Relationship Between Everolimus Blood Concentration Assessed Using the Innofluor Certican Fluorescence Polarization Immunoassay and the Architect i System Sirolimus Chemiluminescent Microparticle Immunoassay

Everolimus, an immunosuppressive macrolide derivative of sirolimus, has a narrow therapeutic index and variable bioavailability. Assessment of blood concentration of everolimus is necessary to improve immunosuppressive efficacy without increasing potential adverse effects. Recently, Seradyn, Inc (Indianapolis, Indiana) introduced a fluorescence polarization immunoassay (Innofluor Certican Fluorescent Polarization Immunoassay [FPIA]) for quantitation of everolimus blood concentration. This immunoassay has concentration-dependent cross-reactivity with sirolimus, which must be considered in patients recently treated with that drug. In this short-term study, treatment in 53 renal transplant recipients was converted from a sirolimus-based regimen to an everolimus-based regimen. Patients were followed up for 3 months. We investigated whether cross-reactivity with everolimus also occurred with the Abbott Laboratories (Abbott Park, Illinois) Architect i System, a sirolimus chemiluminescent microparticle immunoassay (CMIA) used to quantify sirolimus blood concentration. Quantification of everolimus blood concentration using both the CMIA and the FPIA demonstrated a linear regression: CMIA = 0.73 FPIA ± 0.77 (r² = 0.80; P < .001). A high degree of correlation between the CMIA and FPIA methods (r = 0.90) was confirmed using the Bland-Altman test. We conclude that the Abbott Architect i System sirolimus CMIA should be considered an alternative method for everolimus drug monitoring. The cross-reactions of both the FPIA and CMIA techniques with both sirolimus and everolimus must be considered when converting therapy from one drug to the other. In these conditions, use of an equivalent dosage is of particular importance.     

Chitosan microencapsulation of the dispersed phase of an O/W nanoemulsion to hydrochlorothiazide delivery

In view of biopharmaceutical limitations of hydrochlorothiazide (HCTZ), Trojan-type mucoadhesive systems were proposed, aiming to improve HCTZ pharmacological properties by modulating its release. Nanoemulsions were formed spontaneously by combining medium-chain triglycerides (Lipoid^® S75 and Pluronic^® F68) and high encapsulation efficiency was obtained. The mucoadhesive properties were provided by chitosan and microencapsulation of nanoemulsions in spray-dryer was successfully achieved by using Aerosil^® as wall material. The rapid redispersion of nanoemulsion in simulated fluids led to a fast and complete release of HCTZ in gastric medium. The pharmacodynamics of HCTZ was improved, extending the diuretic activity. Once a simple and low-energy method contributed to obtain stable mucoadhesive nanoemulsions, advantages in terms of production could also be achieved, allowing easy scaling up. This novel mucoadhesive Trojan particulate system of HCTZ showed to be a promising approach to overcome limitations in terms of absorption and consequently improve the therapeutic efficacy.     

Quantitative analysis of Langerhans' cells in oral chronic graft-vs.-host disease

Background:  The Langerhans cells (LCs) are scattered throughout the epithelium of skin and mucosa and have been associated with the graft-vs.-host disease (GVHD), which is the highest cause of morbidity and mortality in patients who underwent bone marrow transplant (BMT). This study aims at quantifying the LCs in the oral chronic GVHD (cGVHD).
Methods:  Microscopic sections from biopsies carried out in the buccal mucosa of 40 patients who underwent allogenic BMT and developed (20) or not (20) oral cGVHD (Groups 1 and 2, respectively) were utilised. For the control group, free surgical margins of 20 biopsies of non-inflammatory lesions in the buccal mucosa (Group 3) were used. The sections were studied in routine colouration and immunostained for CD1a.
Results:  Group 1 (with cGVHD) presented a greater number of Langerhans' cells/mm² (50.6 ± 37.2) when compared with the other groups (Group 2, 23.11 ± 19.7; Group 3, 16.6 ± 17.3).
Conclusion:  Our results suggest a greater recruitment of LCs in patients transplanted with cGVHD, probably as a result of cytokines secreted by the inflammatory cells.     

Increased Melanocytic Nevi in Patients with Inherited Ichthyoses: Report of a Previously Undescribed Association

Abstract: Ichthyosis is a heterogeneous cornification disorder. Melanocytic lesions have not been previously described in association with ichthyosis. Their clinical importance lies in the fact that they may simulate melanoma clinically and dermoscopically, as seen in epidermolysis bullosa. The objective of this study was to evaluate the clinical, dermoscopic, and histopathologic features of nevi and lentigines in 16 patients with autosomal recessive congenital ichthyosis—lamellar ichthyosis and nonbullous ichthyosiform congenital erythroderma. Patients underwent general clinical examination dermoscopy. The more suspicious lesions were excised and to histopathologic examination. Most patients (n = 13) reported no personal or familial history of melanoma or atypical nevi. All of the patients had at least five atypical melanocytic lesions. Ten of the 16 patients had at least one atypical nevus or lentigo. This study suggests that increased atypical melanocytic nevi may be a feature of long‐standing congenital ichthyoses. Whether this finding is disease‐related or a coincidental observation is difficult to ascertain. As an unequivocal discrimination from malignant melanoma in vivo is not always possible, regular clinical follow‐up of patients with ichthyosis and increased or unusual nevi is recommended.