Treatment strategy for bilateral severe subepithelial fibrosis after photorefractive keratectomy enhancement / Estratégia de tratamento para fibrose subepitelial grave bilateral após aprimoramento com ceratectomia fotorrefrativa

ABSTRACT A 27-year-old healthy man with a history of bilateral photorefractive keratectomy (PRK) enhancement after femtosecond laser in situ keratomileusis (LASIK) presented with decreased uncorrected distance visual acuity (UDVA) of 20/125 in the right eye (OD) and 20/300 in the left eye (OS) six months after PRK. Examination revealed bilateral dense subepithelial opacities. Both eyes (OU) were treated with superficial keratectomy combined with phototherapeutic keratectomy (PTK) and adjunctive application of mitomycin C 0.02%. At three months follow up UDVA was 20/30 OD and 20/25 OS. Superficial keratectomy combined with PTK seems to be a safe and efficient technique for treatment of dense subepithelial scar formation following PRK enhancement after LASIK.

RESUMO Um homem saudável de 27 anos de idade com história de aprimoramento com ceratectomia fotorrefrativa (PRK) bilateral, após Ceratomileuse Assistida por Excimer Laser In Situ (LASIK) com laser de femtossegundos, apresentou diminuição da acuidade visual à distância não corrigida (AVNC) de 20/125 no olho direito (OD) e 20/300 no olho esquerdo (OE) seis meses após PRK. O exame revelou opacidades subepiteliais densas bilaterais. Ambos os olhos (AO) foram tratados com queratectomia superficial combinada com ceratectomia fototerapêutica (PTK) e aplicação adjuvante de mitomicina C a 0,02%. Aos três meses de acompanhamento, o AVNC foi de 20/30 OD e 20/25 OE. A ceratectomia superficial combinada com PTK parece ser uma técnica segura e eficiente para o tratamento da formação densa de cicatrizes subepiteliais após o aprimoramento com PRK pós-LASIK.

Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes / Pacientes transplantados renais com anticorpos anti-HLA pré-formados: achados precoces de biópsia e desfechos clínicos

Abstract Introduction: Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival. Objective: to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction. Methods: A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed. Results: general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up. Discussion and conclusions: the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

Resumo Introdução: A fibrose renal é o desfecho de um processo iniciado no transplante, com reperfusão, isquemia e inflamação precoce, que progride ao longo do tempo com fenômenos imunológicos e não imunológicos. A identificação de marcadores morfológicos e a intervenção precoce poderiam melhorar a função e a sobrevida do enxerto. Objetivo: Avaliar a correlação entre intensidade e especificidade de anticorpos anti-HLA pré-transplante alterações histológicas do enxerto renal, de forma a identificar fatores de risco ou marcadores de disfunção precoces do aloenxerto. Métodos: O presente estudo incluiu uma coorte retrospectiva de receptores de transplante renal sensibilizados com anticorpos anti-HLA no pré-transplante submetidos a biópsia de enxerto nos primeiros dois anos após o transplante. Os grupos foram divididos em função da especificidade dos anticorpos anti-HLA: sem anticorpos doador-específicos (não-DSA, n = 29) e com anticorpos doador-específicos (DSA+, n = 16). Alterações histológicas do enxerto renal, função renal e proteinúria foram analisados. Resultados: Os dois grupos tinham características gerais semelhantes, exceto pela dose mais elevada de timoglobulina administrada nos indivíduos do grupo DSA+ (p < 0,05). O grupo não-DSA teve escores mais elevados de glomeruloesclerose, inflamação intersticial (i) e fibrose intersticial (ci) (p < 0,05), além de maior incidência de rejeição celular aguda (RCA). Não foi observada diferença estatística na incidência de rejeição mediada por anticorpos, função renal ou proteinúria durante o seguimento. Discussão e Conclusões: A diferença nos escores de inflamação e fibrose intersticial pode estar associada à maior incidência de RCA e nefropatia por poliomavírus no grupo não-DSA. Devemos considerar ainda o efeito protetor das doses mais elevadas de timoglobulina na redução da lesão por isquemia-reperfusão no grupo DSA+. O curto período de seguimento pode ter sido insuficiente para detectar alterações de longo prazo no tecido do aloenxerto, função renal e proteinúria.

Síndrome metabólico, hígado graso no alcohólico y hepatocarcinoma / Metabolic syndrome, nonalcoholic fatty liver disease and hepatocellular carcinoma

En las últimas décadas, los cambios en el estilo de vida pro-vocaron un incremento en la prevalencia del síndrome meta-bólico y que la enfermedad por hígado graso no alcohólico (nonalcoholic fatty liver disease, NAFLD sus siglas en inglés) se convierta en la enfermedad hepática crónica más fre-cuente en todo el mundo. Los componentes del síndrome metabólico no son sólo altamente prevalentes en pacientes con hígado graso no alcohólico, sino que a la vez aumentan el riesgo de desarrollarlo. Esta relación bidireccional ha sido claramente establecida. Asimismo se considera que NAFLD podría ser el componente hepático del síndrome metabólico. Aunque NAFLD se considera principalmente una enfermedad benigna, puede progresar a fibrosis hepática grave y carcino-ma hepatocelular (CHC), incluso se encontraría este último en hígados no cirróticos. El objetivo de esta revisión es determinar los procesos fisio-patológicos comunes a estas entidades, cuáles son las estra-tegias diagnósticas recomendadas y cuáles las intervenciones terapéuticas actualmente aprobadas.

The Effect of Fibroblast Growth Factors in Grafted Fascia into the Vocal Fold of Rabbits

Abstract Introduction The human larynx is a very important organ for communication. Many conditions lead to scarring of the vocal folds, decreasing voice quality. Objective We aimed to determine whether fibroblast growth factors (FGFs) may influence tissue integration of grafted fascia into the vocal folds of an animal model. Methods This is an experimental animal study with 12 adult rabbits that were submitted to a grafting fragment obtained from superficial cervical fascia into the vocal fold lamina propria, bilaterally. The right vocal fold was injected with FGFs. The animals were sacrificed after 1 month or 12 months, depending on the group they were assigned to, and a histological analysis of their vocal folds was performed.We analyzed the histological changes (such as the presence of fibrosis and neovascularization) induced by the acute or chronic inflammatory reactions. Results The FGFs induced acute inflammatory changes in all animals after 1 month of the initial experiment. The presence of FGFs triggered more fibrosis than the expected due to the surgical procedure itself when compared with the control side of all animals after 12 months of the initial experiment. Conclusions Fibroblast growth factors alone do not represent a good therapeutic option in phonosurgery, since we observed higher levels of fibrosis in the vocal fold lamina propria. Further studies combining more substances may be necessary to elucidate the best option to be used in this kind of surgery. (AU)

Beneficial effects of Oltipraz, nuclear factor - erythroid - 2 - related factor 2 (Nrf2), on renal damage in unilateral ureteral obstruction rat model

ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

Comparative study of fibrosis induced by Marlex®, Parietex Composite®, Vicryl® and Ultrapro® meshes1

Abstract Purpose: To evaluate the fibrosis induced by four different meshes: Marlex®, Parietex Composite®, Vicryl® and Ultrapro®. Methods: Histological cutouts of abdominal wall were analyzed with polarized light 28 days after the meshes implants and colorized by picrosirius to identify the intensity of collagen types I and III, and their maturation index. Results: When the four groups were compared, the total collagen area analyzed was bigger in groups A and D, with no difference between them. The collagen type I density was bigger in group A, with an average of 9.62 ± 1.0, and smaller in group C, with an average of 3.86 ± 0.59. The collagen type III density was similar in groups A, B and C, and bigger in group D. The collagen maturation index was different in each of the four groups, bigger in group A with 0.87, group B with 0.66, group D with 0.57 and group C with 0.33 (p = 0.0000). Conclusion: The most prominent fibrosis promotion in the given meshes was found on Marlex® (polypropylene mesh) and the Parietex Composite® (non-biodegradable polyester); the collagen maturation index was higher in the Marlex® mesh, followed by Ultrapro®, Parietex Composite® and Vicryl® meshes.

Avaliação de pacientes portadores de cirrose candidatos a transplante hepático pela ressonância magnética cardíaca / Cardiac magnetic resonance evaluation of patients with cirrhosis eligible to liver transplantation

Fundamento: O transplante hepático (TH) é cirurgia de grande porte indicada para tratamento de portadores de cirrose avançada e está associado a diversos riscos. Por esta razão, faz-se necessário estratificar o risco no período pré- transplante através da avaliação da função miocárdica e pesquisa de doença coronariana. Objetivo: Demonstrar a aplicabilidade da ressonância miocárdica cardíaca (RMC) na avaliação morfofuncional cardíaca, bem como seu uso na avaliação da isquemia miocárdica no pré-transplante. Método: Realizou-se estudo retrospectivo e descritivo, sendo avaliados dados de pacientes cirróticos encaminhados ao ambulatório de TH no período de Janeiro/2014 a Julho/2016 que se submeteram a RMC para avaliação cardíaca e como teste provocativo de isquemia miocárdica. Resultados: Foram encaminhados 135 pacientes; destes, 39 realizaram RMC. A idade média foi de 60 anos (50 a 71). Cerca de 87% (n = 34) eram do sexo masculino. Prevaleceu etiologia etanólica 56% (n = 22). A maioria era de pacientes CHILD C, MELD ≥ 18, (n = 26). A RMC evidenciou isquemia miocárdica em 03 pacientes (7,6%). A cineangiocoronariografia foi realizada nestes pacientes e a presença de doença arterial coronariana grave (obstrução > 70%) foi confirmada em todos, com consequente revascularização miocárdica. Em um seguimento de até 2 anos e 7 meses, a sobrevida dos transplantados foi de 87%, sem intercorrências cardiológicas. Conclusões: A realização da RMC na avaliação de cirróticos no pré-transplante mostrou-se estratégia segura ao evidenciar a presença de alterações morfofuncionais da cardiomiopatia do cirrótico e a presença de isquemia miocárdica. Entretanto, novos estudos devem ser realizados para padronização de métodos e critérios para avaliação cardiovascular em cirróticos

Background: Liver transplantation (LT) is a huge surgery performed to treat patients with advanced liver cirrhosis and is associated with several risks. For this reason, is necessary to stratify the risk in the pre-transplantation period through the evaluation of myocardial function and ischemia Objective: To demonstrate the applicability of cardiac magnetic resonance (CMR) in cardiac morphologic and functional evaluation, as well use in the evaluation of myocardial ischemia in pre-transplantation. Methods: Retrospective, descriptive study. Data from patients with cirrhosis referred to the liver transplant outpatient clinic from January 2014 to July 2016 were analyzed they underwent CMR for cardiac evaluation and as provocative test of myocardial ischemia. Results: 135 patients were referred of these, 39 performed CMR. The mean age was 60 (50 to 71). About 87% (n = 34) were males. Alcoholic etiology prevailed 56% (n = 22). Most were of CHILD C patients with MELD ≥ 18, (n = 26). CMR showed myocardial ischemia in 03 patients (7,6%). Coronary angiography was performed and presence of severe coronary artery disease (obstruction > 70%) was confirmed, with consequent myocardial revascularization. At a follow-up of 2 years and 7 months, the survival of transplanted patients was 87%, without cardiologic complications. Conclusions: The realization of CMR in the evaluation of cirrhotic patients in the pre-transplantation proved to be a safe strategy by showing presence of morphologic and functional changes of the cirrhotic cardiomyopathy and the presence of myocardial ischemia. However, more studies should be performed to standardize methods and criteria for cardiovascular evaluation in cirrhotic patients before the liver transplantation

Formação de membrana fibrótica cicatricial em paciente submetido à ceratoplastia penetrante / Fibrotic scar membrane formation in patients undergoing penetrating keratoplasty

RESUMO O surgimento de uma membrana fibrótica opacificada na córnea transplantada é pouco descrito nas literaturas nacional e mundial. O objetivo é relatar o caso de um paciente com leucoma total de olho esquerdo que foi submetido à ceratoplastia penetrante levando a formação de dupla câmara anterior devido ao surgimento de uma membrana fibrótica cicatricial. Paciente do sexo masculino, 54 anos, com leucoma total secundário a ceratite herpética, diabético há 20 anos, em uso de insulina, com retinopatia diabética não proliferativa. Realizou-se cirurgia de membranectomia com complicações pós-operatória.

ABSTRACT The emergence of opaque fibrotic membrane in transplanted cornea is little described in national and world literature. The goal is to report the case of a patient with leucoma total of left eye that was submitted to the penetrating keratoplasty leading to formation of double anterior chamber due to the emergence of a fibrotic scar membrane. Male patient, 54 years, with total herpetic keratitis secondary leucoma, diabetic for 20 years, using insulin, with non-proliferative diabetic retinopathy. Held membranectomia surgery with postoperative complications.

Immunolocalization of the TGFB1 system in submandibular gland fibrosis after experimental periodontitis in rats

Saliva is the first barrier to entry of bacteria and viruses into the body. The submandibular glands (SMG) contribute to the maintenance of oral health and regulation of immune/ inflam matory responses. Previous studies suggest that transforming growth factor beta 1 (TGFB1) may contribute to salivary gland fibrosis but the expression of the TGFB1 system in the SMG has not been elucidated. Thus, the aim of this study was to analyze in rat SMG the immunolocalization of TGFB1 and its specific receptors ALK5 (profibrotic) and ALK1 (proproliferative) and the coreceptor endoglin (EDG) in a bilateral experimental periodontitis (EP) model (cotton thread ligature around the neck of the first lower molars) for 1 and 6 weeks. Fixed SMG were embedded in paraffin and serially cut for routine hematoxylin-eosin staining for histological analysis or immunohistochemical techniques by diaminobenzidine detection. SMG histology from animals with EP showed timedependent structural changes involving marked reduction in the height of the contoured ducts, cell destruction, loss of secretory granules, periductal congestion and excess connective tissue surrounding these ducts indicative of a fibrotic process, compared to control SMG. TGFB1, ALK5 and ALK1 receptors and the coreceptor EDG were mainly immunolocalized in ductal cells and in the fibrotic areas in EP groups. The expression of the profibrotic ALK5 receptor was increased in areas of fibrosis in SMG of animals with EP. In SMG of rats with EP, the localization of the TGFB1 specific receptors in the ducts and cells from fibrotic areas, due to the expression of TGFB1 in the surrounding areas, might indicate paracrine and autocrine actions exerted by TGFB1 via its specific receptors. The results of this study suggest that TGFB1 promotes fibrosis, inducing cell proliferation via ALK1 and EDG receptors and stimulates fibrosis relatedprocesses via ALK5 receptor, which could lead to abnormal secretor activity of the SMG during periodontal disease.

La saliva es la primera barrera para la entrada de bacterias y virus en el cuerpo. Las glándulas submandibulares (GSM) contribuyen al mantenimiento de la salud oral y a la regulación de las respuestas inmunoinflamatorias. Estudios previos sugieren que el factor de crecimiento transformante beta 1 (TGFB1) puede contribuir a la fibrosis de las glándulas salivales, pero la expresión y localización del sistema TGFB1 en las GSM no ha sido dilucidada. El objetivo del presente trabajo fue analizar por inmunohistoquímica en las GSM de ratas la expresión de TGFB1 y sus receptores específicos ALK5 (profibrótico) y ALK1 (proproliferativo) y el coreceptor endoglina (EDG) en un modelo de periodontitis bilateral experimental (PE) (hilo de algodón alrededor del cuello de los primeros molares inferiores) durante 1 y 6 semanas. Las GSM fueron fijadas y embebidas en parafina para realizar cortes seriados los cuales se tiñeron con hematoxilinaeosina para analizar la histología o se procesaron para realizar la técnica de inmunohistoquímica mediante detección con diaminobenzidine. La histología de las GSM de animales con PE reveló cambios estructurales tiempo dependientes, con una marcada reducción de la altura de los conductos, destrucción celular, pérdida de gránulos secretores, congestión periductal y exceso de tejido conectivo que rodea los conductos, indicando un proceso de fibrosis respecto de las GSM de animales control. TGFB1, ALK5 y ALK1 y el coreceptor EDG fueron principalmente inmunolocalizados en las células que forman los ductos y en las áreas de fibrosis en los grupos con PE. La expresión del receptor profibrótico ALK5 se incrementó en las áreas de fibrosis en GSM de animales con PE. En GSM de ratas con PE, la localización de los receptores específicos de TGFB1 en las células de los conductos y áreas de fibrosis, junto con la expresión de TGFB1 en las áreas circundantes, podría indicar acciones paracrinas y autocrinas ejercidas por TGFB1 a través de sus receptores específicos. Los resultados de este estudio sugieren que TGFB1 podría inducir un proceso de fibrosis promoviendo la proliferación celular a través de los receptores ALK1 y EDG, y favoreciendo procesos relacionados con la fibrosis a través de su receptor ALK5, lo que conduciría a una actividad secretora anormal de la GSM durante la enfermedad periodontal.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Oleuropein prevents the progression of steatohepatitis to hepatic fibrosis induced by a high-fat diet in mice

Nonalcoholic steatohepatitis (NASH) is characterized by hepatocyte injury and inflammatory cell infiltration, which has been linked to peripheral insulin resistance and increased levels of triglycerides in the liver. The purposes of this study were to establish a mouse model of NASH by feeding mice a 60% high-fat diet (HFD) and to demonstrate the anti-fibrotic effects of oleuropein, which has been shown to have anti-oxidant and anti-inflammatory properties, in this HFD-induced mouse model of NASH. C57BL/6 mice were divided into three groups: a regular diet group (Chow), a HFD group and an oleuropein-supplemented HFD group (OSD), which was fed a 0.05% OSD for 6 months. The effects of oleuropein in this model were evaluated using biochemical, histological and molecular markers. The expression levels of alpha-smooth muscle actin (alpha-SMA)and collagen type I in the HFD and OSD groups were evaluated using real-time PCR and western blotting. The body weight, biochemical marker levels, nonalcoholic fatty liver disease activity score, homeostasis model of assessment-insulin resistance (HOMA-IR) and leptin levels observed in the HFD group at 9 and 12 months were higher than those observed in the Chow group. The HOMA-IR and leptin levels in the OSD group were decreased compared with the HFD group. In addition, alpha-SMA and collagen type I expression were decreased by oleuropein treatment. We established a NASH model induced by HFD and demonstrated that this model exhibits the histopathological features of NASH progressing to fibrosis. Our results suggest that oleuropein may be pharmacologically useful in preventing the progression of steatohepatitis and fibrosis and may be a promising agent for the treatment of NASH in humans.

MicroRNAs: their involvement in fibrosis pathogenesis and use as diagnostic biomarkers in scleroderma

miRNAs are important post-transcriptional regulators. The aberrant expression of miRNAs is strongly associated with the initiation and progression of pathophysiologic processes in a wide range of human diseases. Scleroderma (systemic sclerosis; SSc) is a highly heterogeneous autoimmune disease that includes the progressive fibrotic replacement of normal tissue architecture in multiple organs. Our previous studies have suggested that SSc skin tissues display a different miRNA expression signature than that found in normal controls. miRNAs with pro- or antifibrotic properties are found to be dysregulated in SSc skin fibrosis. Serum miRNA levels are associated with SSc activity and severity. miRNAs have the potential to be therapeutic targets and serve as biomarkers for SSc diagnosis and assessment of disease state and severity. This review summarizes the SSc miRNA expression signature and the roles of dysregulation of miRNAs in SSc tissues and serum and examines the future therapeutic potential of targeting miRNAs in the management of SSc patients.

Normal tissue complication probability of fibrosis in radiotherapy of breast cancer: accelerated partial breast irradiation vs conventional external-beam radiotherapy.

AIMS: Radiotherapy forms an integral part of breast-conserving treatment in early-stage breast cancer. Subcutaneous fibrosis of the treated breast is an important late effect in whole-breast irradiation. The aim of this study was to compare the normal tissue complication probability (NTCP) for radiation-induced fibrosis in treated breast using accelerated partial-breast irradiation (APBI) vs conventional treatment. MATERIALS AND METHODS: Ten postoperative early-stage breast cancer patients (T1N0M0) were included in this dosimetric analysis. APBI treatment was planned using conformal radiotherapy technique and conventional treatment plans included two tangential portals. All the APBI treatment plans were made with five non-coplanar beams with 6 MV photons. The prescription dose was 38 Gy in 10 fractions for the APBI treatments and 50 Gy in 25 fractions, followed by a boost dose of 16 Gy in 8 fractions, for the conventional treatments. We used Lyman's relative-seriality model and the breast fibrosis NTCP model fitting parameters for the study. RESULTS: The equivalent uniform dose (EUD) was 30.09 Gy and 50.79 Gy in APBI and conventional treatment, respectively. The mean NTCP values for ipsilateral breast fibrosis in APBI and conventional treatment were 0.51 and 25.66%, respectively. Using the paired t-test, a statistically significant difference was seen in the breast fibrosis NTCP values for APBI vs conventional treatment (P < 0.001). CONCLUSIONS: APBI reduces the ipsilateral breast fibrosis compared to conventional whole-breast treatment in early-stage breast cancer.

Fibrosis in tubularized skin flaps in rats, using silicon catheters with two different degrees of flexibility: experimental model / Fibrose em retalhos tubulizados de pele de ratos usando cateteres de diferentes flexibilidades como molde: modelo experimental

PURPOSE: Microscopically evaluate the intensity of fibrosis in tubularized skin flaps on the back of Wistar rats, using silicon molds with different degrees of flexibility. METHODS: Twenty rats were submitted to three tubularized skin flaps on their backs. In two tubular flaps, we placed, as a mold, silicon catheters with different degrees of flexibility and removed them on the seventh day after the surgery. They were divided into two groups and euthanized, on the seventh and twenty-first days respectively after the surgery for the collection of the pieces, coloration with Masson tricromic, quantification of the area of each sample and comparison among the groups. RESULTS: Fibrosis was less intense on the tubular flaps where a catheter was not used as a mold. No significant difference was verified among the pieces with the silicon catheters, but there was a tendency of less fibrosis on the tubules with the most flexible catheter. CONCLUSION: There was no significant difference among the two catheter types. Fibrosis was less intense in the flaps where the mold was not used.

OBJETIVO: Avaliar microscopicamente a intensidade da fibrose em retalhos tubulares de pele do dorso de ratos Wistar em uso de moldes de silicone de diferentes flexibilidades. MÉTODOS: Vinte animais foram submetidos à confecção de três retalhos tubulizados de pele na região dorsal. Em dois túbulos foram colocados, como molde, cateteres de silicone com flexibilidades diferentes e retirados no sétimo dia após a cirurgia. Foram divididos em dois grupos e sacrificados, respectivamente, no sétimo e vigésimo primeiro dia após a cirurgia para a coleta das peças, coloração pelo tricrômico de Masson, quantificação da área de cada amostra e comparação entre os grupos. RESULTADOS: A fibrose foi menos intensa nos retalhos tubulares em que não se usou cateter como molde. Não se verificou diferença significativa entre os retalhos com os cateteres de silicone, mas sim, tendência de menos fibrose nos túbulos com cateter mais flexível. CONCLUSÃO: Não houve diferença significativa entre os dois tipos de cateter. A fibrose foi menos intensa nos retalhos onde não se utilizou molde.

The effects of intrathecal administration of betamethasone over the dogs' spinal cord and meninges

PURPOSE: To determinate the potential clinical and histological changes due the injection of betamethasone, when administered into the canine intrathecal space. METHODS: Twenty one animals were included in a random and blind manner in the study. After general anesthesia, intrathecal puncture was performed and 1 ml of the random solution was injected. The G1 dogs received 0.9 percent saline solution, the G2 dogs received 1.75 mg betamethasone and the G3 dogs received 3.5 mg of betamethasone. The animals were clinically evaluated for 21 days and then sacrificed. The lumbar and sacral portions of the spinal cord were removed for light microscopy histological analyses. RESULTS: No clinical changes were observed in any of the animals included in this study. No histological changes were observed in G1 animals. Inflammatory infiltration was observed in two dogs, one in G2, another in G3. Hemorrhage and necrosis were also seen in the G2 dog which inflammatory infiltration was detected. In other two dogs, one from G2 and another from G3, there was discreet fibrosis and thickness of the arachnoid layer which was focal in one and diffuse in the other. CONCLUSION: Intrathecal administration of betamethasone caused histological changes in the spinal cord and meninges in some of the dogs involved in this study.

OBJETIVO: Determinar possíveis alterações clínicas e histológicas determinadas pela administração da betametasona no espaço subaracnóideo de cães. MÉTODOS: Vinte e um cães foram incluídos no estudo de forma aleatória e encoberta. Depois de anestesiados, os cães foram submetidos a punção subaracóidea com injeção de 1 ml da solução sorteada. Os animais receberam solução salina 0,9 por cento em G1, betametasona na dose de 1,75 mg em G2 e betametasona na dose de 3,5 mg em G3. Todos os animais foram mantidos em observação clínica por 21 dias, sendo posteriormente sacrificados. Porções da medula espinhal e sacral foram removidas para análise histológica por microscopia óptica. RESULTADOS: Não foram detectadas alterações clínicas em quaisquer dos animais incluídos no estudo. Da mesma forma, nenhum animal do G1 apresentou alterações histológicas. Infiltração inflamatória foi observada em dois cães, um do G2 e outro e G3. No cão do G2 onde a infiltração inflamatória foi observada ocorreu, conjuntamente, hemorragia e necrose. Em dois cães, um de G2 e outro de G3, observou-se discreta fibrose e espessamento da aracnóide, sendo focal em um e difusa no outro. CONCLUSÃO: A administração subaracnóidea de betametasona determinou alterações histológicas em medula e meninges de alguns dos cães envolvidos no estudo.

Hysteroscopic sterilization with occlusion of sheep uterine tube using n-butyl-2-cyanoacrylate adhesive

PURPOSE: To evaluate the fertility and analyze the macroscopic, microscopic and morphometric aspects of sheep uterine tube sterilization with a hysteroscopically insert of n-butyl-2-cyanoacrylate adhesive. METHODS: 12 adult sheep, with one previous pregnancy, were distributed as follows: group L (n=3) subjected to laparotomy and Pomeroy uterine tube ligation, group S (n=3) subjected to hysteroscopic application of saline solution in tube isthmus and group AD(n=6), that was subjected to hysteroscopic application of 0.5 ml of n-2-butil-cyanoacrylate in tube isthmus. They were mated with fertile males for ninety days. The non pregnant sheep, at the 90th day, were subjected to laparotomy with uterus and tubes uterine resection. The fragments of uterine tubes were fixated in 10 percent formalin and processes for histology evaluated, and slices dyes for H.E. Data were evaluated by Wilcoxon and Mann-Whitney and Fisher's exact test. RESULTS: All sheep from groups L and AD did not get pregnant (0 percent) in contrast with sheep from group S (100 percent); the adhesive remained integral in the uterine tube lumen. The percentual of adherences (66.6 percent) and fibrosis responses (100 percent) was significantly higher in the group L than group AD (0 percent) (p<0.01). The diameter of the caudal tube in group AD (2652.15 ± 45.76 mm) was significantly wider than that of the group L (1868.27 ± 56.11* μm) (p < 0.05). CONCLUSION: The hysteroscopic insertion of cyanoacrylate in the uterine tube lumen of sheep was effective to obstruct the uterine tube and to promote the sterilization.

OBJETIVO: Avaliar a fertilidade e aspectos macroscópicos, microscópicos e morfométricos da esterilização histeroscópica de tubas uterinas de ovelhas com o adesivo de n-butil-2-cianoacrilato. MÉTODOS: 12 ovelhas adultas, com uma prenhez anterior, foram distribuídas como segue: o grupo L (n=3) submetidas à laparotomia e laqueadura tipo Pomeroy, grupo S (n=3) submetidas à aplicação histeroscópica de solução salina no istmo tubário e grupo AD (n=6), com aplicação histeroscópica de 0,5 ml de cianoacrilato. As ovelhas foram acasaladas com machos de comprovada fertilidade por noventa dias. As ovelhas não prenhes aos 90 dias, foram submetidas à laparotomia com ressecção do útero e tubas uterinas, que foram fixadas em formalina 10 por centos e os cortes histológicos corados em hematoxilina/eosina. Os resultados foram avaliados pelo teste de Wilcoxon e teste exato de Fisher. RESULTADOS: Todas as ovelhas dos grupos L e AD não ficaram prenhes (0 por cento) ao contrário das ovelhas do grupo S (100 por cento); o adesivo permaneceu íntegro no lúmen tubário. O percentual de aderências (66.6 por cento) e de fibrose (100 por cento) foi significativamente maior no grupo L do que no grupo AD (0 por cento) (p<0,01). O diâmetro da porção caudal no grupo AD (2652,15 ± 45,76 μm) foi significativamente maior do que grupo L (1868,27 ± 56.11 mm) (p<0,05). CONCLUSÃO: A inserção histeroscópica do cianoacrilato no lúmen tubário de ovelhas foi eficaz para obstruir a tuba uterina e promover a esterilização.

Experimental strabismus surgery using triamcinolone: outcomes and effects on inflammatory response

PURPOSE: To evaluate the efficiency of triamcinolone (TRI) in limiting the postoperative inflammatory response and scarring after strabismus surgery. METHODS: A prospective, two-stage, masked, controlled trial was conducted. In the first stage, the inflammatory response at the extraocular muscle reattachment site was analyzed after superior rectus recession in ten rabbits. In the second stage, TRI (40 mg/ml) was applied during surgery to the eyes of 16 rabbits with superior rectus recession. As a control, contralateral eyes were treated with physiological saline. Fifteen days later, exenteration was performed, and the sites of muscle reattachment were processed for histological examinations. The sums of the areas of the granulomas in the extraocular muscle reattachment sites of control and treated eyes were compared. RESULT: There was a preliminary inhibition effect of TRI on the inflammatory response of treated eyes compared with that of control eyes. CONCLUSIONS: In the conditions of conducting this study the introperative use of TRI was effective in controlling the postoperative inflammatory response in rabbit eyes after extraocular muscle surgery.

OBJETIVO: Avaliar a eficiência da triancinolona (TRI) como agente modulador da resposta inflamatória e cicatricial em coelhos submetidos à cirurgia de estrabismo. MÉTODOS: Foi realizado estudo prospectivo, mascarado, em dois estágios. No primeiro estágio 10 coelhos foram submetidos a retrocesso do músculo reto superior em ambos os olhos, aplicando-se triancinolona (40 mg/ml) em um dos olhos e como controle, solução salina nos olhos contralaterais. Quinze dias e trinta dias após, os animais foram exenterados e o material do sítio de reinserção muscular foi submetido à análise qualitativa e quantitativa. No segundo estágio, com incrementação da agressão cirúrgica, 16 coelhos foram submetidos aos mesmos procedimentos com exenteração e análise dos tecidos após 15 dias. RESULTADO: Houve efeito inibitório da TRI na resposta inflamatória dos olhos tratados quando comparados aos olhos-controle. CONCLUSÕES: Nas condições de realização do presente estudo o uso per-operatório da TRI foi efetivo no controle da resposta inflamatória em olhos de coelhos submetidos à cirurgia de estrabismo.