Low Vitamin D Status Is Associated with Systemic and Gastrointestinal Inflammation in Dogs with a Chronic Enteropathy

Introduction

Vitamin D deficiency, as assessed by serum concentrations of 25 hydroxyvitamin D (25(OH)D), has been linked to the development of over-zealous and inappropriate inflammation in humans. However, the relationship between vitamin D status and inflammation in dogs is ill-defined. Chronic enteropathies (CE) are frequently diagnosed in client owned dogs, have a wide range of serum 25(OH)D concentrations, and represent a spontaneous model in which to probe the relationship between vitamin D and inflammation. The hypothesis of this study was that vitamin D status would be negatively associated with systemic and gastrointestinal inflammation in dogs with a CE. The aim of this study was to examine the relationship between serum 25(OH)D concentrations and markers of systemic and gastrointestinal inflammation in a cohort of dogs with CE.

Methods and Materials

Serum 25(OH)D concentrations, together with neutrophil, monocyte, eosinophil and lymphocyte counts, duodenal histopathology scores, serum IL-2, IL-6, IL-8 and TNFα concentrations and were measured in 39 dogs with histologically confirmed CE. A linear regression model examined the relationship between serum 25(OH)D status and measures of inflammation.

Results

Serum 25(OH)D concentrations were negatively associated with neutrophil and monocyte counts, duodenal histopathology scores and serum IL-2 and IL-8 concentrations. Dogs with low serum 25(OH)D concentrations typically had an inflammatory signature characterised by high monocyte and neutrophil numbers together with low lymphocyte numbers. There is a need to establish whether low vitamin D status is a cause or consequence of inflammation.     

急性胰腺炎患者胃肠动力紊乱与胃肠激素的关系分析

目的:探讨急性胰腺炎(AP)患者的胃肠动力紊乱与胃肠激素的关系。方法:收集2014年3月~2015年4月我院消化科收治的90例AP患者为病例组,按病情严重程度分为轻症急性胰腺炎组(MAP组,39例)、中重症急性胰腺炎组(MSAP组,33例)及重症急性胰腺炎组(SAP组,18例),并于同期抽取30例健康体检者作为对照组,通过采用双抗体夹心酶联免疫法(ELASA)测量入院第1、3、7天的血清胃动素(MTL)、血管活性肠肽(VIP)在各组中的水平,同时测量口盲传递时间(OCTT)来衡量AP的严重程度。结果:MAP组、MSAP组及SAP组血清MTL水平均较对照组明显降低,且随着入院治疗时间的延长逐渐升高,差异均有统计学意义(P0.05)。MAP组、MSAP组及SAP组血清VIP水平均较对照组明显升高,且随着入院治疗时间的延长逐渐降低,差异均有统计学意义(P0.05)。血清MTL水平与OCTT呈负相关性(rs=-0.534、-0.629、-0.468,P0.05);血清VIP水平与OCTT呈正相关性(rs=0.464、0.326、0.671,P0.05)。结论:胃肠动力紊乱可能与胃肠激素异常有关,表现为MTL水平降低、VIP水平升高,且其改变幅度与病情的严重程度相一致。     

Nonischemic Cardiomyopathy Associated with Autoimmune Polyglandular Syndrome Type II

ObjectiveTo report a case of nonischemic cardiomyopathy associated with autoimmune polyglandular syndrome type II (APS-II).MethodsWe describe our patient’s clinical features, evaluation, and outcome. In addition, a literature review of cardiomyopathy associated with polyendocrinopathy syndromes is presented.ResultsThe component disorders of APS-II are Addison’s disease in combination with either autoimmune thyroid disease or type 1 (insulin-dependent) diabetes. Although numerous other autoimmune conditions have been reported in conjunction with APS-II, cardiomyopathy has not been previously described as part of this syndrome. The current patient was a 32-year-old man who, during a 5-year period, was diagnosed as having type 1 diabetes mellitus, Crohn’s disease, and Addison’s disease. In 2001, he presented with severe heart failure that progressed rapidly and eventually necessitated cardiac transplantation.ConclusionAlthough autoimmune cardiomyopathy has been associated with other autoimmune disorders, to our knowledge this is the first reported case of cardiomyopathy in association with an autoimmune polyglandular syndrome. Patients with this syndrome should undergo clinical evaluation for heart failure. (Endocr Pract. 2007;13:59-62)     

Gastrointestinal Disturbances Associated with Withdrawal of Ataractic Drugs

The psychological effects of abrupt withdrawal of ataractic drugs have been studied by others. Physical symptoms also occur under such circumstances and include abdominal pain, nausea and vomiting. Forty patients were divided into four groups of 10, each group receiving one of the following drugs: chlorpromazine, thioridazine, perphenazine or chlorprothixene. This medication was then suddenly withdrawn. In each of the chlorpromazine and thioridazine groups, three patients had gastrointestinal symptoms within 48 hours, lasting one to eight days. One patient on chlorprothixene, 450 mg. daily, experienced symptoms for six days. Perphenazine withdrawal produced no such symptoms. Thioridazine has little antiemetic action but perphenazine is prescribed for vomiting; hence it seems unlikely that the reported symptoms are due to a rebound action on the vomiting centre.These findings are relevant to the situation of withdrawal of ataractics prior to administration of anesthetics and to drug studies involving cross-over from an active compound to a placebo. The increasing use of ataractics suggests that this additional diagnostic possibility should be considered in the presence of obscure gastrointestinal symptoms.     

Megaloblastic Anemia Associated with Surgically Produced Gastrointestinal Abnormalities

Two of the mechanisms for vitamin B₁₂ deficiency, leading to megaloblastic anemia, are the result of surgically produced abnormalities of the gastrointestinal tract. The basic mechanism is different for each lesion.Total gastrectomy results in complete lack of intrinsic factor which is necessary for vitamin B₁₂ absorption. It is believed that if patients survive long enough and are not given prophylactic vitamin B₁₂ therapy, all would develop megaloblastic anemia.Intestinal anastomosis leading to stasis of intestinal contents, with overgrowth of bacteria may cause vitamin B₁₂ deficiency through bacterial interference with the utilization of vitamin B₁₂.Use of radioactive vitamin B₁₂ (cobalt⁶⁰-labeled B₁₂) has led to a better understanding of the pathogenesis of both types of megaloblastic anemia. The radioactive vitamin provides a useful tool for study of its absorption from the gastrointestinal tract.     

Transient Warm Autoimmune Hemolytic Anemia and Cryoglobulinemia Associated with Seminoma

A patient with a pure seminoma presented with severe IgG-mediated warm autoimmune hemolytic anemia. Monoclonal IgM-kappa cryoglobulinemia and a biological false positive test for syphilis were also found. Treatment directed at both the seminoma and the hemolysis resulted in the complete disappearance of these antibodies. It is possible that these immunological phenomena occurred in response to the tumor. The occurrence of warm autoimmune hemolytic anemia and monoclonal paraproteinemia in association with solid tumors is reviewed.     

Differential Proteomics of Helicobacter pylori Associated with Autoimmune Atrophic Gastritis

Atrophic autoimmune gastritis (AAG) is a condition of chronic inflammation and atrophy of stomach mucosa, for which development can be partially triggered by the bacterial pathogen Helicobacter pylori (HP). HP can cause a variety of gastric diseases, such as duodenal ulcer (DU) or gastric cancer (GC). In this study, a comparative proteomic approach was used by two-dimensional fluorescence difference gel electrophoresis (DIGE) to identify differentially expressed proteins of HP strains isolated from patients with AAG, to identify markers of HP strain associated with AAG. Proteome profiles of HP isolated from GC or DU were used as a reference to compare proteomic levels. Proteomics analyses revealed 27 differentially expressed spots in AAG-associated HP in comparison with GC, whereas only 9 differential spots were found in AAG-associated HP profiles compared with DU. Proteins were identified after matrix-assisted laser desorption ionization (MALDI)-TOF and peptide mass fingerprinting. Some AAG-HP differential proteins were common between DU- and GC-HP (peroxiredoxin, heat shock protein 70 [HSP70], adenosine 5′-triphosphate [ATP] synthase subunit α, flagellin A). Our results presented here may suggest that comparative proteomes of HP isolated from AAG and DU share more common protein expression than GC and provide subsets of putative AAG-specific upregulated or downregulated proteins that could be proposed as putative markers of AAG-associated HP. Other comparative studies by two-dimensional maps integrated with functional genomics of candidate proteins will undoubtedly contribute to better decipher the biology of AAG-associated HP strains.     

Mesiotemporal Volume Loss Associated with Disorder Severity: A VBM Study in Borderline Personality Disorder

Results of MRI volumetry in Borderline Personality Disorder (BPD) are inconsistent. Some, but not all, studies reported decreased hippocampus, amygdala, and/or prefrontal volumes. In the current study, we used rater-independent voxel-based morphometry (VBM) in 33 female BPD patients and 33 healthy women. We measured gray matter (GM) volumes of the whole brain and of three volumes of interest (VOI), i.e., the hippocampus/parahippocampal gyrus, the amygdala and the anterior cingulate gyrus (ACC). Analyses were conducted using lifetime diagnoses of posttraumatic stress disorder (PTSD) and major depression (MD) as covariates. We used adversive childhood experiences and the numbers of BPD criteria (as an indicator of disorder severity) to investigate associations with GM volumes. We did not find volume differences between BPD patients and healthy subject, neither of the whole brain nor of the three VOIs, independent of presence or absence of comorbid PTSD and MD. We also did not find a relationship between childhood maltreatment and the patients’ brain volumes. However, within the patient group, the number of BPD criteria fulfilled was inversely correlated with left hippocampal/parahippocampal volume (x=-32, y=-23, z=-18, k=496, t=5.08, p=.007). Consequently, mesiotemporal GM volumes do not seem to differentiate patients from healthy subjects, but might be associated with symptom severity within the BPD group.     

A Case of Nonischemic Cardiomyopathy Associated with Autoimmune Polyglandular Syndrome Type III

Objective:To report a case of nonischemic dilated cardiomyopathy associated with autoimmune polyglandular syndrome (APS) type III.MethodsA review of our patient’s medical records was undertaken, and her clinical history, investigations, and outcome are described. In addition, a literature review of nonischemic dilated cardiomyopathy occurring in association with autoimmune polyendocrinopathies was performed.ResultsAPS is diagnosed once a patient has developed at least 2 organ specific autoimmune diseases. APS III involves a combination of autoimmune diabetes and Graves’ disease without adrenal insufficiency. Autoimmune cardiomyopathies are not described as a feature of this condition; however, there are a few reported cases of patients with autoimmune polyendocrinopathies developing a nonischemic dilated cardiomyopathy. In this case, a 30-year-old female developed vitiligo, Graves’ disease, and latent autoimmune diabetes of the adult (LADA) over a 5-year period before presenting with conscious ventricular tachycardia (VT). This evolved into acute severe biventricular failure within a few weeks, which failed to resolve after adequate treatment of her other autoimmune conditions.ConclusionAlthough nonischemic cardiomyopathies have been associated with APS in a few published cases, this is the first case to our knowledge in a patient with APS III. (Endocr Pract. 2014;20:e183-e186)     

Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders

In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4⁺HLA-DR⁺, CD8⁺ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.     

Loci Associated with N-Glycosylation of Human Immunoglobulin G Show Pleiotropy with Autoimmune Diseases and Haematological Cancers

Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27×10⁻⁹) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3), while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3). However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn''s disease, diabetes type 1, multiple sclerosis, Graves'' disease, celiac disease, nodular sclerosis) and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma). Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842). Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein using GWAS. The results may also provide an explanation for the reported pleiotropy and antagonistic effects of loci involved in autoimmune diseases and haematological cancer.     

Maternal Conditions and Perinatal Characteristics Associated with Autism Spectrum Disorder and Intellectual Disability

Background

As well as being highly comorbid conditions, autism spectrum disorders (ASD) and intellectual disability (ID) share a number of clinically-relevant phenomena. This raises questions about similarities and overlap in diagnosis and aetiological pathways that may exist for both conditions.

Aims

To examine maternal conditions and perinatal factors for children diagnosed with an ASD, with or without ID, and children with ID of unknown cause, compared with unaffected children.

Methods

The study population comprised all live singleton births in Western Australia (WA) between January 1984 and December 1999 (N = 383,153). Univariate and multivariate multinomial logistic regression models were applied using a blocked modelling approach to assess the effect of maternal conditions, sociodemographic factors, labour and delivery characteristics and neonatal outcomes.

Results

In univariate analyses mild-moderate ID was associated with pregnancy hypertension, asthma, urinary tract infection, some types of ante-partum haemorrhage, any type of preterm birth, elective C-sections, breech presentation, poor fetal growth and need for resuscitation at birth, with all factors showing an increased risk. Severe ID was positively associated with poor fetal growth and need for resuscitation, as well as any labour or delivery complication. In the multivariate analysis no maternal conditions or perinatal factors were associated with an increased risk of ASD without ID. However, pregnancy hypertension and small head circumference were associated with a reduced risk (OR = 0.64, 95% CI: 0.43, 0.94; OR = 0.58, 95% CI: 0.34, 0.96, respectively). For ASD with ID, threatened abortion before 20 weeks gestation and poor fetal growth were associated with an increased risk.

Conclusion

Findings show that indicators of a poor intrauterine environment are associated with an elevated risk of ID, while for ASD, and particularly ASD without ID, the associations are much weaker. As such, these findings highlight the importance of accounting for the absence or presence of ID when examining ASD, if we are to improve our understanding of the causal pathways associated with these conditions.     

Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil

BackgroundDiabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil.MethodsOral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed.ResultsThe majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB.ConclusionsSustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted.     

Microbiota Associated with the Gastrointestinal Tract of the Common House Cricket, Acheta domestica

The location and morphology of the bacteria associated with the gastrointestinal tract of Acheta domestica were studied, and these bacteria were partially characterized. Bacteria were associated with the peritrophic membrane in the midgut and with the gut wall and cuticular structures of the hindgut. No bacteria were associated with the fat bodies. Colony-forming unit determinations indicated that there were three times more cultivatable bacteria in the hindgut than in the midgut. Of these bacteria, 40 to 85% cleared uric acid anaerobically, and 90 to 100% cleared uric acid aerobically. Of the 25 isolates obtained, 21 belonged to the genera Citrobacter, Klebsiella, Yersinia, Bacteroides, and Fusobacterium.