OBJECTIVE: Cigarette smoking is the main risk factor for bladder cancer development. Among the mediators of this effect of smoking is nuclear factor-kappa B. Curcumin suppresses cellular transformation by downregulating the activity of nuclear factor-kappa B. Prima-1 is a compound that induces apoptosis in human tumor cells, restoring the function of mutant p53. Our study aimed to evaluate the effects of curcumin and prima-1 in an animal model of bladder cancer. METHODS: Tumor implantation was achieved in six- to eight-week-old female C57BL/6 mice by introducing MB49 bladder cancer cells into the bladder. Intravesical treatment with curcumin and Prima-1 was performed on days 2, 6, 10, and 14. On day 15, the animals were sacrificed. Immunohistochemistry was used to determine the expression of cyclin D1, Cox-2, and p21. Cell proliferation was examined using PCNA. RESULTS: Animals treated with curcumin exhibited a higher degree of necrosis than animals in other groups. Immunohistochemistry showed reduced expression of cyclin D1 in the curcumin-treated group. All of the cells in mice treated with curcumin were p21 positive, suggesting that the p53 pathway is induced by this compound. Prima-1 did not induce any change in tumor size, necrosis, cell proliferation, or the expression of proteins related to the p53 pathway in this animal model. CONCLUSION: Curcumin showed activity in this animal bladder cancer model and probably acted via the regulation of nuclear factor-kappa B and p53. Therefore, curcumin is a good choice for the use in clinical trials to treat superficial bladder cancer as an alternative to bacillus Calmette-Guerin. In contrast, Prima-1 does not seem to have an effect on bladder cancer.
The acute phase of Trypanosoma cruzi infection is associated with a strong inflammatory reaction in the heart characterised by a massive infiltration of immune cells that is dependent on the T. cruzi strain and the host response. 15d-PGJ2 belongs to a new class of anti-inflammatory compounds with possible clinical applications. We evaluated the effects of 15d-PGJ2 administered during the acute phase of T. cruzi infection in mice. Mice were infected with the Colombian strain of T. cruzi and subsequently treated with 15d-PGJ2 repeatedly for seven days. The inflammatory infiltrate was examined by histologic analysis. Slides were immunohistochemically stained to count the number and the relative size of parasite nests. Infection-induced changes in serum cytokine levels were measured by ELISA. The results demonstrated that treatment with 15d-PGJ2 reduced the inflammatory infiltrate in the skeletal muscle at the site of infection and decreased the number of lymphocytes and neutrophils in the blood. In addition, we found that 15d-PGJ2 led to a decrease in the relative volume density of amastigote nests in cardiac muscle. T. cruzi-infected animals treated with 15d-PGJ2 displayed a statistically significant increase in IL-10 levels with no change in IFN-γ levels. Taken together, we demonstrate that treatment with 15d-PGJ2 in the acute phase of Chagas disease led to a controlled immune response with decreased numbers of amastigote nests, as measured by the volume density.
PURPOSE: Hyperbaric oxygen therapy (HOT) consists of intermittent inhalations of 100% oxygen at a pressure higher than 1 atm. It is an important adjuvant therapy in pathological processes like soft tissue infections, radiation injury, gas gangrene, osteomyelitis and decompressive diseases. Cisplatin, a potent antineoplastic drug, widely used in cancer therapy is highly ototoxic causing bilateral, irreversible damage to the hearing of high frequency sounds (4-8 KHz). OBJECTIVE:This experimental study conducted at the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo aims to evaluate Hyperbaric Oxygen Therapy as an otoprotection agent against drug toxicity. METHODS: Albino guinea pigs were divided into two groups: in Group A, 5 animals (10 cochlea) received cisplatin, i. p., 8.0 mg/kg/day during three days and afterwards were submitted to HOT; in Group B, 3 animals (6cochlea) received cisplatin, i. p. 8.0mg/kg/day during three days. Guinea pigs were evaluated by acoustic otoemissions (AOE) and scanning electron microscopy (SEM). RESULTS: Group B animals showed loss of auditory functions as measured by AOE and distorted outer hair cells by SEM. In Group A, outer hair cells shown by SEM images were mostly preserved. CONCLUSION: It is presumed that Hyperbaric Oxygen Therapy has a protector effect against cisplatin ototoxicity.
INTRODUÇÃO: A Oxigenoterapia hiperbárica (OHB) envolve a inalação de oxigênio a 100% sob uma pressão maior que 1 atm. E um importante modo de terapia adjuvante para processos patológicos, tais como: infecção de partes moles, lesões actínicas, gangrena gasosa, osteomielite e doença descompressiva. A cisplatina e uma potente droga antineoplásica largamente utilizada para o tratamento de câncer. A ototoxicidade e um importante efeito colateral desta droga, causando dano irreversível, bilateral, na capacidade de ouvir sons de alta freqüência (4 - 8 KHz). Este estudo experimental, realizado na Faculdade de Medicina de Ribeirao Preto da Universidade de São Paulo nos anos de 2005 e 2006. Objetivo: Avaliar o papel da Oxigenoterapia Hiperbárica como agente otoprotector contra a toxicidade de drogas. MÉTODOS: Cobaias albinas divididas em 2 grupos Grupo A: com 5 cobaias (10 cócleas) que receberam cisplatina 8,0 mg/kg/dia, via intraperitoneal por 3 dias, submetidas posteriormente a OHB. Grupo B: com 3 cobaias (6 cócleas) que receberam cisplatina 8,0 mg/kg/dia, via intraperitoneal por 3 dias. As cobaias foram avaliadas através de otoemissões acústicas (OEA) e por microscopia eletrônica de varredura (MEV). Resultados: Encontramos no grupo B perda da função auditiva medida pela OEA e distorção das células ciliares externas a MEV. No grupo A, a MEV as células ciliares externas foram preservadas em sua grande maioria. CONCLUSÃO: Assim podemos supor que a Oxigenoterapia Hiperbárica tem um efeito otoprotetor contra a ototoxicidade induzida pela cisplatina.
PURPOSE: The pneumoperitoneum causes several physiological alterations in humans. Some of these alterations, as hypercapnia and acidosis, are dependent on the use of CO2 or aggravated by its use, and affects mainly the patients with cardiopulmonary problems. The need for a better alternative of cavity insufflation; the observation that open surgeries, as well as the laparoscopic surgeries with mechanical lifting devices are performed in the presence of environmental air; and the shortage of studies investigating the air insufflation as an alternative to CO2 cavity insufflation, were the reasons for carrying out the present work. METHODS: Twenty pigs under anesthesia were submitted to pneumoperitoneum in an hour procedure. The animals were divided in 4 groups of 5 animals: A1 Group - Air Pneumoperitoneum at 10 mmHg; A2 Group - Air Pneumoperitoneum at 16 mmHg; B1 Group - CO2 Pneumoperitoneum at 10 mmHg; B2 Group - CO2 Pneumoperitoneum at 16 mmHg. The pneumoperitoneum was performed by open technique using Hasson trocar. Through a central venous blood catheter, venous blood was collected three times to gas analysis. RESULTS: The blood gas analysis didn't show significant changes related to PaO2 and O2 saturation among the groups. In the Groups A1, A2 and B1, changes related to the acid-basic balance were not observed. In the Group B2 there was a clear tendency to hypercapnia and acidosis after an hour of pneumoperitoneum procedure. CONCLUSION: The air was a safe option for cavity insufflation during diagnostic laparoscopic procedures in swine.
OBJETIVO: O pneumoperitônio produz várias alterações na fisiologia humana. Algumas destas alterações, como hipercapnia e acidose, dependem ou são agravadas com o uso de CO2, tendo maior repercussão em pacientes com problema cardio-respiratório. A necessidade de uma melhor alternativa para insuflação da cavidade; a observação de que as cirurgias abertas, assim como as laparoscópicas com suspensão mecânica, são realizadas na presença de Ar ambiente; e a escassez de trabalhos testando o Ar em substituição ao CO2 para insuflação da cavidade, foram motivos para a realização deste trabalho. MÉTODOS: Vinte (0) suínos anestesiados foram submetidos a pneumoperitônio com 1 hora de duração. Os animais foram distribuídos em 4 grupos de 5 animais: Grupo A1 - Pneumoperitônio de Ar a 10 mmHg; Grupo A - Pneumoperitônio de Ar a 16 mmHg; Grupo B1 - Pneumoperitônio de CO2 a 10 mmHg; Grupo B - Pneumoperitônio de CO2 a 16 mmHg. O pneumoperitônio foi realizado pela técnica aberta com trocater de Hasson. Através de um cateter venoso central colhe-se amostra de sangue para exame de gasometria em 3 momentos. RESULTADOS: A análise da gasometria venosa não revelou alterações significativas entre os grupos em relação a PaO2 e a saturação do O2. Nos Grupos A1, A e B1 não foram observadas alterações no equilíbrio ácido-básico. No Grupo B após uma hora de pneumoperitônio houve nítida tendência a hipercapnia e acidose. CONCLUSÃO: O ar, com a técnica aberta de pneumoperitônio foi uma opção segura para insuflação de cavidade em procedimentos laparoscópicos diagnósticos de suínos.