Mechanisms of antihyperglycaemic action of efaroxan in mice: time for reappraisal of α2A-adrenergic antagonism in the treatment of type 2 diabetes?

Aims/hypothesis  

Inspired by recent speculation about the potential utility of α_2A-antagonism in the treatment of type 2 diabetes, the study examined the contribution of α₂-antagonism vs other mechanisms to the antihyperglycaemic activity of the imidazoline (±)-efaroxan.     

Effects of the inhibition of cytosolic phospholipase A<Subscript>2</Subscript>α in non-small cell lung cancer cells

Purpose  

The aim of this study was to investigate the expression of cPLA₂α in non-small lung cancer cell lines and tissues, and we sought to determine the in vitro effects of the pyrrolidine-2 inhibitor on cPLA₂α sensitivity in three different non-small lung cancer cell lines.     

Serum TNF-α, B2M and sIL-2R levels are biological correlates of outcome in adjuvant IFN-α2b treatment of patients with melanoma

Purpose  

There are no biological markers available to predict outcome in melanoma patients treated with adjuvant interferon-alpha (IFN-α). The clinical activity of IFN-α is thought to be mediated not only by anti-proliferative effects, but also by induction and modulation of secondary cytokines. We examined serum cytokine levels in IFN-α-treated patients to find potential biological markers for response or toxicity.     

Erratum to: The serum levels of soluble interleukin-2 receptor α and lactate dehydrogenase but not of B2-microglobulin correlate with selected clinico-pathological prognostic factors and response to therapy in childhood soft tissue sarcomas

Purpose  

The objective of this study is to establish the clinical utility of serum soluble IL-2 receptor (sIL-2Rα) and B2-Microglobulin (B2-M) as markers for diagnosis, prognosis and treatment monitoring in childhood soft tissue sarcomas (STS).     

α-Lipoic acid regulates lipid metabolism through induction of sirtuin 1 (SIRT1) and activation of AMP-activated protein kinase

Aims/hypothesis  

Sirtuin 1 (SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether α-lipoic acid (ALA) exerts a lipid-lowering effect through regulation of SIRT1 activation and production in C₂C₁₂ myotubes.     

Genetic polymorphisms in <Emphasis Type="Italic">TNF</Emphasis>genes and tuberculosis in North Indians

Background  

Pulmonary tuberculosis, the most common clinical form of mycobacterial diseases, is a granulomatous disease of the lungs caused by Mycobaterium tuberculosis. A number of genes have been identified in studies of diverse origins to be important in tuberculosis. Of these, both tumor necrosis factor α (TNF-α) and lymphotoxin α (LT-α) play important immunoregulatory roles.     

DNA topoisomerase II alpha: a favorable prognostic factor in colorectal caner

Purpose  

There is a lack of study concerning expression of Topoisomerase IIα (Topo IIα) and long-term results in colorectal cancer patients. We aimed to investigate the relationship between expression of Topo IIα and clinicopathological parameters including overall survival in colorectal cancer.     

G protein-coupled receptor (GPR)40-dependent potentiation of insulin secretion in mouse islets is mediated by protein kinase D1

Aims/hypothesis  

Activation of the G protein-coupled receptor (GPR)40 by long-chain fatty acids potentiates glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells, and GPR40 agonists are in clinical development for type 2 diabetes therapy. GPR40 couples to the G protein subunit Gα_q/11 but the signalling cascade activated downstream is unknown. This study aimed to determine the mechanisms of GPR40-dependent potentiation of GSIS by fatty acids.     

mRNA of the pro-apoptotic gene <Emphasis Type="Italic">BBC3</Emphasis> serves as a molecular marker for TNF-α-induced islet damage in humans

Aims/hypothesis  

TNF-α plays important roles in the pathogenesis of type 1 and type 2 diabetes mellitus. In light of this, we examined the involvement of a pro-apoptotic gene, BBC3 (also known as PUMA), in TNF-α-mediated beta cell dysfunction and destruction in human islets.     

Integrin alpha-2 and beta-3 gene polymorphisms and colorectal cancer risk

Background and aims  Integrins such as α₂β₁, α_IIbβ₃, and α_vβ₃ have been suggested as key players for cancer development and progression. Several polymorphisms affecting these molecules, two in integrin α₂ (ITGA2 807C>T and 1648G>A) and one in β₃ (ITGB3 176T>C), influence their levels, structure, and possibly their function. To analyze the role of ITGA2 and ITGB3 polymorphisms for colorectal cancer risk and clinical presentation, we performed a case–control study. Materials and methods  Four hundred thirty-three colorectal cancer patients and 433 healthy sex- and age-matched control subjects were investigated. ITGA2 and ITGB3 polymorphisms were determined by 5′-nuclease assays. Results/findings  The ITGA2 807C>T polymorphism was associated with reduced colorectal cancer risk. In a codominant model, the odds ratio for each additional 807-T allele for colorectal cancer was 0.77 (95% confidence interval 0.64–0.94; p = 0.011). The ITGA2 1648G> and the ITGB3 176T>C polymorphism were not associated with colorectal cancer. None of the three polymorphisms investigated was associated with tumor size, histological grade, presence of primary lymph node metastases, tumor stage, or age at diagnosis. Interpretation/conclusion  We conclude that the ITGA2 807C>T polymorphism may be associated with reduced colorectal cancer risk. Armin Gerger and Günter Hofmann contributed equally to this work.     

HbA1c variability and the development of microalbuminuria in type 2 diabetes: Tsukuba Kawai Diabetes Registry 2

Aims/hypothesis  

The aim of this study was to examine the association between HbA_1c variability and the development of microalbuminuria as defined by an albumin/creatinine ratio ≥3.4 mg/mmol (≥30 mg/g) in at least two of three consecutive urine samples in Japanese patients with type 2 diabetes.     

Tumor necrosis factor and lymphotoxin-alpha genetic polymorphisms and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study of patients treated with BFM therapy

Background  

Circulating levels of tumor necrosis factor (TNF) and lymphotoxin-α (LT-α) have been associated with outcome in solid and hematologic malignancies. Within the TNF gene and the LT-α gene, polymorphisms have been identified at nucleotide positions -308 and +252, respectively. The variant alleles for TNF are designated TNF1 and TNF2, the ones for LT-α LT-α (10.5 kb) and LT-α (5.5 kb). Of interest, TNF2 and LT-α (5.5 kb) were shown to be associated with higher TNF and LT-α plasma levels than their counterparts. In the present study, we investigated the associations of the above mentioned polymorphisms with risk of relapse in childhood acute lymphoblastic leukemia (ALL) treated according to Berlin-Frankfurt-Münster (BFM) protocols.     

Nucleolin as cell surface receptor for tumor necrosis factor-α inducing protein: a carcinogenic factor of Helicobacter pylori

Purpose  

Tumor necrosis factor-α inducing protein (Tipα) is a unique carcinogenic factor released from Helicobacter pylori (H. pylori). Tipα specifically binds to cells and is incorporated into cytosol and nucleus, where it strongly induces expression of TNF-α and chemokine genes mediated through NF-κB activation, resulting in tumor development. To elucidate mechanism of action of Tipα, we studied a binding protein of Tipα in gastric epithelial cells.     

A 2-week,polysomnographic, safety study of sodium oxybate in obstructive sleep apnea syndrome

Purpose  

Sodium oxybate (SXB) is approved for cataplexy and excessive daytime sleepiness in narcolepsy. Obstructive sleep apnea syndrome (OSAS) affects ∼9–50% of narcoleptics. Effects of 2-week SXB administration on apnea–hypopnea index (AHI), oxygen saturation (SaO₂), and sleep architecture were investigated in OSAS patients.     

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

Aims/hypothesis  

Proinflammatory and proapoptotic cytokines such as TNF-α are upregulated in human obesity. We evaluated the association between ghrelin isoforms (acylated and desacyl ghrelin) and TNF-α in obesity and obesity-associated type 2 diabetes, as well as the potential role of ghrelin in the control of apoptosis and autophagy in human adipocytes.     

Acute dengue virus 2 infection in Gabonese patients is associated with an early innate immune response,including strong interferon alpha production

Background  

Dengue is now a leading cause of morbidity and mortality throughout the tropics. We conducted the first ex vivo study of dengue fever (DF) in African patients infected during the first Gabonese dengue virus 2 (DENV-2) outbreak in 2007, in order to investigate cytokine production, including the antiviral cytokine IFN-α, reported to be a potent inhibitor of DENV replication in vitro.     

Reduction of experimental diabetic vascular leakage and pericyte apoptosis in mice by delivery of αA-crystallin with a recombinant adenovirus

Aims/hypothesis  

The study aimed to evaluate the efficacy of recombinant adenovirus expressing αA-crystallin (Ad-αAc-Gfp) in reducing pericyte loss within retinal vasculature in early diabetes.     

A phase II,open-label,multicentre study to evaluate the immunogenicity and safety of an adjuvanted prepandemic (H5N1) influenza vaccine in healthy Japanese adults

Background  

Promising clinical data and significant antigen-sparing have been demonstrated for a pandemic H5N1 influenza split-virion vaccine adjuvanted with AS03_A, an α-tocopherol-containing oil-in-water emulsion-based Adjuvant System. Although studies using this formulation have been reported, there have been no data for Japanese populations. This study therefore aimed to assess the immunogenicity and tolerability of a prepandemic (H5N1) influenza vaccine adjuvanted with AS03_A in Japanese adults.     

Opposite effects of high and low doses of interleukin-2 on T cell-mediated hepatitis in mice (interleukin-2 on hepatitis)

Purpose  

Concanavalin A (Con A)-induced hepatitis is an extensively used animal model of T cell-mediated acute hepatitis. A variety of cytokines, including interleukin 4 (IL-4), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α), have been shown to play important roles in Con A-induced liver injury. However, the role of IL-2, a critical cytokine in the development and function of T cells and a clinical therapeutics for virus infection and tumor, has not been carefully examined in this model.     

Carbachol induces TGF-alpha expression and colonic epithelial cell proliferation in sensory-desensitised rats

Objective/background  

Signals for the expression of the peptide growth factors epidermal growth factor and transforming growth factor-α (TGFα) in the gastrointestinal mucosa are largely unknown. We have shown earlier that extrinsic afferents in the gastrointestinal tract induce TGFα expression in colonic mucosa via the deliberation of neurotransmitters substance P and calcitonin gene-related peptide. The aim of our present study was to determine the effects of carbachol on mucosal TGFα expression and epithelial cell proliferation in vivo.