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    Effects of Diabetogenic Agent Streptozotocin on Hematological Parameters of Wistar Albino Rats "An Experimental Study"

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    Background: Diabetes mellitus has remained the major concern for medical sciences researches due to its deleterious effects on general, physical and mental health of patients. To understand the pathophysiology and to explore better treatment options for such kind of metabolic disorders it is necessary to generate the experimental animal models. To create diabetic animal models, streptozotocin has shown predominance in selectivity as a diabetogenic agent. While studying effects of any intervention in the diabetic animal models, being a cytotoxic drug streptozotocin may affect the study results by inhibiting highly replicating cells especially hematopoietic cells. Keywords: Streptozotocin; animal model; hematological parameters. 1. INTRODUCTION Diabetes mellitus has remained the major concern for medical sciences researches not only due to its high incidence and prevalence rate but also due its deleterious effects on general, physical and mental health of the patients [1]. To understand the pathophysiology and to explore better treatment options for such kind of metabolic disorders it is necessary to generate the experimental animal models [2]. To create diabetic animal models, surgical (pancreatectomy) and pharmacological (alloxan monohydrate and streptozotocin) options have been used in research but pharmacological options particularly use of streptozotocin has shown predominance in selectivity as a diabetogenic agent [1,2]. Chemically, streptozotocin is a derivative of synthetic Nitrosoureido Glucopyranose and has been used for cancer chemotherapies [3], being its potential to inhibit DNA synthesis in bacterial and mammalian cells [4]. While its diabetogenic effect is thought to be attributed to its ability to cause pancreatic β cells’ death by DNA alkylation and hence used to induce diabetes mellitus in experimental animals [5,6]. The methods to induce diabetes in animal models by streptozotocin fall under three categories 1. Multiple small doses (i.e. 40 mg/kg) of streptozotocin over a period of several days 2. A single moderate dose (i.e. 60 mg/kg) of streptozotocin or 3. A single large dose (100 mg/kg) of streptozotocin produce diabetes in 48- 72 hours. Usually a single large dose of streptozotocin is used to induce diabetes in experimental models as reported by Ito et al. 100 mg / kg of streptozotocin produced non-insulin dependent diabetes mellitus in experimental animals [7]. Streptozotocin can be administered by various routes including subcutaneous and intramuscular routes but intraperitoneal and intravenous administration routes are preferred. [8]. After 3-4 days of streptozotocin administration fasting blood glucose levels are obtained to confirm the accuracy of procedure [9] and on 5th day when 180-500 mg/dl serum glucose levels are obtained experimental animals are considered as diabetic [10]. Though streptozotocin is preferred pharmaco- logical method for induction of diabetes [11], many studies have reported spontaneous recovery from hyperglycemia due to reactive hyperinsulinemia insulinoma [12,13,14]. Streptototozin, not only affects pancreas and cause diabetes in experimental animals but also have a potential to produce toxic effects on other body tissues as well. It has been learnt through a number of studies that streptozotocin is associated with high incidence of hepatic and renal tumors [15], increase in permeability of blood brain barrier [16], renal hypertrophy [17] and retinal damage in experimental animal models [18]. As already discussed that streptozotocin damages DNA by alkylation and produces free radicals, therefore it may harm any organ system of animals [19]. Despite of aforementioned, streptozotocin is still employed Aims: The aim of study was to analyze the effects of streptozotocin on various cellular components of blood such as RBCs, WBCs (Lymphocytes, Neutrophils, Eosinophils), Hb%, HCT and Platelets, at baseline, 5th day and 15th day without any intervention. Study Design: Animal based Experimental study. Place and duration of Study: The study was conducted at animal house of faculty of Pharmacy Ziauddin University Karachi, while laboratory work was performed at MDRL-1 Ziauddin University. Methodology: In Group A normal saline and in group B and C 60 mg / kg streptozotocin diluted in normal saline was administered intraperitoneally. After the confirmation of induction of Diabetes in rats, on fifth day blood samples were drawn from Group A and B and were analyzed. While blood samples from group C were drawn on fifteenth day. Results: Analysis of various hematological parameters on 5th day revealed that there was a decrease in the levels of Hb, HCT, RBCs and WBCs with an increase in platelet count in group B in comparison to group A (control). On the other hand, in Group C (15th day), blood cell counts (Hb, HCT, RBCs, WBCs, Lymphocytes, Neutrophils and platelets) seemed to recover from streptozotocin induced decline that was observed in group B, however did not reach the baselines as in group A(control). Conclusion: It is concluded that change in hematological parameters of rats after administration of streptozotocin is reversible. The blood parameters may recover near to base line values without any intervention within two weeks

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Modulation of Altered Immune Parameters IL-2 and TNF-α in Diabetic Animal Models: A Therapeutic Insinuation of Metformin Beyond Diabetes

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    Background: Immunomodulatory drugs target the overall immune system, hence producing numerous toxic effects on the other organs with serious health manifestations. Due to these safety concerns, there is a need to introduce or repurpose a new drug with immunomodulatory effects with good safety, efficacy, and better tolerance. Metformin, a standard antidiabetic drug, was evaluated for its immunomodulatory effects in diabetic models in the current study. Methodology: The diabetic model was developed by intraperitoneal (IP) administration of streptozotocin (60 mg/kg). The experimental rats were divided into six groups (three diabetic and three non-diabetic) with six rats in each group. Metformin (50 mg/kg and 80 mg/kg) was given orally to both diabetic and non-diabetic groups, once a day, for 42 days. Immunomodulatory cytokines interleukin (IL)-2, IL-4, IL-5, tumor necrosis factor (TNF)-α, and interferon gamma (INF-ɣ) were analyzed from blood samples by BD FCAP flow cytometer. Results: The results revealed a significant (p=0.002) decrease in IL-2 and TNF-α in diabetic groups in comparison to control rats. However, no significant changes were observed in IL-4, IL-5, and INF-ɣ levels. Importantly, the treatment of metformin at both doses, i.e., 50 and 80 mg/kg, significantly reduced the elevated levels of IL-2 and TNF-α when compared to untreated diabetic groups. Conclusion: Metformin may be considered as an optimum drug candidate to reduce pro-inflammatory cytokines, IL-2 and TNF-α, that can lead to the reduction of long-term diabetic complications

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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