Characterization of an ester-based core-multishell (CMS) nanocarrier for the topical application at the oral mucosa

Objectives

Topical drug administration is commonly applied to control oral inflammation. However, it requires sufficient drug adherence and a high degree of bioavailability. Here, we tested the hypothesis whether an ester-based core-multishell (CMS) nanocarrier is a suitable nontoxic drug-delivery system that penetrates efficiently to oral mucosal tissues, and thereby, increase the bioavailability of topically applied drugs.

Material and methods

To evaluate adhesion and penetration, the fluorescence-labeled CMS 10-E-15-350 nanocarrier was applied to ex vivo porcine masticatory and lining mucosa in a Franz cell diffusion assay and to an in vitro 3D model. In gingival epithelial cells, potential cytotoxicity and proliferative effects of the nanocarrier were determined by MTT and sulphorhodamine B assays, respectively. Transepithelial electrical resistance (TEER) was measured in presence and absence of CMS 10-E-15-350 using an Endohm-12 chamber and a volt-ohm-meter. Cellular nanocarrier uptake was analyzed by laser scanning microscopy. Inflammatory responses were determined by monitoring pro-inflammatory cytokines using real-time PCR and ELISA.

Results

CMS nanocarrier adhered to mucosal tissues within 5 min in an in vitro model and in ex vivo porcine tissues. The CMS nanocarrier exhibited no cytotoxic effects and induced no inflammatory responses. Furthermore, the physical barrier expressed by the TEER remained unaffected by the nanocarrier.

Conclusions

CMS 10-E-15-350 adhered to the oral mucosa and adhesion increased over time which is a prerequisite for an efficient drug release. Since TEER is unaffected, CMS nanocarrier may enter the oral mucosa transcellularly.

Clinical relevance

Nanocarrier technology is a novel and innovative approach for efficient topical drug delivery at the oral mucosa.

     

Relationship between lung function and physical performance in disabled older women

BACKGROUND: Understanding the association between lung function and physical performance in disabled older women helps in determining the potential for prevention and treatment strategies to decrease disability. The aim of this study was to determine the association of lung function with objective and self-reported physical performance in community-dwelling disabled older women. METHODS: The Women's Health and Aging Study I consists of 1002 disabled community-dwelling women aged > or = 65. Of these women, 840 underwent spirometry with determination of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Cross-sectional analyses included multivariate linear regression to assess the association between FEV1, FVC, FEV1/FVC, and the time to walk four meters after adjusting for confounders, including age, race, geriatric depression scale score, body mass index, muscle strength, osteoarthritis, smoking status, and cardiovascular disease. Multiple logistic regression was used to assess the association between FEV1, FVC, FEV1/FVC, and self-reported disability in physical performance. RESULTS: FEV1 was independently associated with time to walk 4 meters. For every 100 ml decrease in FEV1, there was a 0.15-second (95% confidence interval: 0.24 to 0.06) increase in time to walk 4 meters. There was an 8% increase in the prevalent odds of self-reported disability in physical performance for every 100 ml decrease in FEV1. FVC was also associated with physical performance measures. In contrast, FEV1/FVC was associated with objective but not subjective physical performance. CONCLUSION: Decreasing lung function is independently associated with decrements in objective and self-reported physical performance in disabled older women.     

Living donor intestinal transplant using a standardized technique: first report from India

Aim

We describe the first living donor intestinal transplant (LDIT) in India and discuss the indications and problems of this complex procedure.

Methods

A 43-year-old male patient required massive bowel resection for gangrene due to thrombosis of the superior mesenteric artery. He was maintained on parenteral nutrition but developed cholestasis and well as repeated catheter related infections with progressive loss of venous access due to thrombosis of central veins. A LDIT was performed using 200?cm of small intestine from the patient's son. The graft was based on the continuation of the superior mesenteric vessels beyond the ileocolic branch. The artery was anastomosed directly to the aorta and the vein to the venacava.

Results

The graft functioned well and he was weaned off parenteral nutrition. However, he later developed complications (wound dehiscence and enterocutaneous fistula) and developed sepsis. He succumbed to sepsis with a functioning graft 6?weeks after the transplant. The donor recovered uneventfully and was discharged on the 4th postoperative day.

Conclusions

LDIT can be life saving in patients with intestinal failure and failure of parenteral nutrition. There is a need to introduce this modality in India. In a setting of scarcity of deceased donor organs the living donor option has advantages.     

In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior

Background

Cyclin D1-positive B cells are occasionally found in the mantle zones of reactive lymphoid follicles, a condition that has been called “in situ mantle cell lymphoma”. The clinical significance of this lesion remains uncertain.

Design and Methods

The clinical and pathological characteristics, including SOX11 expression, of 23 cases initially diagnosed as in situ mantle cell lymphoma were studied.

Results

Seventeen of the 23 cases fulfilled the criteria for in situ mantle cell lymphoma. In most cases, the lesions were incidental findings in reactive lymph nodes. The t(11;14) was detected in all eight cases examined. SOX11 was positive in seven of 16 cases (44%). Five cases were associated with other small B-cell lymphomas. In two cases, both SOX11-positive, the in situ mantle cell lymphoma lesions were discovered after the diagnosis of overt lymphoma; one 4 years earlier, and one 3 years later. Twelve of the remaining 15 patients had a follow-up of at least 1 year (median 2 years; range, 1–19.5), of whom 11 showed no evidence of progression, including seven who were not treated. Only one of 12 patients with an in situ mantle cell lymphoma lesion and no diagnosis of mantle cell lymphoma at the time developed an overt lymphoma, 4 years later; this case was also SOX11-positive. The six remaining cases were diagnosed as mantle cell lymphoma with a mantle zone pattern. Five were SOX11-positive and four of them were associated with lymphoma without a mantle zone pattern.

Conclusions

In situ mantle cell lymphoma lesions are usually an incidental finding with a very indolent behavior. These cases must be distinguished from mantle cell lymphoma with a mantle zone pattern and overt mantle cell lymphoma because they may not require therapeutic intervention.     

Ten-year trends in the incidence,clinical profile and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and sutureless,glueless and flapless scleral fixation of intraocular lenses

International Ophthalmology - To evaluate the frequency and outcomes of acute-onset endophthalmitis following combined pars plana vitrectomy and scleral fixation of intraocular lens. We evaluated...     

A comparison of using digitally assisted vitreoretinal surgery during repair of rhegmatogenous retinal detachments to the conventional analog microscope: A prospective interventional study

International Ophthalmology - To compare outcomes and complications of pars plana vitrectomy (PPV) using a three-dimensional heads-up visualisation system (digitally assisted vitreoretinal system,...     

Green synthesis of silver nanoparticles for the control of mosquito vectors of malaria, filariasis, and dengue

A biological method was used to synthesize stable silver nanoparticles that were tested as mosquito larvicides against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus. Annona squamosa leaf broth (5%) reduced aqueous 1?mM AgNO? to stable silver nanoparticles with an average size of 450?nm. The structure and percentage of synthesized nanoparticles was characterized by using ultraviolet spectrophotometry, X-Ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy methods. The median lethal concentrations (LC??) of silver nanoparticles that killed fourth instars of Ae. aegypti, Cx. quinquefasciatus, and An. stephensi were 0.30, 0.41, and 2.12 ppm, respectively. Adult longevity (days) in male and female mosquitoes exposed as larvae to 0.1 ppm silver nanoparticles was reduced by ~30% (p<0.05), whereas the number of eggs laid by females exposed as larvae to 0.1 ppm silver nanoparticles decreased by 36% (p<0.05).     

A comparative study on endothelial cell loss in nanophthalmic eyes undergoing cataract surgery by phacoemulsification

Purpose:The purpose of this study is to compare the endothelial cell loss (ECL) in nanophthalmic eyes and age-matched controls undergoing cataract surgery by phacoemulsification and also to identify the risk factors influencing the endothelial cell density (ECD). This was a prospective comparative interventional case series.Methods:We enrolled 19 nanophthalmic eyes (study group) and 42 age-matched cataract controls (control group) undergoing phacoemulsification after meeting the inclusion criteria. Ocular parameters like best-corrected visual acuity, intraocular pressure, pachymetry, specular microscopy, and slit lamp findings were noted preoperatively and at month 1 and 3 postsurgery. All nanophthalmic eyes underwent cataract surgery with concomitant prophylactic posterior sclerostomy.Results:The median percentage endothelial loss in nanophthalmic eyes was 4.0 (IQR 0–23.5), 7.4 (IQR 1.0–-22.4) at 1 and 3 months postoperatively compared to 6.3 (IQR 1.7–14.1) and 6.4 (IQR 2.6–-12.1) in age controlled normal eyes (P = 0.94, P = 0.46, respectively). Linear regression analysis showed increasing age as the only variable influencing the percentage decrease in corneal ECD in the study group (P = 0.001). Nanophthalmic eyes with ACD <2.5 mm had a significantly greater reduction in ECD at 3 months postcataract surgery compared to baseline (P = 0.039). Visual outcomes and IOP reduction in the study group with ACD >2.5 mm were significantly better postcataract surgery (P = 0.02 and P = 0.002, respectively).Conclusion:The percentage of ECL in nanophthalmic eyes undergoing phacoemulsification is equivalent to normal eyes. However, in the nanophthamic eyes with AC depth <2.5 mm, the percentage cell loss was significantly higher warranting the need for extensive intraoperative care. Increasing age was found to be the only significant risk factor influencing the ECD in short eyes.