Introduction: Psoriasis is a common, immune-mediated skin disease often associated with significant physical and psychosocial impairment. Antipsoriatic biologic agents offer patients unparalleled treatment potential in regard to greater skin clearance and overall improved quality of life. Evaluation of the therapeutic efficacy of biologic agents on the full psoriasis disease burden must account for their impact on both physical symptoms, as well as patient-reported, health-related quality of life (HRQoL) measurements.
Areas covered: Results from numerous clinical trials demonstrate the significant clinical efficacy of biological agents targeting tumor necrosis factor-α (TNF-α) and the interleukin (IL)-12/23 and IL-17 immune pathways. However, relatively limited data is available evaluating their full effect on quality of life outcomes. This review will discuss the most relevant and up-to-date clinical data on HRQoL measurements related to treatment with these aforementioned biologic agents.
Expert commentary: Patient-reported outcomes (i.e. Dermatology Life Quality Index) are being used with increasing frequency in clinical trials, and provide valuable information on the impact of psoriasis on numerous aspects of day-to-day living. These outcomes must also be incorporated in clinical practice, in addition to physical assessment of disease severity, treatment decisions, and therapeutic response in the psoriasis patient population. 相似文献
CUB-domain-containing-protein-1 (CDCP1) is an integral membrane protein whose expression is up-regulated in various cancer types. Although high CDCP1 expression has been correlated with poor prognosis in lung, breast, pancreas, and renal cancer, its functional role in tumor formation or progression is incompletely understood. So far it has remained unclear, whether CDCP1 is a useful target for antibody therapy of cancer and what could be a desired mode of action for a therapeutically useful antibody. To shed light on these questions, we have investigated the cellular effects of a therapeutic antibody candidate (RG7287). In focus formation assays, prolonged RG7287 treatment prevented the loss of contact inhibition caused by co-transformation of NIH3T3 cells with CDCP1 and Src. In a xenograft study, MCF7 cells stably overexpressing CDCP1 reached the predefined tumor volume faster than the parental MCF7 cells lacking endogenous CDCP1. This tumor growth advantage was abolished by RG7287 treatment. In vitro, RG7287 induced rapid tyrosine phosphorylation of CDCP1 by Src, which was accompanied by translocation of CDCP1 to a Triton X-100 insoluble fraction of the plasma membrane. Triggering these effects required bivalency of the antibody suggesting that it involves CDCP1 dimerization or clustering. However, this initial activation of CDCP1 was only transient and prolonged RG7287 treatment induced internalization and down-regulation of CDCP1 in different cancer cell lines. Antibody stimulated CDCP1 degradation required Src activity and was proteasome dependent. Also in three different xenograft models with endogenous CDCP1 expression RG7287 treatment resulted in significant tumor growth inhibition concomitant with substantially reduced CDCP1 levels as judged by immunohistochemistry and Western blotting. Thus, despite transiently activating CDCP1 signaling, the RG7287 antibody has a therapeutically useful mode of action. 相似文献
Tropical pyomyositis (TP) is a life‐threatening bacterial infection of the skeletal muscle that occurs particularly among children, young adults and those with immunocompromised conditions. The appropriate diagnosis and treatment are often delayed due to its non‐specific signs, leading to fatal consequences. Staphylococcus aureus, especially methicillin‐susceptible S. aureus, is responsible for most TP cases. However, other bacteria (i.e. streptococci, Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Candida spp., Mycobacterium spp.) have been reported. This narrative review provides an update on the epidemiology and clinical course of TP. A special focus is laid on the role of toxins (i.e. Panton‐Valentine Leucocidin and α‐toxin) in the pathogenesis of TP and their implication for the clinical management of infection. 相似文献
Aim: Sulphonylureas (SUs) are among the most widely used oral hypoglycaemic drugs that stimulate insulin secretion. In addition, SUs have pleiotropic effects on other tissues. Conflicting findings have been reported regarding the effects of SUs on adipocytes. We have now investigated the actions of glimepiride and glibenclamide (=glyburide) in primary human adipocytes. Methods: Primary cultured human white pre‐adipocytes were differentiated in vitro according to a standard protocol. Lipid accumulation was assessed by Oil Red O staining and determination of triglyceride content; gene expression was measured by RT PCR and Western blotting. Results: Initially, we characterized the genes regulated during human pre‐adipocyte differentiation by performing global microarray analysis. Treatment with glimepiride and glibenclamide caused an increased accumulation of lipid droplets and triglycerides. In addition, genes involved in lipid metabolism were induced and chemokine expression was decreased. Interestingly, the effects of SUs were generally qualitatively and quantitatively similar to those of pioglitazone. In direct comparison, glibenclamide was more potent than glimepiride with respect to the induction of fatty acid binding protein 4 (FABP4) (EC50 0.32 vs. 2.8 µM), an important adipocyte marker gene. SU‐induced differentiation was virtually completely blocked by the peroxisome proliferator‐activated receptor γ (PPARγ)‐antagonist T0070907 but not affected by diazoxide, indicating PPARγ activation by SUs. Repaglinide had no effect on adipogenesis, although it causes insulin liberation like SUs. Conclusions: In primary human pre‐adipocytes, glibenclamide and glimepiride strongly induced differentiation, apparently by activating PPARγ. Thus, SUs but not repaglinide may be used to influence insulin resistance beyond their effect on insulin liberation. 相似文献
Little data is available on the epidemiology of Staphylococcus aureus in Africa. In the present study we aim at characterizing the population structure of S. aureus in healthy subjects from a rural and a semi-urban area in Lambaréné, Gabon as well as in hospital staff and inpatients. In total, 500 subjects were screened for S. aureus colonization of the nares, axillae and inguinal region. Overall, 146 (29%) were positive. We found 46 different spa types. The most frequent spa types were t084 (35%) and the agr II was the most prevalent subtype of the accessory gene regulator (56%, n=82). Five isolates (3%) were methicillin resistant S. aureus (MRSA). Carriage rates of S. aureus in Gabon are comparable to developed countries. MRSA is for the first time described and could pose a significant health threat in this region with limited access to microbiological laboratory facilities and to adequate antimicrobial agents. 相似文献
OBJECTIVE: To investigate the effects of treatment with ibandronate, a highly potent nitrogen-containing bisphosphonate, on bone loss, bone quality, biomechanical properties, and bone concentrations in aged ovariectomized rats. METHODS: Eight-month-old female Wistar rats were ovariectomized (Ovx) or sham-operated. Treatment was started 10 weeks following Ovx with subcutaneous ibandronate in doses of 0.2, 1.0, 5.0, or 25 micro g/kg/day for 12 mo. Additional groups received 25 or 125 micro g/kg intermittently every 25 days, resulting in the same total dose as compared to 1.0 or 5.0 micro g/kg/day, respectively. Bone analyses by x-ray densitometry, peripheral quantitative computed tomography (pQCT), dual energy x-ray absorptiometry (DEXA), histomorphometry, 3-point bending, and compression tests were performed in femora, tibiae, and lumbar vertebrae in separate groups at the beginning and the end of treatment. Ibandronate concentration in tibiae and vertebrae was determined by gas chromatography mass spectroscopy at the end of the study. RESULTS: Ovariectomy resulted in a significant reduction in bone mass (p 相似文献
Using a solid phase enzyme-linked immunospot assay (ELISPOT) for enumerating antibody and interleukin secreting cells it could be demonstrated that arginine-vasopressin (AVP) inhibits the activation process of in vitro cultivated murine spleen lymphocytes. Lipopolysaccharide stimulated B cells could be influenced by high AVP concentrations (10[-5] M), while ConA induced Th1 cells respond also to a lower AVP level (10[-8] M) and such response by the IL-4 secreting Th2 cells may be demonstrated only after the activation with suboptimal doses of Con A. These observations suggest that AVP is not only able to suppress immunological reactions by stimulating proopiomelanocortin processing and secretion of adrenocorticotropic hormone, but also by a direct binding to lymphocytes and, moreover, that the susceptibility in monitoring this signal among the murine lymphocyte subpopulations is different. 相似文献