A reparação de defeitos ósseos é uma preocupação constante em diversas áreas da odontologia. Vários materiais são usados com a finalidade de ajudar e acelerar esta reparação, tais como enxertos autógenos, xenógenos, membranas e alguns medicamentos, assim como a associação de alguns destes métodos. A sinvastatina, medicamento utilizado para redução de colesterol, em alguns estudos, tem demonstrado ação na estimulação de formação óssea. O objetivo do presente estudo foi avaliar a influência da associação da sinvastatina à matriz desmineralizada de osso bovino na reparação de defeitos ósseos em calvária de ratos. Foram confeccionados defeitos ósseos na calvária de 48 ratos, sendo um defeito 5mm de diâmetro em cada parietal do animal. Os ratos foram divididos em três grupos de acordo com o material utilizado: grupo controle, que não recebeu nenhum tipo de substância, grupo sinvastatina-matriz óssea desmineralizada, que recebeu uma associação de sinvastatina e matriz desmineralizada de osso bovino e grupo matriz óssea desmineralizada que recebeu somente matriz desmineralizada de osso bovino como material de enxertia. Os sacrifícios foram realizados após trinta e sessenta dias. Após o sacrifício as calvárias foram radiografadas em aparelho de raios-X digital para análise de densidade radiográfica em tons de cinza e foram submetidas à preparação histológica de rotina, para posterior análise histológica descritiva e histométrica da área de matriz óssea neoformada, utilizando-se programa computacional para análise de imagens. Os dados submetidos à analise estatística ANOVA a 5% demonstraram que os animais que receberam a associação de sinvastatina-MODB apresentaram, na análise histométrica a menor área de neoformação e na análise radiográfica a menor densidade óssea. Concluiu-se, de acordo com a metodologia utilizada, que a associação sinvastatina-MODB influenciou negativamente o reparo ósseo. / Bone defect healing is a constant concern to several areas of Dentistry. A great variety of materials is currently used to help in the healing process as well as to speed it up. Materials such as autografts, xenografts, membranes, some drugs, and the association of some of them are being used. Simvastatin, a substance used to reduce cholesterol levels, has shown, in some studies, a capacity to stimulate bone formation. The purpose of the present experimental study is to evaluate the influence of the association of sinmvastatin with bovine demineralized bone matrix on the healing of bone defects in rats calvariae. Bone defects were produced in the calvariae of 48 rats, thus each animal had a defect in each parietal bone measuring 5mm of diameter. The rats were grouped according to the graft material used: the control group which didnt receive any substance; the simvastatin-demineralized bone matrix group which received an association of simvastatin and bovine demineralized bone matrix; and the demineralized bone matrix group which received bovine demineralized bone matrix. The animals were sacrificed after thirty or sixty days. After the sacrifices, digital radiographies were taken of the calvariae in order to analyse the radiographic density in shades of gray. They were also submitted to routine histological preparation for future descriptive histological and histomorfometric analyses of the new formed bone matrix through the use of a software to analyse the images. The data submitted to statistical analysis ANOVA (5%) showed that the animals which received the association simvastatin-demineralized bone matrix presented the smallest density and area of new bone formation of the three groups. According to the methodology used, we concluded that the association simvastatin demineralized bone matrix influenced negatively the bone healing.

Microchimerism arises from the exchange of cells between genetically distinct individuals. The coexistence of genetically distinct cell populations within a single organism has possible effects on health and functioning of individuals immune systems, but the exact mechanisms of action are often not yet known. With the development of microscopic technologies and software for data analysis, the possibilities of detection and phenotyping of these rare cell populations are expanding. My intention in this work is to find maternal microchimerism in embryonic tissues (E13) and intestines of breastfed pups using MHCII/EGFP knock-in mouse model. Several different technologies potentially suitable for the detection of maternal microchimeric cells in offspring tissues (light sheet fluorescent microscopy - LSFM, virtual slide microscopy and flow cytometry) were selected. Advanced analysis of the obtained samples from the light sheet microscopy using the creation of a neural network was used here. The presence of maternal microchimerism was not demonstrated by flow cytometry. Using LSFM, image data were obtained from intestinal samples of suckling pups, which were processed by the neural network method. Data analysis of embryos (E13) obtained by the same method did not allow data analysis due to high...

INTRODUÇÃO: Infertilidade atinge aproximadamente 15% dos casais em idade reprodutiva e afeta de maneira profunda a vida dessas pessoas. Dentre as causas identificáveis de infertilidade masculina, a varicocele é a mais frequente e acomete cerca de 40% dos homens inférteis ou subférteis. Um dos maiores desafios na abordagem cirúrgica da varicocele é a identificação de indivíduos que apresentarão maior benefício com o tratamento, uma vez que muitos pacientes não apresentam melhora da análise seminal. OBJETIVOS: Identificar um padrão histológico testicular como prognóstico da melhora da capacidade reprodutiva em pacientes submetidos à varicocelectomia microcirúrgica. METODOLOGIA: Estudo retrospectivo composto pela análise de 60 biópsias testiculares bilaterais de homens inférteis atendidos em clínica especializada de fertilidade masculina, entre os anos de 2006 e 2014. Como critérios de inclusão foram considerados homens com diagnóstico de varicocele clínica e subclínica entre 19 e 50 anos de idade com resultados de análise histopatológica testicular. Os sujeitos de pesquisa foram divididos em dois grupos. Grupo 1: homens com diagnóstico de varicocele subclínica (n = 20). Grupo 2: homens com diagnóstico de varicocele clínica (n =40). Foram excluídos do estudo homens com diagnóstico de criptorquidia, azoospermia obstrutiva e não-obstrutiva, usuários de drogas e anabolizantes, além de pacientes portadores de doenças sexualmente transmissíveis e de neoplasias no trato geniturinário. Os participantes foram submetidos ao exame físico urológico com a avaliação do volume testicular por meio de ultrassonografia da bolsa escrotal com Doppler-Colorido. O diagnóstico da varicocele foi realizado por meio da palpação cuidadosa do plexo pampiniforme com o paciente em posição ortostática. A manobra de Valsava foi utilizada para a classificação clínica do grau de varicocele. Para a determinação de um padrão histológico capaz de predizer a melhora da capacidade reprodutiva, foram criados valores de corte que associam os scores de Johnsen, os índices de Copenhagen e o volume testicular à melhora dos parâmetros seminais. RESULTADOS: No grupo 1, para a melhora da concentração espermática o score de Johnsen deve ser superior a 8,2 (lado esquerdo) e o volume testicular acima de 12,8 mL (lado direito). Adicionalmente, para a avaliação da motilidade total de espermatozoides os scores de Johnsen devem ser superiores a 8,2 (bilateral) e o dígito II de Copenhagen inferior a 2,5 em ambos os testículos. Todavia, para a motilidade progressiva de espermatozoides o score de Johnsen deve ultrapassar a 9,1 (bilateral) e na avaliação da morfologia espermática, este deve se apresentar acima de 7,9 e com volume testicular acima de 13,6 mL (lado direito). Quanto aos valores de corte obtidos no grupo 2, para a concentração de espermatozoides, os scores de Johnsen devem ser superiores a 5,5 com volume testicular acima de 11,5 mL em ambos os testículos. Finalmente, quanto à motilidade espermática total e progressiva, o dígito III do índice de Copenhagen deve ser inferior a 1,5 (lado direito). CONCLUSÃO: Valores prognósticos da melhora da capacidade reprodutiva obtidos por meio de biópsia testicular podem auxiliar com eficácia no prognóstico e na avaliação dos pacientes candidatos à correção microcirúrgica da varicocele / BACKGROUND: Infertility affects approximately 15% of couples in reproductive age and profoundly changes the lives of these people. Among the identifiable causes of male infertility, varicocele is the most common and affects about 40% of infertile or subfertile men. One of the challenges in the surgical approach is the identification of individuals who will present benefits with the treatment, since many patients do not show improvement of semen analysis. OBJECTIVE: To identify a testicular histological pattern as prognostic value of improved reproductive capacity in patients submitted to microsurgical correction of varicocele. METHODS: we retrospectively analyzed bilateral testicular biopsies of 60 men attending specialized clinic of male fertility between the years 2006 and 2014. As inclusion criteria were considered men diagnosed with clinical and subclinical varicoceles between 19 and 50 years old with results of testicular histopathology and seminal analysis. The patients were divided into two groups. Group 1: Men diagnosed with subclinical varicocele (n = 20). Group 2: men diagnosed with clinical varicocele (n = 40). Men diagnosed with cryptorchidism, obstructive and non-obstructive azoospermia, users of drugs and anabolic steroids were excluded of the study. All Participants were submitted to urological physical examination with the evaluation of testicular volume by ultrasonography of the scrotum with Color Doppler. The diagnosis of varicocele was performed by careful palpation of pampiniform plexus with the patient in standing position. The Valsalva maneuver was used to classify the grade of varicocele. The determination of a testicular histological pattern as prognostic value of the improved reproductive capacity was performed by the creation of cut-off values that associate Johnsen scores, Copenhagen indices and testicular volume to improvement in semen parameters. RESULTS: In Group 1, for improvement of sperm concentration, the Johnsen score must be greater than 8.2 (in the left testicle) and testicular volume must be greater than 12.8 mL (in the right testicle). Concerning evaluation of sperm total motility, the Johnsen score must be greater than 8.2 (bilateral) and digit II of Copenhagen indices must be less than 2.5 (bilateral). However, for sperm progressive motility, the Johnsen score must exceed 9.1 (bilateral) and evaluation of sperm morphology must be greater than 7.9 with right testicular volume greater than 13.6 mL. In Group 2, the cut-offs values for sperm concentration indicates that Johnsen scores must be greater than 5.5 with testicular volume greater than 11.5 mL in both testicles. Finally, regarding the sperm total and progressive motility, the digit III of Copenhagen indice must be less than 1.5 (in the right testicle). CONCLUSION: Prognostic values of improved reproductive capacity obtained from testicular biopsy can assist effectively in the prognosis and evaluation of patients candidates for microsurgical correction

Queimaduras severas causam trauma às vítimas, pela perda de líquido corpóreo, injúria no sistema vascular cutâneo e demora na cicatrização das lesões. A irradiação com laser em baixa intensidade vem sendo estudada como tratamento alternativo, por ser uma terapia não-invasiva e capaz de acelerar o processo de cicatrização. O objetivo deste estudo foi avaliar os efeitos do laser de baixa potência (λ = 660 nm) em queimaduras de pele por histomorfometria e fluxometria laser Doppler utilizando duas condições de irradiação. Trinta e seis animais com duas queimaduras criadas por vapor foram divididos em três grupos: no grupo dose fracionada (GF), as lesões foram irradiadas com dose de 1 J/cm2 nos dias 1, 3, 8 e 10; no grupo dose única (GU), as lesões foram irradiadas com dose de 4 J/cm2 no dia 1. O grupo controle (GC) não foi irradiado. O fluxo sanguíneo foi monitorado nos dias 3, 8, 10, 15 e 21 e três animais por grupo foram sacrificados nestes momentos. Os grupos irradiados mostraram um pico de vasos neoformados no dia 15, enquanto que o pico do GC foi no dia 21. O número de vasos no GC foi significantemente maior que GF e GU no dia 21. Com relação ao fluxo sangüíneo, os grupos irradiados mostraram um valor mais alto que o controle no dia 8, porém, sem diferenças significantes entre os grupos. Estes achados sugerem que o laser acelera a cicatrização de queimaduras, porém, sem diferenças significativas entre as doses estudadas. / Severe burn injuries cause extensive damage and are notoriously complicated by loss of body fluids, injury in the cutaneous vasculature and delayed wound healing. Low intensity laser therapy (LILT) has been studied as an alternative method since it is a non invasive treatment and is able to accelerate wound healing. The purpose of the present study was to evaluate the effects of LILT (λ = 660 nm) in burned skin with two different doses by histomorphometry and laser Doppler flowmetry. Thirdy six male adult Wistar rats with two burns created on the back using water vapor were divided into 3 groups. In the fractioned dose laser group (GF), the lesions were irradiated with 1 J/cm2 on days 1, 3, 8 and 10; in the single dose laser group (GU), the lesions were irradiated with 4 J/cm2 on day 1. On control group (GC) lesions were not irradiated. The blood flow was measured on days 1, 3, 8, 10, 15 and 21 and three animals per group were sacrificed in these moments. Irradiated groups showed a peak of new blood vessels formation on day 15 while for GC the peak was on day 21. At this moment, the number of vessels in GC was significantly higher than GF and GS. Regarding to blood flux, irradiated groups displayed a higher value than GC on day 8, though no significant differences were observed. These findings suggest that LILT may accelerate skin repair, however, no significant differences were observed between the studied doses.

O presente estudo teve como objetivo avaliar a qualidade da água e o grau de contaminação por metais na água, sedimento e peixes no trecho médio da Bacia do rio Doce, no Estado de Minas Gerais. Para tanto, em fevereiro e setembro de 2001, foram feitas análises físicas, químicas e biológicas de amostras de água e sedimento, testes de toxicidade e análises dos tecidos branquiais de peixes. As amostras de água apresentaram concentrações de amônio e fósforo total mais elevadas que o limite estabelecido pela resolução Conama 20/86 em todos os pontos e períodos de coleta. Maiores valores de condutividade elétrica e de compostos nitrogenados e fosfatados foram verificados no ribeirão Timotinho. Neste local, também foram encontradas as maiores concentrações de material em suspensão, carbono e fenóis totais. Em geral, as amostras de sedimento apresentaram baixos teores de matéria orgânica e maior porcentagem de areia dentre as frações granulométricas, tendo sido verificados os maiores valores de nitrogênio total e fósforo total nas amostras de sedimento do ribeirão Timotinho. As concentrações de metais na água estiveram geralmente acima dos limites máximos estabelecidos pela resolução CONAMA 20/86 para águas classe 2, sendo que os pontos de coleta no ribeirão Timotinho e rio Doce/Cenibra apresentaram concentrações muito acima do estabelecido para a maioria dos metais analisados, nos dois períodos de amostragem. Nas amostras de sedimento, as concentrações de Cr estiveram acima de valores encontrados em regiões não impactadas, em ambos os períodos de amostragem. Nos peixes também foram observadas elevadas concentrações de metais, sendo que Geophagus brasiliensis, Oligosarcus argenteus, Hoplias lacerdae e Loricariichthys castaneus; Leporinus sp e Geophagus brasiliensis apresentaram respectivamente níveis de Cr, Pb e Ni acima do permitido pela legislação, indicando processos de bioconcentração e bioacumulação. Os testes de toxicidade aguda e crônica com amostras de sedimento à Daphnia similis, Chironomus xanthus e Ceriodaphnia silvestrii mostraram maiores efeitos de toxicidade no ribeirão Timotinho e rio Doce/Cenibra. Além disso, foram também verificados efeitos de toxicidade crônica no ribeirão do Turvo, rio Matipó e reservatório de Guilmam-Amorim. As análises dos tecidos branquiais revelaram alterações histopatológicas em Tilapia rendalli (aneurismas) e Rhamdia quelen (fusão lamelar) coletados no ribeirão Timotinho e rio Doce/Cenibra, demonstrando que estas e outras espécies estão seriamente expostas à poluentes. / The present study aimed to evaluate water quality and metals contamination levels in water, sediment and fishes of different sampling sites in the middle Doce river basin in Minas Gerais State. Therefore, in February and September of 2001, physical, chemical and biological analyses of water and sediment samples, toxicity tests and branchial tissues analyses of fishes were carried out. The water samples showed higher ammonium and total phosphorus concentrations than the limit established by CONAMA 20/86 in all sites and sampling periods. Higher electric conductivity and nitrogenous and phosphorus compounds were found in Timotinho stream, where were also found the highest concentrations of suspended matter, carbon and total phenols. In general, the sediment samples presented low organic matter values and higher sand percentage among granulometric fractions, with higher values of total phosphorus and nitrogen being found at Timotinho stream. The concentrations of metals in water were generally above the maximum limit established by CONAMA 20/86 for class 2 waters, with much higher values being found at Timotinho stream and Doce river/Cenibra for most metals determined, in both sampling periods. In the sediment samples, the chromium concentrations were above the values found in unimpacted areas, in both sampling periods. High concentrations of metals were also detected in the fishes. Geophagus brasiliensis, Oligosarcus argenteus, Hoplias lacerdae e Loricariichthys castaneus; Leporinus sp and Geophagus brasiliensis respectively presented chromium, lead and nickel values above the established by legislation, indicating bioconcentration and bioaccumulation processes. The acute and chronic toxicity tests with sediment samples to Daphnia similis, Chironomus xanthus and Ceriodaphnia silvestrii showed more toxicity effects at Timotinho stream and Doce river/Cenibra. Moreover, chronic toxicity effects were also detected at Turvo stream, Matipó river and Guilmam-Amorim reservoir. The branchial tissues analyses revealed histopathological alterations in Tilapia rendalli (aneurisms) and Rhamdia quelen (lamellar fusion) collected at Timotinho stream and Doce river/Cenibra, demonstrating that these and other species are seriously exposed to pollutants.

A Represa Billings apresenta águas eutrofizadas em decorrência da grande quantidade de esgoto proveniente da área urbana próxima, e como conseqüência, os peixes podem representar um problema de saúde pública. As brânquias e o fígado tornam-se órgãos alvo para a ação dos poluentes existentes no meio aquático podendo se manifestar em vários níveis de organização biológica. Estas respostas biológicas ao estresse provocado pelos poluentes podem ser utilizadas para identificar sinais iniciais de danos aos peixes e podem ser denominadas biomarcadores. Desse modo, o presente projeto teve como objetivo a análise histológica de brânquias e fígado de Tilápias do Nilo, por meio de mensurações, Índice de Alterações Histológicas e Valor Médio de Avaliação; também foi realizada a análise da freqüência de micronúcleo. Verficou-se que as Tilápias do Nilo apresentam alterações histológicas das brânquias e do fígado classificadas como moderada a grave, além da presença de micronúcleo. Os resultados permitem um melhor monitoramento ambiental e o controle da qualidade dessa espécie. / The Billings dam shows eutrophic waters due to the large amount of sewage from urban occupation neaby, and consequently, the fish can be a public health problem. The gills and liver become target organs for the action of pollutants in the aquatic environment and may present several levels of biological organization. These biological responses to stress caused by pollutants can be used to identify early signs of damage to fish and can be called biomarkers. Thus, this project aimed to analyze the histological gills and liver of Nile Tilapia, by means of measurements, Histological Alterations Index and Assessment Medium Value; the frequency of micronuclei was done. We observed histological alterations in gills and livers of Nile Tilapia classified as mild to severe, and the presence of micronucleus. The results enable better environmental monitoring and quality control of this species.

Introdução: Alopecia frontal fibrosante (AFF) é um tipo de alopecia cicatricial classificada, atualmente, como uma variante clínica do líquen plano pilar (LPP), afetando o couro cabeludo em um padrão clínico característico e apresentando padrão histológico similar ao LPP. Objetivos: Analisar e comparar as alterações clínico-patológicas e imunopatológicas do LPP e da AFF. Métodos: Neste estudo foram selecionados dez pacientes com AFF e dez com LPP objetivando caracterizar achados clínicos, histológicos e imunológicos. A revisão dos preparados histológicos em cortes longitudinais foi realizada comparando-se infiltrado linfocitário perifolicular, fibrose perifolicular, apoptose nos folículos pilosos, dilatação infundibular, infiltrado linfocitário liquenoide na interface entre a epiderme interfolicular e a derme, e reação granulomatosa tipo corpo estranho. Foram realizados estudos de imunofluorescência direta e imuno-histoquímica para a demonstração da expressão de CD1a, CD3, CD4, CD8, CD68 e IDO (indoleamine 2,3-dioxygenase) em biópsias de pele. Resultados: As principais manifestações clínicas verificadas nos pacientes com AFF incluíram: recesso frontotemporal simétrico e progressivo, ceratose e eritema folicular, pele atrófica desprovida de orifícios foliculares, rarefação dos supercílios e ausência de pelos velus na linha de implantação capilar. Já nos casos de LPP os principais achados clínicos incluíram: envolvimento multifocal e predominantemente difuso do couro cabeludo com presença de eritema, ceratose e descamação perifolicular. A descamação peripilar (80% no LPP e 50% na AFF) e o prurido (60% na AFF e 30% no LPP) foram os sinais e sintomas predominantes em ambas afecções. A histopatologia mostrou achados sobreponíveis entre os casos de LPP e AFF, incluindo alterações vacuolares de interface, infiltrado linfocítico liquenoide perifolicular, fibrose perifolicular, tratos cicatriciais, degeneração de queratinócitos basais e destruição da camada basal. Os achados mais característicos de imunofluorescência direta incluíram a presença de imunofluorescência granulosa moderada e contínua na zona de membrana basal e corpos citoides fluorescentes na derme papilar, principalmente, anti IgM, IgA e IgG presentes no LPP e na AFF. A comparação histopatológica e imunopatológica não mostrou diferenças significativas entre as duas afecções. Conclusão: Embora clinicamente diferentes, nosso estudo não evidenciou diferenças histopatológicas e imunopatológicas entre o líquen plano pilar e a alopecia frontal fibrosante, favorecendo o conceito de tratar-se, em ambos os casos, de aspectos clínicos distintos da mesma doença / Background: Frontal fibrosing alopecia (FFA) is a type of scarring alopecia currently considered as a clinical variant of lichen planopilaris (LPP), affecting the scalp in a distinctive clinical pattern but also presenting both characteristic and similar histological patterns. Objective: Analysing and comparing the clinicalpathological and immunological alterations between LPP and FFA. Methods: For our study, we have selected ten patients, women, with FFA and ten with LPP, so that clinical, histological and immunological findings were better characterized. The analysis of histological preparations in longitudinal sections was performed by comparing the following aspects: perifollicular lymphocytic infiltrate, perifollicular fibrosis, apoptosis in hair follicles, infundibular dilatation, lichenoid lymphocytic infiltrate at the interface between the interfollicular epidermis and the dermis and granulomatous foreign body reaction. Studies of direct immunofluorescence and immunohistochemistry were executed for demonstrating the expression of CD1a, CD3, CD4, CD8, CD68 and IDO (2,3-dioxygenase indoleamine) in skin specimens. Results: The main clinical manifestations observed in the studied patients with AFF include: symmetrical and progressive frontotemporal recession, follicular keratosis and erythema, atrophic skin devoid of hair follicles, thinning eyebrows and absence of vellus hair in the hairline. Concerning LPP cases, the mais clinical manifestations include multifocal and predominantly diffuse scalp involvement with the presence of erythema, perifolicular keratosis and scales. The associated signs and symptoms, for patients with LPP the main findings were perifollicular scale (80% and 50% LPP AFF) and pruritus (60% and 30% AFF LPP). The histopathology of both diseases showed overlapping findings, including interface vacuolar changes, perifollicular lichenoid lymphocytic cell infiltrate, hypergranulosis, hyperkeratosis, hyperacanthosis, degeneration of basal keratinocytes and destruction of the basal layer. The most common immunofluorescence findings of the patients were the presence of continuous and moderate granulous immunofluorescence in the basement membrane zone and cytoid fluorescent bodies in the papillary dermis mainly anti IgG, IgM and IgG present in the LPP and AFF. The immunohistochemical studies showed no significant difference in the two entities. Conclusion: Although clinically distinct, our study has not demonstrated neither histological nor immunological differences between lichen planopilaris and frontal fibrosing alopecia, sustaining, therefore, the concept of both cases being different clinical aspects of the same disease

A lesão de isquemia/reperfusão(I/R) do intestino delgado é de importância fundamental em procedimentos cirúrgicos. Alguns radicais livres de oxigênio gerados atuam durante este período. Utilizamos o ácido ascórbico para atenuar as lesões de I/R. Cinqüenta ratos foram separados e cinco grupos, cada grupo com 10 ratos. Os grupos foram sumetidos à isquemia mesentérica e isquemia/reperfusão. Os grupos experimentos receberam ácido ascórbico. Foi realizada a análise histológica morfométrica. Os grupos com ácido ascórbico mostraram uma redução significativa do infarto anti-mesentérico. (p = 0,009) na isquemia/reperfusão e redução da necrose das vilosidades na isquemia. O ácido ascórbico é eficaz na redução dos danos intestinais causados pela I/R em ratos / Intestinal injury resulting from ischemia-reperfusion (I/R) is of fundamental importance in surgical procedures. Some oxygen-derived free radicals generated during this time possibly play an important role. We used ascorbic acid to attenuate I/R injury. Fifty male rats were divided into five groups, each containing 10 rats. The groups were submitted to mesenteric ischemia and ischemia/reperfusion, experimental groups received ascorbic acid. The intestinal histological morphometric analysis was performed. The ascorbic acid groups showed a significant reduction of antimesenteric villous infarct (p=0,009) in the /R and reduction of villous necrosis ischemia groups. The ascorbic acid is effective in reducing the intestinal damage caused by I/R in the rats

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5.4pt;mso-para-margin-top:0in;mso-para-margin-right:0in;mso-para-margin-bottom:10.0pt;mso-para-margin-left:0in;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"Times New Roman";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;}</style><![endif]--></p><p class="MsoNormal" style="text-align:justify">Uvod: Aristolohična kiselina I je nefrotoksična i kancerogena supstanca koja je odgovorna za nefropatiju koja nastaje usled kori&scaron;ćenja herbalnih preparata i čajeva za mr&scaron;avljenje. S obzirom da se ova supstanca može naći u korovskim biljkama, smatra se jednim od glavnih ekotoksikolo&scaron;kih uzroka za nastanak balkanske endemske nefropatije čiji definitivan uzrok jo&scaron; uvek nije otkriven. Toksičnost ove supstance je dokazana na brojnim animalnim modelima, međutim mehanizmi koji dovode do o&scaron;tećenja bubrežnog parenhima jo&scaron; u potpunosti nisu razja&scaron;njeni.<span style="mso-spacerun:yes">&nbsp; </span>Cilj: Doktorska disertacija je koncipirana sa ciljem da se utvrdi uticaj toksičnog jedinjenja aristolohične kiseline I na histopatolo&scaron;ke i imunohistohemijske karakteristike tubulointersticijuma i glomerula bubrega kod mi&scaron;eva, kao i na biohemijske parametre krvi i urina koji ukazuju na o&scaron;tećenje bubrega. Materijal i metode: U ekperimentu je kori&scaron;ćeno 64 mi&scaron;a soja NMRI koji su podeljeni u tri grupe: eksperimentalna grupa (n=32) koja je dobijala aristolohičnu kiselinu I rastvorenu u polietilen glikolu (2,5% PEG 400) u dozi od 10 mg/kg telesne mase, negativna kontrolna grupa koja je dobijala 2,5% PEG 400 (n=16) i kontrolna grupa koja je dobijala fiziolo&scaron;ki rastovor (n=16). Sve životinje su tretirane intraperitonealno svakodnevno tokom sedam dana. Tokom eksperimenta 8., 17., 29. i 59. dana sakupljan je dvadesetčetvoročasovni urin 8 životinja iz eksperimentalne grupe, 4 životinje iz negativne kontrolne i 4 životinje iz kontrolne grupe. Životinje su žrtvovane 9., 18., 30. i 60. dana, uzeta im je krv, dok su bubrezi posebno odvojeni radi histopatolo&scaron;ke analize. Na bubrežnom tkivu sprovedene su histohemijske, imunohistohemijske i morfometrijske analize, dok su na uzorcima seruma i urina sprovedene biohemijske analize. Dobijeni rezultati su testirani adekvatnim statističkim metodama i prikazani su tabelarno i grafički. Rezultati: Nefrotoksin aristolohična kiselina I nakon 7 dana aplikacije izaziva značajno o&scaron;tećenje bubrežnog parenhima. Pri aplikaciji 2,5% PEG 400 i fiziolo&scaron;kog rastvora ne dolazi do vidljivog o&scaron;tećenja bubrežnog parenhima. Histopatolo&scaron;ku sliku u ranoj fazi eksperimenta (9. i 18. dan) karakteri&scaron;e akutna tubulska nekroza proksimalnih tubula. U kasnijoj fazi (30. i 60. dana) uočava se histopatolo&scaron;ka slika hroničnog intersticijalnog nefritisa sa obilnim mononuklearnim ćelijskim infiltratima limfocitnog porekla kao i postojanje blage intersticijalne fibroze. Kod eksperimentalnih životinja je morfometrijskim metodama utvrđen veći stepen bubrežnog o&scaron;tećenja tubulointersticijuma i smanjen broj podocita u glomerulu u odnosu na kontrolne grupe. Biohemijske analize kod većine eksperimentalnih životinja su pokazale veće koncentracije serumske uree nego kod kontrolnih grupa. Takođe je dokazana albuminurija u kasnijoj fazi eksperimenta koja je veća kod životinja izloženih aristolohičnoj kiselini I nego kod životinja iz kontrolnih grupa. Zaključak: Kori&scaron;ćenjem morfometrijskih metoda u okviru histopatolo&scaron;kih i imunohistohemijskih ispitivanja, uz adekvatne biohemijske analize, može se zaključiti da je aristolohična kiselina I izuzetno nefrotoksično jedinjenje koje izaziva izrazite<span style="mso-spacerun:yes">&nbsp; </span>promene tubulointersticijuma i glomerula. Podaci ovog istraživanja predstavljaju polaznu osnovu za dalja istraživanja dijagnostike u ranoj fazi nefropatija izazvanih aristolohičnim kiselinama.<span style="mso-spacerun:yes">&nbsp; </span></p> / <p>Introduction: Aristolochic acid I is a nephrotoxic and carcinogenic substance responsible for nephropathy caused by the use of herbal preparations and teas for slimminng regimen. Since this substance can be found in plants, it is considered one of the major ecotoxicological causes for the emergence of balkan endemic nephropathy whose definitive cause has not yet been revealed. The toxicity of this substance has been proven on numerous animal models, but pathophysiological mechanisms of kidney injury still remain unclear. Aim: The doctoral dissertation was designed to determine the influence of aristolochic acid on the histopathological and immunohistochemical characteristics of tubulointerstitium and glomerulus in mice, as well as the biochemical parameters of blood and urine that indicate kidney injury. Material and methods: For this study, 64 mouse of NMRI strain is used. They are divided into three groups: an experimental group (n=32) that received aristolochic acid I dissolved in polyethylene glycol (2.5% PEG 400) at a dose of 10 mg/kg of body weight, a negative control group that received 2.5% PEG 400 (n=16) and a control group that received only saline (n=16). All animals were treated intraperitoneally daily for seven days. During the experiment on the 8th, 17th, 29th and 59th day, twenty-four-hour urine was collected from 8 animals from the experimental group, 4 animals from the negative control and 4 animals from the control group. Animals were sacrificed on the 9th, 18th, 30th and 60th days, their blood was taken, while the kidneys were taken for histopathological analysis. Histochemical, immunohistochemical and morphometric analyzes were performed on renal tissue, while biochemical analyzes were performed on serum and urine samples. Obtained results were tested with adequate statistical methods and presented in a tables and graphs. Results: After 7 days of application nefrotoxin aristolochic acid I causes significant kidney injury. After application of 2.5% PEG 400 and saline, there was no visible damage to kidney parenchyma. Histopathological changes at the early stage of the experiment (9th and 18th day) were characterized by acute tubular necrosis of proximal tubules. At a later stage (30th and 60th day), chronic interstitial nephritis was observed in kidneys, with abundant mononuclear cell infiltrates in interstitium and presence of mild interstitial fibrosis. In experimental animals, a higher tubulointerstitial score of kidney injury and a decrease in the number of the podocytes in glomerulus were determined by morphometric methods, compared to the control groups. Biochemical analyzes in most experimental animals showed higher blood urea nitrogen concentrations than in control groups. High concentration of albumin in urine can be found in later stages of the experiment, and those concentrations were higher in animals exposed to aristolochic acid I than in animals from control groups.&nbsp; Conclusion: Using morphometric, histopathological and immunohistochemical methods, with adequate biochemical analysis, aristolochic acid I is proven to be an extremely nephrotoxic compound that causes drastic changes in tubulointerstitium and glomeruli of kidney parenhyma. Data from this study can be used for further research into early diagnosis of aristolochic acid nephropathy.</p>

A lesão de isquemia/reperfusão(I/R) do intestino delgado é de importância fundamental em procedimentos cirúrgicos. Alguns radicais livres de oxigênio gerados atuam durante este período. Utilizamos o ácido ascórbico para atenuar as lesões de I/R. Cinqüenta ratos foram separados e cinco grupos, cada grupo com 10 ratos. Os grupos foram sumetidos à isquemia mesentérica e isquemia/reperfusão. Os grupos experimentos receberam ácido ascórbico. Foi realizada a análise histológica morfométrica. Os grupos com ácido ascórbico mostraram uma redução significativa do infarto anti-mesentérico. (p = 0,009) na isquemia/reperfusão e redução da necrose das vilosidades na isquemia. O ácido ascórbico é eficaz na redução dos danos intestinais causados pela I/R em ratos / Intestinal injury resulting from ischemia-reperfusion (I/R) is of fundamental importance in surgical procedures. Some oxygen-derived free radicals generated during this time possibly play an important role. We used ascorbic acid to attenuate I/R injury. Fifty male rats were divided into five groups, each containing 10 rats. The groups were submitted to mesenteric ischemia and ischemia/reperfusion, experimental groups received ascorbic acid. The intestinal histological morphometric analysis was performed. The ascorbic acid groups showed a significant reduction of antimesenteric villous infarct (p=0,009) in the /R and reduction of villous necrosis ischemia groups. The ascorbic acid is effective in reducing the intestinal damage caused by I/R in the rats