The anti-obesity effect of Lethariella cladonioides in 3T3-L1 cells and obese mice

The aim of this study was to investigate whether a water extract of L. cladonioides (LC) has an anti-obesity effect in 3T3-L1 cells and obese mice. Treatment of differentiated 3T3-L1 adipocytes with LC caused a significant increase in glycerol release and reduced the protein expression of the adipogenic transcription factors, PPARγ and C/EBPα. In an animal model, obese mice were artificially induced by a high fat diet for 10 weeks. Experimental groups were treated with LC (100 mg/kg/day) by gavage for the next 10 weeks. At the end of experiment, the body weight of the LC group mice was reduced by 14.2% compared to the high fat diet (HFD) group. The treatment also decreased liver (31.0%), epididymal (18.0%) and retroperitoneal (19.3%) adipose tissue, and kidney (6.7%) weights, respectively, compared with those of the HFD group. LC prevented diet-induced increases in the serum level of TC (22.6%), TG (11.6%), and glucose (35.0%), respectively, compared with the HFD group. However, the HDL-C level was higher in the LC group (26.1%) than the HFD group. The results of this study thus suggest that LC suppressed lipid accumulation and expression of adipogenic transcription factors, and increased the amount of glycerol release. LC also indicated an anti-obese and anti-hyperlipidemic effect

First report of field evolved resistance to agrochemicals in dengue mosquito, Aedes albopictus (Diptera: Culicidae), from Pakistan

<p>Abstract</p> <p>Background</p> <p>Agrochemicals have been widely used in Pakistan for several years. This exposes mosquito populations, particularly those present around agricultural settings, to an intense selection pressure for insecticide resistance. The aim of the present study was to investigate the toxicity of representative agrochemicals against various populations of <it>Aedes albopictus </it>(Skuse) collected from three different regions from 2008-2010.</p> <p>Results</p> <p>For organophosphates and pyrethroids, the resistance ratios compared with susceptible Lab-PK were in the range of 157-266 fold for chlorpyrifos, 24-52 fold for profenofos, 41-71 fold for triazofos, and 15-26 fold for cypermethrin, 15-53 fold for deltamethrin and 21-58 fold for lambdacyhalothrin. The resistance ratios for carbamates and new insecticides were in the range of 13-22 fold for methomyl, 24-30 fold for thiodicarb, and 41-101 fold for indoxacarb, 14-27 fold for emamectin benzoate and 23-50 fold for spinosad. Pair wise comparisons of the log LC_50sof insecticides revealed correlation among several insecticides, suggesting a possible cross resistance mechanism. Moreover, resistance remained stable across 3 years, suggesting field selection for general fitness had also taken place for various populations of <it>Ae. albopictus</it>.</p> <p>Conclusion</p> <p>Moderate to high level of resistance to agrochemicals in Pakistani field populations of <it>Ae. albopictus </it>is reported here first time. The geographic extent of resistance is unknown but, if widespread, may lead to problems in future vector control.</p

Treatment of ocular allergies:nonpharmacologic, pharmacologic and immunotherapy

Ocular allergy is a significant and growing issue worldwide but for many patients, it is often not differentiated from systemic conditions, such as hay fever. Management of seasonal and perennial allergic conjunctivitis is often poor. Management is principally through avoidance measures (blocking or hygiene), nonpharmaceutical (such as artificial tears and cold compresses) and pharmaceutical (such as topical antihistamines and prophylactic mast cell stabilizers). Vernal and atopic keratoconjunctivitis are more severe and generally need treatment with NSAIDs, steroids and immunomodulators. Giant papillary conjunctivitis can be related to allergy but also is often contact lens related and in such cases can be managed by a period of abstinence and replacement of the lens or a change in lens material and/or design. Immunotherapy can be efficacious in severe, persistent cases of contact lens or allergic conjunctivitis

Practical Use of Infliximab Concentration Monitoring in Pediatric Crohn Disease

OBJECTIVES: Therapeutic drug monitoring (TDM) that guides infliximab (IFX) intensification strategies has been shown to improve IFX efficacy. We conducted a review to evaluate the utility of TDM in the assessment and subsequent management of IFX loss of response in our pediatric population with Crohn disease (CD). METHODS: Single-center retrospective study of patients with CD receiving IFX that had TDM from December 2009 to September 2013. We defined subtherapeutic trough as a drug level below the detection limit of the Prometheus enzyme-linked immunoabsorbant assay and Anser reference values (1.4 and 1 μg/mL, respectively) or a mid-interval level \u3c12 \u3eμg/mL. RESULTS: One hundred ninety-one IFX concentration tests were performed on 72 patients with CD with loss of response to therapy as the primary indication (72%). 34% of all TDM were subtherapeutic. After initial TDM, 25 of the 72 patients received regimen intensification with 72% in clinical remission at 6 months. Including all of the TDM that resulted in IFX dose intensification, we found a significant improvement in 6-month remission rates whether intensification followed mid-interval (88% remission) or trough (56% remission) testing (P = 0.026). Antibody to infliximab was found in 14 patients with 5 occurring in the first year of therapy. Furthermore, 71% of patients with antibody to infliximab that were switched to an alternative anti-tumor necrosis factor achieved clinical remission at six months. In multivariable regression analysis, we found IFX dose (mg/kg), IFX dosing frequency (weeks), and the erythrocyte sedimentation rate at the previous infusion were significantly associated with the IFX concentration. CONCLUSIONS: TDM in our pediatric population with CD led to informed clinical decisions and improved rates of clinical remission

Practical Use of Infliximab Concentration Monitoring in Pediatric Crohn Disease

OBJECTIVES: Therapeutic drug monitoring (TDM) that guides infliximab (IFX) intensification strategies has been shown to improve IFX efficacy. We conducted a review to evaluate the utility of TDM in the assessment and subsequent management of IFX loss of response in our pediatric population with Crohn disease (CD). METHODS: Single-center retrospective study of patients with CD receiving IFX that had TDM from December 2009 to September 2013. We defined subtherapeutic trough as a drug level below the detection limit of the Prometheus enzyme-linked immunoabsorbant assay and Anser reference values (1.4 and 1 μg/mL, respectively) or a mid-interval level \u3c12 \u3eμg/mL. RESULTS: One hundred ninety-one IFX concentration tests were performed on 72 patients with CD with loss of response to therapy as the primary indication (72%). 34% of all TDM were subtherapeutic. After initial TDM, 25 of the 72 patients received regimen intensification with 72% in clinical remission at 6 months. Including all of the TDM that resulted in IFX dose intensification, we found a significant improvement in 6-month remission rates whether intensification followed mid-interval (88% remission) or trough (56% remission) testing (P = 0.026). Antibody to infliximab was found in 14 patients with 5 occurring in the first year of therapy. Furthermore, 71% of patients with antibody to infliximab that were switched to an alternative anti-tumor necrosis factor achieved clinical remission at six months. In multivariable regression analysis, we found IFX dose (mg/kg), IFX dosing frequency (weeks), and the erythrocyte sedimentation rate at the previous infusion were significantly associated with the IFX concentration. CONCLUSIONS: TDM in our pediatric population with CD led to informed clinical decisions and improved rates of clinical remission

Neutrophil FCγ Receptor 1 (CD64) Index As a Non-Invasive Biomarker for Clinical and Mucosal Disease Activity in Pediatric Inflammatory Bowel Disease

Background: Neutrophil expression of the high affinity Fc γ receptor 1(CD64) is up-regulated in adult patients with active inflammatory bowel disease (IBD). Infliximab non-response has been associated with an increased mucosal CD64 mRNA expression. We assessed the clinical utility of whole blood analysis of CD64 in the pediatric IBD population as a reflection of disease activity and severity. We hypothesized that the polymorphonuclear neutrophil (PMN) CD64 index would correlate with fecal calprotectin (FC) and serve as a surrogate biomarker for mucosal activity. Methods: We enrolled children having colonoscopy for suspicion of IBD (18 Crohn\u27s disease [CD], 2 Ulcerative Colitis [UC], 10 healthy controls) and children during routine clinic visits or undergoing colonoscopy with known IBD (82 CD, 14 UC, 2 IBD-U). The polymorphonuclear neutrophil (PMN) CD64 index was determined from each subject\u27s whole blood by flow cytometry using Leuko64 (Trillium Diagnostics, LLC). RNA sequence analysis of CD64 and S100A9 (calprotectin) was performed on ileal tissue obtained at diagnosis from 32 CD patients and 18 healthy controls and provided by the PRO-KIIDS consortium. Results: Mean(SD) PMN CD64 index for new diagnosis IBD was 2.79(0.36) compared with 0.78(0.04) for healthy controls (p=0.0005). For those with known IBD (41 active, 57 quiescent), the mean(SD) PMN CD64 index for active IBD was 2.38(0.26)) compared with 1.048(0.05) for quiescent IBD (p ,0.0001). ROC curve analysis from the two groups demonstrated an AUC of 0.89 (95% CI 0.83-0.95). At a cut off of 1.2, the CD64 index was 85% sensitive and 84% specific for active IBD. In the patients with active disease, the CD64 index was elevated in 35/41 (85%) subjects compared with elevations in FC (81%), CRP (72%), and ESR (57%). The PMN CD64 index did not differ by disease location (ileum only, colon only, ileocolonic) in those with active IBD, but CD64 index was highly correlated with the pediatric CD activity index (PCDAI, Spearman r = 0.68; p , 0.0001) and the pediatric UC activity index (r = 0.88; p , 0.0001). In patients with mild disease activity (PCDAI score 10-27.5), the mean PMN CD64 index was 1.84 compared with 3.03 in those with moderate-severe disease activity (PCDAI 30-100, p=0.014). Importantly, the PMN CD64 index significantly correlated with the simplified endoscopic score-CD (SESCD) in 32 CD patients (r = 0.68, p , 0.0001), while no correlation was found with CRP or ESR and SES-CD. RNA sequencing from ileal tissue revealed Fc γR1A (CD64) correlated significantly with S100A9 (r = 0.879; p , 0.0001). The PMN CD64 index also correlated with FC (r = 0.485; p = 0.002). Conclusions: The PMN CD64 index is a useful biomarker in determining disease activity in pediatric IBD and correlates significantly with FC, disease activity indices, and the SES-CD