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      Nitazoxanide, Ivermectin, and Artemether effects against cryptosporidiosis in diabetic mice: parasitological, histopathological, and chemical studies

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          Abstract

          Human cryptosporidiosis is one of the most significant causes of water borne epidemics of diarrhea worldwide. It is extremely important in immunocompromised hosts and malnourished children as it could cause severe life-threatening diarrhea. Despite the global burden of the disease, there are only few available therapies against cryptosporidiosis. Diabetes mellitus is a common metabolic disorder that impair both the innate and adaptive immune responses of the patient. This study aimed to test the effect of Nitazoxanide, Ivermectin, and Artemether against cryptosporidiosis in diabetic mice. Sixty white albino mice were categorized into 6 groups; 10 mice each: GI: normal non-infected non-treated (healthy- control), GII-GVI (diabetic groups), GII: non-infected non treated (diabetic control), GIII: infected non treated (infected control), GIV: infected and treated with Nitazoxanide (NTZ), GV: infected and treated with Ivermectin (IVC), GVI: infected and treated with Artemether (ART). Parasitological, histopathological, and chemical examinations were done to evaluate the effect of NTZ, IVC, and ART against cryptosporidiosis in diabetic mice. Parasitological examination revealed maximum reduction of oocyst shedding in GVI, while histopathological examination showed the least pathologic changes in GV with mild vascular wall fibrosis and moderate lymphocytic infiltration of islets of Langerhans. Measurement of blood glucose level showed the best results with GIV. Nitazoxanide is effective against cryptosporidiosis in diabetic patients with minimal hyperglycemia, Artemether is especially effective in reducing the oocyst shedding in stool, whereas Ivermectin is associated with the least pathological changes in pancreatic islets of Langerhans.

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          Global aetiology and epidemiology of type 2 diabetes mellitus and its complications

          Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM global epidemic, with China and India the top two epicentres. Although genetic predisposition partly determines individual susceptibility to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic; early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be prevented with lifestyle changes, including maintaining a healthy body weight, consuming a healthy diet, staying physically active, not smoking and drinking alcohol in moderation. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. This Review provides an updated view of the global epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for T2DM and its complications.
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            Type 2 Diabetes and its Impact on the Immune System

            Introduction: Type 2 Diabetes (T2D) is a major health problem worldwide. This metabolic disease is indicated by high blood glucose levels due to insufficient insulin production by the pancreas. An inflammatory response occurs as a result of the immune response to high blood glucose levels as well as the presence of inflammatory mediators produced by adipocytes and macrophages in fat tissue. This low and chronic inflammation damages the pancreatic beta cells and leads to insufficient insulin production, which results in hyperglycemia. Hyperglycemia in diabetes is thought to cause dysfunction of the immune response, which fails to control the spread of invading pathogens in diabetic subjects. Therefore, diabetic subjects are known to more susceptible to infections. The increased prevalence of T2D will increase the incidence of infectious diseases and related comorbidities. Objective: This review provides an overview of the immunological aspect of T2D and the possible mechanisms that result in increased infections in diabetics. Conclusion: A better understanding of how immune dysfunctions occur during hyperglycemia can lead to novel treatments and preventions for infectious diseases and T2D comorbidities, thus improving the outcome of infectious disease treatment in T2D patients.
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              Streptozotocin-Induced Diabetic Models in Mice and Rats.

              Streptozotocin (STZ) is an antibiotic that produces pancreatic islet β-cell destruction and is widely used experimentally to produce a model of type 1 diabetes mellitus (T1DM). Detailed in this unit are protocols for producing STZ-induced insulin deficiency and hyperglycemia in mice and rats. Also described are protocols for creating animal models for type 2 diabetes using STZ. These animals are employed for assessing the pathological consequences of diabetes and for screening potential therapies for the treatment of this condition.
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                Author and article information

                Contributors
                aymanpara@yahoo.com
                Journal
                J Parasit Dis
                J Parasit Dis
                Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
                Springer India (New Delhi )
                0971-7196
                0975-0703
                7 September 2022
                : 1-10
                Affiliations
                [1 ]GRID grid.7269.a, ISNI 0000 0004 0621 1570, Department of Medical Parasitology, Faculty of Medicine, , Ain Shams University, ; Cairo, Egypt
                [2 ]GRID grid.420091.e, ISNI 0000 0001 0165 571X, Department of Medical Parasitology, , Theodor Bilharz Research Institute, ; Giza, Egypt
                [3 ]GRID grid.420091.e, ISNI 0000 0001 0165 571X, Department of Pathology, , Theodor Bilharz Research Institute, ; Giza, Egypt
                Author information
                http://orcid.org/0000-0003-4815-8731
                Article
                1527
                10.1007/s12639-022-01527-w
                9451122
                73c04ce5-169c-4b51-8dca-a68cbe9254bb
                © Indian Society for Parasitology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 26 June 2022
                : 20 August 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002352, Ain Shams University;
                Categories
                Original Article

                artemether,cryptosporidium,ivermectin,nitazoxanide,diabetes mellitus

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