Positive autoantibodies to ZnT8 indicate elevated risk for additional autoimmune conditions in patients with Addison’s disease

Abstract

Autoimmune Addison's disease (AAD) associates with exceptional susceptibility to develop other autoimmune conditions, including type 1 diabetes (T1D), marked by positive serum autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated protein 2 (IA-2A). Zinc transporter 8 (ZnT8) is a new T1D autoantigen, encoded by the SLC30A8 gene. Its polymorphic variant rs13266634C/T seems associated with the occurrence of serum ZnT8 antibodies (ZnT8A). This study was designed to determine the prevalence of serum ZnT8A and their clinical implication in 140 AAD patients. Other beta cell and thyroid-specific autoantibodies were also investigated, and ZnT8A results were confronted with the rs13266634 genotype. ZnT8A were detectable in 8.5 %, GADA in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1–67.8 % individuals. Type 1 diabetes was found in 10 % AAD patients. ZnT8A were positive in 57.1 % of T1D patients and 3.4 % non-diabetic AAD. Analysis of ZnT8A enabled to identify autoimmunity in two (14.3 %) T1D individuals previously classified as autoantibody-negative. ZnT8A-positive patients revealed significantly higher number of autoimmune conditions (p < 0.001), increased prevalence of T1D (p < 0.001) and other beta cell-specific autoantibodies. Carriers of the rs13266634 T-allele displayed increased frequency (p = 0.006) and higher titres of ZnT8A (p = 0.002). Our study demonstrates high incidence of ZnT8A in AAD patients. ZnT8A are associated with coexisting T1D and predictive of T1D in non-diabetic subjects. Moreover, positive ZnT8A in AAD indicate elevated risk for additional autoimmune conditions. Autoantibodies to beta cell antigens, comprising ZnT8, could be included in routine screening panels in AAD.

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An uncommon response to metronomic therapy in a heavily pretreated patient with metastatic carcinosarcoma: a case report

Background: Uterine carcinosarcoma is well known for its aggressive behavior. There is little evidence regarding the gold standard combination chemotherapy in metastatic or locally advanced carcinosarcoma, due to poor survival outcomes obtained with conventional scheduled chemotherapy. This case report represents the first-ever reported objective response to a metronomic chemotherapy regimen and adds to the current literature.Case presentationWe describe a case of a Caucasian woman diagnosed with metastatic carcinosarcoma that had already been treated with multiple lines of conventional chemotherapy, with progressive disease. This patient had a surprising clinical and imaging response when treated with oral metronomic cyclophosphamide. Conclusions: We reviewed the mechanism of action implicated in metronomic chemotherapy, and correlated it with the biology of disease in carcinosarcoma. This information may add to the current literature, providing important insights to future clinical trials in this patient population.

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Akt3 knockdown induces mitochondrial dysfunction in human cancer cells

Akt/PKB plays a pivotal role in cell proliferation and survival. However, the isotype-specific roles of Akt in mitochondrial function have not been fully addressed. In this study, we explored the role of Akt in mitochondrial function after stable knockdown of the Akt isoforms in EJ human bladder cancer cells. We found that the mitochondrial mass was significantly increased in the Akt1- and Akt3-knockdown cells, and this increase was accompanied by an increase in TFAM and NRF1. Akt2 knockdown did not cause a similar effect. Interestingly, Akt3 knockdown also led to severe structural defects in the mitochondria, an increase in doxorubicin-induced senescence, and impairment of cell proliferation in galactose medium. Consistent with these observations, the mitochondrial oxygen consumption rate was significantly reduced in the Akt3-knockdown cells. An Akt3 deficiency-induced decrease in mitochondrial respiration was also observed in A549 lung cancer cells. Collectively, these results suggest that the Akt isoforms play distinct roles in mitochondrial function and that Akt3 is critical for proper mitochondrial respiration in human cancer cells.

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Relationship between Chronic Periodontitis and Erectile Dysfunction: A Narrative Review

Objective. To conduct a descriptive literature review on research studies investigating the association between chronic periodontitis (CP) and erectile dysfunction (ED). Methods. Cohort studies, case-control studies, cross-sectional studies, randomized control trials, and animal studies up to July 2015 that studied the relationship between CP and ED were reviewed and reported. Data sources included PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov. The themes "periodontal disease" and "erectile dysfunction" and the role of periodontal therapy were identified and discussed throughout the narrative review. Results. After reviewing the literature, it was found that an association between CP and vasculogenic ED likely exists. Inflammation resulting from CP promotes endothelial dysfunction by increasing the systemic levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α). Periodontal therapy attempts to decrease the release of TNF-α and could act to restore endothelial function, particularly in the penile vasculature. Conclusion. Although the literature reported a positive association between CP and ED, the studies were few and possess several methodological limitations. Large-scale cohort studies and confounder analysis are recommended. Dentists and physicians should collaborate to manage patients with either CP or ED because of their potential association not only with each other but also with other serious systemic comorbidities.

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Comparative study of occurrence of postpartum low back and pelvic pain (LBPP) after normal delivery versus caesarean section (CS) following spinal anaesthesia and its rehabilitative management

2016-03-13T18-22-34Z
Source: International Journal of Therapies and Rehabilitation Research
ANIL KUMAR JOSHI, CHITRA JOSHI.
Introduction and hypothesis: Low back and pelvic pain is very commonly encountered ailment in pregnancy and post-partum in women of childbearing age group. It can account for around half of the women of childbearing age. The pathophysiology of low back pain during pregnancy and postpartum is still poorly understood. Methods: The study was to compare low backache after normal delivery and after caesarean section following spinal anaesthesia, and its persistence after pregnancy. Moreover women were educated to regain the pre-pregnancy state uneventfully. Results: Postpartum backache at 1 month incidence in our study was 49%. Remission of pain occurred in 51% at 1 month and 78% at 6 months in caesarean section group, while in the normal vaginal delivery group 55% at 1 month and 85% in the 6th month had remission of pain. Conclusions: Women who had caesarean section with spinal anaesthesia had more chances to develop low back pain than women with normal vaginal delivery. Pre-pregnancy state can be achieved by supervised exercise regime.


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Ironing PDT for AMD

Otsuji T, Sho K, Tsumura A, Koike N, Nishimura T, Takahashi K

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International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents.

Related Articles

International GWAS Consortium Identifies Novel Loci Associated with Blood Pressure in Children and Adolescents.

Circ Cardiovasc Genet. 2016 Mar 11;

Authors: Parmar PG, Taal HR, Timpson NJ, Thiering E, Lehtimäki T, Marinelli M, Lind PA, Howe LD, Verwoert G, Aalto V, Uitterlinden AG, Briollais L, Evans DM, Wright MJ, Newnham JP, Whitfield JB, Lyytikäinen LP, Rivadeneira F, Boomsma DI, Viikari J, Gillman MW, St Pourcain B, Hottenga JJ, Montgomery GW, Hofman A, Kähönen M, Martin NG, Tobin MD, Raitakari O, Vioque J, Jaddoe VW, Jarvelin MR, Beilin LJ, Heinrich J, van Duijn CM, Pennell CE, EArly Genetics and Lifecourse Epidemiology Consortium, Lawlor DA, Palmer LJ

Abstract
BACKGROUND: -Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence.
METHODS AND RESULTS: -Genome-wide association study data from participating European ancestry cohorts of the EAGLE ( EA: rly G: enetics and L: ifecourse E: pidemiology) Consortium was meta-analysed across three 'epochs'; pre-puberty [4-7 years], puberty [8-12 years] and post-puberty [13-20 years]. Two novel loci were identified as having genome-wide associations with systolic blood pressure across specific age epochs; rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor CHiP and CpG methylation site) during pre-puberty (p = 2.86 × 10(-8)) and rs872256 during puberty (p = 8.67 × 10(-9)). Several SNP 'clusters' were also associated with childhood BP at p < 5 × 10(-3). Using a p-value threshold of < 5 × 10(-3) we found some overlap in variants across the different age epochs within our study, and between several SNPs in any of the three epochs and adult BP related SNPs.
CONCLUSIONS: -Our results suggest that genetic determinants of blood pressure act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.

PMID: 26969751 [PubMed - as supplied by publisher]

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