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Sample records for autoimmune type-i diabetes

  1. "PREVALENCE OF AUTOANTIBODIES TO THYROID PEROXIDASE AND AUTOIMMUNE THYROID DISEASE IN TYPE I DIABETES MELLITUS"

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    H. Moayeri A. Rabbani

    2004-09-01

    Full Text Available Type I diabetes mellitus (DM is frequently associated with autoimmune thyroid disease (ATD. Association of ATD and type I DM has been described with varying frequencies but there is still debate about the situation in the Iranian population. We investigated the prevalence of anti thyroid peroxidase (anti-TPO antibodies and ATD in children and adolescents with type I DM. A total of 145 patients with type I DM were participated in this study. They were screened for anti-TPO antibodies and TSH levels. Signs and symptoms of hypothyroidism and hyperthyroidism and the presence of goiter were sought. A group of 50 healthy unrelated girls and boys aged 11-16 years served as controls. Anti-TPO antibodies were found in 34 (23.4% diabetic patients and 1 subject (2% in the control group (P<0.001. Frequency of anti TPO antibodies was significantly higher in girls than boys (P<0.05. We failed to show any significant correlation between thyroid autoimmunity and duration of DM. We found that younger patients at diagnosis are more likely to be anti-TPO negative (P<0.001. Out of 145 diabetic patients, 32 (22% had visible goiter. Subclinical hypothyroidism, hypothyroidism and thyrotoxicosis occurred in 1, 9 and 1 patients, respectively. Visible goiter was found in 2 subjects (4% of the control group, but all of them were euthyroid. In conclusion, the evaluation of thyroid autoimmunity in type I diabetic patients may improve the diagnosis of thyroid disease in early stages. Yearly examination of anti-TPO antibodies allows identifying diabetic patients with thyroid autoimmunity.

  2. Extrapancreatic Autoantibody Profiles in Type I Diabetes

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    Burbelo, Peter D.; Lebovitz, Evan E.; Bren, Kathleen E.; Bayat, Ahmad; Paviol, Scott; Wenzlau, Janet M.; Barriga, Katherine J.; Rewers, Marian; Harlan, David M.; Iadarola, Michael J.

    2012-01-01

    Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-β (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together

  3. Streptozotocin, Type I Diabetes Severity and Bone

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    Motyl Katherine

    2009-01-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  4. Streptozotocin, Type I Diabetes Severity and Bone

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    Motyl Katherine

    2009-03-01

    Full Text Available Abstract As many as 50% of adults with type I (T1 diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2. An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.

  5. Genetic homogeneity of autoimmune polyglandular disease type I

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    Bjoerses, P.; Aaltonen, J.; Vikman, A. [Univ. of Helsinki (Finland)] [and others

    1996-10-01

    Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pair-wise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for {approximately}90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21. 21 refs., 3 figs., 3 tabs.

  6. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

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    Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

    2014-06-01

    Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.

  7. Ingested Type I Interferon—State of the Art as Treatment for Autoimmunity Part 2

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    Staley A. Brod

    2010-04-01

    Full Text Available We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity that defines autoimmunity as a type I interferon (IFN immunodeficiency syndrome. We have examined toxicity and potential efficacy in two phase I (type 1 diabetes [T1D], multiple sclerosis [MS] and phase II clinical trials in T1D and MS. In a phase I open label trial in T1D, ingested IFN-alpha preserved residual beta-cell function in recent onset patients. In a second phase I trial in MS, there was a significant decrease in peripheral blood mononuclear cell IL-2 and IFN-gamma production after ingesting IFN-alpha. In a phase II randomized, placebo-controlled, double-blind trial in MS, 10,000 IU ingested IFN-alpha significantly decreased gadolinium enhancements compared to the placebo group at month 5. TNF-alpha and IFN-gamma cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-alpha on decreasing gadolinium enhancements. In a phase II randomized, placebo-controlled, double-blind trial in T1D, patients in the 5,000 unit hrIFN-alpha treatment group maintained more beta-cell function one year after study enrollment compared to individuals in the placebo group. Ingested IFN-alpha was not toxic in these clinical trials. These studies suggest that ingested IFN-alpha may have a potential role in the treatment of autoimmunity.

  8. TNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis.

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    Conrad, Curdin; Di Domizio, Jeremy; Mylonas, Alessio; Belkhodja, Cyrine; Demaria, Olivier; Navarini, Alexander A; Lapointe, Anne-Karine; French, Lars E; Vernez, Maxime; Gilliet, Michel

    2018-01-02

    Although anti-tumor necrosis factor (TNF) agents are highly effective in the treatment of psoriasis, 2-5% of treated patients develop psoriasis-like skin lesions called paradoxical psoriasis. The pathogenesis of this side effect and its distinction from classical psoriasis remain unknown. Here we show that skin lesions from patients with paradoxical psoriasis are characterized by a selective overexpression of type I interferons, dermal accumulation of plasmacytoid dendritic cells (pDC), and reduced T-cell numbers, when compared to classical psoriasis. Anti-TNF treatment prolongs type I interferon production by pDCs through inhibition of their maturation. The resulting type I interferon overexpression is responsible for the skin phenotype of paradoxical psoriasis, which, unlike classical psoriasis, is independent of T cells. These findings indicate that paradoxical psoriasis represents an ongoing overactive innate inflammatory process, driven by pDC-derived type I interferon that does not lead to T-cell autoimmunity.

  9. Redistribution of blood volume in Type I diabetes

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    Ubels, FL; Muntinga, JHJ; Links, TP; Hoogenberg, K; Dullaart, RPF; Smit, AJ

    Aims/hypothesis. Impaired activity of endothelium-derived nitric oxide in Type I (insulin-dependent) diabetes mellitus will cause an increased vascular tone. Considering the lower production of nitric oxide in veins than in arteries, an impaired activity would have less vasoconstrictive effect in

  10. Method for identifying type I diabetes mellitus in humans

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    Metz, Thomas O [Kennewick, WA; Qian, Weijun [Richland, WA; Jacobs, Jon M [Pasco, WA; Smith, Richard D [Richland, WA

    2011-04-12

    A method and system for classifying subject populations utilizing predictive and diagnostic biomarkers for type I diabetes mellitus. The method including determining the levels of a variety of markers within the serum or plasma of a target organism and correlating this level to general populations as a screen for predisposition or progressive monitoring of disease presence or predisposition.

  11. Quality of life of patients with type I diabetes mellitus

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    Hart, HE; Bilo, HJG; Redekop, WK; Stolk, RP; Meyboom-de Jong, B

    2003-01-01

    The objective of this study was to assess health related quality of life (QOL) in patients with type I diabetes mellitus (DMT1) and to compare their QOL with the QOL of persons of comparable age in the general population. Furthermore we wanted to investigate which factors mostly influence QOL. In a

  12. Primary intestinal lymphangiectasia as a component of autoimmune polyglandular syndrome type I: a report of 2 cases.

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    Makharia, Govind K; Tandon, Nikhil; Stephen, Neil de Jesus Rangel; Gupta, Siddhartha Datta; Tandon, Rakesh K

    2007-01-01

    Chronic diarrhea and steatorrhea occur frequently in patients with autoimmune polyglandular syndrome (APS) type I. Intestinal lymphangiectasia has been reported earlier as a cause of steatorrhea in a young girl with APS Type I. We describe 2 patients with APS Type I who were found to have intestinal lymphangiectasia, one of whom had symptomatic protein-losing enteropathy.

  13. Suppressing effect of low-dose ionizing radiation on incidence of type I diabetes of NOD mice

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    Nomura, T.; Makino, N.; Oda, T.; Sakai, K.

    2002-01-01

    In the present study we examined the effects of 0.5 Gy of ionizing radiation, given acutely or chronically, on the incidence of type I diabetes in non-obese diabetic mice was examined. NOD mice are characterized by a progressive loss of insulin-producing cells in the pancreas by autoimmune mechanisms. The results suggest that the suppressive effects on the onset of he diabetes by the low dose irradiation are explain by the induction of the antioxidative activity

  14. Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)

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    Aaltonen, J.; Bjoerses, P.; Peltonen, L. [National Public Health Institute, Helsinki (Finland)] [and others

    1994-09-01

    Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

  15. Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

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    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio; Fromm, M; Schulzke, JD

    2009-01-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type I diabetes (TID), a hyperglycosaemia caused by a destructive autoimmune

  16. Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?

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    Chieko Kyogoku

    Full Text Available Gene expression profiling of peripheral blood mononuclear cells (PBMCs has revealed a crucial role for type I interferon (IFN in the pathogenesis of systemic lupus erythematosus (SLE. However, it is unclear how particular leucocyte subsets contribute to the overall type I IFN signature of PBMCs and whole blood samples.Furthermore, a detailed analysis describing the differences in the IFN signature in autoimmune diseases from that observed after viral infection has not been performed to date. Therefore, in this study, the transcriptional responses in peripheral T helper cells (CD4(+ and monocyte subsets (CD16(- inflammatory and CD16(+ resident monocytes isolated from patients with SLE, healthy donors (ND immunised with the yellow fever vaccine YFV-17Dand untreated controls were compared by global gene expression profiling.It was striking that all of the transcripts that were regulated in response to viral exposure were also found to be differentially regulated in SLE, albeit with markedly lower fold-change values. In addition to this common IFN signature, a pathogenic IFN-associated gene signature was detected in the CD4(+ T cells and monocytes from the lupus patients. IL-10, IL-9 and IL-15-mediated JAK/STAT signalling was shown to be involved in the pathological amplification of IFN responses observed in SLE. Type I IFN signatures identified were successfully applied for the monitoring of interferon responses in PBMCs of an independent cohort of SLE patients and virus-infected individuals. Moreover, these cell-type specific gene signatures allowed a correct classification of PBMCs independent from their heterogenic cellular composition. In conclusion, our data show for the first time that monocytes and CD4 cells are sensitive biosensors to monitor type I interferon response signatures in autoimmunity and viral infection and how these transriptional responses are modulated in a cell- and disease-specific manner.

  17. Dental caries and salivary alterations in Type I Diabetes.

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    Rai, K; Hegde, A M; Kamath, A; Shetty, S

    2011-01-01

    Insulin dependent diabetes mellitus is a severe disease that raises blood glucose levels because of hyperglycemia and insulinopenia. Fluctuations in water and electrolyte levels may result in xerostomia and other changes in the salivary composition. Since diabetes has an influence on oral health, it is important for the dentist to be aware of newer advances in the field of diabetes and to recognize specific oral problems related to diabetes. Thus, the dentist becomes an important part of the health care team for the patients with diabetes. The present study correlated salivary flow rate, salivary pH and total salivary antioxidant levels and dental caries in type I diabetic patients. A total of 200 children that included 100 known diabetic children (study group) and 100 healthy children (controls) of both the sexes and from similar socioeconomic backgrounds formed the part of this study. Dental caries was assessed using DMFT index. The salivary total anti-oxidant level was estimated using phospho molybdic acid using spectrophotometric method. The salivary flow rate was recorded using the Zunt method and the salivary pH using the pH indicating paper. The results were statistically analyzed using t-test. The analyzed parameters showed increase in salivary anti-oxidant levels, reduced salivary flow rate, increase incidence of dental caries, salivary pH was decreased when compared to the control group.

  18. Autoimmune Diabetes and Thyroiditis Complicating Treatment with Nivolumab

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    Li Li

    2017-03-01

    Full Text Available Programmed cell death-1 (PD-1 ligand inhibitors have gained popularity in the treatment of advanced non-small-cell lung cancer. The immune system is regulated by stimulatory and inhibitory signaling and aims to achieve the balance between activation and inhibition. Treatment with immune checkpoint inhibitors enhances immune response, but is also known to diminish immune tolerance and increase autoimmune toxicity. Here we present a case of a patient with advanced squamous cell lung cancer who developed type I diabetes and thyroiditis after treatment with PD-1 checkpoint inhibitor nivolumab. The presence of autoimmune diabetes mellitus and thyroiditis were confirmed by markedly elevated titers of the glutamic acid decarboxylase autoantibody and thyroid peroxidase antibody, respectively. This report serves to heighten awareness of potential autoimmune toxicities related to anti-PD-1 therapy, especially as these toxicities are manageable if identified in a timely manner.

  19. Vestibulocochlear manifestations in patients with type I diabetes mellitus.

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    Klagenberg, Karlin Fabianne; Zeigelboim, Bianca Simone; Jurkiewicz, Ari Leon; Martins-Bassetto, Jackeline

    2007-01-01

    Glucose metabolism has a significant impact on inner ear physiology, and small changes may result in hearing and balance disorders. To investigate vestibulocochlear symptoms in patients with type I diabetes mellitus. a cross-sectional study of a contemporary group. 30 patients referred from Clinical Hospital-UFPR to the Laboratory of Otoneurology-UTP between Mar/2004 to Feb/2005 were evaluated. The following procedures were carried out: a medical history, otological inspections, audiometry, acoustic impedance tests, and vestibular function tests. The prevalence of otoneurologic complaints was: headache (23.3%), vertigo (16.6%), and tinnitus (13.3%). The prevalence of associated complaints and habits was: caffeine abuse (20.0%), allergies (10.0%), and alcohol abuse (10.0%). The prevalence of normal auditory thresholds was 90.0%. Acoustic impedance showed no changes. The vestibular test showed changes in 60.0% of cases. Peripheral vestibular deficiency syndromes were also found. Significant vestibular system changes were found (60.0%) compared to the auditory system (10.0%). Audiometry revealed mostly normal results. The vestibular test showed changes in the peripheral vestibular system and the peripheral vestibular deficiency syndrome.

  20. Bioinformatics analysis of the factors controlling type I IFN gene expression in autoimmune disease and virus-induced immunity

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    Di eFeng

    2013-09-01

    Full Text Available Patients with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS display increased levels of type I IFN-induced genes. Plasmacytoid dendritic cells (PDCs are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell type-specific gene signatures as well as identify distinct transcription factors that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by transcription factors, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as IRF5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease.

  1. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison's disease.

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    Winqvist, O; Gustafsson, J; Rorsman, F; Karlsson, F A; Kämpe, O

    1993-01-01

    Autoimmune polyendocrine syndrome type I (APS I) and idiopathic Addison's disease are both disorders with adrenal insufficiency but with differences in genetic background, clinical presentation, and extent of extraadrenal manifestations. In this study the major adrenal autoantigen identified with sera from patients with APS I was characterized by analyses using indirect immunofluorescence, Western blots of adrenal subcellular fractions and of recombinant proteins, immunoprecipitations of [35S...

  2. Prevalence of left ventricular hypertrophy in Type I diabetic patients with diabetic nephropathy

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    Sato, A; Tarnow, L; Parving, H H

    1999-01-01

    , serum creatinine 109 (53-558) micromol/l], and 140 Type I diabetic patients with persistent normoalbuminuria [79 men, 47+/-10 years, urinary albumin excretion rate 8 (0-30) mg/24 h, and serum creatinine 81 (55-121) micromol/l]. Patients with and without nephropathy were comparable with respect to sex...

  3. Oxytocin as a novel therapeutic option for type I diabetes and diabetic osteopathy.

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    Elabd, S K; Sabry, I; Mohasseb, M; Algendy, A

    2014-04-01

    The aim of the present study was to highlight the newly discovered metabolic role of oxytocin (OT) in the type I diabetic rats. Previous studies have demonstrated that OT has a beneficial role on bone physiology and therefore, the OT effect on the diabetic osteopathy will be assessed as well. Induction of the type I diabetes was carried out by an intraperitoneal injection of 60 mg/kg body weight of streptozotocin. The metabolic role of OT on diabetic rats after OT treatment with intramuscular injection of 40 µIU/kg body weight for 6 weeks was assessed. Histological and ultrastructural studies of rat pancreas samples, before and after the OT injection, were performed and compared with the obtained physiological results. Oxytocin treatment had positive metabolic effects in diabetic rats. This is based on the change in glucose metabolism, lipid profile, and insulin sensitivity in experimental animals. In addition, OT treatment showed histological regenerative changes of pancreatic islet cells of diabetic rats. Moreover, OT administration showed that it has an anabolic effect on the bone biology. The results suggest that activation of the oxytocin receptor (OTR) pathway by infusion of OT, OT analogs, or OT agonists may represent a promising approach for the treatment of diabetes and some of its complications, including diabetic osteopathy.

  4. Riboflavin alleviates cardiac failure in Type I diabetic cardiomyopathy

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    Xue Zhao

    2011-09-01

    Full Text Available Heart failure (HF is a common and serious comorbidity of diabetes. Oxidative stress has been associated with the pathogenesis of chronic diabetic complications including cardiomyopathy. The ability of antioxidants to inhibit injury has raised the possibility of new therapeutic treatment for diabetic heart diseases. Riboflavin constitutes an essential nutrient for humans and animals and it is an important food additive. Riboflavin, a precursor of flavin mononucleotide (FMN and flavin adenine dinucleotide (FAD, enhances the oxidative folding and subsequent secretion of proteins. The objective of this study was to investigate the cardioprotective effect of riboflavin in diabetic rats. Diabetes was induced in 30 rats by a single injection of streptozotocin (STZ (70 mg /kg. Riboflavin (20 mg/kg was orally administered to animals immediately after induction of diabetes and was continued for eight weeks. Rats were examined for diabetic cardiomyopathy by left ventricular (LV remadynamic function. Myocardial oxidative stress was assessed by measuring the activity of superoxide dismutase (SOD, the level of malondialdehyde (MDA as well as heme oxygenase-1 (HO-1 protein level. Myocardial connective tissue growth factor (CTGF level was measured by Western blot in all rats at the end of the study. In the untreated diabetic rats, left ventricular systolic pressure (LVSP rate of pressure rose (+dp/dt, and rate of pressure decay (−dp/dt were depressed while left ventricular enddiastolic pressure (LVEDP was increased, which indicated the reduced left ventricular contractility and slowing of left ventricular relaxation. The level of SOD decreased, CTGF and HO-1 protein expression and MDA content rose. Riboflavin treatment significantly improved left ventricular systolic and diastolic function in diabetic rats, there were persistent increases in significant activation of SOD and the level of HO-1 protein, and a decrease in the level of CTGF. These results suggest

  5. Emotional intelligence and glycemic management among type I diabetes patients.

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    Zysberg, Leehu; Bar Yoseph, Tal; Goldman, Mor

    2017-02-01

    Type 1 diabetes is a lifelong physical and emotional challenge. The concept of emotional intelligence may offer better understanding of personal resources facilitating management of such challenges. We therefore hypothesized that emotional intelligence will negatively associate with two measures of diabetic management: HA1c and blood sugar levels. A total of 78 young adults with type 1 diabetes mellitus reported their last HA1c test result and their blood sugar level, as well as demographics and took the audio-visual test of emotional intelligence. The results showed a negative association between emotional intelligence and HA1c and marginal results in the same direction with blood sugar levels even when controlling for demographics.

  6. Gallic acid attenuates type I diabetic nephropathy in rats.

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    Garud, Mayuresh Sudamrao; Kulkarni, Yogesh Anant

    2018-02-25

    Literature suggests that TGF-β1 has a central role in the progression of diabetic nephropathy and its down regulation can improve the disease condition. Oxidative stress, generation of advanced glycation end products and activation of renin angiotensin system are the connecting links between hyperglycemia and TGF-β1 over expression. Gallic acid is a phytochemical having wide range of biological activities. Gallic acid is reported to have antioxidant and advanced glycation inhibitory activity. It has also shown inhibitory effects on angiotensin converting enzyme. Gallic acid qualifies as a drug candidate to be tested in the diabetic nephropathy, one of the important complication of diabetes. Streptozotocin (55 mg/kg body weight, i.p.) induced diabetic nephropathy was used as an experimental model. Gallic acid was evaluated for its possible effect at the dose of 20 and 40 mg/kg body weight. Gallic acid treatment significantly lowered plasma levels of the creatinine and blood urea nitrogen and elevated the levels of the protein and albumin. Gallic acid also improved creatinine clearance. Determination of oxidative stress parameters showed that the oxidative stress in kidney tissues was reduced significantly in gallic acid treated animals. Results of the plasma, urine and oxidative stress parameters were also reflected in the histopathological evaluation showing improvement in kidney pathophysiology. ELISA assay for circulating TGF-β1 evaluation and immunohistochemical study for determination of kidney expression of TGF-β1 revealed that gallic acid significantly lowered both the circulating and tissue levels of TGF-β1. Results support the hypothesis that gallic acid can be effectively used in the treatment of diabetic nephropathy. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Genetic and immunologic aspects of autoimmune poliendocrine syndrome type I: review

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    Alice Rachel Bandeira de Araújo

    2016-10-01

    Full Text Available The autoimmune polyendocrinopathy syndrome type 1 (APS-1, also known as candidiasis ectodermal-autoimmune polyendocrinopathy-dystrophy (APECED, it is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE. Therefore, it is immunologically characterized by cell attack and / or antibodymediated generating the destruction of target organs. Furthermore, it is characterized by the pathognomonic triad chronic candidiasis, hypoparathyroidism and Addison's disease with many other endocrine and non-endocrine events. Soon, the diagnosis is made based on the presence of two of the three classic features and treatment aims to control the numerous deficiencies that patients may present. This literature review was aimed at understanding the involvement of AIRE gene in relation to immunological aspects present and, consequently, clinical manifestations of this disease. Thus, evidence of the need to broaden the discussion about this disease, in order to improve the quality of life of patients by early diagnosis and treatment and are in accordance with the clinical manifestations of each patient. Thereby, qualitative research involved scientific articles from electronic journals LILACS (Latin American and Caribbean, SCIELO (Scientific Electronic Library Online and NCBI (National Center for Biotechnology Information, between the years 2009 and 2016. Pursuant to, there is the relevance of this review, it is noted that, although the authors converge on views on this syndrome, there are still many unclear matters with regard to the mechanisms of the disease. This highlights the need to promote more discussion on this topic.

  8. Total plasma homocysteine is associated with hypertension in Type I diabetic patients

    DEFF Research Database (Denmark)

    Neugebauer, S; Tarnow, L; Stehouwer, C D

    2002-01-01

    between plasma homocysteine concentrations, methylenetetrahydrofolate reductase gene polymorphism, hypertension, diabetic microvascular and macrovascular complications associated with kidney function. METHODS: Vascular complications, hypertension, methylenetetrahydrofolate reductase genotype (RFLP...... was an independent determinant of plasma homocysteine, the methylenetetrahydrofolate reductase gene polymorphism was neither associated with diabetic vascular complications nor with hypertension. CONCLUSION/INTERPRETATION: Increased plasma homocysteine concentrations but not the T allele per se, enhance the risk...... of hypertension and of CHD in Danish Type I diabetic patients with normal renal function....

  9. Are there any disturbances in vestibular organ of children and young adults with Type I diabetes?

    Science.gov (United States)

    Gawron, W; Pospiech, L; Orendorz-Fraczkowska, K; Noczynska, A

    2002-05-01

    The aim of the work was to evaluate the vestibular organ condition in children and young adults suffering from Type I (insulin-dependent) diabetes mellitus. The group examined consisted of 95 children and young adults aged from 6 to 28 years with Type I diabetes diagnosed. The diabetic group was divided into subgroups according to duration of the disease, compensation of the disease, and presence and character of hypoglycaemic incidents, and presence of diabetic complications. The control group consisted of 44 healthy children and young adults aged 6 to 28 years. After collecting detailed medical history in each case an electronystagmographic test was performed using the computed two-canal electronystagmographer. Within the diabetic group 6 patients complained about vertigo and balance disorders. Spontaneous nystagmus occurred in 10 cases, positional one in 21 cases. Impaired optokinesis occurred in 36 cases and impaired eye tracking test in 33 cases. In caloric tests there was partial canal paresis in 4 cases and directional preponderance in 7 cases. Metabolic disturbances present in Type I diabetes cause disturbances in different parts of vestibular organ but mostly in its central part. Comparing disturbances in the vestibular organ with clinical and biochemical parameters characterising diabetes, the range of vestibular organ impairment in diabetes mellitus type 1 seems to depend mainly on the presence and character of hypoglycaemic incidents and the duration of the disease and to some extent on the compensation of diabetes.

  10. [The implications of the automatic blood pressure monitoring (ABPM) in the type I diabetes].

    Science.gov (United States)

    Cobuz, C

    2009-01-01

    The connection between hypertension and diabetes emerges, in medical practice, from the current belief imposed by the European Society of Cardiology adding to the notion of total cardiovascular risk. An increse in the systolic blood pressure at night time is the first detectable manifestation of the regulation disorders of the blood pressure in type I diabetes. An early increase of the nocturnal blood pressure can play a key role in the detection of the evolution towards diabetic nephropathy. This modification can be a valuable potential marker for the diabetic nephropathy and could provide a reason for treating the high risk patients before the onset of microalbuminuria. The evaluation of the nefropathy risk in the early stages of type I diabetes using Ambulatory Blood Pressure Monitoring (ABPM) method offers the best premisses for preventing the progression of the disease towards microalbuminuria and hypertension.

  11. No association of the IRS1 and PAX4 genes with type I diabetes

    DEFF Research Database (Denmark)

    Bergholdt, R.; Brorsson, C.; Boehm, B.

    2009-01-01

    To reassess earlier suggested type I diabetes (T1D) associations of the insulin receptor substrate 1 (IRS1) and the paired domain 4 gene (PAX4) genes, the Type I Diabetes Genetics Consortium (T1DGC) evaluated single-nucleotide polymorphisms (SNPs) covering the two genomic regions. Sixteen SNPs we...... of tagging SNPs, more than one genotyping platform in high throughput studies, and sufficient power to draw solid conclusions in genetic studies of human complex diseases. Genes and Immunity (2009) 10, S49-S53; doi:10.1038/gene.2009.91 Udgivelsesdato: 2009/12...

  12. Is pancreas development abnormal in the non-obese diabetic mouse, a spontaneous model of type I diabetes?

    Directory of Open Access Journals (Sweden)

    F. Homo-Delarche

    2001-04-01

    Full Text Available Despite extensive genetic and immunological research, the complex etiology and pathogenesis of type I diabetes remains unresolved. During the last few years, our attention has been focused on factors such as abnormalities of islet function and/or microenvironment, that could interact with immune partners in the spontaneous model of the disease, the non-obese diabetic (NOD mouse. Intriguingly, the first anomalies that we noted in NOD mice, compared to control strains, are already present at birth and consist of 1 higher numbers of paradoxically hyperactive ß cells, assessed by in situ preproinsulin II expression; 2 high percentages of immature islets, representing islet neogenesis related to neonatal ß-cell hyperactivity and suggestive of in utero ß-cell stimulation; 3 elevated levels of some types of antigen-presenting cells and FasL+ cells, and 4 abnormalities of extracellular matrix (ECM protein expression. However, the colocalization in all control mouse strains studied of fibroblast-like cells (anti-TR-7 labeling, some ECM proteins (particularly, fibronectin and collagen I, antigen-presenting cells and a few FasL+ cells at the periphery of islets undergoing neogenesis suggests that remodeling phenomena that normally take place during postnatal pancreas development could be disturbed in NOD mice. These data show that from birth onwards there is an intricate relationship between endocrine and immune events in the NOD mouse. They also suggest that tissue-specific autoimmune reactions could arise from developmental phenomena taking place during fetal life in which ECM-immune cell interaction(s may play a key role.

  13. Salivary flow rate and xerostomia in patients with type I and II diabetes mellitus.

    Science.gov (United States)

    Hoseini, Amineh; Mirzapour, Ali; Bijani, Ali; Shirzad, Atena

    2017-09-01

    Diabetes mellitus is one of the most prevalent metabolic diseases, with complications such as decreased salivary flow rate and xerostomia. This study aimed to determine the salivary flow rate and xerostomia in type I and II diabetic patients in comparison with healthy controls. This case-control study was performed on diabetic patients of a private office in Babol, Iran, between May 2015 and October 2016. This study involved two study groups (type I and II diabetes, with 40 in each group) and two control groups (control I and II, with 35 in each group) which were age- and sex-matched with the related study groups. They were all selected through simple sampling. Unstimulated whole saliva was collected through Navazesh method and the salivary flow rate was measured (ml/min). Xerostomia was evaluated via Fox's test. Moreover, the patients' data were recorded including age, sex, disease duration, type of diabetes, fasting blood glucose (FBG) and HbA1C. The obtained data were statistically analyzed by using SPSS version 17. Independent-samples t-test, Chi-square, Pearson correlation and multiple comparison post-hoc tests were employed as appropriated. psalivary flow rate in type I diabetics (0.35±0.11 ml/min) was lower than that in control I (0.50±0.07 ml/min) (p=0.01). The same difference was observed between type II diabetics (0.37±0.13 ml/min) and control II groups (0.47±0.11 ml/min) (p=0.01). No significant difference was observed in the salivary flow rate between type I and II diabetics (p=0.345). Furthermore, xerostomia was higher in type I (2.70±2.50, 1.17±1.60) and II (2.65±2.20-1.62±1.50) diabetics compared with the related control groups (p=0.01), (p=0.02). Type I, II diabetic patients revealed lower salivary flow rate and higher xerostomia compared with healthy controls. The salivary flow rate and xerostomia had inverse correlation.

  14. Bauhinia variegata (Caesalpiniaceae) leaf extract: An effective treatment option in type I and type II diabetes.

    Science.gov (United States)

    Kulkarni, Yogesh A; Garud, Mayuresh S

    2016-10-01

    Among various metabolic disorders, diabetes mellitus is one of the most common disorder. Present study was designed to evaluate the effectiveness of aqueous extract of Bauhinia variegata leaves (AE) in animal models of type I and type II diabetes. Type I diabetes was induced by streptozotocin at the dose of 55mg/kg (i.p.) in male Sprague Dawley rats while type II diabetes was induced by high fat diet and streptozotocin at the dose of 35mg/kg (i.p.). Diabetic animals were treated with AE at the dose of 250, 500 and 1000mg/kg. Glipizide (5mg/kg) was used as standard treatment drug. Treatment was given for 28days. Parameters evaluated were body weight, plasma glucose, cholesterol, triglyceride, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, total proteins, albumin, creatinine and bun urea nitrogen. In type II diabetes, high density lipoprotein levels in plasma and plasma insulin level were also evaluated. Histopathological study of pancreases were carried out in type I study. AE showed significant decrease in plasma glucose significantly. AE was also found to decrease cholesterol, triglyceride, creatinine and blood urea nitrogen level in both types of diabetes. AE did not show any significant effect on plasma levels of aspartate aminotransferase, alanine transaminase, alkaline phosphatase. AE was found to increase the albumin and total protein levels. Histopathological study showed that AE decreases the necrotic changes in the pancreatic tissue. Aqueous extract of B. variegata leaves was found effective in treatment of both type I and type II diabetes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Nature of elevated blood pressure in normoalbuminuric type I diabetic patients. Essential hypertension?

    DEFF Research Database (Denmark)

    Nørgaard, K; Rasmussen, E; Jensen, T

    1993-01-01

    This study was undertaken to characterize type I diabetic patients with essential hypertension with respect to kidney function, renal hormones, and endothelial function. After 4 weeks without antihypertensive treatment, a cross-sectional study was carried out in the following groups: group 1, 14 ...

  16. [Incidence of childhood type I diabetes in Extremadura, Spain, 2003-2007].

    Science.gov (United States)

    Gimeno Benítez, A; Luengo Pérez, L M; Suero Villa, P; Suero Villa, S; Sánchez Vega, J

    2014-01-01

    Studies have shown an increasing incidence of type I diabetes in children in Europe over the last 20 years. The present study was conducted to evaluate the incidence and development of type I diabetes in children under 15 years of age in Extremadura in the period 2003-2007. The study applied the capture-recapture method using the national hospital discharge database as primary source. Data were collected from children under 15 years of age diagnosed with diabetes type I during the study period. Secondary data source were insulin prescriptions from the public health system. Rates were standardised and a Poisson regression was used to assess the development of the disease during the study period. The overall adjusted incidence rate was 25.2/100.000 (95%CI: 21.8-28.6) with 100% completeness; no significant differences were observed by sex or provinces. Age group rates were 20.2/100.000 (95%CI: 10.1-30.3) for aged 0-4 years, 24.8/100.000 (95%CI: 20.1-29.4) for aged 5-9 years, and 30.0/100.000 (95%CI: 25.8-34.1) for aged 10-14 years, with a RR of 1.67 (95%CI: 1.18-2.36; P=.004) for 10-14 year olds relative to 0-4 year olds. The number of cases among children aged 0-4 years increased from 5 cases in 2003 to 15 cases in 2006, although this increase was not significantly different. The overall rates of incidence of type I diabetes were higher than the expected incidence values in Extremadura. Careful surveillance is required to confirm the increased trend in the incidence of type I diabetes observed among children aged 0-4 years. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  17. [Coexistence of autoimmune polyglandular syndrome type 3 with diabetes insipidus].

    Science.gov (United States)

    Krysiak, Robert; Okopień, Bogusław

    2015-01-01

    Autoimmune polyglandular syndromes are conditions characterized by the combination of two or more organ-specific disorders. The underestimation oftheir real frequency probable results from physicians' inadequate knowledge of these clinical entities and sometimes their atypical clinical presentation. Because they comprise a wide spectrum of autoimmune disorders, autoimmune polyglandular syndromes are divided into four types, among which type-3 is the most common one. In this article, we report the case of a young female, initially diagnosed with diabetes mellitus who several years later developed full-blown autoimmune polyglandular syndrome type 3 consisting of autoimmune thyroid disorder and latent autoimmune diabetes in adults.The discussed case suggests that in selected patients diabetes insipidus may coexist with autoimmune endocrinopathies and nonendocrine autoimmunopathies, as well as that in some patients idiopathic diabetes insipidus may be secondary to lymphocytic infiltration and destruction of the hypothalamic supraoptic and paraventricular nuclei and/or the supraoptic-hypophyseal tract

  18. Effect of isocaloric substitution of chocolate cake for potato in type I diabetic patients.

    Science.gov (United States)

    Peters, A L; Davidson, M B; Eisenberg, K

    1990-08-01

    Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake-substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self-monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia.

  19. AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

    OpenAIRE

    N. V. Piven; L. N. Lukhverchyk; A. I. Burakovsky; N. V. Polegenkaya; M. V. Karpovich

    2011-01-01

    Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format) has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to g...

  20. Early evaluation of renal hemodynamic alterations in type I diabetes mellitus with duplex ultrasound

    Directory of Open Access Journals (Sweden)

    Saif Aasem

    2010-01-01

    Full Text Available To evaluate the role of renal duplex ultrasonography in the detection of early alte-ration of renal blood flow in type I diabetic patients, we studied with duplex ultrasound 32 patients with type I diabetes mellitus (19 males, 13 females, age range 8-19 years and 35 age and sex-matched controls. The resistivity indices (RIs and pulsatility indices (PIs of the main renal as well as intra-renal arteries were calculated. Compared with the healthy control subjects, diabetic patients had significantly higher resistivity indices (RIs in the intrarenal (segmental, arcuate and interlobar ar-teries (P= 0.001. The study, also revealed a significantly positive correlation between the RIs in the intrarenal arteries in diabetics and the albumin/creatinine ratio (r= 0.54, 0.52 and 0.51 respectively, glycated hemoglobin (r= 0.61, 0.59 and 0.63 respectively, as well as the estimated GFR (e-GFR (r= 0.53, 0.51 and 0.57 respectively. We conclude that the current study documented early intra-renal hemodynamic alterations in the form of pathologically elevated intrarenal RIs. This denotes the potential usefulness of duplex evaluation of the intrarenal arteries, as a noninvasive procedure, for monitoring type 1 diabetic patients to predict those at risk of diabetic nephropathy.

  1. The Intrauterine Device in Women with Diabetes Mellitus Type I and II: A Systematic Review.

    Science.gov (United States)

    Goldstuck, Norman D; Steyn, Petrus S

    2013-12-11

    Background. Women with diabetes mellitus type I and type II need effective contraception for personal and medical reasons. Long acting reversible contraceptive (LARC) methods are among the most efficient and cost-effective methods. Study Design. We searched the Popline, PubMed, and clinicaltrials.gov databases from 1961 to March 2013 for studies on the efficacy of the IUD in diabetic women and the possible changes it may produce in laboratory parameters. Studies of at least 30 subjects with DM1 or DM2 who were studied for 6 to 12 months depending on the method of analysis were eligible. Results. The search produced seven articles which gave event rate efficacy evaluable results and three which evaluated the effect of the IUD on laboratory parameters. One of the earlier efficacy studies showed an abnormally high pregnancy rate which sparked a controversy which is discussed in the Introduction section. The remaining 6 studies produced acceptable pregnancy rates. The three laboratory studies showed that the copper and levonorgestrel releasing IUD/IUS do not affect the diabetic state in any way. Conclusions. The copper bearing and levonorgestrel releasing IUDs are safe and effective in women with diabetes type I and diabetes type II although the evidence in the latter is limited.

  2. Bacterial Flora Changes in Conjunctiva of Rats with Streptozotocin-Induced Type I Diabetes.

    Science.gov (United States)

    Yang, Chao; Fei, Yuda; Qin, Yali; Luo, Dan; Yang, Shufei; Kou, Xinyun; Zi, Yingxin; Deng, Tingting; Jin, Ming

    2015-01-01

    The microbiota of both humans and animals plays an important role in their health and the development of disease. Therefore, the bacterial flora of the conjunctiva may also be associated with some diseases. However, there are no reports on the alteration of bacterial flora in conjunctiva of diabetic rats in the literature. Therefore, we investigated the changes in bacterial flora in bulbar conjunctiva of rats with streptozotocin (STZ)-induced type I diabetes. A high dose of STZ (60 mg/kg, i.p.) was injected into Sprague-Dawley (SD) rats to induce type I diabetes mellitus (T1DM). The diabetic rats were raised in the animal laboratory and at 8 months post-injection of STZ swab samples were taken from the bulbar conjunctiva for cultivation of aerobic bacteria. The bacterial isolates were identified by Gram staining and biochemical features. The identified bacteria from both diabetic and healthy rats were then compared. The diabetic and healthy rats had different bacterial flora present in their bulbar conjunctiva. In total, 10 and 8 bacterial species were found in the STZ and control groups, respectively, with only three species (Enterococcus faecium, Enterococcus gallinarum and Escherichia coli) shared between the two groups. Gram-positive bacteria were common in both groups and the most abundant was Enterococcus faecium. However, after the development of T1DM, the bacterial flora in the rat bulbar conjunctiva changed considerably, with a reduced complexity evident. STZ-induced diabetes caused alterations of bacterial flora in the bulbar conjunctiva in rats, with some bacterial species disappearing and others emerging. Our results indicate that the conjunctival bacterial flora in diabetic humans should be surveyed for potential diagnostic markers or countermeasures to prevent eye infections in T1DM patients.

  3. Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats.

    Science.gov (United States)

    Abdelhamid, Amir Mohamed; Abdelaziz, Rania Ramadan; Salem, Hatem Abdelrahman Ali

    2018-03-06

    Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA 1c . It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.

  4. Creatine Kinase Activity in Patients with Diabetes Mellitus Type I and Type II

    Directory of Open Access Journals (Sweden)

    Adlija Jevrić-Čaušević

    2006-08-01

    Full Text Available Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.

  5. AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    N. V. Piven

    2011-01-01

    Full Text Available Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to glutamic acid decarboxylase by means of ELISA approach. (Med. Immunol., 2011, vol. 13, N 2-3, pp 257-260

  6. Anaplastic Large-Cell Lymphoma in a Child with Type I Diabetes and Unrecognised Coeliac Disease

    Directory of Open Access Journals (Sweden)

    Jemima Sharp

    2012-01-01

    Full Text Available Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

  7. Urinary albumin excretion and 24-hour blood pressure as predictors of pre-eclampsia in Type I diabetes

    DEFF Research Database (Denmark)

    Ekbom, P; Damm, P; Nøgaard, K

    2000-01-01

    To evaluate the value of 24-h blood pressure monitoring compared to office blood pressure and urinary albumin excretion in predicting pre-eclampsia in Type I (insulin-dependent) diabetes mellitus.......To evaluate the value of 24-h blood pressure monitoring compared to office blood pressure and urinary albumin excretion in predicting pre-eclampsia in Type I (insulin-dependent) diabetes mellitus....

  8. Advanced Therapy Medicinal Products in type I diabetes mellitus: technological and regulatory challenges

    Directory of Open Access Journals (Sweden)

    Camila Leal-Lopes

    2018-02-01

    Full Text Available Introduction: Type 1 Diabetes mellitus (T1DM is an autoimmune disorder which arises from the destruction of insulin-producing pancreatic β-cells. Currently, Brazil’s advanced therapy medicinal products (ATMP, developed for clinical research and therapeutic purposes, take place in the so-called Cellular Technology Centers (CTC, according to the Resolution nº. 9/2011 of the Collegiate Board of Directors (RDC, enacted by the National Health Surveillance Agency (Anvisa. Objective: This study was conducted with the main objective of describing and discussing the development of ATMP for T1DM treatment. Method: A qualitative research, narrative review and critical discussion of the literature were under taken. Results: ATMP promote new therapeutic approaches for Diabetes, holding great potential to restore the patients’ endogenous insulin secretion, improving their life quality, overcoming the chronic complications of Diabetes and reducing the socioeconomic burden. Nowadays, ATMP in T1DM comprise: a cell therapy; b gene therapy products; c tissue engineering and d ATMPassociated to biopharmaceutical products. Conclusions: Further research should contribute to stimulate public and private organizations to effectively act towards reducing the impact of Diabetes on individuals and the society as a whole. It is essential that Brazilian legislation closely follows the biotechnological developments, supporting the scientific progress and benefiting T1DM patients with modern and cutting-edge therapies.

  9. Dendritic cells and anergic type I NKT cells play a crucial role in sulfatide-mediated immune regulation in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Maricic, Igor; Halder, Ramesh; Bischof, Felix; Kumar, Vipin

    2014-08-01

    CD1d-restricted NKT cells can be divided into two groups: type I NKT cells use a semi-invariant TCR, whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the CNS tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. In this article, we have addressed the mechanism of regulation, as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of myelin proteolipid proteins 139-151/I-A(s)-tetramer(+) cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells (DCs) in the periphery, as well as CNS-resident microglia, are inactivated after sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover, tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not α-galactosylceramide, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune-regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Because CD1 molecules are nonpolymorphic, the sulfatide-mediated immune-regulatory pathway can be targeted for development of non-HLA-dependent therapeutic approaches to T cell-mediated autoimmune diseases. Copyright © 2014 by The American Association of Immunologists, Inc.

  10. TREATMENT OF NEUROGENIC ERECTILE DYSFUNCTION IN PATIENTS WITH TYPE I DIABETES

    Directory of Open Access Journals (Sweden)

    D. G. Kurbatov

    2017-01-01

    Full Text Available Introduction. The urogenital form of autonomic diabetic polyneuropathy is a specific lesion of the autonomic nervous system in diabetic patients. It is main pathogenetic cause of sexual disorders in this category of patients. The most common violation of sexual function in patients with diabetes is erectile dysfunction (ED.Objective. Diagnosis of peripheral neuropathy with ED caused by type I diabetes and assessment of the effectiveness phosphodiesterase type 5 inhibitor (PDE5-I in its treatment.Materials and methods. The study included 40 patients with ED due to type 1 diabetes at the age of 25.7 ± 6.1. The duration of type 1 diabetes was 18 ± 9.7 years. All 40 patients, initially and after the course of therapy with the PDE5-Is, underwent a neuromyographic study with the determination of the excitation propagation rate for nervus peroneus and nervus pudendus, endothelial function evaluation on the EndoPat ™ device, and the questionnaire on the international index of erectile function (IIEF-5 scale.Results. In 30 (75.0% men, endothelial dysfunction was determined according to EndoPat ™. In the range of the gray zone of reactive hyperemia index (RHI was detected in 7 men (16.6%. Normal function of the endothelium was revealed in 3 cases (8.4%. In the control study, the following data were found: endothelial dysfunction was detected in 6 patients (16.6% according to Endo Pat ™, in 14 patients (33.4% in the range of gray zone of RHI, endothelial function was normalized in 20 patients (50.0%. According to the neuromyographic study, initially all patients had diabetic neuropathy in both the distal and urogenital forms. After therapy, significant positive dynamics were shown. Based on the results of the questionnaire on the scale of IIEF-5, initially all patients showed ED of varying severity. With the control questionnaire after therapy, there was an improvement in erectile function.Conclusions. Given the high incidence of endothelial

  11. Diabetic peripheral neuropathy, is it an autoimmune disease?

    Science.gov (United States)

    Janahi, Noor M; Santos, Derek; Blyth, Christine; Bakhiet, Moiz; Ellis, Mairghread

    2015-11-01

    Autoimmunity has been identified in a significant number of neuropathies, such as, proximal neuropathies, and autonomic neuropathies associated with diabetes mellitus. However, possible correlations between diabetic peripheral neuropathy and autoimmunity have not yet been fully investigated. This study was conducted to investigate whether autoimmunity is associated with the pathogenesis of human diabetic peripheral neuropathy. A case-control analysis included three groups: 30 patients with diabetic peripheral neuropathy, 30 diabetic control patients without neuropathy, and 30 healthy controls. Blood analysis was conducted to compare the percentages of positive antinuclear antibodies (ANA) between the three groups. Secondary analysis investigated the correlations between the presence of autoimmune antibodies and sample demographics and neurological manifestations. This research was considered as a pilot study encouraging further investigations to take place in the near future. Antinuclear antibodies were significantly present in the blood serum of patients with diabetic peripheral neuropathy in comparison to the control groups (pneuropathy group were 50 times higher when compared to control groups. Secondary analysis showed a significant correlation between the presence of ANA and the neurological manifestation of neuropathy (Neuropathy symptom score, Neuropathy disability score and Vibration Perception Threshold). The study demonstrated for the first time that human peripheral diabetic neuropathy may have an autoimmune aetiology. The new pathogenic factors may lead to the consideration of new management plans involving new therapeutic approaches and disease markers. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. A multidisciplinary guided practical on type I diabetes engaging students in inquiry-based learning.

    Science.gov (United States)

    Mingueneau, M; Chaix, A; Scotti, N; Chaix, J; Reynders, A; Hammond, C; Thimonier, J

    2015-12-01

    In the present article, we describe a 3-day experimental workshop on type I diabetes aimed at helping high school students to understand how fundamental research on glycemia regulation contributes to the development of scientific knowledge and therapeutic strategies. The workshop engaged students in open-ended investigations and guided experiments. Each class was divided into three or four groups, with each group working with a trained doctoral student or postdoctoral fellow. During an initial questioning phase, students observed slides depicting the glycemia of individuals in various situations. Students identified hyperglycemic individuals relative to the average glycemia of the displayed population. Students were asked to devise a treatment for these diabetics. They quickly realized that they couldn't experiment on patients and understood the need for laboratory models. Each group gave ideas of experiments to perform. We then explained, taking into account their propositions, the protocols students could execute to address one of the following questions: Which criteria must an animal model of diabetes fulfill? How do pancreatic cells maintain glycemia? Is there a way to produce an insulin protein similar to the one released by human pancreatic cells? We used two different evaluation metrics of the workshop: a questionnaire filled out by the students before and after the workshop and a poster produced by students at the end of the workshop. We found that this educational approach successfully improved student awareness and understanding of the scientific reasoning and research process. Copyright © 2015 The American Physiological Society.

  13. Speech perception performance of subjects with type I diabetes mellitus in noise

    Directory of Open Access Journals (Sweden)

    Bárbara Cristiane Sordi Silva

    Full Text Available Abstract Introduction: Diabetes mellitus (DM is a chronic metabolic disorder of various origins that occurs when the pancreas fails to produce insulin in sufficient quantities or when the organism fails to respond to this hormone in an efficient manner. Objective: To evaluate the speech recognition in subjects with type I diabetes mellitus (DMI in quiet and in competitive noise. Methods: It was a descriptive, observational and cross-section study. We included 40 participants of both genders aged 18-30 years, divided into a control group (CG of 20 healthy subjects with no complaints or auditory changes, paired for age and gender with the study group, consisting of 20 subjects with a diagnosis of DMI. First, we applied basic audiological evaluations (pure tone audiometry, speech audiometry and immittance audiometry for all subjects; after these evaluations, we applied Sentence Recognition Threshold in Quiet (SRTQ and Sentence Recognition Threshold in Noise (SRTN in free field, using the List of Sentences in Portuguese test. Results: All subjects showed normal bilateral pure tone threshold, compatible speech audiometry and "A" tympanometry curve. Group comparison revealed a statistically significant difference for SRTQ (p = 0.0001, SRTN (p < 0.0001 and the signal-to-noise ratio (p < 0.0001. Conclusion: The performance of DMI subjects in SRTQ and SRTN was worse compared to the subjects without diabetes.

  14. Accelerated progression from islet autoimmunity to diabetes is causing the escalating incidence of type 1 diabetes in young children

    OpenAIRE

    Ziegler, Anette-G.; Pflueger, Maren; Winkler, Christiane; Achenbach, Peter; Akolkar, Beena; Krischer, Jeffrey P.; Bonifacio, Ezio

    2011-01-01

    The incidence of type 1 diabetes is rising worldwide, particularly in young children. Since type 1 diabetes is preceded by autoimmunity to islet antigens, there must be a consequent increase in the incidence of islet autoimmunity in young children or a more rapid rate of progression to diabetes once islet autoimmunity initiates. This study was to determine whether the incidence of islet autoimmunity or the rate of progression from autoimmunity to diabetes onset has changed over a 20-year peri...

  15. Continuous Glucose Monitoring Can Uncover Mistakes in Self-Treatment of Hypoglycemia in Patients with Type I Diabetes Mellitus

    Czech Academy of Sciences Publication Activity Database

    Brož, J.; Urbanová, J.; Janíčková Žďárská, D.; Doničová, V.; Brabec, Marek

    2014-01-01

    Roč. 63, Supplement 1 (2014), A221-A221 ISSN 0012-1797. [American Diabetes Association. Scientific Sessions /74./. 13.06.2014-17.06.2014, San Francisco] Institutional support: RVO:67985807 Keywords : continuous monitoring * type I diabetes * semiparametric modeling Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  16. Continuous Glucose Monitoring Can Uncover Mistakes in Self-Treatment of Hypoglycemia in Patients with Type I Diabetes Mellitus

    Czech Academy of Sciences Publication Activity Database

    Brož, J.; Urbanová, J.; Janíčková Žďárská, D.; Doničová, V.; Brabec, Marek

    2014-01-01

    Roč. 16, Supplement 1 (2014), A35-A35 ISSN 1520-9156. [American Diabetes Association. Scientific Sessions /74./. 13.06.2014-17.06.2014, San Francisco] Institutional support: RVO:67985807 Keywords : continuous monitoring * type I diabetes * semiparametric modeling Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition

  17. Is childhood-onset type I diabetes a wealth-related disease?

    DEFF Research Database (Denmark)

    Patterson, C.C.; Dahlquist, G.; Soltész, G.

    2001-01-01

    AIMS/HYPOTHESIS: To describe the epidemiology of childhood-onset Type I (insulin-dependent) diabetes mellitus in Europe, the EURODIAB collaborative group established prospective, geographically-defined registers of children diagnosed under 15 years of age. A total of 16,362 cases were registered...... by the capture-recapture method. Ecological correlation and regression analyses were used to study the relationship between incidence and various environmental, health and economic indicators. RESULTS: The standardised average annual incidence rate during the period 1989-94 ranged from 3.2 cases per 100......,000 person-years in the Former Yugoslavian Republic of Macedonia to 40.2 cases per 100,000 person-years in Finland. Indicators of national prosperity such as infant mortality (r = -0.64) and gross domestic product (r = 0.58) were most strongly and significantly correlated with incidence rate and previously...

  18. The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors.

    Science.gov (United States)

    Tüzün, Ali; Keskin, Onur; Yakut, Mustafa; Kalkan, Cagdas; Soykan, Irfan

    2014-01-01

    Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

  19. [Comparison of the effect of continuous and intermittent physical loading in type I diabetics].

    Science.gov (United States)

    Rusavý, Z; Lacigová, S; Holecek, T; Srámek, V; Novák, I; Tĕsínský, P

    1994-07-01

    In order to evaluate the optimal mode of physical loads the authors examined 19 diabetics type I without secondary complications. On the second day of an educational-rehabilitation camp the authors subjected the patients to a continuous load-a 40-minute endurance run at a heart rate equal to 60% of the maximal oxygen requirement. On the fifth day an intermittent load with a maximal intensity--training of 4 x 10 minutes with 5-minute intervals was administered. At the onset, during the 20th and 40th minute of the load the titrable acidity, lactate and blood sugar level were assessed. The intermittent load led already after 20 minutes to marked acidosis (titrable acidity = 12) which did not increase after 40 minutes of the load. The authors recorded a statistically significant rise of the lactate level (4.57 mmol/l) which after 40 minutes of the load rose further to 12.3 mmol/l, as compared with values of titrable acidity during the 20th and 40th minute (0.44 and 1.14) and lactate during the 20th and 40th minute (4.57 and 3.86 mmol/l) during a continuous load. After evaluation by the test of linear correlation it appears with regard to the stability of the blood sugar level during a load that an intermittent load is more favourable. The drop of the blood sugar level in time during a continuous load was at the 1 level of significance, in intermittent loads at the 5% of significance. Both types of loads did not lead to hypoglycaemia or other complications and thus both can be used in diabetics type I.

  20. Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes

    Directory of Open Access Journals (Sweden)

    Shih-Chang Chien

    2015-01-01

    Full Text Available Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, anti-inflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes.

  1. Induction of endogenous Type I interferon within the central nervous system plays a protective role in experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Mørch, Marlene Thorsen; Holm, Thomas Hellesøe

    2015-01-01

    show elevated levels of Type I IFNs in the central nervous system (CNS), suggesting a role for endogenous Type I IFN during inflammation. However, the therapeutic benefit of Type I IFN produced in the CNS remains to be established. The aim of this study was to examine whether experimentally induced CNS......-endogenous Type I IFN influences EAE. Using IFN-β reporter mice, we showed that direct administration of polyinosinic-polycytidylic acid (poly I:C), a potent inducer of IFN-β, into the cerebrospinal fluid induced increased leukocyte numbers and transient upregulation of IFN-β in CD45/CD11b-positive cells located...... in the meninges and choroid plexus, as well as enhanced IFN-β expression by parenchymal microglial cells. Intrathecal injection of poly I:C to mice showing first symptoms of EAE substantially increased the normal disease-associated expression of IFN-α, IFN-β, interferon regulatory factor-7 and IL-10 in CNS...

  2. Type 1 diabetes and polyglandular autoimmune syndrome: A review

    Science.gov (United States)

    Hansen, Martin P; Matheis, Nina; Kahaly, George J

    2015-01-01

    Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279

  3. Metabolic effects of dietary fructose and surcose in types I and II diabetic subjects

    International Nuclear Information System (INIS)

    Bantle, J.P.; Laine, D.C.; Thomas, J.W.

    1986-01-01

    To learn more about the metabolic effects of dietary fructose and sucrose, 12 type 1 and 12 type II diabetic subjects were fed three isocaloric (or isoenergic) diets for eight days each according to a randomized, crossover design. The three diets provided, respectively, 21% of the energy as fructose, 23% of the energy as sucrose, and almost all carbohydrate energy as starch. The fructose diet resulted in significantly lower one- and two-hour postprandial plasma glucose levels, overall mean plasma glucose levels, and urinary glucose excretion in both type I and type II subjects than did the starch diet. There were no significant differences between the sucrose and starch diets in any of the measures of glycemic control in either subject group. The fructose and sucrose diets did not significantly increase serum triglyceride values when compared with the starch diet, but both increased postprandial serum lactate levels. The authors conclude that short-term replacement of other carbohydrate sources in the diabetic diet with fructose will improve glycemic control, whereas replacement with sucrose will not aggravate glycemic control

  4. Serum adiponectin predicts all-cause mortality and end stage renal disease in patients with type I diabetes and diabetic nephropathy

    DEFF Research Database (Denmark)

    Jorsal, A.; Tarnow, L.; Frystyk, J.

    2008-01-01

    Adiponectin levels are increased in patients with type I diabetes especially in the presence of microangiopathy. Here we determined the predictive value of serum adiponectin levels and 8 adiponectin gene polymorphisms for mortality, cardiovascular events and end-stage renal disease in type I...... diabetic patients. This prospective, observational follow-up study of type I diabetics consisted of 438 patients with overt diabetic nephropathy that were compared to 440 type I patients with normal albumin excretion. These two groups were followed an average of 8 years and generally matched for gender......, age and duration of diabetes. Cox regression analysis of 373 patients showed a covariate-adjusted hazard ratio for all-cause mortality of 1.46 for a change of one standard deviation in log10 of serum adiponectin. There was no association with cardiovascular events; however, serum adiponectin levels...

  5. Type 1 diabetes : The autoimmune process and islet transplantation

    OpenAIRE

    Jacobson, Stella

    2010-01-01

    Type 1 diabetes (T1D) is an autoimmune disease characterized by the selective loss of the insulin-producing β-cells residing in the islets of Langerhans in the pancreas. Cytokines are involved in diabetes development in the nonobese diabetic (NOD) mouse model. NOD mice over-expressing the suppressor of cytokine signaling (SOCS-1) specifically in the β-cells are protected from T1D. Previous studies showed that immune cells infiltrated the pancreas of SOCS-1-transgenic (tg)...

  6. An investigation into the effect of type I and type II diabetes duration on employment and wages.

    Science.gov (United States)

    Minor, Travis

    2013-12-01

    Using data from the National Longitudinal Survey of Youth 1979, the current study examines the effect of type I and type II diabetes on employment status and wages. The results suggest that both the probability of employment and wages are negatively related to the number of years since the initial diagnosis of diabetes. Moreover, the effect of diabetes duration on the probability of employment appears to be nonlinear, peaking around 16 years for females and 10 years for males. A similar negative effect on wages is found only in male diabetics. Finally, the results suggest that failure to distinguish between type I and type II diabetics may lead to some counterintuitive results. Published by Elsevier B.V.

  7. Humanized in vivo Model for Autoimmune Diabetes

    National Research Council Canada - National Science Library

    Nepom, Gerald T; Gebe, John A

    2008-01-01

    The CD4+ T cell response is critical for cellular autoimmunity in human T1D, but incomplete understanding of issues of specific cell frequency, avidity, function, and correlation with disease status presents...

  8. Linkage of the VNTR/insulin-gene and type I diabetes mellitus: Increased gene sharing in affected sibling pairs

    Energy Technology Data Exchange (ETDEWEB)

    Owerbach, D.; Gabbay, K.H. (Baylor College of Medicine, Houston, TX (United States))

    1994-05-01

    Ninety-six multiplex type I diabetic families were typed at the 5' flanking region of the insulin gene by using a PCR assay that better resolves the VNTR into multiple alleles. Affected sibling pairs shared 2, 1, and 0 VNTR alleles - identical by descent - at a frequency of .47, .45, and .08, respectively, a ratio that deviated from the expected 1:2:1 ratio (P<.001). These results confirm linkage of the chromosome 11p15.5 region with type I diabetes mellitus susceptibility. 20 refs., 2 tabs.

  9. Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes

    International Nuclear Information System (INIS)

    Yang Zandong; Chen Meng; Carter, Jeffrey D.; Nunemaker, Craig S.; Garmey, James C.; Kimble, Sarah D.; Nadler, Jerry L.

    2006-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete pancreatic β-cell destruction. New evidence suggests that β-cell regeneration is possible, but ongoing autoimmune damage prevents restoration of β-cell mass. We tested the hypothesis that simultaneously blocking autoimmune cytokine damage and supplying a growth-promoting stimulus for β-cells would provide a novel approach to reverse T1DM. Therefore, in this study we combined lisofylline to suppress autoimmunity and exendin-4 to enhance β-cell proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic (NOD) mouse model. We found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal. The therapeutic effect of this regimen was associated with improved β-cell metabolism and insulin secretion, while reducing β-cell apoptosis. It is possible that such combined therapy could become a new strategy to defeat T1DM in humans

  10. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.

    Directory of Open Access Journals (Sweden)

    Zhiyuan Zhao

    Full Text Available The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA amongst patients with type 1 diabetes (T1D and autoimmune thyroid disease (AITD in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v. The study also included 145 patients with type 2 diabetes (T2D, 97 patients with non-autoimmune thyroid disease (NAITD, and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001 or NAITD (3.1%; P < 0.0001 or healthy controls (1%; p<0.0001. The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040 or with AITD alone (p = 0.017. T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients.

  11. The Educational Implications of Type I Diabetes Mellitus: A Review of Research and Recommendations for School Psychological Practice

    Science.gov (United States)

    Kucera, Miranda; Sullivan, Amanda L.

    2011-01-01

    Type I diabetes mellitus (T1DM) is one of the most common chronic illnesses in children and youth, with many affected students requiring individualized services and supports within educational settings. This article systematically reviews the research regarding the implications of this illness for students' cognitive and academic functioning to…

  12. Urine albumin is a superior predictor of preeclampsia compared to urine plasminogen in type I diabetes patients

    DEFF Research Database (Denmark)

    Nielsen, Lise Hald; Jensen, Boye L; Fuglsang, Jens

    2018-01-01

    Pregnant women with type I diabetes mellitus (T1DM) are at increased risk of developing preeclampsia (PE). Plasminogen is aberrantly filtrated from plasma into tubular fluid in PE patients and activated to plasmin. Plasmin activates the epithelial sodium channel in the collecting ducts potentially...

  13. Type I Diabetic Akita Mouse Model is Characterized by Abnormal Cardiac Deformation During Early Stages of Diabetic Cardiomyopathy with Speckle-Tracking Based Strain Imaging.

    Science.gov (United States)

    Zhou, Yingchao; Xiao, Hong; Wu, Jianfei; Zha, Lingfeng; Zhou, Mengchen; Li, Qianqian; Wang, Mengru; Shi, Shumei; Li, Yanze; Lyu, Liangkun; Wang, Qing; Tu, Xin; Lu, Qiulun

    2018-01-01

    Diabetes mellitus (DM) has been demonstrated to have a strong association with heart failure. Conventional echocardiographic analysis cannot sensitively monitor cardiac dysfunction in type I diabetic Akita hearts, but the phenotype of heart failure is observed in molecular levels during the early stages. Male Akita (Ins2WT/C96Y) mice were monitored with echocardiographic imaging at various ages, and then with conventional echocardiographic analysis and speckle-tracking based strain analyses. With speckle-tracking based strain analyses, diabetic Akita mice showed changes in average global radial strain at the age of 12 weeks, as well as decreased longitudinal strain. These changes occurred in the early stage and remained throughout the progression of diabetic cardiomyopathy in Akita mice. Speckle-tracking showed that the detailed and precise changes of cardiac deformation in the progression of diabetic cardiomyopathy in the genetic type I diabetic Akita mice were uncoupled. We monitored early-stage changes in the heart of diabetic Akita mice. We utilize this technique to elucidate the underlying mechanism for heart failure in Akita genetic type I diabetic mice. It will further advance the assessment of cardiac abnormalities, as well as the discovery of new drug treatments using Akita genetic type I diabetic mice. © 2018 The Author(s). Published by S. Karger AG, Basel.

  14. Autoimmune Hypoglycemia in Type 1 Diabetes Mellitus.

    Science.gov (United States)

    Ambigapathy, Jayakumar; Sahoo, Jayaprakash; Kamalanathan, Sadishkumar

    2017-07-15

    Antibodies against exogenous insulin are common in type 1 diabetes mellitus patients. They can cause hypoglycemia, albeit uncommonly. A 14-year-old girl with type 1 diabetes mellitus presented with recurrent hypoglycemia. High insulin, low C-peptide and raised insulin antibody levels documented during hypoglycemia. Plasmapheresis led to remission of hypoglycemia. Antibodies to exogenous insulin should be considered as a cause of recurrent refractory hypoglycemia in type 1 diabetes mellitus patients.

  15. HLA non-class II genes may confer type I diabetes susceptibility in a Mapuche (Amerindian) affected family.

    Science.gov (United States)

    Pérez-Bravo, Francisco; Martinez-Laso, Jorge; Martin-Villa, Jose M; Moscoso, Juan; Moreno, Almudena; Serrano-Vela, Juan I; Zamora, Jorge; Asenjo, Silvia; Gleisner, Andrea; Arnaiz-Villena, Antonio

    2006-01-01

    A rare case of type I diabetes is studied in an Amerindian (Mapuche) family from Chile, analyzing glutamic acid decarboxylase, islet-cell autoantibodies and human leukocyte antigen (HLA) genes. The affected sib is the only one that has one specific HLA haplotype combination that differs from the other sibs only in the HLA class I genes. It is concluded that HLA diabetes susceptibility factors may be placed outside the class II region or even that susceptibility factors do not exist in the HLA region in this Amerindian family.

  16. Gastrointestinal motor mechanisms in hyperglycaemia induced delayed gastric emptying in type I diabetes mellitus

    NARCIS (Netherlands)

    Samsom, M.; Akkermans, L. M.; Jebbink, R. J.; van Isselt, H.; vanBerge-Henegouwen, G. P.; Smout, A. J.

    1997-01-01

    BACKGROUND: Hyperglycaemia delays gastric emptying, both in healthy controls and in patients with diabetes mellitus. The effect of hyperglycaemia on antroduodenal motility in diabetes has not yet been studied. AIM: To investigate the gastrointestinal motor mechanisms involved in the hyperglycaemia

  17. Predictive Control of the Blood Glucose Level in Type I Diabetic Patient Using Delay Differential Equation Wang Model.

    Science.gov (United States)

    Esna-Ashari, Mojgan; Zekri, Maryam; Askari, Masood; Khalili, Noushin

    2017-01-01

    Because of increasing risk of diabetes, the measurement along with control of blood sugar has been of great importance in recent decades. In type I diabetes, because of the lack of insulin secretion, the cells cannot absorb glucose leading to low level of glucose. To control blood glucose (BG), the insulin must be injected to the body. This paper proposes a method for BG level regulation in type I diabetes. The control strategy is based on nonlinear model predictive control. The aim of the proposed controller optimized with genetics algorithms is to measure BG level each time and predict it for the next time interval. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. Consequently, this method can decrease the risk of hypoglycemia, a lethal phenomenon in regulating BG level in diabetes caused by a low BG level. Two delay differential equation models, namely Wang model and Enhanced Wang model, are applied as controller model and plant, respectively. The simulation results exhibit an acceptable performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. As a result, if the nutrition of the person decreases instantly, the hypoglycemia will not happen. Furthermore, comparing this method with other works, it was shown that the new method outperforms previous studies.

  18. Transplante de células-tronco hematopoéticas no diabete melito do tipo I Autologous hematopoietic stem cell transplantation in type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Júlio C. Voltarelli

    2004-03-01

    on the course of type I insulin-dependent diabetes mellitus (DM-I, we started in December 2003 a clinical protocol of AHSCT for this disease, in cooperation with the Northwestern University, Chicago, University of Miami and the National Institutes of Health. Under 35-year-old patients with <6 weeks from diagnosis or at the asymptomatic phase ("honey moon" of the disease have their hematopoietic stem cells mobilized with cyclophosphamide (2 g/m² and G-CSF, collected from peripheral blood collected and cryopreserved. After conditioning with cyclophosphamide (200 mg/kg and rabbit anti-thymocyte globulin (4.5 mg/kg and infusion of AHSC, the patients are followed for 5 years in regards to clinical, endocrinological and immunological aspects of the disease. This clinical study may represent an important contribution of the Brazilian bone marrow transplantation community to the modern era of cell therapy for inflammatory and degenerative diseases.

  19. A novel cell-based assay for measuring neutralizing autoantibodies against type I interferons in patients with autoimmune polyendocrine syndrome type 1.

    Science.gov (United States)

    Breivik, Lars; Oftedal, Bergithe E V; Bøe Wolff, Anette S; Bratland, Eirik; Orlova, Elizaveta M; Husebye, Eystein S

    2014-07-01

    An important characteristic of autoimmune polyendocrine syndrome type 1 (APS 1) is the existence of neutralizing autoantibodies (nAbs) against the type I interferons (IFN) -α2 and -ω at frequencies close to 100%. Type 1 IFN autoantibodies are detected by antiviral neutralizing assays (AVA), binding assays with radiolabelled antigens (RLBA), enzyme-linked immunosorbent assay (ELISA), or by reporter-based cell assays. We here present a simple and reliable version of the latter utilizing a commercially available cell line (HEK-Blue IFN-α/β). All 67 APS 1 patients were positive for IFN-ω nAbs, while 90% were positive for IFN-α2 nAbs, a 100% and 96% correlation with RLBA, respectively. All blood donors and non-APS 1 patients were negative. The dilution titer required to reduce the effect of IFN-ω nAbs correlated with the RLBA index. This cell-based autoantibody assay (CBAA) is easy to perform, suitable for high throughput, while providing high specificity and sensitivity. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Ceramide content is higher in type I compared to type II fibers in obesity and type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Kristensen, Ditte Bech; Prats Gavalda, Clara; Larsen, Steen

    2012-01-01

    This study investigated fiber-type-specific muscle ceramide content in obese subjects and type 2 diabetes patients. Two substudies, one which compared type 2 diabetes patients to both lean- and obese BMI-matched subjects and the other study which compared lean body-matched post-obese, obese......, and control subjects, were performed. A fasting blood sample was obtained and plasma insulin and glucose determined. A muscle biopsy was obtained from deltoideus and vastus lateralis, and fiber-type ceramide content was determined by fluorescence immunohistochemistry. Insulin sensitivity estimated by Quicki...... index was higher in lean compared to type 2 diabetes patients and obese controls. Also in control and post-obese subjects, a higher insulin sensitivity was observed compared to obese subjects. Ceramide content was consistently higher in type I than in type II muscle fibers and higher in deltoideus than...

  1. Preclinical carotid atherosclerosis in patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes and classical type 1 diabetes

    OpenAIRE

    Hern?ndez, Marta; L?pez, Carolina; Real, Jordi; Valls, Joan; Ortega-Martinez de Victoria, Emilio; V?zquez, Federico; Rubinat, Esther; Granado-Casas, Minerva; Alonso, Nuria; Mol?, Teresa; Betriu, Angels; Lecube, Albert; Fern?ndez, Elvira; Leslie, Richard David; Mauricio, D?dac

    2017-01-01

    BACKGROUND LADA is probably the most prevalent form of autoimmune diabetes. Nevertheless, there are few data about cardiovascular disease in this group of patients. The aim of this study was to investigate the frequency of carotid atherosclerotic plaques in patients with LADA as compared with patients with classic type 1 diabetes and type 2 diabetes. METHODS Patients with LADA were matched for age and gender in different proportions to patients with type 2 diabetes, and classic type 1 diabete...

  2. The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus

    NARCIS (Netherlands)

    van Deutekom, A.W.; Heine, R.J.; Simsek, S.

    2008-01-01

    Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their

  3. Periodontal disease and type I diabetes mellitus: Associations with glycemic control and complications

    Directory of Open Access Journals (Sweden)

    Ajita Meenawat

    2013-01-01

    Full Text Available Objective: The aim of the study was to evaluate periodontal health status in patients diagnosed with type 1 diabetes mellitus (DM1 and to establish a correlation between metabolic control and periodontal health status. Materials and Methods: Periodontal health parameters namely plaque index (PI, gingival index (GI, probing pocket depth (PPD and clinical attachment loss (CAL were recorded in 28 patients diagnosed with type 1 diabetes mellitus (DM1 and 20 healthy controls. Diabetes history was recorded based on the information provided by the physician and it included date of diagnosis, duration, age of diagnosis, latest values of glycosylated haemoglobin and existing diabetic complications. Statistical analysis was performed to evaluate the relationship between periodontal parameters and degree of metabolic control, the duration of the disease and the appearance of complications. Results: The periodontal health in the diabetic group was compromised and they had greater bleeding index (P < 0.001, probing pocket depth (P < 0.001 and clinical attachment level (P = 0.001. Patients diagnosed for diabetes for shorter duration of time (4-7 years showed bleeding index-disease severity correlation to be 1.760 ΁ 0.434. Conclusion: Periodontal disease was more evident in type 1 diabetes mellitus patients and periodontal inflammation is greatly increased in subjects with longer disease course, poor metabolic control and diabetic complications.

  4. Bouncing forward: families living with a type I diabetic child | Brown ...

    African Journals Online (AJOL)

    ... Despite the multitude of challenges that families living with a child with diabetes face, they have been found to adapt to such an extent that diabetes is viewed as a manageable condition. This study was concerned with the factors that enable these families to adapt. The internationally acclaimed Resiliency Model of Stress, ...

  5. Prevalence of Dental Caries among Type I Diabetic children in Sudan

    African Journals Online (AJOL)

    Background: Diabetes mellitus is one of the most common chronic diseases in the general population. Dental caries is the most prevalent disease affecting the human race. The relation between diabetes mellitus and dental caries is in the ingestion of carbohydrates. The main objective of this study is to determine the ...

  6. Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

    Directory of Open Access Journals (Sweden)

    Ojaimi Caroline

    2010-08-01

    Full Text Available Abstract Background The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM have not been defined completely. We have shown in conscious dogs with DM that: 1 baseline coronary blood flow (CBF was significantly decreased, 2 endothelium-dependent (ACh coronary vasodilation was impaired, and 3 reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes. Methods Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4. Results The array data revealed that 797 genes were differentially expressed (P 2+ cycling genes (ryanodine receptor; SERCA2 Calcium ATPase, structural proteins (actin alpha. Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase, which were markedly down regulated. Conclusion our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.

  7. Substantiation for Approaches to Treatment of Latent Autoimmune Diabetes in Adults

    Directory of Open Access Journals (Sweden)

    T.M. Tykhonova

    2014-10-01

    Conclusions. Analysis of carbohydrate metabolism on the manifestation stage and over time development of latent autoimmune diabetes in adults as well as reduction of β-cells insulin-producing function associated with autoimmune insulitis and progressing while the development of this form of disease, substantiate the rational for insulin administration as this form of diabetes has been diagnosed. If patients with latent autoimmune diabetes in adults have metabolic syndrome clusters it is quite reasonable to add metformin to insulin.

  8. [Type I diabetes mellitus in children less than 5 years: case study conducted at the university clinics of Lubumbashi and review of the literature].

    Science.gov (United States)

    Omoy, Maguy Ngongo; Ngoy, Didier Munganga; Ilunga, Eric Kasamba; Ntumba, DonDieu Bafwafwa; Wakamb, Gray Kanteng A; Okitosho, Stanis Wembonyama; Numbi, Oscar Luboya

    2017-01-01

    Worldwide trends in type I diabetes mellitus (T1DM) are changing. It is increasingly affecting children of less than 5 years. The smaller the child, the greater the complexity of patient management. A delay in diagnosis or poor treatment can cause sudden death due to acute severe complications. It would be worth looking at this, raising public awareness, adapting our healthcare system to face this epidemic of noncommunicable diseases in Africa and establishing registers to analyze the epidemiological characteristics of type I diabetes mellitus in our environment. The aim of our study was to highlight the seriousness of type I diabetes mellitus occurrence at an early stage in children in our environment.

  9. Mitochondrial dysfunction and apoptosis in cumulus cells of type I diabetic mice.

    Directory of Open Access Journals (Sweden)

    Qiang Wang

    2010-12-01

    Full Text Available Impaired oocyte quality has been demonstrated in diabetic mice; however, the potential pathways by which maternal diabetes exerts its effects on the oocyte are poorly understood. Cumulus cells are in direct contact with the oocyte via gap junctions and provide essential nutrients to support oocyte development. In this study, we investigated the effects of maternal diabetes on the mitochondrial status in cumulus cells. We found an increased frequency of fragmented mitochondria, a decreased transmembrane potential and an aggregated distribution of mitochondria in cumulus cells from diabetic mice. Furthermore, while mitochondrial biogenesis in cumulus cells was induced by maternal diabetes, their metabolic function was disrupted as evidenced by lower ATP and citrate levels. Moreover, we present evidence suggesting that the mitochondrial impairments induced by maternal diabetes, at least in part, lead to cumulus cell apoptosis through the release of cytochrome c. Together the deleterious effects on cumulus cells may disrupt trophic and signaling interactions with the oocyte, contributing to oocyte incompetence and thus poor pregnancy outcomes in diabetic females.

  10. Is autoimmune thyroid dysfunction a risk factor for gestational diabetes?

    Science.gov (United States)

    Pascual Corrales, Eider; Andrada, Patricia; Aubá, María; Ruiz Zambrana, Alvaro; Guillén Grima, Francisco; Salvador, Javier; Escalada, Javier; Galofré, Juan C

    2014-01-01

    Some recent studies have related autoimmune thyroid dysfunction and gestational diabetes (GD). The common factor for both conditions could be the existence of pro-inflammatory homeostasis. The study objective was therefore to assess whether the presence of antithyroid antibodies is related to the occurrence of GD. Fifty-six pregnant women with serum TSH levels ≥ 2.5 mU/mL during the first trimester were retrospectively studied. Antithyroid antibodies were measured, and an O'Sullivan test was performed. GD was diagnosed based on the criteria of the Spanish Group on Diabetes and Pregnancy. Positive antithyroid antibodies were found in 21 (37.50%) women. GD was diagnosed in 15 patients, 6 of whom (10.71%) had positive antibodies, while 9 (16.07%) had negative antibodies. Data were analyzed using exact logistic regression by LogXact-8 Cytel; no statistically significant differences were found between GD patients with positive and negative autoimmunity (OR = 1.15 [95%CI = 0.28-4.51]; P=1.00). The presence of thyroid autoimmunity in women with TSH above the recommended values at the beginning of pregnancy is not associated to development of GD. However, GD prevalence was higher in these patients as compared to the Spanish general population, suggesting the need for closer monitoring in pregnant women with TSH levels ≥ 2.5 mU/mL. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  11. Engineering a Clinically Translatable Bioartificial Pancreas to Treat Type I Diabetes

    NARCIS (Netherlands)

    Orive, Gorka; Emerich, Dwaine; Khademhosseini, Ali; Matsumoto, Shinichi; Hernandez, R. M.; Pedraz, J. L.; Desai, Tejal; Calafiore, Riccardo; de Vos, Paul

    Encapsulating, or immunoisolating, insulin-secreting cells within implantable, semipermeable membranes is an emerging treatment for type 1 diabetes. This approach can eliminate the need for immunosuppressive drug treatments to prevent transplant rejection and overcome the shortage of donor tissues

  12. Gastric myoelectrical activity in patients with type I diabetes mellitus and autonomic neuropathy

    NARCIS (Netherlands)

    Jebbink, H. J.; Bruijs, P. P.; Bravenboer, B.; Akkermans, L. M.; vanBerge-Henegouwen, G. P.; Smout, A. J.

    1994-01-01

    In patients with diabetes mellitus and gastroparesis, dysrhythmias of gastric myoelectrical activity, especially tachygastrias, are thought to be involved in the pathogenesis of dyspeptic symptoms. Using surface electrogastrography we studied the prevalence of these abnormalities, and their

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

    Directory of Open Access Journals (Sweden)

    Eduardo L. Nolasco

    2015-07-01

    Full Text Available 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-1β, 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-1β, 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

  14. The Effects of Long-Term Experimental Diabetes Mellitus Type I on Skeletal Muscle Regeneration Capacity

    OpenAIRE

    Jerković, Romana; Bosnar, Alan; Jurišić-Eržen, Dubravka; Ažman, Josip; Starčević-Klasan, Gordana; Peharec, Stanislav; Čoklo, Miran

    2009-01-01

    Muscle fibers are dynamic structures capable of altering their phenotype under various pathological conditions. The aim of the present study was to investigate the influence of long-lasting diabetes mellitus on the process of muscle regeneration in the skeletal muscle. Wistar rats were made diabetic by a single intraperitoneal injection of streptozotocin (STZ). The regeneration process in the skeletal muscle was induced in slow (m. soleus, SOL) and fast (m. extensor digitorum longus, EDL) mus...

  15. Maternal parenting style and adjustment in adolescents with type I diabetes.

    Science.gov (United States)

    Butler, Jorie M; Skinner, Michelle; Gelfand, Donna; Berg, Cynthia A; Wiebe, Deborah J

    2007-01-01

    To investigate the cross-sectional relationship between maternal parenting style and indicators of well-being among adolescents with diabetes. Seventy-eight adolescents (ages 11.58-17.42 years, M = 14.21) with type 1 diabetes and their mothers separately reported perceptions of maternal parenting style. Adolescents reported their own depressed mood, self-efficacy for managing diabetes, and diabetes regimen adherence. Adolescents' perceptions of maternal psychological control were associated with greater depressed mood regardless of age and gender. Firm control was strongly associated with greater depressed mood and poorer self-efficacy among older adolescents, less strongly among younger adolescents. Adolescents' perceptions of maternal acceptance were associated with less depressed mood, particularly for girls and with better self-efficacy for diabetes management, particularly for older adolescents and girls. Maternal reports of acceptance were associated only with adherence. Maternal parenting style is associated with well-being in adolescents with diabetes, but this association is complex and moderated by age and gender.

  16. Serum ADEPONECTIN Level In Children And Adolescents With Type I Diabetes Mellitus And Its Association With Microvascular Complications

    International Nuclear Information System (INIS)

    MOAWAD, A.T.

    2010-01-01

    Adiponectin, an adipo cytokine, is secreted from the adipose tissue and plays an important role in obesity, type II diabetes and cardiovascular disease. This study aimed to determine the concentration of serum adiponectin in type I diabetic children and to establish its association with microvascular complications. For this reason, weight (kg), height (m), body mass index (BMI) (kg/m2), random blood sugar, HbAIc, kidney functions, urinary microalbuminuria, lipid profiles and serum adiponectin were assessed in 25 children (11 males, 14 females) with type I diabetes and twenty healthy control children. Careful history, clinical examination, acetomorphine and pirbuterol assessment were done for all patients and controls. The diabetic patients were stratified depending on the pubertal stage into pre-pubertal group and pubertal group, and according to gender into male group and female group. The results obtained displayed significant elevated values for random blood glucose (P<0.001), HbAIc (P<0.001), total cholesterol (P<0.05), low density lipoprotein (LDL) (P<0.05), BUN (P<0.001), creatinine (P<0.05), urinary microalbuminuria (P<0.001) and serum adiponectin (P<0.001) in diabetic children and control. In patients suffering from microvascular diabetic complications as retinopathy, nephropathy and neuropathy, serum adiponectin level showed high significant increase in patients with diabetic nephropathy and neuropathy than without. On the other hand, patients with retinopathy had no significant increase in serum adiponectin as compared with patients without retinopathy but this result may be due to small sample size. Positive significant correlation was detected between serum adiponectin and HbAIc, total cholesterol and urinary microalbuminuria in the same patients. Negative significant correlation was observed between serum adiponectin level and body mass index (BMI). It could be concluded that serum adiponectin which increased in diabetic children than healthy control

  17. 64,000-Mr autoantigen in type I diabetes. Evidence against its surface location on human islets

    International Nuclear Information System (INIS)

    Colman, P.G.; Campbell, I.L.; Kay, T.W.; Harrison, L.C.

    1987-01-01

    The sera of type I (insulin-dependent) diabetic subjects are reported to contain autoantibodies against a 64,000-Mr protein identified in [ 35 S]methionine biosynthetically labeled pancreatic islet cells. We have attempted to localize this autoantigen to the surface of the beta-cell and to define its properties. Sera from 10 newly diagnosed type I diabetic subjects, including five of the index sera originally used to identify the autoantigen, were shown to specifically precipitate a reduced protein of 67,000 Mr from Triton-solubilized, surface 125 I-labeled cultured adult human islet and rat insulinoma (RINm5F) cells but not from fresh rat spleen cells. Further characterization revealed that this protein was bovine serum albumin (BSA) adsorbed to cells from fetal calf serum (FCS)-supplemented culture medium and precipitated by BSA antibodies present in many diabetic sera. No labeled proteins were specifically precipitated when surface 125 I-labeled and solubilized human islet or RINm5F cells were precleared with anti-BSA immunoglobulins or when cells were first cultured in human serum. In contrast, a 64,000-Mr protein, clearly not BSA, was precipitated by diabetic globulins from human islets but not from RINm5F cells labeled with [ 35 S]methionine. In addition, a protein of the same size as well as proteins of approximately 35,000, 43,000, 140,000, and 200,000 Mr were specifically precipitated by diabetic globulins from freshly isolated human islets solubilized in Triton X-100 and then labeled with 125 I. These findings suggest that the 64,000-Mr antigen is not expressed on the surface of human islet cells, at least in culture, and therefore question its relevance as a target for islet cell surface antibodies in initiating beta-cell damage

  18. Altered insulin distribution and metabolism in type I diabetics assessed by [123I]insulin scanning

    International Nuclear Information System (INIS)

    Hachiya, H.L.; Treves, S.T.; Kahn, C.R.; Sodoyez, J.C.; Sodoyez-Goffaux, F.

    1987-01-01

    Scintigraphic scanning with [ 123 I]insulin provides a direct and quantitative assessment of insulin uptake and disappearance at specific organ sites. Using this technique, the biodistribution and metabolism of insulin were studied in type 1 diabetic patients and normal subjects. The major organ of [ 123 I]insulin uptake in both diabetic and normal subjects was the liver. After iv injection in normal subjects, the uptake of [ 123 I]insulin by the liver was rapid, with peak activity at 7 min. Activity declined rapidly thereafter, consistent with rapid insulin degradation and clearance. Rapid uptake of [ 123 I]insulin also occurred in the kidneys, although the uptake of insulin by the kidneys was about 80% of that by liver. In type 1 diabetic patients, uptake of [ 123 I]insulin in these organ sites was lower than that in normal subjects; peak insulin uptakes in liver and kidneys were 21% and 40% lower than those in normal subjects, respectively. The kinetics of insulin clearance from the liver was comparable in diabetic and normal subjects, whereas clearance from the kidneys was decreased in diabetics. The plasma clearance of [ 123 I]insulin was decreased in diabetic patients, as was insulin degradation, assessed by trichloroacetic acid precipitability. Thirty minutes after injection, 70.9 +/- 3.8% (+/- SEM) of [ 123 I]insulin in the plasma of diabetics was trichloroacetic acid precipitable vs. only 53.9 +/- 4.0% in normal subjects. A positive correlation was present between the organ uptake of [123I]insulin in the liver or kidneys and insulin degradation (r = 0.74; P less than 0.001)

  19. Social support and personal models of diabetes in relation to self-care and well-being in adolescents with type I diabetes mellitus

    DEFF Research Database (Denmark)

    Skinner, T. Chas; Hampson, Sarah E.

    1998-01-01

    , anxiety, perceived social support and personal models of diabetes. Perceived impact of diabetes, but not perceived seriousness, and peer support were significant predictors of depression. Family support was a significant predictor of all self-management measures. However, for dietary self......This study set out to examine whether peer support and illness representation mediates the link between family support, self-management and well-being. Seventy-four participants (12-18-years-old) with type I diabetes mellitus completed questionnaires assessing their self-management, depression...

  20. Role of decreased Plasma Tryptophan in memory deficits observed in Type-I diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, S.; Tabassum, S.; Haider, S. [University of Karachi (Pakistan). Dept. of Biochemistry

    2013-01-15

    Objective: To investigate the relationship between plasma tryptophan and the occurrence of memory dysfunctions in male and female type 1 diabetics. Methods: The case-control study was conducted at two urban healthcare facilities in Karachi from January to June 2009, and comprised 100 diabetic subjects of among whom were 50 men and 50 women. The controls were also similar in number and gender. A questionnaire was used to evaluate the memory impairment in the subjects. Plasma tryptophan was determined by high performance liquid chromatography with ultra-violet method. Students t-test was used to analyse tryptophan data. Results: There was considerable memory impairment in the cases (n=40) compared to the controls (n=5). Results also showed a significant (p<0.01) decrease in plasma tryptophan levels in both male and female diabetic patients. Conclusions: Diabetic subjects exhibited occurrence of memory impairment with concomitant decline in plasma tryptophan levels. The findings indicate that decreased brain uptake of tryptophan and lowered brain 5-hydroxytryptamine levels may be responsible for the memory deficits seen in diabetics. (author)

  1. Role of decreased Plasma Tryptophan in memory deficits observed in Type-I diabetes

    International Nuclear Information System (INIS)

    Ahmad, S.; Tabassum, S.; Haider, S.

    2013-01-01

    Objective: To investigate the relationship between plasma tryptophan and the occurrence of memory dysfunctions in male and female type 1 diabetics. Methods: The case-control study was conducted at two urban healthcare facilities in Karachi from January to June 2009, and comprised 100 diabetic subjects of among whom were 50 men and 50 women. The controls were also similar in number and gender. A questionnaire was used to evaluate the memory impairment in the subjects. Plasma tryptophan was determined by high performance liquid chromatography with ultra-violet method. Students t-test was used to analyse tryptophan data. Results: There was considerable memory impairment in the cases (n=40) compared to the controls (n=5). Results also showed a significant (p<0.01) decrease in plasma tryptophan levels in both male and female diabetic patients. Conclusions: Diabetic subjects exhibited occurrence of memory impairment with concomitant decline in plasma tryptophan levels. The findings indicate that decreased brain uptake of tryptophan and lowered brain 5-hydroxytryptamine levels may be responsible for the memory deficits seen in diabetics. (author)

  2. The relation of age to the severity of Type I diabetes in children

    Directory of Open Access Journals (Sweden)

    Suliman H Al-Fifi

    2010-01-01

    Full Text Available Objective: To study the relationship between the age and severity of Type 1 diabetes in children 0 - 5 years and more than 5 years of age admitted to Aseer Central Hospital, Southwestern Saudi Arabia over a 7-year period. Materials and Methods: A retrospective review of children less than 13 years of age with Type 1 diabetes admitted to the Pediatric Department, between 1st January 2000 to 31st December 2006. Results: A total of 181 children with Type1 diabetes were admitted to the hospital during this period. Of these, 27.6% were children 5 years or less, while 72.4% were more than 5 years of age. The duration of symptoms was longer in younger children compared to older patients. Diabetic ketoacidosis was present in 31.4% of the younger children, and in 15.3% of the children more than 5 years old. Hospital stay was also longer in children less than 5 years of age. Most significant differences were in the younger children′s group and affected the biochemical test results. Conclusion: The present study showed that more younger children present to the hospital late, and in a state of diabetic ketoacidosis compared to older patients. Efforts should be directed at improving the knowledge and skills of the primary health care personnel to be able to diagnose and refer these cases earlier.

  3. Effects of structurally stabilized EGF and bFGF on wound healing in type I and type II diabetic mice.

    Science.gov (United States)

    Choi, Seong Mi; Lee, Kyoung-Mi; Kim, Hyun Jung; Park, Ik Kyu; Kang, Hwi Ju; Shin, Hang-Cheol; Baek, Dawoon; Choi, Yoorim; Park, Kwang Hwan; Lee, Jin Woo

    2018-01-15

    Diabetes mellitus comprises a multiple metabolic disorder that affects millions of people worldwide and consequentially poses challenges for clinical treatment. Among the various complications, diabetic ulcer constitutes the most prevalent associated disorder and leads to delayed wound healing. To enhance wound healing capacity, we developed structurally stabilized epidermal growth factor (ST-EGF) and basic fibroblast growth factor (ST-bFGF) to overcome limitations of commercially available EGF (CA-EGF) and bFGF (CA-bFGF), such as short half-life and loss of activity after loading onto a matrix. Neither ST-EGF nor ST-bFGF was toxic, and both were more stable at higher temperatures than CA-EGF and CA-bFGF. We loaded ST-EGF and ST-bFGF onto a hyaluronate-collagen dressing (HCD) matrix, a biocompatible carrier, and tested the effectiveness of this system in promoting wound healing in a mouse model of diabetes. Wounds treated with HCD matrix loaded with 0.3 μg/cm 2 ST-EGF or 1 μg/cm 2 ST-bFGF showed a more rapid rate of tissue repair as compared to the control in type I and II diabetes models. Our results indicate that an HDC matrix loaded with 0.3 μg/cm 2 ST-EGF or 1 μg/cm 2 ST-bFGF can promote wound healing in diabetic ulcers and are suitable for use in wound dressings owing to their stability for long periods at room temperature. Various types of dressing materials loaded with growth factors, such as VEGF, EGF, and bFGF, are widely used to effect wound repair. However, such growth factor-loaded materials have several limitations for use as therapeutic agents in healing-impaired diabetic wounds. To overcome these limitations, we have developed new materials containing structurally stabilized EGF (ST-EGF) and bFGF (ST-bFGF). To confirm the wound healing capacity of newly developed materials (ST-EGF and ST-bFGF-loaded hyaluronate-collagen dressing [HCD] matrix), we applied these matrices in type I and type II diabetic wounds. Notably, these matrices were

  4. Imaging of the brain in children with type I diabetes mellitus

    International Nuclear Information System (INIS)

    Wootton-Gorges, Sandra L.; Glaser, Nicole S.

    2007-01-01

    Type 1 diabetes mellitus (DM) affects about 1 in 500 children and can cause damage to multiple organ systems. In recent years, growing attention has been given to the effects of type 1 DM on the brain. In this article we review important imaging features of the brain in children with type 1 DM, including (1) imaging the child in diabetic ketoacidosis and the child with hypoglycemia, (2) syndromes associated with type 1 DM, and (3) long-term effects of type 1 DM on brain structure. (orig.)

  5. Imaging of the brain in children with type I diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Wootton-Gorges, Sandra L. [University of California, Davis Medical Center, Department of Radiology, UC Davis Children' s Hospital, Sacramento, CA (United States); Glaser, Nicole S. [University of California, Davis Medical Center, Department of Pediatrics, UC Davis Children' s Hospital, Sacramento, CA (United States)

    2007-09-15

    Type 1 diabetes mellitus (DM) affects about 1 in 500 children and can cause damage to multiple organ systems. In recent years, growing attention has been given to the effects of type 1 DM on the brain. In this article we review important imaging features of the brain in children with type 1 DM, including (1) imaging the child in diabetic ketoacidosis and the child with hypoglycemia, (2) syndromes associated with type 1 DM, and (3) long-term effects of type 1 DM on brain structure. (orig.)

  6. Evaluation of Stress, Anxiety and Depression in Parents with a Child Newly Diagnosed with Diabetes Type I

    Directory of Open Access Journals (Sweden)

    Maryam Nakhaey Moghaddam

    2016-11-01

    Full Text Available BackgroundDiabetes type I (DTI is one of the most common endocrine disorders during childhood and adolescents in which has strong impact on physical and emotional development of individuals with family members. We aimed to evaluate of stress, anxiety and depression in parents with DTI child compared with parents with healthy child.Materials and MethodsIn this case – control study, 60 parents of patients with type 1 diabetes, who had referred to the endocrine clinic of Ali Asghar hospital in Zahedan city and the same number of parents with healthy children, who had referred to the hospital for their children's routine checkup, as control group (n=60, were studied. Depression, anxiety and stress was measurement by Depression Anxiety Stress Scale 42 (DASS. Data were analyzed using SPSS-16.ResultsMean age of children was 6.3 ± 3.6 years. In this study, the score and rate of depression in parents of children with diabetes type I was 21.4 ± 13.8 and 75.4%, respectively. The scores of depression, anxiety and stress in parents of children with DTI were 21.4 + 13.8, 18.8 + 11.3 and 27.1 + 11.5 respectively. Also, the scores of depression, anxiety and stress in parents with healthy children were 14.8 ± 11.3, 8.7 ± 6.9 and 15.8 ± 9.3, respectively; and these scores was significantly lower in control group (P0.05.ConclusionDiabetes in children is a stressful event that can affect the public health of parents. Parents of children who diagnosed with DTI, are at risk for experiencing anxiety, depression and stress.

  7. Exercise practices among persons with Type-I diabetes in South ...

    African Journals Online (AJOL)

    The current study examined the knowledge, attitudes, beliefs, and practices among 200 persons with type-1 diabetes mellitus who have completed outpatient counseling. The results indicated that providing education and support for exercise will over-come barriers to exercise and may increase compliance of exercise to ...

  8. Type I Diabetes Mellitus: Genetic Factors and Presumptive Enteroviral Etiology or Protection

    Directory of Open Access Journals (Sweden)

    Jana Precechtelova

    2014-01-01

    Full Text Available We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses, which are often associated with triggering the disease. Genus Enterovirus is classified into twelve species of which seven (Enterovirus A, Enterovirus B, Enterovirus C, and Enterovirus D and Rhinovirus A, Rhinovirus B, and Rhinovirus C are human pathogens. These viruses are transmitted mainly by the fecal-oral route; they may also spread via the nasopharyngeal route. Enterovirus infections are highly prevalent, but these infections are usually subclinical or cause a mild flu-like illness. However, infections caused by enteroviruses can sometimes be serious, with manifestations of meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis-like syndrome. These viruses are often implicated in chronic (inflammatory diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In this review we discuss the currently suggested mechanisms involved in the viral induction of type 1 diabetes. We recapitulate current basic knowledge and definitions.

  9. Renal, metabolic, and hormonal responses to proteins of different origin in normotensive, nonproteinuric type I diabetic patients.

    Science.gov (United States)

    Kontessis, P A; Bossinakou, I; Sarika, L; Iliopoulou, E; Papantoniou, A; Trevisan, R; Roussi, D; Stipsanelli, K; Grigorakis, S; Souvatzoglou, A

    1995-09-01

    Whether the differences in renal function found in vegetarian compared with omnivorous subjects are related to quantity or quality of the protein is unknown. We have studied the renal function of nine normotensive, nonproteinuric type I diabetic patients who were fed in random order for 4 weeks either an animal protein diet (APD) (protein intake 1.1 g . kg-1 . day-1) or a vegetable protein diet VPD (protein intake 0.95 g . kg-1 . day-1). The two diets were isocaloric. In a crossover study, we measured glomerular filtration rate (GFR) (inulin clearance), renal plasma flow (RPF) (p-aminohippurate clearance), plasma amino acids, growth hormone, glucagon, insulin-like growth factor I-(IGF-I), and microalbuminuria. GFR and RPF were lower with the VPD than with the APD (89.9 +/- 4.1 vs. 105.6 +/- 5.1 ml . min-1 . 1.73 m-2, P protein intake in normotensive type I diabetic patients. This could be explained partly by differences in plasma concentrations of amino acids and IGF-I.

  10. Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ahmadieh H

    2017-05-01

    Full Text Available Hala Ahmadieh,1 Nisrine Ghazal,2 Sami T Azar3 1Faculty of Medicine, Clinical Sciences Department, Beirut Arab University, 2Department of Endocrinology and Metabolism, American University of Beirut, Beirut, Lebanon; 3Department of Internal Medicine, Division of Endocrinology, American University of Beirut, New York, NY, USA Abstract: The burden of diabetes mellitus (DM in general has been extensively increasing over the past few years. Selective sodium glucose cotransporter-2 (SGLT2 inhibitors were extensively studied in type 2 DM and found to have sustained urinary glucose loss, improvement of glycemic control, in addition to their proven metabolic effects on weight, blood pressure, and cardiovascular benefits. Type 1 DM (T1D patients clearly depend on insulin therapy, which till today fails to achieve the optimal glycemic control and metabolic targets that are needed to prevent risk of complications. New therapies are obviously needed as an adjunct to insulin therapy in order to try to achieve optimal control in T1D. Many oral diabetic medications have been tried in T1D patients as an adjunct to insulin treatment and have shown conflicting results. Adjunctive use of SGLT2 inhibitors in addition to insulin therapies in T1D was found to have the potential to improve glycemic control along with decrease in the insulin doses, as has been shown in certain animal and short-term human studies. Furthermore, larger well-randomized studies are needed to better evaluate their efficacy and safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were found to be increased among users of SGLT2 inhibitors, although the incidence remains very low. Recent beneficial effects of ketone body production and this shift in fuel energetics have been suggested based on the findings of protective cardiovascular benefits associated with one of the SGLT2 inhibitors. Keywords: glycemic control, glycosylated hemoglobin, euglucemic diabetic ketoacidosis

  11. Superiority of radiobinding assay over ELISA for detection of IAAs in newly diagnosed type I diabetic children

    International Nuclear Information System (INIS)

    Levy-Marchal, C.; Bridel, M.P.; Sodoyez-Goffaux, F.; Koch, M.; Tichet, J.; Czernichow, P.; Sodoyez, J.C.

    1991-01-01

    Liquid- or solid-phase assays have been used for insulin autoantibody (IAA) determination, and the method of IAA measurement has not been standardized. IAAs were determined by radiobinding assay (RBA) and enzyme-linked immunosorbent assay (ELISA) in two large age-matched groups of nondiabetic and newly diagnosed insulin-dependent (type I) diabetic children. Positivity for IAA by RBA (greater than or equal to nondiabetic mean + 3SD) was 2 of 178 (1.1%) and 55 of 173 (32%) in nondiabetic and diabetic children, respectively. Prevalence of IAA by RBA was significantly higher in the youngest age-group (63% between 0-4 yr). Positivity for IAA by ELISA was 1 of 178 (0.6%) and 8 of 169 (4.7%) in nondiabetic and diabetic children, respectively. Concordance rates between both assays were 0 of 3 (0%) in control subjects and 5 of 58 (8.6%) in diabetic children. We conclude that RBA is more appropriate than ELISA for IAA detection at the onset of the disease. In addition, because available data suggest that IAAs detected by RBA only are high-affinity antibodies, it is tempting to speculate that IAAs reflect a mature immune reaction against endogenous insulin

  12. Dental health in children with type I diabetes mellitus and ways of its improvement

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    A. K. Iordanishvili

    2017-01-01

    Full Text Available The impact of a somatic disease on the status of the hard tissues of the teeth and periodontium and the level of individual oral hygiene were evaluated during one-year follow-up of the dental status in 59 children (31 boys, 28 girls aged 5 to 7 years, of whom 34 children had diabetes mellitus. Upon completion of oral cavity sanation, the children used R.O.C.S. «Kids» toothbrushes with extra-soft bristle and R.O.C.S. PRO Kids «Wild berries» toothpaste for oral care. The children with type 1 diabetes mellitus were established to more frequently suffer from inflammatory periodontal abnormality than the healthy children and dental caries in the former was more intensive than in the children without somatic diseases. To maintain their dental health, the diabetic children should undergo quarterly professional therapeutic and prophylactic measures, by using oral care products in accordance with the patients’ age.

  13. Autoimmunity in diabetics induced by hormonal contaminants of insulin

    International Nuclear Information System (INIS)

    Bloom, S.R.; Barnes, A.J.; Adrian, T.E.; Polak, J.M.

    1979-01-01

    Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment. (author)

  14. Autoimmunity in diabetics induced by hormonal contaminants of insulin

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, S R; Barnes, A J; Adrian, T E; Polak, J M [Royal Postgraduate Medical School, London (UK)

    1979-01-06

    Several commercial insulin preparations were found to contain significant quantities of pancreatic glucagon, pancreatic polypeptide (P.P.), vasoactive intestinal peptide (V.I.P.), and somatostatin, though these substances were effectively absent from the new highly purified or monocomponent insulins. Of 448 insulin-dependent diabetics receiving conventional insulins, 63% had circulating antibodies to human P.P., 6% antibodies to V.I.P., 6% to glucagon, and 0.5% to somatostatin. The antibodies were of high affinity and were commonest in the younger diabetics. No antibodies were detected in 167 maturity-onset diabetics, in 125 healthy controls, or in 22 patients treated only with monocomponent insulin. Immuno-cytochemical testing showed that antibody-positive diabetic plasmas reacted specifically against the corresponding hormone-producing pancreatic endocrine cells, against enteroglucagon and somatostatin cells outside the pancreas, and against V.I.P.-containing autonomic nerves throughout the body. The finding of iatrogenic autoimmunity to naturally occurring hormones in large numbers of insulin-dependent diabetics raises important questions about long-term treatment.

  15. Racial and ethnic differences among children with new-onset autoimmune type 1 diabetes

    Science.gov (United States)

    To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes. We analyzed a single-center series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The m...

  16. An extract from date seeds stimulates endogenous insulin secretion in streptozotocin-induced type I diabetic rats

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    Ahmed F. El Fouhil

    2013-11-01

    Full Text Available Background: The efficacy of an extract from date seeds has been tested successfully on the glycemic control of type I diabetes mellitus in rats. A suggestion that date seed extract could stimulate certain cells to differentiate into insulin-secreting cells has been proposed. In order to investigate such a possibility, this study was conducted to measure C-peptide levels in the serum of type 1 diabetic rats treated with date seed extract. Methods: Two hundred rats were divided into 4 groups. Group I served as the control. Group II was given daily ingestions of 10 ml of date seed extract. Groups III and IV were made diabetic by streptozotocin injection and were given daily subcutaneous injections of 3 IU/day of insulin for 8 weeks. Group IV received, in addition, daily ingestions of 10 ml of seed extract. At the end of experiment, blood samples were collected from each rat, and blood glucose and serum Cpeptide levels were measured. Results: No significant differences in the means of blood glucose and serum C-peptide levels were observed between groups I (control group and II (date seed extract-treated control group. Group IV (date seed extract-insulin-treated diabetic group showed a statistically significant reduction in the mean blood glucose level compared to Group III (insulin-treated diabetic group. The mean serum C-peptide level was significantly higher in group IV compared to group III. Conclusion: Biochemical results suggested an increase in endogenous insulin secretion in the case of type 1 diabetic rats treated with date seed extract, which might be the cause of its hypoglycemic effect.

  17. Chronic disease in child’s life. social and psychological aspects in the context of type i diabetes

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    Lucyna Sochocka

    2011-09-01

    Full Text Available Disease is one of the most undesirable phenomena in life and child’s development. Chronic disease makes very difficult to meet the needs of a child. Chronic failure affects not only the child himself but the child and the whole family. This is often difficult and sometimes even impossible to explain and accept. Lengthiness of type I diabetes often causes the child to stay in hospital where he comes across pain (insulin injections, diagnostic puncture, hospital rigor, impediment in learning.For school-age child is not enough „to be sick”, especially if the disease is associated with sensations such as pain and malaise. In situations like that it is necessary and important to inform the child about the disease. Supply him with basic information of the need for testing, the rules of diet and adverse symptoms such as acidosis, hypoglycemia. Lack of knowledge about the disease exacerbated by stress cause forced isolation of the child. Type I diabetes may be perceived by young people as a disease which limits social contacts. Furthermore may affect sense of otherness in relation to their contemporaries. Peer support is very important. It helps not only in adjusting to the environment but also in overcoming daily duties associated with chronic disease – testing of glucose level, insulin, diet and exercise plan. Treatment of diabetes may not focus solely on achievement of metabolic balance. It also aims at creation of good relationship within therapeutic team (patient, parent, doctor, nurse, laboratory technician, physical therapist, health trainer, psychologist as well as between friends, colleagues and school mates.

  18. Carvedilol and antioxidant proteins in a type I diabetes animal model.

    Science.gov (United States)

    Diogo, Cátia V; Deus, Cláudia M; Lebiedzinska-Arciszewska, Magdalena; Wojtala, Aleksandra; Wieckowski, Mariusz R; Oliveira, Paulo J

    2017-01-01

    Patients with diabetes are at a high risk of developing both micro- and macrovascular disease. Hyperglycaemia seems to be the main factor in the pathogenesis of diabetic cardiomyopathy, often based on increased oxidative stress. Carvedilol, a β-adrenergic blocker, has intrinsic antioxidant properties and was previously described to be effective in the protection of cardiac mitochondria against oxidative stress. The objective of this study was to evaluate the effect of carvedilol on hyperglycaemia-induced oxidative damage and mitochondrial abnormalities in cardiac and skeletal muscle in streptozotocin-treated rats. Body mass, blood glucose, the level of protein carbonylation, caspase-9- and caspase-3-like activities, mitochondrial proteins, the status of antioxidant defence system and stress-related proteins were evaluated in streptozotocin vs streptozotocin + carvedilol (1 mg/kg/day)-treated rats. The results showed that carvedilol decreased blood glucose in streptozotocin-treated animals. Content of catalase in the heart and SOD2, SOD1 and catalase in skeletal muscle were increased by carvedilol treatment in streptozotocin-treated animals. At this particular time point, streptozotocin-induced hyperglycaemia did not cause caspase activation or increase in protein carbonylation status. The data showed that carvedilol increased the level of antioxidant enzymes, what may contribute to preserve cell redox balance during hyperglycaemia. We also showed here for the first time that carvedilol effects on streptozotocin-treated rats are tissue dependent, with a more predominant effect on skeletal muscle. Based on data showing modulation of the antioxidant network in the heart, carvedilol may be beneficial in diabetic patients without advanced disease complications, delaying their progression. © 2016 Stichting European Society for Clinical Investigation Journal Foundation.

  19. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats.

    Science.gov (United States)

    Watts, Tammara; Berti, Irene; Sapone, Anna; Gerarduzzi, Tania; Not, Tarcisio; Zielke, Ronald; Fasano, Alessio

    2005-02-22

    Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.

  20. Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Khosla P

    1994-01-01

    Full Text Available Thirty-five patients of insulin-dependent diabetes mellitus (IDDM were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI levels and serum C-peptide radioimmunoreactivity (CPR as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM

  1. Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients

    DEFF Research Database (Denmark)

    Hvidberg, A; Rasmussen, M H; Christensen, N J

    1994-01-01

    followed by IV infusion of 1 mg/kg/h) was administered from 1 hour before induction of hypoglycemia until the end of the study period. On the other day, NaCl was administered. Plasma glucose before induction of hypoglycemia was equal on the 2 study days. The plasma glucose area under the curve (AUC......). The incremental AUC for cAMP was larger with theophylline for diabetic patients (P = .01). For healthy subjects, cAMP was greater with theophylline 30 minutes after insulin (P = .03). In conclusion, glucose recovery after hypoglycemia is significantly increased when theophylline is administered in an asthma......The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery...

  2. ANTIDIABETIC AND ANTIDYSLIPIDEMIC EFFECTS OF HELIOTROPIUM STRIGOSUM IN RAT MODELS OF TYPE I AND TYPE II DIABETES.

    Science.gov (United States)

    Chaudhry, Shafqat Rasul; Akram, Adnan; Aslam, Naveed; Asif, Muhammad; Wajid, Muhammad; Kinfe, Thomas; Jabeen, Qaiser; Muhammad, Sajjad

    2016-11-01

    Heliotropiumz stnigosum Wilid. (Boraginaceae) is used traditionally as a laxative, diuretic, and as a treatment for snake bites and stings of nettles. Recent investigations have shown anti-inflammatory and antioxidant activity of H. sorigosum. However, antihyperglycemic and antidyslipidemic activity of H. strigosum has not been investigated to date and we aimed to explore these activities of the crude aqueous methanolic extract of thEaerial parts of H. strigosum (Hs.Cr). Hs.Cr was administered orally at doses of 100, 300, and 500 mg/kg in alloxan-induced diabetic rats (type I diabetes) and fructose-fed rats (type II diabetes). The fasting blood glucose (FBG) concentration was assessed by glucometer, while semum total cholesterol, triglycerides and HDL were estimated by using standard kits. The FBG concentration significantly (p < 0.05) decreased in dose-dependent pattern in both alloxan-induced diabetic and fructose-fed rats on Hs.Cr administration. The percentage glucose reductions in alloxanized rats with glibenclamide, Hs.Cr 100, 300, and 500 mg/kg were obeserved to be 67, 36, 56 and 62%, respectively. In fructose-fed rats, the percentage glucose redutions associated with metformin, Hs.Cr 100, 300, and 500 mg/kg were 23, 5, 11 and 12%, respectively. The extract also corrected the dyslipidemia associated with fructose and alloxan-induced diabetes by significantly (p < 0.00 1) decreasing the concentration of serum total cholesterol, triglycerides and LDL and by increasing HDL concentration. Our data demonstrate that the H. stigosum has antidiabetic and antidyslipidemic effects, thus encouraging further studies.

  3. Serum levels of the interferon-gamma-inducing cytokine interleukin-18 are increased in individuals at high risk of developing type I diabetes

    DEFF Research Database (Denmark)

    Nicoletti, F; Conget, I; Di Marco, R

    2001-01-01

    and thought to be involved in its pathogenesis. Because increased production of IFN-gamma could be secondary to a dysregulated synthesis of IL-18, we compared the circulating levels of IL-18 in patients with newly diagnosed Type I diabetes with those of non-diabetic first-degree relatives and healthy control...

  4. Serum levels of activin A and inhibin A are not related to the increased susceptibility to pre-eclampsia in type I diabetic pregnancies

    DEFF Research Database (Denmark)

    Ekbom, Pia; Damm, Peter; Andersson, Anna-Maria

    2006-01-01

    Activin A and inhibin A have been found to be elevated in women without diabetes subsequently developing pre-eclampsia. The aim was to investigate whether activin A and inhibin A in serum were elevated in type I diabetic women after developing pre-eclampsia and, if so, were they clinically useful...

  5. Lipopolysaccharide regulated protein expression is only partly impaired in monocytes from patients with type I diabetes

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    Abke Sabine

    2006-03-01

    Full Text Available Abstract Background Monocytes play an important role in innate immunity and atherosclerosis. A disturbed secretion of cytokines in lipopolysaccharide (LPS activated monocytes from type 1 diabetes (T1D patients has been described and may contribute to the impaired inflammatory response in these individuals. In the present study the influence of LPS on five different proteins with a function in immunity and atherosclerosis was analyzed in monocytes from controls and T1D patients. Methods Monocytes were isolated from controls and T1D patients and the LPS-stimulated increase of IL-6, CXCL8, monocyte chemotactic protein 1 (CCL2, MCP-1 and superoxide dismutase (SOD 2, as well as the LPS-mediated decrease of apolipoprotein E (Apo E in primary human monocytes from controls and T1D patients was determined. Results CCL2 and IL-6 secretion in response to LPS was found significantly reduced in monocytes from T1D patients when compared to controls whereas basal CCL2 release was similar in control and T1D cells. In contrast, CXCL8 and apolipoprotein E secretion and SOD 2 expression upon LPS stimulation is similar from T1D and control monocytes. Conclusion These data indicate that LPS-mediated protein expression is only partly disturbed in monocytes from T1D patients. Reduced secretion of IL-6 and CCL2 in activated monocytes of these patients may contribute to an impaired inflammatory response and vascular disease.

  6. Investigation into the value of trained glycaemia alert dogs to clients with type I diabetes.

    Science.gov (United States)

    Rooney, Nicola J; Morant, Steve; Guest, Claire

    2013-01-01

    Previous studies have suggested that some pet dogs respond to their owners' hypoglycaemic state. Here, we show that trained glycaemia alert dogs placed with clients living with diabetes afford significant improvements to owner well-being. We investigated whether trained dogs reliably respond to their owners' hypoglycaemic state, and whether owners experience facilitated tightened glycaemic control, and wider psychosocial benefits. Since obtaining their dog, all seventeen clients studied reported positive effects including reduced paramedic call outs, decreased unconscious episodes and improved independence. Owner-recorded data showed that dogs alerted their owners, with significant, though variable, accuracy at times of low and high blood sugar. Eight out of the ten dogs (for which owners provided adequate records) responded consistently more often when their owner's blood sugars were reported to be outside, than within, target range. Comparison of nine clients' routine records showed significant overall change after obtaining their dogs, with seven clients recording a significantly higher proportion of routine tests within target range after obtaining a dog. HbA1C showed a small, non significant reduction after dog allocation. Based on owner-reported data we have shown, for the first time, that trained detection dogs perform above chance level. This study points to the potential value of alert dogs, for increasing glycaemic control, client independence and consequent quality of life and even reducing the costs of long-term health care.

  7. Investigation into the value of trained glycaemia alert dogs to clients with type I diabetes.

    Directory of Open Access Journals (Sweden)

    Nicola J Rooney

    Full Text Available Previous studies have suggested that some pet dogs respond to their owners' hypoglycaemic state. Here, we show that trained glycaemia alert dogs placed with clients living with diabetes afford significant improvements to owner well-being. We investigated whether trained dogs reliably respond to their owners' hypoglycaemic state, and whether owners experience facilitated tightened glycaemic control, and wider psychosocial benefits. Since obtaining their dog, all seventeen clients studied reported positive effects including reduced paramedic call outs, decreased unconscious episodes and improved independence. Owner-recorded data showed that dogs alerted their owners, with significant, though variable, accuracy at times of low and high blood sugar. Eight out of the ten dogs (for which owners provided adequate records responded consistently more often when their owner's blood sugars were reported to be outside, than within, target range. Comparison of nine clients' routine records showed significant overall change after obtaining their dogs, with seven clients recording a significantly higher proportion of routine tests within target range after obtaining a dog. HbA1C showed a small, non significant reduction after dog allocation. Based on owner-reported data we have shown, for the first time, that trained detection dogs perform above chance level. This study points to the potential value of alert dogs, for increasing glycaemic control, client independence and consequent quality of life and even reducing the costs of long-term health care.

  8. Trans-arterial xenotransplantation (Tx) of newborn porcine islet (NPI). A clinic trial for type I diabetes

    International Nuclear Information System (INIS)

    Wang Wei; Mo Zhaohui; Huang Zufa; Luo Xianming; Liu Sheng; Ye Bin; Li Bing; Liu Yingxin

    2002-01-01

    Objective: Liver is an important site to host transplanted islets, and implanting of islets by hepatic artery is simpler than by portal vein. Authors' study evaluated efficiency of the method and possible complication in a clinical setting. Methods: From October 1998 to June 2000, 4 type I diabetic patients received 4 x 10 6 (2 cases) and 8 x 10 6 (2 cases) of NPI through hepatic artery. Before Tx, all cases had the history with ketosis and acidosis. Exogenous insulin doses used for these cases were 25-48 units and their GHb was 9%-11%. After Tx, the NPI recipients were treated with immunosuppressants including cyclosporin 8 mg/kg for 12 months, cellcept 2 g/d for 25 days, and methylprednisolone 500 mg at 1 st day, then reduced to 50 mg for 3 days until to 10 mg for 1 month. Liver function and CD4/CD8 of the recipients were measured before and after Tx. Results: After Tx, the dose of exogenous insulin was increased to 60 mg due to methylprednisolone treatment. When methylprednisolone dose was decreased, the requirement for insulin was reduced to 32%-58% of the dose used before Tx. The reduction of required insulin for NPI recipients was proportional to the number of implanted NPI. In addition, GHb was also reduced to normal level (4%-6%) 3 months after Tx. No significant alterations of liver function and CD4 and CD8 in blood were observed after Tx. Conclusion: Trans-arterial intro-hepatic xenotransplantation of NPI is an efficient and safe therapeutic method for type I diabetes. Combination of cyclosporin, cellcept, and methylprednisolone is an effective immunosuppressive strategy for NPI xenograft transplantation

  9. Role of adipose tissue derived stem cells differentiated into insulin producing cells in the treatment of type I diabetes mellitus.

    Science.gov (United States)

    Amer, Mona G; Embaby, Azza S; Karam, Rehab A; Amer, Marwa G

    2018-05-15

    Generation of new β cells is an important approach in the treatment of type 1 diabetes mellitus (type 1 DM). Adipose tissue-derived stem cells (ADSCs) might be one of the best sources for cell replacement therapy for diabetes. Therefore, this work aimed to test the possible role of transplanted insulin-producing cells (IPCs) differentiated from ADSCs in treatment of streptozotocin (STZ) induced type I DM in rats. Type 1 DM was induced by single intra peritoneal injection with STZ (50 mg/kg BW). Half of the diabetic rats were left without treatment and the other half were injected with differentiated IPCs directly into the pancreas. ADSCs were harvested, cultured and identified by testing their phenotypes through flow cytometry. They were further subjected to differentiation into IPCs using differentiation medium. mRNA expression of pancreatic transcription factors (pdx1), insulin and glucose transporter-2 genes by real time PCR was done to detect the cellular differentiation and confirmed by stimulated insulin secretion. The pancreatic tissues from all groups were examined 2 months after IPC transplantation and were subjected to histological, Immunohistochemical and morphometric study. The differentiated IPCs showed significant expression of pancreatic β cell markers and insulin secretion in glucose dependent manner. Treatment with IPCs induced apparent regeneration, diffused proliferated islet cells and significant increase in C-peptide immune reaction. We concluded that transplantation of differentiated IPCs improved function and morphology of Islet cells in diabetic rats. Consequently, this therapy option may be a promising therapeutic approach to patient with type 1 DM if proven to be effective and safe. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Pneumococcal polysaccharide vaccination elicits IgG anti-AB blood group antibodies in healthy individuals and patients with Type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Wendelin Wolfram

    2016-11-01

    Full Text Available Hypothesis: Blood group antibodies are natural antibodies that develop early in life in response to cross-reactive environmental antigens in the absence of antigen encounter. Even later in life structural similarities in saccharide composition between environmental antigens such as bacterial polysaccharides and blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype and affinity maturation of blood group anti-A/B antibodies. We adressed the question whether immunization with pneumococcal polysaccharide (PnP vaccine (PPV Pneumovax®23 could have such an effect in patients with with type I diabetes mellitus (DM I, an autoimmune disease where an aberrant immune response to microbial antigens likely plays a role.Methods: Anti-PnP IgM and IgG responses were determined by ELISA and the Diamed-ID Micro Typing System was used to screen anti-A/B antibody titer before and after Pneumovax®23 immunization in 28 healthy individuals and 16 patients with DM I. In addition, surface plasmon resonance (SPR technology using the Biacore® device and a synthetic blood group A/B trisaccharide as the antigen was applied to investigate IgM and IgG anti-A/B antibodies and to measure antibody binding dynamics. Results: All healthy individuals and DM I patients responded with anti-PnP IgM and IgG antibody production four to six weeks after Pneumovax®23 (Pn23 immunization, while no increase in blood group anti-A/B antibody titer was observed when measured by the Diamed-ID Micro Typing System. Interestingly, isotype-specific testing by SPR-technology revealed an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization in both patients and controls. No change in binding characteristics of blood group anti-A/B antibodies could be detected following Pn23 vaccination, supporting the assumption of an increase in IgG antibody titer with no or very little affinity maturation.Conclusion: The study provides evidence for epitope sharing

  11. Effects of irradiation at different dose rates on the onset of type I diabetes in model mice

    International Nuclear Information System (INIS)

    Nomura, Takashi; Sakai, Kazuo

    2003-01-01

    We previously demonstrated that low-dose irradiation (0.5 Gy) increased the level of antioxidants and decreased the level of lipid peroxide in normal mice. We also found that 0.5 Gy-irradiation of NOD mice suppressed the onset of type I diabetes. These results were obtained by the irradiation at high dose rate. The aim of the present study is to examine the effects at the low dose rate. The mice were acutely irradiated with 0.5 Gy of X-rays (300 kVp) at 94.2 Gy/hr at 10, 11, 12, 13 or 14 weeks of age, or chronically irradiated with 0.5 Gy of 137 Cs γ-rays at 0.95 mGy/hr starting at 10,11,12,13 or 14 weeks of age. When irradiated at 12th week with the high dose rate X-rays, the onset of diabetes suppressed, and the increase in the specific activity of superoxide dismutase (SOD) in pancreas was observed. On the other hand, the low dose rate γ-rays delivered from 12th week of age to 14th was less effective in the suppression of the incidence of diabetes than the high dose rate X-rays at the 12-14 weeks of age. Furthermore, the significant increase in pancreatic SOD activity was not observed after the low dose irradiation. Splenic macrophage activities of superoxide generation were not affected by the high dose rate irradiation nor the low dose rate irradiation. (author)

  12. Decreased quality of life and treatment satisfaction in patients with latent autoimmune diabetes of the adult

    Directory of Open Access Journals (Sweden)

    Minerva Granado-Casas

    2017-10-01

    Full Text Available Objectives Our main aim was to assess the quality of life (QoL and treatment satisfaction (TS of subjects with LADA (latent autoimmune diabetes of the adult and compare these measures with those of patients with other diabetes types, i.e., type 1 (T1DM and type 2 diabetes mellitus (T2DM. Methods This was a cross-sectional study with a total of 48 patients with LADA, 297 patients with T2DM and 124 with T1DM. The Audit of Diabetes-Dependent Quality of Life (ADDQoL-19 questionnaire and the Diabetes Treatment Satisfaction Questionnaire (DTSQ were administered. Relevant clinical variables were also assessed. The data analysis included comparisons between groups and multivariate linear models. Results The LADA patients presented lower diabetes-specific QoL (p = 0.045 and average weighted impact scores (p = 0.007 than the T2DM patients. The subgroup of LADA patients with diabetic retinopathy (DR who were treated with insulin had a lower ADDQoL average weighted impact score than the other diabetic groups. Although the overall measure of TS was not different between the LADA and T2DM (p = 0.389 and T1DM (p = 0.091 groups, the patients with LADA showed a poorer hyperglycemic frequency perception than the T2DM patients (p < 0.001 and an improved frequency of hypoglycemic perception compared with the T1DM patients (p = 0.021. Conclusions The current findings suggest a poorer quality of life, especially in terms of DR and insulin treatment, among patients with LADA compared with those with T1DM and T2DM. Hyperglycemia frequency perception was also poorer in the LADA patients than in the T1DM and T2DM patients. Further research with prospective studies and a large number of patients is necessary.

  13. Obesity, islet cell autoimmunity, and cardiovascular risk factors in youth at onset of type 1 autoimmune diabetes.

    Science.gov (United States)

    Cedillo, Maribel; Libman, Ingrid M; Arena, Vincent C; Zhou, Lei; Trucco, Massimo; Ize-Ludlow, Diego; Pietropaolo, Massimo; Becker, Dorothy J

    2015-01-01

    The current increase in childhood type 1 diabetes (T1D) and obesity has led to two conflicting hypotheses and conflicting reports regarding the effects of overweight on initiation and spreading of islet cell autoimmunity vs earlier clinical manifestation of preexisting autoimmune β-cell damage driven by excess weight. The objective of the study was to address the question of whether the degree of β-cell autoimmunity and age are related to overweight at diabetes onset in a large cohort of T1D youth. This was a prospective cross-sectional study of youth with autoimmune T1D consecutively recruited at diabetes onset. The study was conducted at a regional academic pediatric diabetes center. Two hundred sixty-three consecutive children younger than 19 years at onset of T1D participated in the study. Relationships between body mass index and central obesity (waist circumference and waist to height ratio) and antigen spreading (islet cell autoantibody number), age, and cardiovascular (CVD) risk factors examined at onset and/or 3 months after the diagnosis were measured. There were no significant associations between number of autoantibodies with measures of adiposity. Age relationships revealed that a greater proportion of those with central obesity (21%) were in the youngest age group (0-4 y) compared with those without central obesity (6%) (P = .001). PATIENTS with central obesity had increased CVD risk factors and higher onset C-peptide levels (P obesity accelerates progression of autoantibody spreading once autoimmunity, marked by standard islet cell autoantibody assays, is present. Central obesity was present in almost one-third of the subjects and was associated with early CVD risk markers already at onset.

  14. Tumor necrosis factor-alpha and interleukin -6 as diagnostic markers of diabetic complications in children with type I diabetes mellitus

    International Nuclear Information System (INIS)

    El-Nashar, N.A.; Moawad, A.T.; Nassar, E.M.

    2010-01-01

    This study aimed to determine the role of cellular auto immunity and its humoral mediators in pathogenesis and following up of type I diabetes mellitus (TIDM). Therefore, serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), glycemic control, body mass index, duration of the disease and microalbuminuria in children with TIDM were evaluated. This study was conducted on 30 patients suffered from type I diabetes mellitus (TIDM), 14 males and 16 females with mean age of 11.40 ±3.67 years and 20 apparently healthy children served as control (10 male and 10 female). Children with TIDM were classified according to duration: diabetic children for 5 years or less duration (n= 15, duration means: 2.74 ± 1.34 years) and diabetic children > 5 years (n=15, duration means: 7.35 ± 1.49 years); according to glycemic control: children with good glycemic control (n=16, HbAIc: 7.82 ± 2.70) and diabetic children with poor glycemic control (n=14, HbAIc: 10.49 ± 2.72) and according to complication: diabetic children without complications (n= 20) and diabetic children with microvascular or neurological complications (n= 10, nephritic, retinal or neurological complications). Patients and controls were subjected to careful history, clinical examination and laboratory investigations. The following investigations were done for all children; random blood glucose, Glycated hemoglobin (HbAIc %), microalbuminuria and kidney function tests. Serum tumour necrosis factor-alpha (TNF-alpha) and serum interleukin-6 (IL-6) were measured using immuno-enzymometric assay (ELISA). Patients with TIDM with duration more than 5 years, with poor glycemic control and with complications had higher serum glucose levels, higher HbAIc%, higher level of blood urea nitrogen (BUN), serum creatinine, microalbuminuria and elevated serum TNF-alpha (p<0.0001) and IL-6 (p<0.0001) in comparison to the same diabetic patients with 5 years duration or less, with good glycemic control

  15. Type I diabetes mellitus decreases in vivo macrophage-to-feces reverse cholesterol transport despite increased biliary sterol secretion in mice

    NARCIS (Netherlands)

    de Boer, Jan Freark; Annema, Wijtske; Schreurs, Marijke; van der Veen, Jelske N; van der Giet, Markus; Nijstad, Niels; Kuipers, Folkert; Tietge, Uwe J F

    Type I diabetes mellitus (T1DM) increases atherosclerotic cardiovascular disease; however, the underlying pathophysiology is still incompletely understood. We investigated whether experimental T1DM impacts HDL-mediated reverse cholesterol transport (RCT). C57BL/6J mice with alloxan-induced T1DM had

  16. Hyperthyroidism from autoimmune thyroiditis in a man with type 1 diabetes mellitus: a case report

    Directory of Open Access Journals (Sweden)

    Hirsch Irl B

    2011-07-01

    Full Text Available Abstract Introduction The presentation, diagnosis, clinical course and treatment of a man with hyperthyroidism secondary to autoimmune thyroiditis in the setting of type 1 diabetes mellitus has not previously been described. Case presentation A 32-year-old European-American man with an eight-year history of type 1 diabetes mellitus presented with an unintentional 22-pound weight loss but an otherwise normal physical examination. Laboratory studies revealed a suppressed thyroid-stimulating hormone concentration and an elevated thyroxine level, which are consistent with hyperthyroidism. His anti-thyroid peroxidase antibodies were positive, and his thyroid-stimulating immunoglobulin test was negative. Uptake of radioactive iodine by scanning was 0.5% at 24 hours. The patient was diagnosed with autoimmune thyroiditis. Six weeks following his initial presentation he became clinically and biochemically hypothyroid and was treated with thyroxine. Conclusion This report demonstrates that autoimmune thyroiditis presenting as hyperthyroidism can occur in a man with type 1 diabetes mellitus. Autoimmune thyroiditis may be an isolated manifestation of autoimmunity or may be part of an autoimmune polyglandular syndrome. Among patients with type 1 diabetes mellitus who present with hyperthyroidism, Graves' disease and other forms of hyperthyroidism need to be excluded as autoimmune thyroiditis can progress quickly to hypothyroidism, requiring thyroid hormone replacement therapy.

  17. Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in type I diabetic patients

    DEFF Research Database (Denmark)

    Tarnow, L; Kjeld, T; Knudsen, E

    2000-01-01

    AIMS/HYPOTHESIS: Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three...... studied Caucasian patients with Type I (insulin-dependent) diabetes mellitus and nephropathy (120 men 74 women, age 41.1 +/- 9.6 years, diabetes duration 28 +/- 8 years) and long-standing Type I diabetic patients with persistent normoalbuminuria (112 men 69 women, age 42.5 +/- 10.0 years, diabetes...... duration 27 +/- 9 years). Genotyping was PCR-based and metabolic control estimated from all measurements of HbA1c done in each patient [average (range) n = 31 (6-74)]. The median observation time (range) was 13.5 (2-14) years. RESULTS: Type I diabetic patients with a history of poor glycaemic control (HbA1...

  18. Relationship of radionuclide measurements of left ventricular diastolic filling in patients with type I diabetes mellitus to subsequent clinical cardiac disease

    International Nuclear Information System (INIS)

    Ohashi, K.; Gerson, M.C.; Khoury, J.C.; Fischer, E.A.; Smith, H.S.

    1990-01-01

    This paper evaluates left ventricular diastolic filling (LVDF) in patients with type I diabetes mellitus (DM) in order to identify increased risk for subsequent cardiac events. The authors obtained radionuclide ventriculograms in 54 patients with type I DM. Median follow-up for cardiac complications was 63 months. We assessed peak filling rate (PFR; in end diastolic volume [EDV] per second), first 1/2 filling fraction (1/2 FF), and first 1/2 filling fraction/R-R interval (1/2 FF/R-R) by analysis of convariance to account for effects of age and R-R interval. Cardiac complications ere found in 15 of 54 patients

  19. Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms

    Science.gov (United States)

    Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio

    2010-01-01

    Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type 1 diabetes (T1D), a hyperglycosaemia caused by a destructive autoimmune process targeting the insulin-producing pancreatic islet cells. Even if environmental factors and genetic susceptibility are clearly involved in the pathogenesis of autoimmunity, for most autoimmune disorders there is no or little knowledge about the causing agent or genetic makeup underlying the disease. In this respect, CD represents a unique autoimmune disorder because a close genetic association with HLA-DQ2 or HLA-DQ8 haplotypes and, more importantly, the environmental trigger (the gliadin fraction of gluten-containing grains wheat, barley, and rye) are known. Conversely, the trigger for autoimmune destruction of pancreatic ß cells in T1D is unclear. Interestingly, recent data suggest that gliadin is also involved in the pathogenesis of T1D. There is growing evidence that increased intestinal permeability plays a pathogenic role in various autoimmune diseases including CD and T1D. Therefore, we hypothesize that besides genetic and environmental factors, loss of intestinal barrier function is necessary to develop autoimmunity. In this review, each of these components will be briefly reviewed. PMID:19538307

  20. Importance of the 31-p-nmr-spectroscopy for prediction and early detection of coronary heart disease in patients with diabetes mellitus type I

    International Nuclear Information System (INIS)

    Steinboeck, P.

    2001-06-01

    Microvascular abnormalities and dysfunction via thickening of the basement membrane are known to occur in diabetic patients. Myocardial high energy phosphates have been shown to be reduced by ischemia and alterations of the cardiac metabolism are the primary consequence of myocardial ischemia. The present study involved 30 male patients with diabetes mellitus type I and 36 healthy male volunteers as age-matched controls. Phosphorus-31-P-nuclear-magnetic-resonance-spectroscopic-imaging of the heart was performed in all subjects using a 1.5 Tesla whole-body-magnetic-resonance-scanner. The ratios of phosphocreatinine (PCr) to adenosine-triphosphate (ATP) were calculated. Moreover, echocardiographic evaluation and stress tests were performed in all individuals. The myocardium of patients with diabetes mellitus type I showed significantly decreased ratios of PCr/ATP compared with healthy controls. This study demonstrates for the first time a decreased ratio of PCr/ATP in the myocardium of patients with diabetes mellitus type I without a known history of coronary heart disease. (author)

  1. Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

    NARCIS (Netherlands)

    Langeveld, M.; de Fost, M.; Aerts, J. M. F. G.; Sauerwein, H. P.; Hollak, C. E. M.

    2008-01-01

    Type I Gaucher disease, a lysosomal storage disorder is associated with metabolic abnormalities such as high resting energy expenditure, low circulating adiponectin and peripheral insulin resistance. Treatment with enzyme replacement therapy (enzyme therapy) leads to a decrease in resting energy

  2. Type 1 Diabetes Mellitus Associated With Autoimmune Thyroid Disorders in Iranian Children: A Review

    Directory of Open Access Journals (Sweden)

    Daniel Zamanfar

    2015-01-01

    Full Text Available Context: Type one diabetes mellitus (T1DM is an autoimmune disorder that is yet the most common type of diabetes in children and adolescents. Several genetic risk factors have been associated with T1DM, auto immune thyroiditis and other autoimmune disorder. Among autoimmune disorders, autoimmune thyroid disease (ATD is the most frequent disorder associated with T1DM. Its prevalence varies depending on age, sex and ethnic origin of the subjects and is considerably higher than the general population and increases with duration of T1DM. The aim of this study was to review the prevalence of ATD in Iranian children with T1DM compared with other countries. Evidence Acquisition: We conducted a review on all papers published on the association between autoimmune thyroiditis and T1DM, which was available on Google Scholar, Scientific Information Database (SID, Magiran and Iran Medex databases up to June 2014. Both Persian and English articles were checked. The searched terms were: diabetes mellitus, autoimmune thyroiditis, prevalence, frequency, Iranian children and adolescents. All papers which were done on patients with age under 20 years old and have used Anti-TPO and Anti-TG to evaluate patients were included. Results: Six papers met all the criteria. A total of 736 participants were included in this review. After review of all the papers, the prevalence of Anti-TPO was reported between 8% and 30% and Anti-TG was reported 6.06% to 23.6% in diabetic children in Iran. Conclusions: Autoimmune thyroid disorders are the most prevalent immunological diseases in patients with type 1 diabetes. All these studies have shown a higher prevalence of the disorder in patients with T1DM compared to the Iranian healthy population. Anti-TPO reported between 8% and 30% and Anti-TG reported 6.06% to 23.6% in diabetic children in Iran that was similar to the studies in other countries.

  3. The role of monocytes and monocyte-derived dendritic cells in type 1 diabetes mellitus and autoimmune thyroid disease

    NARCIS (Netherlands)

    W.K. Lam-Tse

    2003-01-01

    textabstractType 1 diabetes mellitus (DM1) and autoimmune thyroid disease (AITD) are organ specific autoimmune diseases in which the immune system is directed against the ß cells and the thyrocytes respectively. The etio-pathogenesis of organ-specific or endocrine autoimmune diseases is complex,

  4. Anterior Hypopituitarism is Rare and Autoimmune Disease is Common in Adults with Idiopathic Central Diabetes Insipidus.

    LENUS (Irish Health Repository)

    2012-02-01

    Objective: Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, though many of these are thought to have an autoimmune basis. Published data has suggested that anterior hypopituitarism is common in childhood onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. Design and Patients: We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone MRI scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH\\/arginine and short synacthen testing) to assess anterior pituitary function. Results: One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. 33% had at least one autoimmune disease in addition to central diabetes insipidus. Conclusions: Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not therefore be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology.

  5. Topical Application of Propolis Enhances Cutaneous Wound Healing by Promoting TGF-Beta/Smad-Mediated Collagen Production in a Streptozotocin-Induced Type I Diabetic Mouse Model

    Directory of Open Access Journals (Sweden)

    Wael N. Hozzein

    2015-09-01

    Full Text Available Background/Aims: Impaired wound healing is considered to be one of the most serious complications associated with diabetes as it significantly increases the susceptibility of patients to infection. Propolis is a natural bee product used extensively in foods and beverages that has significant benefits to human health. In particular, propolis has antioxidant, anti-inflammatory and analgesic effects that could be useful for improving wound healing. In this study, we investigated the effects of topical application of propolis on the healing and closure of diabetic wounds in a streptozotocin (STZ-induced type I diabetic mouse model. Methods: Sixty male mice were distributed equally into 3 experimental groups: group 1, non-diabetic control mice; group 2, diabetic mice; and group 3, diabetic mice treated daily with a topical application of propolis. Results: We found that diabetic mice exhibited delayed wound closure characterized by a significant decrease in the levels of TGF-β1 and a prolonged elevation of the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α and MMP9 in wound tissues compared with control non-diabetic mice. Moreover, the wound tissues of diabetic mice showed a marked reduction in the phosphorylation of Smad2 and Smad3 as well as a marked reduction in collagen production. Interestingly, compared with untreated diabetic mice, topical application of propolis significantly enhanced the closure of diabetic wounds and decreased the levels of IL-1β, IL-6, TNF-α and MMP9 to near normal levels. Most importantly, compared with untreated diabetic mice, the treatment of diabetic mice with propolis significantly enhanced the production of collagen via the TGF-β1/Smad2,3 signaling axis in wounded tissues. Conclusion: Our findings reveal the molecular mechanisms underlying the improved healing and closure of diabetic wounds following topical propolis application.

  6. Impaired autoregulation of cerebral blood flow in long-term type I (insulin-dependent) diabetic patients with nephropathy and retinopathy

    DEFF Research Database (Denmark)

    Kastrup, J; Rørsgaard, S; Parving, H H

    1986-01-01

    Autoregulation of cerebral blood flow, i.e., the maintenance of cerebral blood flow within narrow limits during changes in arterial perfusion pressure, was studied in nine healthy control subjects and in 12 long-term Type I (insulin-dependent) diabetic patients with clinical microangiopathy...... the previous findings suggesting that autoregulation of cerebral blood flow is impaired in some long-term Type I diabetic patients with clinical microangiopathy (arteriolar hyalinosis)........ Cerebral blood flow was measured by the intravenous 133Xenon method. Mean arterial blood pressure was elevated approximately 30 mmHg by intravenous infusion of angiotensin amide II and lowered about 10 mmHg by intravenous infusion of trimethaphan camsylate. In the control subjects the flow/pressure curve...

  7. CD4+ CD25+ cells in type 1 diabetic patients with other autoimmune manifestations

    Directory of Open Access Journals (Sweden)

    Dalia S. Abd Elaziz

    2014-11-01

    Full Text Available The existence of multiple autoimmune disorders in diabetics may indicate underlying primary defects of immune regulation. The study aims at estimation of defects of CD4+ CD25+high cells among diabetic children with multiple autoimmune manifestations, and identification of disease characteristics in those children. Twenty-two cases with type 1 diabetes associated with other autoimmune diseases were recruited from the Diabetic Endocrine and Metabolic Pediatric Unit (DEMPU, Cairo University along with twenty-one normal subjects matched for age and sex as a control group. Their anthropometric measurements, diabetic profiles and glycemic control were recorded. Laboratory investigations included complete blood picture, glycosylated hemoglobin, antithyroid antibodies, celiac antibody panel and inflammatory bowel disease markers when indicated. Flow cytometric analysis of T-cell subpopulation was performed using anti-CD3, anti-CD4, anti-CD8, anti-CD25 monoclonal antibodies. Three cases revealed a proportion of CD4+ CD25+high below 0.1% and one case had zero counts. However, this observation did not mount to a significant statistical difference between the case and control groups neither in percentage nor absolute numbers. Significant statistical differences were observed between the case and the control groups regarding their height, weight centiles, as well as hemoglobin percentage, white cell counts and the absolute lymphocytic counts. We concluded that, derangements of CD4+ CD25+high cells may exist among diabetic children with multiple autoimmune manifestations indicating defects of immune controllers.

  8. Effect of resistance training on plasma nitric oxide and asymmetric dimethylarginine concentrations in type I diabetic rats

    Directory of Open Access Journals (Sweden)

    Parivash Shekarchizadeh Esfahani

    2013-01-01

    Conclusion: Elevated ADMA level in diabetic animals can normalize during resistance exercise. Reduced ADMA level and increased NO level following resistance training might improve cardiovascular risk in diabetic subjects.

  9. Latent Autoimmune Diabetes of the Adult (LADA in a Brazilian Indian

    Directory of Open Access Journals (Sweden)

    João Paulo Botelho Vieira Filho

    Full Text Available CONTEXT: Latent autoimmune diabetes of the adult (LADA as originally described represents perhaps as many as 10 -- 20% of adult-onset patients with diabetes. DESIGN: case report. CASE REPORT: A 38-year-old Brazilian Xavante-Jê Indian with Latent Autoimmune Diabetes of the Adult (LADA is described, coming from the Sangradouro community in Poxoréu, Mato Grosso. The onset of diabetes after reaching 25 years of age, the evolution to insulin deficiency after a period of insulin-independence and the presence of auto-antibodies to glutamic acid decarboxylase (GAD characteristic of LADA were present. This patient may represent the first case of LADA in a Brazilian with full Indian heritage. Further studies are necessary to verify the prevalence of this new type of diabetes in this population that does not have Caucasoid admixture and has a particular environmental background.

  10. Correlation between spermatogenesis disorders and rat testes CYP2E1 mRNA contents under experimental alcoholism or type I diabetes.

    Science.gov (United States)

    Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M

    2014-09-01

    The aim of the study was to investigate the correlation between spermatogenesis disorders and CYP2E1 mRNA contents in testes of rats with experimental alcoholism or type I diabetes. Two pathological states characterized by CYP2E1 induction were simulated on Wistar male rats: experimental alcoholism and type I diabetes. As controls for each state, equal number of animals (of the same age and weight) were used. Morphological evaluation of rat testes was carried out. The spermatogenic epithelium state was estimated by four points system. CYP2E1 mRNA expression was rated by method of reverse transcriptase polymerase chain reaction. Pearson correlation coefficients were used for describing relationships between variables. The presence of alcoholism and diabetes-mediated quantitative and qualitative changes in male rat spermatogenic epithelium in comparison with norm has been demonstrated. The increased levels of testes CYP2E1 have been fixed simultaneously. CYP2E1 mRNA content negatively strongly correlated with spermatogenic index value (r=-0.99; Palcoholism. The strong correlation between CYP2E1 mRNA content and number of spermatogonia (r=0.99; P<0.001) and "windows" occurrence (r=0.96; P<0.001) has been fixed in diabetic rats testes. Present investigation has demonstrated that the testicular failure following chronic ethanol consumption and diabetes type I in male rats accompanied CYP2E1 mRNA over-expression in testes. The correlation between the levels of CYP2E1 mRNA in testes and spermatogenesis disorders allow supposing the involvement of CYP2E1 into the non-specific pathogenetic mechanisms of male infertility under above-mentioned pathologies. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice

    Directory of Open Access Journals (Sweden)

    Sytwu Huey-Kang

    2009-08-01

    Full Text Available Abstract Pancreatic islet transplantation is considered an appropriate treatment to achieve insulin independence in type I diabetic patients. However, islet isolation and transplantation-induced oxidative stress and autoimmune-mediated destruction are still the major obstacles to the long-term survival of graft islets in this potential therapy. To protect islet grafts from inflammatory damage and prolong their survival, we transduced islets with an antioxidative gene thioredoxin (TRX using a lentiviral vector before transplantation. We hypothesized that the overexpression of TRX in islets would prolong islet graft survival when transplanted into diabetic non-obese diabetic (NOD mice. Methods Islets were isolated from NOD mice and transduced with lentivirus carrying TRX (Lt-TRX or enhanced green fluorescence protein (Lt-eGFP, respectively. Transduced islets were transplanted under the left kidney capsule of female diabetic NOD mice, and blood glucose concentration was monitored daily after transplantation. The histology of the islet graft was assessed at the end of the study. The protective effect of TRX on islets was investigated. Results The lentiviral vector effectively transduced islets without altering the glucose-stimulating insulin-secretory function of islets. Overexpression of TRX in islets reduced hydrogen peroxide-induced cytotoxicity in vitro. After transplantation into diabetic NOD mice, euglycemia was maintained for significantly longer in Lt-TRX-transduced islets than in Lt-eGFP-transduced islets; the mean graft survival was 18 vs. 6.5 days (n = 9 and 10, respectively, p Conclusion We successfully transduced the TRX gene into islets and demonstrated that these genetically modified grafts are resistant to inflammatory insult and survived longer in diabetic recipients. Our results further support the concept that the reactive oxygen species (ROS scavenger and antiapoptotic functions of TRX are critical to islet survival after

  12. Proximal gastric motor activity in response to a liquid meal in type I diabetes mellitus with autonomic neuropathy

    NARCIS (Netherlands)

    Samsom, M.; Roelofs, J. M.; Akkermans, L. M.; van Berge Henegouwen, G. P.; Smout, A. J.

    1998-01-01

    Disordered gastric emptying occurs in 30-50% of patients with diabetes mellitus. Although the rate of gastric emptying is dependent on the integration of motor activity in different regions of the stomach, there is limited information about the function of the proximal stomach in diabetes mellitus.

  13. Hexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart

    NARCIS (Netherlands)

    Gurel, Ebru; Ustunova, Savas; Kapucu, Aysegul; Yilmazer, Nadim; Eerbeek, Otto; Nederlof, Rianne; Hollmann, Markus W.; Demirci-Tansel, Cihan; Zuurbier, Coert J.

    2013-01-01

    Diabetes mellitus (DM) has been reported to alter the cardiac response to ischemia-reperfusion (IR). In addition, cardioprotection induced by ischemic preconditioning (IPC) is often impaired in diabetes. We have previously shown that the subcellular localisation of the glycolytic enzyme hexokinase

  14. Hyperthyroidism from autoimmune thyroiditis in a man with type 1 diabetes mellitus: a case report

    OpenAIRE

    Hirsch Irl B; Amory John K

    2011-01-01

    Abstract Introduction The presentation, diagnosis, clinical course and treatment of a man with hyperthyroidism secondary to autoimmune thyroiditis in the setting of type 1 diabetes mellitus has not previously been described. Case presentation A 32-year-old European-American man with an eight-year history of type 1 diabetes mellitus presented with an unintentional 22-pound weight loss but an otherwise normal physical examination. Laboratory studies revealed a suppressed thyroid-stimulating hor...

  15. The Effect of Diabetes-Associated Autoantigens on Cell Processes in Human PBMCs and Their Relevance to Autoimmune Diabetes Development

    Czech Academy of Sciences Publication Activity Database

    Včeláková, J.; Blatný, R.; Halbhuber, Z.; Kolář, Michal; Neuwirth, Aleš; Petruželková, L.; Ulmannová, T.; Koloušková, S.; Sumnik, Z.; Pithová, P.; Krivjanská, M.; Filipp, Dominik; Štechová, K.

    2013-01-01

    Roč. 2013, May (2013), s. 589451 ISSN 2314-6745 Grant - others:GA MŠk(CZ) 2B06019 Institutional support: RVO:68378050 Keywords : type 1 diabetes * autoimmune disease * Th17 * TGF-beta Subject RIV: EB - Genetics ; Molecular Biology

  16. Use of autoantigen-loaded phosphatidylserine-liposomes to arrest autoimmunity in type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Irma Pujol-Autonell

    Full Text Available The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes.To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes.A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides.We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4+ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4+ T cell expansion.We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for

  17. Multiple differences in gene expression in regulatory Vα24JαQ T cells from identical twins discordant for type I diabetes

    Science.gov (United States)

    Wilson, S. Brian; Kent, Sally C.; Horton, Heidi F.; Hill, Andrew A.; Bollyky, Paul L.; Hafler, David A.; Strominger, Jack L.; Byrne, Michael C.

    2000-01-01

    Quantitative and qualitative defects in CD1d-restricted T cells have been demonstrated in human and murine autoimmune diseases. To investigate the transcriptional consequences of T cell receptor activation in human Vα24JαQ T cell clones, DNA microarrays were used to quantitate changes in mRNA levels after anti-CD3 stimulation of clones derived from identical twins discordant for type 1 diabetes and IL-4 secretion. Activation resulted in significant modulation of 226 transcripts in the IL-4 secreting clone and 86 in the IL-4-null clone. Only 28 of these genes were in common. The differences observed suggest both ineffective differentiation of diabetic Vα24JαQ T cells and a role for invariant T cells in the recruitment and activation of cells from the myeloid lineage. PMID:10840051

  18. Mesenchymal stem cells and differentiated insulin producing cells are new horizons for pancreatic regeneration in type I diabetes mellitus.

    Science.gov (United States)

    Domouky, Ayat M; Hegab, Ashraf S; Al-Shahat, Amal; Raafat, Nermin

    2017-06-01

    Diabetes mellitus has become the third human killer following cancer and cardiovascular disease. Millions of patients, often children, suffer from type 1 diabetes (T1D). Stem cells created hopes to regenerate damaged body tissues and restore their function. This work aimed at clarifying and comparing the therapeutic potential of differentiated and non-differentiated mesenchymal stem cells (MSCs) as a new line of therapy for T1D. 40 Female albino rats divided into group I (control): 10 rats and group II (diabetic), III and IV, 10 rats in each, were injected with streptozotocin (50mg/kg body weight). Group III (MSCs) were transplanted with bone marrow derived MSCs from male rats and group IV (IPCs) with differentiated insulin producing cells. Blood and pancreatic tissue samples were taken from all rats for biochemical and histological studies. MSCs reduced hyperglycemia in diabetic rats on day 15 while IPCs normalizes blood glucose level on day 7. Histological and morphometric analysis of pancreas of experimental diabetic rats showed improvement in MSCs-treated group but in IPCs-treated group, β-cells insulin immunoreactions were obviously returned to normal, with normal distribution of β-cells in the center and other cells at the periphery. Meanwhile, most of the pathological lesions were still detected in diabetic rats. MSCs transplantation can reduce blood glucose level in recipient diabetic rats. IPCs initiate endogenous pancreatic regeneration by neogenesis of islets. IPCs are better than MSCs in regeneration of β-cells. So, IPCs therapy can be considered clinically to offer a hope for patients suffering from T1D. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. LEW.1WR1 RATS DEVELOP AUTOIMMUNE DIABETES SPONTANEOUSLY AND IN RESPONSE TO ENVIRONMENTAL PERTURBATION

    Science.gov (United States)

    Mordes, John P.; Leif, Jean H.; Woda, Bruce A.; Flanagan, Joan F.; Greiner, Dale L.; Kislauskis, Edward H.; Tirabassi, Rebecca S.

    2005-01-01

    We describe a new rat model of autoimmune diabetes that arose in a major histocompatibility complex (MHC) congenic LEW rat. Spontaneous diabetes in LEW.1WR1 rats (RT1u/u/a) occurs with a cumulative frequency of ∼2% at a median age of 59 days. The disease is characterized by hyperglycemia, glycosuria, ketonuria and polyuria. Both sexes are affected, and islets of acutely diabetic rats are devoid of beta cells whereas alpha and delta cell populations are spared. The peripheral lymphoid phenotype is normal, including the fraction of ART2+ regulatory T cells (Tregs). We tested the hypothesis that the expression of diabetes would be increased by immunological perturbation of innate or adaptive immunity. Treatment of young rats with depleting anti-ART2.1 mAb increased the frequency of diabetes to 50%. Treatment with the toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid increased the frequency of diabetes to 100%. All diabetic rats exhibited end-stage islets. The LEW.1WR1 rat is also susceptible to collagen-induced arthritis but is free of spontaneous thyroiditis. The LEW.1WR1 rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation. PMID:16123363

  20. Systemic Toll-like receptor stimulation suppresses experimental allergic asthma and autoimmune diabetes in NOD mice.

    Directory of Open Access Journals (Sweden)

    Aude Aumeunier

    Full Text Available BACKGROUND: Infections may be associated with exacerbation of allergic and autoimmune diseases. Paradoxically, epidemiological and experimental data have shown that some microorganisms can also prevent these pathologies. This observation is at the origin of the hygiene hypothesis according to which the decline of infections in western countries is at the origin of the increased incidence of both Th1-mediated autoimmune diseases and Th2-mediated allergic diseases over the last decades. We have tested whether Toll-like receptor (TLR stimulation can recapitulate the protective effect of infectious agents on allergy and autoimmunity. METHODS AND FINDINGS: Here, we performed a systematic study of the disease-modifying effects of a set of natural or synthetic TLR agonists using two experimental models, ovalbumin (OVA-induced asthma and spontaneous autoimmune diabetes, presenting the same genetic background of the non obese diabetic mouse (NOD that is highly susceptible to both pathologies. In the same models, we also investigated the effect of probiotics. Additionally, we examined the effect of the genetic invalidation of MyD88 on the development of allergic asthma and spontaneous diabetes. We demonstrate that multiple TLR agonists prevent from both allergy and autoimmunity when administered parenterally. Probiotics which stimulate TLRs also protect from these two diseases. The physiological relevance of these findings is further suggested by the major acceleration of OVA-induced asthma in MyD88 invalidated mice. Our results strongly indicate that the TLR-mediated effects involve immunoregulatory cytokines such as interleukin (IL-10 and transforming growth factor (TGF-beta and different subsets of regulatory T cells, notably CD4+CD25+FoxP3+ T cells for TLR4 agonists and NKT cells for TLR3 agonists. CONCLUSIONS/SIGNIFICANCE: These observations demonstrate that systemic administration of TLR ligands can suppress both allergic and autoimmune responses

  1. Time to insulin initiation can not be used in defining Latent Autoimmune Diabetes in Adults [LADA

    DEFF Research Database (Denmark)

    Brophy, S; Yderstræde, K; Mauricio, D

    2007-01-01

    and clinicians reported on criteria for initiating insulin. All patients were tested for glutamic acid decarboxylase autoantibodies (GADA) in a central laboratory. We examined time to insulin treatment for GADA positive patients in 6 participating centres. Results: There was inter-centre variation......Objective: Latent Autoimmune Diabetes in Adults [LADA] is type 1 diabetes presenting as non-insulin dependent diabetes. One feature of the selection criteria is time independent of insulin treatment. We examine the validity of this criterion. Methods: Patients were recruited in 9 European centres...

  2. Comparison of oral and intravenous routes of administration of dipyridamole for thallium imaging of type I diabetics with end-stage renal disease

    International Nuclear Information System (INIS)

    Boudreau, R.J.; Stony, J.T.; du Cret, R.P.; Kuni, C.C.; Wang, Y.; Wilson, R.F.; Schwartz, J.F.; Castaneda-Zuniga, W.R.

    1989-01-01

    The authors have frequently seen myocardial infarction after renal transplantation in patient with type I diabetes, and treadmill T1-201 testing in these patients have been inadequate. The authors evaluated dipyridamole (DP) as a substitute for treadmill stress. Because intravenous DP was not approved in the United States at the time of the study, the oral formulation wax used for some patients. The authors have prospectively evaluated 80 uremic diabetics (40 received oral T1-201; 40 received intravenous T1-201). Angiogram and scan observers were blinded. There was not difference in the accuracy of the two routes of administration. Pooling the data gave a sensitivity of 86% and a specificity of 79%. However, their disease prevalence was high (52%), which precluded the use of any screening test. The authors now have recommended angiography for these patients

  3. AAV-mediated pancreatic overexpression of Igf1 counteracts progression to autoimmune diabetes in mice.

    Science.gov (United States)

    Mallol, Cristina; Casana, Estefania; Jimenez, Veronica; Casellas, Alba; Haurigot, Virginia; Jambrina, Claudia; Sacristan, Victor; Morró, Meritxell; Agudo, Judith; Vilà, Laia; Bosch, Fatima

    2017-07-01

    Type 1 diabetes is characterized by autoimmune destruction of β-cells leading to severe insulin deficiency. Although many improvements have been made in recent years, exogenous insulin therapy is still imperfect; new therapeutic approaches, focusing on preserving/expanding β-cell mass and/or blocking the autoimmune process that destroys islets, should be developed. The main objective of this work was to test in non-obese diabetic (NOD) mice, which spontaneously develop autoimmune diabetes, the effects of local expression of Insulin-like growth factor 1 (IGF1), a potent mitogenic and pro-survival factor for β-cells with immunomodulatory properties. Transgenic NOD mice overexpressing IGF1 specifically in β-cells (NOD-IGF1) were generated and phenotyped. In addition, miRT-containing, IGF1-encoding adeno-associated viruses (AAV) of serotype 8 (AAV8-IGF1-dmiRT) were produced and administered to 4- or 11-week-old non-transgenic NOD females through intraductal delivery. Several histological, immunological, and metabolic parameters were measured to monitor disease over a period of 28-30 weeks. In transgenic mice, local IGF1 expression led to long-term suppression of diabetes onset and robust protection of β-cell mass from the autoimmune insult. AAV-mediated pancreatic-specific overexpression of IGF1 in adult animals also dramatically reduced diabetes incidence, both when vectors were delivered before pathology onset or once insulitis was established. Transgenic NOD-IGF1 and AAV8-IGF1-dmiRT-treated NOD animals had much less islet infiltration than controls, preserved β-cell mass, and normal insulinemia. Transgenic and AAV-treated islets showed less expression of antigen-presenting molecules, inflammatory cytokines, and chemokines important for tissue-specific homing of effector T cells, suggesting IGF1 modulated islet autoimmunity in NOD mice. Local expression of Igf1 by AAV-mediated gene transfer counteracts progression to diabetes in NOD mice. This study suggests a

  4. Thyroid dysfunction during pregnancy and in the first postpartum year in women with diabetes mellitus type I

    NARCIS (Netherlands)

    Gallas, PRJ; Stolk, RP; Bakker, Krista; Endert, E; Wiersinga, WM

    2002-01-01

    Background: The prevalence of thyroid dysfunction in pregnancy and in the first postpartum year (postpartum thyroid dysfunction (PPTD)) in women with diabetes mellitus type 1 (DM1) is known to be higher than in the general population. To assess prevalence, incidence and risk factors in The

  5. Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

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    Marco A. S. Fortes

    2017-10-01

    Full Text Available Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus or glycolytic (EDL muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK, Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1, mechano-growth factor (MGF and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group.

  6. Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

    Science.gov (United States)

    Fortes, Marco A. S.; Scervino, Maria V. M.; Marzuca-Nassr, Gabriel N.; Vitzel, Kaio F.; da Justa Pinheiro, Carlos H.; Curi, Rui

    2017-01-01

    Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus) or glycolytic (EDL) muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK), Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK) and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1), mechano-growth factor (MGF) and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group. PMID:29123487

  7. Evaluation of PD/PID controller for insulin control on blood glucose regulation in a Type-I diabetes

    Science.gov (United States)

    Mahmud, Farhanahani; Isse, Nadir Hussien; Daud, Nur Atikah Mohd; Morsin, Marlia

    2017-01-01

    This project introduces a simulation of Proportional-Derivative (PD) and Proportional-Integral-Derivative (PID) controller based on a virtual Type 1 Diabetes Mellitus (T1DM) patient: Hovorka diabetic model using MATLAB-Simulink software. The results of these simulations are based on three tuning responses for each controller which are fast, slow and oscillation responses. The main purpose of this simulation is to achieve an acceptable stability and fastness response towards the regulation of glucose concentration using PD and PID controller response with insulin infusion rate. Therefore, in order to analyze and compare the responses of both controller performances, one-day simulations of the insulin-glucose dynamic have been conducted using a typical day meal plan that contains five meals of different bolus size. It is found that the PID closed-loop control with a short rise time is required to retrieve a satisfactory glucose regulation.

  8. Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

    OpenAIRE

    Alkan , Manal; Machavoine , François; Rignault , Rachel; Dam , Julie; Dy , Michel; Thieblemont , Nathalie

    2015-01-01

    International audience; Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC −/− m...

  9. Implication of the intestinal microbiome as a potential surrogate marker of immune responsiveness to experimental therapies in autoimmune diabetes

    NARCIS (Netherlands)

    Needell, J.C.; Dinarello, C.A.; Ir, D.; Robertson, C.E.; Ryan, S.M.; Kroehl, M.E.; Frank, D.N.; Zipris, D.

    2017-01-01

    Type 1 diabetes (T1D) is an autoimmune proinflammatory disease with no effective intervention. A major obstacle in developing new immunotherapies for T1D is the lack of means for monitoring immune responsiveness to experimental therapies. The LEW1.WR1 rat develops autoimmunity following infection

  10. Increased seroreactivity to proinsulin and homologous mycobacterial peptides in latent autoimmune diabetes in adults.

    Directory of Open Access Journals (Sweden)

    Magdalena Niegowska

    Full Text Available Latent Autoimmune Diabetes in Adults (LADA is a slowly progressing form of immune-mediated diabetes that combines phenotypical features of type 2 diabetes (T2D with the presence of islet cell antigens detected in type 1 diabetes (T1D. Heterogeneous clinical picture have led to the classification of patients based on the levels of antibodies against glutamic acid decarboxylase 65 (GADA that correlate with clinical phenotypes closer to T1D or T2D when GADA titers are high or low, respectively. To date, LADA etiology remains elusive despite numerous studies investigating on genetic predisposition and environmental risk factors. To our knowledge, this is the first study aimed at evaluation of a putative role played by Mycobacterium avium subsp. paratuberculosis (MAP as an infective agent in LADA pathogenesis. MAP is known to cause chronic enteritis in ruminants and has been associated with autoimmune disorders in humans. We analyzed seroreactivity of 223 Sardinian LADA subjects and 182 healthy volunteers against MAP-derived peptides and their human homologs of proinsulin and zinc transporter 8 protein. A significantly elevated positivity for MAP/proinsulin was detected among patients, with the highest prevalence in the 32-41-year-old T1D-like LADA subgroup, supporting our hypothesis of a possible MAP contribution in the development of autoimmunity.

  11. E2-2 Dependent Plasmacytoid Dendritic Cells Control Autoimmune Diabetes.

    Directory of Open Access Journals (Sweden)

    Lisbeth Hansen

    Full Text Available Autoimmune diabetes is a consequence of immune-cell infiltration and destruction of pancreatic β-cells in the islets of Langerhans. We analyzed the cellular composition of the insulitic lesions in the autoimmune-prone non-obese diabetic (NOD mouse and observed a peak in recruitment of plasmacytoid dendritic cells (pDCs to NOD islets around 8-9 weeks of age. This peak coincides with increased spontaneous expression of type-1-IFN response genes and CpG1585 induced production of IFN-α from NOD islets. The transcription factor E2-2 is specifically required for the maturation of pDCs, and we show that knocking out E2-2 conditionally in CD11c+ cells leads to a reduced recruitment of pDCs to pancreatic islets and reduced CpG1585 induced production of IFN-α during insulitis. As a consequence, insulitis has a less aggressive expression profile of the Th1 cytokine IFN-γ and a markedly reduced diabetes incidence. Collectively, these observations demonstrate a disease-promoting role of E2-2 dependent pDCs in the pancreas during autoimmune diabetes in the NOD mouse.

  12. Insulinotropic and anti-inflammatory effects of rosiglitazone in experimental autoimmune diabetes.

    Science.gov (United States)

    Awara, Wageh M; el-Sisi, Alaa E; el-Refaei, Mohamed; el-Naa, Mona M; el-Desoky, Karima

    2005-01-01

    Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). The anti-inflammatory and immunomodulating properties of PPAR-gamma have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-alpha, IFN-gamma and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression.

  13. New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with [sup 123]I-labelled interleukin 2

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    Signore, S.; Chianelli, M.; Ferretti, E.; Toscano, A.; Britton, K.E.; Andreani, D.; Gale, E.A.M.; Pozzilli, P. (Clinical Medica II, Univ. of Rome (Italy))

    1994-10-01

    Insulitis is considered the histopathological hallmark of type I diabetes. In the non-obese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, the authors have labelled recombinant inter-leukin 2 with [sup 123]I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. The authors studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled [alpha]-lactalbumin was used as the control protein. In the first set of experiments the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points was studied. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving labelled [alpha]-lactalbumin. In another set of experiments, gamma camera images have been acquired after injection of [sup 123]I-labelled interleukin 2. Radioactivity in the pancreatic region of prediabetic NOD and Balb/c mice showed similar kinetics to those observed by single organ counting, with higher accumulation in the pancreatic region of NOD mice. Finally, a positive correlation was found between the radioactivity in the pancreas and the extent of lymphocytic infiltration. This study demonstrates that [sup 123]I-labelled interleukin 2 administered intravenously accumulates specifically in the inflamed pancreas of diabetes-prone NOD mice, suggesting its potential application in human insulin-dependent diabetes mellitus. 34 refs., 6 figs., 1 tab.

  14. New approach for in vivo detection of insulitis in type I diabetes: activated lymphocyte targeting with 123I-labelled interleukin 2

    International Nuclear Information System (INIS)

    Signore, S.; Chianelli, M.; Ferretti, E.; Toscano, A.; Britton, K.E.; Andreani, D.; Gale, E.A.M.; Pozzilli, P.

    1994-01-01

    Insulitis is considered the histopathological hallmark of type I diabetes. In the non-obese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, the authors have labelled recombinant inter-leukin 2 with 123 I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. The authors studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled α-lactalbumin was used as the control protein. In the first set of experiments the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points was studied. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving labelled α-lactalbumin. In another set of experiments, gamma camera images have been acquired after injection of 123 I-labelled interleukin 2. Radioactivity in the pancreatic region of prediabetic NOD and Balb/c mice showed similar kinetics to those observed by single organ counting, with higher accumulation in the pancreatic region of NOD mice. Finally, a positive correlation was found between the radioactivity in the pancreas and the extent of lymphocytic infiltration. This study demonstrates that 123 I-labelled interleukin 2 administered intravenously accumulates specifically in the inflamed pancreas of diabetes-prone NOD mice, suggesting its potential application in human insulin-dependent diabetes mellitus. 34 refs., 6 figs., 1 tab

  15. The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

    Directory of Open Access Journals (Sweden)

    Mami Shimizu

    Full Text Available Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C. In addition, injection of high-dose poly(I: C to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

  16. Aspartic acid at position 57 of the HLA-DQ beta chain protects against type I diabetes: a family study.

    OpenAIRE

    Morel, P A; Dorman, J S; Todd, J A; McDevitt, H O; Trucco, M

    1988-01-01

    One hundred seventy-two members from 27 randomly selected multiple case Caucasian families of patients with insulin-dependent diabetes mellitus (IDDM) were studied at the DNA level to ascertain the reliability of codon 57 of the HLA-DQ beta-chain gene as a disease protection/susceptibility marker. The analysis was carried out by polymerase chain reaction amplification of DNA encoding the first domain of the DQ beta chain and by dot blot analysis of the amplified material with allele-specific ...

  17. Manifestações vestibulococleares em pacientes com diabetes melito tipo I Vestibulocochlear manifestations in patients with type I diabetes mellitus

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    Karlin Fabianne Klagenberg

    2007-06-01

    Full Text Available Ometabolismo da glicose tem muita influência na fisiologia da orelha interna e pequenas variações glicêmicas podem provocar alterações na audição e no equilíbrio corporal. OBJETIVO: Verificar as manifestações vestibulococleares em pacientes com diabetes melito tipo I. FORMA DE ESTUDO: Coorte contemporânea com corte transversal. MATERIAL E MÉTODO: Avaliaram-se 30 pacientes (17 homens e 13 mulheres encaminhados do Hospital de Clínicas da UFPr para o Laboratório de Otoneurologia da Universidade Tuiuti do Paraná no período de março/2004 a fevereiro/2005. Realizaram-se os seguintes procedimentos: anamnese, inspeção otológica, avaliação audiológica convencional, medida de imitância acústica e avaliação vestibular. RESULTADOS: Observaram-se entre as queixas otoneurológicas a prevalência de cefaléia (23,3%, tontura rotatória (16,6% e zumbido (13,3%. Nas queixas associadas e hábitos, a prevalência foi do abuso de cafeína (20,0%, álcool e alergia (10,0%, em cada. Houve prevalência de limiares auditivos normais (90,0%. A medida de imitância acústica mostrou-se sem alteração. O exame vestibular esteve alterado em 60,0%. Houve predomínio das síndromes vestibulares periféricas deficitárias. CONCLUSÕES: Verificou-se um maior número de alteração do sistema vestibular (60,0% em relação ao sistema auditivo (10,0%. Houve predomínio da normalidade no exame auditivo. Houve prevalência de alteração no sistema vestibular periférico e da síndrome vestibular periférica deficitária.Glucose metabolism has a significant impact on inner ear physiology, and small changes may result in hearing and balance disorders. AIM: To investigate vestibulocochlear symptoms in patients with type I diabetes mellitus. STUDY DESIGN: a cross-sectional study of a contemporary group. MATERIAL AND METHOD: 30 patients referred from Clinical Hospital-UFPR to the Laboratory of Otoneurology-UTP between Mar/2004 to Feb/2005 were evaluated

  18. Evaluation of thyroid dysfunction and autoimmunity in gestational diabetes mellitus and its relationship with postpartum thyroiditis.

    Science.gov (United States)

    Maleki, N; Tavosi, Z

    2015-02-01

    To evaluate thyroid dysfunction and autoimmunity in women with gestational diabetes and to investigate the frequency of postpartum thyroiditis in women with gestational diabetes. A total of 350 women with gestational diabetes and 350 healthy pregnant women were enrolled in the study. We studied the thyroid hormone profiles of the women in each group during pregnancy (at 24-28 weeks' gestation) and after delivery (at 6 weeks, 3, 6 and 9 months, and 1 year postpartum). A total of 342 women with gestational diabetes and 313 healthy pregnant women completed the follow-up during pregnancy and 1 year after delivery. Of the women with gestational diabetes, 16.6% had thyroid dysfunction, while of the healthy pregnant women, 6.1% had thyroid dysfunction. The prevalence of postpartum thyroiditis was higher in the women with a history of gestational diabetes (19.6%) than in the healthy pregnant women (10.2%), and this difference was statistically significant. According to the results of the present study, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes than in healthy women. We recommend that all women with gestational diabetes and women who have previous thyroid dysfunction should be screened for thyroid hormonal abnormalities during pregnancy and for 1 year after pregnancy. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  19. Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

    Directory of Open Access Journals (Sweden)

    Manal Alkan

    2015-01-01

    Full Text Available Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD mouse model. To this end, we used mice (inactivated knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC−/− mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC−/− mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC−/− mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response.

  20. Meta-analysis of STAT4 and IFIH1 polymorphisms in type 1 diabetes mellitus patients with autoimmune polyglandular syndrome type III.

    Science.gov (United States)

    de Azevêdo Silva, J; Tavares, N A C; Santos, M M S; Moura, R; Guimarães, R L; Araújo, J; Crovella, S; Brandão, L A C

    2015-12-22

    Type 1 diabetes mellitus (T1D) is an organ-specific autoimmune disease characterized by T-cell mediated self-destruction of insulin-producing β cells in the pancreas. T1D patients are prone to develop other glandular autoimmune disorders, such as autoimmune thyroid disease that occurs simultaneously with autoimmune polyglandular syndrome type III (APSIII). Signal transducer and activator of transcription 4 (STAT4) is a well-known regulator of proinflammatory cytokines, and interferon-induced with helicase C domain 1 (IFIH1) is activated in the interferon type I response. Both genes have been examined separately in autoimmune diseases and, in this study, we assessed their joint role in T1D and APSIII. We conducted a case-control study, enrolling 173 T1D patients and 191 healthy controls from northeastern Brazil, to assess the distribution of the rs7574865 and rs3024839 SNPs in STAT4 and the rs3747517 and rs1990760 SNPs in IFIH1 in T1D and APSIII patients. Additionally, we conducted a meta-analysis with the rs7574865 SNP in STAT4 (1392 T1D patients and 1629 controls) and the rs1990760 SNP in IFIH1 (25092 T1D patients and 28544 controls) to examine their association with T1D. Distribution of STAT4 and IFIH1 allelic frequencies did not show statistically significant differences between T1D patients and controls in our study population; however, the meta-analysis indicated that SNPs in STAT4 and IFIH1 are associated with T1D worldwide. Our findings indicate that although STAT4 and IFIH1 SNPs are not associated with T1D in a Brazilian population, they might play a role in susceptibility to T1D on a larger worldwide scale.

  1. B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model.

    Science.gov (United States)

    Da Rosa, Larissa C; Boldison, Joanne; De Leenheer, Evy; Davies, Joanne; Wen, Li; Wong, F Susan

    2018-06-01

    Type 1 diabetes is a T cell-mediated autoimmune disease characterised by the destruction of beta cells in the islets of Langerhans, resulting in deficient insulin production. B cell depletion therapy has proved successful in preventing diabetes and restoring euglycaemia in animal models of diabetes, as well as in preserving beta cell function in clinical trials in the short term. We aimed to report a full characterisation of B cell kinetics post B cell depletion, with a focus on pancreatic islets. Transgenic NOD mice with a human CD20 transgene expressed on B cells were injected with an anti-CD20 depleting antibody. B cells were analysed using multivariable flow cytometry. There was a 10 week delay in the onset of diabetes when comparing control and experimental groups, although the final difference in the diabetes incidence, following prolonged observation, was not statistically significant (p = 0.07). The co-stimulatory molecules CD80 and CD86 were reduced on stimulation of B cells during B cell depletion and repopulation. IL-10-producing regulatory B cells were not induced in repopulated B cells in the periphery, post anti-CD20 depletion. However, the early depletion of B cells had a marked effect on T cells in the local islet infiltrate. We demonstrated a lack of T cell activation, specifically with reduced CD44 expression and effector function, including IFN-γ production from both CD4 + and CD8 + T cells. These CD8 + T cells remained altered in the pancreatic islets long after B cell depletion and repopulation. Our findings suggest that B cell depletion can have an impact on T cell regulation, inducing a durable effect that is present long after repopulation. We suggest that this local effect of reducing autoimmune T cell activity contributes to delay in the onset of autoimmune diabetes.

  2. Organ-specific autoimmunity in type 1 diabetes mellitus: Screening with respect to glycemic control

    Directory of Open Access Journals (Sweden)

    Mohamed Ghada A

    2016-01-01

    Full Text Available Type 1 diabetes (T1D is a tissue-specific autoimmune disease and often associated with other autoimmune diseases; so our study aimed to define the occurrence of thyroid peroxidase antibody (TPOAb and thyroglobulin antibody (TGAb in autoimmune thyroid disease (AIT, tissue transglutaminase antibody (TTGAb in celiac disease, And to evaluate the relationship between the presence of these antibodies and glycemic control. Our retrospective study included 60 Kuwaiti patients with T1D who attended and follow in Diabetes outpatient clinics of Kuwait primary health care centers during the period of 2014-2015. For them, recorded data for age, sex, duration of diabetes, Body Mass Index (BMI, HbA1c was reviewed. Patients were screened for the presence of Specific antibodies to islet antigens (ICAb, glutamic acid decarboxylase autoantibodies (GADAb, insulin autoantibodies (IAA, TPOAb, TGAb, TTGAb and also thyroid stimulating hormone (TSH were measured by ELISA. Of the total 60 patients (20 men, 40women, mean age was17.95 ± (5.44 y; the mean duration of diabetes was 6.63 ± (4.27 y; mean HbA1c was 10.41± (1.96 %. Only 58 (96.7% wer e positive for GADAb, 32 (53.3% were positive for ICAb, and 48 (80% were positive for IAA, 14 (23.3% patients were positive for TPOAb, 11 (18.3% were positive for TGAb, 10 (16.7 % were positive for both TPOAb and TGAb; furthermore 8 (13.3% patients were positive for TTGAb. Neither organ-specific autoimmune disease (AIT and celiac disease nor pancreatic β cells autoantibodies had a significant association with the glycemic control. In our study, we confirmed the high prevalence of a second organ-specific autoimmune disease in individuals with type 1 diabetes. Also Subclinical forms of these disorders have no influence on diabetes control. Further research will be necessary to test these relationships in a prospective follow-up study

  3. High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block.

    Science.gov (United States)

    Lisney, Anna R; Szelinski, Franziska; Reiter, Karin; Burmester, Gerd R; Rose, Thomas; Dörner, Thomas

    2017-08-01

    Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB. Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied. SIGLEC1 expression was measured by flow cytometry and was correlated to plasma IFN-α levels measured by ELISA, and IFN-γ-induced protein 10 (IP-10) levels measured by Bio-Plex technique. Mothers of affected children had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children. SIGLEC1 and IFN-α expression were reduced by hydroxychloroquine and oral glucocorticoids. High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development, and these women may benefit especially from IFN-α directed therapy, for example with hydroxychloroquine. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Type I diabetes among children and young adults: the role of country of birth, socioeconomic position and sex.

    Science.gov (United States)

    Hussen, Hozan Ismael; Yang, Dong; Cnattingius, Sven; Moradi, Tahereh

    2013-03-01

    To investigate associations between country of birth, parental country of birth, and education with respect to incidence rate and time trends of type 1 diabetes mellitus (T1DM) among children and young adults. We followed a nation-wide cohort of 4 469 671 males and 4 231 680 females aged 0-30 years between 1969 and 2008. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) for T1DM were calculated using Poisson regression models. We further calculated age-standardized rates (ASRs) of T1DM, using the world population as standard. During the study period, the ASR of T1DM increased among children younger than 15 years, but not among young adults (15-30 years). Compared with Swedish-born children, male and female immigrant children had 44 and 42% lower IRR of TIDM, respectively. Among offspring to immigrants, corresponding decreases in IRRs were 27 and 24%, respectively. Compared with children to parents with high education, male children to parents with low education had a 10% decreased IRR of T1DM, while no effect was observed among females. The IRR of T1DM increased with increasing age and calendar time of follow-up in both sexes (p-for trend <0.0001). In young adults, the IRR among immigrants decreased by 32% in males and 22% in females, while corresponding reductions in IRRs were less in offspring to immigrants. We found a lower IRR of T1DM among offspring to immigrants, but especially among young immigrants compared with Sweden-born individuals. The findings show that environmental factors are important in the etiology of T1DM. © 2012 John Wiley & Sons A/S.

  5. Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18.

    Science.gov (United States)

    Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christidis, M; Sarri, C; Karadima, G; Petersen, M B; Xaidara, A; Kanariou, M; Nicolaidou, P

    1999-02-01

    A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.

  6. Autoimmunity in type 1 diabetes mellitus: a rat model

    International Nuclear Information System (INIS)

    Liu, Z.

    1987-01-01

    In this study, we have sought to isolate in vitro, from acutely diabetic BB rats, cytotoxic T lymphocytes, which exhibit specific cytotoxicity toward islet cells. Thoracic duct lymphocytes (TDL) from acutely diabetic BB rats cultured with irradiated MHC matched (RT1.u) islet cells and dendritic cells in vitro were shown to be specifically cytotoxic to MHC matched and mismatched allogeneic (RT1.1) and xenogeneic (hamster) islet target cells in a 3 H-leucine release assay. Two cell lines (V1A8 and V1D11) derived from the TDL culture showed similar patterns of non-MHC restricted islet cell killing which could be blocked by islet cells and cultured rat insulinoma cells (RIN5mF) but not by non-islet cells of various tissue origins. Both V1A8 and V1D11 were not cytotoxic to Natural Killer (NK) sensitive target cells, G1TC and YAC-1. Conventional surface markers for rat helper and suppressor/cytotoxic T cells were not detectable on either cell lines. The V1D11 cell line was positive for W 3/13 (rat T/NK marker) on OX-19 (rat T/macrophage marker), whereas the V1A8 cell line was only positive for W 3/13

  7. Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aleksandra Krzewska

    2016-01-01

    Full Text Available Type 1 diabetes mellitus (T1DM is one of the most common chronic diseases developing in childhood. The incidence of the disease in children increases for unknown reasons at a rate from 3 to 5% every year worldwide. The background of T1DM is associated with the autoimmune process of pancreatic beta cell destruction, which leads to absolute insulin deficiency and organ damage. Complex interactions between environmental and genetic factors contribute to the development of T1DM in genetically predisposed patients. The T1DM-inducing autoimmune process can also affect other organs, resulting in development of additional autoimmune diseases in the patient, thereby impeding diabetes control. The most common T1DM comorbidities include autoimmune thyroid diseases, celiac disease, and autoimmune gastritis; additionally, diabetes can be a component of PAS (Polyglandular Autoimmune Syndrome. The aim of this review is to assess the prevalence of T1DM-associated autoimmune diseases in children and adolescents and their impact on the course of T1DM. We also present suggestions concerning screening tests.

  8. [Evaluation of blood pressure changes by 24-hours ambulatory blood pressure monitoring (ABPM) in young, normotensive patients with diabetes mellitus type I].

    Science.gov (United States)

    Markuszewski, Leszek; Ruxer, Monika; Szadkowska, Agnieszka; Bodalska, Joanna; Bissinger, Andrzej

    2006-01-01

    The aim of this study was to evaluate usefulness of ambulatory blood pressure monitoring (ABPM) to examine circadian patterns of blood pressure (BP) alterations in young, normotensive patients with type I diabetes mellitus (DM1). We studied 43 patients with DM1 aged 18-28 years, with 9-23 years of DM1, without long-term complications. Control group consisted of 32 healthy persons, matched to the DM1 group. 24h ABPM was performed by a Spacelab 90207 device to obtain daytime (7 AM to 11 PM, readings at 20-min interval) and nighttime (11 PM to 7 AM, readings at 30-min interval) measurements in both groups. During the daytime systolic BP (sBP) and diastolic BP (dBP) were not significantly different from the control group. We noted nighttime sBP and dBP higher in DM1 group: sBE 119.7+/-12.6 mmHg vs. 103.817.1; p = 0.001 l dBP 65.5+/-6.2 vs. 61.5+/-3.1; p = 0.001. The loss of fall in BP ('non-dippers') was more prevalent in DM1 group: 49% vs. 9%; p = 0.003. Pulse pressure (PP) was significantly higher in DM1 patients: 50.9+/-6.9 mmHg vs. 44.8+/-5.6 mmHg; p = 0.0001. ABPM is a useful method in detecting early BP alterations in young normotensive patients with diabetes mellitus type 4 1. Increased PP and suppressed diurnal BP variations could represent a increased risk of cardiovascular complications in young patients with diabetes mellitus type 1.

  9. Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance.

    Science.gov (United States)

    Zhang, Chengliang; Gui, Ling; Xu, Yanjiao; Wu, Tao; Liu, Dong

    2013-08-01

    Andrographolide, an active component in traditional anti-diabetic herbal plants, is a diterpenoid lactone isolated from Andrographis paniculata because of its potent anti-inflammatory and hypoglycemic effects. However, the effect of andrographolide on the development of diabetes in autoimmune non-obese diabetic (NOD) mice remains unknown. This study aimed to investigate the protective effects of andrographolide on the development of autoimmune diabetes and clarify the underlying mechanism. NOD mice were randomly divided into four groups and administered with water and andrographolide at 50, 100, and 150mg/kg body weight for four weeks. ICR mice were also selected as the control group. Oral glucose tolerance and histopathological insulitis were examined. Th1/Th2/Th17 cytokine secretion was determined by ELISA. The transcriptional profiles of T-bet, GATA3, and RORγt in the pancreatic lymphatic node samples derived from the NOD mice were detected by RT-PCR. After four weeks of oral supplementation, andrographolide significantly inhibited insulitis, delayed the onset, and suppressed the development of diabetes in 30-week-old NOD mice in a dose dependent manner. This protective status was correlated with a substantially decreased production of interferon (IFN)-γ and interleukin (IL)-2, increased IL-10 and transforming growth factor (TGF)-β, and a reduced IL-17. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and RORγt mRNA expressions. Our results suggested that andrographolide prevented type 1 diabetes by maintaining Th1/Th2/Th17 homeostasis. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Genetic disassociation of autoimmunity and resistance to costimulation blockade-induced transplantation tolerance in nonobese diabetic mice.

    Science.gov (United States)

    Pearson, Todd; Markees, Thomas G; Serreze, David V; Pierce, Melissa A; Marron, Michele P; Wicker, Linda S; Peterson, Laurence B; Shultz, Leonard D; Mordes, John P; Rossini, Aldo A; Greiner, Dale L

    2003-07-01

    Curing type 1 diabetes by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. Most islet allotransplant tolerance induction protocols have been tested in nonobese diabetic (NOD) mice, and most have failed. Failure has been attributed to the underlying autoimmunity, assuming that autoimmunity and resistance to transplantation tolerance have a common basis. Out of concern that NOD biology could be misleading in this regard, we tested the hypothesis that autoimmunity and resistance to transplantation tolerance in NOD mice are distinct phenotypes. Unexpectedly, we observed that (NOD x C57BL/6)F(1) mice, which have no diabetes, nonetheless resist prolongation of skin allografts by costimulation blockade. Further analyses revealed that the F(1) mice shared the dendritic cell maturation defects and abnormal CD4(+) T cell responses of the NOD but had lost its defects in macrophage maturation and NK cell activity. We conclude that resistance to allograft tolerance induction in the NOD mouse is not a direct consequence of overt autoimmunity and that autoimmunity and resistance to costimulation blockade-induced transplantation tolerance phenotypes in NOD mice can be dissociated genetically. The outcomes of tolerance induction protocols tested in NOD mice may not accurately predict outcomes in human subjects.

  11. Racial and ethnic differences among children with new-onset autoimmune Type 1 diabetes.

    Science.gov (United States)

    Gandhi, K; Tosur, M; Schaub, R; Haymond, M W; Redondo, M J

    2017-10-01

    To compare demographic and clinical characteristics among children from ethnic minorities and non-Hispanic white children with new-onset autoimmune Type 1 diabetes. We analysed a single-centre series of 712 children with new-onset autoimmune Type 1 diabetes between January 2008 and March 2011. The median (range) age was 9.7 (0.3-18.1) years, the mean (sd) BMI percentile was 69.7 (25.4) and 48.3% of the cohort were girls. The cohort comprised 57.3% non-Hispanic white, 20.5% Hispanic and 14.8% African-American children, and 7.4% were of other, mixed or unknown race. The Hispanic subgroup, compared with non-Hispanic white subgroup, had a higher mean (sd) C-peptide level [0.82 (1.62) vs 0.55 (0.47) ng/ml; P=0.004), and a greater proportion of children with elevated BMI (overweight or obesity; 49.6% vs 32.5%; P1) and diabetic ketoacidosis (51.8% vs 38.2%; P=0.006). The African-American group had a higher mean (sd) glucose level [24.4 (12.8) vs 21.4 (10.7) mmol/l; P=0.017], a greater proportion of children with ketoacidosis (56.7% vs 38.2%; P=0.001), a greater proportion with elevated BMI (52.9% vs 32.5%; P1), and a lower proportion of children at pre-pubertal stage (49.0% vs 61.6%; P=0.01), and tended to have higher C-peptide levels [0.65 (0.59) vs 0.55 [0.47] ng/ml; P=0.079) compared with the non-Hispanic white children. The differences in C-peptide levels compared with non-Hispanic white children persisted for Hispanic (P=0.01) but not African-American children (P=0.29) after adjustment for age, sex, BMI, ketoacidosis, glucose, Tanner stage and autoantibody number. At the onset of paediatric autoimmune Type 1 diabetes, Hispanic, but not African-American children had higher C-peptide levels, after adjustment for potential confounders, compared with non-Hispanic white children. These findings suggest that ethnicity may contribute to the heterogeneity of Type 1 diabetes pathogenesis, with possible implications for intervention. © 2017 Diabetes UK.

  12. Ethnic differences in progression of islet autoimmunity and type 1 diabetes in relatives at risk.

    Science.gov (United States)

    Tosur, Mustafa; Geyer, Susan M; Rodriguez, Henry; Libman, Ingrid; Baidal, David A; Redondo, Maria J

    2018-06-21

    We hypothesised that progression of islet autoimmunity and type 1 diabetes mellitus differs among races/ethnicities in at-risk individuals. In this study, we analysed the data from the Type 1 Diabetes TrialNet Pathway to Prevention Study. We studied 4873 non-diabetic, autoantibody-positive relatives of individuals with type 1 diabetes followed prospectively (11% Hispanic, 80.9% non-Hispanic white [NHW], 2.9% non-Hispanic black [NHB] and 5.2% non-Hispanic other [NHO]). Primary outcomes were time from single autoantibody positivity confirmation to multiple autoantibody positivity, and time from multiple autoantibody positivity to type 1 diabetes mellitus diagnosis. Conversion from single to multiple autoantibody positivity was less common in Hispanic individuals than in NHW individuals (HR 0.66 [95% CI 0.46, 0.96], p = 0.028) adjusting for autoantibody type, age, sex, Diabetes Prevention Trial Type 1 Risk Score and HLA-DR3-DQ2/DR4-DQ8 genotype. In participants who screened positive for multiple autoantibodies (n = 2834), time to type 1 diabetes did not differ by race/ethnicity overall (p = 0.91). In children who were <12 years old when multiple autoantibody positivity was determined, being overweight/obese had differential effects by ethnicity: type 1 diabetes risk was increased by 36% in NHW children (HR 1.36 [95% CI 1.04, 1.77], p = 0.024) and was nearly quadrupled in Hispanic children (HR 3.8 [95% CI 1.6, 9.1], p = 0.0026). We did not observe this interaction in participants who were ≥12 years old at determination of autoantibody positivity, although this group size was limited. No significant differential risks were observed between individuals of NHB and NHW ethnicity. The risk and rate of progression of islet autoimmunity were lower in Hispanic compared with NHW at-risk individuals, while significant differences in the development of type 1 diabetes were limited to children <12 years old and were modified by BMI.

  13. Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nishida Yayoi

    2012-05-01

    Full Text Available Abstract Background Both angiotensin II type I receptor blockers (ARBs and calcium channel blockers (CCBs are widely used antihypertensive drugs. Many clinical studies have demonstrated and compared the organ-protection effects and adverse events of these drugs. However, few large-scale studies have focused on the effect of these drugs as monotherapy on laboratory parameters. We evaluated and compared the effects of ARB and CCB monotherapy on clinical laboratory parameters in patients with concomitant hypertension and type 2 diabetes mellitus. Methods We used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of new ARB users (n = 601 and propensity-score matched new CCB users (n = 601, with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We used a multivariate-adjusted regression model to adjust for differences between ARB and CCB users, and compared laboratory parameters including serum levels of triglyceride (TG, total cholesterol (TC, non-fasting blood glucose, hemoglobin A1c (HbA1c, sodium, potassium, creatinine, alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyltransferase (GGT, hemoglobin and hematocrit, and white blood cell (WBC, red blood cell (RBC and platelet (PLT counts up to 12 months after the start of ARB or CCB monotherapy. Results We found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and RBC count and a significant increase of serum potassium in ARB users, and a reduction of serum TC and hemoglobin in CCB users, from the baseline period to the exposure period. The reductions of RBC count, hemoglobin and hematocrit in ARB users were significantly greater than those in CCB users. The increase of serum potassium in ARB users was significantly greater than that in CCB users. Conclusions Our study suggested that hematological adverse effects and

  14. Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response.

    Science.gov (United States)

    Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco

    2015-12-01

    Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

  15. Alkaptonuria in a boy with type 1 diabetes mellitus, vitiligo, autoimmune thyroiditis and immunoglobulin A deficiency - a case report.

    Science.gov (United States)

    Hogendorf, Anna; Pietrzak, Iwona; Antosik, Karolina; Borowiec, Maciej; Młynarski, Wojciech

    2016-01-01

    We present a 15-year-old Caucasian boy with an exceptional coincidence of a rare monogenic metabolic disease - alkaptonuria (AKU) and a cluster of autoimmune disorders: type 1 diabetes (T1DM), autoimmune thyroiditis (AIT), vitiligo, insulin infusion induced lipoatrophy and immunoglobulin A deficiency (IgAD) Alkaptonuria and type 1 diabetes in a child, especially in such an interesting coincidence with other autoimmune conditions, has not been reported so far. Our investigation, including comprehensive genetic evaluation using next generation sequencing technology, shows that alkaptonuria and T1DM were independently inherited. We also show that alkaptonuria in its pre-ochronotic phase seems to have no effect on the course of diabetes. © Polish Society for Pediatric Endocrinology and Diabetology.

  16. Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus in Kearns-Sayre syndrome

    Directory of Open Access Journals (Sweden)

    A. Berio

    2013-06-01

    Full Text Available Kearns-Sayre syndrome is characterized by onset before 20 years, chronic progressive external opthalmoplegia, pigmentary retinal degeneration, and ataxia (and/or hearth block, and/or high protein content in the cerebrospinal fluid in the presence of mtDNA rearrangements. Multiple endocrine dysfunction associated with this syndrome was rarely reported. In this paper, the Authors report on a female patient with Kearns-Sayre syndrome with large heteroplasmic mtDNA deletion, absence of cytochrome c oxidase in many muscle fibers, partial GH deficiency, hypothyroidism and subsequently insulin dependent diabetes mellitus (IDDM. Anti-thyroid peroxidase and antithyreoglobulin antibodies were present in high titer in serum while anti-islet cell antibodies were absent. The patient developed thyroiditis with Hashimoto encephalopathy. The presence of GH deficiency, autoimmune thyroiditis with hypothyroidism and IDDM distinguishes this case from others and confirms the association of Kearns-Sayre syndrome with multiple endocrine dysfunction. Hashimoto encephalopathy and anti-thyroideal antibodies suggest that in this patient, predisposed by a genetic factor (a mitochondrial deletion anti-thyroideal antibodies may have contributed to the hypothyroidism and, by interfering with cerebral mitochondrial function, may have caused the encephalopathy. GH deficiency and IDDM can be attributed to oxidative phosphorylation deficiency but the autoimmunity may also have played a role in the production of glandular insufficiencies. It seems important to search for endocrine autoimmunity in every case of KSS.

  17. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Directory of Open Access Journals (Sweden)

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  18. Autoimmune Diabetes Associated With Pembrolizumab: A Review of Published Case Reports.

    Science.gov (United States)

    Cheema, Anmol; Makadia, Bhaktidevi; Karwadia, Tejas; Bajwa, Ravneet; Hossain, Mohammad

    2018-02-01

    The utility of immunotherapy, such as pembrolizumab, is becoming essential in the treatment of certain cancers. Pembrolizumab works through binding of programmed cell death 1 receptor that blocks the binding of the programmed cell death ligand 1 and is commonly used in non-small cell lung cancer and melanoma. Pembrolizumab has been reported to be associated with multiple adverse reactions such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes; however, pembrolizumab causing type 1 diabetes was only reported in 0.1% of the patients in clinical trials. A review of the literature generated 1,001 unique citations of which six reported cases of autoimmune diabetes associated with pembrolizumab were selected and compared. Review of the cases showed no sexual predilection and the average age of onset was 58 years old. The majority of the patients were treated for melanoma (5/6 cases), initially presented with diabetic ketoacidosis (4/6 cases), and had at one point taken ipilimumab (4/6 cases). There was no association found between the number of treatments received and the development of diabetes. With the increasing use of pembrolizumab in cancer treatment regular blood glucose monitoring during treatment, especially in patients who had also taken ipilimumab, may prevent the onset of this life-threatening complication.

  19. Effects of Non-HLA Gene Polymorphisms on Development of Islet Autoimmunity and Type 1 Diabetes in a Population With High-Risk HLA-DR,DQ Genotypes

    NARCIS (Netherlands)

    Steck, Andrea K.; Wong, Randall; Wagner, Brandie; Johnson, Kelly; Liu, Edwin; Romanos, Jihane; Wijmenga, Cisca; Norris, Jill M.; Eisenbarth, George S.; Rewers, Marian J.

    We assessed the effects of non-HLA gene polymorphisms on the risk of islet autoimmunity (IA) and progression to type 1 diabetes in the Diabetes Autoimmunity Study in the Young. A total of 1,743 non-Hispanic, white children were included: 861 first-degree relatives and 882 general population children

  20. Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.

    Science.gov (United States)

    Lin, Marvin; Yin, Na; Murphy, Barbara; Medof, M Edward; Segerer, Stephan; Heeger, Peter S; Schröppel, Bernd

    2010-09-01

    The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model. The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.

  1. Etiology of Organ-Specific Autoimmunity: Basic Research and Clinical Implications in IBD

    Directory of Open Access Journals (Sweden)

    George S Eisenbarth

    1996-01-01

    Full Text Available Autoimmunity develops in the setting of genetic susceptibility and can be monogenic (eg, autoimmune polyendocrine syndrome type I with Addison’s disease, mucocutaneous candidiasis and hypoparathyroidism, which is autosomal recessive with the causative gene on the tip of chromosome 21 or polygenic (usually with important alleles within the major histocompatibility complex [eg, type I diabetes]. In addition to genetic susceptibility, many autoimmune disorders can be classified into etiological categories (oncogenic, drug-induced, diet-induced, infectious or idiopathic. For most autoimmune disorders there are multiple target autoantigens and, for type I diabetes, a combinatorial approach (eg, expression of at least two autoantibodies of insulin, glutamic acid decarboxylase and/or ICA512/IA-2 is the best predictor of diabetes risk. Finally, antigen-specific therapies hold promise for the prevention and therapy of autoimmunity, eg, parenteral or oral therapy with insulin delays or prevents type I diabetes in animal models, and a small pilot trial of parenteral insulin in humans suggests that such therapy may similarly prevent diabetes in humans.

  2. [From gene to disease; mutations in the WFS1-gene as the cause of juvenile type I diabetes mellitus with optic atrophy (Wolfram syndrome)

    NARCIS (Netherlands)

    Pennings, R.J.E.; Dikkeschei, L.D.; Cremers, C.W.R.J.; Ouweland, J.M.W. van den

    2002-01-01

    Wolfram syndrome patients are mainly characterised by juvenile onset diabetes mellitus and optic atrophy. A synonym is the acronym DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy, deafness. Diabetes insipidus and sensorineural high-frequency hearing impairment are important additional

  3. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    International Nuclear Information System (INIS)

    Lee, Y.S.; Kim, D.; Lee, E.K.; Kim, S.; Choi, C.S.; Jun, H.S.

    2015-01-01

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  4. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.S.; Kim, D.; Lee, E.K. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Kim, S. [Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827 (Korea, Republic of); Choi, C.S. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Endocrinology, Internal Medicine, Gachon University Gil Medical Center, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Jun, H.S., E-mail: hsjun@gachon.ac.kr [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of)

    2015-04-15

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  5. The association between Helicobacter pylori infection, type 1 diabetes mellitus, and autoimmune thyroiditis.

    Science.gov (United States)

    Zekry, Osama A; Abd Elwahid, Hassan A

    2013-12-01

    Type 1 diabetes mellitus (T1DM) can be associated with an increased prevalence of Helicobacter pylori infection, which could contribute to the pathogenesis of autoimmune thyroiditis observed in this disease. The aim of this study was to assess the relationship between H. pylori infection and T1DM and to identify of the interconnection between H. pylori infection and autoimmune thyroiditis in patients with T1DM. A case-control design was used. The study group included 60 children and adolescents with T1DM who were selected from the pediatric outpatient clinic of Suez Canal University Hospital by a systematic random sampling method. The control group included 60 healthy children and adolescents matched for age and sex and selected from among relatives (brothers or cousins) of the patients with T1DM. The study participants were subjected to several investigations including estimation of levels of HbA1c, thyroid stimulating hormone (TSH), T3, T4, anti-thyroglobulin (anti-Tg), and anti-thyroid peroxidase (anti-TPO). The mean age of the patients with T1DM was 12.53±2.35 years, whereas that of the control group was 12.30±1.98 years, with no statistically significant difference between the two groups. The patients with diabetes had significantly higher levels of H. pylori IgG, TSH, anti-TPO, and anti-Tg (20.43±14.84  μ/ml, 4.03±1.53 mIu/l, 14.98 ±5.04 Iu/ml, and 5.66±3.37 Iu/ml, respectively) and significantly lower levels of T3 and T4 (120±15.86 μg/dl and 4.93±0.93 μg/dl, respectively) compared with the control group. In addition, the seroprevalence rate of H. pylori, anti-Tg, and anti-TPO was significantly higher in diabetic patients, and the duration of diabetes was significantly longer in H. pylori-positive patients with higher levels of HbA1c, insulin requirement, TSH, anti-TPO, and anti-Tg. The association between H. pylori infection and autoimmune thyroiditis in patients with T1DM was revealed in this study. Hence, screening and treatment of

  6. Latent autoimmune diabetes of adults: From oral hypoglycemic agents to early insulin

    Directory of Open Access Journals (Sweden)

    Resham R Poudel

    2012-01-01

    Full Text Available Approximately 10% of phenotypic type 2 diabetics have islet autoantibodies and are referred to as having latent autoimmune diabetes of adults (LADA, and they land on early sulfonylurea failure and require insulin. Diagnosing LADA has treatment implications because of high risk of progression to insulin dependency. But often there is delay in insulin therapy, as there are no recommendations for islet antibody testing in adult-onset diabetes currently. LADA clinical risk score can identify adults at high risk who may benefit from antibody testing. The optimal treatment of LADA is not established. Early insulin therapy helps to achieve good metabolic control and better long-term outcomes by preserving b-cells and endogenous C-peptide secretion. Sulfonylureas are better avoided as they exhaust b-cells; glitazones and exenatide have favorable outcomes, whereas metformin needs to be used with caution. Understanding LADA will also bring new windows in managing type 1 diabetes. Information acquisition was done by reviewing the medical literature published since 1987, with particular attention to the natural history, genetic factors, and treatment of LADA.

  7. Autoimmunity and Gastric Cancer

    Science.gov (United States)

    Bizzaro, Nicola; Antico, Antonio; Villalta, Danilo

    2018-01-01

    Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms. PMID:29373557

  8. Whole body glucose kinetics in type I diabetes studied with [6,6-2H] and [U-13C]-glucose and the artificial B-cell

    International Nuclear Information System (INIS)

    Darmaun, D.; Cirillo, D.; Koziet, J.; Chauvet, D.; Young, V.R.; Robert, J.J.

    1988-01-01

    Dynamic aspects of whole body glucose metabolism were assessed in ten young adult insulin-dependent (type I) diabetic men. Using a primed, continuous intravenous infusion of [6,6- 2 H]glucose and [U- 13 C]glucose, endogenous production, tissue uptake, carbon recycling, and oxidation of glucose were measured in the postabsorptive state. These studies were undertaken after blood glucose had been maintained overnight at 5.9 +/- 0.4 mmol/L (n = 10), and on another night at 10.5 +/- 0.4 mmol/L (n = 4) or 15.2 +/- 0.6 mmol/L (n = 6). In the normoglycemic state, endogenous glucose production averaged 2.15 +/- 0.13 mg x kg-1 x min-1. This value, as well as the rate of glucose carbon recycling (0.16 +/- 0.04 mg x kg-1 x min-1) and glucose oxidation (1.52 +/- 0.16 mg x kg-1 x min-1) are comparable to those found in nondiabetic controls. In the hyperglycemic states at 10 or 15 mmol/L, endogenous glucose production was increased by 11% (P less than .01) and 60% (P less than .01) compared to the normoglycemic states, respectively. Glucose carbon recycling contributed only a small percentage to this variation in glucose production (15% at the 15 mmol/L glucose level). This suggests that if gluconeogenesis participates in the increased glucose output, it is not dependent on a greater systemic supply of three-carbon precursors. The increased rate of glucose production in the hyperglycemic state was quantitatively offset by a rise in urinary glucose excretion. Glucose tissue uptake, as well as glucose oxidation, did not vary between normoglycemic and hyperglycemic states

  9. Type I supernova models

    International Nuclear Information System (INIS)

    Canal, Ramon; Labay, Javier; Isern, Jordi

    1987-01-01

    We briefly describe the characteristics of Type I supernova outbursts and we present the theoretical models so far advanced to explain them. We especially insist on models based on the thermonuclear explosion of a white dwarf in a close binary system, even regarding the recent division of Type I supernovae into the Ia and Ib subtypes. Together with models assuming explosive thermonuclear burning in a fluid interior, we consider in some detail those based on partially solid interiors. We finally discuss models that incorporate nonthermonuclear energy contributions, suggested in order to explain Type Ib outbursts. (Author)

  10. Analysis of antibody responses against Coxsackie virus B4 protein 2C and the diabetes autoantigen GAD65.

    NARCIS (Netherlands)

    Vreugdenhil, G.R.; Batstra, M.R.; Aanstoot, H.J.; Melchers, W.J.G.; Galama, J.M.D.

    1999-01-01

    Type I diabetes mellitus results from the autoimmune destruction of insulin producing beta cells in the pancreas. Certain viral infections, especially those caused by coxsackie B viruses and related enteroviruses, have been associated with the development of type I diabetes. The sequence homology

  11. Diabetes insipidus is an unfavorable prognostic factor for response to glucocorticoids in patients with autoimmune hypophysitis.

    Science.gov (United States)

    Lupi, Isabella; Cosottini, Mirco; Caturegli, Patrizio; Manetti, Luca; Urbani, Claudio; Cappellani, Daniele; Scattina, Ilaria; Martino, Enio; Marcocci, Claudio; Bogazzi, Fausto

    2017-08-01

    Autoimmune hypophysitis (AH) has a variable clinical presentation and natural history; likewise, its response to glucocorticoid therapy is often unpredictable. To identify clinical and radiological findings associated with response to glucocorticoids. 12 consecutive patients with AH, evaluated from 2008 to 2016. AH was the exclusion diagnosis after ruling out other pituitary masses and secondary causes of hypophysitis. Mean follow-up time was 30 ± 27 months (range 12-96 months). MRI identified two main patterns of presentation: global enlargement of the pituitary gland or panhypophysitis ( n  = 4, PH), and pituitary stalk abnormality only, or infundibulo-neuro-hypophysitis ( n  = 8, INH). Multiple tropin defects were more common in PH (100%) than those in INH (28% P  = 0.014), whereas diabetes insipidus was more common in INH (100%) than that in PH (50%; P  = 0.028). All 4 PH and 4 out of 8 INH were treated with glucocorticoids. Pituitary volume significantly reduced in all PH patients ( P  = 0.012), defective anterior pituitary function recovered only in the two patients without diabetes insipidus (50%) and panhypopituitarism persisted, along with diabetes insipidus, in the remaining 2 (50%). In all INH patients, either treated or untreated, pituitary stalk diameter reduced ( P  = 0.008) but diabetes insipidus persisted in all. Glucocorticoid therapy may improve anterior pituitary function in a subset of patients but has no effect on restoring posterior pituitary function. Diabetes insipidus appears as a negative prognostic factor for response to glucocorticoids. © 2017 European Society of Endocrinology.

  12. A bispecific protein capable of engaging CTLA-4 and MHCII protects non-obese diabetic mice from autoimmune diabetes.

    Directory of Open Access Journals (Sweden)

    Hongmei Zhao

    Full Text Available Crosslinking ligand-engaged cytotoxic T lymphocyte antigen-4 (CTLA-4 to the T cell receptor (TCR with a bispecific fusion protein (BsB comprised of a mutant mouse CD80 and lymphocyte activation antigen-3 (LAG-3 has been shown to attenuate TCR signaling and to direct T-cell differentiation toward Foxp3(+ regulatory T cells (Tregs in an allogenic mixed lymphocyte reaction (MLR. Here, we show that antigen-specific Tregs can also be induced in an antigen-specific setting in vitro. Treatment of non-obese diabetic (NOD female mice between 9-12 weeks of age with a short course of BsB elicited a transient increase of Tregs in the blood and moderately delayed the onset of autoimmune type 1 diabetes (T1D. However, a longer course of treatment (10 weeks of 4-13 weeks-old female NOD animals with BsB significantly delayed the onset of disease or protected animals from developing diabetes, with only 13% of treated animals developing diabetes by 35 weeks of age compared to 80% of the animals in the control group. Histopathological analysis of the pancreata of the BsB-treated mice that remained non-diabetic revealed the preservation of insulin-producing β-cells despite the presence of different degrees of insulitis. Thus, a bifunctional protein capable of engaging CTLA-4 and MHCII and indirectly co-ligating CTLA-4 to the TCR protected NOD mice from developing T1D.

  13. Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18

    OpenAIRE

    Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christid..., M; Sarri, C; Karadima, G; Petersen, M; Xaidara, A; Kanariou, M; Nicolaidou, P

    1999-01-01

    A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimm...

  14. Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes

    Science.gov (United States)

    Thornley, Thomas B.; Ma, Lingzhi; Chipashvili, Vaja; Aker, Jonathan E.; Korniotis, Sarantis; Csizmadia, Eva; Strom, Terry B.; Koulmanda, Maria

    2016-01-01

    The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D) pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs) from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D. PMID:26943809

  15. Contrasting Roles of Islet Resident Immunoregulatory Macrophages and Dendritic Cells in Experimental Autoimmune Type 1 Diabetes.

    Directory of Open Access Journals (Sweden)

    Thomas B Thornley

    Full Text Available The innate immune system critically shapes diabetogenic adaptive immunity during type 1 diabetes (T1D pathogenesis. While the role of tissue-infiltrating monocyte-derived macrophages in T1D is well established, the role of their tissue-resident counterparts remains undefined. We now demonstrate that islet resident macrophages (IRMs from non-autoimmune mice have an immunoregulatory phenotype and powerfully induce FoxP3+ Tregs in vitro. The immunoregulatory phenotype and function of IRMs is compromised by TLR4 activation in vitro. Moreover, as T1D approaches in NOD mice, the immunoregulatory phenotype of IRMs is diminished as is their relative abundance compared to immunostimulatory DCs. Our findings suggest that maintenance of IRM abundance and their immunoregulatory phenotype may constitute a novel therapeutic strategy to prevent and/or cure T1D.

  16. Prevalence of celiac disease autoimmunity in children with type 1 diabetes

    DEFF Research Database (Denmark)

    Adlercreutz, Emma H; Svensson, Jannet; Hansen, Dorte

    2015-01-01

    OBJECTIVES: The aim was to determine the prevalence of celiac disease autoimmunity in children with type 1 diabetes (T1D) diagnosed in Denmark and Sweden. METHODS: A total of 662 Swedish children with T1D were matched with 1080 Danish children with T1D and 309 healthy children from Sweden and 283...... was equally distributed among 89 children with T1D positive for both IgAG-DGP/tTG and IgG-tTG. CONCLUSION: The discrepancy in levels of IgAG-DGP/tTG and IgG-tTG between Swedish and Danish T1D cohorts was independent of HLA and suggests that regional variations in comorbidity of celiac disease in T1D is caused...

  17. Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

    Science.gov (United States)

    Yokoi, N; Hidaka, S; Tanabe, S; Ohya, M; Ishima, M; Takagi, Y; Masui, N; Seino, S

    2012-01-01

    Although the MHC class II ‘u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a' and ‘u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II ‘a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis. PMID:21918539

  18. Prevalence of thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes and diabetes type 1.

    Science.gov (United States)

    Velkoska Nakova, V; Krstevska, B; Dimitrovski, Ch; Simeonova, S; Hadzi-Lega, M; Serafimoski, V

    2010-01-01

    The aim of the present study was to determine the prevalence of abnormal thyroid function and antithyroid antibodies during pregnancy in women with diabetes type 1 and gestational diabetes mellitus (GDM). The study group included 83 pregnant women who attended the Outpatient Department of the Endocrinology, Diabetes and Metabolic Disorders Clinic in the period from 05.2009 to 11.2009. The one hundred-g. oral glucose tolerance test (OGTT) was conducted on the pregnant women except for women with diabetes type 1. Thyroid functions were evaluated in all the pregnant women. After routine screening for GDM, thirty of the pregnant women were healthy and GDM was diagnosed in forty of them. The rest, thirteen women, had diabetes type 1. The women who developed GDM showed a mean free thyroxin concentration (fT4) significantly lower than that observed in the healthy pregnant women and women with diabetes type 1. Among the pregnant women with GDM, 10 women or 25% had fT4 concentrations below the lower cut-off with normal thyroid-stimulating hormone concentrations (TSH). A statistically significant difference was found in the prevalence of antithyroid antibodies (anti-TPO) between the (30%) women with diabetes type 1 and (10%) healthy pregnant women (p<0.05). In the women positive for anti-TPO, TSH was significantly higher (p<0.05). The significantly higher prevalence of hypothyroxinemia in GDM pregnancies and anti-TPO titres in pregnancies with diabetes type 1, than in healthy pregnant women warrants routine screening for thyroid abnormalities in these groups of pregnant women.

  19. [Myasthenia gravis, Graves-Basedow disease and other autoimmune diseases in patient with diabetes type 1 - APS-3 case report, therapeutic complications].

    Science.gov (United States)

    Klenczar, Karolina; Deja, Grażyna; Kalina-Faska, Barbara; Jarosz-Chobot, Przemysława

    2017-01-01

    Diabetes type 1(T1D) is the most frequent form of diabetes in children and young people, which essence is autoimmune destruction of pancreatic B cells islet. Co-occurrence of other autoimmune diseases is observed in children with T1D, the most often are: Hashimoto disease or coeliac disease. We report the case of the patient, who presents coincidence of T1D with other rare autoimmune diseases such as: Graves - Basedow disease, myasthenia gravis, vitiligo and IgA deficiency. All mentioned diseases significantly complicated both endocrine and diabetic treatment of our patient and they negatively contributed her quality of life. The clinical picture of the case allows to recognize one of the autoimmune polyendocrine syndromes: APS-3 and is associated with still high risk of developing another autoimmune disease. © Polish Society for Pediatric Endocrinology and Diabetology.

  20. [Diabetes and autoimmune diseases: prevalence of celiac disease in children and adolescents with type 1 diabetes].

    Science.gov (United States)

    Mont-Serrat, Camila; Hoineff, Claudio; Meirelles, Ricardo M R; Kupfer, Rosane

    2008-12-01

    Determine the prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus (DM1) in attendance in Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione (IEDE). Blood samples were analyzed in 120 children and adolescents with DM1 from IEDE Diabetes Clinic for the IgA antitissue-transglutaminase antibody and dosage of the seric IgA. Those with positive serology were guided for upper endoscopy with small-bowel biopsy to confirm the celiac disease. The antibody was positive in 3 of the 120 patients. The small-bowel biopsy was confirmatory in all of the positive patients, leading to a prevalence of celiac disease of 2.5% in the studied group. The prevalence of celiac disease is increased in children and adolescents with DM1 when compared with normality. As most are asymptomatic, it is recommended periodical screening of celiac disease in children with DM1.

  1. Association of sarcopenia with both latent autoimmune diabetes in adults and type 2 diabetes: a cross-sectional study.

    Science.gov (United States)

    Bouchi, Ryotaro; Fukuda, Tatsuya; Takeuchi, Takato; Nakano, Yujiro; Murakami, Masanori; Minami, Isao; Izumiyama, Hajime; Hashimoto, Koshi; Yoshimoto, Takanobu; Ogawa, Yoshihiro

    2017-06-01

    To investigate the association of both latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2DM) with muscle mass and function (sarcopenia). Japanese patients with LADA (N=20), T2DM (N=208), and control subjects (N=41) were included in this cross-sectional study. The definition of LADA was based on age of onset (≥30), positive glutamic acid decarboxylase autoantibodies, and insulin requirement within the first 6months after diagnosis. Sarcopenia was diagnosed by the criteria for Asians, using skeletal muscle index (male sarcopenia was higher in LADA (35.0%) than in either T2DM (13.3%) or control subjects (9.8%). LADA was significantly associated with an increased risk for sarcopenia in a multivariate model in which age and body mass index were incorporated (OR: 9.57, 95% CI: 1.86-49.27). In contrast, T2DM tended to be associated with an increased risk for sarcopenia (OR: 2.99, 95% CI: 0.83-10.80). This study provides evidence that patients with LADA are at a high risk for sarcopenia compared to those with T2DM or to control subjects. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Adam L. Burrack

    2017-12-01

    Full Text Available Type 1 diabetes (T1D results from destruction of pancreatic beta cells by T cells of the immune system. Despite improvements in insulin analogs and continuous blood glucose level monitoring, there is no cure for T1D, and some individuals develop life-threatening complications. Pancreas and islet transplantation have been attractive therapeutic approaches; however, transplants containing insulin-producing cells are vulnerable to both recurrent autoimmunity and conventional allograft rejection. Current immune suppression treatments subdue the immune system, but not without complications. Ideally a successful approach would target only the destructive immune cells and leave the remaining immune system intact to fight foreign pathogens. This review discusses the autoimmune diabetes disease process, diabetic complications that warrant a transplant, and alloimmunity. First, we describe the current understanding of autoimmune destruction of beta cells including the roles of CD4 and CD8 T cells and several possibilities for antigen-specific tolerance induction. Second, we outline diabetic complications necessitating beta cell replacement. Third, we discuss transplant recognition, potential sources for beta cell replacement, and tolerance-promoting therapies under development. We hypothesize that a better understanding of autoreactive T cell targets during disease pathogenesis and alloimmunity following transplant destruction could enhance attempts to re-establish tolerance to beta cells.

  3. Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes.

    Science.gov (United States)

    Redondo, M J; Rodriguez, L M; Haymond, M W; Hampe, C S; Smith, E O; Balasubramanyam, A; Devaraj, S

    2014-12-01

    Obesity increases the risk of cardiovascular disease and diabetic complications in type 1 diabetes. Adipokines, which regulate obesity-induced inflammation, may contribute to this association. We compared serum adipokines and inflammatory cytokines in obese and lean children with new-onset autoimmune type 1 diabetes. We prospectively studied 32 lean and 18 obese children (age range: 2-18 yr) with new-onset autoimmune type 1 diabetes and followed them for up to 2 yr. Serum adipokines [leptin, total and high molecular weight (HMW) adiponectin, omentin, resistin, chemerin, visfatin], cytokines [interferon (IFN)-gamma, interleukin (IL)-10, IL-12, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha] and C-reactive protein (CRP) were measured at a median of 7 wk after diagnosis (range: 3-16 wk). Lean children were 71.9% non-Hispanic White, 21.9% Hispanic, and 6.3% African-American, compared with 27.8, 55.6, and 16.7%, respectively, for obese children (p = 0.01). Compared with lean children, obese children had significantly higher serum leptin, visfatin, chemerin, TNF-alpha and CRP, and lower total adiponectin and omentin after adjustment for race/ethnicity and Tanner stage. African-American race was independently associated with higher leptin among youth ≥10 yr (p = 0.007). Leptin levels at onset positively correlated with hemoglobin A1c after 1-2 yr (p = 0.0001) independently of body mass index, race/ethnicity, and diabetes duration. Higher TNF-alpha was associated with obesity and female gender, after adjustment for race/ethnicity (p = 0.0003). Obese children with new-onset autoimmune type 1 diabetes have a proinflammatory profile of circulating adipokines and cytokines that may contribute to the development of cardiovascular disease and diabetic complications. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Genetic analysis of autoimmune sialadenitis in nonobese diabetic mice: a major susceptibility region on chromosome 1.

    Science.gov (United States)

    Boulard, Olivier; Fluteau, Guy; Eloy, Laure; Damotte, Diane; Bedossa, Pierre; Garchon, Henri-Jean

    2002-04-15

    The nonobese diabetic (NOD) mouse strain provides a good study model for Sjögren's syndrome (SS). The genetic control of SS was investigated in this model using different matings, including a (NOD x C57BL/6 (B6))F(2) cross, a (NOD x NZW)F(2) cross, and ((NOD x B6) x NOD) backcross. Multiple and different loci were detected depending on parent strain combination and sex. Despite significant complexity, two main features were prominent. First, the middle region of chromosome 1 (chr.1) was detected in all crosses. Its effect was most visible in the (NOD x B6)F(2) cross and dominated over that of other loci, including those mapping on chr.8, 9, 10, and 16; the effect of these minor loci was observed only in the absence of the NOD haplotype on chr.1. Most critically, the chr.1 region was sufficient to trigger an SS-like inflammatory infiltrate of salivary glands as shown by the study of a new C57BL/6 congenic strain carrying a restricted segment derived from NOD chr.1. Second, several chromosomal regions were previously associated with NOD autoimmune phenotypes, including Iddm (chr.1, 2, 3, 9, and 17, corresponding to Idd5, Idd13, Idd3, Idd2, and Idd1, respectively), accounting for the strong linkage previously reported between insulitis and sialitis, and autoantibody production (chr.10 and 16, corresponding to Bana2 and Bah2, respectively). Interestingly, only two loci were detected in the (NOD x NZW)F(2) cross, on chr.1 in females and on chr.7 in males, probably because of the latent autoimmune predisposition of the NZW strain. Altogether these findings reflect the complexity and heterogeneity of human SS.

  5. Diabetes mellitus de tipo I y púrpura trombocitopénica inmunitaria en una niña Diabetes mellitus type I and immune thrombocytopenic purpura in a girl

    Directory of Open Access Journals (Sweden)

    José Raúl Zaldívar Ochoa

    2009-02-01

    Full Text Available Se detalla el caso clínico de una paciente de 11 años de edad, con antecedentes de diabetes mellitus de tipo I, que comenzó a presentar manchas de color rojo oscuro en la piel (similares a moretones en brazos, frente y piernas desde hacía 3 meses. Fue ingresada en el Hospital Infantil Norte Docente de Santiago de Cuba y luego de ser tratada con prednisona e insulina, al quinto día de administrarle esteroides comenzaron a disminuir las lesiones hemorrágicas cutáneas y otras a desaparecer. Egresó con un plan terapéutico específico e indicaciones para seguimiento clínico en las respectivas consultas de hematología y endocrinología pediátricasThe clinical case of an 11 year-old patient, with a history of diabetes mellitus type I who began to present spots of dark red color in the skin (similar to contusions arms, forehead and legs for 3 months is detailed. She was admitted to the Northern Teaching Hospital from Santiago de Cuba and after being treated with prednisona and insulin, on the fifth day of treatment with steroids the skin hemorrhagic lesions began to decrease and others to disappear. She was discharged with a specific therapeutic plan and indications for clinical follow-up in the respective hematologic and pediatric Endocrinology visits.

  6. Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

    Science.gov (United States)

    Hoffmanová, I; Sánchez, D; Hábová, V; Anděl, M; Tučková, L; Tlaskalová-Hogenová, H

    2015-01-01

    Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (PCLD when compared to healthy controls. However, the levels of cCK-18 (PCLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (PCLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.

  7. [Prevalence of the Diabetic Retinopathy and Genetic Factors Significance in the Development of Diabetic Retinopathy in Patients with Diabetes Mellitus type I and II in Slovakia (DIARET SK study). Overview of Actual Findings and Design of the Epidemiological DIARET SK Study].

    Science.gov (United States)

    Krásnik, V; Štefaničková, J; Fabková, J; Bucková, D; Helbich, M

    2015-09-01

    Diabetic retinopathy (DR) is the second most common microvascular complication and the most common cause of blindness in patients with diabetes mellitus (DM). Despite the ongoing research, the findings of diabetic retinopathy epidemiological and risk factors are, until now, not consistent. More finding may be revealed by epidemiological studies, consistently mapping DR epidemiology under the current possibilities of investigations and treatment of the DM. DIARET SK Study, with 5 000 enrolled patients with diabetes mellitus in the Slovak Republic, is, until now, the largest epidemiological study to set the prevalence of diabetic retinopathy. The primary aim is to establish the prevalence of diabetic retinopathy in patients with diabetes mellitus type I and II, according to the duration of the disease. The secondary aim is to establish prevalence of the different stages of the DR and diabetic macular edema (DME) and analysis of the risk factors influence. Included are patients with DM type I and II regardless to the ocular complications history and the period of DM duration. Each enrolled patient has both complex diabetic and ophthalmic examinations.Projects to establish DR prevalence: Tens of projects concerned with diabetic retinopathy epidemiology with different approaches to establish the prevalence and with different patients population. Results from different studies vary significantly (from 12.3 % to 66.9 %). The results depend on the design of the study and the patients recruitment, used examination methods, specific patients population with regard to the geography, prevalence of risk factors, period of diabetes duration, glycated hemoglobin (HbA1C) level, blood pressure, and is higher in type I diabetic patients. The most accurate results are from population epidemiological studies with well-controlled patient recruitment and uniform complex examination that are similar to the DIARET SK study. The DIARET SK study represents the largest epidemiological study

  8. Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes

    Directory of Open Access Journals (Sweden)

    Sean Linkes

    2010-01-01

    Full Text Available Following proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a population of such cells remained after secondary and tertiary TCR stimulation and produced cytokines upon antigenic challenge. However, when NOD blasts were induced in the presence of rIL-15, the number of antigen-experienced “CD4lo” T cells was significantly reduced. Clonal contraction, mediated in part by CD95-dependent activation-induced cell death (AICD, normally regulates the accumulation of “CD4hi” effectors. Interestingly, CD95 expression was dramatically reduced on the AICD-resistant NOD “CD4lo” T cells. Thus, while autoimmune disease has often been attributed to the engagement of robust autoimmunity, we suggest that the inability to effectively contract the immune response distinguishes benign autoimmunity from progressive autoimmune diseases that are characterized by chronic T cell-mediated inflammation.

  9. Downregulation of cathepsin G reduces the activation of CD4+ T cells in murine autoimmune diabetes.

    Science.gov (United States)

    Zou, Fang; Lai, Xiaoyang; Li, Jing; Lei, Shuihong; Hu, Lei

    2017-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM. To this end, mouse studies were conducted to demonstrate that CatG impacts the activation of CD4+ T cells in non-obese diabetic (NOD) mice. CatG gene expression and the activation of CD4+ T cells were examined in NOD mice. The effect of CatG inhibitor was investigated in NOD mice on the activation of CD4+ T cells, islet β cell function, islet inflammation and β-cell apoptosis. Furthermore, NOD mice were injected with CatG siRNA in early stage to observe the effect of CatG knockdown on the activation status of CD4+ T cells and the progression of diabetes. During the pathogenesis of diabetes, the expression level of CatG in NOD mice gradually increased and the CD4+ T cells were gradually activated, resulting in more TH1 cells and less TH2 and Treg cells. Treatment with CatG-specific inhibitor reduced the blood glucose level, improved the function of islet β cells and reduced the activation of CD4+ T cells. Early application of CatG siRNA improved the function of islet β cells, reduced islet inflammation and β cell apoptosis, and lowered the activation level of CD4+ T cells, thus slowing down the progression of diabetes.

  10. Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

    Science.gov (United States)

    Rogowicz-Frontczak, Anita; Pilacinski, Stanislaw; Chwialkowska, Anna Teresa; Naskret, Dariusz; Zozulinska-Ziolkiewicz, Dorota

    2018-04-19

    To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

  11. Getting “Inside” Type I IFNs: Type I IFNs in Intracellular Bacterial Infections

    Directory of Open Access Journals (Sweden)

    Deann T. Snyder

    2017-01-01

    Full Text Available Type I interferons represent a unique and complex group of cytokines, serving many purposes during innate and adaptive immunity. Discovered in the context of viral infections, type I IFNs are now known to have myriad effects in infectious and autoimmune disease settings. Type I IFN signaling during bacterial infections is dependent on many factors including whether the infecting bacterium is intracellular or extracellular, as different signaling pathways are activated. As such, the repercussions of type I IFN induction can positively or negatively impact the disease outcome. This review focuses on type I IFN induction and downstream consequences during infection with the following intracellular bacteria: Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Salmonella enterica serovar Typhimurium, Francisella tularensis, Brucella abortus, Legionella pneumophila, and Coxiella burnetii. Intracellular bacterial infections are unique because the bacteria must avoid, circumvent, and even co-opt microbial “sensing” mechanisms in order to reside and replicate within a host cell. Furthermore, life inside a host cell makes intracellular bacteria more difficult to target with antibiotics. Because type I IFNs are important immune effectors, modulating this pathway may improve disease outcomes. But first, it is critical to understand the context-dependent effects of the type I IFN pathway in intracellular bacterial infections.

  12. [The influence of metabolic disturbances present in diabetes mellitus type I on vestibulo-spinal reflexes in children and young adults].

    Science.gov (United States)

    Gawron, Wojciech; Pośpiech, Lucyna; Orendorz-Fraczkowska, Krystyna; Noczyńska, Anna

    2002-01-01

    Diabetic neuropathy encompasses various disturbances concerning somatic and autonomic nervous system and has significant impact on prognosis and course of diabetes mellitus. The aim of the work is an evaluation of vestibulo-spinal reflexes in children and young adults suffering from diabetes mellitus type 1. Material--95 children and young adults aged from 6 to 28 years with diabetes mellitus type 1 diagnosed. The control group consisted of 44 otoneurologically healthy subjects aged from 6 to 28 years. After detailed medical history collection and physical ENT examination stato-posturography was performed in each case. Posturographer PE 62 Model 04 was applied in the studies. Static posturography as well as dynamic one (one leg standing test) was performed in each case. 6 patients belonging to diabetic group complained about vertigo or dizziness. There were worse stabilograms parameters in diabetic group in comparison to control one, statistically significant in younger children. There were better stabilogram parameters in diabetic patients with longer history of the disease. The parameters analysed were significantly worse in the subgroup with not compensated diabetes. The parameters were slightly better in relation to the presence of hypoglycaemic incidents. No apparent differences in stabilograms parameters were present in relation to the presence of diabetic complications. Diabetes mellitus type 1 with slight or without complications does not have significant influence on vestibulo-spinal reflexes and posture stability of the patients. Balance organ disturbances in diabetes mellitus type 1 in children and young adults despite their presence have subclinical course. Perhaps one should consider monitoring of those disturbances in the course of the disease.

  13. Glutaric aciduria type I

    International Nuclear Information System (INIS)

    Mandel, H.; Berant, M.; Braun, J.; Technion-Israel Inst. of Tech., Haifa; El-Peleg, O.; Christensen, E.

    1991-01-01

    Serial CT findings in an infant with glutaric aciduria type I (GA-I) are reported. The major CT features were dilatation of the insular cisterns, regression of the temporal lobes, with 'bat wings' dilatation of the Sylvian fissures and hypodensity of the lenticular nuclei. CT changes preceded the onset of symptoms by 3 months. An improvement in the temporal lobe atrophy was seen after a period of treatment, coinciding with marked clinical improvement. A peculiar feature was the presence of external hydrocephalus, which diverted the attention from manifestations of the primary disease and thus constituted a diagnostic pitfall. The delineation and recognition of the characteristic radiologic manifestations of GA-I are essential for allowing an adequate radiologist/clinician interaction in diagnosing this inborn error of metabolism. (orig.)

  14. Metabolic risk profiles in diabetes stratified according to age at onset, islet autoimmunity and fasting C-peptide

    DEFF Research Database (Denmark)

    Wod, Mette; Yderstræde, Knud B; Halekoh, Ulrich

    2017-01-01

    OBJECTIVE: Islet autoimmunity, age at onset and time to insulin treatment are often used to define subgroups of diabetes. However, the latter criterion is not clinical useful. Here, we examined whether an unbiased stratification of diabetes according to age at onset, fasting C-peptide and GAD......, fasting C-peptide above or below 300 pmol/l (CPEPhigh or CPEPlow), and presence or absence of GADab (GADpos or GADneg). HbA1c, BMI, blood pressure (BP), lipid profile, alanine aminotransferase (ALT) and creatinine were evaluated. RESULTS: GADab were present in 13% of the cohort. Age at onset...... as GADposCPEPhigh; n=327) and patients with type 2 diabetes (GADnegCPEPhigh; n=3,544). Patients with LADA defined an intermediate group with higher HbA1c but otherwise lower cardiometabolic risk than patients with type 2 diabetes. CONCLUSIONS: Our results demonstrate that fasting C-peptide and GADab status...

  15. Similar weight-adjusted insulin secretion and insulin sensitivity in short-duration late autoimmune diabetes of adulthood (LADA) and Type 2 diabetes

    DEFF Research Database (Denmark)

    Juhl, C B; Bradley, U; Holst, Jens Juul

    2014-01-01

    AIMS: To explore insulin sensitivity and insulin secretion in people with latent autoimmune diabetes in adulthood (LADA) compared with that in people with Type 2 diabetes. METHODS: A total of 12 people with LADA, defined as glutamic acid decarboxylase (GAD) antibody positivity and > 1 year...... of insulin independency (group A) were age-matched pairwise to people with Type 2 diabetes (group B) and to six people with Type 2 diabetes of similar age and BMI (group C). β-cell function (first-phase insulin secretion and assessment of insulin pulsatility), insulin sensitivity (hyperinsulinemic......-euglycemic clamp) and metabolic response during a mixed meal were studied. RESULTS: Both first-phase insulin secretion and insulin release during the meal were greater (P = 0.05 and P = 0.009, respectively) in Type 2 diabetes as compared with LADA; these differences were lost on adjustment for BMI (group C...

  16. Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells

    International Nuclear Information System (INIS)

    Lin, Gu-Jiun; Sytwu, Huey-Kang; Yu, Jyh-Cherng; Chen, Yuan-Wu; Kuo, Yu-Liang; Yu, Chiao-Chi; Chang, Hao-Ming; Chan, De-Chuan; Huang, Shing-Hwa

    2015-01-01

    Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells. - Highlights: • We report a therapeutic potential of DMSO in autoimmune diabetes. • DMSO exhibits an immune modulatory effect. • DMSO treatment increases regulatory T cell differentiation. • The increase in STAT5 signaling pathway explains the effect of DMSO in Tregs

  17. Dimethyl sulfoxide inhibits spontaneous diabetes and autoimmune recurrence in non-obese diabetic mice by inducing differentiation of regulatory T cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gu-Jiun [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Sytwu, Huey-Kang [Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, ROC (China); Yu, Jyh-Cherng [Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Chen, Yuan-Wu [School of Dentistry, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Kuo, Yu-Liang [Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC (China); School of Medical Imaging and Radiological Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC (China); Yu, Chiao-Chi [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Chang, Hao-Ming; Chan, De-Chuan [Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China); Huang, Shing-Hwa, E-mail: h610129@gmail.com [Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC (China); Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (China)

    2015-01-15

    Type 1 diabetes mellitus (T1D) is caused by the destruction of insulin-producing β cells in pancreatic islets by autoimmune T cells. Islet transplantation has been established as an effective therapeutic strategy for T1D. However, the survival of islet grafts can be disrupted by recurrent autoimmunity. Dimethyl sulfoxide (DMSO) is a solvent for organic and inorganic substances and an organ-conserving agent used in solid organ transplantations. DMSO also exerts anti-inflammatory, reactive oxygen species scavenger and immunomodulatory effects and therefore exhibits therapeutic potential for the treatment of several human inflammatory diseases. In this study, we investigated the therapeutic potential of DMSO in the inhibition of autoimmunity. We treated an animal model of islet transplantation (NOD mice) with DMSO. The survival of the syngeneic islet grafts was significantly prolonged. The population numbers of CD8, DC and Th1 cells were decreased, and regulatory T (Treg) cell numbers were increased in recipients. The expression levels of IFN-γ and proliferation of T cells were also reduced following DMSO treatment. Furthermore, the differentiation of Treg cells from naive CD4 T cells was significantly increased in the in vitro study. Our results demonstrate for the first time that in vivo DMSO treatment suppresses spontaneous diabetes and autoimmune recurrence in NOD mice by inhibiting the Th1 immune response and inducing the differentiation of Treg cells. - Highlights: • We report a therapeutic potential of DMSO in autoimmune diabetes. • DMSO exhibits an immune modulatory effect. • DMSO treatment increases regulatory T cell differentiation. • The increase in STAT5 signaling pathway explains the effect of DMSO in Tregs.

  18. Estudo Comparativo dos Resultados Maternos e Perinatais entre Pacientes com Diabetes Pré-gestacional Tipo I e Tipo II Comparative Study of Maternal and Perinatal Outcomes among Patients with Pregestational Type I and Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Micheline Monte de Carvalho

    2000-06-01

    Full Text Available Objetivos: avaliar a evolução da gestação, controle metabólico e resultados perinatais de pacientes diabéticas pré-gestacionais e fazer um estudo comparativo entre os resultados de pacientes com diabetes insulino-dependente e não-insulino-dependente. Métodos: análise retrospectiva de prontuários de 57 pacientes com diagnóstico de diabetes pré-gestacional que iniciaram pré-natal no Serviço de Medicina Materno-Fetal da Maternidade-Escola Assis Chateaubriand da Universidade Federal do Ceará, no período de janeiro 1995 a dezembro de 1998. As 57 grávidas incluídas no estudo foram divididas em dois grupos: grupo I, composto de 28 pacientes portadoras de diabetes insulino-dependente (tipo I, e grupo II, com 29 gestantes com diabetes não-insulino-dependente (tipo II controladas com dieta ou com hipoglicemiante oral antes da gestação. Resultados: não houve diferença estatisticamente significante entre os dois grupos em relação à necessidade de internamento para controle glicêmico (39,2% x 27,5% e complicações maternas, tais como: hipertensão arterial crônica (14,2% x 27,5%, doença hipertensiva específica da gravidez (14,2% x 17,2%, amniorrexe prematura (3,5% x 10,3%, infecção do trato urinário (10,7% x 6,8% e trabalho de parto prematuro (3,5% x 6,8%. Foi observado, porém, maior número de episódios de hipoglicemia materna entre as pacientes insulino-dependentes (35,7% x 3,4%. Os resultados perinatais foram semelhantes. Observamos elevados índices de malformações e morbimortalidade perinatal. Conclusão: não houve diferença na incidência de intercorrências clínicas e obstétricas entre as pacientes insulino-dependentes e não-insulino-dependentes, excluindo-se hipoglicemia materna.Purpose: to evaluate the evolution of gestation, metabolic control and perinatal outcome of pregestational diabetic patients and to perform a comparative study of the results of patients with insulin-dependent diabetes (type I and

  19. [Prevalence of autoimmune diseases and microangiopathy in children with diabetes type 1 over the years 2000-2010].

    Science.gov (United States)

    Głowińska-Olszewska, Barbara; Ordowska, Urszula; Golonko, Magdalena; Tobiaszewska, Monika; Florys, Bożena; Jabłońska, Jolanta; Otocka, Agnieszka; Łuczyński, Włodzimierz; Zasim, Aneta; Jakubowska, Ewa; Michalak, Justyna; Bossowski, Artur

    2013-01-01

    In the past decade the number of patients with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) has increased rapidly. Treatment of the disease is focused on proper physical development and the prevention of complications. Aim of the study was to analyze changes in the treatment and clinical picture of type 1 diabetes in children over the years 2000 to 2010 with particular emphasis on the presence of autoimmune diseases and microangiopathy. The study included 567 children diagnosed with type 1 diabetes under the care of outpatient diabetes clinic. We compared 251 children, diabetes outpatient clinic patients in 2000, with 316 children in 2010. Data were obtained from the outpatient and hospital records. We compared baseline demographic, anthropometric data, treatment regimen, type of insulin, metabolic control, prevalence of autoimmune diseases and microangipathy. In 2010 there was a reduction in the age of diagnosis of diabetes from 10 to 8 years (p=0.039). Significantly increased the proportion of children treated with CSII (up to 60.1%) and decreased the percentage of children using conventional insulin for the benefit of insulin analogs. The increase in HbA1c from 7.4 to 8.0% (p7.5% in 2010. The percentage of children with obesity increased from 5.2 to 13.7% (p=0.004) and there was a significant increase in SDS-BMI. The percentage of children with autoimmune diseases such as celiac (from 0,4 to 7,3%, p<0,001) and thyroid (from 6.9 to 21.3%, p<0.001) has increased. The incidence of retinopathy decreased from 6 to 1% (p=0.04), and albuminuria decreased insignificantly. Over the last decade, a significant change in the method of treatment in children diagnosed with type 1 diabetes has occurred. The deterioration of metabolic control, despite the frequent use in the treatment of CSII, may be due to increased frequency of obesity and additional autoimmune diseases in today´s patients. More similar to physiologic way of insulin infusion

  20. Autoimmune liver disease and therapy in childhood

    Directory of Open Access Journals (Sweden)

    Matjaž Homan

    2013-10-01

    Full Text Available Autoimmune hepatitis is a chronic immune-mediated disease of the liver. In childhood, autoimmune liver disorders include autoimmune hepatitis type I and II, autoimmune sclerosing cholangitis, Coombs-positive giant cell hepatitis, and de novo autoimmune hepatitis after liver transplantation. Autoimmune liver disease has a more aggressive course in children, especially autoimmune hepatitis type II. Standard therapy is a combination of corticosteroids and azathioprine. Around 80 % of children with autoimmune liver disease show a rapid response to combination therapy. The non-responders are treated with more potent drugs, otherwise autoimmune disease progresses to cirrhosis of the liver and the child needs liver transplantation as rescue therapy.

  1. Worldwide differences in the incidence of type I diabetes are associated with amino acid variation at position 57 of the HLA-DQ beta chain.

    OpenAIRE

    Dorman, J S; LaPorte, R E; Stone, R A; Trucco, M

    1990-01-01

    The presence of an amino acid other than aspartic acid at position 57 of the HLA-DQ beta chain (non-Asp-57) is highly associated with susceptibility to insulin-dependent diabetes mellitus (IDDM), whereas an aspartic acid at this position (Asp-57) appears to confer resistance to the disease. We hypothesize that the 30-fold difference in IDDM incidence across racial groups and countries is related to variability in the frequency of these alleles. Diabetic and nondiabetic individuals were evalua...

  2. THE CONTENT OF MICROELEMENTS IN BLOOD SERUM AND ERYTHROCYTES IN CHILDREN WITH DIABETES MELLITUS TYPE I DEPENDING ON LEVEL OF GLYCEMIC CONTROL.

    Science.gov (United States)

    Gluschenko, N; Vasylyshyn, Kh; Roschupkin, A; Lekishvili, S; Gladchenko, O

    2016-01-01

    The aim of this paper is to investigate the content of chromium, cobalt and nickel in serum and erythrocytes in children with type 1 diabetes mellitus, depending on the level of glycemic control. The study was conducted on 68 children with type 1 diabetes mellitus. The patients were divided into four groups based on glycemic control. Group I was composed of 9 children with optimal level of glycemic control. Group II - 25 children with suboptimal level of glycemic control. Group III - 34 children with a high risk to life level of glycemic control. Group IV (control group) consisted of 30 healthy children. Compensation state of type 1 diabetes was evaluated according to ISPAD (Consensus for the Management of Type 1 Diabetes Mellitus in Children and Adolescens 2000). The content of trace elements in biological agents was determined by atomic absorbtion spectrophotometry method with C-115M1 mass-spectrophotometer, manufactured by «Selmi» enterprise (Ukraine). It is found that there is a decrease in serum concentrations of chromium and erythrocyte content of cobalt in patients with optimal level of glycemic control. The deficiency of chromium is accompanied by the deficiency of cobalt in patients with suboptimal level of glycemic control. The lower levels of cobalt and nickel are recorded simultaneously, but there is theexcess of chromium in the erythrocytes of these patients. Patients, who suffer from 1 type diabetes mellitus and high risk for life level of glycemic control have considerable polideficiency of cobalt, nickel and chromium in serum.The increasing level of chromium was recorded only in the erythrocytes. The level of glycemic control and the duration of 1 type diabetes mellitus are important in the forecasting of the development of chronic diabetic complications. It is found that the duration of 1 type diabetes mellitus influences the levels of cobalt and nickel in serum mostly, while the level of glycemic control influences the chromium content.

  3. Impaired hapten sensitization in patients with autoimmune disease

    DEFF Research Database (Denmark)

    Bangsgaard, N; Engkilde, K; Menné, T

    2011-01-01

    An inverse relation between contact allergy and autoimmune diseases is suggested from epidemiological studies. The aim of this study was to investigate susceptibility and reactivity in patients with psoriasis, patients with diabetes and healthy controls in an experimental sensitization study. We......-regulatory mechanisms with immunohistochemistry and gene-expression profiles using microarray technology. The sensitization ratios were 26%, 36% and 65% for the psoriatic, diabetic and healthy groups, respectively. Logistic regression analysis gave an odds ratio (OR) for a patient with psoriasis or diabetes type I...

  4. Psychological screening in children with diabetes mellitus type-I at the Children's Hospital and the Institute of Child Health, Multan

    International Nuclear Information System (INIS)

    Khan, W.I.; Waqar, M.; Rabbani, M.W.; Afzal, E.; Adnan, M.

    2013-01-01

    Objective: To determine the frequency of psychological problems in diabetic children. Methods: The cross-sectional study was conducted at the Diabetic clinic of the Children's Hospital and the Institute of Child Health, Multan, Pakistan, from March to December 2011. Diabetic patients aged 7-15 years, who were on insulin therapy for at least one year were included in the study. Demographic data, history and physical examination were recorded. Glycosylated haemoglobin level was checked in all cases, and the Childhood Depression Inventory was used to assess the psychological well-being of the children. A minimum score of 13/54 was used to screen for depression. SPSS 19 was used for statistical analysis. Results: Out of 86 diabetic children, clinical depression was observed in 29 (33.7%). Poor socioeconomic status (21/29; 72.4%), longstanding disease (16/29; 55.1%) and adolescence age (20/29; 69%) were the major factors associated with depressive symptoms. Conclusion: Depression is a commonly associated psychological disorder in diabetic children, and should be addressed along with medical and dietary management. (author)

  5. Cholinergic stimulation prevents the development of autoimmune diabetes: Evidence for the modulation of Th17 effector cells via an IFNgamma-dependent mechanism

    Directory of Open Access Journals (Sweden)

    Junu George

    2016-10-01

    Full Text Available Type I diabetes (T1D results from T cell-mediated damage of pancreatic β-cells and loss of insulin production. The cholinergic anti-inflammatory pathway represents a physiological link connecting the central nervous and immune systems via vagus nerve, and functions to control the release of proinflammatory cytokines. Using the multiple-low-dose streptozotocin (MLD-STZ model to induce experimental autoimmune diabetes, we investigated the potential of regulating the development of hyperglycemia through administration of paraoxon, a highly specific acetylcholinesterase inhibitor (AChEI. We demonstrate that pretreatment with paraoxon prevented hyperglycemia in STZ-treated C57BL/6 mice. This correlated with a reduction in T cell infiltration into pancreatic islets and preservation of the structure and functionality of β-cells. Gene expression analysis of pancreatic tissue revealed that increased peripheral cholinergic activity prevented STZ-mediated loss of insulin production, this being associated with a reduction in IL-1β, IL-6, and IL-17 proinflammatory cytokines. Intracellular cytokine analysis in splenic T cells demonstrated that inhibition of AChE led to a shift in STZ-induced immune response from a predominantly disease-causing IL-17-expressing Th17 cells to IFNγ-positive Th1 cells. Consistent with this conclusion, inhibition of AChE failed to prevent STZ-induced hyperglycemia in IFNγ-deficient mice. Our results provide mechanistic evidence for the prevention of murine T1D by inhibition of AChE and suggest a promising strategy for modulating disease severity.

  6. Treated Autoimmune Thyroid Disease Is Associated with a Decreased Quality of Life among Young Persons with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Alena Spirkova

    2015-01-01

    Full Text Available Type 1 diabetes (T1D in children and adolescents is relatively often accompanied by other immunopathological diseases, autoimmune thyroid disease (AITD or celiac disease (CD. Our aim was to assess whether these conditions are associated with changes in the health-related quality of life (HRQOL in pediatric patients with T1D. In a cross-sectional study we identified eligible 332 patients with T1D aged 8–18 years, of whom 248 (75% together with their parents responded to the PedsQL Generic and Diabetes Modules. Compared to 143 patients without thyroid autoantibodies, 40 patients with a thyroxine-treated AITD scored lower in the overall generic HRQOL (P=0.014, as well as in the overall diabetes-specific HRQOL (P=0.013. After adjustment for age, gender, duration of diabetes, type of diabetes treatment, and diabetes control, this association remained statistically significant for the generic HRQOL (P=0.023. Celiac disease was not associated with a change in the generic or diabetes-specific HRQOL (P=0.07  and   P=0.63, resp.. Parental scores showed no association with AITD or celiac disease, except a marginally significant decrease in the overall generic HRQOL (P=0.039 in the T1D + AITD compared to T1D group. Our study indicates that, in pediatric patients with T1D, concomitant thyroxine-treated AITD is associated with lower quality of life.

  7. Caracterización del control metabólico en niños y adolescentes con diabetes mellitus tipo 1 Characterization of the metabolic control in children and adolescents with type I diabetes mellitus

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    Pedro González Fernández

    2012-08-01

    children and adolescents with type I diabetes mellitus. Methods: a prospective study was conducted in 84 patients with type 1 diabetes mellitus, who had been seen at the endocrinology service of "William Soler" university pediatric hospital from February 2010 to August 2011. Glycated haemoglobin (HbA1c was estimated in a period of 90 to 120 days. The quantitative turbidimetric method served to determine hemoglobin A1c by using Futura System reagent. The quarterly results of HbA1c were compared by age, sex, time of evolution of diabetes mellitus, body weight in kg and total daily dosage of insulin. Results: the average age of male patients was 11.6 years (SD= 4,6 and of female patients was 12.4 years (SD= 4.5. The mean age at the beginning of the study was 12.23 years (SD= 4.42 and the mean age at time of diagnosis was 8.27 years (SD= 4.28. The average time of evolution for diabetes was 3.79 years (SD= 3.17 and the daily mean dose of insulin per kg of bodyweight was 0.91 units (SD= 0.26. The HbA1c values were kept over 10 %, except for the two last estimations that showed significantly lower values than those of previous months and were not dependent on the variables sex, time of evolution, age at time of diagnosis and daily average dose of insulin per kilogram of bodyweight. Conclusions: adequate clinical relation and improved adherence to treatment are decisive elements for the improvement of the metabolic control in these patients.

  8. An Average Daily Number of Steps Negatively Correlates with an Average Glycemic Value in Type I Diabetic Patients: Comparison between CGM and Pedometer Records

    Czech Academy of Sciences Publication Activity Database

    Brož, J.; Holubová, A.; Mužík, J.; Oulická, M.; Mužný, M.; Poláček, M.; Fiala, D.; Arsand, E.; Brabec, Marek; Kvapil, M.

    2016-01-01

    Roč. 18, Suppl. 1 (2016), A70-A70 ISSN 1520-9156. [ATTD 2016. International Conference on Advanced Technologies & Treatments for Diabetes /9./. 03.02.2016-06.02.2016, Milan] Institutional support: RVO:67985807 Subject RIV: BB - Applied Statistics, Operational Research

  9. Goal disturbance and coping in children with Type I Diabetes Mellitus : Relationships with health-related quality of life and A1C

    NARCIS (Netherlands)

    van Bussel, A.; Nieuwesteeg, A.M.; Janssen, E.; van Bakel, H.J.A.; Van den Bergh, B.R.H.; Maas-van Schaaijk, N.; Odink, R.; Rijk, C.H.A.M.; Hartman, E.E.

    2013-01-01

    Objective Our first objective was to compare the health-related quality of life (HRQoL) of children with type 1 diabetes mellitus (8–12 years) with that of a healthy reference group, and to compare glycated hemoglobin (A1C) values of these children to recommended guidelines. Our second objective was

  10. The Effect of Chang Run Tong on Biomechanical Colon Remodeling in STZ-Induced Type I Diabetic Rats - Is It Related to Advanced Glycation End Product Formation?

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Gregersen, Hans

    2015-01-01

    BACKGROUND AND AIM: The Chinese medicine Chang Run Tong (CRT) effectively improved senile constipation in the clinics. The aims of the present study were to investigate the effect of CRT on colonic remodeling in streptozotocin (STZ) induced diabetic rats and to explore the mechanisms of the CRT...

  11. Type I interferon signature in systemic lupus erythematosus.

    Science.gov (United States)

    Bezalel, Shira; Guri, Keren Mahlab; Elbirt, Daniel; Asher, Ilan; Sthoeger, Zev Moshe

    2014-04-01

    Type I interferons (IFN) are primarily regarded as an inhibitor of viral replication. However, type I IFN, mainly IFNalpha, plays a major role in activation of both the innate and adaptive immune systems. Systemic lupus erythematosus (SLE) is a chronic, multi-systemic, inflammatory autoimmune disease with undefined etiology. SLE is characterized by dysregulation of both the innate and the adaptive immune systems. An increased expression of type I IFN-regulated genes, termed IFN signature, has been reported in patients with SLE. We review here the role of IFNalpha in the pathogenesis and course of SLE and the possible role of IFNalpha inhibition as a novel treatment for lupus patients.

  12. Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C

    OpenAIRE

    Liu, Xi-yu; Li, Hong

    2017-01-01

    Aims. Latent autoimmune diabetes in adults (LADA) is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods. Blood CD4+ T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results. Reduced global H3 lysine 9 methylation was observed in LADA patients’ CD4+ T lymphocytes, compared to healthy controls (P < 0.05). H3 l...

  13. “The Same or Different”: Strategies of Coping With the “Difference” in the Relationship Among Adolescents With Type I Diabetes and Teenagers

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    Vilma Ražanauskaitė

    2017-09-01

    Full Text Available When child is diagnosed with chronic disease family may face with the crisis. Usually, family and child are left alone, because there is a lack of social aid. There are not many social workers who are capable to offer support for mentioned clients. Social worker’s activity is focused to interaction between individual and environment (Campton, Galaway, 1999 and can address the need for social aid. The individual and family will be able to function independently if they could get social aid on time, the consequences of social exclusion could be avoided or relieved. Diabetes Mellitus type 1 is an invisible illness which can lead to the disability. Very intensive illness management is needed in order to avoid disabling or danger to life complications. In turn, it requires to change personal routine, learn unusual skills and manage various information. Adolescents with diabetes may become “different” because of the illness management requirements. The goal of article is to reveal strategies of coping with the sense of “difference” in the context of relationships between adolescents with type 1 diabetes and teenagers.. What does experience adolescent with diabetes who would like to adapt into teenagers’ group? The qualitative research was implemented with 14 adolescents. Thematic analysis revealed that illness management requirements create a pressure while adolescent feels “not normal” because of the loss of spontaneity, strict planning of everyday activity or if he/she is not able to have a meal with friends. The feeling of “difference” can be managed by keeping trying to maintain imaginable “normalcy”, accepting “difference” as “normalcy” especially in the particular social situations and by the inclusion of “difference” and “normalcy” in adolescent’s identity. The data revealed that research‘s participants experience being “different” in their social environment. Adolescents with diabetes in

  14. Aberrant accumulation of the diabetes autoantigen GAD65 in Golgi membranes in conditions of ER stress and autoimmunity

    DEFF Research Database (Denmark)

    Phelps, Edward A; Cianciaruso, Chiara; Michael, Iacovos P

    2016-01-01

    Pancreatic islet beta cells are particularly susceptible to endoplasmic reticulum (ER) stress, which is implicated in beta cell dysfunction and loss during the pathogenesis of type 1 diabetes (T1D). The peripheral membrane protein GAD65 is an autoantigen in human T1D. GAD65 synthesizes GABA......, an important autocrine and paracrine signaling molecule and a survival factor in islets. We show that ER stress in primary beta cells perturbs the palmitoylation cycle controlling GAD65 endomembrane distribution, resulting in aberrant accumulation of the palmitoylated form in trans-Golgi membranes...... release from stressed and/or damaged beta cells, triggering autoimmunity....

  15. Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammation.

    Science.gov (United States)

    Askenasy, Nadir

    2016-04-01

    The mechanisms of autoimmune reactivity onset in type 1 diabetes (T1D) remain elusive despite extensive experimentation and discussion. We reconsider several key aspects of the early stages of autoimmunity at four levels: islets, pancreatic lymph nodes, thymic function and peripheral immune homeostasis. Antigen presentation is the islets and has the capacity to provoke immune sensitization, either in the process of physiological neonatal β cell apoptosis or as a consequence of cytolytic activity of self-reactive thymocytes that escaped negative regulation. Diabetogenic effectors are efficiently expanded in both the islets and the lymph nodes under conditions of empty lymphoid niches during a period of time coinciding with a synchronized wave of β cell apoptosis surrounding weaning. A major drive of effector cell activation and expansion is inherent peripheral lymphopenia characteristic of neonates, though it remains unclear when is autoimmunity triggered in subjects displaying hyperglycemia in late adolescence. Our analysis suggests that T1D evolves through coordinated activity of multiple physiological mechanisms of stimulation within specific characteristics of the neonate immune system.

  16. The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Price

    2015-06-01

    Full Text Available Dendritic cells (DCs are key antigen presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are 4 main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in autoimmune pathogenesis and regulation, as well as the genetic and environmental signals that influence their function. Specific topics to be addressed include: impact of susceptibility loci on DC subsets, alterations in DC subset development, the role of infection- and host-derived innate inflammatory signals, and the role of the intestinal microbiota on DC phenotype. The effects of these various signals on disease progression and the relative effects of DC subset composition and maturation level of DCs will be examined. These areas will be explored using examples from several autoimmune diseases but will focus mainly on type 1 diabetes.

  17. High Prevalence of Autoimmune Diabetes and Poor Glycaemic Control among Adults in Madagascar: A Brief Report from a Humanitarian Health Campaign in Ambanja

    Directory of Open Access Journals (Sweden)

    Ernesto Maddaloni

    2017-01-01

    Full Text Available Madagascar is a geographically isolated country considered a biodiversity hotspot with unique genomics. Both the low-income and the geographical isolation represent risk factors for the development of diabetes. During a humanitarian health campaign conducted in Ambanja, a rural city in the northern part of Madagascar, we identified 42 adult subjects with diabetes and compared their features to 24 randomly enrolled healthy controls. 42.9% (n=18 of diabetic subjects showed HbA1c values ≥ 9.0%. Unexpectedly, waist circumference and BMI were similar in people with diabetes and controls. Different from the healthy controls, diabetic subjects showed a low prevalence of obesity (5.7% versus 30%, p=0.02. Accordingly, we found a high prevalence of autoimmune diabetes as 12% of people with diabetes showed positivity for the autoantibody against glutamic acid decarboxylase. Diabetic subjects with positive autoantibody had higher HbA1c values (11.3 ± 4.1% versus 8.3 ± 2.6%, p=0.03 compared to diabetic subjects with negative autoantibody. In conclusion, here we describe the presence of diabetes and its features in a rural area of Northern Madagascar, documenting poor glycaemic control and a high prevalence of autoimmune diabetes. These data highlight that the diabetes epidemic involves every corner of the world possibly with different patterns and features.

  18. Hydroethanolic Extract of Strychnos pseudoquina Accelerates Skin Wound Healing by Modulating the Oxidative Status and Microstructural Reorganization of Scar Tissue in Experimental Type I Diabetes

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    Mariáurea M. Sarandy

    2017-01-01

    Full Text Available The effect of topical application of ointment based on Strychnos pseudoquina hydroethanolic extract in the cutaneous wounds healing in diabetic rats was evaluated. Samples of S. pseudoquina were submitted to phytochemical prospection and in vitro antioxidant assay. Thirty Wistar rats were divided into 5 groups: Sal-wounds treated with 0.9% saline solution; VH-wounds treated with 0.6 g of lanolin cream (vehicle; SS-wounds treated with silver sulfadiazine cream (10 mg/g; ES5- and ES10-wounds treated with an ointment of S. pseudoquina extract, 5% and 10%, respectively. Fragments of wounds were removed for histological and biochemical analysis every 7 days during 21 days. ES showed equivalent levels per gram of extract of total phenols and flavonoids equal to 122.04 mg for TAE and 0.60 mg for RE. The chlorogenic acid was one of the major constituents. S. pseudoquina extract presented high antioxidant potential in vitro. ES5 and ES10 showed higher wound healing rate and higher amount of cells, blood vessels, and type III and I collagen. The oxidative stress markers were lower in the ES5 and ES10 groups, while the antioxidants enzymes levels were higher. Ointment based on S. pseudoquina extract promotes a fast and efficient cutaneous repair in diabetic rats.

  19. Mid-term results of bariatric surgery in morbidly obese Japanese patients with slow progressive autoimmune diabetes.

    Science.gov (United States)

    Uno, Kohei; Seki, Yosuke; Kasama, Kazunori; Wakamatsu, Kotaro; Hashimoto, Kenkichi; Umezawa, Akiko; Yanaga, Katsuhiko; Kurokawa, Yoshimochi

    2017-12-11

    Bariatric surgery is recognized as an effective treatment for type 2 diabetes mellitus, but data on its efficacy for type 1 diabetes mellitus, especially slowly progressive insulin-dependent diabetes mellitus, are limited. We investigated five Japanese patients with slowly progressive insulin-dependent diabetes mellitus who underwent bariatric surgery at our center. Five morbidly obese glutamic acid decarboxylase antibody-positive diabetic patients underwent two different types of bariatric surgery. The mean titer of anti-glutamic acid decarboxylase antibody was 4.6 U/mL, and the mean preoperative bodyweight and BMI were 113 kg and 39.6 kg/m 2 , respectively. The mean hemoglobin A1c was 8.4%. The mean fasting serum C-peptide was 5.0 ng/mL. Laparoscopic sleeve gastrectomy was performed in two patients, while laparoscopic sleeve gastrectomy with duodenojejunal bypass was performed in three patients. At one year after surgery, the mean bodyweight and BMI significantly dropped, and the mean percentage of excess weight loss was 96.4%. The mean hemoglobin A1c was 5.7%. This favorable trend was maintained at mid-term. Bariatric surgery for morbidly obese patients with anti-glutamic acid decarboxylase antibody-positive type 1 diabetes mellitus, especially slow progressive autoimmune diabetes, seemed effective in achieving mid-term glycemic control. Longer follow-up with a larger number of patients, as well as validation with more advanced patients with slowly progressive insulin-dependent diabetes mellitus, will be needed. © 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  20. Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients

    DEFF Research Database (Denmark)

    Creutzfeldt, W O; Kleine, N; Willms, B

    1996-01-01

    . kg-1 . min-1 GLP-1 or placebo was infused intravenously in the morning (plasma glucose 13.7 +/- 0.9 mmol/l; plasma insulin 26 +/- 4 pmol/l). Glucose (glucose oxidase method), insulin, C-peptide, glucagon, GLP-1, cortisol, growth hormone (immunoassays), triglycerides, cholesterol, and nonesterified......OBJECTIVE: Glucagon-like peptide I(7-36) amide (GLP-1) is a physiological incretin hormone that, in slightly supraphysiological doses, stimulates insulin secretion, lowers glucagon concentrations, and thereby normalizes elevated fasting plasma glucose concentrations in type II diabetic patients...... fatty acids (enzymatic tests) were measured. RESULTS: Glucagon was reduced from approximately 8 to 4 pmol/l, and plasma glucose was lowered from 13.4 +/- 1.0 to 10.0 +/- 1.2 mmol/l with GLP-1 administration (plasma concentrations approximately 100 pmol, P

  1. Effects of Low Dose Metformin in Adolescents with Type I Diabetes Mellitus: A Randomized, Double-Blinded Placebo-Controlled Study

    Science.gov (United States)

    Nadeau, Kristen; Chow, Kelsey; Alam, Lyla; Lindquist, Kara; Cambell, Sarah; McFann, Kim; Klingensmith, Georgeanna; Walravens, Phillipe

    2014-01-01

    Background Insulin resistance increases during adolescence in those with type 1 diabetes (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, Setting, and Participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages 13–20 years) with T1DM. Participants were randomized to receive either metformin or placebo for six months. HbA1c, insulin dose, waist circumference, BMI, and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI Z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. PMID:24698216

  2. Peripheral blood mononuclear cells of patients with latent autoimmune diabetes secrete higher levels of pro- & anti-inflammatory cytokines compared to those with type-1 diabetes mellitus following in vitro stimulation with β-cell autoantigens

    Directory of Open Access Journals (Sweden)

    Darshan Badal

    2017-01-01

    Interpretation & conclusions: There are differences in the portfolio of cytokine secretion in diabetic subjects with varying rates of β-cell destruction as LADA subjects secrete higher levels of both pro- and anti-inflammatory cytokines on exposure to β-cell autoantigens, thus highlighting another distinguishing feature in the pathophysiology of the two forms of autoimmune diabetes.

  3. Hereditary sensory neuropathy type I

    Directory of Open Access Journals (Sweden)

    Auer-Grumbach Michaela

    2008-03-01

    Full Text Available Abstract Hereditary sensory neuropathy type I (HSN I is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7 identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN, especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra

  4. Hereditary sensory neuropathy type I.

    Science.gov (United States)

    Auer-Grumbach, Michaela

    2008-03-18

    Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin

  5. Interleukin 6 -174(G>C) gene polymorphism is related to celiac disease and autoimmune thyroiditis coincidence in diabetes type 1 children.

    Science.gov (United States)

    Myśliwiec, Małgorzata; Myśliwska, Jolanta; Zorena, Katarzyna; Balcerska, Anna; Malinowska, Ewa; Wiśniewski, Piotr

    2008-10-01

    The aim of the study was to assess the relationship between IL-6 gene polymorphism at -174(G>C) and the coincidence of celiac and autoimmune thyroid diseases with type 1 diabetes mellitus (DM1) in children. 200 children with DM1 aged 13.23+/-3.54 years and 172 healthy controls were analyzed. The IL-6 gene -174(G>C) polymorphism at the promoter region of the gene was analyzed by the PCR-RFLP method. The genotype distribution was significantly different in diabetic children as compared to the healthy controls (p=0.01). In DM1 patients GC heterozygotes were the most common (52.5%), while CC homozygotes accuted for 29% and GG homozygotes only for 18% of cases. In contrast, GG homozygotes were much more frequent among healthy children (31%). Besides, the GG homozygotes were significantly more frequent among diabetic children with celiac disease (p=0.04) in relation to those without autoimmune complications. In children with autoimmune thyroiditis, the distribution of the IL-6 genotypes was similar to that seen in diabetic patients without autoimmune complications (p=0.24). The results of our study suggest that the diabetic children, who have IL-6 gene -174GG genotype may have an increased risk for celiac disease development.

  6. The effects of Low Level LASER Therapy (LLLT) on blood glucose levels in patients with Diabetes Mellitus type I : a case report

    Science.gov (United States)

    Longo, Leonardo; Postiglione, Marco; Buccioni, Tommaso; Longo, Diego

    2009-06-01

    Diabetes Mellitus (DM) is a widespread disease and a serious public health problem. Low Level LASER Therapy (LLLT) has been found to reduce glycaemia on DM type 1 patients, an observation requiring further research especially as regards characteristics of treatment protocol. The purpose of this work is to continue the line of research and propose a specific protocol for LLLT use. In spring 2008 a 48 year old man, DM type 1 insulin dependent patient has been submitted to 810 nm wavelength LLLT treatment in specific body areas daily for 3 weeks and then once a week for 4 weeks until normalization of glycaemia. Medical supervision was present before, during and after application. Insulin was reduced progressively and then stopped. A gradual reduction of glycaemia was noted during the course of treatment. In successive follow-ups a reduction in HbA1c was noted. Results confirm previous observations and need for further research on large cohorts. The indication that LASER may become a valuable addition to DM type 1 treatment is confirmed and the proposed protocol appears to be effective. The case presented merits review since it reports a therapeutic challenge, contributes to advance in medical science and spawns research.

  7. Insulin autoantibodies: evidence of autoimmune disease among a group of Puerto Rican children with newly diagnosed type 1 diabetes mellitus.

    Science.gov (United States)

    González de Pijem, L; Nieves-Rivera, F

    2001-06-01

    Type 1 diabetes is a chronic disease caused by a cell-specific destruction of the insulin producing cells of the pancreas. Although Puerto Rico has the highest incidence of type 1 diabetes among Latin American countries, there is scanty data on the presence of antibodies against insulin producing cells. To this end, 20 children (8 males, 12 females), ages 1-15 years, admitted to the University Pediatric Hospital with type 1 diabetes de novo between November 2000 and April 2001 were prospectively studied to determine the presence of serum antibodies against Islet cells (ICA), glutamic acid decarboxylase (GAD-65) and insulin autoantibodies (IAA). IAA was found to be present in 45% of the subjects with 85% of positive rate in subjects under age 5. GAD-65 was present in 66% and ICA was present in 23% of the subjects. We found evidence of autoimmunity against islet cell surface and intracellular components among a cohort of Puerto Rican children with newly diagnosed type 1 diabetes. These findings compared favorably with reports from other ethnicities.

  8. A unique combination of autoimmune limbic encephalitis, type 1 diabetes, and Stiff person syndrome associated with GAD-65 antibody

    Directory of Open Access Journals (Sweden)

    Chandra Mohan Sharma

    2016-01-01

    Full Text Available Antibodies to GAD-65 have been implicated in the pathogenesis of type 1 diabetes , limbic encephalitis and Stiff person syndrome, however these diseases rarely occur concurrently. We intend to present a rare case of 35 year old female who was recently diagnosed as having type 1 diabetes presented with 1½ month history of recurrent seizures, subacute onset gait ataxia, dysathria, psychiatric disturbance and cognitive decline. No tumor was found on imaging and the classic paraneoplastic panel was negative. Cerebrospinal fluid and blood was positive for GAD-65 antibodies.Patient showed significant improvement with immunomodulatory therapy. Association of GAD-65 antibodies has been found with various disorders including type 1 diabetes, limbic encephalitis, Stiff person syndrome,cerebellar ataxia and palatal myoclonus.This case presents with unique combination of type 1 diabetes, Stiff person syndrome and limbic encephalitis associated with GAD-65 antibodies that is responsive to immunotherapy. It also highlights the emerging concept of autoimmunity in the causation of various disorders and there associations.

  9. Decreased A20 mRNA and protein expression in peripheral blood mononuclear cells in patients with type 2 diabetes and latent autoimmune diabetes in adults.

    Science.gov (United States)

    Cheng, Liqing; Zhang, Dongmei; Jiang, Youzhao; Deng, Wuquan; Wu, Qi'nan; Jiang, Xiaoyan; Chen, Bing

    2014-12-01

    A20 is a negative regulator of nuclear factor kappa B activation and the central gatekeeper in inflammation and immunity. While its role in type 1 diabetes has been widely studied, its expression level in immune cells from type 2 diabetes (T2D) and latent autoimmune diabetes in adult (LADA) patients remains unclear. This study aimed to clarify whether the expression of A20 is altered in patients with T2D or LADA. Quantitative real-time polymerase chain reaction and western blotting were utilized to determine the expression of A20 mRNA and protein respectively in peripheral blood mononuclear cells (PBMCs) from patients with T2D (n=36) or LADA (n=17) and sex- and age-matched healthy controls (n=34). The mRNA and protein expression of A20 in PBMCs from T2D and LADA patients was significantly decreased compared with healthy controls (P1 year since diagnosis) (P<0.05). Our results suggest that decreased expression of A20 in PBMCs may be involved in the pathogenesis of diabetes, and targeting A20 may offer a potential therapeutic tool in the treatment of diabetes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. The prevalence of autoimmune disease in patients with esophageal achalasia.

    Science.gov (United States)

    Booy, J D; Takata, J; Tomlinson, G; Urbach, D R

    2012-04-01

    Achalasia is a rare disease of the esophagus that has an unknown etiology. Genetic, infectious, and autoimmune mechanisms have each been proposed. Autoimmune diseases often occur in association with one another, either within a single individual or in a family. There have been separate case reports of patients with both achalasia and one or more autoimmune diseases, but no study has yet determined the prevalence of autoimmune diseases in the achalasia population. This paper aims to compare the prevalence of autoimmune disease in patients with esophageal achalasia to the general population. We retrospectively reviewed the charts of 193 achalasia patients who received treatment at Toronto's University Health Network between January 2000 and May 2010 to identify other autoimmune diseases and a number of control conditions. We determined the general population prevalence of autoimmune diseases from published epidemiological studies. The achalasia sample was, on average, 10-15 years older and had slightly more men than the control populations. Compared to the general population, patients with achalasia were 5.4 times more likely to have type I diabetes mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjögren's syndrome (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI 12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall, patients with achalasia were 3.6 times more likely to suffer from any autoimmune condition (95% CI 2.5-5.3). Our findings are consistent with the impression that achalasia's etiology has an autoimmune component. Further research is needed to more conclusively define achalasia as an autoimmune disease. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  11. A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 diabetes

    NARCIS (Netherlands)

    Magitta, N. F.; Wolff, A. S. Boe; Johansson, S.; Skinningsrud, B.; Lie, B. A.; Myhr, K-M; Undlien, D. E.; Joner, G.; Njolstad, P. R.; Kvien, T. K.; Forre, O.; Knappskog, P. M.; Husebye, E. S.

    Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider

  12. The induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

    Science.gov (United States)

    Yuksel, M; Xiao, X; Tai, N; Vijay, G M; Gülden, E; Beland, K; Lapierre, P; Alvarez, F; Hu, Z; Colle, I; Ma, Y; Wen, L

    2016-11-01

    Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (T regs ), which had decreased programmed death (PD)-1 expression. Splenic T regs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8 + T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of T regs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8 + T effectors, facilitating the induction of AIH and persistent liver damage. © 2016 British Society for Immunology.

  13. The induction of autoimmune hepatitis in the human leucocyte antigen‐DR4 non‐obese diabetic mice autoimmune hepatitis mouse model

    Science.gov (United States)

    Yuksel, M.; Xiao, X.; Tai, N.; Vijay, G. M.; Gülden, E.; Beland, K.; Lapierre, P.; Alvarez, F.; Hu, Z.; Colle, I.; Ma, Y.

    2016-01-01

    Summary Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti‐smooth muscle actin and/or anti‐nuclear, anti‐liver kidney microsomal type 1 (anti‐LKM1) and anti‐liver cytosol type 1 (anti‐LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)‐DR3, ‐DR7 and ‐DR13. HLA‐DR4 has the second strongest association with adult AIH, after HLA‐DR3. We investigated the role of HLA‐DR4 in the development of AIH by immunization of HLA‐DR4 (DR4) transgenic non‐obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti‐LKM1/anti‐LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs), which had decreased programmed death (PD)‐1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild‐type (WT) NOD mice. Our results demonstrate that HLA‐DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD‐1 expression may result in spontaneous activation of key immune cell subsets, such as antigen‐presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage. PMID:27414259

  14. Predictors of associated autoimmune diseases (AAID) in families with type 1 diabetes (T1D). Results from the Type 1 Diabetes Genetics Consortium (T1DGC)

    Science.gov (United States)

    Wägner, Ana M; Santana, Ángelo; Hernández, Marta; Wiebe, Julia C; Nóvoa, Javier; Mauricio, Didac

    2011-01-01

    Background Type 1 diabetes (T1D) is a clinically heterogeneous disease. The presence of associated autoimmune diseases (AAID) may represent a distinct form of autoimmune diabetes, with involvement of specific mechanisms. The aim of this study was to find predictors of AAID in the Type 1 Diabetes Genetics Consortium (T1DGC) data set. Methods 3263 families with at least 2 siblings with T1D were included. Clinical information was obtained using questionnaires, anti-GAD and anti-IA-2 were measured and HLA-genotyping was performed. Siblings with T1D with and without AAID were compared and a multivariate regression analysis was performed to find predictors of AAID. T1D-associated HLA haplotypes were defined as the 4 most susceptible and protective, respectively. Results AAID was present in 14.4% of the T1D affected siblings. Age of diabetes onset, current age and time since diagnosis were higher, and there was a female predominance and more family history of AAID in the group with AAID, as well as more frequent anti-GAD and less frequent anti-IA2 positivity. Risk and protective HLA haplotype distributions were similar, though DRB1*0301-DQA1*0501-DQB1*0201 was more frequent in the group with AAID. In the multivariate analysis, female gender, age of onset, family history of AAID, time since diagnosis and anti-GAD positivity were significantly associated with AAID. Conclusions In patients with T1D, the presence of AAID is associated with female predominance, more frequent family history of AAID, later onset of T1D and more anti-GAD antibodies, despite longer duration of the disease. The predominance of certain HLA haplotypes suggests that specific mechanisms of disease may be involved. PMID:21744463

  15. Clinical characteristics of non-obese children with type 2 diabetes mellitus without involvement of β-cell autoimmunity.

    Science.gov (United States)

    Urakami, Tatsuhiko; Kuwabara, Remi; Habu, Masako; Okuno, Misako; Suzuki, Junichi; Takahashi, Shori; Mugishima, Hideo

    2013-02-01

    We examined the clinical characteristics of non-obese Japanese children with type 2 diabetes mellitus (T2DM) not associated with β-cell autoimmunity. Of 218 children who were diagnosed as having T2DM by a school urine glucose screening program in Tokyo, 24 were identified as being non-obese and were enrolled in this study. None of the children had any evidence of β-cell autoimmunity or genetic disorders. The mean ages at diagnosis and at the study were 12.5 ± 1.7 and 22.4 ± 5.7 years, respectively. Females were predominant (M/F ratio: 4/20). Family history of T2DM, mostly of the non-obese type, was present in 62.5% of the cases. In regard to the birth weight, 20.8% had a history of low birth weight, and 8.3% were large for gestational age. The mean fasting insulin level, HOMA-R, HOMA-β, and an insulinogenic index on the OGTT at the time of diagnosis were 11.8 ± 7.8 μU/ml, 5.4 ± 3.8, 96.1 ± 55.0 and 0.16 ± 0.14, respectively. Most patients were treated by either oral hypoglycemic drug (45.8%) or insulin (50.0%) therapy at the study, with the mean interval to the start of pharmacological treatment of 3.1 ± 2.3 years. Non-obese children with T2DM seemed to show lower insulin secretory capacities with mild, but evident, insulin resistance even from the time of diagnosis, and also earlier requirement of pharmacological therapies during the clinical course. Some genetic factors not associated with autoimmunity may play a role in the etiology of T2DM in non-obese children. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid.

    Science.gov (United States)

    Arranz Martín, Alfonso; Lecumberri Pascual, Edurne; Brito Sanfiel, Miguel Ángel; Andía Melero, Víctor; Nattero Chavez, Lia; Sánchez López, Iván; Cánovas Molina, Gloria; Arrieta Blanco, Francisco; González Perez Del Villar, Noemí

    2017-01-01

    To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m 2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. AUTOIMMUNE DISEASE DURING PREGNANCY AND THE MICROCHIMERISM LEGACY OF PREGNANCY

    Science.gov (United States)

    Adams Waldorf, Kristina M.; Nelson, J. Lee

    2009-01-01

    Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus. PMID:18716941

  18. Targeted delivery of antigen to intestinal dendritic cells induces oral tolerance and prevents autoimmune diabetes in NOD mice.

    Science.gov (United States)

    Chen, Yulin; Wu, Jie; Wang, Jiajia; Zhang, Wenjing; Xu, Bohui; Xu, Xiaojun; Zong, Li

    2018-03-15

    The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice. A targeting NP delivery system was developed to encapsulate H6P, and the ability of this system to protect and facilitate H6P delivery to gut DCs was assessed. NOD mice were immunised with H6P-loaded targeting NPs orally once a week for 7 weeks and the onset of diabetes was assessed by monitoring blood glucose levels. H6P-loaded targeting NPs protected the encapsulated H6P from degradation in the gastrointestinal tract environment and significantly increased the uptake of H6P by DCs in the gut Peyer's patches (4.1 times higher uptake compared with the control H6P solution group). Oral vaccination with H6P-loaded targeting NPs induced antigen-specific T cell tolerance and prevented diabetes in 100% of NOD mice. Immune deviation (T helper [Th]1 to Th2) and CD4 + CD25 + FOXP3 + regulatory T cells were found to participate in the induction of immune tolerance. In this study, we successfully induced antigen-specific T cell tolerance and prevented the onset of diabetes in NOD mice. To our knowledge, this is the first attempt at delivering antigen to gut DCs using targeting NPs to induce T cell tolerance.

  19. MIF inhibition interferes with the inflammatory and T cell-stimulatory capacity of NOD macrophages and delays autoimmune diabetes onset.

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    Hannelie Korf

    Full Text Available Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D. However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF and its transmembrane receptor, CD74, in the progression of T1D. Our data indicated elevated MIF concentrations especially in long-standing T1D patients and mice. Additionally, NOD mice featured increased MIF gene expression and CD74+ leukocyte frequencies in the pancreas. We identified F4/80+ macrophages as the main immune cells in the pancreas expressing CD74 and showed that MIF antagonism of NOD macrophages prevented their activation-induced cytokine production. The physiological importance was highlighted by the fact that inhibition of MIF delayed the onset of autoimmune diabetes in two different diabetogenic T cell transfer models. Mechanistically, macrophages pre-conditioned with the MIF inhibitor featured a refractory capacity to trigger T cell activation by keeping them in a naïve state. This study underlines a possible role for MIF/CD74 signaling pathways in promoting macrophage-mediated inflammation in T1D. As therapies directed at the MIF/CD74 pathway are in clinical development, new opportunities may be proposed for arresting T1D progression.

  20. Linking chronic infection and autoimmune diseases: Mycobacterium avium subspecies paratuberculosis, SLC11A1 polymorphisms and type-1 diabetes mellitus.

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    Daniela Paccagnini

    2009-09-01

    Full Text Available The etiology of type 1 diabetes mellitus (T1DM is still unknown; numerous studies are performed to unravel the environmental factors involved in triggering the disease. SLC11A1 is a membrane transporter that is expressed in late endosomes of antigen presenting cells involved in the immunopathogenic events leading to T1DM. Mycobacterium avium subsp. paratuberculosis (MAP has been reported to be a possible trigger in the development of T1DM.Fifty nine T1DM patients and 79 healthy controls were genotyped for 9 polymorphisms of SLC11A1 gene, and screened for the presence of MAP by PCR. Differences in genotype frequency were evaluated for both T1DM patients and controls. We found a polymorphism in the SLC11A1 gene (274C/T associated to type 1 diabetic patients and not to controls. The presence of MAP DNA was also significantly associated with T1DM patients and not with controls.The 274C/T SCL11A1 polymorphism was found to be associated with T1DM as well as the presence of MAP DNA in blood. Since MAP persists within macrophages and it is also processed by dendritic cells, further studies are necessary to evaluate if mutant forms of SLC11A1 alter the processing or presentation of MAP antigens triggering thereby an autoimmune response in T1DM patients.

  1. Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

    Science.gov (United States)

    Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

    2016-06-01

    Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers

  2. Prevalences of autoimmune diseases in schizophrenia, bipolar I and II disorder, and controls.

    Science.gov (United States)

    Cremaschi, Laura; Kardell, Mathias; Johansson, Viktoria; Isgren, Anniella; Sellgren, Carl M; Altamura, A Carlo; Hultman, Christina M; Landén, Mikael

    2017-12-01

    Previous studies on the relationship between autoimmune diseases, schizophrenia, and bipolar disorder are mainly based on hospital discharge registers with insufficient coverage of outpatient data. Furthermore, data is scant on the prevalence of autoimmune diseases in bipolar subgroups. Here we estimate the self-reported prevalences of autoimmune diseases in schizophrenia, bipolar disorder type I and II, and controls. Lifetime prevalence of autoimmune diseases was assessed through a structured interview in a sample of 9076 patients (schizophrenia N = 5278, bipolar disorder type I N = 1952, type II N = 1846) and 6485 controls. Comparative analyses were performed using logistic regressions. The prevalence of diabetes type 1 did not differ between groups. Hyperthyroidism, hypothyroidism regardless of lithium effects, rheumatoid arthritis, and polymyalgia rheumatica were most common in bipolar disorder. Systemic lupus erythematosus was less common in bipolar disorder than in the other groups. The rate of autoimmune diseases did not differ significantly between bipolar subgroups. We conclude that prevalences of autoimmune diseases show clear differences between schizophrenia and bipolar disorder, but not between the bipolar subgroups. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Enteroviruses and type 1 diabetes mellitus putative pathogenic pathways

    NARCIS (Netherlands)

    Vreugdenhil, Gienke Rolien

    2001-01-01

    Type I diabetes mellitus is a chronic autoimmune disease that results from the destruction of the insulin-producing beta-cells in the endocrine pancreas. There is strong evidence that besides genetic factors, environmental factors are involved in the pathogenesis of the disease. Increasing

  4. Oral Probiotic VSL#3 Prevents Autoimmune Diabetes by Modulating Microbiota and Promoting Indoleamine 2,3-Dioxygenase-Enriched Tolerogenic Intestinal Environment

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    Jayashree Dolpady

    2016-01-01

    Full Text Available The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut microbiota induced by oral treatment with Lactobacillaceae-enriched probiotic VSL#3, alone or in combination with retinoic acid (RA, protect NOD mice from T1D by affecting inflammasome at the intestinal level. In particular, we show that VSL#3 treatment inhibits IL-1β expression while enhancing release of protolerogenic components of the inflammasome, such as indoleamine 2,3-dioxygenase (IDO and IL-33. Those modifications of the intestinal microenvironment in VSL#3-treated NOD mice modulate gut immunity by promoting differentiation of tolerogenic CD103+ DCs and reducing differentiation/expansion of Th1 and Th17 cells in the intestinal mucosa and at the sites of autoimmunity, that is, within the pancreatic lymph nodes (PLN of VSL#3-treated NOD mice. Our data provide a link between dietary factors, microbiota composition, intestinal inflammation, and immune homeostasis in autoimmune diabetes and could pave the way for new therapeutic approaches aimed at changing the intestinal microenvironment with probiotics to counterregulate autoimmunity and prevent T1D.

  5. Longitudinal three-dimensional visualisation of autoimmune diabetes by functional optical coherence imaging

    DEFF Research Database (Denmark)

    Berclaz, Corinne; Schmidt-Christensen, Anja; Szlag, Daniel

    2016-01-01

    AIMS/HYPOTHESIS: It is generally accepted that structural and functional quantitative imaging of individual islets would be beneficial to elucidate the pathogenesis of type 1 diabetes. We here introduce functional optical coherence imaging (FOCI) for fast, label-free monitoring of beta cell destr...

  6. Latent Autoimmune Diabetes Mellitus in Adults (LADA and it’s characteristics in a subset of Nigerians initially managed for type 2 diabetes

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    Adeleye Olufunmilayo O

    2012-08-01

    Full Text Available Abstract Introduction Latent autoimmune diabetes in adults (LADA is an entity characterized by the presence of GAD autoantibodies. LADA is largely understudied and underreported amongst Nigerians with Diabetes Mellitus (DM. We undertook to document the Prevalence, clinical and biochemical characteristics of LADA in a subset of Nigerians who hitherto had been treated for type 2 DM. Methods This is a cross-sectional study conducted on 235 patients being managed for type 2 DM. The diagnosis of LADA was made in the presence of Glutamic Acid Decarboxylase autoantibody (GADA positivity in the study subjects. Thereafter persons with LADA were compared with those without LADA. Clinical parameters such as demographic data, history of diabetes mellitus (DM and its complications were obtained, biochemical parameters including Fasting blood glucose (FBG, C-peptide, glycated haemoglobin (HbA1c and lipid parameters were compared in both groups of Study subject. Test statistics used were Student t- test and χ 2. SPSS was used for data analysis. Results Thirty three out of 235 of the Study subjects were GADA positive, giving a prevalence of 14%. The mean age (SD of the subjects with LADA is 53.24(7.22 with an age range of 30–63 years. Majority (48% of LADA subjects were in the 50–59 age category. There was no significant difference in the proportion of males and females with LADA (p = 0.3. 37% of patients with LADA were on insulin for glycaemic control. Three (3 LADA subjects had history/clinical evidence of autoimmune thyroid disease. 66% of LADA were in the overweight/obese category. LADA subjects had significant poor long term glycaemic control compared with anti-GAD negative subjects (p = 0.026. About half of LADA subjects were insulinopaenic. LADA subjects had lower levels of total cholesterol than GADA-ve subjects (p = 0.03. A higher proportion of LADA had evidence of microvascular complications of DM compared with antiGAD negative individuals

  7. Simulating an infection growth model in certain healthy metabolic pathways of Homo sapiens for highlighting their role in Type I Diabetes mellitus using fire-spread strategy, feedbacks and sensitivities.

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    Somnath Tagore

    Full Text Available Disease Systems Biology is an area of life sciences, which is not very well understood to date. Analyzing infections and their spread in healthy metabolite networks can be one of the focussed areas in this regard. We have proposed a theory based on the classical forest fire model for analyzing the path of infection spread in healthy metabolic pathways. The theory suggests that when fire erupts in a forest, it spreads, and the surrounding trees also catch fire. Similarly, when we consider a metabolic network, the infection caused in the metabolites of the network spreads like a fire. We have constructed a simulation model which is used to study the infection caused in the metabolic networks from the start of infection, to spread and ultimately combating it. For implementation, we have used two approaches, first, based on quantitative strategies using ordinary differential equations and second, using graph-theory based properties. Furthermore, we are using certain probabilistic scores to complete this task and for interpreting the harm caused in the network, given by a 'critical value' to check whether the infection can be cured or not. We have tested our simulation model on metabolic pathways involved in Type I Diabetes mellitus in Homo sapiens. For validating our results biologically, we have used sensitivity analysis, both local and global, as well as for identifying the role of feedbacks in spreading infection in metabolic pathways. Moreover, information in literature has also been used to validate the results. The metabolic network datasets have been collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG.

  8. Simulating an Infection Growth Model in Certain Healthy Metabolic Pathways of Homo sapiens for Highlighting Their Role in Type I Diabetes mellitus Using Fire-Spread Strategy, Feedbacks and Sensitivities

    Science.gov (United States)

    Tagore, Somnath; De, Rajat K.

    2013-01-01

    Disease Systems Biology is an area of life sciences, which is not very well understood to date. Analyzing infections and their spread in healthy metabolite networks can be one of the focussed areas in this regard. We have proposed a theory based on the classical forest fire model for analyzing the path of infection spread in healthy metabolic pathways. The theory suggests that when fire erupts in a forest, it spreads, and the surrounding trees also catch fire. Similarly, when we consider a metabolic network, the infection caused in the metabolites of the network spreads like a fire. We have constructed a simulation model which is used to study the infection caused in the metabolic networks from the start of infection, to spread and ultimately combating it. For implementation, we have used two approaches, first, based on quantitative strategies using ordinary differential equations and second, using graph-theory based properties. Furthermore, we are using certain probabilistic scores to complete this task and for interpreting the harm caused in the network, given by a ‘critical value’ to check whether the infection can be cured or not. We have tested our simulation model on metabolic pathways involved in Type I Diabetes mellitus in Homo sapiens. For validating our results biologically, we have used sensitivity analysis, both local and global, as well as for identifying the role of feedbacks in spreading infection in metabolic pathways. Moreover, information in literature has also been used to validate the results. The metabolic network datasets have been collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG). PMID:24039701

  9. Nonsegmental Vitiligo and Autoimmune Mechanism

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    Naoki Oiso

    2011-01-01

    Full Text Available Nonsegmental vitiligo is a depigmented skin disorder showing acquired, progressive, and depigmented lesions of the skin, mucosa, and hair. It is believed to be caused mainly by the autoimmune loss of melanocytes from the involved areas. It is frequently associated with other autoimmune diseases, particularly autoimmune thyroid diseases including Hashimoto's thyroiditis and Graves' disease, rheumatoid arthritis, type 1 diabetes, psoriasis, pernicious anemia, systemic lupus erythematosus, Addison's disease, and alopecia areata. This indicates the presence of genetically determined susceptibility to not only vitiligo but also to other autoimmune disorders. Here, we summarize current understanding of autoimmune pathogenesis in non-segmental vitiligo.

  10. The role of Th1/Th2 disbalanced immune response in the determination of clinical features of autoimmune diabetes mellitus

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    Tatiana Vladimirovna Saprina

    2011-06-01

    compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response. Conclusion. The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.

  11. The Clinical Significance of Glycoprotein Phospholipase D Levels in Distinguishing Early Stage Latent Autoimmune Diabetes in Adults and Type 2 Diabetes.

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    Wen Qin

    Full Text Available Autoantibodies have been widely used as markers of latent autoimmune diabetes in adults (LADA; however, the specificity and sensitivity of autoantibodies as markers of LADA are weak compared with those found in type 1 diabetes (T1DM. In this study, we aimed to identify other plasma proteins as potential candidates that can be used effectively to determine early stage LADA and type 2 diabetes (T2DM to facilitate early diagnosis and treatment. These issues were addressed by studying new-onset 'classic' T1DM (n = 156, LADA (n = 174, T2DM (n = 195 and healthy cohorts (n = 166. Plasma samples were obtained from the four cohorts. We employed isobaric tag for relative and absolute quantitation (iTRAQ together with liquid chromatography tandem mass spectrometry (LC-MS to identify plasma proteins with significant changes in LADA. The changes were validated by Western blot and ELISA analyses. Among the four cohorts, 311 unique proteins were identified in three iTRAQ runs, with 157 present across the three data sets. Among them, 49/311 (16.0% proteins had significant changes in LADA compared with normal controls, including glycoprotein phospholipase D (GPLD1, which was upregulated in LADA. Western blot and ELISA analyses showed that GPLD1 levels were higher in both LADA and T1DM cohorts than in both T2DM and healthy cohorts, while there were no significant differences in the plasma concentrations of GPLD1 between the LADA and T1DM cohorts. GPLD1 is implicated as a potential candidate plasma protein for determining early stage LADA and T2DM.

  12. Genetically Engineered Islets and Alternative Sources of Insulin-Producing Cells for Treating Autoimmune Diabetes: Quo Vadis?

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    Feng-Cheng Chou

    2012-01-01

    Full Text Available Islet transplantation is a promising therapy for patients with type 1 diabetes that can provide moment-to-moment metabolic control of glucose and allow them to achieve insulin independence. However, two major problems need to be overcome: (1 detrimental immune responses, including inflammation induced by the islet isolation/transplantation procedure, recurrence autoimmunity, and allorejection, can cause graft loss and (2 inadequate numbers of organ donors. Several gene therapy approaches and pharmaceutical treatments have been demonstrated to prolong the survival of pancreatic islet grafts in animal models; however, the clinical applications need to be investigated further. In addition, for an alternative source of pancreatic β-cell replacement therapy, the ex vivo generation of insulin-secreting cells from diverse origins of stem/progenitor cells has become an attractive option in regenerative medicine. This paper focuses on the genetic manipulation of islets during transplantation therapy and summarizes current strategies to obtain functional insulin-secreting cells from stem/progenitor cells.

  13. Neuromyelitis optica-like pathology is dependent on type I interferon response.

    Science.gov (United States)

    Khorooshi, Reza; Wlodarczyk, Agnieszka; Asgari, Nasrin; Owens, Trevor

    2013-09-01

    Neuromyelitis optica is an antibody-mediated autoimmune inflammatory disease of the central nervous system. Reports have suggested that interferon beta which is beneficial for multiple sclerosis, exacerbates neuromyelitis optica. Our aim was to determine whether type I interferon plays a role in the formation of neuromyelitis optica lesions. Immunoglobulin G from a neuromyelitis optica patient was injected intracerebrally with human complement to type I interferon receptor deficient and wildtype mice. Loss of aquaporin-4 and glial fibrillary acidic protein was reduced in type I interferon receptor deficient mice brain. Our findings suggest that type I interferon signaling contributes to neuromyelitis optica pathogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Vaccinations in early life are not associated with development of islet autoimmunity in type 1 diabetes high-risk children: Results from prospective cohort data.

    Science.gov (United States)

    Beyerlein, Andreas; Strobl, Andreas N; Winkler, Christiane; Carpus, Michaela; Knopff, Annette; Donnachie, Ewan; Ankerst, Donna P; Ziegler, Anette-G

    2017-03-27

    Vaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth. A total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination. Most vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96-1.21] per additional vaccination against measles, mumps and rubella at age 0-24months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06-1.96] per additional vaccination at age 0-24months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90-1.16]). We found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat

    NARCIS (Netherlands)

    Visser, J. T. J.; Lammers, K.; Hoogendijk, A.; Boer, M. W.; Brugman, S.; Beijer-Liefers, S.; Zandvoort, A.; Harmsen, H.; Welling, G.; Stellaard, F.; Bos, N. A.; Fasano, A.; Rozing, J.

    2010-01-01

    Aims/hypothesis Impaired intestinal barrier function is observed in type I diabetes patients and animal models of the disease. Exposure to diabetogenic antigens from the intestinal milieu due to a compromised intestinal barrier is considered essential for induction of the autoimmune process leading

  16. Evidence of Stage- and Age-Related Heterogeneity of Non-HLA SNPs and Risk of Islet Autoimmunity and Type 1 Diabetes: The Diabetes Autoimmunity Study in the Young

    Directory of Open Access Journals (Sweden)

    Brittni N. Frederiksen

    2013-01-01

    Full Text Available Previously, we examined 20 non-HLA SNPs for association with islet autoimmunity (IA and/or progression to type 1 diabetes (T1D. Our objective was to investigate fourteen additional non-HLA T1D candidate SNPs for stage- and age-related heterogeneity in the etiology of T1D. Of 1634 non-Hispanic white DAISY children genotyped, 132 developed IA (positive for GAD, insulin, or IA-2 autoantibodies at two or more consecutive visits; 50 IA positive children progressed to T1D. Cox regression was used to analyze risk of IA and progression to T1D in IA positive children. Restricted cubic splines were used to model SNPs when there was evidence that risk was not constant with age. C1QTNF6 (rs229541 predicted increased IA risk (HR: 1.57, CI: 1.20–2.05 but not progression to T1D (HR: 1.13, CI: 0.75–1.71. SNP (rs10517086 appears to exhibit an age-related effect on risk of IA, with increased risk before age 2 years (age 2 HR: 1.67, CI: 1.08–2.56 but not older ages (age 4 HR: 0.84, CI: 0.43–1.62. C1QTNF6 (rs229541, SNP (rs10517086, and UBASH3A (rs3788013 were associated with development of T1D. This prospective investigation of non-HLA T1D candidate loci shows that some SNPs may exhibit stage- and age-related heterogeneity in the etiology of T1D.

  17. Is glycated albumin useful for differential diagnosis between fulminant type 1 diabetes mellitus and acute-onset autoimmune type 1 diabetes mellitus?

    Science.gov (United States)

    Koga, Masafumi; Kanehara, Hideo; Bando, Yukihiro; Morita, Shinya; Kasayama, Soji

    2015-12-07

    Markedly elevated plasma glucose and relatively low HbA1c compared to plasma glucose is one diagnostic criterion for fulminant type 1 diabetes mellitus (FT1DM). Glycated albumin (GA) is a glycemic control marker that reflects glycemic control in shorter period than HbA1c. This study investigated whether GA is useful for differential diagnosis between FT1DM and acute-onset autoimmune type 1 diabetes mellitus (T1ADM) or not. This study included 38 FT1DM patients and 31 T1ADM patients in whom both HbA1c and GA were measured at the time of diagnosis. In FT1DM patients, as compared to T1ADM patients, both HbA1c and GA were significantly lower (HbA1c; 6.6±0.9% vs. 11.7±2.6%, P1, GA; 22.9±4.8% vs. 44.3±8.3%, P1). For differential diagnosis between FT1DM and T1ADM, ROC analysis showed that the optimum cut-off value for GA was 33.5% with sensitivity and specificity of 97.4% and 96.8%, respectively, while the optimum cut-off value for HbA1c was 8.7% with sensitivity and specificity of 100% and 83.9%, respectively. GA also may be useful for the differential diagnosis between FT1DM and T1ADM when the cut-off value can be set at 33.5%. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Imaging dynamics of CD11c+ cells and Foxp3+ cells in progressive autoimmune insulitis in the NOD mouse model of type 1 diabetes

    DEFF Research Database (Denmark)

    Schmidt-Christensen, Anja; Hansen, Lisbeth; Ilegems, Erwin

    2013-01-01

    the endocrine pancreas during initiation and progression of insulitis in the NOD mouse. Individual, ACE-transplanted islets of Langerhans were longitudinally and repetitively imaged by stereomicroscopy and two-photon microscopy to follow fluorescently labelled leucocyte subsets. Results We demonstrate that......, in spite of the immune privileged status of the eye, the ACE-transplanted islets develop infiltration and beta cell destruction, recapitulating the autoimmune insulitis of the pancreas, and exemplify this by analysing reporter cell populations expressing green fluorescent protein under the Cd11c or Foxp3......Aims/hypothesis The aim of this study was to visualise the dynamics and interactions of the cells involved in autoimmune-driven inflammation in type 1 diabetes. Methods We adopted the anterior chamber of the eye (ACE) transplantation model to perform non-invasive imaging of leucocytes infiltrating...

  19. Prognosis of type 1 autoimmune pancreatitis after corticosteroid therapy-induced remission in terms of relapse and diabetes mellitus.

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    Masaki Miyazawa

    Full Text Available Relapse and diabetes mellitus (DM are major problems for the prognosis of autoimmune pancreatitis (AIP. We examined the prognosis of type 1 AIP after corticosteroid therapy (CST-induced remission in terms of relapse and DM.The study enrolled 82 patients diagnosed with type 1 AIP who achieved remission with CST. We retrospectively evaluated the relapse rate in terms of the administration period of CST, clinical factors associated with relapse, and the temporal change in glucose tolerance.During follow-up, 32 patients (39.0% experienced relapse. There was no significant clinical factor that could predict relapse before beginning CST. AIP patients who ceased CST within 2 or 3 years experienced significantly earlier relapse than those who had the continuance of CST (p = 0.050 or p = 0.020. Of the 37 DM patients, 15 patients (40.5% had pre-existing DM, 17 (45.9% showed new-onset DM, and 5 (13.5% developed CST-induced DM. Patients with new-onset DM were significantly more likely to show improvement (p = 0.008 than those with pre-existing DM.It was difficult to predict relapse of AIP based on clinical parameters before beginning CST. Relapse was likely to occur within 3 years after the beginning of CST and maintenance of CST for at least 3 years reduced the risk of relapse. The early initiation of CST for AIP with impaired glucose tolerance is desirable because pre-existing DM is refractory to CST.

  20. Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes.

    Science.gov (United States)

    Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria; Arafah, Baha M

    2017-09-01

    Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.

  1. Pesquisa do nistagmo/vertigem de posição e avaliação eletronistagmográfica em um grupo de indivíduos portadores de diabetes Mellitus tipo I Search of the nystagmus/ positional vertigo and electronystagmographic evaluation in a group of diabetics Mellitus type I

    Directory of Open Access Journals (Sweden)

    Lílian P. Scherer

    2002-05-01

    search the nystagmus/ positional vertigo and electronystagmographic evaluation, and to identify possible alterations. Study design: Prospective clinical. Material and method: 12 Diabetics Type I, insulin dependents, between 12 and 27 years old, and members of Associação Riograndense de Apoio aos Diabéticos (ARAD. To observe the vestibular reactions, we did a specific interview, otoscopy, tympanometric, search of the Nystagmus/ Positional Vertigo and Electronystagmographic Evaluation in the selected sample. Results: We verified Periferic Irritable Vestibular Syndrome in 75% of the altered results. 62,5% in this group didn't present otoneurologyc symptom. Conclusions: We note that the effect of Diabetes Type I in the vestibular function may be taken into consideration like any other usual complications, since the same may occur in asymptomatic patients, and also because with the early etiologic diagnostic it is possible to help in the prevention of this disease's complications.

  2. Thyroid autoimmunity

    NARCIS (Netherlands)

    Wiersinga, Wilmar M.

    2014-01-01

    Autoimmune thyroid disease (AITD) is a multifactorial disease in which autoimmunity against thyroid antigens develops against a particular genetic background facilitated by exposure to environmental factors. Immunogenicity of the major thyroid antigens thyroid peroxidase, thyroglobulin (TG) and

  3. [MEDICAL CANNABIS - A SOURCE FOR A NEW TREATMENT FOR AUTOIMMUNE DISEASE?].

    Science.gov (United States)

    Katz, Daphna; Katz, Itay; Golan, Amir

    2016-02-01

    Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of diffefent axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis.

  4. [Morphological alterations in nailfold capillaroscopy and the clinical picture of vascular involvement in autoimmune diseases: systemic lupus erythematosus and type 1 diabetes].

    Science.gov (United States)

    Kuryliszyn-Moskal, Anna; Ciołkiewicz, Mariusz; Dubicki, Artur

    2010-01-01

    Systemic lupus erythematosus (SLE) and type 1 diabetes mellitus (DM) belong to the group of autoimmune diseases presenting with a wide range of organ manifestations. Microvascular abnormalities seem to play a crucial role in the development of persistent multi-organ complications in both diseases. The aim of this study was to determine the relationship between microvascular changes examined with nailfold capillaroscopy and organ involvement. We eurolled 76 SLE patients, 106 patients with type 1 diabetes, and 40 healthy controls. Morphological changes were observed with nailfold capillaroscopy in 86 (81%) diabetics and in 70 (92.1%) SLE patients. Severe capillaroscopic changes were disclosed in 32 out of 54 (59%) diabetic patients with microangiopathy and in only 7 out of 52 (13%) patients without microangiopathy. In the SLE group, severe capillaroscopic abnormalities were found in 18 out of 34 (52.9%) patients with organ involvement and in 9 out of 42 (21.4%) patients without organ involvement. The capillaroscopic score was significantly higher in diabetic patients with microangiopathic complications in comparison to patients without microangiopathy (p nailfold capillaroscopy reflect the extent of microvascular involvement and are associated with organ involvement in SLE and diabetes.

  5. Type I signal peptidases of Bacillus subtilis

    NARCIS (Netherlands)

    Tjalsma, Harold; Bolhuis, Albert; Bron, Sierd; Jongbloed, Jan; Meijer, Wilfried J.J.; Noback, Michiel; van Roosmalen, Maarten; Venema, Gerhardus; van Dijl, Jan Maarten; Hopsu Havu, VK; Jarvinen, M; Kirschke, H

    1997-01-01

    Bacillus subtilis contains at least three chromosomally-encoded type I signal peptidases (SPases; SipS, SipT, and SipU), which remove signal peptides from secretory proteins. In addition, certain B. subtilis (natto) strains contain plasmid-encoded type I SPases (SipP). The known type I SPases from

  6. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes.

    Science.gov (United States)

    Candon, Sophie; Perez-Arroyo, Alicia; Marquet, Cindy; Valette, Fabrice; Foray, Anne-Perrine; Pelletier, Benjamin; Milani, Christian; Milani, Cristian; Ventura, Marco; Bach, Jean-François; Chatenoud, Lucienne

    2015-01-01

    Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD) mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin) or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.

  7. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes.

    Directory of Open Access Journals (Sweden)

    Sophie Candon

    Full Text Available Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.

  8. Reduced Histone H3 Lysine 9 Methylation Contributes to the Pathogenesis of Latent Autoimmune Diabetes in Adults via Regulation of SUV39H2 and KDM4C

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    Xi-yu Liu

    2017-01-01

    Full Text Available Aims. Latent autoimmune diabetes in adults (LADA is an autoimmune disease of which the mechanism is not clear. Emerging evidence suggests that histone methylation contributes to autoimmunity. Methods. Blood CD4+ T lymphocytes from 26 LADA patients and 26 healthy controls were isolated to detect histone H3 lysine 4 and H3 lysine 9 methylation status. Results. Reduced global H3 lysine 9 methylation was observed in LADA patients’ CD4+ T lymphocytes, compared to healthy controls (P < 0.05. H3 lysine 4 methylation was not statistically different. The reduced H3 lysine 9 methylation was associated with GADA titer but not correlated with glycosylated hemoglobin (HbA1c. When the LADA patient group was divided into those with complication and those without, relatively reduced global H3 lysine 9 methylation was observed in LADA patients with complication (P < 0.05. The expression of histone methyltransferase SUV39H2 for H3 lysine 9 methylation was downregulated in LADA patients, and the expression of histone demethylase KDM4C which made H3 lysine 9 demethylation was upregulated. Conclusion. The reduction of histone H3 lysine 9 methylation which may due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C was found in CD4+ T lymphocytes of LADA patients.

  9. [An evaluation of HLA class 2 alleles and anti-islet antibodies as evidence for non-autoimmune diabetes in Wolfram syndrome].

    Science.gov (United States)

    Zmysłowska, Agnieszka; Borowiec, Maciej; Antosik, Karolina; Wyka, Krystyna; Cieślik-Heinrich, Agnieszka; Klich, Izabela; Młynarski, Wojciech

    2010-01-01

    A clinical criterion of the Wolfram syndrome is the coexistence of diabetes and optic atrophy recognized before the age of 15. Diabetes present in Wolfram syndrome is a result of the selective β cell loss and failed insulin secretion which is probably associated with non-autoimmune pathogenesis. The aim of the study was an evaluation of HLA subtypes and presence of β-cell autoantibodies in patients with molecularly confirmed Wolfram syndrome. 9 patients with Wolfram syndrome aged 10-24 years were examined. We also studied 218 patients with type 1 diabetes as a reference group. A control group of 176 healthy individuals was included in the study. Besides the clinical assessment the HLA typing by PCR-SSO was performed. Islet cell antibodies (ICA), antibodies to glutamic acid decarboxylase (GADA), thyrosine phosphatase antibodies (IA2A) and insulin antibodies (IAA) were also detected. In all nine patients the coexistence of diabetes with optic atrophy was observed and in 8/9 individuals additional symptoms were recognized. In patients with Wolfram syndrome a significantly lower age of diagnosis of diabetes (Me=5.0 years) than in type 1 diabetic children (Me=10.4; p=0.002) was observed. Studies of HLA subtypes demonstrated an increased prevalence of HLA-DQw1, DRB1⋅03 and/or 04 and DR2. A comparison of the frequency of the HLA alleles in patients with Wolfram syndrome with type 1 diabetic children showed a more frequent presence of the DRB1⋅1501 (p=0.03; OR=13.28 (2.44-72.12)) and DQB1⋅06 (p=0.016; OR=10.15 (2.49-41.35)) alleles in patients with Wolfram syndrome. Polish patients with Wolfram syndrome have a different profile of the HLA antigens with the presence of DR2, DQw1 and DRB3/4 allele and are negative for diabetes-related autoantibodies, which may confirm non-autoimmune β-cell destruction in this syndrome.

  10. Human LT-alpha-mediated resistance to autoimmune diabetes is induced in NOD, but not NOD-scid, mice and abrogated by IL-12.

    Science.gov (United States)

    Miyaguchi, S; Satoh, J; Takahashi, K; Sakata, Y; Nakazawa, T; Miyazaki, J; Toyota, T

    2001-01-01

    Systemic administration of human lymphotoxin-alpha (hLT-alpha) made NOD mice resistant not only to spontaneous autoimmune type 1 diabetes mellitus but also to cyclophosphamide (CY)-induced diabetes and diabetes transfer by diabetic NOD spleen cells (triple resistance). In this study we analyzed the mechanisms of hLT-alpha-induced resistance, focusing on (1) hLT-alpha-induced resistance in the pancreatic beta cell, (2) CY-resistant suppressor cells, (3) suppression of induction or function of effector cells for beta cell destruction, or (4) others. To examine the first possibility in vitro, a NOD-derived beta cell line (MIN6N) was pretreated with hLT-alpha and then mixed with diabetic NOD spleen cells and MIN6N cell viability was measured. Treatment with hLT-alpha did not protect MIN6N cells but rather enhanced cytotoxicity. Next NOD-scid mice were pretreated with hLT-alpha and then transferred with diabetic NOD spleen. All the recipients developed diabetes. These results excluded the first possibility. The second possibility was also excluded by a cotransfer experiment, in which diabetic NOD spleen cells were cotransferred to NOD-scid mice with nontreated or hLT-alpha-treated nondiabetic NOD spleens. There was no significant difference in diabetes incidence between the two groups. To observe the third possibility, spleen cells of hLT-alpha-treated triple-resistant NOD mice were transferred to NOD-scid mice. Diabetes developed in the recipients, although the onset of diabetes was slightly delayed. Finally, hLT-alpha-treated triple-resistant NOD mice developed diabetes 1 week after daily IL-12 treatment. In summary, hLT-alpha administration made NOD mice resistant to effector cells for beta cell destruction. This resistance was induced in NOD, but not in NOD-scid, mice, indicating that lymphocytes were obligatory for the resistance. However, it was not mediated by transferable suppressor cells. Because effector cells were present in hLT-alpha-treated NOD spleen and

  11. Autoimmune diseases in asthma.

    Science.gov (United States)

    Tirosh, Amir; Mandel, Dror; Mimouni, Francis B; Zimlichman, Eyal; Shochat, Tzippora; Kochba, Ilan

    2006-06-20

    Previous research has suggested an inverse relationship between T-helper 2-related atopic disorders, such as asthma, and T-helper 1-related autoimmune diseases. One controversial hypothesis postulates that asthma provides a protective effect for the development of autoimmune-related disorders. To assess the rate of newly diagnosed autoimmune disorders in a large cohort of young adults. Using cross-sectional data from the Israeli Defense Force database, the authors analyzed the prevalence of autoimmune disorders in asthmatic and nonasthmatic military personnel between 1980 and 2003. A follow-up study traced newly diagnosed autoimmune disorders among asthmatic and nonasthmatic individuals from the time of enrollment in military service until discharge (22 and 36 months for women and men, respectively). General community. 307,367 male and 181,474 female soldiers in compulsory military service who were between 18 and 21 years of age. Cases of type 1 diabetes mellitus, vasculitis, immune thrombocytopenic purpura, inflammatory bowel disease, rheumatoid arthritis, and the antiphospholipid syndrome. Of 488,841 participants at enrollment, significantly more women than men had autoimmune disorders. Compared with asthmatic women, nonasthmatic women had a significantly higher prevalence of all autoimmune disorders except for the antiphospholipid syndrome. Type 1 diabetes mellitus, vasculitis, and rheumatoid arthritis were less prevalent in men with asthma than in those without. During the follow-up period, vasculitis and rheumatoid arthritis were more frequently diagnosed in nonasthmatic persons of both sexes. There was a significantly higher incidence of immune thrombocytopenic purpura, inflammatory bowel disease, and the antiphospholipid syndrome in nonasthmatic women and a statistically significantly higher incidence of type 1 diabetes mellitus in nonasthmatic men. The study was limited to a population of young military recruits; therefore, its findings are not necessarily

  12. Neuromyelitis optica-like pathology is dependent on type I interferon response

    DEFF Research Database (Denmark)

    Khorooshi, Reza; Wlodarczyk, Agnieszka; Asgari, Nasrin

    2013-01-01

    Neuromyelitis optica is an antibody-mediated autoimmune inflammatory disease of the central nervous system. Reports have suggested that interferon beta which is beneficial for multiple sclerosis, exacerbates neuromyelitis optica. Our aim was to determine whether type I interferon plays a role in ...

  13. GCN2 and FGF21 are likely mediators of the protection from cancer, autoimmunity, obesity, and diabetes afforded by vegan diets.

    Science.gov (United States)

    McCarty, Mark F

    2014-09-01

    Third World quasi-vegan cultures have been characterized by low risks for "Western" cancers, autoimmune disorders, obesity, and diabetes. The relatively low essential amino acid contents of many vegan diets may play a role in this regard. It is proposed that such diets modestly activate the kinase GCN2 - a physiological detector of essential amino acid paucity - within the liver, resulting in up-regulated production of fibroblast growth factor 21 (FGF21). FGF21, by opposing the stimulatory effect of growth hormone on hepatic IGF-I production, may be responsible for the down-regulation of plasma IGF-I observed in vegans consuming diets of modest protein content. Decreased IGF-I bioactivity throughout life can be expected to have a favorable impact on cancer risk, as observed in rodents that are calorie restricted or genetically defective in IGF-I activity. Increased FGF21 in vegans might also contribute to their characteristic leanness and low LDL cholesterol by promoting hepatic lipid oxidation while inhibiting lipogenesis. Direct trophic effects of FGF21 on pancreatic beta-cells may help to explain the low risk for diabetes observed in vegans, and the utility of vegan diets in diabetes management. And up-regulation of GCN2 in immune cells, by boosting T regulatory activity, might play some role in the reduced risk for autoimmunity reported in some quasi-vegan cultures. The fact that bone density tends to be no greater in vegans than omnivores, despite consumption of a more "alkaline" diet, might be partially attributable to the fact that FGF21 opposes osteoblastogenesis and decreases IGF-I. If these speculations have merit, it should be possible to demonstrate that adoption of a vegan diet of modest protein content increases plasma FGF21 levels. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Multiple Autoimmune Syndromes Associated with Psoriasis: A Rare Clinical Presentation

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    Sadia Masood

    2014-03-01

    Full Text Available Autoimmune diseases are known to have association with each other but it is very rare to see multiple autoimmune diseases in one patient. The combination of at least three autoimmune diseases in the same patient is referred to as multiple autoimmune syndrome. The case we are reporting features multiple autoimmune syndrome with five different conditions. The patient had type 1 diabetes mellitus, autoimmune hemolytic anemia, systemic lupus erythematosus, vitiligo, and psoriasis. Psoriasis has rarely been reported previously under the spectrum of autoimmune syndrome. Although the relationship of autoimmune conditions with each other has been explored in the past, this case adds yet another dimension to the unique evolution of autoimmune pathologies. The patient presented with a combination of five autoimmune diseases, which makes it consistent type three multiple autoimmune syndromes with the addition of psoriasis. The current case is unique in this aspect that the combination of these five autoimmune disorders has never been reported in the past.

  15. Prediction of autoimmune diabetes and celiac disease in childhood by genes and perinatal environment: Design and initial aims of the PAGE study

    Directory of Open Access Journals (Sweden)

    Lars C. Stene

    2014-12-01

    Full Text Available Type 1 diabetes and celiac disease result from misdirected immune mediated destruction of host cells, and are among the most common chronic diseases in children. Despite changes in incidence over the past 3 decades, little is known about non-genetic risk factors (except for dietary gluten for celiac disease. Norway is among the countries in the world with the highest incidence of these two diseases. We describe here plans and study design for the PAGE study (Prediction of Autoimmune diabetes and celiac disease in childhood by Genes and perinatal Environment. PAGE is a sub-study within the Norwegian Mother and Child Cohort study, including follow-up of more than 100,000 pregnancies. Children who develop type 1 diabetes or celiac disease are identified via linkage to the Norwegian Patient Register and the Norwegian Childhood Diabetes Registry, with complementing information from questionnaires. The overall aim is to test hypotheses about potential non-genetic risk factors for type 1 diabetes and for celiac disease, with focus on factors operating early in life. In addition to a full cohort analysis of factors registered in questionnaires, we will analyse biomarkers in maternal blood plasma and cord blood plasma. Mothers and children will be genotyped for well-established susceptibility polymorphisms. Biomarkers will be analysed in cases and controls within the cohort. Factors to be tested in the full cohort include infant feeding, diet and dietary supplements in the mother during pregnancy and in the child, and use of antibiotics and non-prescription drugs. Biomarkers to be tested include 25-hydroxyvitamin D, markers of immune activation, and small metabolites (metabolomics. We will also explore the potential role of maternal cells in the fetal circulation (maternal microchimerism in later risk of celiac disease and type 1 diabetes.

  16. Curcumin and autoimmune disease.

    Science.gov (United States)

    Bright, John J

    2007-01-01

    The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

  17. Chronic type-I diabetes could not impede the anti-inflammatory and anti-apoptotic effects of combined postconditioning with ischemia and cyclosporine A in myocardial reperfusion injury.

    Science.gov (United States)

    Badalzadeh, Reza; Azimi, Ako; Alihemmati, Alireza; Yousefi, Bahman

    2017-02-01

    It has been shown that diabetes modifies the myocardial responses to ischemia/reperfusion (I/R) and to cardioprotective agents. In this study, we aimed to investigate the effects of combined treatment with ischemic postconditioning (IPostC) and cyclosporine A (CsA) on inflammation and apoptosis of the diabetic myocardium injured by I/R. Eight weeks after induction of diabetes in Wistar rats, hearts were mounted on a Langendorff apparatus and were subsequently subjected to a 30-min regional ischemia followed by 45-min reperfusion. IPostC was induced at the onset of reperfusion, by 3 cycles of 30-s reperfusion/ischemia (R/I). The concentration of creatine kinase (CK), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were determined; the levels of total and phosphorylated glycogen synthase kinase 3 beta (p-GSK3β) and B-cell lymphoma 2 (Bcl-2) were quantified by western blotting, and the rate of apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. Administration of either IPostC or CsA alone in nondiabetic animals significantly reduced CK, TNF-α, IL-1β, and IL-6 concentrations, increased the p-GSK3β and Bcl-2, and decreased the level of apoptosis (P GSK3β and Bcl-2 and decreasing apoptosis and inflammation were restored in comparison with nonpostconditioned diabetic hearts. IPostC or CsA failed to affect apoptosis and inflammation and failed to protect the diabetic myocardium against I/R injury. However, combined administration of IPostC and CsA at reperfusion can protect the diabetic myocardium by decreasing the inflammatory response and apoptosis.

  18. Dietary avocado oil supplementation attenuates the alterations induced by type I diabetes and oxidative stress in electron transfer at the complex II-complex III segment of the electron transport chain in rat kidney mitochondria.

    Science.gov (United States)

    Ortiz-Avila, Omar; Sámano-García, Carlos Alberto; Calderón-Cortés, Elizabeth; Pérez-Hernández, Ismael H; Mejía-Zepeda, Ricardo; Rodríguez-Orozco, Alain R; Saavedra-Molina, Alfredo; Cortés-Rojo, Christian

    2013-06-01

    Impaired complex III activity and reactive oxygen species (ROS) generation in mitochondria have been identified as key events leading to renal damage during diabetes. Due to its high content of oleic acid and antioxidants, we aimed to test whether avocado oil may attenuate the alterations in electron transfer at complex III induced by diabetes by a mechanism related with increased resistance to lipid peroxidation. 90 days of avocado oil administration prevented the impairment in succinate-cytochrome c oxidoreductase activity caused by streptozotocin-induced diabetes in kidney mitochondria. This was associated with a protection against decreased electron transfer through high potential chain in complex III related to cytochromes c + c1 loss. During Fe(2+)-induced oxidative stress, avocado oil improved the activities of complexes II and III and enhanced the protection conferred by a lipophilic antioxidant against damage by Fe(2+). Avocado oil also decreased ROS generation in Fe(2+)-damaged mitochondria. Alterations in the ratio of C20:4/C18:2 fatty acids were observed in mitochondria from diabetic animals that not were corrected by avocado oil treatment, which yielded lower peroxidizability indexes only in diabetic mitochondria although avocado oil caused an augment in the total content of monounsaturated fatty acids. Moreover, a protective effect of avocado oil against lipid peroxidation was observed consistently only in control mitochondria. Since the beneficial effects of avocado oil in diabetic mitochondria were not related to increased resistance to lipid peroxidation, these effects were discussed in terms of the antioxidant activity of both C18:1 and the carotenoids reported to be contained in avocado oil.

  19. [Type 2 autoimmune polyendocrine syndromes (APS-2)].

    Science.gov (United States)

    Vialettes, Bernard; Dubois-Leonardon, Noémie

    2013-01-01

    Type 2 autoimmune polyendocrine syndromes (APS-2) are the most frequent disorders associating several organ-specific autoimmune diseases. Their high prevalence is due to the fact that the main manifestations of APS-2, such as thyroidal autoimmunity, type 1 diabetes, autoimmune gastric atrophy and vitiligo, are common diseases. APS-2 represents a clinical model that can serve to help unravel the mechanisms underlying autoimmunity. Diagnosis of APS-2 is a challenge for the clinician, especially in poorly symptomatic forms, and may require systematic screening based on measurement of autoantibodies and functional markers.

  20. Type I Interferon in the Pathogenesis of Lupus

    Science.gov (United States)

    Crow, Mary K.

    2014-01-01

    Investigations of patients with systemic lupus erythematosus (SLE) have applied insights from studies of the innate immune response to define type I interferon (IFN-I), with IFN-α the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFNI-induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained anti-virus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients. PMID:24907379

  1. The comorbidity of bipolar disorder, diabetes mellitus, and autoimmune hypothyroidism in an adult woman with Turner’s syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Li J

    2017-09-01

    Full Text Available Jinling Li, Xiaohong Hong, Haiyun Xu The Mental Health Center, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Turner’s syndrome (TS is the most common sex chromosome abnormality in females and characterized with short stature and ovarian dysgenesis. Patients with TS may also present many other physical diseases and mental disorders. In this case report, we present a 49-year-old woman with TS, who also met criteria for bipolar disorder, type 2 diabetes mellitus, and autoimmune hypothyroidism. The patient was admitted to the mental health center for depressive symptoms in 1991 and was misdiagnosed as hypopituitarism, which was not corrected until 2005 when her karyotype of 45, X/46, X, i(Xq was identified. Due to the misdiagnosis and other specific reasons, the patient missed the optimal time for hormone replacement therapy. Keywords: Turner’s syndrome, bipolar disorder, karyotype, comorbidity

  2. Autoimmune gastritis.

    Science.gov (United States)

    Kulnigg-Dabsch, Stefanie

    2016-10-01

    Autoimmune gastritis is a chronic inflammatory disease with destruction of parietal cells of the corpus and fundus of the stomach. The known consequence is vitamin B12 deficiency and, consequently, pernicious anemia. However, loss of parietal cells reduces secretion of gastric acid which is also required for absorption of inorganic iron; thus, iron deficiency is commonly found in patients with autoimmune gastritis. This usually precedes vitamin B12 deficiency and is found mainly in young women. Patients with chronic iron deficiency, especially those refractory to oral iron therapy, should therefore be evaluated for the presence of autoimmune gastritis.

  3. High density lipoproteins as indicators of endothelial dysfunction in children with diadetes type I

    Directory of Open Access Journals (Sweden)

    Lobanova S.M.

    2011-12-01

    Full Text Available The aim of the investigation was to study the level of blood high density lipoproteins (HDL in the groups of children with different course of diadetes type I in order to find out the dependence of course and complications of diabetes on that level. Materials and methods: Blood high density lipoprotein (HDL levels were investigated in children and adolescents with diadetes type I, depending on the duration of diadetes type I, age, stage of sexual development, the stage of diabetic nephropathy and levels of plasma endothelin-1 (E-1. Results: Decrease in HDL level with increasing duration of diadetes type I in prepubertate patients, higher indices of HDL cholesterol were determined in girls, especially with impaired puberty. HDL cholesterol was higher in diabetic nephropathy at the stage of proteinuria and high level of blood endothelin-1. Conclusion: The revealed changes were considered to cause deregulation of vascular endothelium as a manifestation of the initial stages of endothelial dysfunction

  4. Autoimmune disorders

    Science.gov (United States)

    ... exact cause of autoimmune disorders is unknown. One theory is that some microorganisms (such as bacteria or ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  5. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  6. Nueva definición, prevalencia, caracterización y tratamiento de la diabetes autoinmune latente del adulto A new definition, prevalence, characterization, and treatment of the latent autoimmune diabetes of adult

    Directory of Open Access Journals (Sweden)

    Eduardo Cabrera Rode

    2008-12-01

    hasta a los 12 años después del diagnóstico de la enfermedad, aunque el deterioro de la respuesta de las células ß a la glucosa intravenosa o al glucagón puede ser detectado en algunos sujetos al diagnóstico de la diabetes. Por tal razón, no estamos en presencia de una enfermedad latente. Existen varios estudios que sugieren que el tratamiento con insulina es el más indicado al momento del diagnóstico de la enfermedad para contrarrestar el daño de la función de las células ß. En este trabajo, se revisó lo relacionado con su definición, la genética, la presencia de autoanticuerpos antiislotes y su patogenia, así como las experiencias con la función de las células y los tratamientos en discusión. Además, como la diabetes autoinmune la podemos encontrar no solo en adultos sino también en niños y adolescentes, así como en adultos jóvenes, sugerimos el epónimo de diabetes autoinmune de progresión lenta como más apropiado.Latent autoimmune diabetes of adult is a way of autoimmune diabetes present in some subjects erroneously classified as Type 2 diabetics. Progression of autoimmune damage of ß cells in this entity is slower than in children presenting with Type 1 diabetes. At diagnosis, persons affected by this condition, have a greater preservation of ß cells function than those presenting with the classic Type 1 diabetes. Their present diagnosis is based on 3 features: age similar o greater than 30 years (however, it may be present in subjects in ages lower than 30 years; presence of at least 1 of the 5 antibodies to pancreatic antigens of islet-cells (anti-islet [AI] auto-antibodies, anti-descarboxylase of glutamic acid [AGAD], antibodies to phosphatase tyrosine [AIA2], and to zinc-cation transporter within ß islet-cells [AZnT8], and the need of insulin requirements, at least 6 months after diagnosis. It is present in 10 % of subjects presenting with Type 2 diabetes in ³35 years, and in 25 % of those younger than 35 years. Some genes of

  7. PROTOPLANETARY DISK RESONANCES AND TYPE I MIGRATION

    International Nuclear Information System (INIS)

    Tsang, David

    2011-01-01

    Waves reflected by the inner edge of a protoplanetary disk are shown to significantly modify Type I migration, even allowing the trapping of planets near the inner disk edge for small planets in a range of disk parameters. This may inform the distribution of planets close to their central stars, as observed recently by the Kepler mission.

  8. Fatal Attraction: Interactions between antigen-presenting cells and islets of Langerhans in the pathogenesis of autoimmune diabetes

    NARCIS (Netherlands)

    J.G.M. Rosmalen (Judith)

    2000-01-01

    textabstractThe onset of diabetes mellitus is characterized by various symptoms, all the result of a disturbed glucose metabolism. The main symptoms are thirst and an excessive production of urine. The disturbed glucose metabolism underlying these symptoms is due to an absolute deficiency of insulin

  9. Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis

    NARCIS (Netherlands)

    Chen, Kang; Chen, Hao; Faas, Marijke M; de Haan, Bart J; Li, Jiahong; Xiao, Ping; Zhang, Hao; Diana, Julien; de Vos, Paul; Sun, Jia

    Scope: Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on

  10. Autoimmun hypophysitis

    DEFF Research Database (Denmark)

    Krarup, Therese; Hagen, Claus

    2010-01-01

    during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...

  11. Screening of ZnT8 autoantibodies in the diagnosis of autoimmune diabetes in a large French cohort.

    Science.gov (United States)

    Garnier, Lorna; Marchand, Lucien; Benoit, Marine; Nicolino, Marc; Bendelac, Nathalie; Wright, Catherine; Moulin, Philippe; Lombard, Christine; Thivolet, Charles; Fabien, Nicole

    2018-03-01

    Evaluate the added value of screening anti-ZnT8 antibodies (ZnT8A) in addition to the classical anti-GAD (GADA) and anti-IA-2 (IA-2A) antibodies for the diagnosis of type-1 diabetes (T1D) within a large cohort of both children and adults. Retrospective 2-year study including 516 patients (215 children, 301 adults) who had blood tests at diabetes onset and/or for diabetes classification. ZnT8A, GADA, and IA-2A were analyzed in all samples. Among those individuals included, 142 (28%) were ZnT8A-positive. A total of 228/516 suffered from T1D, of whom 110 (48%) were ZnT8A-positive and 166 (73%) GADA and/or IA-2A positive. When adding ZnT8A to GADA/IA-2A, 184 (81%) patients were positive for ≥1 Ab. Regarding the 122 patients at T1D onset, 75 (61%) were positive for ZnT8A and the proportion of patients with T1D with ≥1 Ab reached 89%. The highest prevalence of ZnT8A was observed in children aged 6-10years. Fourteen of the 124 patients positive for ZnT8A with a known clinical diagnosis suffered from a disease other than T1D. ZnT8A should be included in routine evaluation at diabetes onset and is a valuable biological marker to classify newly-diagnosed diabetics. The predictive value in our high-risk subjects has to be confirmed. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Potential mechanisms explaining why hydrolyzed casein-based diets outclass single amino acid-based diets in the prevention of autoimmune diabetes in diabetes-prone BB rats

    NARCIS (Netherlands)

    Visser, J. T. J.; Bos, N. A.; Harthoorn, L. F.; Stellaard, F.; Beijer-Liefers, S.; Rozing, J.; van Tol, E. A. F.

    Background It remains controversial whether avoidance of dietary diabetogenic triggers, such as cow's milk proteins, can prevent type 1 diabetes in genetically susceptible individuals. Here, different extensive casein hydrolysates (HC) and single amino acid (AA) formulations were tested for their

  13. Association of serum microRNAs with islet autoimmunity, disease progression and metabolic impairment in relatives at risk of type 1 diabetes.

    Science.gov (United States)

    Snowhite, Isaac V; Allende, Gloria; Sosenko, Jay; Pastori, Ricardo L; Messinger Cayetano, Shari; Pugliese, Alberto

    2017-08-01

    MicroRNAs (miRNAs) are key regulators of gene expression and novel biomarkers for many diseases. We investigated the hypothesis that serum levels of some miRNAs would be associated with islet autoimmunity and/or progression to type 1 diabetes. We measured levels of 93 miRNAs most commonly detected in serum. This retrospective cohort study included 150 autoantibody-positive and 150 autoantibody-negative family-matched siblings enrolled in the TrialNet Pathway to Prevention Study. This was a young cohort (mean age = 11 years), and most autoantibody-positive relatives were at high risk because they had multiple autoantibodies, with 39/150 (26%, progressors) developing type 1 diabetes within an average 8.7 months of follow-up. We analysed miRNA levels in relation to autoantibody status, future development of diabetes and OGTT C-peptide and glucose indices of disease progression. Fifteen miRNAs were differentially expressed when comparing autoantibody-positive/negative siblings (range -2.5 to 1.3-fold). But receiver operating characteristic (ROC) analysis indicated low specificity and sensitivity. Seven additional miRNAs were differentially expressed among autoantibody-positive relatives according to disease progression; ROC returned significant AUC values and identified miRNA cut-off levels associated with an increased risk of disease in both cross-sectional and survival analyses. Levels of several miRNAs showed significant correlations (r values range 0.22-0.55) with OGTT outcomes. miR-21-3p, miR-29a-3p and miR-424-5p had the most robust associations. Serum levels of selected miRNAs are associated with disease progression and confer additional risk of the development of type 1 diabetes in young autoantibody-positive relatives. Further studies, including longitudinal assessments, are warranted to further define miRNA biomarkers for prediction of disease risk and progression.

  14. Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

    Science.gov (United States)

    Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

    1991-07-01

    To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

  15. Usefulness of postmortem biochemistry in identification of ketosis: Diagnosis of ketoacidosis at the onset of autoimmune type 1 diabetes in an autopsy case with cold exposure and malnutrition.

    Science.gov (United States)

    Tani, Naoto; Michiue, Tomomi; Chen, Jian-Hua; Oritani, Shigeki; Ishikawa, Takaki

    2016-09-01

    A severely malnourished, Japanese female in her twenties was found dead in her apartment. On autopsy, most of the findings from the internal examination were suggestive of hypothermia. Postmortem biochemistry, however, showed severely increased levels of glycated hemoglobin (HbA1c) and blood and urine glucose levels. Levels of acetone, 3-hydroxybutyric acid, and acetoacetate in various body fluids were also highly increased, indicating ketosis. The serum insulin and c-peptide levels were severely low, and subsequent testing was positive for anti-GAD antibodies. Immunohistochemical examination of the pancreatic islet cells revealed few insulin-positive cells but many glucagon-positive cells on staining. Furthermore, slight invasion of CD8-positive lymphocytes in the pancreatic islets of Langerhans was observed. Results of immunostaining of the pancreatic and bronchial epithelial tissues were partly positive for the Influenza A virus. We concluded that severe ketoacidosis associated with rapid-onset hyperglycemia due to autoimmune type 1 diabetes (AT1D) had occurred shortly before death. However, the ketosis was accompanied by hypothermia and malnutrition as well as diabetic ketoacidosis (DKA). Therefore, we retrospectively collected biochemical data on cases of hypothermia and malnutrition and compared them with the present case. Serum glucose, acetone, 3-hydroxybutyric acid, and acetoacetic acid can be used for screening and diagnosis to distinguish DKA from ketosis due to hypothermia and malnutrition. Therefore, in the present case, we diagnosed that the natural cause of death was due to AT1D. In conclusion, screening investigations for relevant biochemical markers can provide essential information for the diagnosis of metabolic disturbances, which fail to demonstrate characteristic autopsy findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Specific inulin-type fructan fibers protect against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis.

    Science.gov (United States)

    Chen, Kang; Chen, Hao; Faas, Marijke M; de Haan, Bart J; Li, Jiahong; Xiao, Ping; Zhang, Hao; Diana, Julien; de Vos, Paul; Sun, Jia

    2017-08-01

    Dietary fibers capable of modifying gut barrier and microbiota homeostasis affect the progression of type 1 diabetes (T1D). Here, we aim to compare modulatory effects of inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root, on T1D development in nonobese diabetic mice. Female nonobese diabetic mice were weaned to long- and short-chain ITFs [ITF(l) and ITF(s), 5%] supplemented diet up to 24 weeks. T1D incidence, pancreatic-gut immune responses, gut barrier function, and microbiota composition were analyzed. ITF(l) but not ITF(s) supplementation dampened the incidence of T1D. ITF(l) promoted modulatory T-cell responses, as evidenced by increased CD25 + Foxp3 + CD4 + regulatory T cells, decreased IL17A + CD4 + Th17 cells, and modulated cytokine production profile in the pancreas, spleen, and colon. Furthermore, ITF(l) suppressed NOD like receptor protein 3 caspase-1-p20-IL-1β inflammasome in the colon. Expression of barrier reinforcing tight junction proteins occludin and claudin-2, antimicrobial peptides β-defensin-1, and cathelicidin-related antimicrobial peptide as well as short-chain fatty acid production were enhanced by ITF(l). Next-generation sequencing analysis revealed that ITF(l) enhanced Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli. Our data demonstrate that ITF(l) but not ITF(s) delays the development of T1D via modulation of gut-pancreatic immunity, barrier function, and microbiota homeostasis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Autoimmune hepatitis.

    Science.gov (United States)

    Vergani, D; Mieli-Vergani, G

    2004-06-01

    Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

  18. The Role of GAD65 Autoantibody in Diabetes Mellitus and their First-Degree Relatives and Comparison with Healthy Persons

    Directory of Open Access Journals (Sweden)

    M Nakhjavani

    2001-06-01

    Full Text Available The diabetes is an autoimmune disease, in which the role of autoantibodies is of a specific importance. The appearance of these autoantibodies can be the first symptom in the serum of type I diabetic patients, which may appear ten years before onset of the disease. The most important autoantibodies include Glutamic acid decarboxylase autoantibodies (GAD65-Ab. This can be used as a good tool for prediction in screening tests in type I diabetic patients. In the present study with prosedure RIA, we investigated the level of GAD65-Ab in patients with diabetes type I and their close relatives, and compared them with healthy persons. From the type I diabetic patients who have been suffering from the disease for periods of one week to twenty years, 63.3% of them had positive Anti-GAD65. This ratio was 8% in their close trelatives, and 0% in healthy persons. The difference in Anti-GAD65 between the healthy persons and close relative of patients was significant. This test may be employed in diabetes type I, as a screening test, and confirms the results of studies which have been conducted so far outside this country.

  19. Celiac disease and endocrine autoimmunity.

    Science.gov (United States)

    Kahaly, George J; Schuppan, Detlef

    2015-01-01

    Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.

  20. Pryce type I sequestration: no mosquito shooting.

    Science.gov (United States)

    Barik, Ramachandra; Patnaik, Amar Narayan; Malempati, Amaresh Rao; Nemani, Lalita

    2015-06-01

    We report a case of a 40-year-old woman with congenital dual arterial supply to an otherwise normal left lower lobe, causing hyperperfusion lung injury. In addition to near normal pulmonary arterial supply, the lower lobe of the left lung received a systemic arterial supply from the descending thoracic aorta. The patient was successfully managed by surgical ligation of the systemic arterial supply without lobectomy. We discuss when to defer lobectomy in Pryce type I sequestration. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  1. Survey of Type I ELM dynamics measurements

    International Nuclear Information System (INIS)

    Leonard, A W; Asakura, N; Boedo, J A; Becoulet, M; Counsell, G F; Eich, T; Fundamenski, W; Herrmann, A; Horton, L D; Kamada, Y; Kirk, A; Kurzan, B; Loarte, A; Neuhauser, J; Nunes, I; Oyama, N; Pitts, R A; Saibene, G; Silva, C; Snyder, P B; Urano, H; Wade, M R; Wilson, H R

    2006-01-01

    This report summarizes Type I edge localized mode (ELM) dynamics measurements from a number of tokamaks, including ASDEX-Upgrade, DIII-D, JET, JT-60U and MAST, with the goal of providing guidance and insight for the development of ELM simulation and modelling. Several transport mechanisms are conjectured to be responsible for ELM transport, including convective transport due to filamentary structures ejected from the pedestal, parallel transport due to edge ergodization or magnetic reconnection and turbulent transport driven by the high edge gradients when the radial electric field shear is suppressed. The experimental observations are assessed for their validation, or conflict, with these ELM transport conjectures

  2. Bipolar nebulae and type I planetary nebulae

    International Nuclear Information System (INIS)

    Calvet, N.; Peimbert, M.

    1983-01-01

    It is suggested that the bipolar nature of PN of type I can be explained in terms of their relatively massive progenitors (Msub(i) 2.4 Msub(o)), that had to lose an appreciable fraction of their mass and angular momentum during their planetary nebulae stage. The following objects are discussed in relation with this suggestion: NGC 6302, NGC 2346, NGC 2440, CRL 618, Mz-3 and M2-9. It is found that CRL 618 is overbundant in N/O by a factor of 5-10 relative to the Orion Nebula. (author)

  3. Radiative transfer in type I supernovae atmospheres

    International Nuclear Information System (INIS)

    Isern, J.; Lopez, R.; Simonneau, E.

    1987-01-01

    Type I Supernovae are thought to be the result of the thermonuclear explosion of a carbon oxygen white dwarf in a close binary system. As the only direct information concerning the physics and the triggering mechanism of supernova explosions comes from the spectrophotometry of the emitted radiation, it is worthwhile to put considerable effort on the understanding of the radiation transfer in the supernovae envelopes in order to set constraints on the theoretical models of such explosions. In this paper we analyze the role played by the layers curvature on the radiative transfer. (Author)

  4. Therapeutic itinerary of the family and adolescent with type i mellitus diabetes El itinerario terapéutico del adolescente con diabetes mellitus tipo i y sus familiares Itinerário terapêutico do adolescente com diabetes mellitus tipo 1 e seus familiares

    Directory of Open Access Journals (Sweden)

    Mariza Maria Serafim Mattosinho

    2007-12-01

    Full Text Available This is a qualitative assistential convergent study. Its main objective is to understand the therapeutic itinerary of adolescents with type 1 mellitus diabetes, as well as that of their families. The sample was composed of adolescents, between 15 and 25 years old, involved with a health institution in Florianópolis through the Health Care model that includes professional, family, and popular subsystems. Data were obtained through in-depth interviews and field observation of 20 people (relatives and adolescents with diabetes. The data analysis included data codification and categorization. Two categories were constructed: Decisions and negotiations about health, care and treatment; and the journey through the three subsystems of health care. The study permitted to understand that the treatment and care within the professional subsystem are not the only ones available. There are different practices in health performed from the evaluation each family makes, of what they believe adequate for their adolescent with diabetes.Estudio de naturaleza cualitativa, de tipo convergente-asistencial, tuvo como objetivo comprender el camino terapéutico de los adolescentes con diabetes mellitus tipo I y sus familiares, vinculados a una institución de salud de Florianópolis, entre las edades de 15 y 25 años, a través del modelo del Cuidado para la Salud, que incluye los subsistemas profesional, familiar y popular. Los datos fueron obtenidos a través de la entrevista en profundidad y la observación de campo con 20 personas (familiares y adolescentes con diabetes. El análisis incluye la codificación y la categorización de los datos. Fueron construidos dos categorias: Las decisiones y negociaciones sobre la salud, los cuidados y los tratamientos y El percurso en los tres subsistemas de la salud. El estudio permitió comprender que los tratamientos y los cuidados del subsistema profesional no son los únicos, existiendo diferentes prácticas en la salud que

  5. AUTOIMMUNE HEPATITIS

    Directory of Open Access Journals (Sweden)

    Yusri Dianne Jurnalis

    2010-05-01

    Full Text Available AbstrakHepatitis autoimun merupakan penyakit inflamasi hati yang berat dengan penyebab pasti yang tidak diketahui yang mengakibatkan morbiditas dan mortalitas yang tinggi. Semua usia dan jenis kelamin dapat dikenai dengan insiden tertinggi pada anak perempuan usia prepubertas, meskipun dapat didiagnosis pada usia 6 bulan. Hepatitis autoimun dapat diklasifikasikan menjadi 2 bagian berdasarkan adanya antibodi spesifik: Smooth Muscle Antibody (SMA dengan anti-actin specificity dan/atau Anti Nuclear Antibody (ANA pada tipe 1 dan Liver-Kidney Microsome antibody (LKM1 dan/atau anti-liver cytosol pada tipe 2. Gambaran histologisnya berupa “interface hepatitis”, dengan infiltrasi sel mononuklear pada saluran portal, berbagai tingkat nekrosis, dan fibrosis yang progresf. Penyakit berjalan secara kronik tetapi keadaan yang berat biasanya menjadi sirosis dan gagal hati.Tipe onset yang paling sering sama dengan hepatitis virus akut dengan gagal hati akut pada beberapa pasien; sekitar sepertiga pasien dengan onset tersembunyi dengan kelemahan dan ikterik progresif ketika 10-15% asimptomatik dan mendadak ditemukan hepatomegali dan/atau peningkatan kadar aminotransferase serum. Adanya predominasi perempuan pada kedua tipe. Pasien LKM1 positif menunjukkan keadaan lebih akut, pada usia yang lebih muda, dan biasanya dengan defisiensi Immunoglobulin A (IgA, dengan durasi gejala sebelum diagnosis, tanda klinis, riwayat penyakit autoimun pada keluarga, adanya kaitan dengan gangguan autoimun, respon pengobatan dan prognosis jangka panjang sama pada kedua tipe.Kortikosteroid yang digunakan secara tunggal atau kombinasi azathioprine merupakan terapi pilihan yang dapat menimbulkan remisi pada lebih dari 90% kasus. Strategi terapi alternatif adalah cyclosporine. Penurunan imunosupresi dikaitkan dengan tingginya relap. Transplantasi hati dianjurkan pada penyakit hati dekom-pensata yang tidak respon dengan pengobatan medis lainnya.Kata kunci : hepatitis Autoimmune

  6. Type I supernova models vs observations

    International Nuclear Information System (INIS)

    Weaver, T.A.; Axelrod, T.S.; Woosley, S.E.

    1980-01-01

    This paper explores tHe observational consequences of models for Type I supernovae based on the detonation (or deflagration) of the degenerate cores of white dwarfs or intermediate mass (approx. = 9 M/sub sun/) stars. Such nuclear burning can be initiated either at the center of the core or near its edge. The model examined in most detail is that of a 0.5M/sub sun/ C/O white dwarf which undergoes an edge-lit He/C/O detonation after accreting 0.62 M/sub sun/ of he at 10 -8 M/sub sun//yr. The light curve resulting from this model is found to be in excellent agreement with those observed for Type I supernovae, particularly those in the fast subclass. The physical processes involved in the detailed numerical calculations which lead to this conclusion are quantitatively elucidated by simple analytic models, and effects of uncertainties in the input physics are explored

  7. [Autoimmune hepatitis].

    Science.gov (United States)

    Färkkilä, Martti

    2013-01-01

    Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.

  8. The influence of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency and other comorbid autoimmune diseases on treatment outcome in patients with rheumatoid arthritis: An exploratory cohort study

    DEFF Research Database (Denmark)

    Emamifar, Amir; Jensen Hansen, Inger Marie

    2018-01-01

    To investigate the impact of comorbid diseases on rheumatoid arthritis (RA) outcome. All patients diagnosed with RA since 2006, who were registered in our local Danbio registry, were included in this cohort study. Patients’ demographics, serology results, and Disease Activity Score in 28 joints......-C-reactive protein (DAS28-CRP) at the time of diagnosis and after 4 months of treatment initiation were collected. Patients’ electronic hospital records were evaluated for a positive history of thyroid diseases, diabetes mellitus, primary hyperparathyroidism, vitamin B12 deficiency, and the presence of other...... diagnosed autoimmune diseases. 1035 RA patients were included. The observed prevalence of thyroid diseases was 11.8%, DM 10.4%, primary hyperparathyroidism 2.8%, vitamin B12 deficiency 5.8%, and other diagnosed autoimmune diseases 1.6%. There were significant associations between presence of thyroid...

  9. Association of cytomegalo virus with type I diabetes mellitus among ...

    African Journals Online (AJOL)

    groups. Group Ia (newly diagnosed) comprised 20 patients, with ages ranging between 7 and 18 years; 10 were males (50 %), and 10 were females (50 %). Whilst group Ib (duration of disease >1 year) comprised 33 patients, with ages ranging ...

  10. Can we predict and/or prevent type I diabetes?

    African Journals Online (AJOL)

    1990-10-20

    Oct 20, 1990 ... detecting 64KA using Western bloning with rat islet prepara- tions has been ... Although the model appears to give a good correlation, it must be .... DNA repair using cyrosolic nicotinamide adenine dinucleotide. (NAD) as a ...

  11. Endocrine autoimmune disease: genetics become complex.

    Science.gov (United States)

    Wiebolt, Janneke; Koeleman, Bobby P C; van Haeften, Timon W

    2010-12-01

    The endocrine system is a frequent target in pathogenic autoimmune responses. Type 1 diabetes and autoimmune thyroid disease are the prevailing examples. When several diseases cluster together in one individual, the phenomenon is called autoimmune polyglandular syndrome. Progress has been made in understanding the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases such as autoimmune polyglandular syndrome type 1, immunodysregulation, polyendocrinopathy, enteropathy, X-linked and primary immune deficiencies helped uncover the role of key regulators in the preservation of immune tolerance. Alleles of the major histocompatibility complex have been known to contribute to the susceptibility to most forms of autoimmunity for more than 3 decades. Furthermore, sequencing studies revealed three non-major histocompatibility complex loci and some disease specific loci, which control T lymphocyte activation or signalling. Recent genome-wide association studies (GWAS) have enabled acceleration in the identification of novel (non-HLA) loci and hence other relevant immune response pathways. Interestingly, several loci are shared between autoimmune diseases, and surprisingly some work in opposite direction. This means that the same allele which predisposes to a certain autoimmune disease can be protective in another. Well powered GWAS in type 1 diabetes has led to the uncovering of a significant number of risk variants with modest effect. These studies showed that the innate immune system may also play a role in addition to the adaptive immune system. It is anticipated that next generation sequencing techniques will uncover other (rare) variants. For other autoimmune disease (such as autoimmune thyroid disease) GWAS are clearly needed. © 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.

  12. Autoimmune liver disease panel

    Science.gov (United States)

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...

  13. High Risk First Degree Relatives of Type 1 Diabetics: An Association with Increases in CXCR3+ T Memory Cells Reflecting an Enhanced Activity of Th1 Autoimmune Response

    Directory of Open Access Journals (Sweden)

    Tanja Milicic

    2014-01-01

    Full Text Available We analyzed the level of (a CXCR3+ (Th1 and CCR4+ (Th2 T memory cells (b interferon-γ inducible chemokine (IP-10(Th1 and thymus and activation-regulated chemokine (TARC(Th2, in 51 first degree relatives (FDRs of type 1 diabetics (T1D (17 high risk FDRs (GADA+, IA-2+ and 34 low risk FDRs (GADA−, IA-2−, 24 recent-onset T1D (R-T1D, and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., P<0.001. Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, P<0.05. Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response.

  14. Do we really need to differentiate mesenchymal stem cells into insulin-producing cells for attenuation of the autoimmune responses in type 1 diabetes: immunoprophylactic effects of precursors to insulin-producing cells.

    Science.gov (United States)

    Sharma, Anshu; Rani, Rajni

    2017-07-12

    Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are lost before the clinical manifestations of the disease. Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into insulin-producing cells (IPCs) have yielded limited success when used therapeutically. We have evaluated the immunoprophylactic potentials of precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD) mice to ask a basic question: do we need to differentiate MSCs into IPCs or will pIPCs suffice to attenuate autoimmune responses in T1D? Bone marrow-derived MSCs from Balb/c mice were characterized following the International Society for Cellular Therapy (ISCT) guidelines. MSCs cultured in high-glucose media for 11 to 13 passages were characterized for the expression of pancreatic lineage genes using real-time polymerase chain reaction. Expression of the PDX1 gene in pIPCs was assessed using Western blot and fluorescence-activated cell sorting (FACS). Triple-positive MSCs were differentiated into IPCs using a three-step protocol after sorting them for cell surface markers, i.e. CD29, CD44, and SCA-1. Nonobese diabetic mice were administered pIPCs, IPCs, or phosphate-buffered saline (PBS) into the tail vein at weeks 9 or 10 and followed-up for 29-30 weeks for fasting blood glucose levels. Two consecutive blood sugar levels of more than 250 mg/dl were considered diabetic. MSCs grown in high-glucose media for 11 to 13 passages expressed genes of the pancreatic lineage such as PDX1, beta2, neurogenin, PAX4, Insulin, and glucagon. Furthermore, Western blot and FACS analysis for PDX-1, a transcription factor necessary for beta cell maturation, confirmed that these cells were precursors of insulin-producing cells (pIPCs). NOD mice administered with pIPCs were better protected from developing diabetes with a protective efficacy of 78.4% (p cells seem to have better potential to arrest autoimmune response in type 1 diabetes when

  15. Light curve of type I supernovae

    International Nuclear Information System (INIS)

    Colgate, S.A.; Petschek, A.G.; Kriese, J.T.

    1980-01-01

    Calculations of the intermediate and late time luminosity of type I supernovae based on 100% efficiency for optical emission of energy deposited by the Ni 56 decay chain give good agreement with observations provided M/sub ej/ v -2 = (2.2 +- 0.5) x 10 17 M. s 2 cm -2 where M/sub ej/ is the ejected mass an v is the expansion velocity. Account must be taken of the escape of both gamma rays and positrons. These two escape processes as well as the early luminosity peak as calculated by Colgate and McKee are all consistent with the same value of M/sub ej//v 2

  16. Update in Endocrine Autoimmunity

    OpenAIRE

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.

  17. Monogenic autoimmune diseases of the endocrine system.

    Science.gov (United States)

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Insulin gene VNTR polymorphisms -2221MspI and -23HphI are associated with type 1 diabetes and latent autoimmune diabetes in adults: a meta-analysis.

    Science.gov (United States)

    Zhang, Na; Huang, Weihuang; Dong, Fang; Liu, Yang; Zhang, Baohuan; Jing, Lipeng; Wang, Man; Yang, Guang; Jing, Chunxia

    2015-12-01

    A variable number of tandem repeat (VNTRs) region in the insulin gene (INS) possibly influences the progression of type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA). However, effects of INS VNTR polymorphisms in these contexts remain inconclusive. We performed a systematic review of work on the INS VNTR -2221MspI and -23HphI polymorphisms to estimate the overall effects thereof on disease susceptibility; we included 17,498 T1D patients and 24,437 controls, and 1960 LADA patients and 5583 controls. For T1D, the C allele at -2221MspI and the A allele at -23HphI were associated with estimated relative risks of 2.13 (95 % CI 1.94, 2.35) and 0.46 (95 % CI 0.44, 0.48), which contributed to absolute increases of 46.76 and 46.98 % in the risk of all T1D, respectively. The estimated lambda values were 0.44 and 0.42, respectively, suggesting that a co-dominant model most likely explained the effects of -2221MspI and -23HphI on T1D. For -23HphI, the A allele carried an estimated relative risk of 0.55 (95 % CI 0.50, 0.61) for LADA and increased the risk of all LADA by 36.94 %. The λ value was 0.43, suggesting that a co-dominant model most likely explained the effect of -23HphI on LADA. Our results support the existence of associations of INS with T1D and LADA.

  19. Immunogenetics of type 1 diabetes mellitus

    African Journals Online (AJOL)

    EL-HAKIM

    to other autoimmune diseases, the etiology of T1D remains obscure but ..... T1D, type 1 diabetes; AIT, autoimmune thyroiditis; CD, celiac disease; AD, Addison's disease. Table 5. .... (GAD65Ab) in prediabetic adults developing diabetes.

  20. Ameloblasts express type I collagen during amelogenesis.

    Science.gov (United States)

    Assaraf-Weill, N; Gasse, B; Silvent, J; Bardet, C; Sire, J Y; Davit-Béal, T

    2014-05-01

    Enamel and enameloid, the highly mineralized tooth-covering tissues in living vertebrates, are different in their matrix composition. Enamel, a unique product of ameloblasts, principally contains enamel matrix proteins (EMPs), while enameloid possesses collagen fibrils and probably receives contributions from both odontoblasts and ameloblasts. Here we focused on type I collagen (COL1A1) and amelogenin (AMEL) gene expression during enameloid and enamel formation throughout ontogeny in the caudate amphibian, Pleurodeles waltl. In this model, pre-metamorphic teeth possess enameloid and enamel, while post-metamorphic teeth possess enamel only. In first-generation teeth, qPCR and in situ hybridization (ISH) on sections revealed that ameloblasts weakly expressed AMEL during late-stage enameloid formation, while expression strongly increased during enamel deposition. Using ISH, we identified COL1A1 transcripts in ameloblasts and odontoblasts during enameloid formation. COL1A1 expression in ameloblasts gradually decreased and was no longer detected after metamorphosis. The transition from enameloid-rich to enamel-rich teeth could be related to a switch in ameloblast activity from COL1A1 to AMEL synthesis. P. waltl therefore appears to be an appropriate animal model for the study of the processes involved during enameloid-to-enamel transition, especially because similar events probably occurred in various lineages during vertebrate evolution.

  1. Type I interferon is critical for the homeostasis and functional maturation of type 3 γδ T cells

    DEFF Research Database (Denmark)

    Agerholm, Rasmus; Kadekar, Darshana Dattatraya; Rizk, John

    2017-01-01

    Type I IFN (IFN-I) is highly expressed during viral infection and many autoimmune pathologies such as SLE and psoriasis. In addition, IFN-I is important to maintain the homeostasis of a number of different immune populations. Our aim was to identify whether IFN-I regulates type 3 γδ T (γδT3) cells...... behavior. Such γδT3 anergy is characterized by failure to induce skin inflammation and unresponsiveness to cytokine stimuli. Moreover, IFNAR deficient mice display deregulated γδT3homeostasis due to a neonatal maturation defect. In conclusion, our data show that tonic type I IFN signaling during neonatal...

  2. Complete synchronization in coupled type-I neurons

    Indian Academy of Sciences (India)

    Keywords. Complete synchronization; noise; coupled type-I neurons. Abstract. For a system of type-I neurons bidirectionally coupled through a nonlinear feedback mechanism, we discuss the issue of ... Pramana – Journal of Physics | News.

  3. Compensating for Type-I Errors in Video Quality Assessment

    DEFF Research Database (Denmark)

    Brunnström, Kjell; Tavakoli, Samira; Søgaard, Jacob

    2015-01-01

    This paper analyzes the impact on compensating for Type-I errors in video quality assessment. A Type-I error is to incorrectly conclude that there is an effect. The risk increases with the number of comparisons that are performed in statistical tests. Type-I errors are an issue often neglected...

  4. Type I Interferons Direct Gammaherpesvirus Host Colonization.

    Directory of Open Access Journals (Sweden)

    Cindy S E Tan

    2016-05-01

    Full Text Available Gamma-herpesviruses colonise lymphocytes. Murid Herpesvirus-4 (MuHV-4 infects B cells via epithelial to myeloid to lymphoid transfer. This indirect route entails exposure to host defences, and type I interferons (IFN-I limit infection while viral evasion promotes it. To understand how IFN-I and its evasion both control infection outcomes, we used Mx1-cre mice to tag floxed viral genomes in IFN-I responding cells. Epithelial-derived MuHV-4 showed low IFN-I exposure, and neither disrupting viral evasion nor blocking IFN-I signalling markedly affected acute viral replication in the lungs. Maximising IFN-I induction with poly(I:C increased virus tagging in lung macrophages, but the tagged virus spread poorly. Lymphoid-derived MuHV-4 showed contrastingly high IFN-I exposure. This occurred mainly in B cells. IFN-I induction increased tagging without reducing viral loads; disrupting viral evasion caused marked attenuation; and blocking IFN-I signalling opened up new lytic spread between macrophages. Thus, the impact of IFN-I on viral replication was strongly cell type-dependent: epithelial infection induced little response; IFN-I largely suppressed macrophage infection; and viral evasion allowed passage through B cells despite IFN-I responses. As a result, IFN-I and its evasion promoted a switch in infection from acutely lytic in myeloid cells to chronically latent in B cells. Murine cytomegalovirus also showed a capacity to pass through IFN-I-responding cells, arguing that this is a core feature of herpesvirus host colonization.

  5. Reversible lacrimal gland-protective regulatory T-cell dysfunction underlies male-specific autoimmune dacryoadenitis in the non-obese diabetic mouse model of Sjögren syndrome

    Science.gov (United States)

    Lieberman, Scott M; Kreiger, Portia A; Koretzky, Gary A

    2015-01-01

    CD4+ CD25+ Foxp3+ regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ-protective Treg cell functions have not been demonstrated in organ-specific autoimmunity. Non-obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well-characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male-specific, but the role of Treg cells in this sex-specificity is not known. This study aimed to determine if male-specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland-protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland-draining cervical lymph nodes of NOD mice to lymphocyte-deficient NOD-SCID mice. Transfer of bulk cervical lymph node cells modelled the male-specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4+ CD25+ Treg-enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male-specific factors promote reversible dysfunction of lacrimal gland-protective Treg cells and, to our knowledge, form the first evidence for reversible organ-protective Treg cell dysfunction in organ-specific autoimmunity. PMID:25581706

  6. Autoimmune Pancreatitis.

    Science.gov (United States)

    Majumder, Shounak; Takahashi, Naoki; Chari, Suresh T

    2017-07-01

    Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP. Histologically, lymphoplasmacytic acinar inflammation and storiform fibrosis are seen in both. In addition, the histologic hallmark of IDCP is the granulocyte epithelial lesion: intraluminal and intraepithelial neutrophils in medium-sized and small ducts with or without granulocytic acinar inflammation often associated with destruction of ductal architecture. Initial treatment of both AIP and IDCP is with oral corticosteroids for duration of 4 weeks followed by a gradual taper. Relapses are common in AIP and relatively uncommon in IDCP, a relatively rare disease for which the natural history is not well understood. For patients with relapsing AIP, treatment with immunomodulators and more recently rituximab has been recommended. Although rare instances of pancreaticobiliary malignancy has been reported in patients with AIP, overall the lifetime risk of developing pancreatic cancer does not appear to be elevated.

  7. Efeito da hidratação com carboidratos na resposta glicêmica de diabéticos tipo 1 durante o exercício Efecto de la hidratación con carbohidratos en la respuesta glicemica de diabéticos tipo 1 durante el exercício Effect of hydration with carbohydrates on the glycemic response in type I diabetics during exercise

    Directory of Open Access Journals (Sweden)

    Rudinei Andrade

    2005-02-01

    Full Text Available Não está claro se a ingestão de carboidratos (CHO através de bebidas esportivas pode manter a glicemia em diabéticos tipo 1. A finalidade deste estudo foi examinar a glicemia em adolescentes com diabetes tipo 1 que ingeriram bebidas esportivas com 6% de CHO durante e após o exercício. Dez adolescentes (5 meninas e 5 meninos, 15,3 ± 2,4 anos com o diabetes controlado (HbA1c 0,05, e diminuiu significativamente na situação placebo (282,9 ± 85 para 160,2 ± 77mg·dL-1, p No está claro se la ingestión de carbohidratos (CHO a través de bebidas deportivas puede mantener la glicemia en diabéticos tipo 1. La finalidad de este estudio fué examinar la glicemia en adolescentes con diabetes tipo 1 que ingerirían bebidas deportivas con 6% de CHO durante y después del ejercicio. Diez adolescentes (5 chicas y 5 chicos, 15,3 ± 2,4 años con la diabetes controlada (HbA1c 0,05, y disminuyó significativamente en la situación placebo (282,9 ± 85 para 160,2 ± 77 mg·dL-1, p It is not clear whether the carbohydrate (CHO ingestion through sports drinks can maintain blood glucose concentrations in type I diabetics. The objective of this study was to examine blood glucose concentrations in adolescents with type I diabetics who ingest a sport drink with 6% CHO during and after exercise. Ten (5 males and 5 females adolescents (15.3 ± 2.4 years with a well-controlled type 1 diabetics (HbA1C 0.05 as it did in the placebo situation (282.9 ± 85.1 to 160.2 ± 77.0 mg· dL-1, p < 0,05 (9 vs 43.2%. After 30 min of recovery, blood glucose concentrations were 177.2 ± 107 mg·dL-1 with CHO-6% and 149.1 ± 69.6 mg·dL-1 in the placebo situation, representing 20.1% and 47.3% of pre-exercise levels. No significant differences between situations were found in heart rate, rate of perceived exertion or in blood insulin and electrolytes levels. No changes in hematocrit and hemoglobin were found during exercise, indicating that subjects remained euhydrated. In

  8. Clinical implications of shared genetics and pathogenesis in autoimmune diseases

    NARCIS (Netherlands)

    Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca

    2013-01-01

    Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the

  9. Identification of a Sj?gren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons

    OpenAIRE

    Li, He; Reksten, Tove Ragna; Ice, John A.; Kelly, Jennifer A.; Adrianto, Indra; Rasmussen, Astrid; Wang, Shaofeng; He, Bo; Grundahl, Kiely M.; Glenn, Stuart B.; Miceli-Richard, Corinne; Bowman, Simon; Lester, Sue; Eriksson, Per; Eloranta, Maija-Leena

    2017-01-01

    Sjogrens syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performe...

  10. Prevalence of Diabetes Type 1 in Patients Suffered From Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dayer

    2016-04-01

    Full Text Available Background Because IL2RA is considered a predisposing factor in the incidence of both type I diabetes and multiple sclerosis (MS, and considering that both are autoimmune diseases, some studies suggest a correlation between type I diabetes and MS. Objectives The aim of this study was to examine the prevalence of type I diabetes among people with MS. Patients and Methods The study subjects comprised 100 patients with MS from the Khuzestan multiple sclerosis center at rehabilitation school of Jundishapur University of Medical Sciences, whose diagnosis of MS had been confirmed by a specialist, and were not being treated with steroids. Subjects were selected from patients younger than 30 years old. After filling out an application form, 5 mL fasting venous blood and 5 mL after 2 hours were taken. The blood glucose level was measured with a kit (Zist Shimi using the enzymatic method. Results The mean age of the participants was 24.28 years. The rate of type I diabetes was equal to 4% of the total sample, while 18% of all patients had impaired fasting glucose. Conclusions Given the high level of impaired fasting glucose among patients in this study, it is likely that MS provides the basis for the incidence of glucose metabolism disorders. To prove this, further studies with larger sample sizes are required.

  11. Loss of insulin response to glucose but not arginine during the development of autoimmune diabetes in BB/W rats: relationships to islet volume and glucose transport rate.

    OpenAIRE

    Tominaga, M; Komiya, I; Johnson, J H; Inman, L; Alam, T; Moltz, J; Crider, B; Stefan, Y; Baetens, D; McCorkle, K

    1986-01-01

    The insulin and glucagon responses to 10 mM glucose and 10 mM arginine were studied in pancreata isolated from nondiabetic diabetes-prone and diabetes-resistant BB/W rats at 60, 80, and 140 days of age and in diabetic BB/W rats on the 1st and 14th days of their diabetes. In the former group the insulin response to glucose declined progressively with age (r = -0.575; P less than 0.01) and at 140 days was significantly below age-matched diabetes-resistant controls (P less than 0.05). The insuli...

  12. Autoimmune polyglandular syndrome type 1 in a 12-year-old ...

    African Journals Online (AJOL)

    Autoimmune polyglandular syndrome type 1 in a 12-year-old Ugandan girl. ... Journal of Endocrinology, Metabolism and Diabetes of South Africa ... Autoimmune polyglandular syndrome type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasisectodermal dystrophy syndrome, is a very rare disorder of ...

  13. Achalasia in a Patient with Polyglandular Autoimmune Syndrome Type II

    Directory of Open Access Journals (Sweden)

    Bashar S. Amr

    2015-05-01

    Full Text Available Achalasia is a rare disease characterized by aperistalsis of the esophageal body and failure of the lower esophageal sphincter to relax. The etiology of this disease remains unknown. Polyglandular autoimmune syndrome type II is a well-identified disease characterized by the occurrence of autoimmune Addison's disease in combination with autoimmune thyroid disease and/or type 1 diabetes mellitus. We report a case that suggests autoimmunity and immunogenicity as a probable contributing factor for association of these two rare disorders.

  14. Intestinal lymphangiectasia in a patient with autoimmune polyglandular syndrome type III.

    Science.gov (United States)

    Choudhury, Bipul Kumar; Saiki, Uma Kaimal; Sarm, Dipti; Choudhury, Bikash Narayan; Choudhury, Sarojini Dutta; Saharia, Dhiren; Saikia, Mihir

    2011-11-01

    Autoimmune polyglandular syndromes (APS) comprise a wide clinical spectrum of autoimmune disorders. APS is divided into Type I, Type II, Type I and Type IV depending upon the pattern of disease combination. Ghronic diarrhoea is one of the many manifestations of APS and many aetiological factors have been suggested for it. Apart from the established aetiological factors, intestinal lymphangiectasia may be responsible for chronic diarrhea in some cases.Intestinal lymphangiectasia has been reported in Type I APS. We report a case of Type III APS with hypocalcaemia and hypothyroidism who had chronic diarrhea of long duration and was finally diagnosed to have intestinal lymphangiectasia.

  15. A Case of Autoimmune Pancreatitis Presenting as a Deterioration in Glycaemic Control in a Patient with Pre-Existing Type 2 Diabetes

    LENUS (Irish Health Repository)

    Forde, H

    2017-05-01

    Autoimmune pancreatitis (AIP) was first described in 1961 and accounts for 5-6% of cases of chronic pancreatitis, though the prevalence is increasing with increasing awareness of the disease1,2. There are two types of autoimmune pancreatitis with different clinical and pathological features. Type 1 AIP is an IgG4 related disease and tends to occur in elderly patients in the 7th decade, with a male preponderance3. Type 1 AIP is associated with other organ involvement and commonly affects the biliary system3. In contrast, Type 2 AIP occurs in patients in the 5th-6th decade of life and other organ involvement is uncommon3. Both types of AIP respond well to steroids with reported remission rates of 99% and 92% for Type 1 and Type 2 AIP respectively4.\\r\

  16. The type I interferon response during viral infections: a "SWOT" analysis.

    Science.gov (United States)

    Gaajetaan, Giel R; Bruggeman, Cathrien A; Stassen, Frank R

    2012-03-01

    The type I interferon (IFN) response is a strong and crucial moderator for the control of viral infections. The strength of this system is illustrated by the fact that, despite some temporary discomfort like a common cold or diarrhea, most viral infections will not cause major harm to the healthy immunocompetent host. To achieve this, the immune system is equipped with a wide array of pattern recognition receptors and the subsequent coordinated type I IFN response orchestrated by plasmacytoid dendritic cells (pDCs) and conventional dendritic cells (cDCs). The production of type I IFN subtypes by dendritic cells (DCs), but also other cells is crucial for the execution of many antiviral processes. Despite this coordinated response, morbidity and mortality are still common in viral disease due to the ability of viruses to exploit the weaknesses of the immune system. Viruses successfully evade immunity and infection can result in aberrant immune responses. However, these weaknesses also open opportunities for improvement via clinical interventions as can be seen in current vaccination and antiviral treatment programs. The application of IFNs, Toll-like receptor ligands, DCs, and antiviral proteins is now being investigated to further limit viral infections. Unfortunately, a common threat during stimulation of immunity is the possible initiation or aggravation of autoimmunity. Also the translation from animal models to the human situation remains difficult. With a Strengths-Weaknesses-Opportunities-Threats ("SWOT") analysis, we discuss the interaction between host and virus as well as (future) therapeutic options, related to the type I IFN system. Copyright © 2011 John Wiley & Sons, Ltd.

  17. A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant.

    Science.gov (United States)

    Paris, Liliana P; Usui, Yoshihiko; Serino, Josefina; Sá, Joaquim; Friedlander, Martin

    2015-06-01

    Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing.

  18. A Challenging Form of Non-autoimmune Insulin-Dependent Diabetes in a Wolfram Syndrome Patient with a Novel Sequence Variant

    Science.gov (United States)

    Paris, Liliana P; Usui, Yoshihiko; Serino, Josefina; Sá, Joaquim; Friedlander, Martin

    2015-01-01

    Wolfram syndrome type 1 is a rare, autosomal recessive, neurodegenerative disorder that is diagnosed when insulin-dependent diabetes of non-auto-immune origin and optic atrophy are concomitantly present. Wolfram syndrome is also designated by DIDMOAD that stands for its most frequent manifestations: diabetes insipidus, diabetes mellitus, optic atrophy and deafness. With disease progression, patients also commonly develop severe neurological and genito-urinary tract abnormalities. When compared to the general type 1 diabetic population, patients with Wolfram Syndrome have been reported to have a form of diabetes that is more easily controlled and with less microvascular complications, such as diabetic retinopathy. We report a case of Wolfram syndrome in a 16-year-old male patient who presented with progressive optic atrophy and severe diabetes with very challenging glycemic control despite intensive therapy since diagnosis at the age of 6. Despite inadequate metabolic control he did not develop any diabetic microvascular complications during the 10-year follow-up period. To further investigate potential causes for this metabolic idiosyncrasy, we performed genetic analyses that revealed a novel combination of homozygous sequence variants that are likely the cause of the syndrome in this family. The identified genotype included a novel sequence variant in the Wolfram syndrome type 1 gene along with a previously described one, which had initially been associated with isolated low frequency sensorineural hearing loss (LFSNHL). Interestingly, our patient did not show any abnormal findings with audiometry testing. PMID:26819810

  19. Vitamin D and autoimmune diseases

    Directory of Open Access Journals (Sweden)

    E. A. Potrokhova

    2017-01-01

    Full Text Available The review discusses the effect of vitamin D on the tolerogenic modulation of an immune response, its relationship to cells of the monocyte-macrophage series, including dendritic cells, monocytes, and macrophages, in the context of the impact of the expression of anti-inflammatory proinflammatory cytokines in some autoimmune diseases (rheumatoid arthritis, systemic scleroderma, multiple sclerosis, type 1 diabetes mellitus, systemic lupus erythematosus, and Crohn`s disease. It discusses the role of vitamin D in the development of innate and adaptive immunity. Despite some conflicting evidence, the immune regulatory function of vitamin D is generally directed toward inhibition of the components of innate and acquired immunity, which are responsible for the induction of autoimmune reactions; in this connection there are a growing number of publications devoted to the issues of vitamin D supplementation in patients with autoimmune diseases, the preventive effect of vitamin D intake on the risk of an abnormality and that of therapeutic doses of the vitamin on its course. The maintenance of the threshold value for serum 25(OHD3 at least 30 ng/ml, which is achieved by the intake of about 2000 IU of vitamin D, is shown to be required for its immune regulatory function. The data given raise the question as to whether it is necessity to revise the Russian recommended daily dietary allowances for vitamin D through its infant food fortification.

  20. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  1. Galectin-3 in autoimmunity and autoimmune diseases.

    Science.gov (United States)

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

    2015-08-01

    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell-cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte-macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. © 2015 by the Society for Experimental Biology and Medicine.

  2. The Peculiar Characteristics of Fish Type I Interferons

    Directory of Open Access Journals (Sweden)

    Pierre Boudinot

    2016-11-01

    Full Text Available Antiviral type I interferons (IFNs have been discovered in fish. Genomic studies revealed their considerable number in many species; some genes encode secreted and non-secreted isoforms. Based on cysteine motifs, fish type I IFNs fall in two subgroups, which use two different receptors. Mammalian type I IFN genes are intronless while type III have introns; in fish, all have introns, but structurally, both subgroups belong to type I. Type I IFNs likely appeared early in vertebrates as intron containing genes, and evolved in parallel in tetrapods and fishes. The diversity of their repertoires in fish and mammals is likely a convergent feature, selected as a response to the variety of viral strategies. Several alternative nomenclatures have been established for different taxonomic fish groups, calling for a unified system. The specific functions of each type I gene remains poorly understood, as well as their interactions in antiviral responses. However, distinct induction pathways, kinetics of response, and tissue specificity indicate that fish type I likely are highly specialized, especially in groups where they are numerous such as salmonids or cyprinids. Unravelling their functional integration constitutes the next challenge to understand how these cytokines evolved to orchestrate antiviral innate immunity in vertebrates.

  3. The mirror transform of type I vacua in six dimensions

    International Nuclear Information System (INIS)

    Sen, A.; Sethi, S.

    1997-01-01

    We study certain compactifications of the type I string on K3. The three topologically distinct choices of gauge bundles for the type I theory are shown to be equivalent to type IIB orientifolds with different choices of background anti-symmetric tensor field flux. Using a mirror transformation we relate these models to orientifolds with fixed seven planes, and without any anti-symmetric tensor field flux. This map allows us to relate these type I vacua to particular six-dimensional F-theory and heterotic string compactifications. (orig.)

  4. Rotational KMS States and Type I Conformal Nets

    Science.gov (United States)

    Longo, Roberto; Tanimoto, Yoh

    2018-01-01

    We consider KMS states on a local conformal net on S 1 with respect to rotations. We prove that, if the conformal net is of type I, namely if it admits only type I DHR representations, then the extremal KMS states are the Gibbs states in an irreducible representation. Completely rational nets, the U(1)-current net, the Virasoro nets and their finite tensor products are shown to be of type I. In the completely rational case, we also give a direct proof that all factorial KMS states are Gibbs states.

  5. Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study.

    Science.gov (United States)

    Cinek, Ondrej; Stene, Lars C; Kramna, Lenka; Tapia, German; Oikarinen, Sami; Witsø, Elisabet; Rasmussen, Trond; Torjesen, Peter A; Hyöty, Heikki; Rønningen, Kjersti S

    2014-10-01

    Only a few longitudinal molecular studies of enterovirus and islet autoimmunity have been reported, and positive results seem to be limited to Finland. We aimed to investigate an association between enterovirus RNA in blood and islet autoimmunity in the MIDIA study from Norway, a country which largely shares environmental and economic features with Finland. We analysed serial blood samples collected at ages 3, 6, and 9 months and then annually from 45 children who developed confirmed positivity for at least two autoantibodies (against insulin, GAD65 and IA-2) and 92 matched controls, all from a cohort of children with a single high-risk HLA-DQ-DR genotype. Enterovirus was tested in RNA extracted from frozen blood cell pellets, using real-time RT-PCR with stringent performance control. Out of 807 blood samples, 72 (8.9%) were positive for enterovirus. There was no association between enterovirus RNA and islet autoimmunity in samples obtained strictly before (7.6% cases, 10.0% controls, OR 0.75 [95% CI 0.36, 1.57]), or strictly after the first detection of islet autoantibodies (10.5% case, 5.8% controls, OR 2.00 [95% CI 0.64, 6.27]). However, there was a tendency towards a higher frequency of enterovirus detection in the first islet autoantibody-positive sample (15.8%) compared with the corresponding time point in matched controls (3.2%, OR 8.7 [95% CI 0.97, 77]). Neither of these results was changed by adjusting for potential confounders, restricting to various time intervals or employing various definitions of enterovirus positivity. Positivity for enterovirus RNA in blood did not predict the later induction of islet autoantibodies, but enterovirus tended to be detected more often at the islet autoantibody seroconversion stage.

  6. Risk of Celiac Disease Autoimmunity is Modified by Non-HLA Genetic Markers During the First Year of Clinical Type 1 Diabetes

    DEFF Research Database (Denmark)

    Adlercreutz, Emma H.; Hansen, Dorthe; Mortensen, Henrik B.

    2014-01-01

    Aims: This study plotted the prevalence of celiac disease associated antibodies in relation to demographic patterns, genetic and metabolic markers during the first year after diagnosis in a multinational cohort of children with T1D. Material and Methods: Sera from a total of 261 children (128 males...... measuring IgG-tTG. Children positive in both assays in two consecutive samples were defined as having celiac disease autoimmunity (CDA). Associations between CDA and genotypes of HLA, IL18 rap, CCR 5, PTPN2 and correlations with islet autoantibodies (ICA, GADA, IA2 and IA) and HbA1C and C-peptide were...

  7. Autoimmune gastritis: histology phenotype and OLGA staging.

    Science.gov (United States)

    Rugge, M; Fassan, M; Pizzi, M; Zorzetto, V; Maddalo, G; Realdon, S; De Bernard, M; Betterle, C; Cappellesso, R; Pennelli, G; de Boni, M; Farinati, F

    2012-06-01

    Among Western populations, the declining incidence of Helicobacter pylori infection coincides with a growing clinical impact of autoimmune gastritis. To describe the histological phenotype of autoimmune gastritis, also to test the prognostic impact of OLGA staging in the autoimmune setting. A single-institutional series (spanning the years 2003-2011) of 562 consecutive patients (M:F ratio: 1:3.7; mean age = 57.6 ± 14.4 years) with serologically confirmed autoimmune gastritis underwent histology review and OLGA staging. Helicobacter pylori infection was ascertained histologically in 44/562 cases (7.8%). Forty six biopsy sets (8.2%) featured OLGA stages III-IV; they included all four cases of incidental epithelial neoplasia (three intraepithelial and one invasive; three of these four cases had concomitant H. pylori infection). There were 230 (40.9%) and 139 (24.7%) cases, respectively, of linear and micro-nodular enterochromaffin-like cell hyperplasia; 19 (3.4%) type I carcinoids were detected. The series included 116 patients who underwent repeated endoscopy/biopsy sampling (mean time elapsing between the two procedures = 54 months; range 24-108). Paired histology showed a significant (P = 0.009) trend towards a stage progression [the stage increased in 25/116 cases (22%); it remained unchanged in 87/116 cases (75%)]. In autoimmune gastritis, the cancer risk is restricted to high-risk gastritis stages (III-IV), and is associated mainly with concomitant H. pylori infection. OLGA staging consistently depicts the time-dependent organic progression of the autoimmune disease and provides key information for secondary gastric cancer prevention strategies. © 2012 Blackwell Publishing Ltd.

  8. Diabetes autoinmune latente del adulto o diabetes tipo 1 de lenta progresión: definición, patogenia, clínica, diagnóstico y tratamiento Latent autoimmune diabetes of the adult or type 1 diabetes of slow progression: definition, pathogeny, clinic, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Eduardo Cabrera Rode

    2002-04-01

    Full Text Available Se sabe que la diabetes mellitus es un síndrome heterogéneo que tiene como elemento común una hiperglucemia crónica, como consecuencia de una deficiencia de insulina o una insuficiente efectividad de su acción. Nos propusimos en este trabajo describir los aspectos más relevantes de la diabetes autoinmune del adulto (LADA y exponer el resultado de nuestra experiencia. Se considera que un sujeto la padece cuando es clasificado inicialmente como diabético tipo 2, el inicio es después de los 34 años, tiene generalmente peso corporal, normal o bajo y en un tiempo relativamente corto necesita tratamiento insulínico para lograr un buen control metabólico y presenta además una mayor asociación con la producción de anticuerpos antiislotes (ICA, antiglutámico descarboxilasa (AGAD65, microsomales tiroideos y antigástricos parietales, con una susceptibilidad genética por la presencia de haplotipos HLA-DR. Al momento del diagnóstico clínico puede presentar o no una insulinodeficiencia. Se ha demostrado que la insulinoterapia es el tratamiento ideal para los individuos con LADA, con el mismo se ha evidenciado una alta tasa de conversión negativa de los ICA con un incremento de los niveles de péptido C en el suero. Por el contrario, el tratamiento con sulfonilureas produce una persistencia de los ICA, los que probablemente sean responsables de una destrucción progresiva de las células b del páncreas. Por tanto, estas observaciones justifican la elección de la insulinoterapia desde el mismo momento del diagnóstico.It is known that diabetes mellitus is an heterogeneous syndrome that has as a common element a chronic hyperglycaemia resulting from an insulin deficiency or from an insufficient effectiveness of its action. It is our purpose to describe the most significant aspects of the autoimmune diabetes of the adult and to show the result of our experience. It is considered that subjects suffer from it when they are initially classified

  9. GBAmutations in Gaucher type I Venezuelan patients: ethnic origins ...

    Indian Academy of Sciences (India)

    Gilberto GÓmez

    2017-09-08

    Sep 8, 2017 ... In Venezuela, 20 unrelated index cases with GD type I were ..... S, splenomegaly; T, thrombocytopenia; Bc, bone crisis; Hy, hypotonia; NA, data not available; ..... Management of neuronopathic Gaucher disease: a European.

  10. D-strings in unconventional type I vacuum configurations

    International Nuclear Information System (INIS)

    Bianchi, M.; Gava, E.; Morales, F.; Narain, K.S.

    1998-11-01

    We determine the spectrum of D-string bound states in various classes of generalized type I vacuum configurations with sixteen and eight supercharges. The precise matching of the BPS spectra confirms the duality between unconventional type IIB orientfolds with quantized NS-NS antisymmetric tensor and heterotic CHL models in D=8. A similar analysis puts the duality between type II (4,0) models and type I strings without open strings on a firmer ground. The analysis can be extended to type II (2,0) asymmetric orbifolds and their type I duals that correspond to unconventional K3 compactifications. Finally we discuss BPS-saturated threshold corrections to the corresponding low-energy effective lagrangians. In particular we show how the exact moduli dependence of some F 4 terms in the eight-dimensional type II (4,0) orbifold is reproduced by the infinite sum of D-instanton contributions in the dual type I theory. (author)

  11. PERFORMANCE EVALUATION OF TYPE I MARINE SANITATION DEVICES

    Science.gov (United States)

    This performance test was designed to evaluate the effectiveness of two Type I Marine Sanitation Devices (MSDs): the Electro Scan Model EST 12, manufactured by Raritan Engineering Company, Inc., and the Thermopure-2, manufactured by Gross Mechanical Laboratories, Inc. Performance...

  12. Characterization of a propylthiouracil-insensitive type I iodothyronine deiodinase

    NARCIS (Netherlands)

    J.P. Sanders (Jo); S. van der Geyten; E. Kaptein (Ellen); V.M. Darras (Veerle); E.R. Kuhn; J.L. Leonard; T.J. Visser (Theo)

    1997-01-01

    textabstractMammalian type I iodothyronine deiodinase (D1) activates and inactivates thyroid hormone by outer ring deiodination (ORD) and inner ring deiodination (IRD), respectively, and is potently inhibited by propylthiouracil (PTU). Here we describe the cloning and

  13. Mechanism of the thermal conductivity of type-I clathrates

    International Nuclear Information System (INIS)

    Ikeda, M. S.

    2015-01-01

    Due to their intrinsically low thermal conductivity, intermetallic type-I clathrates are promising candidates for thermoelectric energy conversion, most notably for waste-heat recovery above room temperature. Combining their low thermal conductivity with the enhanced electrical power factor of strongly correlated materials can be considered as one of the most promising routes to a next generation thermoelectric material. However, although much investigated, the physical origin of the low thermal conductivity of type-I clathrates is still debated. Therefore, the main goal of this thesis was to gain deeper insight into the mechanism of the low thermal conductivity of type-I clathrates. On the basis of recent inelastic neutron and X-ray scattering studies on type-I clathrates and skutterudites, an analytical model for describing the phonon thermal conductivity of such filled cage compounds was developed within this thesis. This model is based on the phononic filter effect and on strongly enhanced Umklapp scattering. Data on several Ge-based single crystalline type-I clathrates are discussed in the context of this model, revealing the influence of host framework vacancies, charge carriers, and large defects such as grain boundaries on the low-temperature thermal conductivity of type-I clathrates. Since for waste heat recovery the thermal conductivity at elevated temperatures is of interest, a sophisticated 3w-experiment for accurate measurements of bulk and thin film materials at elevated temperatures was developed. With the help of this experiment, a universal dependence of the intrinsic phonon thermal conductivity of type-I clathrates on the sound velocity and the lowest-lying guest Einstein mode was demonstrated for the first time. Further investigations on thermoelectric materials including the first Ce-containing type-I clathrate, skutterudites, and thin films complete this doctoral work. (author)

  14. The autoimmunity risk variant LYP-W620 cooperates with CSK in the regulation of TCR signaling.

    Directory of Open Access Journals (Sweden)

    María Luisa de la Puerta

    Full Text Available The protein tyrosine phosphatase LYP, a key regulator of TCR signaling, presents a single nucleotide polymorphism, C1858T, associated with several autoimmune diseases such as type I diabetes, rheumatoid arthritis, and lupus. This polymorphism changes an R by a W in the P1 Pro rich motif of LYP, which binds to CSK SH3 domain, another negative regulator of TCR signaling. Based on the analysis of the mouse homologue, Pep, it was proposed that LYP and CSK bind constitutively to inhibit LCK and subsequently TCR signaling. The detailed study of LYP/CSK interaction, here presented, showed that LYP/CSK interaction was inducible upon TCR stimulation, and involved LYP P1 and P2 motifs, and CSK SH3 and SH2 domains. Abrogating LYP/CSK interaction did not preclude the regulation of TCR signaling by these proteins.

  15. Immuno-chemistry of hydroxyl radical modified GAD-65: A possible role in experimental and human diabetes mellitus.

    Science.gov (United States)

    Moinuddin; Ansari, Nadeem A; Shahab, Uzma; Habeeb, Safia; Ahmad, Saheem

    2015-10-01

    The repertoire of known auto-antigens is limited to a very small proportion of all human proteins, and the reason why only some proteins become auto-antigens is unclear. The 65 kDa isoform of the enzyme glutamic acid decarboxylase (GAD-65) is a major auto-antigen in type I diabetes, and in various neurological diseases. Most patients with type I diabetes (70-80%) have auto-antibodies against GAD-65, which often appear years before clinical onset of the autoimmune diabetes. Thus, the aim of the study is to focus on the immunogenicity of GAD65 and its reactive oxygen species (ROS) conformer in STZ-induced diabetic rats and on human diabetic patients. In the present study, GAD-65 was modified by hydroxyl radical following Fenton's reaction. The modifications in the structure of the GAD-65 are supported by UV-vis and fluorescence spectral studies. Immunogenicity of both native and hydroxyl radical modified GAD-65 (ROS-GAD-65) was studied in experimental rabbits and was confirmed by inducing type I diabetes in experimental male albino rats using streptozotocin (45 mg/kg). We found that ROS-GAD-65 was a better immunogen as compared to the native GAD-65. A considerable high binding to ROS-GAD-65 was observed as compared to native GAD-65 in both the serum antibodies from diabetes animal models and as well as in the serum samples of type I diabetes. Hydrogen peroxide under the exposure of UV light produces hydroxyl radical (·OH) which is most potent oxidant, and could cause protein damage (GAD-65) to the extent of generating neo-epitopes on the molecule, thus making it immunogenic. © 2015 International Union of Biochemistry and Molecular Biology.

  16. Plasmacytoid dendritic cells and type I interferon in the immunological response against warts.

    Science.gov (United States)

    Saadeh, D; Kurban, M; Abbas, O

    2017-12-01

    Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), and are involved in the pathogenesis of several cutaneous infectious (especially viral), inflammatory/autoimmune and neoplastic entities. Their role in the pathogenesis and regression of human papilloma virus (HPV)-induced skin lesions has not been well studied. To investigate pDC occurrence and activity in HPV-induced skin lesions, including inflamed and uninflamed warts as well as epidermodysplasia verruciformis (EDV)-associated lesions. In total 20 inflamed and 20 uninflamed HPV-induced skin lesions (including 7 EDV lesions) were retrieved from our database, and the tissue was immunohistochemically tested for pDC occurrence and activity using anti-BDCA-2 and anti-MxA antibodies, respectively. pDCs were present in all 20 inflamed warts and absent from all 20 uninflamed cases. MxA expression was also diffuse and strong in 75% (15/20) inflamed warts, but not in any of the uninflamed warts. pDCs constitute a central component of the inflammatory host response in inflamed warts, possibly contributing to their regression through production of type I interferons. © 2017 British Association of Dermatologists.

  17. Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2005-06-01

    Full Text Available Abstract Background Interferon (IFN-α is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs. This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS stimulation in vitro. Results Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-β, IFN-α2b/α2, IFN-αI, IFN-α2, IFN-αC, IFN-αJ1, IFN-αH2, and INF-α4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-γ. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their sub-classification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. Conclusion Seven IFN-α isoforms and IFN-β participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-α in

  18. The Autoimmune Ecology.

    Science.gov (United States)

    Anaya, Juan-Manuel; Ramirez-Santana, Carolina; Alzate, Maria A; Molano-Gonzalez, Nicolas; Rojas-Villarraga, Adriana

    2016-01-01

    Autoimmune diseases (ADs) represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology), which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation). As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology). In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics) to favor or protect against autoimmunity and its outcomes. Herein, we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status (SES), gender and sex hormones, vitamin D, organic solvents, and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  19. Bistability in autoimmune diseases

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Mosekilde, Erik; Lund, Ole

    2011-01-01

    Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state...

  20. Update in endocrine autoimmunity.

    Science.gov (United States)

    Anderson, Mark S

    2008-10-01

    The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders.

  1. THE AUTOIMMUNE ECOLOGY.

    Directory of Open Access Journals (Sweden)

    Juan-Manuel eAnaya

    2016-04-01

    Full Text Available Autoimmune diseases (ADs represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology, which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation. As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology. In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics to favor or protect against autoimmunity and its outcomes. Herein we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status, gender and sex hormones, vitamin D, organic solvents and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.

  2. Type I interferons in tuberculosis: Foe and occasionally friend.

    Science.gov (United States)

    Moreira-Teixeira, Lúcia; Mayer-Barber, Katrin; Sher, Alan; O'Garra, Anne

    2018-05-07

    Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis. Since then, additional studies in human tuberculosis and experimental mouse models of M. tuberculosis infection support the concept that type I IFN promotes both bacterial expansion and disease pathogenesis. More recently, studies in a different setting have suggested a putative protective role for type I IFN. In this study, we discuss the mechanistic and contextual factors that determine the detrimental versus beneficial outcomes of type I IFN induction during M. tuberculosis infection, from human disease to experimental mouse models of tuberculosis. © 2018 Moreira-Teixeira et al.

  3. [Vertebral fractures in children with Type I Osteogenesis imperfecta].

    Science.gov (United States)

    Sepúlveda, Andrea M; Terrazas, Claudia V; Sáez, Josefina; Reyes, María L

    2017-06-01

    Osteogenesis imperfecta (OI) is an hereditary disease affecting conective tissue, mainly associated to growth retardation and pathological fractures. OI type I (OI type I), is the mildest, most often, and homogeneous in its fenotype. Vertebral fractures are the most significant complications, associated to skeletical and cardiopulmonary morbidity. To characterize clinically a cohort of children with OI type I. A cohort of OI type I children younger than 20 year old was evaluated. Demographic, clinical, biochemical and radiological data were registered. Sixty seven patients were included, 55% male, 69% resident in the Metropolitan Region. The mean age of diagnose was 2.9 years, 70% presented vertebral fractures on follow-up, mostly thoracic, and 50% before the age of 5 years. Fifty percentage presented vertebral fractures at diagnose, which was about the age of 5 years. Bone metabolic parameters were in the normal range, without significant change at the moment of vertebral fractures. Calcium intake was found to be below American Academy of Pediatrics recommendations at the time of the first fracture. In this study OI type I has an early diagnose, and vertebral fractures show a high incidence, mostly in toddlers. Calcium intake was found to be below reccomended values, and should be closely supervised in these patients.

  4. ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

    Science.gov (United States)

    Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

    2017-10-01

    Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Heterotic/type I duality and D-brane instantons

    Science.gov (United States)

    Bachas, C.; Fabre, C.; Kiritsis, E.; Obers, N. A.; Vanhove, P.

    1998-01-01

    We study heterotic/type I duality in d = 8, 9 uncompactified dimensions. We consider the special ("BPS-saturated") F4 and R4 terms in the effective one-loop heterotic action, which are expected to be non-perturbatively exact. Under the standard duality map these translate to tree-level, perturbative and non-perturbative contributions on the type I side. We check agreement with the one-loop open string calculation, and discuss the higher-order perturbative contributions, which arise because of the mild non-holomorphicities of the heterotic elliptic genus. We put the heterotic world-sheet instanton corrections in a form that can be motivated as arising from a D-brane instanton calculation on the type I side.

  6. Heterotic/type I duality and D-brane instantons

    International Nuclear Information System (INIS)

    Bachas, C.; Fabre, C.; Vanhove, P.

    1998-01-01

    We study heterotic/type I duality in d=8,9 uncompactified dimensions. We consider the special (''BPS-saturated'') F 4 and R 4 terms in the effective one-loop heterotic action, which are expected to be non-perturbatively exact. Under the standard duality map these translate to tree-level, perturbative and non-perturbative contributions on the type I side. We check agreement with the one-loop open string calculation, and discuss the higher-order perturbative contributions, which arise because of the mild non-holomorphicities of the heterotic elliptic genus. We put the heterotic world-sheet instanton corrections in a form that can be motivated as arising from a D-brane instanton calculation on the type I side. (orig.)

  7. Heterotic / type-I duality and D-brane instantons

    CERN Document Server

    Bachas, C P; Kiritsis, Elias B; Obers, N A; Vanhove, P

    1998-01-01

    We study heterotic/type-I duality in d=8,9 uncompactified dimensions. We consider the special (``BPS saturated'') F^4 and R^4 terms in the effective one-loop heterotic action, which are expected to be non-perturbatively exact. Under the standard duality map these translate to tree-level, perturbative and non-perturbative contributions on the type I side. We check agreement with the one-loop open string calculation, and discuss the higher-order perturbative contributions, which arise because of the mild non-holomorphicities of the heterotic elliptic genus. We put the heterotic world-sheet instanton corrections in a form that can be recognized easily as arising from a D-brane instanton calculation on the type-I side.

  8. Type I interferons instigate fetal demise after Zika virus infection.

    Science.gov (United States)

    Yockey, Laura J; Jurado, Kellie A; Arora, Nitin; Millet, Alon; Rakib, Tasfia; Milano, Kristin M; Hastings, Andrew K; Fikrig, Erol; Kong, Yong; Horvath, Tamas L; Weatherbee, Scott; Kliman, Harvey J; Coyne, Carolyn B; Iwasaki, Akiko

    2018-01-05

    Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-deficient mice are highly susceptible to ZIKV infection. Severe fetal growth restriction with placental damage and fetal resorption is observed after ZIKV infection of type I IFN receptor knockout ( Ifnar1 -/- ) dams mated with wild-type sires, resulting in fetuses with functional type I IFN signaling. The role of type I IFNs in limiting or mediating ZIKV disease within this congenital infection model remains unknown. In this study, we challenged Ifnar1 -/- dams mated with Ifnar1 +/- sires with ZIKV. This breeding scheme enabled us to examine pregnant dams that carry a mixture of fetuses that express ( Ifnar1 +/- ) or do not express IFNAR ( Ifnar1 -/- ) within the same uterus. Virus replicated to a higher titer in the placenta of Ifnar1 -/- than within the Ifnar1 +/- concepti. Yet, rather unexpectedly, we found that only Ifnar1 +/- fetuses were resorbed after ZIKV infection during early pregnancy, whereas their Ifnar1 -/- littermates continue to develop. Analyses of the fetus and placenta revealed that, after ZIKV infection, IFNAR signaling in the conceptus inhibits development of the placental labyrinth, resulting in abnormal architecture of the maternal-fetal barrier. Exposure of midgestation human chorionic villous explants to type I IFN, but not type III IFNs, altered placental morphology and induced cytoskeletal rearrangements within the villous core. Our results implicate type I IFNs as a possible mediator of pregnancy complications, including spontaneous abortions and growth restriction, in the context of congenital viral infections. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  9. MRI-visible pericochlear lesions in osteogenesis imperfecta type I

    International Nuclear Information System (INIS)

    Ziyeh, S.; Berger, R.; Reisner, K.

    2000-01-01

    Osteogenesis imperfecta (OI) is an inherited generalized disorder of type-I collagen synthesis often associated with hearing loss. We present a case of OI type I in which hearing loss led to examination of the temporal bone with MRI. In the osseous otic capsule MRI demonstrated pericochlear lesions with soft tissue signal intensity and contrast enhancement. Changes similar to otosclerosis have been described in the temporal bone of OI patients when applying CT, but reports on MRI findings do not yet exist. (orig.)

  10. MRI-visible pericochlear lesions in osteogenesis imperfecta type I

    Energy Technology Data Exchange (ETDEWEB)

    Ziyeh, S.; Berger, R.; Reisner, K. [Radiologische Klinik, St. Vincentiuskrankenhaeuser, Karlsruhe (Germany)

    2000-10-01

    Osteogenesis imperfecta (OI) is an inherited generalized disorder of type-I collagen synthesis often associated with hearing loss. We present a case of OI type I in which hearing loss led to examination of the temporal bone with MRI. In the osseous otic capsule MRI demonstrated pericochlear lesions with soft tissue signal intensity and contrast enhancement. Changes similar to otosclerosis have been described in the temporal bone of OI patients when applying CT, but reports on MRI findings do not yet exist. (orig.)

  11. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Ana M. C. Faria

    2006-01-01

    Full Text Available Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10 and Th3 (TGF-β regulatory T cells (Tregs plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB, Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE, uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral, formulation, mucosal adjuvants, combination therapy and early therapy.

  12. [Non-autoimmune thyroiditis].

    Science.gov (United States)

    Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

    2014-01-01

    The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

  13. Polyglandular Autoimmune Syndrome Type III with Primary Hypoparathyroidism

    Directory of Open Access Journals (Sweden)

    Sang Jin Kim

    2013-09-01

    Full Text Available Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84, and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.

  14. Clostridium butyricum CGMCC0313.1 Protects against Autoimmune Diabetes by Modulating Intestinal Immune Homeostasis and Inducing Pancreatic Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Lingling Jia

    2017-10-01

    Full Text Available Recent evidence indicates that indigenous Clostridium species induce colonic regulatory T cells (Tregs, and gut lymphocytes are able to migrate to pancreatic islets in an inflammatory environment. Thus, we speculate that supplementation with the well-characterized probiotics Clostridium butyricum CGMCC0313.1 (CB0313.1 may induce pancreatic Tregs and consequently inhibit the diabetes incidence in non-obese diabetic (NOD mice. CB0313.1 was administered daily to female NOD mice from 3 to 45 weeks of age. The control group received an equal volume of sterile water. Fasting glucose was measured twice a week. Pyrosequencing of the gut microbiota and flow cytometry of mesenteric lymph node (MLN, pancreatic lymph node (PLN, pancreatic and splenic immune cells were performed to investigate the effect of CB0313.1 treatment. Early oral administration of CB0313.1 mitigated insulitis, delayed the onset of diabetes, and improved energy metabolic dysfunction. Protection may involve increased Tregs, rebalanced Th1/Th2/Th17 cells and changes to a less proinflammatory immunological milieu in the gut, PLN, and pancreas. An increase of α4β7+ (the gut homing receptor Tregs in the PLN suggests that the mechanism may involve increased migration of gut-primed Tregs to the pancreas. Furthermore, 16S rRNA gene sequencing revealed that CB0313.1 enhanced the Firmicutes/Bacteroidetes ratio, enriched Clostridium-subgroups and butyrate-producing bacteria subgroups. Our results provide the basis for future clinical investigations in preventing type 1 diabetes by oral CB0313.1 administration.

  15. Factors associated with elevated serum chromogranin A levels in patients with autoimmune gastritis.

    Science.gov (United States)

    Kalkan, Çağdaş; Karakaya, Fatih; Soykan, İrfan

    2016-11-01

    Chromogranin A is an important tool in the diagnosis of neuroendocrine tumors. Autoimmune gastritis is an autoimmune disorder marked by hypergastrinemia, which stimulates enterochromaffin-like cell proliferation. Chromogranin A is also elevated in autoimmune gastritis patients with a different level of increase in each patient. The goal of this study is to explore constituents that influence serum chromogranin A levels in autoimmune gastritis patients. One hundred and eighty-eight autoimmune gastritis patients and 20 patients with type I gastric carcinoid tumors were analyzed retrospectively and compared to 110 functional dyspepsia patients in terms of factors that might affect serum chromogranin A levels. The mean serum chromogranin A level was 171.17±67.3 ng/mL in autoimmune gastritis patients (n=62) without enterochromaffin-like cell hyperplasia, and 303.3±102.82 ng/mL in patients (n=126) with enterochromaffin-like cell hyperplasia (pgastritis were the presence of ECL cell hyperplasia and serum gastrin levels. Serum chromogranin A levels maybe helpful in distinguishing autoimmune gastritis patients and gastric carcinoid type I from the control group, but not useful in the differentiation of individuals with autoimmune gastritis from patients with gastric carcinoids.

  16. The expression of the beta cell-derived autoimmune ligand for the killer receptor nkp46 is attenuated in type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Chamutal Gur

    Full Text Available NK cells rapidly kill tumor cells, virus infected cells and even self cells. This is mediated via killer receptors, among which NKp46 (NCR1 in mice is prominent. We have recently demonstrated that in type 1 diabetes (T1D NK cells accumulate in the diseased pancreas and that they manifest a hyporesponsive phenotype. In addition, we found that NKp46 recognizes an unknown ligand expressed by beta cells derived from humans and mice and that blocking of NKp46 activity prevented diabetes development. Here we investigated the properties of the unknown NKp46 ligand. We show that the NKp46 ligand is mainly located in insulin granules and that it is constitutively secreted. Following glucose stimulation the NKp46 ligand translocates to the cell membrane and its secretion decreases. We further demonstrate by using several modalities that the unknown NKp46 ligand is not insulin. Finally, we studied the expression of the NKp46 ligand in type 2 diabetes (T2D using 3 different in vivo models and 2 species; mice and gerbils. We demonstrate that the expression of the NKp46 ligand is decreased in all models of T2D studied, suggesting that NKp46 is not involved in T2D.

  17. Stress proteins, autoimmunity, and autoimmune disease.

    Science.gov (United States)

    Winfield, J B; Jarjour, W N

    1991-01-01

    At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and

  18. 33 CFR 159.123 - Coliform test: Type I devices.

    Science.gov (United States)

    2010-07-01

    ... as follows: During each of the 10-test days, one sample must be taken at the beginning, middle, and end of an 8-consecutive hour period with one additional sample taken immediately following the peak...: Type I devices. (a) The arithmetic mean of the fecal coliform bacteria in 38 of 40 samples of effluent...

  19. Bianchi Type-I Universe with wet dark fluid

    Indian Academy of Sciences (India)

    Bianchi-type Universe; wet dark fluid; cosmological parameters. Abstract. The Bianchi Type-I Universe filled with dark energy from a wet dark fluid has been considered. A new equation of ... Pramana – Journal of Physics | News. © 2017 Indian ...

  20. Dentin dysplasia type I : Five cases within one family

    NARCIS (Netherlands)

    Kalk, WWI; Batenburg, RHK; Vissink, A

    Five cases of dentin dysplasia type I within one family are described. Clinically and radiologically, such patients are characterized by a delayed eruption pattern, opacity of the incisional margins, hypermobility of the teeth, short and defective roots, and obliterated pulp chambers. A conservative

  1. Bianchi Type-I Universe with wet dark fluid

    Indian Academy of Sciences (India)

    Abstract. The Bianchi Type-I Universe filled with dark energy from a wet dark fluid has ... model is in the spirit of the generalized Chaplygin gas (GCG) [9], where a physically motivated .... From the mechanical point of view, eq. (2.28) can be ...

  2. Bianchi type I inflationary universe in general relativity

    Indian Academy of Sciences (India)

    In this paper, we have investigated Bianchi type I inflationary universe in the presence of massless scalar field with a flat potential. To get an inflationary solution, we have considered a flat region in which potential is constant. The inflationary scenario of the model is discussed in detail.

  3. Bianchi type I inflationary universe in general relativity

    Indian Academy of Sciences (India)

    In this paper, we have investigated Bianchi type I inflationary universe in the presence of massless scalar field with a flat potential. To get an inflationary solution, we have considered a flat region in which potentialV is constant. The inflationary scenario of the model is discussed in detail. Keywords. Inflationary universe ...

  4. Audiological findings in children with mucopolysaccharidoses type i-iv.

    Science.gov (United States)

    Vargas-Gamarra, María F; de Paula-Vernetta, Carlos; Vitoria Miñana, Isidro; Ibañez-Alcañiz, Isabel; Cavallé-Garrido, Laura; Alamar-Velazquez, Agustín

    The aim of our study is to reflect hearing impairment of 23children diagnosed with mucopolysaccharidosis (MPS) typeI, II, III and IV. Retrospective study of the clinical, audiological and treatment (medical vs surgical) findings of 23children diagnosed with MPS typeI, II, III or IV followed at a Tertiary Referral Hospital between 1997 and 2015. Six cases of MPSI, 8 of MPSII, 4 of MPSIII and 5 of MPSIV were reviewed. 71.2% of patients had secretory otitis media (SOM) and 54% of patients had some type of hearing loss (HL). The behaviour of hearing loss was variable in each of the subgroups of MPS, finding greater involvement and variability in typesI and II. Children with MPS have a high risk of hearing loss. A significant percentage of transmissive HL progressing to mixed or sensorineural HL was observed. This was more common in typesI and II. Periodic follow up of these patients is mandatory because of hearing impairment and consequences for their development and quality of life. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  5. Type I collagen from bullfrog ( Rana catesbeiana ) fallopian tube ...

    African Journals Online (AJOL)

    Rana catesbeiana) with a yield of 16.4%, on a dry weight basis. Sodium dodecyl sulphate polyacylamide-gel electrophoresis (SDS-PAGE) showed that the PSC contained two alpha components (α1 and α2) and was classified as type I collagen ...

  6. Type I supernovae and angular anisotropy of the Hubble constant

    International Nuclear Information System (INIS)

    Le Denmat, Gerard; Vigier, J.-P.

    1975-01-01

    The observation of type I supernovae in distant galaxies yields an homogeneous sample of sources to evaluate their true distance. An examination of their distribution in the sky provides a significant confirmation of the angular anisotropy of the Hubble constant already observed by Rubin, Rubin and Ford [fr

  7. Genomic Analysis of Pathogenicity Determinants in Mycobacterium kansasii Type I

    KAUST Repository

    Guan, Qingtian

    2016-05-01

    Mycobacteria, a genus within Actinobacteria Phylum, are well known for two pathogens that cause human diseases: leprosy and tuberculosis. Other than the obligate human mycobacteria, there is a group of bacteria that are present in the environment and occasionally cause diseases in immunocompromised persons: the non-tuberculosis mycobacteria (NTM). Mycobacterium kansasii, which was first discovered in the Kansas state, is the main etiologic agent responsible for lung infections caused by NTM and raises attention because of its co-infection with human immunodeficiency virus (HIV). Five subspecies of M. kansasii (Type I-V) were described and only M. kansasii Type I is pathogenic to humans. M. kansasii is a Gram-positive bacteria that has a unique cell wall and secretion system, which is essential for its pathogenicity. We undertook a comparative genomics and transcriptomic approach to identify components of M. kansasii Type I pathogenicity. Our previous study showed that espA (ESX-1 essential protein) operon, a major component of the secretion system, is exclusively present in M. kansasii Type I. The purpose of this study was to test the functional role of the espA operon in pathogenicity and identify other components that may also be involved in pathogenicity. This study provides a new molecular diagnostic method for M. kansasii Type I infection using PCR (Polymerase Chain Reaction) technique to target the espAoperon. With detailed manual curation of the comparative genomics datasets, we found several genes exclusively present in M. kansasii Type I including ppsA/ppsC and whiB6, that we believe are involved, or have an effect on ESX-mediated secretion system. We have also highlighted, in our study, the differences in genetic components coding for the cell membrane composition between the five subspecies of M. kansasii. These results shed light on genetic components that are responsible for pathogenicity determinants in Type I M. kansasii and may help to design better

  8. Autoantibodies in Autoimmune Hepatitis.

    Science.gov (United States)

    Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo

    2015-01-01

    The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

  9. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Eosinophils in Autoimmune Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Čiháková

    2017-04-01

    Full Text Available Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs.

  11. Eosinophils in Autoimmune Diseases

    Science.gov (United States)

    Diny, Nicola L.; Rose, Noel R.; Čiháková, Daniela

    2017-01-01

    Eosinophils are multifunctional granulocytes that contribute to initiation and modulation of inflammation. Their role in asthma and parasitic infections has long been recognized. Growing evidence now reveals a role for eosinophils in autoimmune diseases. In this review, we summarize the function of eosinophils in inflammatory bowel diseases, neuromyelitis optica, bullous pemphigoid, autoimmune myocarditis, primary biliary cirrhosis, eosinophilic granulomatosis with polyangiitis, and other autoimmune diseases. Clinical studies, eosinophil-targeted therapies, and experimental models have contributed to our understanding of the regulation and function of eosinophils in these diseases. By examining the role of eosinophils in autoimmune diseases of different organs, we can identify common pathogenic mechanisms. These include degranulation of cytotoxic granule proteins, induction of antibody-dependent cell-mediated cytotoxicity, release of proteases degrading extracellular matrix, immune modulation through cytokines, antigen presentation, and prothrombotic functions. The association of eosinophilic diseases with autoimmune diseases is also examined, showing a possible increase in autoimmune diseases in patients with eosinophilic esophagitis, hypereosinophilic syndrome, and non-allergic asthma. Finally, we summarize key future research needs. PMID:28496445

  12. A rare combination of type 3 autoimmune polyendocrine syndrome (APS-3) or multiple autoimmune syndrome (MAS-3).

    Science.gov (United States)

    Betterle, Corrado; Garelli, Silvia; Coco, Graziella; Burra, Patrizia

    2014-06-01

    Type 3 autoimmune polyendocrine syndrome (APS-3) is defined by the presence of an autoimmune thyroid disease and another autoimmune illness, excluding Addison's disease; this is a frequent combination. We report the case of a 55 years old female patient with APS-3, with seven clinical or latent autoimmune manifestations. At 49 years of age she was admitted at the General Hospital for leukopenia, weight loss, tremors, anxiety and diarrhea. The personal history revealed ulcerative colitis and, during the last year, episodes of fever with migrant arthralgia and cutaneous lesions. The patient was evaluated for thyroid function and imaging, mielobiopsy, glycaemic control, gastrointestinal and rheumatologic disorders with specific biochemical tests, imaging and endoscopic procedures. We concluded that the patient was affected by APS-3, characterized by the association of Graves' disease, autoimmune leukopenia, latent autoimmune diabetes of the adult (LADA), autoimmune gastritis, ulcerative colitis, Sjögren's and anti-phospholipid syndromes. The patient started low doses of corticosteroid drugs for leukopenia, underwent (131)I therapy for hyperthyroidism and later started substitutive thyroid therapy with l-thyroxine, insulin therapy for LADA, mesalazine for ulcerative colitis and artificial tears for Sjögren's syndrome. In this article we report a complex case of APS-3, characterized by the association of seven different autoimmune diseases, which required a complex therapeutic strategy.

  13. Guidelines for management of glycogen storage disease type I - European study on glycogen storage disease type I (ESGSD I)

    NARCIS (Netherlands)

    Rake, JP; Visser, G; Labrune, P; Leonard, JV; Ullrich, K; Smit, GPA

    2002-01-01

    Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods

  14. Type 1 Diabetes Facts

    Science.gov (United States)

    ... Affiliates JDRF Celebrity Ambassadors JDRF Logo Usage Contact Us Donate Events More Type 1 Diabetes Facts Type 1 diabetes (T1D) is an autoimmune ... about Insulin and T1D Learn More What Is Diabetes? Causes of T1D The Complexity of Diagnosing ... US CAREERS NEWSROOM FOR RESEARCHERS © JDRF 2018 • Privacy Policy • ...

  15. Search for harmonic emission in solar type I radio bursts

    Energy Technology Data Exchange (ETDEWEB)

    Jaeggi, M.; Benz, A.O.

    1982-03-01

    We have made a statistical analysis of the harmonic emission of type I bursts, based upon the latest plasma wave theories for the emission mechanism. No systematic harmonic emission is found within the detection limit. This is also the case for a superposed epoch analysis of many bursts. The derived upper limit of the Langmuir wave energy density is Wsub(L)<5 10/sup -7/.lsub(km)/sup -1/ erg cm/sup -3/, where lsub(km) is the depth of the source. In a few single cases there is emission at the harmonic frequency but we could not exclude that this are change hits of an independent activity present at that frequency. These observations provide a considerable constraint on plasma emission models of type I bursts.

  16. Theoretical models for Type I and Type II supernova

    International Nuclear Information System (INIS)

    Woosley, S.E.; Weaver, T.A.

    1985-01-01

    Recent theoretical progress in understanding the origin and nature of Type I and Type II supernovae is discussed. New Type II presupernova models characterized by a variety of iron core masses at the time of collapse are presented and the sensitivity to the reaction rate 12 C(α,γ) 16 O explained. Stars heavier than about 20 M/sub solar/ must explode by a ''delayed'' mechanism not directly related to the hydrodynamical core bounce and a subset is likely to leave black hole remnants. The isotopic nucleosynthesis expected from these massive stellar explosions is in striking agreement with the sun. Type I supernovae result when an accreting white dwarf undergoes a thermonuclear explosion. The critical role of the velocity of the deflagration front in determining the light curve, spectrum, and, especially, isotopic nucleosynthesis in these models is explored. 76 refs., 8 figs

  17. Imaging collagen type I fibrillogenesis with high spatiotemporal resolution

    International Nuclear Information System (INIS)

    Stamov, Dimitar R; Stock, Erik; Franz, Clemens M; Jähnke, Torsten; Haschke, Heiko

    2015-01-01

    Fibrillar collagens, such as collagen type I, belong to the most abundant extracellular matrix proteins and they have received much attention over the last five decades due to their large interactome, complex hierarchical structure and high mechanical stability. Nevertheless, the collagen self-assembly process is still incompletely understood. Determining the real-time kinetics of collagen type I formation is therefore pivotal for better understanding of collagen type I structure and function, but visualising the dynamic self-assembly process of collagen I on the molecular scale requires imaging techniques offering high spatiotemporal resolution. Fast and high-speed scanning atomic force microscopes (AFM) provide the means to study such processes on the timescale of seconds under near-physiological conditions. In this study we have applied fast AFM tip scanning to study the assembly kinetics of fibrillar collagen type I nanomatrices with a temporal resolution reaching eight seconds for a frame size of 500 nm. By modifying the buffer composition and pH value, the kinetics of collagen fibrillogenesis can be adjusted for optimal analysis by fast AFM scanning. We furthermore show that amplitude-modulation imaging can be successfully applied to extract additional structural information from collagen samples even at high scan rates. Fast AFM scanning with controlled amplitude modulation therefore provides a versatile platform for studying dynamic collagen self-assembly processes at high resolution. - Highlights: • Continuous non-invasive time-lapse investigation of collagen I fibrillogenesis in situ. • Imaging of collagen I self-assembly with high spatiotemporal resolution. • Application of setpoint modulation to study the hierarchical structure of collagen I. • Observing real-time formation of the D-banding pattern in collagen I

  18. Type-I integrable quantum impurities in the Heisenberg model

    Energy Technology Data Exchange (ETDEWEB)

    Doikou, Anastasia, E-mail: adoikou@upatras.gr

    2013-12-21

    Type-I quantum impurities are investigated in the context of the integrable Heisenberg model. This type of defects is associated to the (q)-harmonic oscillator algebra. The transmission matrices associated to this particular type of defects are computed via the Bethe ansatz methodology for the XXX model, as well as for the critical and non-critical XXZ spin chain. In the attractive regime of the critical XXZ spin chain the transmission amplitudes for the breathers are also identified.

  19. The 1974 Type I supernova in NGC 4414

    International Nuclear Information System (INIS)

    Patchett, B.; Wood, R.

    1976-01-01

    Spectra of Miss Burgat's supernova in NGC 4414 were taken with the Isaac Newton 2.5-m reflector during 1974 April and May. The spectra cover the period from just before maximum light to 20 days post-maximum, and show many features typical of Type I supernovae. In addition secondary features in the spectrum indicate the presence of thin shell or filamentary structure. A photographic light curve and direct plate are presented. (author)

  20. Imaging collagen type I fibrillogenesis with high spatiotemporal resolution

    Energy Technology Data Exchange (ETDEWEB)

    Stamov, Dimitar R, E-mail: stamov@jpk.com [JPK Instruments AG, Bouchéstrasse 12, 12435 Berlin (Germany); Stock, Erik [JPK Instruments AG, Bouchéstrasse 12, 12435 Berlin (Germany); Franz, Clemens M [DFG-Center for Functional Nanostructures (CFN), Karlsruhe Institute of Technology (KIT), Wolfgang-Gaede-Strasse 1a, 76131 Karlsruhe (Germany); Jähnke, Torsten; Haschke, Heiko [JPK Instruments AG, Bouchéstrasse 12, 12435 Berlin (Germany)

    2015-02-15

    Fibrillar collagens, such as collagen type I, belong to the most abundant extracellular matrix proteins and they have received much attention over the last five decades due to their large interactome, complex hierarchical structure and high mechanical stability. Nevertheless, the collagen self-assembly process is still incompletely understood. Determining the real-time kinetics of collagen type I formation is therefore pivotal for better understanding of collagen type I structure and function, but visualising the dynamic self-assembly process of collagen I on the molecular scale requires imaging techniques offering high spatiotemporal resolution. Fast and high-speed scanning atomic force microscopes (AFM) provide the means to study such processes on the timescale of seconds under near-physiological conditions. In this study we have applied fast AFM tip scanning to study the assembly kinetics of fibrillar collagen type I nanomatrices with a temporal resolution reaching eight seconds for a frame size of 500 nm. By modifying the buffer composition and pH value, the kinetics of collagen fibrillogenesis can be adjusted for optimal analysis by fast AFM scanning. We furthermore show that amplitude-modulation imaging can be successfully applied to extract additional structural information from collagen samples even at high scan rates. Fast AFM scanning with controlled amplitude modulation therefore provides a versatile platform for studying dynamic collagen self-assembly processes at high resolution. - Highlights: • Continuous non-invasive time-lapse investigation of collagen I fibrillogenesis in situ. • Imaging of collagen I self-assembly with high spatiotemporal resolution. • Application of setpoint modulation to study the hierarchical structure of collagen I. • Observing real-time formation of the D-banding pattern in collagen I.

  1. Notes on Type I Subjective Motion Expressions in English

    OpenAIRE

    Onozuka, Hiromi

    2012-01-01

    In this paper we deal with what Matsumoto calls Type I subjective motion expressions in English. According to Matsumoto they cannot occur with frequency adverbs and do not generally allow the progressive aspect. We show that his observation is not valid by presenting naturally occurring examples of the expressions which involve frequency adverbs and the progressive aspect, respectively. Further we investigate how the frequency adverbs are allowed and what functions the progressive aspect has....

  2. Type I supergravity effective action from pure spinor formalism

    International Nuclear Information System (INIS)

    Alencar, Geova

    2009-01-01

    Using the pure spinor formalism, we compute the tree-level correlation functions for three strings, one closed and two open, in N = 1 D = 10 superspace. Expanding the superfields in components, the respective terms of the effective action for the type I supergravity are obtained. All terms found agree with the effective action known in the literature. This result gives one more consistency test for the pure spinor formalism.

  3. Type-I integrable quantum impurities in the Heisenberg model

    International Nuclear Information System (INIS)

    Doikou, Anastasia

    2013-01-01

    Type-I quantum impurities are investigated in the context of the integrable Heisenberg model. This type of defects is associated to the (q)-harmonic oscillator algebra. The transmission matrices associated to this particular type of defects are computed via the Bethe ansatz methodology for the XXX model, as well as for the critical and non-critical XXZ spin chain. In the attractive regime of the critical XXZ spin chain the transmission amplitudes for the breathers are also identified

  4. Type I Gaucher disease: extraosseous extension of skeletal disease

    International Nuclear Information System (INIS)

    Poll, L.W.; Koch, J.A.; Moedder, U.; Dahl, S. vom; Haeussinger, D.; Sarbia, M.; Niederau, C.

    2000-01-01

    Objective. To investigate the frequency and morphology of extraosseous extension in patients with Gaucher disease type I.Design and patients. MRI examinations of the lower extremities were analyzed in 70 patients with Gaucher disease type I. Additionally, the thoracic spine and the midface were investigated on MRI in two patients.Results. Four cases are presented in which patients with Gaucher disease type I and severe skeletal involvement developed destruction or protrusion of the cortex with extraosseous extension into soft tissues. In one patient, Gaucher cell deposits destroyed the cortex of the mandible and extended into the masseter muscle. In the second patient, multiple paravertebral masses with localized destruction of the cortex were apparent in the thoracic spine. In the third and fourth patient, cortical destruction with extraosseous tissue extending into soft tissues was seen in the lower limbs.Conclusions. Extraosseous extension is a rare manifestation of Gaucher bone disease. While an increased risk of cancer, especially hematopoietic in origin, is known in patients with Gaucher disease, these extraosseous benign manifestations that may mimic malignant processes should be considered in the differential diagnosis of extraosseous extension into soft tissues. A narrow neck of tissue was apparent in all cases connecting bone and extraosseous extensions. (orig.)

  5. Identification of type I iodothyronine 5'-deiodinase as a selenoenzyme

    International Nuclear Information System (INIS)

    Behne, D.; Kyriakopoulos, A.; Meinhold, H.; Koehrle, J.

    1990-01-01

    A 27.8 kDa membrane selenoprotein was previously identified in rat thyroid, liver and kidney, the tissues with the highest activities of type I iodothyronine 5'-deiodinase. This membrane enzyme catalyzes the deiodination of L-thyroxine to the biologically active thyroid hormone 3,3',5-triiodothyronine. A decrease in the activity of this enzyme, observed here in the liver of selenium-deficient rats, was found to be due to the absence of a selenium-dependent membrane-bound component. By chemical and enzymatic fragmentation of the 75 Se-labeled selenoprotein and of the 27 kDa substrate binding type I 5'-deiodinase subunit, affinity-labeled with N-bromoacetyl-[ 125 I]L-thyroxine, and comparison of the tracer distribution in the peptide fragments the identity of the two proteins was shown. The data indicate that the deiodinase subunit contains one selenium atom per molecule and suggest that a highly reactive selenocysteine is the residue essential for the catalysis of 5'-deiodination. From the results it can be concluded that type I iodothyronine 5'-deiodinase is a selenoenzyme

  6. Central Role of ULK1 in Type I Interferon Signaling

    Directory of Open Access Journals (Sweden)

    Diana Saleiro

    2015-04-01

    Full Text Available We provide evidence that the Unc-51-like kinase 1 (ULK1 is activated during engagement of the type I interferon (IFN receptor (IFNR. Our studies demonstrate that the function of ULK1 is required for gene transcription mediated via IFN-stimulated response elements (ISRE and IFNγ activation site (GAS elements and controls expression of key IFN-stimulated genes (ISGs. We identify ULK1 as an upstream regulator of p38α mitogen-activated protein kinase (MAPK and establish that the regulatory effects of ULK1 on ISG expression are mediated possibly by engagement of the p38 MAPK pathway. Importantly, we demonstrate that ULK1 is essential for antiproliferative responses and type I IFN-induced antineoplastic effects against malignant erythroid precursors from patients with myeloproliferative neoplasms. Together, these data reveal a role for ULK1 as a key mediator of type I IFNR-generated signals that control gene transcription and induction of antineoplastic responses.

  7. Type I-II laryngeal cleft: clinical course and outcome.

    Science.gov (United States)

    Slonimsky, Guy; Carmel, Eldar; Drendel, Michael; Lipschitz, Noga; Wolf, Michael

    2015-04-01

    Laryngeal cleft (LC) is a rare congenital anomaly manifesting in a variety of symptoms, including swallowing disorders and aspirations, dyspnea, stridor and hoarseness. The mild forms (types I-II) may be underdiagnosed, leading to protracted symptomatology and morbidity. To evaluate the diagnostic process, clinical course, management and outcome in children with type I-II laryngeal clefts. We conducted a retrospective case analysis for the years 2005-2012 in a tertiary referral center. Seven children were reviewed: five boys and two girls ranging in age from birth to 5 years. The most common presenting symptoms were cough, aspirations and pneumonia. Evaluation procedures included fiber-optic laryngoscopy (FOL), direct laryngoscopy (DL) and videofluoroscopy. Other pathologies were seen in three children. Six children underwent successful endoscopic surgery and one child was treated conservatively. The postoperative clinical course was uneventful in most of the cases. Types I-II LC should be considered in the differential diagnosis of children presenting with protracted cough and aspirations. DL is crucial for establishing the diagnosis. Endoscopic surgery is safe and should be applied promptly when conservative measures fail.

  8. Wild type measles virus attenuation independent of type I IFN

    Directory of Open Access Journals (Sweden)

    Horvat Branka

    2008-02-01

    Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

  9. Involvement of hypothalamus autoimmunity in patients with autoimmune hypopituitarism: role of antibodies to hypothalamic cells.

    Science.gov (United States)

    De Bellis, A; Sinisi, A A; Pane, E; Dello Iacovo, A; Bellastella, G; Di Scala, G; Falorni, A; Giavoli, C; Gasco, V; Giordano, R; Ambrosio, M R; Colao, A; Bizzarro, A; Bellastella, A

    2012-10-01

    Antipituitary antibodies (APA) but not antihypothalamus antibodies (AHA) are usually searched for in autoimmune hypopituitarism. Our objective was to search for AHA and characterize their hypothalamic target in patients with autoimmune hypopituitarism to clarify, on the basis of the cells stained by these antibodies, the occurrence of autoimmune subclinical/clinical central diabetes insipidus (CDI) and/or possible joint hypothalamic contribution to their hypopituitarism. We conducted a cross-sectional cohort study. Ninety-five APA-positive patients with autoimmune hypopituitarism, 60 without (group 1) and 35 with (group 2) lymphocytic hypophysitis, were studied in comparison with 20 patients with postsurgical hypopituitarism and 50 normal subjects. AHA by immunofluorescence and posterior pituitary function were evaluated; then AHA-positive sera were retested by double immunofluorescence to identify the hypothalamic cells targeted by AHA. AHA were detected at high titer in 12 patients in group 1 and in eight patients in group 2. They immunostained arginine vasopressin (AVP)-secreting cells in nine of 12 in group 1 and in four of eight in group 2. All AVP cell antibody-positive patients presented with subclinical/clinical CDI; in contrast, four patients with GH/ACTH deficiency but with APA staining only GH-secreting cells showed AHA targeting CRH- secreting cells. The occurrence of CDI in patients with lymphocytic hypophysitis seems due to an autoimmune hypothalamic involvement rather than an expansion of the pituitary inflammatory process. To search for AVP antibody in these patients may help to identify those of them prone to develop an autoimmune CDI. The detection of AHA targeting CRH-secreting cells in some patients with GH/ACTH deficiency but with APA targeting only GH-secreting cells indicates that an autoimmune aggression to hypothalamus is jointly responsible for their hypopituitarism.

  10. Autoimmune gastritis: Pathologist's viewpoint.

    Science.gov (United States)

    Coati, Irene; Fassan, Matteo; Farinati, Fabio; Graham, David Y; Genta, Robert M; Rugge, Massimo

    2015-11-14

    Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling.

  11. Autoimmune polyglandular syndrome type 1 in a 12-year-old ...

    African Journals Online (AJOL)

    2011-12-20

    Dec 20, 2011 ... hypoparathyroidism, which may be asymptomatic or which typically presents with tetany and seizures. Adrenal insufficiency often develops later. Other conditions which are associated with APS-1 include autoimmune thyroid disease, type 1 diabetes, hypo- gonadism, alopecia, vitiligo, autoimmune hepatitis,.

  12. Headache in autoimmune diseases.

    Science.gov (United States)

    John, Seby; Hajj-Ali, Rula A

    2014-03-01

    Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics. © 2014 American Headache Society.

  13. [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].

    Science.gov (United States)

    Dilas, Ljiljana Todorović; Icin, Tijana; Paro, Jovanka Novaković; Bajkin, Ivana

    2011-01-01

    Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sjögren, systemic sclerosis and mixed connective tissue disease. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Otherwise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

  14. High salt intake does not exacerbate murine autoimmune thyroiditis

    Science.gov (United States)

    Kolypetri, P; Randell, E; Van Vliet, B N; Carayanniotis, G

    2014-01-01

    Recent studies have shown that high salt (HS) intake exacerbates experimental autoimmune encephalomyelitis and have raised the possibility that a HS diet may comprise a risk factor for autoimmune diseases in general. In this report, we have examined whether a HS diet regimen could exacerbate murine autoimmune thyroiditis, including spontaneous autoimmune thyroiditis (SAT) in non-obese diabetic (NOD.H2h4) mice, experimental autoimmune thyroiditis (EAT) in C57BL/6J mice challenged with thyroglobulin (Tg) and EAT in CBA/J mice challenged with the Tg peptide (2549–2560). The physiological impact of HS intake was confirmed by enhanced water consumption and suppressed aldosterone levels in all strains. However, the HS treatment failed to significantly affect the incidence and severity of SAT or EAT or Tg-specific immunoglobulin (Ig)G levels, relative to control mice maintained on a normal salt diet. In three experimental models, these data demonstrate that HS intake does not exacerbate autoimmune thyroiditis, indicating that a HS diet is not a risk factor for all autoimmune diseases. PMID:24528002

  15. Increased prevalence of autoimmunity in Turner syndrome

    DEFF Research Database (Denmark)

    Mortensen, K H; Cleemann, L; Hjerrild, B E

    2009-01-01

    and karyotype. In conclusion, TS girls and women face a high prevalence of autoimmunity and associated disease with a preponderance towards hypothyroidism and CD. Thus, health care providers dealing with this patient group should be observant and test liberally for these conditions even before clinical symptoms......Individuals with Turner syndrome (TS) are prone to develop autoimmune conditions such as coeliac disease (CD), thyroiditis and type 1 diabetes (T1DM). The objective of the present study was to examine TS of various karyotypes for autoantibodies and corresponding diseases. This was investigated...... hypothyroid. Overall, 18% (19) presented with CD autoantibodies, of whom 26% (five) had CD. Anti-TPO and CD autoantibodies co-existed in 9% (10). Immunoglobulin A deficiency was found in 3% (three) of patients, who all had CD autoantibodies without disease. Among four patients with anti-GAD-65 none had T1DM...

  16. Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

    Science.gov (United States)

    Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2015-09-01

    Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

  17. Regulatory CD8{sup +} T cells induced by exposure to all-trans retinoic acid and TGF-{beta} suppress autoimmune diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Minoru [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Yasuda, Hisafumi, E-mail: yasuda@med.kobe-u.ac.jp [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Abe, Yasuhisa; Sasaki, Hirotomo; Shimizu, Mami; Arai, Takashi; Okumachi, Yasuyo; Moriyama, Hiroaki; Hara, Kenta; Yokono, Koichi; Nagata, Masao [Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

    2010-03-26

    Antigen-specific regulatory CD4{sup +} T cells have been described but there are few reports on regulatory CD8{sup +} T cells. We generated islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-specific regulatory CD8{sup +} T cells from 8.3-NOD transgenic mice. CD8{sup +} T cells from 8.3-NOD splenocytes were cultured with IGRP, splenic dendritic cells (SpDCs), TGF-{beta}, and all-trans retinoic acid (ATRA) for 5 days. CD8{sup +} T cells cultured with either IGRP alone or IGRP and SpDCs in the absence of TGF-{beta} and ATRA had low Foxp3{sup +} expression (1.7 {+-} 0.9% and 3.2 {+-} 4.5%, respectively). In contrast, CD8{sup +} T cells induced by exposure to IGRP, SpDCs, TGF-{beta}, and ATRA showed the highest expression of Foxp3{sup +} in IGRP-reactive CD8{sup +} T cells (36.1 {+-} 10.6%), which was approximately 40-fold increase compared with that before induction culture. CD25 expression on CD8{sup +} T cells cultured with IGRP, SpDCs, TGF-{beta}, and ATRA was only 7.42%, whereas CD103 expression was greater than 90%. These CD8{sup +} T cells suppressed the proliferation of diabetogenic CD8{sup +} T cells from 8.3-NOD splenocytes in vitro and completely prevented diabetes onset in NOD-scid mice in cotransfer experiments with diabetogenic splenocytes from NOD mice in vivo. Here we show that exposure to ATRA and TGF-{beta} induces CD8{sup +}Foxp3{sup +} T cells ex vivo, which suppress diabetogenic T cells in vitro and in vivo.

  18. [Pseudohypoaldosteronisme type I: a rare cause of failure to thrive].

    Science.gov (United States)

    Derache, A-F; Rousseau, S; Holder-Espinasse, M; Bouquillon, S; Bresson, S; Ythier, H; Ganga-Zandzou, P-S

    2012-05-01

    We report on a boy, born on term, presenting with a weight loss and a persistent failure to thrive after 10 days despite a normal behavior under bottle-feeding. The clinical examination was normal and biological assessment revealed hyponatremia with hyponatriuria, normal kaliemia and elevated aldosterone values, leading to type I pseudohypoaldosteronism diagnosis. Treatment with salt supplementation allowed growth improvement. The diagnosis was confirmed by the identification of a mutation in the mineralocorticoid receptor. This change was also found in several family members. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  19. Type-I superconductivity and neutron star precession

    International Nuclear Information System (INIS)

    Sedrakian, Armen

    2005-01-01

    Type-I proton superconducting cores of neutron stars break up in a magnetic field into alternating domains of superconducting and normal fluids. We examine two channels of superfluid-normal fluid friction where (i) rotational vortices are decoupled from the nonsuperconducting domains and the interaction is due to the strong force between protons and neutrons; (ii) the nonsuperconducting domains are dynamically coupled to the vortices and the vortex motion generates transverse electric fields within them, causing electronic current flow and Ohmic dissipation. The obtained dissipation coefficients are consistent with the Eulerian precession of neutron stars

  20. Raman scattering of type-I clathrate compounds

    International Nuclear Information System (INIS)

    Takasu, Y.; Hasegawa, T.; Ogita, N.; Udagawa, M.; Avila, M.A.; Takabatake, T.

    2006-01-01

    Lattice dynamical properties of the type-I clathrate compounds of A 8 Ga 16 Ge 30 (A=Eu, Sr, Ba) have been investigated by Raman scattering. We are successful in the assignment of the observed Raman active phonons to proper symmetry and are able to separate the guest atom origin modes from framework origin modes for the first time experimentally. From the measurements of temperature dependence of the guest origin peaks, we also demonstrate the difference of the behavior of the guest atom at high temperature and low temperature

  1. Nonlinear Spinor Fields in Bianchi type-I spacetime reexamined

    OpenAIRE

    Saha, Bijan

    2013-01-01

    The specific behavior of spinor field in curve space-time with the exception of FRW model almost always gives rise to non-trivial non-diagonal components of the energy-momentum tensor. This non-triviality of non-diagonal components of the energy-momentum tensor imposes some severe restrictions either on the spinor field or on the metric functions. In this paper within the scope of an anisotropic Bianchi type-I Universe we study the role of spinor field in the evolution of the Universe. It is ...

  2. Orthopedic Pathology in Children with Mucopolysaccharidosis Type I

    Directory of Open Access Journals (Sweden)

    Nato D. Vashakmadze

    2016-01-01

    Full Text Available Mucopolysaccharidosis type I is inherited in an autosomal recessive manner and results from the defective activity of the enzyme alpha-L-iduronidase, which leads to the accumulation of glycosaminoglycans (mainly heparan and dermatan sulfate in the lysosomes and further multiple organ dysfunction. This severe genetic progressive disease can be detected at an early age by skeletal deformities and phenotypic data. Early enzyme replacement therapy and/or bone marrow transplantation can slow down irreversible damages to various organs and systems or reduce their severity and improve the quality of life for a child.

  3. Type I procollagen propeptide in patients on CAPD

    DEFF Research Database (Denmark)

    Joffe, P; Heaf, J G; Jensen, L T

    1995-01-01

    Serum procollagen type I carboxyterminal propeptide (PICP) has been shown to be a useful marker of bone formation in patients undergoing haemodialysis. However, PICP levels has not been evaluated in depth in patients maintained on continuous ambulatory peritoneal dialysis (CAPD). Therefore serum...... and dialysate levels of PICP, its peritoneal clearance (Clp), mass transfer (MTp), and its possible relationship with osteocalcin, parathyroid hormone (PTH), and bone histomorphometry were studied in a group of CAPD patients. Serum PICP was just above the normal range with significant amounts detected...

  4. [Seric 21-hydroxilase antibodies in patients with anti-microsomal fraction antibodies. Autoimmune polyendocrine syndrome].

    Science.gov (United States)

    Botta, Silvia; Roveto, Silvana; Rimoldi, Daniel

    2007-01-01

    Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

  5. The thyroid and autoimmunity

    International Nuclear Information System (INIS)

    Drexhage, H.A.; Wiersinga, W.M.

    1986-01-01

    These proceedings give an almost complete picture of what is presently known on the autoimmune aspects of both functional and growth disturbances of the thyroid gland. It comprises 12 reviews on main areas of present research, each followed by shorter communications of work in progress relevant to the topic. (Auth.)

  6. Paraneoplastic autoimmune movement disorders.

    Science.gov (United States)

    Lim, Thien Thien

    2017-11-01

    To provide an overview of paraneoplastic autoimmune disorders presenting with various movement disorders. The spectrum of paraneoplastic autoimmune disorders has been expanding with the discovery of new antibodies against cell surface and intracellular antigens. Many of these paraneoplastic autoimmune disorders manifest as a form of movement disorder. With the discovery of new neuronal antibodies, an increasing number of idiopathic or neurodegenerative movement disorders are now being reclassified as immune-mediated movement disorders. These include anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis which may present with orolingual facial dyskinesia and stereotyped movements, CRMP-5 IgG presenting with chorea, anti-Yo paraneoplastic cerebellar degeneration presenting with ataxia, anti-VGKC complex (Caspr2 antibodies) neuromyotonia, opsoclonus-myoclonus-ataxia syndrome, and muscle rigidity and episodic spasms (amphiphysin, glutamic acid decarboxylase, glycine receptor, GABA(A)-receptor associated protein antibodies) in stiff-person syndrome. Movement disorders may be a presentation for paraneoplastic autoimmune disorders. Recognition of these disorders and their common phenomenology is important because it may lead to the discovery of an occult malignancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. [Autoimmune hepatitis: Immunological diagnosis].

    Science.gov (United States)

    Brahim, Imane; Brahim, Ikram; Hazime, Raja; Admou, Brahim

    2017-11-01

    Autoimmune hepatopathies (AIHT) including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune cholangitis (AIC), represent an impressive entities in clinical practice. Their pathogenesis is not perfectly elucidated. Several factors are involved in the initiation of hepatic autoimmune and inflammatory phenomena such as genetic predisposition, molecular mimicry and/or abnormalities of T-regulatory lymphocytes. AIHT have a wide spectrum of presentation, ranging from asymptomatic forms to severe acute liver failure. The diagnosis of AIHT is based on the presence of hyperglobulinemia, cytolysis, cholestasis, typical even specific circulating auto-antibodies, distinctive of AIH or PBC, and histological abnormalities as well as necrosis and inflammation. Anti-F actin, anti-LKM1, anti-LC1 antibodies permit to distinguish between AIH type 1 and AIH type 2. Anti-SLA/LP antibodies are rather associated to more severe hepatitis, and particularly useful for the diagnosis of seronegative AIH for other the antibodies. Due to the relevant diagnostic value of anti-M2, anti-Sp100, and anti-gp210 antibodies, the diagnosis of PBC is more affordable than that of PSC and AIC. Based on clinical data, the immunological diagnosis of AIHT takes advantage of the various specialized laboratory techniques including immunofluorescence, immunodot or blot, and the Elisa systems, provided of a closer collaboration between the biologist and the physician. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  8. Sulfatide-activated type II NKT cells prevent allergic airway inflammation by inhibiting type I NKT cell function in a mouse model of asthma.

    Science.gov (United States)

    Zhang, Guqin; Nie, Hanxiang; Yang, Jiong; Ding, Xuhong; Huang, Yi; Yu, Hongying; Li, Ruyou; Yuan, Zhuqing; Hu, Suping

    2011-12-01

    Asthma is a common chronic inflammatory disease involving many different cell types. Recently, type I natural killer T (NKT) cells have been demonstrated to play a crucial role in the development of asthma. However, the roles of type II NKT cells in asthma have not been investigated before. Interestingly, type I and type II NKT cells have been shown to have opposing roles in antitumor immunity, antiparasite immunity, and autoimmunity. We hypothesized that sulfatide-activated type II NKT cells could prevent allergic airway inflammation by inhibiting type I NKT cell function in asthma. Strikingly, in our mouse model, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells result in reduced-inflammation cell infiltration in the lung and bronchoalveolar lavage fluid, decreased levels of IL-4 and IL-5 in the BALF; and decreased serum levels of ovalbumin-specific IgE and IgG1. Furthermore, it is found that the activation of sulfatide-reactive type II NKT cells leads to the functional inactivation of type I NKT cells, including the proliferation and cytokine secretion. Our data reveal that type II NKT cells activated by glycolipids, such as sulfatide, may serve as a novel approach to treat allergic diseases and other disorders characterized by inappropriate type I NKT cell activation.

  9. Autoimmune paediatric liver disease.

    Science.gov (United States)

    Mieli-Vergani, Giorgina; Vergani, Diego

    2008-06-07

    Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a

  10. Glycogen storage disease type I: clinical and laboratory profile

    Directory of Open Access Journals (Sweden)

    Berenice L. Santos

    2014-12-01

    Full Text Available OBJECTIVES: To characterize the clinical, laboratory, and anthropometric profile of a sample of Brazilian patients with glycogen storage disease type I managed at an outpatient referral clinic for inborn errors of metabolism. METHODS: This was a cross-sectional outpatient study based on a convenience sampling strategy. Data on diagnosis, management, anthropometric parameters, and follow-up were assessed. RESULTS: Twenty-one patients were included (median age 10 years, range 1-25 years, all using uncooked cornstarch therapy. Median age at diagnosis was 7 months (range, 1-132 months, and 19 patients underwent liver biopsy for diagnostic confirmation. Overweight, short stature, hepatomegaly, and liver nodules were present in 16 of 21, four of 21, nine of 14, and three of 14 patients, respectively. A correlation was found between height-for-age and BMI-for-age Z-scores (r = 0.561; p = 0.008. CONCLUSIONS: Diagnosis of glycogen storage disease type I is delayed in Brazil. Most patients undergo liver biopsy for diagnostic confirmation, even though the combination of a characteristic clinical presentation and molecular methods can provide a definitive diagnosis in a less invasive manner. Obesity is a side effect of cornstarch therapy, and appears to be associated with growth in these patients.

  11. An unusual presentation of osteogenesis imperfecta type I

    Directory of Open Access Journals (Sweden)

    Rebelo M

    2011-04-01

    Full Text Available Marta Rebelo, Jandira Lima, José Diniz Vieira, José Nascimento CostaDepartment of Internal Medicine, University Hospital of Coimbra, Coimbra, PortugalAbstract: Osteogenesis imperfecta (OI is a rare inherited disorder with a broad spectrum of clinical and genetic variability. The genetic diversity involves, in the majority of the cases, mutations in one of the genes that encodes the type 1 collagen protein (COL1 A1 and COL1 A2, but it is not a requirement for the diagnosis. The most benign form is OI type I. The authors present a case report of a 25-year-old woman who had severe low back pain associated with incapacity to walk and breast-feed post-partum. Symptoms developed 2 weeks after delivery. The radiological examination revealed severe osteoporosis with no abnormalities in the laboratory findings. The clinical signs and a positive personal and family history of multiple fractures in childhood suggested OI type I, although other diagnosis, such as pregnancy-associated osteoporosis, was also considered. The atypical presentation of this rare disorder in adulthood calls attention to the need for early diagnosis for prompt treatment. Treatment of OI is never curative, but it improves the quality of the patient’s life.Keywords: osteogenesis imperfecta, collagen, pregnancy, osteoporosis

  12. Mucopolysaccharidosis type I: current knowledge on its pathophysiological mechanisms.

    Science.gov (United States)

    Campos, Derbis; Monaga, Madelyn

    2012-06-01

    Mucopolysaccharidosis type I is one of the most frequent lysosomal storage diseases. It has a high morbidity and mortality, causing in many cases severe neurological and somatic damage in the first years of life. Although the clinical phenotypes have been described for decades, and the enzymatic deficiency and many of the mutations that cause this disease are well known, the underlying pathophysiological mechanisms that lead to its development are not completely understood. In this review we describe and discuss the different pathogenic mechanisms currently proposed for this disease regarding its neurological damage. Deficiency in the lysosomal degradation of heparan sulfate and dermatan sulfate, as well as its primary accumulation, may disrupt a variety of physiological and biochemical processes: the intracellular and extracellular homeostasis of these macromolecules, the pathways related to gangliosides metabolism, mechanisms related to the activation of inflammation, receptor-mediated signaling, oxidative stress and permeability of the lysosomal membrane, as well as alterations in intracellular ionic homeostasis and the endosomal pathway. Many of the pathogenic mechanisms proposed for mucopolysaccharidosis type I are also present in other lysosomal storage diseases with neurological implications. Results from the use of methods that allow the analysis of multiple genes and proteins, in both patients and animal models, will shed light on the role of each of these mechanisms and their combination in the development of different phenotypes due to the same deficiency.

  13. Autoimmune diseases incidence in Belarus after Chernobyl accident

    International Nuclear Information System (INIS)

    Yanovich, O.O.; Titov, L.P

    2010-01-01

    The statistical analysis has shown undulation the incidence of thyroiditis since 1998. The prevalence of diabetes mellitus is characterized by a constant increase of cases. Data testify to the tendency of increasing the prevalence autoimmune diseases in Republic of Belarus. (authors)

  14. Diabetes

    Science.gov (United States)

    ... you, discussing your symptoms, and going over your health history, your doctor may test for diabetes if he or she suspects you are at risk. To check for diabetes, your doctor may request the following tests: Fasting blood sugar test. This test is usually done ...

  15. Diabetes

    DEFF Research Database (Denmark)

    Damm, Peter; Mathiesen, Elisabeth R

    2015-01-01

    For >30 years, insulin has been the drug of choice for the medical treatment of gestational diabetes mellitus. However, the use of oral hypoglycaemic agents has increased during the past 1–2 decades, so a recent comparison of treatment with glibenclamide, metformin or insulin in women...... with gestational diabetes mellitus is highly relevant....

  16. Human plasmacytoid dentritic cells elicit a Type I Interferon response by sensing DNA via the cGAS-STING signaling pathway.

    Science.gov (United States)

    Bode, Christian; Fox, Mario; Tewary, Poonam; Steinhagen, Almut; Ellerkmann, Richard K; Klinman, Dennis; Baumgarten, Georg; Hornung, Veit; Steinhagen, Folkert

    2016-07-01

    Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN) and are important for host defense by sensing microbial DNA via TLR9. pDCs also play a critical role in the pathogenesis of IFN-driven autoimmune diseases. Yet, this autoimmune reaction is caused by the recognition of self-DNA and has been linked to TLR9-independent pathways. Increasing evidence suggests that the cytosolic DNA receptor cyclic GMP-AMP (cGAMP) synthase (cGAS) is a critical component in the detection of pathogens and contributes to autoimmune diseases. It has been shown that binding of DNA to cGAS results in the synthesis of cGAMP and the subsequent activation of the stimulator of interferon genes (STING) adaptor to induce IFNs. Our results show that the cGAS-STING pathway is expressed and activated in human pDCs by cytosolic DNA leading to a robust type I IFN response. Direct activation of STING by cyclic dinucleotides including cGAMP also activated pDCs and knockdown of STING abolished this IFN response. These results suggest that pDCs sense cytosolic DNA and cyclic dinucleotides via the cGAS-STING pathway and that targeting this pathway could be of therapeutic interest. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. [An adult form of type-I. Gaucher's disease].

    Science.gov (United States)

    Múzes, G; Pitlik, E; Gohér, A; Somogyi, A; Tulassay, Z

    2000-03-26

    A young woman with no previous history of any diseases was admitted for further evaluation of a mild thrombocytopenia she has had for some months. No signs of bleeding have so far occurred. Physical examination was normal except for a moderately enlarged spleen. Routine investigations showed lower platelet count. There was no laboratory evidence of disease conditions with autoimmune/inflammatory or hematologic origin. Bone marrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies (with the characteristic tubular structures) in crista biopsy specimens. However, definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult form or type-1 Gaucher's disease.

  18. DNA targeting by the type I-G and type I-A CRISPR–Cas systems of Pyrococcus furiosus

    Science.gov (United States)

    Elmore, Joshua; Deighan, Trace; Westpheling, Jan; Terns, Rebecca M.; Terns, Michael P.

    2015-01-01

    CRISPR–Cas systems silence plasmids and viruses in prokaryotes. CRISPR–Cas effector complexes contain CRISPR RNAs (crRNAs) that include sequences captured from invaders and direct CRISPR-associated (Cas) proteins to destroy corresponding invader nucleic acids. Pyrococcus furiosus (Pfu) harbors three CRISPR–Cas immune systems: a Cst (Type I-G) system with an associated Cmr (Type III-B) module at one locus, and a partial Csa (Type I-A) module (lacking known invader sequence acquisition and crRNA processing genes) at another locus. The Pfu Cmr complex cleaves complementary target RNAs, and Csa systems have been shown to target DNA, while the mechanism by which Cst complexes silence invaders is unknown. In this study, we investigated the function of the Cst as well as Csa system in Pfu strains harboring a single CRISPR–Cas system. Plasmid transformation assays revealed that the Cst and Csa systems both function by DNA silencing and utilize similar flanking sequence information (PAMs) to identify invader DNA. Silencing by each system specifically requires its associated Cas3 nuclease. crRNAs from the 7 shared CRISPR loci in Pfu are processed for use by all 3 effector complexes, and Northern analysis revealed that individual effector complexes dictate the profile of mature crRNA species that is generated. PMID:26519471

  19. Classical Bianchi Type I Cosmology in K-Essence Theory

    International Nuclear Information System (INIS)

    Pimentel, Luis O.; Socorro, J.; Espinoza-García, Abraham

    2014-01-01

    We use one of the simplest forms of the K-essence theory and we apply it to the classical anisotropic Bianchi type I cosmological model, with a barotropic perfect fluid (p=γρ) modeling the usual matter content and with cosmological constant Λ. Classical exact solutions for any γ≠1 and Λ=0 are found in closed form, whereas solutions for Λ≠0 are found for particular values in the barotropic parameter. We present the possible isotropization of the cosmological model Bianchi I using the ratio between the anisotropic parameters and the volume of the universe. We also include a qualitative analysis of the analog of the Friedmann equation.

  20. Complex regional pain syndrome type I following pacemaker implantation

    Directory of Open Access Journals (Sweden)

    Sangita Kamath

    2015-12-01

    Full Text Available A 70-year-old woman presented with burning pain and swelling over dorsum of right hand and small joints of the fingers, associated with redness, feeling of warmth, and stiffness of the fingers, with inability to bend the fingers since 2 months. The symptoms were progressively increasing in intensity for the past 1 month. There was no history of fever or trauma to the hand. Two months before her symptoms started, she had permanent pacemaker implanted for complete heart block with syncope. She was hypertensive and was on regular medication. Her X-ray of right hand showed decreased bone density (demineralisation, suggestive of osteopenia. A diagnosis of reflex sympathetic dystrophy syndrome or complex regional pain syndrome type I induced by pacemaker insertion was made. She was treated with amitriptyline and steroids, after which her symptoms improved dramatically.

  1. Fivebrane instantons and higher derivative couplings in type I theory

    International Nuclear Information System (INIS)

    Hammou, Amine B.; Morales, Jose F.

    2000-01-01

    We express the infinite sum of D5-brane instanton corrections to R 2 couplings in N=4 type I string vacua, in terms of an elliptic index counting 1/2-BPS excitations in the effective Sp(N) brane theory. We compute the index explicitly in the infrared, where the effective theory is argued to flow to an orbifold CFT. The form of the instanton sum agrees completely with the predicted formula from a dual one-loop computation in type IIA theory on K3xT 2 . The proposed CFT provides a proper description of the whole spectrum of masses, charges and multiplicities for 1/2- and 1/4-BPS states, associated to bound states of D5-branes and KK momenta. These results are applied to show how fivebrane instanton sums, entering higher derivative couplings which are sensitive to 1/4-BPS contributions, also match the perturbative results in the dual type IIA theory

  2. Clustered chimera states in systems of type-I excitability

    International Nuclear Information System (INIS)

    Vüllings, Andrea; Omelchenko, Iryna; Hövel, Philipp; Hizanidis, Johanne

    2014-01-01

    The chimera state is a fascinating phenomenon of coexisting synchronized and desynchronized behaviour that was discovered in networks of nonlocally coupled identical phase oscillators over ten years ago. Since then, chimeras have been found in numerous theoretical and experimental studies and more recently in models of neuronal dynamics as well. In this work, we consider a generic model for a saddle-node bifurcation on a limit cycle representative of neural excitability type I. We obtain chimera states with multiple coherent regions (clustered chimeras/multi-chimeras) depending on the distance from the excitability threshold, the range of nonlocal coupling and the coupling strength. A detailed stability diagram for these chimera states and other interesting coexisting patterns (like traveling waves) is presented. (paper)

  3. The decorin sequence SYIRIADTNIT binds collagen type I

    DEFF Research Database (Denmark)

    Kalamajski, Sebastian; Aspberg, Anders; Oldberg, Ake

    2007-01-01

    Decorin belongs to the small leucine-rich repeat proteoglycan family, interacts with fibrillar collagens, and regulates the assembly, structure, and biomechanical properties of connective tissues. The decorin-collagen type I-binding region is located in leucine-rich repeats 5-6. Site......-directed mutagenesis of this 54-residue-long collagen-binding sequence identifies Arg-207 and Asp-210 in leucine-rich repeat 6 as crucial for the binding to collagen. The synthetic peptide SYIRIADTNIT, which includes Arg-207 and Asp-210, inhibits the binding of full-length recombinant decorin to collagen in vitro....... These collagen-binding amino acids are exposed on the exterior of the beta-sheet-loop structure of the leucine-rich repeat. This resembles the location of interacting residues in other leucine-rich repeat proteins....

  4. Pulmonary Arterial Hypertension in Glycogen Storage Disease Type I

    Directory of Open Access Journals (Sweden)

    Rachel D. Torok MD

    2017-05-01

    Full Text Available Pulmonary arterial hypertension (PAH is a rare and highly fatal disease that has been reported in 8 patients with glycogen storage disease type I (GSDI. We describe an additional case of an acute presentation of PAH in a 14-year-old patient with GSDI, which was successfully treated with inhaled nitric oxide and sildenafil. We investigated the incidence of PAH in 28 patients with GSDI on routine echocardiography and found no evidence of PAH and no significant cardiac abnormalities. This study highlights that PAH is a rare disease overall, but our case report and those previously described suggest an increased incidence in patients with GSDI. Should cardiopulmonary symptoms develop, clinicians caring for patients with GSDI should have a high degree of suspicion for acute PAH and recognize that prompt intervention can lead to survival in this otherwise highly fatal disease.

  5. Diabetes

    Science.gov (United States)

    ... including: Blurry vision Excess thirst Fatigue Frequent urination Hunger Weight loss Because type 2 diabetes develops slowly, ... must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get ...

  6. Diabetes

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — These datasets provide de-identified insurance data for diabetes. The data is provided by three managed care organizations in Allegheny County (Gateway Health Plan,...

  7. Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity.

    Science.gov (United States)

    Rinaldi, Maurizio; Perricone, Roberto; Blank, Miri; Perricone, Carlo; Shoenfeld, Yehuda

    2013-10-01

    Saccharomyces cerevisiae is best known as the baker's and brewer's yeast, but its residual traces are also frequent excipients in some vaccines. Although anti-S. cerevisiae autoantibodies (ASCAs) are considered specific for Crohn's disease, a growing number of studies have detected high levels of ASCAs in patients affected with autoimmune diseases as compared with healthy controls, including antiphospholipid syndrome, systemic lupus erythematosus, type 1 diabetes mellitus, and rheumatoid arthritis. Commensal microorganisms such as Saccharomyces are required for nutrition, proper development of Peyer's aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence. Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn's disease years later. Our results strongly suggest that ASCAs' role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.

  8. Peptides Against Autoimmune Neurodegeneration.

    Science.gov (United States)

    Stepanov, Alexey; Lomakin, Yakov; Gabibov, Alexander; Belogurov, Alexey

    2017-01-01

    The mammalian immune system is a nearly perfect defensive system polished by a hundred million years of evolution. Unique flexibility and adaptivity have created a virtually impenetrable barrier to numerous exogenous pathogens that are assaulting us every moment. Unfortunately, triggers that remain mostly enigmatic will sometimes persuade the immune system to retarget against self-antigens. This civil war remains underway, showing no mercy and taking no captives, eventually leading to irreversible pathological changes in the human body. Research that has emerged during the last two decades has given us hope that we may have a chance to overcome autoimmune diseases using a variety of techniques to "reset" the immune system. In this report, we summarize recent advances in utilizing short polypeptides - mostly fragments of autoantigens - in the treatment of autoimmune neurodegeneration. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Sarcoidosis and Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Piera Fazzi

    2017-08-01

    Full Text Available Most of the studies have shown a higher risk for subclinical and clinical hypothyroidism, antithyroid autoantibodies [overall antithyroid peroxidase antibodies (TPOAb], and in general, thyroid autoimmunity, overall in the female gender in patients with sarcoidosis (S. A significantly higher prevalence of clinical hypothyroidism and Graves’ disease was also described in female S patients with respect to controls. Gallium-67 (Ga-67 scyntigraphy in S patients, in the case of thyroid uptake, suggests the presence of aggressive autoimmune thyroiditis and hypothyroidism. For this reason, ultrasonography and thyroid function should be done in the case of Ga-67 thyroid uptake. In conclusion, thyroid function, TPOAb measurement, and ultrasonography should be done to assess the clinical profile in female S patients, and the ones at high risk (female individuals, with TPOAb positivity, and hypoechoic and small thyroid should have periodically thyroid function evaluations and suitable treatments.

  10. Autoimmune Addison's disease.

    Science.gov (United States)

    Napier, Catherine; Pearce, Simon H S

    2012-12-01

    Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.

  11. Autoimmune thyrotoxicosis: diagnostic challenges.

    Science.gov (United States)

    Ponto, Katharina A; Kahaly, George J

    2012-09-01

    Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. Published by Elsevier Inc.

  12. Autoimmune liver disease 2007.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

    2008-01-01

    Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

  13. Autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis

    Directory of Open Access Journals (Sweden)

    Pejin Radoslav

    2012-01-01

    Full Text Available Introduction. Autoimmune polyglandula