Evaluation of thyroid functions in leprosy. III. Circulating auto-antibodies against thyroid and nuclear components.

Sera from twenty six patients of various types of leprosy were tested for the detection of circulating auto-antibodies and nuclear components against thyroid using various methods. Four patients of lepromatous leprosy had higher levels of thyroid auto-antibodies by latex agglutination. Three patients showed the presence of anti-nuclear antibodies, two belonged to the TT and one to the LL group.     

CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma

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Asymmetric Cell–Matrix and Biomechanical Abnormalities in Elastin Insufficiency Induced Aortopathy

Aortopathy is characterized by vascular smooth muscle cell (VSMC) abnormalities and elastic fiber fragmentation. Elastin insufficient (Eln ^+/? ) mice demonstrate latent aortopathy similar to human disease. We hypothesized that aortopathy manifests primarily in the aorto-pulmonary septal (APS) side of the thoracic aorta due to asymmetric cardiac neural crest (CNC) distribution. Anatomic (aortic root vs. ascending aorta) and molecular (APS vs. non-APS) regions of proximal aorta tissue were examined in adult and aged wild type (WT) and mutant (Eln ^+/? ) mice. CNC, VSMCs, elastic fiber architecture, proteoglycan expression, morphometrics and biomechanical properties were examined using histology, 3D reconstruction, micropipette aspiration and in vivo magnetic resonance imaging (MRI). In the APS side of Eln ^+/? aorta, Sonic Hedgehog (SHH) is decreased while SM22 is increased. Elastic fiber architecture abnormalities are present in the Eln ^+/? aortic root and APS ascending aorta, and biglycan is increased in the aortic root while aggrecan is increased in the APS aorta. The Eln ^+/? ascending aorta is stiffer than the aortic root, the APS side is thicker and stiffer than the non-APS side, and significant differences in the individual aortic root sinuses are observed. Asymmetric structure–function abnormalities implicate regional CNC dysregulation in the development and progression of aortopathy.     

HIV with Juvenile Dermatomyositis

Dermatomyositis with HIV infection has been very rarely reported. The authors report an 8-y-old boy who presented with skin rashes and edema, muscle weakness and polymicrobial infection along with mild immunosupression. Diagnosis of dermatomyositis was established by raised enzymes, suggestive MRI and muscle biopsy findings. Child responded to systemic steroids and low dose weekly methotrexate.     

A novel DPP IV-resistant C-terminally extended glucagon analogue exhibits weight-lowering and diabetes-protective effects in high-fat-fed mice mediated through glucagon and GLP-1 receptor activation

Aims/hypothesis

Modification of the structure of glucagon could provide useful compounds for the potential treatment of obesity-related diabetes.

Methods

This study evaluated N-acetyl-glucagon, (d-Ser²)glucagon and an analogue of (d-Ser²)glucagon with the addition of nine amino acids from the C-terminal of exendin(1-39), namely (d-Ser²)glucagon-exe.

Results

All analogues were resistant to dipeptidyl peptidase IV degradation. N-Acetyl-glucagon lacked acute insulinotropic effects in BRIN BD11 cells, whereas (d-Ser²)glucagon and (d-Ser²)glucagon-exe evoked significant (p?d-Ser²)glucagon-exe stimulated cAMP production (p?GLP-1-receptor (GLP-1R)-transfected cells but not in glucose-dependent insulinotropic polypeptide-receptor-transfected cells. In normal mice, N-acetyl-glucagon and (d-Ser²)glucagon retained glucagon-like effects of increasing (p?d-Ser²)glucagon-exe was devoid of hyperglycaemic actions but substantially (p?d-Ser²)glucagon-exe reduced the glycaemic excursion (p?p?d-Ser²)glucagon-exe. Twice-daily administration of (d-Ser²)glucagon-exe to high-fat-fed mice for 28 days significantly (p?p?p?2 consumption and locomotor activity were (p?p?p?p?p?Conclusions/interpretation This study emphasises the potential of (d-Ser²)glucagon-exe for the treatment of obesity-related diabetes.