Novo sistema de aplicação de drogas em cirurgias oftalmológicas

The topical corneal application of antimitotic mitomycin-C (MMC) during refractive surgery is still characterized by a lack of standardization and considerable empirism. For this reason the creation of a system capable of reliable drug delivery represents a beneficial innovation for patients submitted to these procedures. Objective: Elaborate a new MMC delivery system during the transoperatory period of photorefractive keratectomy (PRK) followed by patent application. Methods: The project consists of an in vitro experimental study to create an MMC (0.02%) release system. The drug was impregnated in sterile Whatman® 41 paper filter discs with a diameter of 8 mm. After drying, the discs were applied to antibiogram plates seeded with Staphylococcus epidermidis (American Type Culture Collection ATCC 12228), followed by the addition of a drop of sterile water. At the end of 1 minute, the discs were removed and the plates incubated for 48 hours at 35oC. Mean drop volume in the collyrium flasks was measured using analytical balance weighing. The inhibition halo (mm) was correlated with the MMC impregnated into the disc. After completion of the invention design a patent application was lodged at the National Institute of Industrial Property. Results: The correspondence between MMC-produced inhibition halos indicated that a dose of 16μg was ideal for impregnating into the discs. The mean drop volume obtained from the collyrium flasks was 37.7 μL. A minute after the application of one drop of balanced saline solution, the system released an adequate concentration for PRK surgery. Conclusion: A new MMC delivery system was created for transoperatory application in photorefractive keratectomy (PRK). Publication of the patent application (number PI 0704739-8) gives the authors exclusive intellectual property rights. The study was sponsored by Ophthalmos Indústria e Comércio de Produtos Farmacêuticos S.A. (São Paulo-SP, Brazil) and received the indispensable scientific contribution of researchers from the fields of Pharmacy, Medicine, Biology, Statistics and Law, characterizing the work as multidisciplinary, in accordance with norms established by the Postgraduate Health Sciences Program of the Federal University of Rio Grande do Norte (UFRN)

Efeito da Olmesartana na resposta inflamatória em modelo de mucosite intestinal em ratos

Intestinal Mucositis is inflammation and/or ulceration of mucosa of the gastrointestinal tract caused by anticancer therapies. Histologically, villous atrophy, damage to enterocytes and infiltration of inflammatory cells. Methotrexate (MTX) is a compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. The aim of this study was to evaluate the effect of Olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i.p.) administration of MTX (7 mg/kg) for three consecutive days. The animals were pretreated with oral OLM at 0.5, 1 or 5 mg/kg or with vehicle 30 min prior to exposure to MTX, for three days. Small intestinal (duodenum, jejunum and ileum) homogenates were assayed for levels of the IL-1β, IL-10 and TNF-α cytokines, malondialdehyde and myeloperoxidase activity. Additionally, immunohistochemical analyses of MMP-2, MMP-9, COX-2, RANK/RANKL and SOCS-1 and confocal microscopy analysis of SOCS-1 expression were performed. Treatment with MTX+OLM (5 mg/kg) resulted in a reduction of mucosal inflammatory infiltration, ulcerations, vasodilatation and hemorrhagic areas (p<0.05) as well as reduced concentrations of MPO (p<0.001) and the pro-inflammatory cytokines IL-1β and TNF-α (p<0.01), and increase antiinflammatory cytosine IL-10 (p,0.05). Additionally, the combined treatment reduced expression of MMP-2, MMP-9, COX-2, RANK and RANKL (p<0.05) and increased cytoplasmic expression of SOCS-1 (p<0.05). Our findings confirm the involvement of OLM in reducing the inflammatory response through increased immunosuppressive signaling in an IMM. We also suggest that the beneficial effect of Olmesartan treatment is specifically exerted during the damage through blocking inflammatory cytosines.

Transplantes de córneas no estado do Rio Grande do Norte: aspectos epidemiológicos e clínicos

This study aimed to characterize in a clinical and epidemiological way the patients who are on a waiting list for transplantation and the patients transplanted with corneal tissue in a corneal transplants reference service in the state of Rio Grande do Norte. It is an epidemiological study of a quantitative approach, with cross-sectional, descriptive and analytical cut including all patients on the waiting list for transplantation (population A) and the patients already transplanted with a corneal tissue (population B) in a reference service. In population A, there was a census conducted of patients on the waiting list for corneal transplantation (n=62 patients). In population B, the sample was non-probabilistic and corresponded to all corneal transplants performed in the service in the period from 2010 to 2014 (n=258). This study is approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte, in Opinion 876 177 and CAAE 37533014.8.0000.5537. Data were collected in full in the period from January to April 2015, by two instruments built to systematize the necessary data collection. After being coded and tabulated, data were analyzed using the Statistical Package for Social Sciences software, version 20.0. The definition of variables and their distribution patterns were presented as frequencies and measures of central tendency while, for multivariate analysis, the effect of magnitude measures were applied (prevalence ratio) and measures of association (chi-square test or Fisher's exact test) for a 0.05 significance level. The results are shown in two scientific articles coming from the field survey data. It was found that the epidemiological profile of patients on the waiting list (n=62) showed a prevalence of individuals aged over 50 years old, female (54.84%) and residents of the middle region of East Rio Grande do Norte (66.13%). The clinical profile of patients with corneal transplantation (n=258) was characterized by being male (51.16%) with an average age of 49.33 years old and 57.75% were coming from East Rio Grande do Norte. The average time on the waiting list was 172.63 days in elective transplants and 9.03 days in urgent transplants. Keratoconus was the main indicator condition to perform the transplant. For patients on the waiting list, the variable “type of disorder of the cornea” showed statistically significant association with gender and age. For patients with corneal transplants, the variable "type of disorder of the cornea" was associated with the variables gender, age, previous surgery, failure of previous graft, classification of the eye and glaucoma. By characterizing the clinical and epidemiological profile of corneal transplants, it is possible to question the reality, pointing about the care that should be offered and develop targeted interventions to collective and individual needs intrinsic to patients who need this surgery as a treatment option.

Efeito anti-inflamatório e antioxidante do extrato hidroalcóolico de Turnera subulata na colite ulcerativa induzida por ácido acético em ratos

Inflammatory bowel diseases is composed by a set of chronic and inflammatory disorders, among them is ulcerative colitis (UC). UC treatment is based on anti-inflammatory administration; however, this group of drugs clearly leads to development of undesirable side effects, what stimulate the search for new therapies alternatives. The aim of this study was to evaluate the effect of hydroalcholic Turnera subulata extract on acetic acid-induced acute UC in rats. UC was induced by 1 mL injection of 4% acetic acid via rectal in Wistar mouse. 42 animals were distributed among 6 experimental groups: Control, UC, Sulfasalazine 500 mg/Kg/day (SSZ), T. subulata 50mg/Kg/day (TS 50), T. subulata 100mg/Kg/day (TS 100), T. subulata 200mg/Kg/day (TS 200). Throughout the experiment, body weight, food and water ingestion was daily evaluated. At the end of the experiment, the animals were euthanized and a colon fragment was observed by macroscopic analysis. Colon fragments were also collected for microscopic analysis and oxidative stress evaluation. The means from each group was compared by ANOVA test with a significance level of 5% (p<0.05) using GraphPad Prism Software. As results, we can clearly observe that SSZ group had the greater body weight decrease among the groups throughout the experiments, 14.78%, as well as, the lowest food intake, 6.23 g of food/day. The animals treated with T. subulata extracts showed no important body weight loss when compared to control. UC group showed the highest tissue damage macroscope score, 6.5, while TS 50 showed the lowest tissue damage score: 1. Microscope evaluation showed the presence of edema, haemorraghia and ulceration in all group of animals, except for Control. Nevertheless, TS 50 showed the lowest inflammatory damage among all groups. Oxidative stress analysis revealed that T. subulata treatment modulate catalase and superoxide dismutase activity, we also observed a decrease in protein and lipid peroxidation in response to extract administration. Taken together, these results shows that T. subulata extract exerts anti-inflammatory and anti-oxidant effects on experimental UC.

Efeito anti-inflamatório e antioxidante do extrato hidroalcóolico de Turnera subulata na colite ulcerativa induzida por ácido acético em ratos

Inflammatory bowel diseases is composed by a set of chronic and inflammatory disorders, among them is ulcerative colitis (UC). UC treatment is based on anti-inflammatory administration; however, this group of drugs clearly leads to development of undesirable side effects, what stimulate the search for new therapies alternatives. The aim of this study was to evaluate the effect of hydroalcholic Turnera subulata extract on acetic acid-induced acute UC in rats. UC was induced by 1 mL injection of 4% acetic acid via rectal in Wistar mouse. 42 animals were distributed among 6 experimental groups: Control, UC, Sulfasalazine 500 mg/Kg/day (SSZ), T. subulata 50mg/Kg/day (TS 50), T. subulata 100mg/Kg/day (TS 100), T. subulata 200mg/Kg/day (TS 200). Throughout the experiment, body weight, food and water ingestion was daily evaluated. At the end of the experiment, the animals were euthanized and a colon fragment was observed by macroscopic analysis. Colon fragments were also collected for microscopic analysis and oxidative stress evaluation. The means from each group was compared by ANOVA test with a significance level of 5% (p<0.05) using GraphPad Prism Software. As results, we can clearly observe that SSZ group had the greater body weight decrease among the groups throughout the experiments, 14.78%, as well as, the lowest food intake, 6.23 g of food/day. The animals treated with T. subulata extracts showed no important body weight loss when compared to control. UC group showed the highest tissue damage macroscope score, 6.5, while TS 50 showed the lowest tissue damage score: 1. Microscope evaluation showed the presence of edema, haemorraghia and ulceration in all group of animals, except for Control. Nevertheless, TS 50 showed the lowest inflammatory damage among all groups. Oxidative stress analysis revealed that T. subulata treatment modulate catalase and superoxide dismutase activity, we also observed a decrease in protein and lipid peroxidation in response to extract administration. Taken together, these results shows that T. subulata extract exerts anti-inflammatory and anti-oxidant effects on experimental UC.