Desquamation Is A Novel Phenomenon For Collective Prostate Epithelial Cell Deletion After Castration.

The mechanism underlying castration-induced prostate regression, which is a classical physiological concept translated into the therapeutic treatment of advanced prostate cancer, involves epithelial cell apoptosis. In searching for events and mechanisms contributing to prostate regression in response to androgen modulation, we have frequently observed the collective deletion of epithelial cells. This work was undertaken to characterize this phenomenon hereafter named desquamation and to verify its presence after 17β-estradiol (E2) administration. Electron microscopy revealed that the desquamating cells had preserved cell-cell junctions and collapsed nuclear contents. The TUNEL reaction was negative for these cells, which were also negative for cleaved caspases-8, -9, -3 and nuclear apoptosis-inducing factor. Detailed analyses revealed that the condensed chromatin was first affected detaching from the nuclear lamina, which was observable after lamin A immunohistochemistry, suggesting the lack of lamin A degradation. A search in animals treated with supraphysiological E2 employed as an alternative anti-androgen treatment revealed no desquamation. The combined treatment (Cas + E2 group) caused changes particular to each treatment, including desquamation. In conclusion, desquamation appeared as a novel phenomenon contributing to collective prostate epithelial cell deletion, distinct from the classical castration-induced apoptosis and particular to the androgen deprivation resulting from surgical castration, and should be considered as part of the mechanisms promoting organ regression.

Antioxidant And Antiproliferative Activities Of Methanolic Extract From A Neglected Agricultural Product: Corn Cobs.

Neglected agricultural products (NAPs) are defined as discarded material in agricultural production. Corn cobs are a major waste of agriculture maize. Here, a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro and in vivo antioxidant potential of MEC. Furthermore, its antiproliferative property against tumor cells was assessed through MTT assays and proteins related to apoptosis in tumor cells were examined by western blot. MEC showed no hydroxyl radical scavenger capacity, but it showed antioxidant activity in Total Antioxidant Capacity and DPPH scavenger ability assays. MEC showed higher Reducing Power than ascorbic acid and exhibited high Superoxide Scavenging activity. In tumor cell culture, MEC increased catalase, metallothionein and superoxide dismutase expression in accordance with the antioxidant tests. In vivo antioxidant test, MEC restored SOD and CAT, decreased malondialdehyde activities and showed high Trolox Equivalent Antioxidant Capacity in animals treated with CCl4. Furthermore, MEC decreased HeLa cells viability by apoptosis due an increase of Bax/Bcl-2 ratio, caspase 3 active. Protein kinase C expression increased was also detected in treated tumor cells. Thus, our findings pointed out the biotechnological potential of corn cobs as a source of molecules with pharmacological activity.

Suplementação com caldo de cana de açucar comparado com outros carboidratos na reposição do glicogenio e cinetica de biomarcadores pos-exercicio agudo em ratos

Universidade Estadual de Campinas . Faculdade de Educação Física

Bone quality associated with daily intake of coffee: a biochemical, radiographic and histometric study

Caffeine induces loss of calcium and influences the normal development of bone. This study investigated the effects of coffee on bone metabolism in rats by biochemical measurement of calcium, bone densitometry and histometry. Male rats, born of female treated daily with coffee and with coffee intake since born, were anesthetized, subjected to extraction of the upper right incisor, and sacrificed 7, 21 and 42 days after surgery. Blood and urine samples were taken, and their maxilla radiographed and processed to obtain 5-µm-thick semi-serial sections stained with hematoxylin and eosin. The volume and bone quality were estimated using an image-analysis software. The results showed significantly greater amount of calcium in the plasma (9.40 ± 1.73 versus 9.80 ± 2.05 mg%) and urine (1.00 ± 0.50 versus 1.25 ± 0.70 mg/24 h) and significantly less amount in bone (90.0 ± 1.94 versus 86.0 ± 2.12 mg/mg bone), reduced bone mineral density (1.05 ± 0.11 versus 0.65 ± 0.15 mmAL), and lower amount of bone (76.19 ± 1.6 versus 53.41 ± 2.1 %) (ANOVA; p≤0.01) in animals treated with coffee sacrificed after 42 days. It may be concluded that coffee/caffeine intake caused serious adverse effects on calcium metabolism in rats, including increased levels of calcium in the urine and plasma, decreased bone mineral density and lower volume of bone, thus delaying the bone repair process.

Correlação entre as escalas visual analógica, de Melbourne e filamentos de Von Frey na avaliação da dor pós-operatória em cadelas submetidas à ovariossalpingohisterectomia

A avaliação da dor em animais necessita da utilização de escalas de avaliação, que dependem da interpretação realizada por observadores. O objetivo do presente estudo foi avaliar a correlação entre a escala visual analógica (EVA), escala de Melbourne e os filamentos de Von Frey, na avaliação da dor pós-operatória em 42 cadelas adultas e saudáveis, submetidas à ovariossalpingohisterectomia (OSH). A dor pós-operatória foi avaliada por dois observadores cegos aos tratamentos analgésicos, em intervalos de uma hora, utilizando a EVA, a escala de Melbourne e os filamentos de Von Frey, aplicados ao redor da incisão cirúrgica. Foram considerados como critérios para realização da analgesia resgate uma pontuação de 50mm na EVA ou de 13 pontos na escala de Melbourne. A EVA revelou-se a escala mais sensível, uma vez que 100% dos animais receberam resgate seguindo esse método. Os valores obtidos na EVA e na escala de Melbourne determinaram boa correlação, com r=0,74, o que não ocorreu com os filamentos de Von Frey (r=-0,18). Já a correlação entre a escala de Melbourne e os filamentos de Von Frey foi de -0.37. Apesar de a EVA e a escala de Melbourne apresentarem boa correlação, sugere-se que se considere uma pontuação menor na escala de Melbourne como critério para administração de analgesia resgate.

Avaliação da cicatrização de feridas em dorso de ratos tratados com mitomicina C tópica e posterior reforço com injetável

Estudo experimental em animais. A mitomicina C vem sendo usada como inibidor de fibroblastos, acarretando, com isso, diminuição do processo cicatricial em feridas cirúrgicas. OBJETIVO: Este trabalho visa avaliar o uso de Mitomicina C para diminuir o processo cicatricial, através de seu uso tópico com reforços posteriores injetáveis. MATERIAL E MÉTODOS: Foi usado um modelo de feridas em dorso de ratos, com retirada circular da pele e cicatrização por segunda intenção. Foram usados 18 ratos, divididos em três grupos: controle; com uso tópico; e com reforço de mitomicina C injetável, mensalmente e por 2 meses. Após 3 meses os animais foram sacrificados e as cicatrizes retiradas cirurgicamente e submetidas a estudo histológico. RESULTADOS: Notou-se sob vários critérios que a cicatrização com o uso tópico é menos intensa, mas ao se usar o reforço injetável os parâmetros voltam a ser comparados ao do grupo controle. DISCUSSÃO: Acreditamos que a administração injetável de mitomicina C nas cicatrizes, pela sua elevada característica tóxica, acarreta destruição tecidual e neoformação cicatricial. CONCLUSÕES: A mitomicina C diminui o processo cicatricial quando usada topicamente, mas acarreta aumento da cicatrização quando nestas feridas são feitos reforços injetáveis.

Medidas murinométricas e eficiência alimentar em ratos provenientes de ninhadas reduzidas na lactação e submetidos ou não ao exercício de natação

INTRODUÇÃO: Excesso de alimentação no início da vida pode modificar persistentemente consumo e peso corporal. Adoção de exercício físico é uma estratégia útil para evitar excessivo ganho de peso. OBJETIVO: Avaliar o crescimento corporal e a eficiência alimentar em ratos provenientes de ninhada reduzida no aleitamento. MÉTODOS: Ao terceiro dia de vida, ninhadas foram formadas com quatro (GN4) ou 10 animais (GN10), (n = 25). Ao desmame, ratos machos Wistar permaneceram em gaiolas individuais, e, aos 60 (± 2) dias foram subdivididos em sedentários (SED) e exercitados (NAT), formando quatro grupos: GN4SED, GN10SED, GN4-NAT e GN10NAT. Avaliou-se o peso, ganho de peso e taxa específica de ganho de peso, gordura epididimal, índices de massa corporal e Lee, consumo e eficiência alimentar, glicemia e lactemia. RESULTADOS: Aos 21 dias, o GN4 apresentava peso corporal 52% acima do GN10 (P = 0,001). Contudo, aos 30 e 60 dias os pesos não diferiram. Ao final do período, GN10NAT demonstrou menor peso (356,82 ± 23,04) que GN10SED (409,28 ± 17,30). Mas GN4NAT possuía maior peso (417,85 ± 37,91) que GN4SED (413,69 ± 57,45) e GN10NAT. O GN4 exibiu elevada taxa de ganho de peso na lactação, mas, redução da mesma pós-desmame. Independente do tamanho da ninhada, a taxa de ganho de peso reduz com o aumento da idade. Ao final do período, glicemia, gordura epididimal total e relativa, e os índices de Lee e IMC não diferiram entre os grupos. Os valores de lactato antes e após o exercício condizem com esforço de intensidade moderada. Na periadolescência, GN4 apresentou menor ingestão de alimentos, mas sem diferenças na vida adulta. CONCLUSÃO: A redução da ninhada no aleitamento não alterou o peso corporal ou ingestão alimentar persistentemente. Entretanto, o protocolo de natação foi eficaz em reduzir o ganho de peso em animais controles, mas não naqueles de ninhada reduzida.

Aerobic and anaerobic metabolism for the zebrafish, Danio rerio, reared under normoxic and hypoxic conditions and exposed to acute hypoxia during development

In order to verify the influence of chronic and acute ambient oxygen levels from egg to adult stage of the zebrafish, in vivo oxygen consumption (MO2), critical tensions of oxygen (Pcrit), heart rate (fH) and total body lactate concentration (Lc) were determined for Danio rerio (Hamilton, 1822) raised at 28 °C under normoxic (7.5 mgO2.L-1 or 80 mm.Hg-1) and hypoxic conditions (4.3 mgO2.L-1) and exposed to acute hypoxia during different developmental stages. Our findings confirmed that very early stages do not respond effectively to ambient acute hypoxia. However, after the stage corresponding to the age of 30 days, D. rerio was able to respond to acute hypoxia through effective physiological mechanisms involving aerobic and anaerobic metabolism. Such responses were more efficient for the fishes reared under hypoxia which showed that D. rerio survival capability increased during acclimation to mild hypoxia. Measurements of body mass and length showed that moderate hypoxia did not affect growth significantly until the fish reached the stage of 60 days. Moreover, a growth delay was verified for the hypoxic-reared animals. Also, the D. rerio eggs-to-larvae survival varied from 87.7 to 62.4% in animals reared under normoxia and mild hypoxia, respectively. However, the surviving animals raised under moderated hypoxia showed a better aptitude to regulate aerobic and anaerobic capacities when exposed to acute hypoxia.

Mecanismos de ação de compostos bioativos dos alimentos no contexto de processos inflamatórios relacionados à obesidade

É indiscutível o papel da dieta e dos alimentos na manutenção da saúde e na redução do risco de DCNT. Estudos epidemiológicos mostram que o aumento do consumo de alimentos de origem vegetal influencia positivamente a saúde, enquanto estudos in vitro e in vivo em modelo animal elucidam os mecanismos pelos quais compostos bioativos não nutrientes, presentes nos alimentos, atuam na manutenção da saúde e na redução do risco de doenças. A modulação da expressão de genes que codificam proteínas envolvidas em vias de sinalização celular ativadas em DCNT é um dos mecanismos de ação dos compostos bioativos, sugerindo que estes possam ser essenciais à manutenção da saúde. A biodisponibilidade dos compostos bioativos de alimentos, as suas rotas metabólicas e o modo de ação de seus metabólitos são importantes fatores no seu efeito nas DCNT. Todos esses aspectos são temas de investigações recentes, cujos resultados contribuem para a compreensão da ocorrência e desenvolvimento das DCNT e da sua relação com a dieta. Essa revisão visou discutir alguns dos mecanismos envolvidos na resposta inflamatória induzida pela obesidade, apresentar os compostos bioativos de alimentos que modulam essa resposta inflamatória e sua relação com o metabolismo desses compostos.

Vitamina D e doenças endocrinometabólicas

Atualmente, a insuficiência/deficiência de vitamina D tem sido considerada um problema de saúde pública no mundo todo, em razão de suas implicações no desenvolvimento de diversas doenças, entre elas, o diabetes melito tipo 2 (DMT2), a obesidade e a hipertensão arterial. A deficiência de vitamina D pode predispor à intolerância à glicose, a alterações na secreção de insulina e, assim, ao desenvolvimento do DMT2. Esse possível mecanismo ocorre em razão da presença do receptor de vitamina D em diversas células e tecidos, incluindo células-β do pâncreas, no adipócito e no tecido muscular. Em indivíduos obesos, as alterações do sistema endócrino da vitamina D, caracterizada por elevados níveis de PTH e da 1,25(OH)2D3 são responsáveis pelo feedback negativo da síntese hepática de 25-OHD3 e também pelo maior influxo de cálcio para o meio intracelular, que pode prejudicar a secreção e a sensibilidade à insulina. Na hipertensão, a vitamina D pode atuar via sistema renina-angiotensina e também na função vascular. Há evidências de que a 1,25(OH)2D3 inibe a expressão da renina e bloqueia a proliferação da célula vascular muscular lisa. Entretanto, estudos prospectivos e de intervenção em humanos que comprovem a efetividade da adequação do status da vitamina D sob o aspecto "prevenção e tratamento de doenças endocrinometabólicas" são ainda escassos. Mais pesquisas são necessárias para se garantir o benefício máximo da vitamina D nessas situações.

Electrocardiographic study on geriatric dogs undergoing general anesthesia with isoflurane

The purpose of this study was to clarify the degree of influence of anesthetic agents commonly used during anesthesia on the heart conduction systems of geriatric dogs, with or without the presence of electrocardiographic changes in the pre-anesthetic electrocardiogram and also to determine the possible causes of ST-segment and T-wave changes during anesthesia, by monitoring ventilation and oxygenation. 36 geriatric dogs were evaluated. In addition to electrocardiographic evaluation, the pre-anesthetic study included serum levels of urea, creatinine, total protein, albumin and electrolytes. The pre-anesthetic medication consisted of acepromazine (0.05mg kg-1) in association with meperidine (3.0mg kg-1) by IM injection. Anesthesia was induced with propofol (3.0 to 5.0mg kg-1) by IV injection and maintained with isoflurane in 100% oxygen. During the anesthesia, the animals were monitored by continued computerized electrocardiogram. Systemic blood pressure, heart rate, respiratory rate, end-tidal carbon dioxide, partial pressure of carbon dioxide in arterial blood, arterial oxygen saturation, partial pressure of arterial oxygen and oxygen saturation of hemoglobin were closely monitored. During maintenance anesthesia, normal sinus rhythm was more common (78%). ST-segment and T-wave changes during the anesthetic procedure were quite common and were related to hypoventilation. The use of isoflurane did not result in arrhythmia, being therefore a good choice for this type of animal; Electrocardiographic findings of ST-segment and T-wave changes during the maintenance anesthesia were evident in animals with hypercapnia, a disorder that should be promptly corrected with assisted or controlled ventilation to prevent complicated arrhythmias.

Anticorpos anti-rickettsias do grupo da febre maculosa em equídeos e caninos no norte do Estado do Paraná, Brasil

The Brazilian Spotted Fever (BSF) is a zoonosis that can be fatal if not trteated. As there are few studies of the BSF in the Paraná State, the occurrence of BSF was serologically investigated in dogs and horses by indirect immunofluorescence assay (IFA), in the North of that State, in animals that are regarded as sentinels for BSF. A total of 241 samples of sera of equine, four of asinine, and 29 of dogs were collected in nine farms of three municipalities in the North of Paraná: Arapongas, Douradina, and Umuarama. From fifteen samples of equine serum with positive titres for RIFI, eight (53.3 %) had titre of 64 against R. rickettsii, two (13.3 %) 128 against R. rickettsii, and five (33.3 %) were reactants for R. parkeri and R. rickettsii, with titres ranging from 64 to 2048, and 128 to 1024, respectively. The results showed that domestic animals, sentinels for BSF, are under low exposition to ticks infected with spotted fever group Rickettsia, indicating low risk of human infection by these agents in the studied area.

Hematological profile of Chelonia mydas (Testudines, Cheloniidae) according to the severity of fibropapillomatosis or its absence

The green turtle Chelonia mydas feeds and nests in the Brazilian coastal area and is considered an endangered species by the World Conservation Union (IUCN 2009) and threatened by the Red List of Brazilian Fauna (Ministério do Meio Ambiente 2009). Fibropapillomatosis is a disease characterized by benign skin tumors (fibropapillomas), and it is one of the main threats to the survival of this species. Studies suggest the involvement of viruses as infectious agents associated with environmental and genetic factors. Blood samples were collected from 45 turtles captured in the coastal area of the state of Sao Paulo, Brazil. From these, 27 were affected by fibropapillomas and 18 were tumor free. Biometrical data on the turtles, size, location and quantity of tumors were recorded. The area occupied by fibropapillomas per animal was calculated and four groups were determined according to severity of the disease or its absence. The objective of the study was to compare hemogram results of the sea turtles classified in these four groups. The lowest hematocrit value was observed in severely affected animals. In the hemoglobin assay, the highest value was observed in the group of tumor free turtles and the lowest, in animals severely affected. Lymphocyte counts and curved carapace length were on the verge of statistical significance.

BALB/c Mice Infected with Antimony Treatment Refractory Isolate of Leishmania braziliensis Present Severe Lesions due to IL-4 Production

Background: Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis-infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. Methodology/Principal Findings: Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-gamma, TNF-alpha, IL-10 and TGF-beta were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). Conclusion/Significance: We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention.

Cortisol plasmático como indicador de estresse em colopexias laparoscópicas com implante de tela de polipropileno em cães

The realization of conventional surgical procedures, even using the recommended doses of analgesics drugs, generally are associated with a long recovery period, post-surgical trauma, stress and pain in animals. That can vary according with the procedure, extension and time of the surgery. Considering the increased interest in procedures that minimize surgical stress and the recovery period after the surgical procedure in dogs, this present work was developed to evaluate a new technique of laparoscopic colopexy with the alterations of cortisol levels, heart rate and respiratory frequencies in dogs. For this study, nine female dogs were submitted to a colopexy. Blood samples and data of heart rate and respiratory frequency were sampled in intervals of 10min. from the preoperative period until the end of the procedure. After, these parameters were assessed every three hours for 12 hours. Cortisol levels were measured using an ELISA Kit for cortisol. Results were analyzed by ANOVA and comparisons were made using Tukey's test. Significance levels was set at p <= 0.05. The increase of the heart rate, respiratory frequency and cortisol levels were mainly observed in the period after shaving and after the end of the anesthesia. Values were kept stable during all the surgery, and coming to the basal conditions after nine hours in the post-operative period. The laparoscopic colopexy is a stress-associated surgery, but it produces lower increasing of cortisol levels returning to normal in 9 hours after the surgery.