Modified-release prednisone: in patients with rheumatoid arthritis.

Prednisone is a well-established treatment option in rheumatoid arthritis. Low-dose glucocorticoid therapy alleviates disease signs and symptoms, is better tolerated than high-dose therapy, and its addition to disease-modifying anti-rheumatic drugs (DMARDs) inhibits radiographic disease progression. A low-dose, modified-release (MR) formulation of prednisone, administered in the evening, was developed to counter the circadian rise in pro-inflammatory cytokine levels that contributes to disease activity.

Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement.

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix).

Management of Merkel tumours: an evidence-based review.

(1) Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer of neuroendocrine origin generally seen in patients over 50 years of age. It has a high propensity for recurrence post-treatment; 5-year overall survival rates range from 23% to 80%. (2) The rarity of MCC means that there is a lack of prospective controlled trials in these patients.

Corticosteroids reduce IL-6 in ASM cells via up-regulation of MKP-1.

The mechanisms by which corticosteroids reduce airway inflammation are not completely understood. Traditionally, corticosteroids were thought to inhibit cytokines exclusively at the transcriptional level. Our recent evidence, obtained in airway smooth muscle (ASM), no longer supports this view.

Pharmacological interventions in the prevention of type 2 diabetes.

(1) Diabetes is a chronic disease whose incidence is increasing worldwide. The long-term complications of diabetes place a large health and economic burden onto individuals, their families and communities as a whole.(2) Guidelines on the prevention of diabetes recommend lifestyle changes such as smoking cessation and weight loss to decrease type 2 diabetes incidence in patients with impaired glucose tolerance or impaired fasting glucose.

Current drug therapy for scleroderma and secondary Raynaud's phenomenon: evidence-based review.

(1) Scleroderma and secondary Raynaud's phenomenon are frequently associated with increased morbidity for which no specific standardised treatment guidelines exist. (2) Current therapies for scleroderma target the immune system, with the goal of reducing inflammation and secondary tissue injury and fibrosis. Therapy targeting underlying vascular disease is designed to improve the symptoms of Raynaud's phenomenon and to reduce ischemic injury to involved organs.

Ocular carteolol: a review of its use in the management of glaucoma and ocular hypertension.

Ocular carteolol (Mikelan), Teoptic, Ocupress) is a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA). Ocular carteolol effectively reduces intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). Twice-daily administration of standard carteolol has generally similar IOP-lowering efficacy to other ocular beta-adrenoceptor antagonists such as timolol, betaxolol and metipranolol in patients with OAG or OH.

Rimonabant.

Rimonabant is the first of a new class of selective cannabinoid receptor-1 blockers. It reduces the overactivity of the endocannabinoid system, improving lipid and glucose metabolism and regulating food intake and energy balance. In four randomised, double-blind clinical trials in overweight or obese adults with or without type 2 diabetes and/or dyslipidaemia, oral rimonabant 20mg once daily reduced weight and waist circumference to a significantly greater extent than placebo.

Vildagliptin.

Vildagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is being evaluated in the treatment of patients with type 2 diabetes mellitus. It improves glycaemic control by inhibiting DPP-4 from inactivating the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide, prolonging incretin activity in response to ingestion of nutrients. This allows for increased insulin sensitivity, decreased glucagon secretion and improved beta-cell function in a glucose-dependent manner.

Orlistat: a review of its use in the management of obesity.

Orlistat (Xenical) is a reversible inhibitor of gastric and pancreatic lipases. In conjunction with a hypocaloric diet and moderate exercise, orlistat is an effective drug for use in the management of obesity in adults with or without comorbidities. Recent data have shown that orlistat is also effective as a component of weight management strategies in obese adolescents.

Gingerol metabolite and a synthetic analogue Capsarol inhibit macrophage NF-kappaB-mediated iNOS gene expression and enzyme activity.

Ginger (Zingiber officinale) is widely used in traditional Chinese medicine, with beneficial effects reported in numerous diseases, including inflammation. Inducible nitric oxide synthase (iNOS), a proinflammatory enzyme responsible for the generation of nitric oxide (NO), has been implicated in the pathogenesis of inflammatory diseases. Gingerols, the main pungent principles of ginger, have anti-inflammatory properties in vitro.

Gadofosveset.

Gadofosveset is the first gadolinium-based magnetic resonance (MR) imaging agent designed to image the blood pool. At clinically relevant concentrations, gadofosveset is highly bound to human serum albumin, which has the effect of increasing its signal-enhancing properties above that of non-protein bound imaging agents, as well as increasing its plasma half-life, allowing for increased imaging times. The use of gadofosveset-enhanced MR angiography was compared with non-enhanced MR angiography in four open-label, multicentre studies in adults with known or suspected arterial disease.

IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.

Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells.

IL-17A augments TNF-alpha-induced IL-6 expression in airway smooth muscle by enhancing mRNA stability.

Background: IL-17A is implicated in the regulation of inflammation and is found in increased amounts in the asthmatic airway. Human airway smooth muscle (ASM) cells synthesize cell adhesion molecules and cytokines in response to inflammatory mediators.

Objective: In this study, we examined whether IL-17A modulated the synthetic function of ASM cells.

Changes in gene expression associated with stable drug and radiation resistance in small cell lung cancer cells are similar to those caused by a single X-ray dose.

Small cell lung cancer (SCLC) initially responds well to chemotherapy and fractionated radiotherapy, but resistance to these treatments eventually develops in the vast majority of cases. To understand how resistance develops in the H69 SCLC cell line, we compared the changes in gene expression associated with 37.5 Gy fractionated X-ray treatment that produced the stable radiation- and drug-resistant H69/R38 cell subline to the changes associated with a single 4- or 8-Gy X-ray treatment.

Cellular models of drug- and radiation-resistant small cell lung cancer.

Background: The H69-EPR, H69-CP, H69-VP and H69/R38 resistant sublines of the classic small cell lung cancer (SCLC) line have proven useful in studies of resistance and its circumvention with paclitaxel.

Materials And Methods: The suppressor/oncogene profile of these sublines determined by Western and Northern blot was compared to the variant H82 SCLC cell profile. Two-dimensional electrophoresis/mass spectrometry was used to determine the effect of paclitaxel on protein expression.

Gypenosides derived from Gynostemma pentaphyllum suppress NO synthesis in murine macrophages by inhibiting iNOS enzymatic activity and attenuating NF-kappaB-mediated iNOS protein expression.

Gypenosides isolated from Gynostemma pentaphyllum are widely used in traditional Chinese medicine, with beneficial effects reported in numerous diseases, including inflammation and atherosclerosis, although the mechanism underlying these therapeutic effects is unknown. Because increased nitric oxide (NO) plays a role in these pathological conditions, we investigated whether the pharmacological activity of gypenosides is due to suppression of NO synthesis. The markedly increased production of nitrite by stimulation of RAW 264.

Fractionated irradiation of H69 small-cell lung cancer cells causes stable radiation and drug resistance with increased MRP1, MRP2, and topoisomerase IIalpha expression.

Purpose: After standard treatment with chemotherapy and radiotherapy, small-cell lung cancer (SCLC) often develops resistance to both treatments. Our aims were to establish if fractionated radiation treatment alone would induce radiation and drug resistance in the H69 SCLC cell line, and to determine the mechanisms of resistance.

Methods And Materials: H69 SCLC cells were treated with fractionated X-rays to an accumulated dose of 37.