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PURPOSE: The aim of this study was to investigate the possible association of insulin-like growth factor-1 (IGF-1) with the pathogenesis of non-functioning adrenocortical adenomas (NFAs). METHODS: This study included 50 female patients (mean age 54 years) with NFAs, 55 patients (mean age 48 years; 20 male, 35 female) with acromegaly and 38 female control subjects (mean age 58 years). Body mass index (BMI) and waist circumference (WC) of the subjects were recorded and blood samples for IGF-1 were taken. Insulin resistance was calculated using the homeostatic model assessment (HOMA) score. Since most of the acromegaly patients had been using medicine that could have effected insulin resistance, HOMA scores were calculated only in patients with NFAs and the controls. Computerized tomography or magnetic resonance imaging was taken of the acromegalics and controls to detect adrenal mass frequency. RESULTS: The mean age was similar among the groups. As expected, the serum IGF-1 levels were significantly higher in patients with acromegaly than in patients with NFAs and the controls (p < 0.001). Although BMI, WC, and serum IGF-1 levels were significantly higher (p < 0.001) in patients with NFAs, the HOMA scores were similar between patients with NFAs and control groups. Although none of the control subjects had adrenal masses, NFAs were detected in 14 (25%) out of 55 acromegalic patients. CONCLUSIONS: Higher serum IGF-1 levels in patients with NFAs compared to the control group and an increased prevalence of NFAs in acromegaly patients compared to control subjects and the general population suggest an association of IGF-1 with the etiopathogenesis of NFA.
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Neoplasias do Córtex Suprarrenal/sangue , Adenoma Adrenocortical/sangue , Resistência à Insulina/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Acromegalia/sangue , Acromegalia/patologia , Neoplasias do Córtex Suprarrenal/patologia , Adenoma Adrenocortical/patologia , Adulto , Glicemia , Índice de Massa Corporal , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Gossypol, a naturally occurring compound in cottonseeds, has anticancer effects against several tumor cell lines. It has been extensively studied in clinical trials and is well tolerated with a favorable safety profile. AT-101, a derivative of R (-)-gossypol, binds to Bcl-2 family proteins and induces apoptosis in vitro. Although transsphenoidal surgical excision of the pituitary corticotroph adenoma is the gold standard of care, it is not successful all the time. Medical therapy for Cushing's disease still remains a challenge for the clinicians. We aimed to investigate the cytotoxic and apoptotic effects of AT-101 in mouse pituitary corticotroph tumor AtT20 cells. METHODS: Cytotoxic effect of AT-101 was assessed by XTT cell viability assay. Apoptosis was shown by measuring DNA fragmentation and Caspase-3/7 activity. Changes in mRNA expressions of apoptosis-related genes were investigated by qPCR array after treatment with AT-101. ACTH was measured by ACTH-EIA Kit. RESULTS: AT-101 induced cytotoxicity and apoptosis in AtT20 cells. mRNA levels of pro-apoptotic genes such as TNFR-SF-10B, Bid, PYCARD, Caspase-8, Caspase-3, and Caspase-7 were induced by 2.0-, 1.5-, 1.7-, 1.5-, 1.6-, and 2-fold, respectively, in AtT20 cells by AT-101 treatment. Moreover, some of the anti-apoptotic genes such as BCL2L10, NAIP1, and PAK-7 were reduced by 2.1-, 2.3-, 4.0-fold, respectively, in AtT20 cells. AT-101 also decreased ACTH secretion significantly. CONCLUSION: AT-101 induces apoptosis in mouse pituitary corticotroph tumor cells.
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Adenoma Hipofisário Secretor de ACT/tratamento farmacológico , Adenoma/tratamento farmacológico , Hormônio Adrenocorticotrópico/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Gossipol/análogos & derivados , Neoplasias Hipofisárias/tratamento farmacológico , Adenoma Hipofisário Secretor de ACT/metabolismo , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma/metabolismo , Adenoma/patologia , Hormônio Adrenocorticotrópico/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Proteínas Reguladoras de Apoptose/metabolismo , Gossipol/farmacologia , Camundongos , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Células Tumorais CultivadasRESUMO
OBJECTIVE: Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. METHODS: The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. RESULTS: One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. CONCLUSION: Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.
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Adenoma/patologia , Neoplasias Hipofisárias/patologia , Complicações Neoplásicas na Gravidez/patologia , Prolactinoma/patologia , Adenoma/sangue , Adulto , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Hipofisárias/sangue , Gravidez , Complicações Neoplásicas na Gravidez/sangue , Resultado da Gravidez , Prolactina/sangue , Prolactinoma/sangue , Estudos Retrospectivos , TurquiaRESUMO
The purpose of this study was to examine potential long-term post-torsion changes that can occur in the histopathology, biochemistry and spermatogenesis of both torsioned and nontorsioned opposite testes. The study also determines the effect of zinc (Zn) administration on the testicular torsion/detorsion (T/D) damage on both testes. Forty-eight male rats, divided equally into eight groups: (SHAM), (SHAM+,Zn+), (T/D+, Zn- 1 month), (T/D+,Zn- 2 months), (T/D+,Zn- 3 months), (T/D+,Zn+ 1 months), (T/D+,Zn+ 2 months), (T/D+,Zn+ 3 months), have been used. Drug administration was carried out by adding 100 µg (0.016 ml/rat) Zn per rat to drinking water in related groups. Testicular damage decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in the testis tissues of rats, while Zn administration increased SOD and GSH and decreased MDA in the testis tissues in comparison with the SHAM group. The beneficial effect of zinc sulphate was more evident on the nonrotated testis than the rotated testis. In the histopathological study, a significant decrease in torsion and detorsion injuries was observed in the treatment groups compared to the torsion and detorsion groups. We found a protective effect of zinc sulphate on oxidative stress as a result of T/D injuries in rats, especially for the nonrotated testis; results were supported histopathologically.
Assuntos
Antioxidantes/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Torção do Cordão Espermático/tratamento farmacológico , Testículo/efeitos dos fármacos , Zinco/administração & dosagem , Animais , Antioxidantes/uso terapêutico , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Torção do Cordão Espermático/metabolismo , Torção do Cordão Espermático/patologia , Superóxido Dismutase/metabolismo , Testículo/irrigação sanguínea , Zinco/uso terapêuticoRESUMO
INTRODUCTION: Salusins are multifunctional endogenous peptides shown in human and rat tissues. Serum salusin α level is decreased in coronary artery disease and lack of salusin α enhances coronary atherosclerosis. Hypothyroidism is a chronic inflammatory disease that has a high risk of developing cardiovascular disease. Here we aimed to search the relationship of overt hypothyroidism and subclinical hypothyroidism with salusin α and other inflammatory markers, also the effect of L-thyroxine treatment on these findings. MATERIAL AND METHODS: 32 patients with overt hypothyroidism taking L-thyroxine treatment, 18 patients with subclinical hypothyroidism without treatment and 25 healthy patients as control group were included in the study. Serum salusin α, TNF α, sCRP, glucose, insulin and lipid levels were tested for all groups and results were evaluated with SPSS statistical analysis method. RESULTS: HDL, sCRP, salusin mean values were statistically significantly different in all 3 groups. HDL level was statistically significantly higher in control group compared to treatment group. sCRP level was higher and salusin level was lower in both treatment and non-treatment hypothyroidism groups compared to control group. When treatment and non-treatment hypothyroidism groups were compared, there was no statistically significant difference for salusin α, but HDL level was high and insulin level was low statistically significant in treatment group. CONCLUSIONS: Salusin α that is shown to be protective for coronary artery disease and hypertension, is found to be significantly low in hypothyroidism, thus it is a marker that increases the cardiovascular disease risk in this specific patient group.
RESUMO
BACKGROUND: Alpha lipoic acid (ALA) acts as essential co-factor for mitochondrion respiratory enzymes. It has an increasing importance in diabetic neuropathy treatment. Its positive effects on weight gain and metabolic parameters have also been discussed. In this study, we aimed to search for the effect of ALA on weight, appetite, adiponectin and metabolic parameters in type 2 diabetes mellitus patients. METHODS: This study is designed as a randomised, double-blind, placebo controlled, prospective study. 23 type 2 diabetes mellitus patients with peripheral neuropathy (6 normal weight, 17 obese) and 21 normal weight control group were included in the study. Patients were given 600mg/day oral ALA for 6 weeks, added to their routine therapy. Body mass index (BMI), adiponectin, fasting plasma glucose, HbA1C, lipid parameters and CRP levels were tested before and after ALA treatment. Results were evaluated using SPSS 15.0 for Windows. RESULTS: Adiponectin levels were statistically significantly lower and CRP levels were higher in diabetes group when compared to control group. Although ALA treatment caused a slight weight loss, it was not statistically significant. Appetite scores were decreased in the diabetes group but it did not cause statistically significant weight loss. There was no significant change in metabolic parameters or adiponectin after the treatment. CONCLUSIONS: 600mg/dL ALA treatment for 6 weeks did not favor for metabolic parameters in type 2 diabetes patients. This result might be due to the dose or the duration of the treatment, genetic predisposition or dietery habits. Trial of higher doses for long terms might be needed for recovery.
RESUMO
The purpose of this study was to examine the effects bosentan (which is a strong vasoconstrictor) on bone fracture pathophysiology, and investigate the roles of the nonselective endothelin 1 receptor blocker bosentan on the bone fractures formed in rats through radiographic, histopathologic, and immunohistochemical methods. The rats were divided into three groups (six rats in each group): a femoral fracture control group, a femoral fracture plus bosentan at 50 mg/kg group, and a femoral fracture plus bosentan at 100 mg/kg group. The femoral fracture model was established by transversely cutting the femur at the midsection. After manual reduction, the fractured femur was fixed with intramedullary Kirschner wires. The radiographic healing scores of the bosentan 100 and 50 mg/kg groups were significantly better that those of the fracture control group. The fracture callus percent of new bone in the bosentan 100 mg/kg group was significantly greater than that in the control group. Also, semiquantitative analysis showed higher positive vascular endothelial growth factor and osteocalcin staining and lower positive endothelin receptor type A staining in the treatment groups than in the control group. Bosentan treatment also decreased tissue endothelin 1 expression relative to that in the fracture control group. As a result of our study, the protective effect of bosentan was shown in experimental femoral fracture healing in rats by radiographic, histopathologic, and molecular analyses.
Assuntos
Fraturas do Fêmur/tratamento farmacológico , Fêmur/efeitos dos fármacos , Consolidação da Fratura/efeitos dos fármacos , Sulfonamidas/farmacologia , Animais , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/metabolismo , Bosentana , Modelos Animais de Doenças , Fraturas do Fêmur/metabolismo , Fêmur/metabolismo , Masculino , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: The aim of this study is to show the effect of a new mechanism on endothelin (ET) receptors in the physiopathology of diabetes-related pulmonary injury. We tested the hypothesis that dual ET-1 receptor antagonism via bosentan can reverse diabetes-induced lung injury. METHODS: The rats (24 male) were separated into four groups: group 1 (HEALTHY): Control group; group 2 (DM): Streptozotocin 60 mg/kg (i.p.); group 3 (DM + BOS-1): Diabetes + bosentan 50 mg/kg per-os; group 4 (DM + BOS-2): Diabetes + bosentan 100 mg/kg per-os. The bosentan treatment was initiated immediately after the onset of STZ-induced diabetes and continued for 6 weeks. RESULTS: In the treatment group, SOD activity was significantly increased, although GSH and MDA levels and TNF-α and TGF-ß gene expression were decreased. Bosentan 50 mg/kg and bosentan 100 mg/kg showed a significantly down-regulatory effect on ET-1, ET-A, and ET-B mRNA expression. CONCLUSIONS: In conclusion, increased endothelin levels in the lung associated with diabetes may be one cause of endothelial dysfunction, cytokine increase, and oxidant/antioxidant imbalance in the pathogenesis of complications that may develop during diabetes. With its multiple effects, bosentan therapy may be an effective option against complications that may develop in association with diabetes.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Antagonistas dos Receptores de Endotelina/uso terapêutico , Pulmão/metabolismo , Sulfonamidas/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Bosentana , Diabetes Mellitus Experimental/metabolismo , Antagonistas dos Receptores de Endotelina/farmacologia , Glutationa/metabolismo , Pulmão/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Sulfonamidas/farmacologia , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Three-dimensional (3D) models created with computers and educational applications designed using such models are used in the medical field every day. However, there is a lack of macroscopic demonstration applications built with digital 3D models in the field of veterinary pathology. The aim is to build a fully interactive 3D educational web-based augmented reality application, to demonstrate macroscopic lesions in kidneys for educational purposes. We used open source and free software for all 3D modelling, Augmented Reality and website building. Sixteen 3D kidney pathology models were created. Kidney models modelled in 3D and published as WebAR are as follows: normal kidney, unilateral neurogenic shutdown with atrophy, hydronephrosis, hypercalcemia of malignancy tubular nephrosis, interstitial corticomedullary nephritis, renal infarct, multifocal petechial hemorrhages, polycystic kidneys, renal masses, multifocal nephritis, pigmentary nephrosis, papillary necrosis, glucose-related rapid autolysis (pulpy kidney), pyelonephritis, renomegaly and kidney stones. With the workflow shown here, it has been presented as a feasible model application for human pathology and presented to educators, researchers and developers who have 3D models and AR in their field of interest. To the best of the authors' knowledge, this is the first study on Web-Augmented Reality application for veterinary pathology education.
Assuntos
Realidade Aumentada , Educação em Veterinária/métodos , Nefropatias/veterinária , Animais , Humanos , Internet , Modelos Biológicos , SoftwareRESUMO
Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug-refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immunosorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 microM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings.
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Apoptose/efeitos dos fármacos , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Difosfonatos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Hormônio-Dependentes/patologia , Neoplasias da Próstata/patologia , Western Blotting , Conservadores da Densidade Óssea/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Reabsorção Óssea/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Caspase 3/metabolismo , Caspase 7/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Ácido Ibandrônico , Masculino , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Células Tumorais CultivadasRESUMO
PURPOSE: many drugs have been tested to increase the sensitivity of prostate cancer cells to radiotherapy. Gossypol, a natural polyphenolic compound extracted from the cotton plant, is one of the agents the efficacy of which has been investigated in the treatment of prostate cancer for this purpose. The main aim of this study was to investigate the best gossypol application with irradiation, when gossypol was applied either sequentially (24 h before and after irradiation) or concurrently in PC-3 hormone-refractory and radioresistant prostate cancer cells. METHODS: The XTT viability assay was used to evaluate the cytotoxicity of different concentrations of gossypol in PC- 3 cells. Irradiation was applied to PC-3 cells via 6 MV photon linear accelerator and delivered 24 h before, 24 h after radiation or at the same time with gossypol administration. RESULTS: gossypol caused radiosensitization of PC-3 cells that are known to be radioresistant, with high Bcl-2 levels. Among different applications of gossypol and irradiation (before, after and concurrent) in prostate cancer cells, the best results were observed by the application of gossypol 24 h before irradiation. CONCLUSION: our study suggests that gossypol represents a promising novel anticancer treatment for radiosensitization of human hormone-refractory prostate cancer cells.
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Anticoncepcionais Masculinos/uso terapêutico , Gossipol/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Western Blotting , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Terapia Combinada , Raios gama , Humanos , Masculino , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/radioterapia , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer.
Assuntos
Apoptose/efeitos dos fármacos , Difosfonatos/farmacologia , Gossipol/farmacologia , Imidazóis/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Proteínas Reguladoras de Apoptose/metabolismo , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Anticoncepcionais Masculinos/farmacologia , Anticoncepcionais Masculinos/uso terapêutico , Fragmentação do DNA/efeitos dos fármacos , Difosfonatos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Gossipol/uso terapêutico , Hormônios/metabolismo , Humanos , Imidazóis/uso terapêutico , Masculino , Neoplasias da Próstata/patologia , Ácido ZoledrônicoRESUMO
Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer.
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Antineoplásicos/farmacologia , Apoptose , Difosfonatos/farmacologia , Imidazóis/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Taxoides/farmacologia , Androgênios/fisiologia , Antineoplásicos/uso terapêutico , Caspase 3/metabolismo , Caspase 7/metabolismo , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Difosfonatos/uso terapêutico , Docetaxel , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Imidazóis/uso terapêutico , Masculino , Neoplasias da Próstata/metabolismo , Taxoides/uso terapêutico , Ácido ZoledrônicoRESUMO
PURPOSE: Gossypol is a natural polyphenolic compound extracted from cotton plant (Gossypium species) which has shown potent inhibitory effect on cell growth of many types of cancers. In this study, we aimed to evaluate the interaction of gossypol with some conventional drugs known to be effective in the treatment of breast cancer, like taxanes, doxorubicin, gemcitabine, cisplatin and vinorelbine, in MCF-7 breast cancer cells. MATERIALS AND METHODS: The XTT viability assay was used to evaluate the cytotoxicity of various cytotoxic agents alone and in combination with gossypol in MCF-7 breast cancer cells. The combination effect analysis of Chou and Talalay was used to identify the most synergistic drug combinations. The possible synergistic effects of the combination of drugs on apoptosis were also evaluated by using two different apoptosis assays. RESULTS: We identified strong synergistic cytotoxic and apoptotic activity of gossypol with taxanes among all other studied cytotoxic drugs. CONCLUSION: This study provides proof that gossypol combined with taxanes may have potential as a novel future treatment for breast cancer.
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Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Gossipol/farmacologia , Taxoides/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , HumanosRESUMO
The present study was designed to investigate the relationship between the serum levels of oxidant-antioxidant system (malondialdehyde (MDA) level, Paraoxonase (PON1) activity, nitric oxide (NO) level and superoxide dismutase (SOD) activity) and thyroid hormone status in hypothyroidism pre and posttreatment. The study group comprised 33 patients with primary hypothyroidism. 18 of these patients were reevaluated after euthyroid state i.e. at least 6 months of thyroxine replacement. The patients were compared with 26 normal healthy controls. Serum MDA level, PON1 activity, NO level and SOD activity were measured according to an enzymatic spectrophotometric method. MDA levels were found higher in patients with hypothyroidism before the treatment than the controls. MDA levels were also found to be decreased after the treatment in patients with hypothyroidism. However MDA were found still higher than the controls after the treatment. PON1 activity was found to be lower in patients pretreatment when compared to posttreatment hypothyroidism and controls. Posttreatment of hypothyroidism mean PON1 activity significantly increased compared to pretreatment level but it was still significantly lower than control level. NO level was higher in pretreatment hypothyroidism when compared to controls. SOD activity was not found different in patients before treatment when compared to controls. SOD activity was significantly higher in after treatment when compared to both pretreatment and control levels. In conclusion, increased ROS levels in hypothyroidism may result in a pro-oxidation environment, which in turn could result in decreased antioxidant PON1 activity, increased MDA and NO levels. As a result, lipid peroxidation may have a role in the pathogenesis of the atherosclerosis in hypothyroidism.
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Antioxidantes/metabolismo , Arildialquilfosfatase/sangue , Hipotireoidismo/sangue , Hipotireoidismo/tratamento farmacológico , Malondialdeído/sangue , Estresse Oxidativo , Adulto , Idoso , Feminino , Doença de Hashimoto/sangue , Doença de Hashimoto/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Superóxido Dismutase/sangue , Tiroxina/sangue , Tiroxina/uso terapêutico , Tri-Iodotironina/sangueRESUMO
INTRODUCTION: Resection of the distal aspect of clavicle has a well-documented treatment modality in case of acromioclavicular joint osteoarthritis resistant to conservative treatment. HYPOTHESIS: Limited (mean â¼0.5cm distal end of clavicle resection) distal clavicle excision of A-C joint arthritis in cases resistant to conservative treatment may reduce the pain and improve the shoulder function. MATERIAL AND METHODS: In this study, we retrospectively evaluated the results of limited distal clavicle excision of acromioclavicular joint osteoarthritis resistant to conservative treatment. All patients were evaluated by using the Visual Analogue Scale (VAS) and UCLA shoulder rating scale (University of California Los Angeles), either before surgery or final follow-up period for pain and functional results, respectively. RESULTS: A total of 110 patients (48 male, 62 female) with AC joint arthritis, treated between the years of 2008-2012, were retrospectively analyzed. A total of 30 patients (12 male, 18 female) who failed to show improvement with conservative treatment underwent limited surgical open excision of distal clavicle. The mean age of the study population was 52.5±1.2 years. The mean follow-up period was 27±1.3 months. The mean preoperative VAS score was 83.6±5.58 (range, 70-90) while mean VAS was 26.6±9.3 (range, 10-50) at the final follow-up. There was a statistically significant difference between pre- and postoperative VAS scores in patients who had treated by surgical approach (P<0.001). The mean UCLA score of the patients increased postoperatively from 11.5 (range, 9-14) to 29.2 (range, 27-32) at the final follow-up. There was a statistically significant difference between the two time periods with respect to UCLA scores (P<0.001). DISCUSSION AND CONCLUSION: In patients with AC osteoarthritis resistant to conservative therapy, the hypothesized limited clavicle excision (mean â¼0.5cm distal end of clavicle resection with preserving coracoclavicular ligaments and inferior capsule) reduced the pain and improved the shoulder function. CONCLUSION: Our midterm follow-up (mean 27 months) results showed that limited distal clavicle excision of patients with AC joint osteoarthritis resistant to conservative treatment (0.5cm distal end of clavicle resection with preserving inferior capsule, and coracoclavicular ligaments) reduced the pain and improved the shoulder function. LEVEL OF EVIDENCE: IV (Retrospective study).
Assuntos
Articulação Acromioclavicular/cirurgia , Clavícula/cirurgia , Procedimentos Ortopédicos/métodos , Osteoartrite/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 1.5-month-old Kangal breed puppy from a dairy cattle farm died after showing severe diarrhoea and incoordination. Necropsy examination revealed multifocal pulmonary consolidation and necrosis and fibrinohaemorrhagic enteritis. Microscopically, there was necrotic and purulent bronchopneumonia, myocarditis and non-purulent encephalitis. In the jejunum and ileum there was villous atrophy and crypt hyperplasia with oocyst-like and schizont-like structures in the epithelia. Immunohistochemically, Neospora caninum antigen was detected in association with the intestinal protozoal structures, degenerative neurons and areas of necrosis in the lungs and heart. Polymerase chain reaction confirmed that the organism was N. caninum and not Toxoplasma gondii. The seroprevalence for N. caninum was 74.2% (49/66 animals) for the cattle and 57.1% (4/7 animals) for dogs on this farm. This report documents fatal systemic neosporosis and enteroepithelial stages of N. caninum in a naturally infected puppy. To the authors' knowledge, this is the first definition of intestinal neosporosis in a naturally infected dog as well as the first evidence of fatal canine neosporosis in Turkey.
Assuntos
Coccidiose/veterinária , Doenças do Cão/microbiologia , Intestinos/microbiologia , Neospora , Animais , Coccidiose/microbiologia , Coccidiose/patologia , Doenças do Cão/patologia , Cães , Evolução Fatal , Imuno-Histoquímica , Intestinos/patologia , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: The treatment of castrate-resistant prostate cancer (CRPC) still remains as an important challenge of daily oncology practice. Docetaxel significantly prolongs overall survival in men with CRPC. Thymoquinone (TQ), one of the flavonoid compounds isolated from Nigealla sativa, has been shown to possess cytotoxic activity against a variety of cancer cell lines. MATERIALS AND METHODS: The aim of the study was to investigate the possible synergistic cytotoxic/apoptotic effects of a novel combination, docetaxel and TQ in DU-145 hormone- and drug-refractory prostate cancer cells and their effects on PI3K and ERK signaling pathways. RESULTS: We observed that the combination of docetaxel and TQ resulted in a significant synergistic cytotoxicy and apoptosis as compared to any single agent alone, in a dose-dependent manner. It was found that viability of the combination treated cells was not significantly changed in the presence of LY294002 as compared to inhibitor treated cells. However, in the presence of FR180204, viability of combination treated cells was significantly decreased as compared to inhibitor treated cells. In conclusion, cytotoxic effect of the docetaxel and TQ combination is correlated with the block of the PI3K/Akt signaling pathway in DU-145 cells. CONCLUSION: Therefore, this combination strategy may be an alternative approach for the challenging era of daily oncologic practice. Also, the combination of docetaxel and TQ might allow a reduction in docetaxel doses and diminish adverse effects of docetaxel while maintaining the therapeutic effect in patients with CRPC.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Sinergismo Farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Taxoides/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica , Western Blotting , Proliferação de Células/efeitos dos fármacos , Docetaxel , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
Hirsutism is a common clinical problem in women and the treatment depends on the cause of hirsutism. The study was designed to determine the various causes of hirsutism and their prevalences in a Turkish population. 168 women with hirsutism attending to Endocrinology Outpatient Clinic of Erciyes University Hospital were investigated in detail. Medical history, physical examination, and basal levels of free testosterone (fT), androstenedione, follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone-sulphate (DHEAS), 17 hydroxyprogesterone (17-OHP), 11-deoxycortisol (11-S), thyroid hormones, thyroid stimulating hormone (TSH), and prolactin were determined. ACTH stimulation test was performed for the diagnosis of non-classic congenital adrenal hyperplasia (NCAH). Pelvic/vaginal and adrenal ultrasonographies were performed for the detection of tumors and polycystic ovarian changes. Polycystic ovary syndrome (PCOS) was diagnosed in 96 (57.1 %) patients, idiopathic hirsutism in 27 (16 %), NCAH in 12 (7.1 %), adrenal carcinoma in 3 (1.8 %), and Cushing's disease in 1 (0.6 %) patient. Among patients with NCAH, 11 (91.7 %) patients had 11-beta hydroxylase (11-beta OH) deficiency, and 1 (8.3 %) had 21-hydroxylase deficiency. The etiology of hyperandrogenemia was not clear in 29 (17.4 %) patients and these patients were named as idiopathic hyperandrogenemia. The clinical presentation of 11-beta OH deficiency is indistinguishable from that of other hyperandrogenic states and ACTH stimulation test is the only way to diagnose this entity. Although PCOS is the most common cause of hirsutism, it is notable that nearly one fifth of hirsute women have no apparent cause of hyperandrogenemia.