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1.
Anticancer Res ; 39(11): 6373-6378, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704870

RESUMO

BACKGROUND/AIM: Radiotherapy (RT) with adjuvant hormone therapy (HT) improves prognosis in prostate cancer (PC) patients. Gonadotrophin-releasing hormone agonist (GnRHa) with luteinizing hormone-releasing hormone (LH-RH) analogues is the standard HT. High-dose antiandrogen therapy also improves survival in patients with locally advanced PC. The aim of this study was to compare the results of patients treated with RT plus GnRHa and patients treated with RT plus bicalutamide. PATIENTS AND METHODS: Our institutional PC database was used to identify patients treated with definitive or postoperative RT +/- HT which were included in this study. RESULTS: Three hundred and eighteen patients were retrospectively reviewed (median follow-up=56 months). Five-year biochemical relapse-free survival was 85.5% and 88.3% in patients treated with GnRHa and bicalutamide, respectively (p=0.712). CONCLUSION: Bicalutamide may be offered as an adjuvant treatment to RT in patients who refuse GnRHa because of related side effects. Furthermore, our study justifies randomized trials comparing RT plus GnRHa and RT plus bicalutamide.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Anilidas/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Hormônio Liberador de Gonadotropina/agonistas , Nitrilos/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Compostos de Tosil/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/efeitos adversos , Anilidas/efeitos adversos , Antineoplásicos Hormonais/efeitos adversos , Estudos de Casos e Controles , Terapia Combinada/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Prognóstico , Antígeno Prostático Específico/sangue , Estudos Retrospectivos , Compostos de Tosil/efeitos adversos
3.
Environ Health Prev Med ; 24(1): 39, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153359

RESUMO

BACKGROUND: Cervical vestibular evoked myogenic potential (cVEMP) testing is a strong tool that enables objective determination of balance functions in humans. However, it remains unknown whether cVEMP correctly expresses vestibular disorder in mice. OBJECTIVE: In this study, correlations of cVEMP with scores for balance-related behavior tests including rotarod, beam, and air-righting reflex tests were determined in ICR mice with vestibular disorder induced by 3,3'-iminodipropiontrile (IDPN) as a mouse model of vestibular disorder. METHODS: Male ICR mice at 4 weeks of age were orally administered IDPN in saline (28 mmol/kg body weight) once. Rotarod, beam crossing, and air-righting reflex tests were performed before and 3-4 days after oral exposure one time to IDPN to determine balance functions. The saccule and utricles were labeled with fluorescein phalloidin. cVEMP measurements were performed for mice in the control and IDPN groups. Finally, the correlations between the scores of behavior tests and the amplitude or latency of cVEMP were determined with Spearman's rank correlation coefficient. Two-tailed Student's t test and Welch's t test were used to determine a significant difference between the two groups. A difference with p < 0.05 was considered to indicate statistical significance. RESULTS: After oral administration of IDPN at 28 mmol/kg, scores of the rotarod, beam, and air-righting reflex tests in the IDPN group were significantly lower than those in the control group. The numbers of hair cells in the saccule, utricle, and cupula were decreased in the IDPN group. cVEMP in the IDPN group was significantly decreased in amplitude and increased in latency compared to those in the control group. cVEMP amplitude had significant correlations with the numbers of hair cells as well as scores for all of the behavior tests in mice. CONCLUSIONS: This study demonstrated impaired cVEMP and correlations of cVEMP with imbalance determined by behavior tests in a mouse model of vestibular disorder.


Assuntos
Equilíbrio Postural/fisiologia , Transtornos das Sensações/fisiopatologia , Doenças Vestibulares/fisiopatologia , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Células Ciliadas Vestibulares/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nitrilos/efeitos adversos , Equilíbrio Postural/efeitos dos fármacos , Sáculo e Utrículo/patologia , Transtornos das Sensações/induzido quimicamente , Doenças Vestibulares/induzido quimicamente , Doenças Vestibulares/diagnóstico , Doenças Vestibulares/patologia , Potenciais Evocados Miogênicos Vestibulares/efeitos dos fármacos , Testes de Função Vestibular
4.
Rinsho Shinkeigaku ; 59(7): 418-424, 2019 Jul 31.
Artigo em Japonês | MEDLINE | ID: mdl-31243247

RESUMO

A 76-year-old man, diagnosed with chronic myeloid leukemia in 2010, had been on nilotinib for 7 years. He presented with right hemiparesis in September 2017. He had no history of hypertension, diabetes, hyperlipidemia, heart disease, or smoking. Brain MRI revealed a border-zone infarction of the left cerebral hemisphere and a rapidly progressing severe left internal carotid artery (ICA) stenosis. He was initiated on clopidogrel and bosutinib instead of nilotinib. He presented with right hemiparesis once again in December 2017. Brain MRI revealed the border-zone infarction of the left cerebral hemisphere and a more progressed, severe bilateral ICA stenosis. A carotid ultrasound demonstrated iso-intense and concentrically narrowed ICA on both sides. Carotid artery stenting of the left ICA was performed in February 2018, and clopidogrel was replaced by cilostazol to provide a drug-induced rush. Carotid artery stenting of the right ICA was performed in June 2018 and cervical angiogram demonstrated that there were no residual artery stenoses in the bilateral stent. In recent years, several case reports suggest that tyrosine kinase inhibitors (TKIs) are associated with progressive artery stenosis and cause cerebral infarction. Brain imaging tests should be conducted to evaluate arterial stenosis progression for patients with a history of taking TKI when an arterial vascular event occurs.


Assuntos
Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Infarto Cerebral/induzido quimicamente , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Nitrilos/administração & dosagem , Nitrilos/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Administração Oral , Idoso , Artéria Carótida Interna , Estenose das Carótidas/induzido quimicamente , Estenose das Carótidas/cirurgia , Infarto Cerebral/diagnóstico por imagem , Clopidogrel/administração & dosagem , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Recidiva , Stents
5.
Ann Hematol ; 98(8): 1885-1890, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31044260

RESUMO

There is little information about cardiovascular adverse event (CV-AE) incidence in chronic myeloid leukemia (CML) patients treated with bosutinib in the real-life practice. We identified 54 consecutive CML patients treated with bosutinib, stratified according to the Systematic Coronary Risk Evaluation (SCORE) assessment, based on sex, age, smoking habits, systolic blood pressure, and total cholesterol levels. The 40-month cumulative incidence of CV-AEs was 25.2 ± 8.1%. Patients with the SCORE of high-very high showed a significantly higher incidence of CV-AEs (55 ± 12.9% vs 9 ± 9.5%; p = 0.002). Overall, 9 CV-AEs were reported, with 2 deaths attributed to CV-AE. In conclusion, the SCORE assessment before starting treatment is helpful in identifying CV-AE high-risk patients during bosutinib treatment.


Assuntos
Compostos de Anilina/efeitos adversos , Antineoplásicos/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Infarto do Miocárdio/induzido quimicamente , Nitrilos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/induzido quimicamente , Angina Pectoris/diagnóstico , Angina Pectoris/fisiopatologia , Compostos de Anilina/administração & dosagem , Antineoplásicos/administração & dosagem , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Dasatinibe/administração & dosagem , Dasatinibe/efeitos adversos , Suscetibilidade a Doenças , Esquema de Medicação , Feminino , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Nitrilos/administração & dosagem , Doenças Vasculares Periféricas/induzido quimicamente , Doenças Vasculares Periféricas/diagnóstico , Doenças Vasculares Periféricas/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Quinolinas/administração & dosagem , Estudos Retrospectivos
6.
Ecotoxicology ; 28(5): 569-577, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31129746

RESUMO

Chlorothalonil is a commonly used fungicide to control the karnal bunt caused by Tilletia indica Mitra in wheat production from the Yaqui Valley, Mexico. Here, the effect of Chlorothalonil on the growth of 132 bacterial strains associated with wheat rhizosphere from the Yaqui Valley was evaluated, as well as their ability to produce indoles. Thirty-three percent of the evaluated strains were inhibited by Chlorothalonil, being Bacillus and Paenibacillus the most inhibited genera, observing an inhibition >50% of their strains. In addition, 49% of the inhibited strains showed the ability to produce indoles (>5 µg/mL), where the genus Bacillus was the most abundant (80%). The remaining strains (67%) were tolerant to the evaluated fungicide, but only 37% of those showed the ability to produce indoles, which could be considered as Plant Growth Promoting Rhizobacteria (PGPR). These results showed that Chlorothalonil is not only an antifungal compound but also inhibits the growth of bacterial strains with the ability to produce indoles. Thus, the intensive application of fungicides to agro-systems needs more validation in order to develop sustainable agricultural practices for food production.


Assuntos
Bacillus/efeitos dos fármacos , Fungicidas Industriais/efeitos adversos , Nitrilos/efeitos adversos , Paenibacillus/efeitos dos fármacos , Rizosfera , Bacillus/metabolismo , Bacillus/fisiologia , Indóis/metabolismo , México , Paenibacillus/metabolismo , Paenibacillus/fisiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Triticum/microbiologia
7.
Curr Med Sci ; 39(1): 21-27, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30868487

RESUMO

Increased use of pyrethroids and the exposure to pyrethroids for pregnant women and children have raised the concerns over the potential effect of pyrethroids on developmental cardiotoxicity and other abnormalities. The purpose of this study was to investigate whether long term perinatal deltamethrin exposure altered embryonic cardiac electrophysiology in mice. Pregnant mice were administered with 0 or 3 mg/kg of deltamethrin by gavage daily from gestational day (gd) 10.5 to gd 17. 5. Whole cell patch-clamp technique was used in electrophysiological study, and real time RT-PCR was applied to analyze the molecular changes for the electrophysiological properties. Deltamethrin exposure resulted in increased mortality of pregnant mice and decreased viability of embryos. Moreover, deltamethrin slowed the maximum depolarization velocity (Vmax), prolonged the action potential duration (APD) and depolarized the maximum diastolic potential (MDP) of embryonic cardiomyocytes. Additionally, perinatal deltamethrin exposure decreased the mRNA expression of Na+ channel regulatory subunit Navß1, inward rectifier K+ channel subunit Kir2.1, and delayed rectifier K+ channel subunit MERG while the L-type Ca2+ channel subunit, Cav1.2 expression was increased. On the contrary, deltamethrin administration did not significantly alter the regulation of ß-adrenergic or muscarinic receptor on embryonic cardiomyocytes. In conclusion, deltamethrin exposure at perinatal stage significantly alters mRNA expression of embryonic cardiac ion channels and therefore influences embryonic cardiac electrophysiological properties. This highlights the need to understand the persistent effects of pyrethroid exposure on cardiac function during embryonic development due to potential for cardiac arrhythmogenicity.


Assuntos
Embrião de Mamíferos/efeitos dos fármacos , Exposição Materna/efeitos adversos , Miócitos Cardíacos/citologia , Nitrilos/efeitos adversos , Piretrinas/efeitos adversos , Potenciais de Ação/efeitos dos fármacos , Animais , Canais de Cálcio Tipo L/genética , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Canal de Potássio ERG1 , Embrião de Mamíferos/química , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Idade Gestacional , Humanos , Camundongos , Mortalidade , Miócitos Cardíacos/efeitos dos fármacos , Canais de Potássio Corretores do Fluxo de Internalização/genética , Gravidez
8.
Mycoses ; 62(6): 534-541, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30851214

RESUMO

BACKGROUND: Isavuconazole use in the real-world setting has not been extensively described. Subgroups of patients with particular prognostic significance, such as previous triazole prophylaxis or treatment and the important subgroup treated empirically for invasive fungal infection, have beforehand been excluded from trials. OBJECTIVES: We aimed to determine treatment response and safety in these patients at a large US transplant and cancer centre. PATIENTS/METHODS: We conducted a retrospective cohort study of all adult inpatients administered ≥3 doses of isavuconazole between June 2015 and October 2017. RESULTS: Ninety-one adults were identified. Six (7%) received primary prophylaxis, 10 (11%) treatment then secondary prophylaxis and 75 (82%) treatment only. Overall treatment response was 62%. Six-week mortality was 24%. Sixty-three per cent of 32 patients treated with isavuconaozle following prophylaxis with another antifungal agent exhibited a treatment response. Among 49 patients switched from treatment with another agent, 53% had a treatment response. Thirty-four patients received isavuconazole empirically, and 65% demonstrated a treatment response. Individuals given isavuconazole prophylaxis developed no breakthrough invasive fungal infections. One patient discontinued isavuconazole due to hepatotoxicity. CONCLUSIONS: Real-world isavuconazole use appears safe and is associated with treatment responses in varied patients including critically important subgroups previously unreported.


Assuntos
Antifúngicos/uso terapêutico , Quimioprevenção/métodos , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Centros Médicos Acadêmicos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/efeitos adversos , Substituição de Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Piridinas/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Triazóis/efeitos adversos , Estados Unidos
9.
Life Sci ; 220: 76-83, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30695709

RESUMO

AIMS: Deltamethrin (DM), a type II synthetic pyrethroid insecticide, is widely used in agriculture and home pest control. The evaluation of their toxic effects is of major concern to public health. However, the molecular mechanism of DM-induced neurodegenerative disease is still far from clear. This study was designed to investigate the potential role of ubiquitin proteasome system (UPS) in DM-induced neurotoxicity where the proteasome inhibitor MG-132 could mitigate the neurotoxic effects. MAIN METHODS: Male Sprague-Dawley rats were divided into two batches. The first batch of rats was administrated with a single dose of DM (12.5 mg/kg) by intraperitoneal injections (i.p.) and the animals were then euthanized at 5, 24, and 48 h post injection. The second batch was treated as follow: control group, DM (12.5 mg/kg) groups for 24 h, MG-132 (0.5 mg/kg, i.p.) 2 h plus DM 24 h group, and MG-132 alone group. Ubiqutinatied proteins, DNA damage and apoptosis were investigated. KEY FINDINGS: DM treatment induced the ubiquitinated proteins expression with the peaks at 5 h. Moreover, DM increased DNA damage, early apoptotic rate, the expression level of Cleaved Caspase-3, caspase-3 activity and decreased the expression level of Bcl-2 at DM 24 h group. Compared to DM 24 h group, MG-132 pretreatment significantly down-regulated ubiquitinated proteins, lowered the DNA damage and apoptosis by decreasing Caspase-3 and increasing Bcl-2 expression. SIGNIFICANCE: These results indicate that MG-132 effectively alleviates DM-induced DNA damage and apoptosis by inhibiting ubiquitinated proteins. UPS may play a role in DM-induced neurodegenerative disorders.


Assuntos
Leupeptinas/farmacologia , Nitrilos/toxicidade , Piretrinas/toxicidade , Complexos Ubiquitina-Proteína Ligase/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Caspase 3/efeitos dos fármacos , Caspase 3/metabolismo , Hipocampo/metabolismo , Inseticidas , Leupeptinas/metabolismo , Masculino , Doenças Neurodegenerativas/induzido quimicamente , Síndromes Neurotóxicas/metabolismo , Nitrilos/efeitos adversos , Complexo de Endopeptidases do Proteassoma/metabolismo , Substâncias Protetoras/farmacologia , Proteostase/efeitos dos fármacos , Piretrinas/efeitos adversos , Ratos , Ratos Sprague-Dawley , Ubiquitina/metabolismo , Complexos Ubiquitina-Proteína Ligase/metabolismo
10.
Leuk Lymphoma ; 60(1): 189-199, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29741440

RESUMO

The tyrosine kinase inhibitors (TKIs), nilotinib, ponatinib, and dasatinib (but not bosutinib or imatinib), are associated with vascular adverse events (VAEs) in chronic myeloid leukemia (CML). Though the mechanism is inadequately understood, an effect on vascular cells has been suggested. We investigated the effect of imatinib, nilotinib, dasatinib, bosutinib, and ponatinib on tube formation, cell viability, and gene expression of human vascular endothelial cells (HUVECs). We found a distinct genetic profile in HUVECs treated with dasatinib, ponatinib, and nilotinib compared to bosutinib and imatinib, who resembled untreated samples. However, unique gene expression and molecular pathway alterations were detected between dasatinib, ponatinib, and nilotinib. Angiogenesis/blood vessel-related pathways and HUVEC function (tube formation/viability) were adversely affected by dasatinib, ponatinib, and nilotinib but not by imatinib or bosutinib. These results correspond to the differences in VAE profiles of these TKIs, support a direct effect on vascular cells, and provide direction for future research.


Assuntos
Antineoplásicos/efeitos adversos , Endotélio Vascular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Compostos de Anilina/efeitos adversos , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Dasatinibe/efeitos adversos , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mesilato de Imatinib/efeitos adversos , Imidazóis/efeitos adversos , Neovascularização Fisiológica/efeitos dos fármacos , Nitrilos/efeitos adversos , Piridazinas/efeitos adversos , Pirimidinas/efeitos adversos , Quinolinas/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Testes de Toxicidade , Transcrição Genética/efeitos dos fármacos
11.
Mycoses ; 62(1): 81-86, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30230043

RESUMO

BACKGROUND: Posaconazole (PCZ) is widely used for prophylaxis or treatment of invasive fungal infections (IFIs) in leukaemia patients. However, issues with PCZ tolerability can result in treatment interruption. Isavuconazole (ISA) has a similar broad spectrum of activity to PCZ; however, real-world data regarding the tolerability of ISA after PCZ toxicity are lacking. OBJECTIVES: To describe the tolerability of ISA after PCZ toxicity in leukaemia patients. PATIENTS/METHODS: We retrospectively assessed tolerability of ISA after PCZ toxicity in adult leukaemia patients (March 2015 to November 2017). We included all patients who received ≥7 days of ISA within 48 hours of PCZ discontinuation. Laboratory markers for liver toxicity were collected at three time points: prior to PCZ, at switch to ISA and after ISA therapy. RESULTS: We identified 23 such patients. Increased liver function tests (LFTs) were noted in 20 patients on PCZ, while three patients had Grade 3/4 QTc prolongation. No patient discontinued subsequent ISA due to toxicity. Grade 3/4 elevations in LFTs were decreased after changing to ISA (30% after PCZ vs 5% after ISA). No patient had significant QTc prolongation after switching to ISA. CONCLUSIONS: Isavuconazole was well-tolerated in patients discontinuing PCZ due to toxicity, with no patient discontinuing ISA due to toxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Leucemia/complicações , Micoses/tratamento farmacológico , Micoses/prevenção & controle , Nitrilos/efeitos adversos , Piridinas/efeitos adversos , Triazóis/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Nitrilos/administração & dosagem , Piridinas/administração & dosagem , Estudos Retrospectivos , Triazóis/administração & dosagem , Adulto Jovem
12.
FASEB J ; 33(2): 2782-2795, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30307764

RESUMO

Fenvalerate (FEN), a mainstream pyrethroid pesticide, was initially recommended as a low-toxicity agent for controlling agricultural and domestic pests. Despite the widespread use of FEN worldwide, little data are available on FEN-induced hepatic lesions and molecular mechanisms. In the present study, we first performed an occupational cross-sectional study on FEN factory workers and found that the levels of serum alanine aminotransferase (ALT) and total antioxidant capacity increased, whereas malondialdehyde decreased in laborers in the working areas where the levels of airborne FEN were much higher compared with the office area. The results were then confirmed by animal experiments that abnormal hepatic histology, increased ALT level, and compromised hepatic oxidative capability were observed in rats exposed to a high concentration of FEN. Furthermore, the bioinformatics analysis of gene microarray in rat liver tissue showed that FEN significantly changed the expressions of genes related to the regulation of intracellular calcium ion homeostasis and the calcium signal pathway. Finally, the functional experiments in Buffalo rat liver (BRL) cells demonstrated that FEN first activated ERK MAPK, followed by IKK and NF-κB, which triggered the transcription of genes responsible for accelerating an overload of intracellular calcium ions, prompted reactive oxygen species generation in the mitochondria, and finally, induced hepatic cellular apoptosis. The calcium signaling pathway and in particular, an overload of intracellular calcium play a critical role in this pathophysiological process via the ERK/IKK/NF-κB pathway. Our study furthers the understanding of the mechanism of FEN-induced hepatic injuries and may have implications in the prevention and control of liver diseases induced by environmental pesticides.-Qiu, L.-L., Wang, C., Yao, S., Li, N., Hu, Y., Yu, Y., Xia, R., Zhu, J., Ji, M., Zhang, Z., Wang S.-L. Fenvalerate induces oxidative hepatic lesions through an overload of intracellular calcium triggered by the ERK/IKK/NF-κB pathway.


Assuntos
Cálcio/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Nitrilos/efeitos adversos , Exposição Ocupacional/efeitos adversos , Piretrinas/efeitos adversos , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Inseticidas/efeitos adversos , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
13.
Ann Hematol ; 98(2): 321-330, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30446802

RESUMO

Bosutinib is a second-generation tyrosine kinase inhibitor (2GTKI) approved at 400 mg once daily (QD) as first-line therapy in patients with chronic myeloid leukemia (CML) patients and at 500 mg QD in patients who are resistant to or intolerant of prior therapy. In clinical practice, bosutinib is often given to patients who have failed imatinib, nilotinib, and dasatinib (i.e., as fourth-line treatment), despite the limited data on its clinical benefit in this setting. We have retrospectively evaluated the results of bosutinib in a series of 62 CML patients who have failed to prior treatment with all three, imatinib, nilotinib, and dasatinib. Median time on TKI treatment before bosutinib start was 105 (9-163) months, and median duration on bosutinib was 9 months (1-30). Overall, probabilities to achieve complete cytogenetic response (CCyR) and major molecular response (MMR) were 25% and 24% respectively. After a median follow-up period of 14 months, the event-free survival and progression-free survival were 68 and 85%, respectively. Sixty-four percent of patients in CCyR at the time of bosutinib start were able to achieve MMR. In contrast, patients without CCyR, probabilities to obtain CCyR and MMR were 25% and 14%. Bosutinib was well tolerated in this heavily pretreated patients' cohort. Pleural effusions and diarrhea were the most frequent grade II-IV side effects, leading to treatment discontinuation in 16% of patients. Bosutinib is an effective treatment option for patients who have failed previous 2GTKIs due to intolerance. However, efficacy seems to be related to the molecular response that the patient achieved prior to bosutinib.


Assuntos
Compostos de Anilina/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Nitrilos/administração & dosagem , Quinolinas/administração & dosagem , Adulto , Compostos de Anilina/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Nitrilos/efeitos adversos , Quinolinas/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
14.
Environ Pollut ; 244: 247-256, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30340169

RESUMO

The pyrethroid deltamethrin and the organophosphate insecticide dimethoate are widely used in agriculture and in urban areas. Both plant protection products (PPPs) unintendedly result in adverse effects in pollinators. Currently, the sublethal effects of both compounds are poorly known, particularly on the molecular and biochemical level. Here we analysed effects of deltamethrin and dimethoate at environmental and sublethal concentrations in honey bee workers by focusing on transcriptional changes of target genes in the brain. In addition, expression of vitellogenin protein and activity of acetylcholinesterase were assessed upon dimethoate exposure to assess physiological effects. Deltamethrin resulted in induction of the cyp9q2 transcript at 0.53 ng/bee, while dimethoate led to induction of vitellogenin on the mRNA and protein level at 2 ng/bee. Transcripts of additional cytochrome P450-dependent monooxygenases (cyps) and genes related to immune system regulation were not differentially expressed upon PPP exposure. Dimethoate but not deltamethrin led to a strong and concentration-related inhibition of the acetylcholinesterase at 2 and 20 ng/bee. Our data demonstrate that deltamethrin and dimethoate exhibit transcriptional effects at environmental concentrations in the brain of honey bees. Dimethoate also strongly affected physiological traits, which may translate to adverse effects in forager bees.


Assuntos
Abelhas , Encéfalo/metabolismo , Dimetoato/efeitos adversos , Expressão Gênica/efeitos dos fármacos , Nitrilos/efeitos adversos , Piretrinas/efeitos adversos , Animais , Inibidores da Colinesterase/efeitos adversos , Sistema Enzimático do Citocromo P-450/metabolismo , Vitelogeninas/biossíntese
15.
Chemosphere ; 219: 155-164, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30537588

RESUMO

Deltamethrin is widely used because of its low toxicity and high efficiency. Although its potential toxicity has been reported, its effects on cardiovascular system and motor behavior and its underlying mechanisms have remained unclear. In this study, the effects of deltamethrin on the development, cardiovascular system and motor behavior of zebrafish larvae and their possible mechanisms were evaluated using the transgenic zebrafish Tg (kdrl:mCherry) and Tg(myl7:GFP). At 72 hpf, the body length of larvae shortened, the head and eye area decreased, and the hatching rate increased. Acridine orange staining showed that treated zebrafish larvae produced different degrees of apoptosis in the head, body, heart and tail regions. Quantitative fluorescence intensity showed a dose-dependent increase in apoptosis signal, indicating that deltamethrin could induce apoptosis. Confocal images and fluorescence intensity quantification of red fluorescent protein-labeled vascular endothelial cell and green fluorescent protein-labeled transgenic zebrafish more clearly reflected the dose-dependent cardiac and vascular morphology and the damage caused by deltamethrin. Deltamethrin significantly induced vascular endothelial growth factor flk1 and fli-1, cardiac development-related gene myl7 decreased in a dose-dependent manner. In addition, deltamethrin increased the thigmotaxis of zebrafish larvae, causing anxiety-like behavior. Our study showed that deltamethrin could cause developmental toxicity, apoptosis, cardiovascular system damage and anxiety-like behavior, which provided a reference for the use of deltamethrin in agricultural production.


Assuntos
Ansiedade/etiologia , Coração/efeitos dos fármacos , Larva/efeitos dos fármacos , Nitrilos/efeitos adversos , Piretrinas/efeitos adversos , Animais , Apoptose , Peixe-Zebra
16.
Mycoses ; 62(3): 217-222, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30570179

RESUMO

BACKGROUND: Long-term oral triazole antifungal therapy is the cornerstone of management for patients with chronic pulmonary aspergillosis (CPA). Itraconazole is the first-line choice of treatment. Voriconazole, posaconazole or isavuconazole can be used as alternative treatments in case of resistance or intolerance. All of these can cause significant adverse drug reactions. OBJECTIVES: To evaluate how CPA patients tolerate voriconazole and isavuconazole after prior triazole therapy. METHODS: We performed a retrospective observational study at the UK National Aspergillosis Centre. Medical records for all consecutive CPA patients started on isavuconazole and voriconazole during an observation period of 12 and 6 months respectively were analysed. RESULTS: During this study period, 20 patients were started on isavuconazole and 21 patients on voriconazole. Adverse events were seen in 18 of 21 (86%) the patients in the voriconazole group and 12 of 20 (60%) in the isavuconazole group (P = 0.02). For those who developed adverse events to these agents, the rates of discontinuation of therapy were comparable (ie 10/18 [56%], voriconazole vs 8/12 [67%], isavuconazole; P = 0.54). Five (25%) patients in the isavuconazole group who were intolerant to other triazoles tolerated the standard dose of isavuconazole. CONCLUSIONS: Compared with isavuconazole, adverse events were significantly higher in CPA patients commenced on voriconazole. Isavuconazole may be an option for those patients who are intolerant to other triazoles.


Assuntos
Antifúngicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Nitrilos/efeitos adversos , Aspergilose Pulmonar/tratamento farmacológico , Piridinas/efeitos adversos , Triazóis/efeitos adversos , Voriconazol/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/administração & dosagem , Doença Crônica , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilos/administração & dosagem , Piridinas/administração & dosagem , Estudos Retrospectivos , Triazóis/administração & dosagem , Reino Unido , Voriconazol/administração & dosagem
17.
J Hematol Oncol ; 11(1): 143, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30587215

RESUMO

Bosutinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI), has been available for several years as a treatment for chronic-, accelerated-, and blast-phase chronic myeloid leukemia (CML), for patients with resistance or intolerance to prior therapy. In 2017, the BFORE trial demonstrated efficacy of bosutinib as first-line treatment in adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). The most common adverse events (AEs) of any grade in bosutinib-treated patients in BFORE were diarrhea, nausea, thrombocytopenia, increased alanine aminotransferase, and increased aspartate aminotransferase, consistent with the most commonly reported AEs in earlier studies. To balance the efficacy and tolerability of treatment to optimize patient adherence with medications, treating physicians commonly use various strategies such as initiating treatment at a lower dose, dose reduction, or dose interruption, depending on the type and severity of the AEs and the clinical setting. In light of the recent data from first-line treatment, an expert panel of hematologists reviewed management strategies for the use of bosutinib in treatment of CP-CML and made the recommendations reported here. Although the panel focused on first-line treatment, the principles can be for the most part extended to bosutinib use in later lines of treatment. Recommendations include advice regarding prophylaxis and management for diarrhea. The panel also considered optimum timing for referral to a specialist for specific AEs. Across the commonly occurring AEs, the panel highlighted the importance of education and communication with patients about anticipated AEs.


Assuntos
Compostos de Anilina/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Nitrilos/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Compostos de Anilina/farmacologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Nitrilos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia
18.
Korean J Parasitol ; 56(5): 491-494, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30419735

RESUMO

Multipurpose contact lens disinfecting solutions (MPDS) are widely used to cleanse and disinfect microorganisms. However, disinfection efficacy of these MPDS against Acanthamoeba cyst remain insufficient. 2, 6-dichlorobenzonitrile (DCB), a cellulose synthesis inhibitor, is capable of increasing the amoebical effect against Acanthamoeba by inhibiting its encystation. In this study, we investigated the possibility of DCB as a disinfecting agent to improve the amoebicidal activity of MPDS against Acanthamoeba cyst. Eight commercial MPDS (from a to h) were assessed, all of which displayed insufficient amoebicidal activity against the mature cysts. Solution e, f, and h showed strong amoebicidal effect on the immature cysts. Amoebicidal efficacy against mature cysts remained inadequate even when the 8 MPDS were combined with 100 µM DCB. However, 4 kinds of MPDS (solution d, e, f, and h) including 100 µM DCB demonstrated strong amoebicidal activity against the immature cysts. The amoebicidal activity of solution d was increased by addition of DCB. Cytotoxicity was absent in human corneal epithelial cells treated with either DCB or mixture of DCB with MPDS. These results suggested that DCB can enhance the amoebicical activity of MPDS against Acanthamoeba immature cyst in vitro.


Assuntos
Acanthamoeba/efeitos dos fármacos , Amebicidas/farmacologia , Soluções para Lentes de Contato/farmacologia , Nitrilos/farmacologia , Acanthamoeba/metabolismo , Células Cultivadas , Celulose/metabolismo , Soluções para Lentes de Contato/efeitos adversos , Lentes de Contato/parasitologia , Células Epiteliais/efeitos dos fármacos , Epitélio Anterior/efeitos dos fármacos , Humanos , Nitrilos/efeitos adversos , Encistamento de Parasitas/efeitos dos fármacos
19.
Medicine (Baltimore) ; 97(44): e13038, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30383669

RESUMO

This retrospective study investigated the efficacy and safety of letrozole for patients with polycystic ovary syndrome (PCOS).Totally, 136 cases of infertility women with PCOS were analyzed. Of those, 68 patients received letrozole, and were assigned to Letrozole group. The other 68 cases received clomiphene, and were assigned to clomiphene group. Patients in both groups were treated up to 5 treatment cycles. The primary endpoint included infant outcomes. The secondary endpoints consisted of the number of women in conception, pregnancy, pregnancy loss, and ovulation. In addition, any kinds of adverse events were also recorded.Cases in the Letrozole group did not show better outcomes neither in primary endpoint (live birth, P = .11; birth weight, P = .95; infant gender, P = .85), nor in secondary endpoints (the number of women in conception, P = .07; pregnancy, P = .12; pregnancy loss, P = .47; pregnancy loss in first trimester, P = .70; and ovulation, P = .09), compared with cases in the clomiphene group. Moreover, no adverse events differ significantly between 2 groups.This study demonstrated that the efficacy of letrozole is not superior to the clomiphene in patients with PCOS.


Assuntos
Inibidores da Aromatase/uso terapêutico , Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Nitrilos/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Triazóis/uso terapêutico , Adulto , Inibidores da Aromatase/efeitos adversos , Clomifeno/efeitos adversos , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Humanos , Infertilidade Feminina/tratamento farmacológico , Letrozol , Nitrilos/efeitos adversos , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Triazóis/efeitos adversos
20.
J Insect Sci ; 18(5)2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30272218

RESUMO

The honey bee is a widely managed crop pollinator that provides the agricultural industry with the sustainability and economic viability needed to satisfy the food and fiber needs of our society. Excessive exposure to apicultural pesticides is one of many factors that has been implicated in the reduced number of managed bee colonies available for crop pollination services. The goal of this study was to assess the impact of exposure to commonly used, beekeeper-applied apicultural acaricides on established biochemical indicators of bee nutrition and immunity, as well as morphological indicators of growth and development. The results described here demonstrate that exposure to tau-fluvalinate and coumaphos has an impact on 1) macronutrient indicators of bee nutrition by reducing protein and carbohydrate levels, 2) a marker of social immunity, by increasing glucose oxidase activity, and 3) morphological indicators of growth and development, by altering body weight, head width, and wing length. While more work is necessary to fully understand the broader implications of these findings, the results suggest that reduced parasite stress due to chemical interventions may be offset by nutritional and immune stress.


Assuntos
Acaricidas/efeitos adversos , Abelhas/efeitos dos fármacos , Cumafos/efeitos adversos , Imunidade Inata/efeitos dos fármacos , Nitrilos/efeitos adversos , Piretrinas/efeitos adversos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Criação de Abelhas , Abelhas/crescimento & desenvolvimento , Abelhas/imunologia , Abelhas/fisiologia
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