Biological variability and targeted delivery of therapeutics for inflammatory bowel diseases: an in silico approach

Existing treatments of IBD adopt targeted oral drug delivery route for delivering bioactive agents more efficiently and with fewer side effects. However, the complex and dynamic luminal environment of the GIT and major intra/inter patient variability greatly affects treatment, resulting in variable clinical response in patients. Mathematical simulation model can be employed to consider the complex luminal environment to asses the performance of drug delivery systems for clinical efficacy. The objective of this paper was to evaluate existing targeted oral drug delivery system for the treatment of IBD subject to inter/intra patient luminal variability using in silico experiments employing previously developed mathematical model. Simulation results indicated that the average small intestinal drug release was 44+/-19% and 48+/-21% for healthy and UC subjects, respectively. The systemic absorption of drug approached 10-25% in healthy controls and 16-32% in UC subjects. Calculated drug release from the simulations for different scenario of pH and TT had a good agreement with the clinical in vivo data (13-36% and 17-35% for healthy and UC subjects, respectively). This agreement was also true for 5-ASA and its metabolite (N-acetyl-5-ASA) recovery in the colon. The computational model has a high degree of agreement with data obtained from literature. Physicians can use characteristic performance curves of different delivery systems produced in silico to select a delivery system that would work best for their patients based upon the patient's pH and transit time profiles. It also could be used by the pharmaceutical industry to improve their medicine efficacy by altering the design.     

The relationship between IL-17A and IL-22 expression and clinical severity in patients with moderate/severe persistent allergic rhinitis

Purpose

Several reactions leading to numerous effects are regulated by IL-22. However, the relationship between IL-22 and immunopathogensis of allergic rhinitis (AR) has been rarely investigated. The aim of the present study was to investigate the levels of IL-22 and IL-17A in AR patients and their association with clinical severity of persistent allergic rhinitis (PAR).

Use of topical human amniotic fluid in the treatment of acute ocular alkali injuries in mice

PURPOSE: To evaluate the efficacy of topical human amniotic fluid (HAF) in the treatment of ocular acute alkali burns in mice. DESIGN: Experimental study. METHODS: A chemical burn with 2 microl of sodium hydroxide 0.15 mol/l was created in one eye of 30 mice. The animals were divided into gender- and age-matched groups according to the topical treatment that was administered: group 1 was treated with preterm HAF (n = 10 mice); group 2 was treated with term HAF (n = 10 mice), and group 3 was treated with saline solution (n = 10 mice). Treatment consisted of one drop that was applied to the burned eye five times per day (week one), and three times per day (week two). The epithelial defect was photographed and measured on days two and four. Ocular burn damage was assessed at days two, seven, and 14 after a pre-established classification. On day 14, both eyes of each mouse were enucleated and assessed histopathologically. RESULTS: Median epithelial defect (interquartile range [IQR], 25th, 75th percentile) at day four was 9.93% (IQR, 8.57, 11.27) for group 1, 7.30% (IQR, 5.96, 8.97) for group 2, and 18.92% (IQR, 11.71, 27.64) for group 3 (P < .0076). The overall change (difference in slope) in ocular burn score between days 2 and 14 was -0.127 (P = .009) in group 1 vs 3, -0.134 (P = .012) in group 2 vs 3, and 0.007 (P = .88) in group 1 vs 2. On histologic examination saline solution-treated corneas had more inflammatory cells and blood vessels than HAF-treated corneas. CONCLUSION: Topical preterm/term HAF was an effective topical therapy for limiting the damage after acute alkali burns of the eye in this animal model.     

Inflow of ocular surface fluid into the anterior chamber after phacoemulsification through sutureless corneal cataract wounds

PURPOSE: To report inflow of extraocular fluid after phacoemulsification with use of sutureless corneal incisions. DESIGN: Interventional case series. METHODS: setting: Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland. patients: Eight patients (three women), aged 58 to 91 years, showing minimal bleeding from the limbal capillary bed during phacoemulsification. intervention: Surgery was performed through a 2.8-mm limbal incision. External pressure simulating patient manipulation was applied before and after wound hydrosealing with an irrigation cannula. main outcome measures: Inflow of blood-tinged tear fluid into the anterior chamber through the wound was monitored by using digital video. RESULTS: Inflow of extraocular fluid was observed in all eyes when the cannula was released, even after wound hydrosealing. Two patients showed spontaneous fluid inflow. CONCLUSIONS: Tested sutureless corneal incisions allow inflow of extraocular fluid into the anterior chamber after phacoemulsification. This may permit intraocular contamination leading to endophthalmitis.     

Deep brain stimulation for the treatment of chronic, intractable pain

Deep brain stimulation (DBS) was first used for the treatment of pain in 1954. Since that time, remarkable advances have been made in the field of DBS, largely because of the resurgence of DBS for the treatment of movement disorders. Although DBS for pain has largely been supplanted by motor cortex and spinal cord stimulation during the last decade, no solid evidence exists that these alternative modalities truly offer improved outcomes. Furthermore, nuclei not yet fully explored are known to play a role in the transmission and modulation of pain. This article outlines the history of DBS for pain, pain classification, patient selection criteria, DBS target selection, surgical techniques, indications for DBS (versus ablative techniques), putative new DBS targets, complications, and the outcomes associated with DBS for pain.     

A Monocyte chemoattractant protein-1 (MCP-1) polymorphism and outcome after renal transplantation

Among the factors modulating transplant rejection and cardiovascular disease, chemokines and their respective receptors deserve special attention. In this respect, increased expression of MCP-1 and the corresponding receptor CCR2 have been demonstrated in renal transplant rejection and coronary artery disease. The impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function was investigated in 232 patients who underwent transplantation over an 11-yr period. Genomic DNA was genotyped using PCR with sequence-specific primers followed by restriction fragment length polymorphism analysis. Eighteen (7.8%) patients were homozygous for the MCP-1-2518G mutation. The G/G allele of MCP-1 -2518 behaved as a determinant for long-term allograft survival and resulted in reduction of the mean graft survival, as compared with the heterozygous (A/G) or wild-type (A/A) allele (67 +/- 14 versus 95 +/- 4 mo; Log rank P = 0.0052). The 64I mutation of CCR2 had no effect on kidney graft failure (93 +/- 6 and 91 +/- 5 mo, respectively; P = 0.81). None of the investigated polymorphisms showed a significant shift in gene frequency in acute rejection and rejection-free groups. In conjunction with these findings, peripheral blood mononuclear cells from kidney transplant recipients carrying the G-allele were characterized by a 2.5-fold higher MCP-1 secretion (P < 0.05). In conclusion, recipients of renal transplants homozygous for the -2518 G mutation of the MCP-1 gene are at risk for premature kidney graft failure. This variant of MCP-1 may be a future predictor for long-term kidney graft failure.