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.     

Development of Lectin-Linked Immunomagnetic Separation for the Detection of Hepatitis A Virus

The accuracy and sensitivity of PCR-based methods for detection of hepatitis A virus (HAV) are dependent on the methods used to separate and concentrate the HAV from the infected cells. The pH and ionic strength affect the binding affinity of the virus to cells. In this study, we initially investigated the effects of pH (4.0–10.0) and metal ions (Fe²⁺, Co²⁺, Cu²⁺, Mg²⁺, K⁺, and Ca²⁺) on the binding of HAV to oyster digestive cells. The lowest relative binding (RB) of HAV to the cells was found at pH 4.0 and in FeSO₄ solution (64.6% and 68.1%, respectively). To develop an alternative to antibody-dependent immunomagnetic separation prior to detection of HAV using RT-PCR, the binding of HAV to five lectins, peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Helix pomatia agglutinin (HPA), Ulex europaeus agglutinin (UEA-1) and soybean agglutinin (SBA), was evaluated using ELISAs. SBA showed significantly higher RB to HAV than the other lectins tested. In addition, HAV could be concentrated within 30 min using SBA-linked magnetic bead separation (SMS) prior to the RT-PCR assay. Our findings demonstrate the feasibility of using SMS combined with RT-PCR to detect HAV at dilutions ranging from 10⁻¹–10⁻⁴ of a HAV stock (titer: 10⁴ TCID₅₀/mL).     

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.     

The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes

Vitamin D has been implicated in the pathophysiology of extraskeletal conditions such as hypertension, kidney disease, and diabetes via its ability to negatively regulate the renin-angiotensin system (RAS). This article reviews the evidence supporting a link between vitamin D and the RAS in these conditions, with specific emphasis on translational observations and their limitations. A literature review of animal and human studies evaluating the role of vitamin D in hypertension, kidney disease, and diabetes was performed. Excess activity of the RAS has been implicated in the pathogenesis of hypertension, chronic kidney disease, decreased insulin secretion, and insulin resistance. Animal studies provide strong support for 1,25-dihydroxyvitamin D(3)-mediated downregulation of renin expression and RAS activity via its interaction with the vitamin D receptor. Furthermore, the activity of vitamin D metabolites in animals is associated with reductions in blood pressure, proteinuria and renal injury, and with improved β-cell function. Many observational, and a few interventional, studies in humans have supported these findings; however, there is a lack of well-designed prospective human interventional studies to definitively assess clinical outcomes. There is a need for more well-designed prospective interventional studies to validate this hypothesis in human clinical outcomes.     

Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection

HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10(-4)) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4(+) T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4(+) T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir.     

Plasma cytokines in polycythemia vera: Phenotypic correlates,prognostic relevance,and comparison with myelofibrosis

Plasma cytokine milieu is abnormal in primary myelofibrosis (PMF) and correlates with disease phenotype and prognosis. In this study, we show that several plasma cytokines are also abnormally expressed in polycythemia vera (PV; n = 65), compared to normal controls (n = 35), but with a significantly different pattern than that of PMF (n = 127). Direct phenotypic correlation in PV included levels of IL‐12 with hematocrit; IL‐1b, IL‐2, IL‐7, FGF‐b, and HGF with leukocytosis; and IFN‐α and IFN‐γ with thrombocytosis. In univariate analysis, levels of 13 cytokines (out of 30 analyzed) correlated with survival but only MIP‐1β remained significant on multivariable analysis that included the other cytokines as covariates. Increased level of MIP‐1β (P < 0.01), older age (P < 0.01), and leukocytosis (P = 0.03) maintained their association with shortened survival, on multivariable analysis. This study provides preliminary observations that warrant a larger scale study and suggests the value of plasma cytokines as prognostic biomarkers in PV. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.