seven days. The following parameters were determined: serum levels of 25-hydroxyvitamin D, phosphorus, calcium, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, red blood cell count, white blood cell count (WBC), hematocrit, hemoglobin, differential cell counts of peritoneal lavage (PeL), and bronchoalveolar lavage (BAL) fluids and morphological analysis of lung, kidney, and liver tissues. Results. Relative to controls, cholecalciferol supplementation increased serum levels of 25-hydroxyvitamin D, calcium, hemoglobin, hematocrit, and red blood cell counts and decreased leukocyte cell counts of PeL and BAL fluids in diabetic mice. Diabetic mice that were not treated with cholecalciferol had lower serum calcium and albumin levels and hemoglobin, WBC, and mononuclear blood cell counts and higher serum creatinine and urea levels than controls. Conclusion. Our results suggest that cholecalciferol supplementation improves the hematological parameters and reduces leukocyte migration into the PeL and BAL lavage of diabetic mice.

Insulin Modulates Liver Function in a Type I Diabetes Rat Model.

BACKGROUND/AIMS: Several studies have been performed to unravel the association between diabetes and increased susceptibility to infection. This study aimed to investigate the effect of insulin on the local environment after cecal ligation and puncture (CLP) in rats. METHODS: Diabetic (alloxan, 42 mg/kg i.v., 10 days) and non-diabetic (control) male Wistar rats were subjected to a two-puncture CLP procedure and 6 h later, the following analyses were performed: (a) total and differential cell counts in peritoneal lavage (PeL) and bronchoalveolar lavage (BAL) fluids; (b) quantification of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL- 6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2 in the PeL and BAL fluids by enzyme-linked immunosorbent assay (ELISA); (c) total leukocyte count using a veterinary hematology analyzer and differential leukocyte counts on stained slides; (d) biochemical parameters (urea, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) by colorimetric analyses); and (e) lung, kidney, and liver morphological analyses (hematoxylin and eosin staining). RESULTS: Relative to controls, non-diabetic and diabetic CLP rats exhibited an increased in the concentration of IL-1ß, IL-6, IL-10, CINC-1, and CINC-2 and total and neutrophil in the PeL fluid. Treatment of these animals with neutral protamine Hagedorn insulin (NPH, 1IU and 4IU, respectively, s.c.), 2 hours before CLP procedure, induced an increase on these cells in the PeL fluid but it did not change cytokine levels. The levels of ALT, AST, ALP, and urea were higher in diabetic CLP rats than in non-diabetic CLP rats. ALP levels were higher in diabetic sham rats than in non-diabetic sham rats. Treatment of diabetic rats with insulin completely restored ALT, AST, and ALP levels. CONCLUSION: These results together suggest that insulin attenuates liver dysfunction during early two-puncture CLP-induced peritoneal inflammation in diabetic rats.