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BACKGROUND: Methotrexate (MTX), a folate antagonist, is commonly used in the treatment of many different types of cancer and inflammatory diseases, including pancreatic cancer, although its side effects on the pancreas have not yet been researched. The mechanism of MTX-induced toxicity is not well known, and it has been reported in high-dose toxicity studies that the pancreas is sensitive to toxic effects. OBJECTIVES: The aim of our study was to determine whether adalimumab (ADA) has a preventive effect on MTX-induced pancreas toxicity in rats. MATERIAL AND METHODS: The rats were equally and randomly divided into 3 groups (Group 1 comprised the healthy controls, Group 2 was the MTX group, and Group 3 was the MTX + ADA group). The rats in Groups 2 and 3 received an intraperitoneal (ip.) single-dose injection of MTX (20 mg/kg). A single dose of 5 mg/kg ADA (REMICADE®) was administered ip. to Group 3. All the rats were sacrificed under anesthesia 5 days after receiving the MTX injection. RESULTS: Significantly higher mean edema, necrotic cell, and inflammatory scores were recorded in Groups 2 and 3 compared to those recorded in Group 1. Significantly decreased edema, number of necrotic cells, and inflammatory scores were noted in Group 3 than in Group 2. A decrease in islets of Langerhans cell insulin and somatostatin-positive interneurons was demonstrated after the administration of MTX. An increase in insulin and somatostatin-positive cells in islets of Langerhans, as well as a remodeling of the structure of the pancreas, was shown following treatment with ADA. CONCLUSIONS: Adalimumab was demonstrated to have a protective effect against MTX-induced pancreatic injury in this study.
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Adalimumab/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/toxicidade , Metotrexato/toxicidade , Pâncreas/efeitos dos fármacos , Animais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Round ligament leiomyoma of uterus is rare. It can be presented as inguinal swelling mimicking the inguinal hernia or lymph node. Surgical excision is its curative treatment. Definitive diagnosis is made by histopathological examination.A32 year old pregnant patient having round ligament leiomyoma as diagnosed histopathologically in Recep Tayyip Erdogan University Hospital in 2014 was presented here as the sixth case in literature.
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BACKGROUND: Cisplatin (Cis) is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. AIMS: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. STUDY DESIGN: Animal experimentation. METHODS: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection. RESULTS: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhydrase (CA)-II and low carbamoyl phosphate synthetase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. CONCLUSION: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and CA-II enzyme levels.
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BACKGROUND: c-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter. OBJECTIVE: To investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV. METHODS: A total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked. RESULTS: Although c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001). CONCLUSION: c-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects.
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Antígeno Ki-67/análise , Volume Plaquetário Médio , Proteínas Proto-Oncogênicas c-kit/análise , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Plaquetas/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Proto-Oncogene Mas , Valores de Referência , Fatores Sexuais , Estatísticas não ParamétricasRESUMO
OBJECTIVES: Carbon tetrachloride (CCl4) causes pulmonary toxicity. Infliximab (Ib) is a potent inhibitor of tumor necrosis factor-alpha (TNF-α). We aimed to investigate whether Ib has a protective effect on CCl4 induced lung injury. MATERIALS AND METHODS: Rats were divided into control, CCl4, and CCl4+Ib groups. A single dose of 2 ml/kg CCI4 was administered to CCI4 group and a single dose of 7 mg/kg Ib was given to CCl4+Ib group 24 hr before applying CCI4. RESULTS: TNF-α, malondialdehyde (MDA), nitric oxide (NO) and caspase-3 levels of the CCl4 group were markedly higher than both the control and CCl4+Ib groups. The CCI4+Ib group had lower histopathological injury than the CCl4 group. CONCLUSION: Ib as a strong TNF-α blocker decreases the production of proinflammatory cytokines, MDA, and oxidative stress leading to a protective effect against CCl4 induced lung tissue injury.
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Abstract: Background: c-Kit is a proto-oncogene that encodes tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker, providing information on platelet function and diameter. Objective: To investigate c-Kit expression and intensity in patients with Kaposi's sarcoma (KS) and to investigate the relation between Ki-67 proliferation and MPV. Methods: A total of 32 patients, diagnosed with classic cutaneous KS, were included in this study. We reevaluated the histopathological reports with the preparations, confirmed the diagnosis and then determined the patients' histopathological stages. c-Kit expression and Ki-67 proliferation were investigated immunohistochemically in KS cases, while MPV in all cases was checked. Results: Although c-Kit expression was detected in 22 cases (68.8%), it was not expressed in 10 cases (31.2%). We detected 8 cases with + (25%), 6 with ++ (18.8%) and 8 with +++ (25%). Ki-67 expression was 5.0% (min-max 1.0-20.0). Relapse was observed in 5 cases (15.6%) out of 32. There was positive correlation between c-Kit expression and MPV (rs=0.598, p<0.001), and between c-Kit intensity and MPV (rs=0.588, p<0.001). Conclusion: c-Kit is highly positive in KS. c-Kit positivity indicates a high risk of tumor growth, invasion and relapse. Furthermore, c-Kit expression stimulates megakaryocytes to release young and large thrombocytes into the periphery. Thus, high MPV, c-Kit expression and immunostaining intensity indicate high invasion and relapse in KS subjects.
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Sarcoma de Kaposi/patologia , Neoplasias Cutâneas/patologia , Proteínas Proto-Oncogênicas c-kit/análise , Antígeno Ki-67/análise , Volume Plaquetário Médio , Valores de Referência , Plaquetas/patologia , Imuno-Histoquímica , Biomarcadores Tumorais , Fatores Sexuais , Estatísticas não Paramétricas , Recidiva Local de Neoplasia/patologia , Estadiamento de NeoplasiasRESUMO
BACKGROUND: Distinguishing squamous cell carcinoma (SCC) from keratoacanthoma (KA) by histopathological features may not be sufficient for a differential diagnosis, as KAs may, in some cases, imitate well-differentiated SCCs. AIMS: In this study, we investigated whether the expression of the p16, p21, p27, p53 genes and a Ki-67 proliferation index are useful in distinguishing between these two tumors. STUDY DESIGN: Cross-sectional study. METHODS: Immunohistochemistry was used to investigate the expression of the p16, p21, p27, p53 genes and the Ki-67 proliferation index was investigated in well-differentiated SCC with KA-like features (n=40) and KA (n=30). RESULTS: The results of all of the examined markers, except for p27 (p16, p21, p53, and Ki-67) were found to be significantly different between the SCC and KA samples (p<0.05). CONCLUSION: In well-differentiated SCC with KA-like features and KA cases where the differential diagnosis is difficult from a histopathological perspective, the use of p16, p21, p53 expression and a Ki-67 proliferation index can be useful for the differential diagnosis of SCCs and KAs.
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This study compared the expression profile of HBME-1 and claudin-1 in 90 papillary thyroid carcinomas (PTCs) with respect to the tumor architecture and invasive growth as reflected in 46 BRAF-like, 31 non-invasive RAS, and 13 invasive RAS-like phenotypes. Individual tumors were given an expression score (max 300) by multiplying the percent positive tumor cells by the intensity score (range 0-3). The higher expression of HBME-1 and claudin-1 distinguished BRAF-like phenotype from RAS-like phenotype. The same correlation was also retained for both markers when comparing BRAF-like phenotype with non-invasive and invasive RAS-like phenotypes. The expression scores and positivity rates for both markers did not yield any statistical difference among BRAF-like PTCs. Except the higher positivity rate of HBME-1, invasive RAS-like tumors were not statistically different than their non-invasive counterparts with respect to the positivity rate of claudin-1 and the expression scores of both markers. A central lymph node dissection or selective lymph node sampling was available in 20 specimens. The absence of claudin-1 expression has not been a feature of lymph node metastasis in this series. Despite the limited number of nodal sampling, BRAF-like phenotype and claudin-1 positivity status have been considered the best determinants of positive predictive value and negative predictive value in the prediction of lymph node metastasis among variables, respectively. Adoption of the simplified architectural classification approach to PTCs showed distinct biomarker expression profile in this series; however, immunohistochemistry for HBME-1 and claudin-1 does not seem to be useful in the distinction of invasive RAS-like PTCs from their non-invasive counterparts. Given the overlapping molecular signatures within the RAS-like phenotype, further studies with additional biomarkers are still needed to identify distinct protein expression signatures of non-invasive RAS-like phenotype as this diagnostic category still remains a surgical diagnosis at this time.
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Biomarcadores Tumorais/análise , Carcinoma/patologia , Claudina-1/biossíntese , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/biossíntese , Carcinoma Papilar , Claudina-1/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Proteínas Proto-Oncogênicas B-raf , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Transcriptoma , Adulto JovemRESUMO
PURPOSE: To investigated the effects of exposure to an 1800 MHz electromagnetic field (EMF) on bone development during the prenatal period in rats. METHODS: Pregnant rats in the experimental group were exposed to radiation for six, 12, and 24 hours daily for 20 days. No radiation was given to the pregnant rats in the control group. We distributed the newborn rats into four groups according to prenatal EMF exposure as follows: Group 1 was not exposed to EMF; groups 2, 3, and 4 were exposed to EMF for six, 12, and 24 hours a day, respectively. The rats were evaluated at the end of the 60th day following birth. RESULTS: Increasing the duration of EMF exposure during the prenatal period resulted in a significant reduction of resting cartilage levels and a significant increase in the number of apoptotic chondrocytes and myocytes. There was also a reduction in calcineurin activities in both bone and muscle tissues. We observed that the development of the femur, tibia, and ulna were negatively affected, especially with a daily EMF exposure of 24 hours. CONCLUSION: Bone and muscle tissue development was negatively affected due to prenatal exposure to 1800 MHz radiofrequency electromagnetic field.
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Desenvolvimento Ósseo/efeitos da radiação , Calcineurina/metabolismo , Campos Eletromagnéticos/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Apoptose/efeitos da radiação , Cartilagem/patologia , Condrócitos/metabolismo , Condrócitos/patologia , Feminino , Cabeça do Fêmur/patologia , Humanos , Recém-Nascido , Masculino , Modelos Animais , Gravidez , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Ratos Sprague-Dawley , Fatores de TempoRESUMO
PURPOSE: To investigated the effects of exposure to an 1800 MHz electromagnetic field (EMF) on bone development during the prenatal period in rats. METHODS: Pregnant rats in the experimental group were exposed to radiation for six, 12, and 24 hours daily for 20 days. No radiation was given to the pregnant rats in the control group. We distributed the newborn rats into four groups according to prenatal EMF exposure as follows: Group 1 was not exposed to EMF; groups 2, 3, and 4 were exposed to EMF for six, 12, and 24 hours a day, respectively. The rats were evaluated at the end of the 60th day following birth. RESULTS: Increasing the duration of EMF exposure during the prenatal period resulted in a significant reduction of resting cartilage levels and a significant increase in the number of apoptotic chondrocytes and myocytes. There was also a reduction in calcineurin activities in both bone and muscle tissues. We observed that the development of the femur, tibia, and ulna were negatively affected, especially with a daily EMF exposure of 24 hours. CONCLUSION: Bone and muscle tissue development was negatively affected due to prenatal exposure to 1800 MHz radiofrequency electromagnetic field.
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Humanos , Animais , Masculino , Feminino , Recém-Nascido , Efeitos Tardios da Exposição Pré-Natal/patologia , Desenvolvimento Ósseo/efeitos da radiação , Calcineurina/metabolismo , Campos Eletromagnéticos/efeitos adversos , Fatores de Tempo , Gravidez , Cartilagem/patologia , Ratos Sprague-Dawley , Apoptose/efeitos da radiação , Condrócitos/metabolismo , Condrócitos/patologia , Modelos Animais , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Cabeça do Fêmur/patologiaRESUMO
AIM: To evaluate the antioxidant effects of thymoquinone (TQ) and to investigate the biochemical, histopathological and immunohistochemical changes in experimental rat ovarian torsion. METHODS: A total of 48 female adult rats were used in this study and randomly divided into 7 groups: (1) sham operation; (2) bilateral 3-hour ovarian ischemia; (3) 3-hour ischemia and 3-hour reperfusion; (4) and (5) rats were administered 20 and 40 mg/kg of TQ, respectively, before 0.5 h of ischemia, and then 3 h of ovarian ischemia was applied; (6) and (7) 3-hour ovarian ischemia was applied; 2.5 h after the induction of ischemia, rats were administered the same doses of TQ; at the end of 3 h of ischemia, a 3-hour reperfusion was applied. Histologic changes under light microscopy, immunoreactivity for anticaspase-3 and serum levels of malondialdehyde, interleukin-6, catalase and glutathione peroxidase were noted and compared between the 7 groups. RESULTS: Ischemia and ischemia/reperfusion cause a deterioration of biochemical and histopathological parameters. Administration of TQ seems to reverse these alterations and alleviate the injury. Antioxidant defense mechanisms appear to be enhanced by the administration of TQ. CONCLUSION: TQ at different doses attenuates ovarian ischemia and ischemia/reperfusion injury in rats.
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Benzoquinonas/farmacologia , Isquemia/terapia , Doenças Ovarianas/terapia , Traumatismo por Reperfusão/terapia , Animais , Benzoquinonas/administração & dosagem , Modelos Animais de Doenças , Feminino , Isquemia/prevenção & controle , Doenças Ovarianas/prevenção & controle , Ratos , Ratos Wistar , Traumatismo por Reperfusão/prevenção & controleRESUMO
OBJECTIVES: Electromagnetic radiation (ER) emitted from cell phones may exert a detrimental influence on human health and may affect the man reproductive system. We aimed to study the biological and morphological effects on the testes of 60-day-old male rats after ER exposure (900 MHz), which was applied continuously throughout embryogenesis. METHODS: A total of six pregnant Sprague Dawley rats were included in the study. Three pregnant rats (experimental group) were exposed to radiation from a cell phone set to talking mode for 24 hours a day for 20 days, and the other 3 pregnant rats (control group) were not to exposed to radiation. Newborn male rats were included from the experimental group (n=7) and the control group (n=7). At the end of 60 days, the rats' testes were excised, and testis length, width, depth, and weight were measured. Histopathological examinations were compared and serum testosterone (T) levels were assayed biochemically. RESULTS: While serum T level (3.51±0.21 ng/ml) of ER Exposed group was significantly lower than the control group (4.04±0.47 ng/ml, p=0.018), Caspase-3 enzyme activity (2.00±0.88) was significantly higher than the control group control (1.00±0.63, p=0.026). Johnsen score (8.4±0.5) of ER group was fairly lower than the control group (9.4±0.5, p=0.010). CONCLUSION: Our study demonstrated that ER exposure throughout embryogenesis may cause reductions in serum total T levels and in the size and weight of the testes of male rats, while causing modest increase in apoptosis.
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Campos Eletromagnéticos , Testículo/efeitos da radiação , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Testículo/química , Testículo/embriologia , Testículo/patologia , Testosterona/análiseRESUMO
Endometrioid-type endometrial carcinoma (EEC) developing on the ground of endometrial hyperplasia (EH) is amongst the most commonly observed type of cancer in the world. Folate receptor α (FRα) is a vitamin molecule that has a role in cell proliferation. The fact that FRα, which is known to be needed extremely by the cells of malignancies that proliferate rapidly, is present in limited amounts in normal tissues while it is overexpressed in malignant cells of the same tissues makes folate a candidate for target molecular therapy. In our study, FRα expression in 214 cases, with 95 diagnosed within EEC and 119 with EH, was studied immunohistochemically. FRα expression in EEC was found significantly high compared to EH and normal endometrium (P<0.01). Similarly, FRα expression in EH cases with complex atypia were significantly high compared to other hyperplasia subgroups (P<0.01). The findings of our results make us think that FRα overexpression may play a role in the EEC carcinogenesis and carcinoma progression from EH. Furthermore, we suggest that it can be helpful in the treatment of EEC and/or transition from hyperplasia stage to EEC as a molecular therapy targeting receptors labeled with antibody-based props containing FRα. Finally, we suggest that FRα may be used, based on the expression intensity, as a supplemental option to determine the patients that shall be directed to radical therapy amongst patients with complex atypical EH.
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Biomarcadores Tumorais/análise , Carcinoma Endometrioide/química , Hiperplasia Endometrial/metabolismo , Neoplasias do Endométrio/química , Receptor 1 de Folato/análise , Carcinoma Endometrioide/patologia , Progressão da Doença , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise Serial de Tecidos , Regulação para CimaRESUMO
BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GNs) are slow growing and although their incidence has increased in recent years, they are relatively rarely seen. Somatostatin analogues are used in the treatment of GNs that express somatostatin receptor (SR). We aimed to investigate the expression of SR2 and SR5 in GNs. MATERIALS AND METHODS: In this study the expression of SR2 and SR5 was investigated immunohistochemically in 49 cases (26 males, 23 females) diagnosed and graded with GN according to the World Health Organization classification 2010. RESULTS: The percentage of SR2 staining was 91.0% in grade 1, 82.8% in grade 2 and 100% in grade 3. On the other hand, the percentage of SR5 staining was 81.8% % in grade 1, 60.0% in grade 2 and 0% in grade 3. According to the tumor localization, the percentages of SR2 expression were as follows: pancreas 85.7%, stomach 100%, small bowel 70%, appendix 85.7% and rectum 100%. The percentages of SR5 expression were: pancreas 61,9%, stomach 37.5%, small bowel 70%, appendix 71.5% and rectum 66.6%. There was a significant negative correlation between ki67 percentage and SR5 expression (r=-0.341, p=0.016). CONCLUSIONS: In this study, GNs were found to highly express SR2 and SR5. Although the expression of SR2 and SR5 changed according to tumor localization, the expression of SR2 was higher than the expression of SR5 in GN. There was a significant negative correlation between ki67 and SR5. Accordingly, SR5 may be a prognostic indicator of GN.
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Neoplasias Gastrointestinais/química , Tumores Neuroendócrinos/química , Neoplasias Pancreáticas/química , Receptores de Somatostatina/análise , Adulto , Idoso , Neoplasias do Apêndice/química , Neoplasias do Apêndice/patologia , Feminino , Neoplasias Gastrointestinais/patologia , Humanos , Antígeno Ki-67/análise , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Neoplasias Retais/química , Neoplasias Retais/patologia , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , TurquiaRESUMO
Carbon tetrachloride (CCl4), a solvent frequently used in industry, can cause acute liver failure and liver fibrosis. Infliximab (Ib), a potent tumor necrosis factor alpha blocker, has a protective effect on the liver. Therefore, we investigated the protective effect of Ib against CCl4-induced acute liver injury. In this study, 24 male Sprague Dawley rats were randomly divided into three groups: the control group (n = 8), the CCl4 group (n = 8), and the CCl4 + Ib group (n = 8). A single dose of 2 mL/kg CCL4 was administered to the CCL4 group. The CCl4 + Ib group was injected with a single dose (7 mg/kg) of Ib 24 h before CCl4 was administered. In the CCl4 group, the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and the liver tissue levels of transforming growth factor beta 1 (TGF-ß1), interleukin 1 beta (IL-1ß), and adenosine deaminase (ADA) were significantly higher than the levels of these same substances in the control and CCl4 + Ib groups. The histopathological investigation revealed that although there was excessive liver injury in the CCl4 group, there was reduced injury in the CCl4 + Ib group. In addition, the carbamoyl phosphate synthetase I (CPS-I) and carbonic anhydrase II (CA-II) levels in the CCl4 group were significantly lower than those in the control and CCl4 + Ib groups. The results show that during CCl4-induced hepatotoxicity, Ib prevents liver injury by suppressing TGF-ß1 and IL-1ß levels, decreasing ADA levels, and regulating CPS-I and CA-II enzyme levels.
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Anti-Inflamatórios não Esteroides/farmacologia , Anticorpos Monoclonais/farmacologia , Tetracloreto de Carbono/toxicidade , Fígado/efeitos dos fármacos , Solventes/toxicidade , Animais , Citocinas/genética , Citocinas/metabolismo , Infliximab , Fígado/enzimologia , Fígado/lesões , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Methotrexate (MTX) is used to treat cancers, several forms of arthritis and other rheumatic conditions, although MTX may cause pulmonary toxicity related to the production of free oxygen radicals, various cytokines. Infliximab (IB) with its potent effect on tumor necrosis factor-alpha (TNF-α) inhibition also inhibits the release of endothelin-1 (ET-1). We aimed to investigate whether IB reduces pulmonary damage induced by an overdose of MTX. METHOD: The rats were divided into 3 groups of 8 animals. The control group was given only saline. One dose of 20mg/kg MTX intraperitoneal was administered in the MTX group. IB 7 mg/kg was given to the MTX+IB (MI) group. Three days after IB was administered, 20mg/kg MTX was given. Five days after MTX was administered, all rats were sacrificed. RESULTS: The TNF-α, ET-1, malondialdehyde (MDA), myeloperoxidase (MPO) and caspase-3 levels in MTX group were significantly higher than in control groups of TNF-α (P=.001), ET-1 (P=.001), MDA (P=.001), MPO (P=.001) and caspase-3 levels (P=.001) and MI groups of TNF-α (P=.009), ET-1 (P=.001), MDA (P=.047), MPO (P=.007) and caspase-3 levels (P=.003). The MI group had less histopathological damage in lung tissue than the MTX group. CONCLUSION: Overdose of MTX leads to cytokine release and the formation of reactive oxygen species in addition to increased ET-1 secretion release that causes lung damage. IB, as a potent proinflammatory agent, TNF-α blocker, can decrease ET-1 release and oxidative stress, it may show significant protective effects in lung tissue against damage caused by MTX overdose.
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Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/uso terapêutico , Infliximab/uso terapêutico , Metotrexato/efeitos adversos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/análise , Avaliação Pré-Clínica de Medicamentos , Endotelina-1/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Infiltração de Neutrófilos , Peroxidase/análise , Alvéolos Pulmonares/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVES: Stroke poses a crucial risk for mortality and morbidity. Our study aimed to investigate the effect of p-coumaric acid on focal cerebral ischemia in rats. MATERIAL AND METHODS: Rats were randomly divided into four groups, namely Group I (control rats), Group II (ischemia rats), Group III (6 hr ischemia + p-coumaric acid rats) and Group IV (24 hr ischemia + p-coumaric acid rats). Cerebral ischemia was induced via intraluminal monofilament occlusion model. In all groups, the brain was removed after the procedure and rats were sacrificed. Malondialdehyde, superoxide dismutase and nuclear respiratory factor-1 were measured in the ischemic hemisphere. The histopathological changes were observed in the right hemisphere within the samples. Functional assessment was performed for neurological deficit scores. RESULTS: Following the treatment, biochemical factors changed significantly. Histopathologically, it was shown that p-coumaric acid decreased the oxidative damage. The neurological deficit scores of p-coumaric acid-treated rats were significantly improved after cerebral ischemia. CONCLUSION: Our results showed that p-coumaric acid is a neuroprotective agent on account of its strong anti-oxidant and anti-apoptotic features. Moreover, p-coumaric acid decreased the focal ischemia. Extra effort should be made to introduce p-coumaric acid as a promising therapeutic agent to be utilized for treatment of human cerebral ischemia in the future.
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BACKGROUND: c-Kit is a proto-oncogene that encodes a tyrosine kinase receptor (CD117). Mean platelet volume (MPV) is a useful marker for demonstrating thrombocyte function. We aimed to investigate whether c-kit is expressed in benign, preneoplastic and neoplastic endometrial tissues and whether MPV has a relation with c-kit expression and its intensity. MATERIALS AND METHODS: c-Kit expression was investigated immunohistochemically in 10 samples of normal endometrium (n=10), simple endometrial hyperplasia (5 cases with atypia and 10 cases without atypia), complex endometrial hyperplasia (10 cases with atypia and 10 cases without atypia) and endometrial cancer (EC) (10 cases grade I and 10 cases grade II) and MPV of all cases was checked. RESULTS: c-Kit expression was observed at very low rates in cases with normal endometrial tissues (NE) and in hyperplasia without atypia. c-Kit expression and immunostaining were strong in endometrial atypia and EC. MPV levels of complex atypical endometrial hyperplasia (CAEH) (p:0.002), EC grade I (ECG I) (p<0.001) and EC grade II (ECG II) (p<0.001) were significantly elevated when compared with the NE group. Both c-kit expression and intensity of immunostaining had a positive correlation with MPV level. CONCLUSIONS: While c-kit expression and intensity of immunostaining were mildly positive in NE and hyperplasia without atypia, they were clearly observed in EC and hyperplasia with atypia. As c-kit expression is related to the mutagenesis a long-term follow- up may be needed in these cases. A high MPV level may be a good test for demonstrating c-kit expression and intensity of immunostaining.