Anti-IgE treatment of eosinophil-associated gastrointestinal disorders

BACKGROUND: Eosinophil-associated gastrointestinal disorders (EGIDs) are commonly associated with atopy and are being recognized with increasing frequency. Current therapy for EGIDs is inadequate. OBJECTIVE: We sought to determine the efficacy of anti-IgE therapy in EGIDs and investigate the role of IgE in disease pathogenesis. METHODS: Nine subjects with EGIDs received omalizumab every 2 weeks for 16 weeks while other therapy was held constant. Blood absolute eosinophil counts, tissue eosinophil counts, symptom scores, and free IgE levels were serially measured. Allergen skin testing and flow cytometry for basophil activation and FcepsilonRI were determined at baseline and at week 16. RESULTS: Omalizumab was associated with a decrease in absolute eosinophil count at both the week 16 (34%, P = .004) and combined weeks 12 to 16 (42%, P = .012) time points. Tissue eosinophils decreased in the duodenum (59%) and gastric antrum (69%) but did not reach statistical significance (P = .074 and .098, respectively). Esophageal eosinophil counts remained unchanged. Basophil and dendritic cell FcepsilonRI expression and free IgE levels were all significantly decreased (P < .005). Omalizumab increased the concentration of allergen required to trigger half-maximal basophil activation by 170-fold. Allergen skin test wheal and erythema responses decreased by 78% and 82%, respectively. Symptom scores were decreased at both the midstudy (63%) and end of study (70%) time points (P < .005 for both). CONCLUSION: These results demonstrate that IgE-mediated processes contribute to the generation of eosinophilic inflammation in EGIDs and suggest that anti-IgE therapy might be effective in these disorders. CLINICAL IMPLICATIONS: Anti-IgE might be a potential therapy for EGIDs.     

A label-free electrochemical biosensor based on 3D cubic Eu3+/Cu2O nanostructures with clover-like faces for the determination of anticancer drug cytarabine

The present research utilized a simplified procedure for developing a novel electro-chemical DNA biosensor based on a carbon paste electrode (CPE) modified with three-dimensional (3D) cubic Eu³⁺/Cu₂O nanostructures with clover-like faces (Eu³⁺/Cu₂O CLFNs). The modified electrode was applied to monitor electro-chemical interactions between dsDNA and cytarabine for the first time. Then, the decreased oxidation signal of guanine following the interactions between cytarabine and dsDNA was utilized as an indicator for selectively determining cytarabine using differential pulse voltammetry (DPV). According to the findings, the oxidation peak current of guanine was linearly proportionate with the cytarabine concentration in the range between 0.01 and 90 μM. Additionally, the limit of quantification (LOQ) and the limit of detection (LOD) respectively equaled 9.4 nM and 2.8 nM. In addition, the repeatability, applicability and reproducibility of this analysis to drug dosage forms and human serum samples were investigated. Furthermore, UV-vis spectroscopy, DPV, docking and viscosity measurements were applied to elucidate the interaction mechanism of dsDNA with cytarabine. It was found that this DNA biosensor may be utilized to sensitively, accurately and rapidly determine cytarabine.

Electrochemical biosensor based on three-dimensional (3D) cubic of Eu³⁺/Cu₂O with clover-like face nano-structures and ds-DNA modified carbon paste electrode for detecting cytarabine was fabricated.     

Associated coronary anomalies in 135 Iranian patients with tetralogy of Fallot

Coronary artery anomalies are common among patients with tetralogy of Fallot. One hundred and thirty-five patients (80 males and 55 females) with tetralogy of Fallot who underwent repair between 1995 and 2002 were studied to determine the incidence of coronary anomalies in Iranian patients. Eight (5.9%) patients (4 males and 4 females) had a surgically relevant coronary artery anomaly: single coronary ostium in 5, origin of the left anterior descending artery from the right coronary artery in 2, and origin of the right coronary artery from the left coronary artery in 1. The surgical technique in 3 of these patients was repair of the ventricular septal defect with a transverse incision on the right ventricle, without damage to the coronary arteries. In another patient, an allograft aortic valve cylinder was inserted. In the other 4 patients with a single coronary ostium, placement of a limited transannular patch was adequate. Consideration of these anomalies during primary repair could decrease the risk of operation in such patients. However, it seems that the presence of anomalous coronary arteries does not affect incremental risk after surgical repair.     

Identification of undeclared active pharmaceutical ingredients in counterfeit herbal medicines used as opioid substitution therapy

Adulteration of traditional herbal drugs with undeclared active pharmaceutical ingredients is a global problem with the increase in popularity of herbal-based medications. Many unprofessional herbal stores introduce herbal medicines as traditional formulations, but there are poor regulations for traditional herbal products’ consistency and safety in Iran. The current study aimed to identify undeclared active pharmaceutical ingredients in traditional herbal medicines used as opioid substitution therapy. In this research study, systematic toxicological analysis was performed for the analysis of 80 traditional herbal medicine samples. Samples were prepared and analysed by gas chromatography/mass spectrometry (GC/MS) instrumentation. More than 96% of samples contained at least one pharmaceutical active ingredient. Diphenoxylate and tramadol were detected in 90% and 67% of samples respectively. Moreover, some other pharmaceutical ingredients such as acetaminophen, codeine, sertraline, and fluoxetine were found in the samples. Quantitative analysis of samples showed that capsules contained diphenoxylate and tramadol at concentrations of 1.4–4 mg/capsule and 67–150 mg/capsule respectively. Traditional herbal preparations are not regulated as medicines in Iran. Herbal drugs with undeclared active ingredients are potentially dangerous for consumers; therefore, serious safety concerns must be associated with their production, distribution and use.     

Bulk collagen incorporation rates into knitted stiff fibre polymer in tissue-engineered scaffolds: the rate-limiting step

Fabrication of tissue-engineered constructs in vitro relies on sufficient synthesis of extracellular matrix (ECM) by cells to form a material suitable for normal function in vivo. Collagen synthesis by human dermal fibroblasts grown in vitro on two polymers, polyethylene terephthalate (PET) and polyglycolic acid (PGA), was measured by high-performance liquid chromatography (HPLC). Cells were either cultured in a dynamic environment, where meshes were loaded onto a pulsing tube in a bioreactor, or in a static environment without pulsing. Collagen synthesis by cells cultured on a static mesh increased by six-fold compared to monolayer culture, and increased by up to a further 5.4-fold in a pulsed bioreactor. However, little of the collagen synthesized was deposited onto the meshes, almost all being lost to the medium. The amount of collagen deposited onto meshes was highest when cells were cultured dynamically on PET meshes (17.6 microg), but deposition still represented only 1.4% of the total synthesized. Although total collagen synthesis was increased by the use of 3D culture and the introduction of pulsing, the results suggest that the limiting factor for fabrication of a tissue-engineered construct within practical timescales is not the amount of collagen synthesized but the quantity retained (i.e. deposited) within the construct during culture. This may be enhanced by systems which promote or assemble true 3D multi-layers of cells.     

Grafting without a donor site: an easy approach to pretibial lacerations

Pretibial lacerations are a common soft tissue injury especially amongst elderly women. An alternative repair approach to this problem is described. The traumatized and often necrosed-looking flap of skin from the injured area is made into a full thickness 'fenestrated' skin graft to cover the defect. Experience of 30 cases shows the method to be useful for accident and emergency departments as well as surgical units. The healing time is shorter than in conservative methods and similar to 'meshed split skin grafting' as an out-patient procedure, but the great advantage is the absence of a donor site.     

Pupil size as a measure of within‐task learning

Pupillometry is commonly used in research to determine how much mental effort an individual is exerting while completing tasks. Traditionally, larger pupils are associated with increased mental effort when completing more difficult tasks. However, little research has investigated how pupils change as individuals learn a new task. In theory, as one repeatedly completes a task, the task demands should reduce, reliance on working memory should decrease, and the task should become more automatic. This should translate to faster completion times and smaller peak pupil dilations. We tested this hypothesis by having participants complete multiple trials of a cognitive task that requires individuals to orient themselves in space relative to a target. We found that trial completion times and maximum pupil size significantly reduced across trials. These data suggest that measuring changes in pupil dilation may help researchers determine whether individuals have shifted from a learned procedure to an automatic processing of information when learning a new task.     

Grey matter volume in adolescents with anorexia nervosa and associated eating disorder symptoms

Anorexia nervosa (AN) is a mental health disorder of complex aetiology. Previous neuroimaging studies have found consistent global reductions in global grey matter volume of underweight girls with AN; however, differences in regional grey matter volumes are less consistent. The aims of this study were to investigate grey matter regional volumes of adolescent girls with AN before and after weight recovery and the relationship of any changes with clinical characteristics. We collected high‐resolution T1‐weighted images from 26 underweight girls with AN before weight gain and 20 healthy control volunteers. Clinical features were assessed using the Eating Disorder Examination Questionnaire. AN subjects displayed reduced grey matter volumes in the insula, amygdala, prefrontal, hippocampal and cingulate cortices and the precuneus, relative to healthy controls. In a subset of 10 AN subjects who were followed after weight recovery, grey matter volumes increased to near‐control levels in the orbito‐ and medial prefrontal, insular, left hippocampal and mid‐ and posterior cingulate cortices and precuneus. The recovery of the right anterior thalamus and the left orbitofrontal cortex was correlated with improvements in eating concerns and shape concerns, respectively. However, large parts of the anterior cingulate cortex, caudate nuclei and right hippocampus did not display any grey matter recovery following a short‐term of treatment. These results show that in adolescents with AN, some brain regions display marked recovery in grey matter volume following weight recovery, whereas others do not, considering grey mater recovery possibly linked to symptom improvement.