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In the present study, combined treatment with etanercept and anakinra were tested in the streptozotocin-induced diabetic rats. Forty male Wistar albino rats were divided into 5 groups: healthy control (HC), diabetic control (DC), diabetic + anakinra (DAT), diabetic + etanercept (DET), and diabetic + etanercept + anakinra (DEAT). HC and DC groups received subcutaneous (s.c.) injection with a saline solution, while DAT and DET groups received anakinra (10 mg/kg per day, s.c.) or etanercept (10 mg/kg, twice a week, s.c.), and DEAT rats received both anakinra and etanercept treatments for 21 days after diabetes has developed. Anakinra and etanercept treatments significantly increased insulin and homeostatic model assessment β-cell function levels and decreased glucose levels compared to the DC group as single (DAT and DET) and combined treatments (DEAT). The thiobarbituric acid reactive substances level was significantly decreased in DAT group. The combine use of etanercept and anakinra can improve insulin and blood glucose in type 2 diabetic rats. The combined treatment of anakinra and etanercept together was more effective than single treatment and might have a potential new treatment strategy and to reduce the mortality and morbidity resulting from diabetes.

IntroductionType 2 diabetes is defined as a chronic inflammatory metabolic disease that is characterized with the impaired insulin effect and high blood glucose level [1]. The disease has degenerative effects on many tissues and a high incidence worldwide. Although many drugs are used for the treatment of this disease, more effective treatment strategies have yet to be found [2,3].Adenosine 5′-monophosphate activated protein kinase (AMPK) is considered to be an important potential therapeutic target for the treatment of type 2 diabetes (T2D). AMPK is defined as serine/threonine protein kinase complex. The kinase consists catalytic α (α1, α2), regulatory β (β1, β2), and regulatory γ (γ1, γ2, γ3) subunits and express in each tissue [3]. Although the isoforms have been reported to have different effects and tissue-specific, the effects of isoforms have not been fully cleared. However, α1 isoform predominates in the liver and adipose tissue; whereas, α2 predominates in the brain, heart, and skeletal muscles [4]. The AMPK acts as a sensor that determines the AMP/ATP or ADP/ATP ratio. The AMPK is activated by phosphorylation of Thr-172 residue in the α subunit and increasing AMP/ATP ratio in the cell [3][4][5][6]. The activated AMPK provides the phosphorylation of key metabolic proteins that inhibits anabolic activities and increase catabolic activities [3]. The AMPK activation suppresses genes mediating gluconeogenesis and lipogenesis in the liver [7], and the activation of AMPK has been reported to increase insulin secretion from pancreatic β cells [3,8]. On the contrary, the excessive increased insulin, leptin and diacylglycerol levels and hyperglycemia, hyperlipidemia inhibit the AMPK activation [6]. Therefore, the AMPK activation increases insulin sensitivity, stimulates glycogen synthesis while inhibits glycolysis. Thus, it is an important Aim: The aim of this study is to determine the effects of different concentrations of albendazole and lansoprazole, which were benzimidazole derivatives, on endocrinologic and biochemical parameters in experimental type 2 diabetic (T2D) rats. Materials and methods:In this study, 46 male Wistar Albino rats were used. Animals were divided as healthy control (0.1 mL/rat/day saline, s.c, n = 6), diabetes control (0.1 mL/rat/day saline, s.c, n = 8), diabetes+low-dose albendazole (5 mg/kg, oral, n = 8), diabetes+highdose albendazole (10 mg/kg, oral n = 8), diabetes+low-dose lansoprazole (15 mg/kg, subcutaneous, n = 8), and diabetes+high-dose lansoprazole (30 mg/kg, subcutaneous, n = 8). All groups were treated for 8 weeks. The blood samples were analyzed by autoanalyzer and ELISA kits for biochemical and endocrinological parameters, respectively.Results: Glucose, HbA1c, triglyceride, low density cholesterol (LDL), leptin, and Homeostatic Model Assessment for insulin resistance (HOMA-IR) levels increased and insulin and HOMA-β levels decreased in the diabetic rats compared to the healthy control group. The glucose, HbA1c, and triglyceride levels were partially decreased; however, insu...

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This study aimed to evaluate the effects of Peste des petits ruminants (PPR) vaccine on cytokine and antibody levels in sheep when administered alone or in combination with Corynebacterium cutis lysate (CCL). The PPR vaccine group received a single subcutaneous axillary injection of the PPR vaccine (1 mL containing tissue culture infectious dose (TCID) attenuated live PPRV, n = 6) and the combination treatment (1 mL CCL and 1 mL PPR vaccine, n = 6) groups received a single subcutaneous axillary injection of both CCL and PPR vaccine. Blood samples were collected from sheep before the treatment and at different points after treatment (1, 3, 7, 14, 21, and 28 days). Plasma and serum samples were evaluated for antibody percentage, levels of cytokines IL-6, IL-10, IFN-γ, IL-4, IL-12, and IL-18, oxidative stress marker Thiobarbituric acid reactive substances, and hematological and biochemical parameters. Maximum protective antibody levels reach 3-4 weeks after vaccine administration. The combination treatment resulted in significant changes in IFN-γ, IL-4, IL-12, and IL-18 cytokine levels. These changes were not evident when only the PPR vaccine was administered and antibody percentage against PPRV was short term in PPR vaccine group. In conclusion, combined usage of the PPR vaccine with CCL resulted in a heightened cytokine response, leading to improved antibody level against PPR virus. Repeated CCL treatments can lead to earlier vaccine potency, provide protective efficacy for a longer time, and increase passive immunity.