Plasma Gelsolin Levels Decrease in Diabetic State and Increase upon Treatment with F-Actin Depolymerizing Versions of Gelsolin

The study aims to map plasma gelsolin (pGSN) levels in diabetic humans and mice models of type II diabetes and to evaluate the efficacy of gelsolin therapy in improvement of diabetes in mice. We report that pGSN values decrease by a factor of 0.45 to 0.5 in the blood of type II diabetic humans and mice models. Oral glucose tolerance test in mice models showed that subcutaneous administration of recombinant pGSN and its F-actin depolymerizing competent versions brought down blood sugar levels comparable to Sitagliptin, a drug used to manage hyperglycemic condition. Further, daily dose of pGSN or its truncated versions to diabetic mice for a week kept sugar levels close to normal values. Also, diabetic mice treated with Sitagliptin for 7 days, showed increase in their pGSN values with the decrease in blood glucose as compared to their levels at the start of treatment. Gelsolin helped in improving glycemic control in diabetic mice. We propose that gelsolin level monitoring and replacement of F-actin severing capable gelsolin(s) should be considered in diabetic care

EFFICACY AND SAFETY OF KNOTLESS BARBED SUTURES IN CAPSULAR CLOSURE FOLLOWING DISTAL FEMUR FRACTURE FIXATION

ABSTRACT Introduction: Good wound closure is an important step in management of distal femur fracture to prevent infection and faster rehabilitation. Knotless barbed sutures can save time and distribute wound tension evenly. However, its role in terms of functional outcome, closure time, and postoperative complications has not been studied in a distal femur fracture. Material and methods: A total of 47 patients aged more than 18 years of distal femur fracture treated with distal femur locking plate were randomized either into either barbed or traditional suture groups. in the barbed group, capsular wound closure was carried out with 2-0 bidirectional barbed knotless sutures (Quill SRS® PDO, Angiotech, Vancouver, BC, Canada). In patients assigned to group B, capsular closure was done with 1-0 Vicryl® (Ethicon inc. Somerville, NJ) and 5-0 Ethibond® alternatively. Results: The mean flexion at the knee joint was 105.7±15.6 degrees in the study group while it was 110.4±13.7 in the control group (p= 0.2133). Mean estimated closure time was significantly shorter in the study group as compared to the control group (p<0.05). Cases of needle prick injury were higher in traditional suture group. Patients developed stitch abscess and superficial infection in both groups. However, the difference in incidence between the two was not statistically significant Conclusion: Barbed suture is an efficient method of wound closure. It reduces wound closure time with similar complication rate as with use of conventional sutures. Evidence Level II; Randomized Clinical Trial

Assessment of vitamin D status in rheumatoid arthritis patients

Background: Vitamin D is a secosteroid hormone involved in bone and calcium metabolism. It is involved in the regulation of calcium homeostasis, as it regulates calcium absorption from the gastrointestinal system. The present study was conducted to assess vitamin D status in RA patients. Materials &amp; Methods: 112 Rheumatoid arthritis patients of both genders were put in group I. Healthy subjects were also enrolled and put in group II. Disease activity score of RA patients was calculated. Disease severity was assessed according to the value of DAS28 score as follows- Remission: DAS28 ≤2.6 Low disease activity: 2.6 5.1. 25 (OH)-Vitamin D Xpress ELISA Kit was used for the quantitative measurement of Vitamin D3 {25 (OH)-D3} in serum. Results: Group I had 62 males and 50 females and group II had 70 males and 42 females. Disease activity was remission, low, moderate and high with mean serum calcium level (mg/dl) as 8.92, 8.34, 8.22 and 8.01 and vitamin D (mg/dl) as 35.6, 31.4, 22.3 and 14.8 respectively.&nbsp

Edible vaccines: A new approach to oral immunization

283-294Edible vaccines offer exciting possibilities for significantly reducing the burden of diseases like hepatitis and diarrhoea, particularly in developing world where storing and administering vaccines are the major problems. Edible vaccines are prepared by molecular farming using the science of genetic engineering. Selected genes are introduced into the plants. The transgenic plant is then induced to manufacture the encoded protein. Owing to its low cost, it will be suitable for developing countries like India. Edible vaccines are mucosal-targeted vaccines, which cause stimulation of both systematic and mucosal immune response. Edible vaccines are being developed for various diseases, such as measles, cholera and hepatitis B, and many more are in the process of development. Thus, they may also help to suppress autoimmune disorders such as Type-I diabetes, diarrhoea, multiple sclerosis, rheumatoid arthritis, etc. Human trials conducted by the National Institute of Allergy and Infectious Diseases (NIAID), US Department of Health and Human Services, USA show that edible vaccines are feasible. ProdiGene, a biotech company, has a patent for vaccine against, viral diseases of hepatitis and transmissible gastroenteritis virus. This review comprises methods of preparation, mechanism of action, recent developments, clinical trials and therapeutic applications of edible vaccines

Liposomes as adjuvant for combination vaccines

237-241In the present study tetanus toxoid (TT) loaded liposomes and diphtheria toxoid (DT) loaded liposomes were prepared by reverse phase evaporation method and after combining these two vaccines the potential advantages were investigated. Prepared systems were characterized for the size, shape and entrapment efficiency. SDS-PAGE analysis of TT and DT was also performed. The selected liposomal formulations were administered subcutaneously to Balb/c mice and their immune responses were determined using ELISA after 15, 30, 45 days. After boosting the maximum immune response was observed after 45 days and was found to be 0.831 and 0.749 for TT loaded liposome and DT loaded liposomes respectively. When the mice were immunized subcutaneously with the physical mixture of TT loaded liposomes and DT loaded liposomes the immune response for the combination vaccine was found to be 1.44 and 0.741 for the TT and DT respectively. The result showed that the immune response of TT increased when it was combined with DT in liposomes. This confirms adjuvantcity of DT vis-a-vis immunogenicity. Thus, carrier mediated cocktail vaccination holds promise for clinical applications

Antioxidant and Wound Healing Property of Gelsolin in 3T3-L1 Cells

Delineation of factors which affect wound healing would be of immense value to enable on-time or early healing and reduce comorbidities associated with infections or biochemical stress like diabetes. Plasma gelsolin has been identified earlier to significantly enable injury recovery compared to placebo. This study evaluates the role of rhuGSN for its antioxidant and wound healing properties in murine fibroblasts (3T3-L1 cell line). Total antioxidant capacity of rhuGSN increased in a concentration-dependent manner (0.75-200 μg/mL). Cells pretreated with 0.375 and 0.75 μg/mL rhuGSN for 24 h exhibited a significant increase in viability in a MTT assay. Preincubation of cells with rhuGSN for 24 h followed by oxidative stress induced by exposure to H2O2 for 3 h showed cytoprotective effect. rhuGSN at 12.5 and 25 μg/mL concentration showed an enhanced cell migration after 20 h of injury in a scratch wound healing assay. The proinflammatory cytokine IL-6 levels were elevated in the culture supernatant. These results establish an effective role of rhuGSN against oxidative stress induced by H2O2 and in wound healing of 3T3-L1 fibroblast cells

Plasma Gelsolin Levels Decrease in Diabetic State and Increase upon Treatment with F-Actin Depolymerizing Versions of Gelsolin

The study aims to map plasma gelsolin (pGSN) levels in diabetic humans and mice models of type II diabetes and to evaluate the efficacy of gelsolin therapy in improvement of diabetes in mice. We report that pGSN values decrease by a factor of 0.45 to 0.5 in the blood of type II diabetic humans and mice models. Oral glucose tolerance test in mice models showed that subcutaneous administration of recombinant pGSN and its F-actin depolymerizing competent versions brought down blood sugar levels comparable to Sitagliptin, a drug used to manage hyperglycemic condition. Further, daily dose of pGSN or its truncated versions to diabetic mice for a week kept sugar levels close to normal values. Also, diabetic mice treated with Sitagliptin for 7 days, showed increase in their pGSN values with the decrease in blood glucose as compared to their levels at the start of treatment. Gelsolin helped in improving glycemic control in diabetic mice. We propose that gelsolin level monitoring and replacement of F-actin severing capable gelsolin(s) should be considered in diabetic care

Protective effects of gelsolin in acute pulmonary thromboembolism and thrombosis in the carotid artery of mice.

The present study provides first evidence on the role of plasma gelsolin in protecting pulmonary thromboembolism and thrombosis in a mouse model. Gelsolin is the most abundant actin depolymerizing protein in plasma and its significantly depleted values have been reported in metabolic disorders including cardiovascular diseases and myocardial infarction. Though gelsolin replacement therapy (GRT) has been shown to be effective in some animal models, no such study has been reported for thrombotic diseases that are acutely in need of bio-therapeutics for immediate and lasting relief. Here, using mice model and recombinant human gelsolin (rhuGSN), we demonstrate the antithrombotic effect of gelsolin in ferric chloride induced thrombosis in carotid artery and thrombin induced acute pulmonary thromboembolism. In thrombosis model, arterial occlusion time was significantly enhanced upon subcutaneous (SC) treatment with 8 mg of gelsolin per mice viz. 15.83 minutes vs. 8 minutes in the placebo group. Pertinently, histopathological examination showed channel formation within the thrombi in the carotid artery following injection of gelsolin. Fluorescence molecular tomography imaging further confirmed that administration of gelsolin reduced thrombus formation following carotid artery injury. In thrombin-induced acute pulmonary thromboembolism, mice pretreated with aspirin or gelsolin showed 100 and 83.33% recovery, respectively. In contrast, complete mortality of mice was observed in vehicle treated group within 5 minutes of thrombin injection. Overall, our studies provide conclusive evidence on the thrombo-protective role of plasma gelsolin in mice model of pulmonary thromboembolism and thrombosis