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1.
Niger J Clin Pract ; 27(5): 612-619, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38842711

RESUMO

BACKGROUND: Controlling Nutritional Assessment (CONUT) score has been shown to have a higher predictive value compared to other nutritional scores in acute coronary syndrome. AIM: To determine the relationship between CONUT score and long-term mortality in patients with chronic coronary syndrome (CCS). METHODS: Between 2017 and 2020, 585 consecutive patients newly diagnosed and proven to have CCS by coronary angiography were included in the study. CONUT score and demographic and laboratory data of all patients were evaluated. The relationship between results and mortality was evaluated. RESULTS: The mean age of the patients was 64 years and 75% were male. Mortality was observed in 56 (9.6%) patients after a median follow-up period of 3.5 years. The median CONUT score was significantly higher in patients with mortality (P < 0.001). In multivariate regression analysis, the CONUT score was associated with mortality (Hazard ratio (HR): 1.63 (95% confidence interval (CI): 1.34-1.98 P < 0.001)). The area under curve (AUC) for long-term mortality estimation for the CONUT score was 0.75 (95% CI 0.67-0.82 P < 0.001). When the CONUT score value was accepted as 0.5, the sensitivity was 78% and the specificity was 60. CONCLUSION: CONUT score was found to be predictive of mortality in long-term follow-up of patients with CCS.


Assuntos
Avaliação Nutricional , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Turquia/epidemiologia , Angiografia Coronária , Estado Nutricional , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/diagnóstico , Valor Preditivo dos Testes , Fatores de Risco , Medição de Risco/métodos
2.
Niger J Clin Pract ; 26(7): 863-870, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37635568

RESUMO

Background: Sonographic measurement of optic nerve sheath diameter (ONSD) can reflect intracranial pressure (ICP) indirectly and determine the neurology intensive care unit (NICU) requirement and mortality in acute ischemic stroke (AIS). Aim: To demonstrate the effectiveness of ONSD to determine mortality, morbidity, and NICU requirement on patients with the AIS. Methods: The sonographic ONSD measurements were performed on each patient with AIS, over 18 years old. All patients were categorized according to the Oxfordshire Community Stroke Project (OCSP) classification system. MRI images were examined for increased ICP, and the patients were categorized into two groups as increased ICP (i-ICP) and normal ICP. The ONSD results were evaluated in terms of classifications, outcomes, and prognosis of the patients. Results: One hundred and five patients were included and 31 (35.2%) were in the i-ICP group. The median ONSDs were 5.26 mm in the i-ICP group and 4.62 mm in the normal ICP group (P < 0.001). The median ONSDs were 5.13 mm in the NICU group and 4.69 mm in the neurology ward (NW) group (P = 0.001). The total anterior circulation infarction (TACI) subgroup had higher ONSDs than the others (TACI: 5.27 mm; PACI: 4.73 mm; POCI: 4.77 mm; and LACI: 4.64 mm, P < 0.001). The NICU requirements were higher in the TACI subgroup. The median ONSD was 5.42 mm in the deceased group (survived: 4.77 mm, P < 0.001). Conclusion: ONSD may be favorable for predicting the increased ICP and the NICU requirement in OCSP subgroups. Moreover, ONSD can be used to foresee the mortality of AIS.


Assuntos
Hipertensão Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Adolescente , Estudos de Casos e Controles , Prognóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Serviço Hospitalar de Emergência , Nervo Óptico/diagnóstico por imagem
3.
Eur Rev Med Pharmacol Sci ; 26(12): 4403-4408, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35776041

RESUMO

OBJECTIVE: Cancer is the second most common non-communicable disease group in the world and its frequency is increasing. In parallel, side effects of drugs used in cancer treatment are frequently encountered. Doxorubicin (DOX) is one of the most effective multi-purpose anticancer drugs. However, its use is significantly limited due to the risk of cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors are a group of antidiabetic drugs that have been shown to reduce cardiovascular events. Our aim is to examine the preventive effect of dapagliflozin on DOX-induced cardiac damage. SUBJECTS AND METHODS: We used 30 albino rats. 20 of 30 rats were administered doxorubicin for cardiomyopathy model. The rats in the DOX arm were divided into two groups: those given penicillin and placebo. After the rats were terminated, tissues were prepared for histopathological and immunohistochemical examination. TNF-α, pro-BNP, troponin T and plasma FGF-21 levels were also measured in plasma. RESULTS: The mean concentrations of cTnT and pro-BNP in the plasma of the DOX treated rats demonstrated a significantly higher value compared to the control group. Treatment with dapagliflozin caused a significant reduction in plasma cTnT, pro-BNP and TNF-α levels concentrations compared to the DOX control group (p < 0.001). The group of rats treated with dapagliflozin was effective in significantly decreasing the FGF-21 concentration and the percentage of fibronectin immunoexpression compared to the DOX control group (p  < 0.0001). CONCLUSIONS: This study revealed, for the first time, that dapagliflozin can improve DOX-induced cardiac dysfunction and pathological changes in non-diabetic rats. This result has shown that dapaglifozin, may be promising in terms of preventing cardiac damage that may develop in cancer treatment.


Assuntos
Cardiomiopatias , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Ratos , Compostos Benzidrílicos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/prevenção & controle , Doxorrubicina/efeitos adversos , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Fator de Necrose Tumoral alfa
4.
Balkan J Med Genet ; 22(2): 43-50, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31942416

RESUMO

Matrix Gla protein (MGP) is an important regulatory protein for inhibition of calcification in the vessel wall and cartilage. The MGP gene polymorphisms are suspected to increase the risk of extracellular calcification through altering the related gene expression and serum MGP levels. The goal of this study was to examine the correlation between rs4236 (Thr83-Ala), rs12304 (Glu60-X) and rs1800802 (T138-C) polymorphisms of the MGP gene and coronary artery calcification. Serum MGP levels of 168 subjects who had undergone coronary angiography were analyzed along with genotyping of MGP gene polymorphisms. The results indicated that serum MGP levels were significantly associated with rs4236 and rs1800802 polymorphisms of the MGP gene with the occurrence of coronary artery diseases (CAD). Allelic distributions of MGP gene polymorphisms and serum MGP levels, respectively, were not significantly interconnected with the presence of CAD. Our results revealed that serum MGP levels of CAD patients show association with rs4236 and rs1800802 polymorphisms, but serum MGP levels alone do not directly reflect the risk of CAD. The role of MGP genetic variants on formation and progression of arterial calcification should be regarded in cardiovascular diseases.

5.
Braz J Cardiovasc Surg ; 33(1): 104-106, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29617509

RESUMO

Cardiac angiosarcomas are extremely rare in childhood, they are rapidly progressive tumours that often present themselves as diagnostic dilemmas, resulting in delayed diagnosis. Also, extracardiac manifestations, including abdominal pain, are extremely rare in patients with intracardiac tumors. We herein present the case of a 15-year-old girl who presented with abdominal pain. Echocardiography and thoracic computed tomography showed right atrial mass. The patient underwent surgery, chemotherapy, and radiotherapy. Eight months after treatment, abdominal recurrence was detected. The abdominal mass was resected, and radiotherapy and new chemotherapy protocol were given. The present case illustrates a rare case of primary cardiac angiosarcoma posing a diagnostic dilemma in an adolescent girl.


Assuntos
Dor Abdominal/etiologia , Neoplasias Cardíacas/complicações , Hemangiossarcoma/complicações , Dor Abdominal/diagnóstico por imagem , Adolescente , Feminino , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Hemangiossarcoma/diagnóstico por imagem , Hemangiossarcoma/cirurgia , Humanos , Doenças Raras , Tomografia Computadorizada por Raios X
6.
Rev. bras. cir. cardiovasc ; 33(1): 104-106, Jan.-Feb. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-897986

RESUMO

Abstract Cardiac angiosarcomas are extremely rare in childhood, they are rapidly progressive tumours that often present themselves as diagnostic dilemmas, resulting in delayed diagnosis. Also, extracardiac manifestations, including abdominal pain, are extremely rare in patients with intracardiac tumors. We herein present the case of a 15-year-old girl who presented with abdominal pain. Echocardiography and thoracic computed tomography showed right atrial mass. The patient underwent surgery, chemotherapy, and radiotherapy. Eight months after treatment, abdominal recurrence was detected. The abdominal mass was resected, and radiotherapy and new chemotherapy protocol were given. The present case illustrates a rare case of primary cardiac angiosarcoma posing a diagnostic dilemma in an adolescent girl.


Assuntos
Humanos , Feminino , Adolescente , Dor Abdominal/etiologia , Neoplasias Cardíacas/complicações , Hemangiossarcoma/complicações , Tomografia Computadorizada por Raios X , Dor Abdominal/diagnóstico por imagem , Doenças Raras , Neoplasias Cardíacas/cirurgia , Neoplasias Cardíacas/diagnóstico por imagem , Hemangiossarcoma/cirurgia , Hemangiossarcoma/diagnóstico por imagem
7.
Environ Entomol ; 46(4): 1035-1040, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28505238

RESUMO

Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is one of the most important insect pests worldwide including Turkey. Although there are substantial data regarding species composition of Turkish B. tabaci populations, the situation is still not clear and further investigations are needed. Therefore, in this study, species and subgroups of B. tabaci collected from cotton fields in southwestern part of Turkey (Antalya, Aydin, Denizli, and Mugla) were determined using microsatellite analysis, AluI-based mtCOI polymerase chain reaction-random length polymorphism, and sequencing. Secondary endosymbionts were also determined using diagnostic species-specific PCR. Middle East Asia Minor 1 (MEAM1), Mediterranean (MED) Q1, and MED Q2 were the species and subgroups found in this study. The MED species (85.3%) were found to be more dominant than MEAM1. Species status of B. tabaci varied depending on the location. Although all samples collected from Aydin were found to be Q1, three species and subgroups were found in Mugla. Secondary endosymbionts varied according to species and subgroups. Arsenophonus was found only from Q2, while Hamiltonella was detected in MEAM1 and Q1. In addition, high Rickettsia and low Wolbachia infections were detected in MEAM1 and Q1 populations, respectively. In conclusion, for the first time, we report the presence and symbiotic communities of Q1 from Turkey. We also found that the symbiont complement of the Q1 is more congruent with Q1 from Greece than other regions of the world, which may have some interesting implications for movement of this invasive subgroup.


Assuntos
Bactérias/isolamento & purificação , Fenômenos Fisiológicos Bacterianos , Hemípteros/classificação , Hemípteros/microbiologia , Simbiose , Animais , Bactérias/classificação , Bactérias/genética , Feminino , Gossypium/crescimento & desenvolvimento , Filogenia , Reação em Cadeia da Polimerase , Turquia
8.
Andrologia ; 49(7)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27596009

RESUMO

Epigenetics has become a major field of reproductive medicine after the epigenetic regulation of gene expression was discovered. The aim of this study was to find out whether or not methylenetetrahydrofolate reductase (MTHFR) gene promoter hypermethylation in the spermatozoa of men who were offered assisted reproduction is associated with idiopathic male infertility. Sperm DNAs from 40 idiopathic infertile men with normozoospermia and 40 controls consisting of healthy fertile men were isolated. Following the modification of DNAs by sodium bisulphite, the methylation status of the MTHFR gene promoter was quantified by pyrosequencing. No significant differences were observed between the clinical characteristics of patients and controls. The percentage of MTHFR promoter methylation in infertile men with normozoospermia (11%) was significantly higher than that in the healthy control (4.3%) group (p = .01). A 9.5% of methylation level was determined via receiver operator characteristic (ROC) analysis as the cut-off value. There were 21 (53%) hypermethylated men among the infertile men and 2 (5%) in the control group (p = .0001). The intragroup analysis of the infertile group did not reveal any statistically significant differences in terms of overall clinical characteristics between hyper- and normo-methylated infertile men. Our results suggest that epigenetic silencing (hypermethylation) of MTHFR could result in an elevated risk of male infertility.


Assuntos
Metilação de DNA , Infertilidade Masculina/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Regiões Promotoras Genéticas/genética , Adulto , DNA/química , Epigênese Genética/genética , Inativação Gênica , Humanos , Masculino , Curva ROC , Espermatozoides/química , Espermatozoides/enzimologia
10.
Biochim Biophys Acta ; 1850(2): 343-51, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25445712

RESUMO

BACKGROUND: Plasma levels of pancreatic polypeptide (PP) rise upon food intake. Although other pancreatic islet hormones, such as insulin and glucagon, have been extensively investigated, PP secretion and actions are still poorly understood. METHODS: The release of PP upon glucose stimulation and the effects of PP on glucagon and insulin secretion were analyzed in isolated pancreatic islets. Expression of PP receptor (PPYR1) was investigated by immunoblotting, quantitative RT-PCR on sorted pancreatic islet cells, and immunohistochemistry. RESULTS: In isolated mouse pancreatic islets, glucose stimulation increased PP release, while insulin secretion was up and glucagon release was down. Direct exposure of islets to PP inhibited glucagon release. In mouse islets, PPYR1 protein was observed by immunoblotting and quantitative RT-PCR revealed PPYR1 expression in the FACS-enriched glucagon alpha-cell fraction. Immunohistochemistry on pancreatic sections showed the presence of PPYR1 in alpha-cells of both mouse and human islets, while the receptor was absent in other islet cell types and exocrine pancreas. CONCLUSIONS: Glucose stimulates PP secretion and PP inhibits glucagon release in mouse pancreatic islets. PP receptors are present in alpha-cells of mouse and human pancreatic islets. GENERAL SIGNIFICANCE: These data demonstrate glucose-regulated secretion of PP and its effects on glucagon release through PPYR1 receptors expressed by alpha-cells.


Assuntos
Regulação da Expressão Gênica/fisiologia , Células Secretoras de Glucagon/metabolismo , Glucagon/metabolismo , Polipeptídeo Pancreático/metabolismo , Receptores de Neuropeptídeo Y/biossíntese , Animais , Células Cultivadas , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células Secretoras de Glucagon/citologia , Glucose/farmacologia , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Edulcorantes/farmacologia
11.
Sci Total Environ ; 499: 74-88, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25173864

RESUMO

The Chernobyl Nuclear Power Plant (CNPP) accident occurred on April 26 of 1986, it is still an episode of interest, due to the large amount of radionuclides dispersed in the atmosphere. Caesium-137 ((137)Cs) is one of the main radionuclides emitted during the Chernobyl accident, with a half-life of 30years, which can be accumulated in humans and animals, and for this reason the impacts on population are still monitored today. One of the main parameters in order to estimate the exposure of population to (137)Cs is the concentration in the air, during the days after the accident, and the deposition at surface. The transport and deposition of (137)Cs over Europe occurred after the CNPP accident has been simulated using the WRF-HYSPLIT modeling system. Four different vertical and temporal emission rate profiles have been simulated, as well as two different dry deposition velocities. The model simulations could reproduce fairly well the observations of (137)Cs concentrations and deposition, which were used to generate the 'Atlas of Caesium deposition on Europe after the Chernobyl accident' and published in 1998. An additional focus was given on (137)Cs deposition and air concentrations over Turkey, which was one of the main affected countries, but not included in the results of the Atlas. We estimated a total deposition of 2-3.5 PBq over Turkey, with 2 main regions affected, East Turkey and Central Black Sea coast until Central Anatolia, with values between 10 kBq m(-2) and 100 kBq m(-2). Mean radiological effective doses from simulated air concentrations and deposition has been estimated for Turkey reaching 0.15 mSv/year in the North Eastern part of Turkey, even if the contribution from ingestion of contaminated food and water is not considered, the estimated levels are largely below the 1 mSv limit indicated by the International Commission on Radiological Protection.


Assuntos
Radioisótopos de Césio/análise , Acidente Nuclear de Chernobyl , Doses de Radiação , Monitoramento de Radiação , Poluentes Radioativos/análise , Atmosfera/química , Meia-Vida , Centrais Nucleares , Turquia
12.
Cardiovasc J Afr ; 23(1): 34-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22331249

RESUMO

BACKGROUND: Postoperative atrial fibrillation is common after cardiac surgery. In this study, we aimed to investigate the value of interatrial conduction time for the prediction of early postoperative atrial fibrillation, using intra-operative transoesophageal echocardiography. METHODS: A total of 65 patients undergoing cardiac surgery in our hospital between January and March 2007 were prospectively evaluated, and 59 patients with sinus rhythm were included in the study. We performed transoesophageal echocardiography on all patients, and intra-operatively measured the interatrial conduction time, as recently described. The patients with episodes of atrial fibrillation during the postsurgery hospitalisation period were defined as group 1 and those without episodes were defined as group 2. RESULTS: Mean interatrial conduction time was 74 ± 15.9 ms in group 1 and 54 ± 7.9 ms in group 2. The difference in interatrial conduction time between the two groups was statistically significant (p < 0.05). In this study we found a statistically significant interatrial conduction delay between the groups. Postoperative atrial fibrillation was more frequent in patients with a longer interatrial conduction time. CONCLUSION: Increased interatrial conduction time may cause postoperative atrial fibrillation and it can be measured intraoperatively by transoesophageal echocardiography.


Assuntos
Fibrilação Atrial , Sistema de Condução Cardíaco , Procedimentos Cirúrgicos Cardíacos , Ecocardiografia Transesofagiana , Eletrocardiografia , Humanos
13.
JIMD Rep ; 3: 17-23, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23430869

RESUMO

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder caused by defective cellular carnitine transport. Patients usually present with predominant metabolic or cardiac manifestations. SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5) gene. Mutation analysis of SLC22A5 gene was carried out in eight Turkish patients from six families. Six patients presented with signs and symptoms of heart failure, cardiomyopathy, and low plasma carnitine levels, five of them with concurrent anemia. A patient with dilated cardiomyopathy had also facial dysmorphia, microcephaly, and developmental delay. Tandem MS analyses in siblings of the patients revealed two more cases with low plasma carnitine levels. SCD diagnosis was confirmed in these two cases by mutation screening. These two cases were asymptomatic but echocardiography revealed left ventricular dilatation in one of them. Carnitine treatment was started before the systemic signs and symptoms developed in these patients. Mean value of serum carnitine levels of the patients was 2.63±1.92µmol/L at the time of diagnosis. After 1year of treatment, carnitine values increased to 16.62±5.11 (p<0.001) and all responded to carnitine supplementation clinically. Mutation screening of the OCTN2 gene study in the patients revealed two novel (p.G411V, p.G152R), and four previously identified mutations (p.R254X, p.R282X, p.R289X, p.T337Pfs12X). Early recognition and carnitine supplementation can be lifesaving in this inborn error of fatty acid oxidation.

14.
Artigo em Inglês | MEDLINE | ID: mdl-24779694

RESUMO

Analysis of residual levels of tetracyclines (TCs) in chicken meat was performed using a validated liquid chromatography coupled with a tandem mass spectrometry (LC-MS/MS) technique. Overall, the recoveries for TCs ranged from 56.9% to 101.2%, with standard deviations of 4.5-13.2%. Detection limits ranged from 7.9 to 14.6 µg kg⁻¹. In four of 60 samples, doxycycline (DXC) was determined in a range from 19.9 to 35.6 µg kg⁻¹; and in one sample tetracycline was detected at 17.2 µg kg⁻¹. Chlortetracycline (CTC) and oxytetracycline (OTC) were not detected in any of the tested samples. This study indicates that chicken meat sold in Bursa, Turkey, contained some residues of TCs. Therefore, stricter regulations for the use of antibiotics in the poultry industry and the monitoring of drug residues in chicken meat prior to marketing are needed. Finally, this method has been applied successfully for the confirmation of TCs in chicken meat.


Assuntos
Antibacterianos/análise , Resíduos de Drogas/análise , Contaminação de Alimentos , Carne/análise , Tetraciclinas/análise , Animais , Antibacterianos/química , Galinhas , Cromatografia Líquida de Alta Pressão , Doxiciclina/análise , Doxiciclina/química , União Europeia , Inspeção de Alimentos , Fidelidade a Diretrizes , Limite de Detecção , Carne/economia , Carne/normas , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Tetraciclina/análise , Tetraciclina/química , Tetraciclinas/química , Turquia , Drogas Veterinárias/normas
15.
Clin Exp Obstet Gynecol ; 38(3): 276-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21995165

RESUMO

Nabothian cysts generally being small-sized and multiple are common gynecopathological conditions of women in reproductive age. We report a case of a giant nabothian cyst compressing the rectum apparently without gynecologic symptoms. Initial symptoms of pain and difficulty in defecation due to compression on the rectal wall because of the huge size of the cyst might be the first case in the literature. We made the differential diagnosis from adenoma malignum (minimal-deviation adenocarsinoma) by using immunhistochemical and histopathological techniques.


Assuntos
Cistos/diagnóstico , Doenças Retais/etiologia , Doenças do Colo do Útero/diagnóstico , Cistos/cirurgia , Diagnóstico Diferencial , Feminino , Exame Ginecológico , Humanos , Pessoa de Meia-Idade , Doenças Retais/cirurgia , Doenças do Colo do Útero/cirurgia
16.
Oncogene ; 29(22): 3208-16, 2010 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-20383201

RESUMO

Activation of androgen receptor (AR) may have a role in the development of castration-resistant prostate cancer. Two intracellular tyrosine kinases, Ack1 (activated cdc42-associated kinase) and Src, phosphorylate and enhance AR activity and promote prostate xenograft tumor growth in castrated animals. However, the upstream signals that activate these kinases and lead to AR activation are incompletely characterized. In this study, we investigated AR phosphorylation in response to non-androgen ligand stimulation using phospho-specific antibodies. Treatment of LNCaP and LAPC-4 cells with epidermal growth factor (EGF), heregulin, Gas6 (ligand binding to the Mer receptor tyrosine kinase and activating Ack1 downstream), interleukin (IL)-6 or bombesin stimulated cell proliferation in the absence of androgen. Treatment of LNCaP and LAPC-4 cells with EGF, heregulin or Gas6 induced AR phosphorylation at Tyr-267, whereas IL-6 or bombesin treatment did not. AR phosphorylation at Tyr-534 was induced by treatment with EGF, IL-6 or bombesin, but not by heregulin or Gas6. Small interfering RNA-mediated knockdown of Ack1 or Src showed that Ack1 mediates heregulin- and Gas6-induced AR Tyr-267 phosphorylation, whereas Src mediates Tyr-534 phosphorylation induced by EGF, IL-6 and bombesin. Dasatinib, a Src inhibitor, blocked EGF-induced Tyr-534 phosphorylation. In addition, we showed that dasatinib also inhibited Ack1 kinase. Dasatinib inhibited heregulin-induced Ack1 kinase activity and AR Tyr-267 phosphorylation. In addition, dasatinib inhibited heregulin-induced AR-dependent reporter activity. Dasatinib also inhibited heregulin-induced expression of endogenous AR target genes. Dasatinib inhibited Ack1-dependent colony formation and prostate xenograft tumor growth in castrated mice. Interestingly, Ack1 or Src knockdown or dasatinib did not inhibit EGF-induced AR Tyr-267 phosphorylation or EGF-stimulated AR activity, suggesting the existence of an additional tyrosine kinase that phosphorylates AR at Tyr-267. These data suggest that specific tyrosine kinases phosphorylate AR at distinct sites and that dasatinib may exert antitumor activity in prostate cancer through inhibition of Ack1.


Assuntos
Antagonistas de Receptores de Andrógenos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacologia , Tiazóis/farmacologia , Quinases da Família src/antagonistas & inibidores , Animais , Células COS , Processos de Crescimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Chlorocebus aethiops , Dasatinibe , Humanos , Immunoblotting , Masculino , Camundongos , Fosforilação/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Transdução de Sinais , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases da Família src/genética , Quinases da Família src/metabolismo
17.
Cardiovasc J Afr ; 20(2): 119-21, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19421647

RESUMO

The left internal mammary artery (LIMA) is the most commonly used arterial graft for coronary artery bypass graft (CABG) surgery, and occluding the LIMA side branches during surgery is important to avoid myocardial ischaemia afterwards. In this study we investigated the incidence of patent LIMA graft side branches in our coronary angiography series, and compared LIMA flow rate changes by means of the thrombolysis in myocardial infarction (TIMI) frame count in patients with and without LIMA graft side branches. Patients with a history of CABG surgery and who were scheduled for coronary angiography in our centre between 1 January and 15 December 2006 were enrolled in the study. We compared LIMA graft TIMI frame counts between patients with and without side branches. The incidence of LIMA graft side branches in our study was 18% (seven patients). Mean TIMI frame count was 27.28 +/- 3.4 in patients with LIMA graft side branches and 15.67 +/- 2.3 in patients without. There was a significant difference between the two groups (p < 0.0001). Patients with LIMA graft side branches were more likely to have anterior ischaemia, determined by myocardial perfusion scintigraphy. We suggest that TIMI frame count may be helpful in evaluating the effect of side branches on LIMA graft flow rate. The increased TIMI frame count of a LIMA graft with side branch is associated with insufficient LIMA flow.


Assuntos
Ponte de Artéria Coronária/métodos , Circulação Coronária/fisiologia , Artéria Torácica Interna/fisiopatologia , Isquemia Miocárdica/cirurgia , Fluxo Sanguíneo Regional/fisiologia , Idoso , Angiografia Coronária , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Oclusão de Enxerto Vascular/fisiopatologia , Oclusão de Enxerto Vascular/prevenção & controle , Humanos , Masculino , Artéria Torácica Interna/transplante , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatologia , Imagem de Perfusão do Miocárdio/métodos , Estudos Retrospectivos , Terapia Trombolítica/métodos , Resultado do Tratamento
18.
Diabetes Metab ; 35(2): 77-84, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19251449

RESUMO

In the adult, the pancreatic beta-cell mass adapts insulin secretion to meet long-term changes in insulin demand and, in particular, in the presence of insulin resistance that is either physiological, such as pregnancy, or pathophysiological, such as obesity. The failure of beta cells to compensate for insulin resistance is a major component of impaired glucose homeostasis and overt diabetes. This defect is clearly the consequence of a decline of insulin response to glucose due to functional beta-cell deficiency. It is also the consequence of an inability of the endocrine pancreas to adapt the beta-cell mass to insulin demand (pancreas plasticity), which eventually leads to a decrease in functional beta-cell mass. This idea has resulted in considerable attention being paid to the development of new therapeutic strategies aiming to preserve and/or regenerate functional beta-cell mass. The latter is governed by a constant balance between beta-cell growth (replication from pre-existing beta cells and neogenesis from precursor cells) and beta-cell death (mainly apoptosis). Disruption of this balance may lead to rapid and marked changes in beta-cell mass. Glucagon-like peptide-1 (GLP-1), an incretin, enhances beta-cell survival (by activating beta-cell proliferation and differentiation, and inhibiting beta-cell apoptosis), thus contributing to the long-term regulation of insulin secretion by maintaining a functional beta-cell mass. The development of drugs regulating this parameter will be the major challenge of the next few years in the management of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Incretinas/fisiologia , Células Secretoras de Insulina/fisiologia , Adaptação Fisiológica , Dipeptidil Peptidase 4 , Inibidores da Dipeptidil Peptidase IV , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Humanos , Incretinas/uso terapêutico , Resistência à Insulina , Células Secretoras de Insulina/citologia
20.
J Int Med Res ; 36(3): 471-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18534128

RESUMO

This study investigated the effects of chronic arsenic exposure on QT- and QTc-interval prolongation, QTc dispersion (QTcd) and transmural dispersion of repolarization (TDR). We compared cardiac parameters from 40 male subjects chronically exposed to arsenic (group A) with those of 40 male subjects not exposed to arsenic (group B). Although subjects in both groups had non-corrected QT intervals within normal limits, subjects in group A had significantly longer QTc and QTcd intervals compared with group B. A total of 70% of group A compared with 10% of group B had QTcd values > 50 ms. The mean TDR value was also significantly higher in group A compared with group B. Although non-corrected QT intervals were within normal limits, those subjects chronically exposed to arsenic had a slight QT prolongation and a higher prevalence of subtle repolarization abnormalities, which might be clinically relevant.


Assuntos
Intoxicação por Arsênico/fisiopatologia , Exposição Ambiental , Sistema de Condução Cardíaco/fisiopatologia , Abastecimento de Água , Adulto , Estudos de Casos e Controles , Doença Crônica , Demografia , Eletrocardiografia , Humanos , Masculino
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