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1.
Arerugi ; 69(8): 669-677, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32963190

RESUMO

BACKGROUND: The causative chemicals responsible for nitrile rubber glove-induced allergic contact dermatitis have not been fully elucidated. SUBJECT: This case involved a 36-year-old female, who developed an erythematous rash on her hands after one and a half months of wearing nitrile rubber gloves at her workplace. METHODS: Patch tests were performed using the gloves as is, and the Japanese standard allergen 2008 and their components. The gloves were chemically analyzed and several detected substances were subjected to further patch testing. RESULTS: The patient exhibited positive patch test reactions to nitrile rubber gloves as is, as well as to the dithiocarbamate mix and thiuram mix in the Japanese standard allergen 2008. Further patch testing revealed positive reactions to zinc diethyldithiocarbamate (ZDEC) and tetraethylthiuram disulfide (TETD) and weak positive reactions to zinc dimethyldithiocarbamate (ZDMC) and tetramethylthiuram monosulfide (TMTM). Chemical analysis revealed that ethyl isothiocyanate (EITC) and butyl isothiocyanate (BITC), which might have been produced from dithiocarbamate-type accelerators (DTCs) or thiuram-type accelerators (thiurams) during the vulcanization process, were present in the nitrile rubber gloves the patient used at her workplace, as was ZDBC. No other DTCs or thiurams were detected. Patch testing of the detected materials produced positive reactions to EITC and BITC, but not to ZDBC. CONCLUSION: We diagnosed the patient with allergic contact dermatitis due to the EITC and BITC present in nitrile rubber gloves, and considered that alkyl isothiocyanate might also have played a causative role. We propose that nitrile rubber gloves should be produced without using vulcanization accelerators.


Assuntos
Dermatite Alérgica de Contato , Luvas Protetoras/efeitos adversos , Nitrilos/efeitos adversos , Adulto , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Feminino , Humanos , Isotiocianatos/efeitos adversos , Testes do Emplastro
2.
Cochrane Database Syst Rev ; 8: CD009966, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32803882

RESUMO

BACKGROUND: Kidney transplantation is the preferred management for patients with end-stage kidney disease (ESKD). However, it is often complicated by worsening or new-onset diabetes. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. This is an update of a review first published in 2017. OBJECTIVES: To evaluate the efficacy and safety of glucose-lowering agents for treating pre-existing and new onset diabetes in people who have undergone kidney transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Four authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Ten studies (21 records, 603 randomised participants) were included - three additional studies (five records) since our last review. Four studies compared more intensive versus less intensive insulin therapy; two studies compared dipeptidyl peptidase-4 (DPP-4) inhibitors to placebo; one study compared DPP-4 inhibitors to insulin glargine; one study compared sodium glucose co-transporter 2 (SGLT2) inhibitors to placebo; and two studies compared glitazones and insulin to insulin therapy alone. The majority of studies had an unclear to a high risk of bias. There were no studies examining the effects of biguanides, glinides, GLP-1 agonists, or sulphonylureas. Compared to less intensive insulin therapy, it is unclear if more intensive insulin therapy has an effect on transplant or graft survival (4 studies, 301 participants: RR 1.12, 95% CI 0.32 to 3.94; I2 = 49%; very low certainty evidence), delayed graft function (2 studies, 153 participants: RR 0.63, 0.42 to 0.93; I2 = 0%; very low certainty evidence), HbA1c (1 study, 16 participants; very low certainty evidence), fasting blood glucose (1 study, 24 participants; very low certainty evidence), kidney function markers (1 study, 26 participants; very low certainty evidence), death (any cause) (3 studies, 208 participants" RR 0.68, 0.29 to 1.58; I2 = 0%; very low certainty evidence), hypoglycaemia (4 studies, 301 participants; very low certainty evidence) and medication discontinuation due to adverse effects (1 study, 60 participants; very low certainty evidence). Compared to placebo, it is unclear whether DPP-4 inhibitors have an effect on hypoglycaemia and medication discontinuation (2 studies, 51 participants; very low certainty evidence). However, DPP-4 inhibitors may reduce HbA1c and fasting blood glucose but not kidney function markers (1 study, 32 participants; low certainty evidence). Compared to insulin glargine, it is unclear if DPP-4 inhibitors have an effect on HbA1c, fasting blood glucose, hypoglycaemia or discontinuation due to adverse events (1 study, 45 participants; very low certainty evidence). Compared to placebo, SGLT2 inhibitors probably do not affect kidney graft survival (1 study, 44 participants; moderate certainty evidence), but may reduce HbA1c without affecting fasting blood glucose and eGFR long-term (1 study, 44 participants, low certainty evidence). SGLT2 inhibitors probably do not increase hypoglycaemia, and probably have little or no effect on medication discontinuation due to adverse events. However, all participants discontinuing SGLT2 inhibitors had urinary tract infections (1 study, 44 participants, moderate certainty evidence). Compared to insulin therapy alone, it is unclear if glitazones added to insulin have an effect on HbA1c or kidney function markers (1 study, 62 participants; very low certainty evidence). However, glitazones may make little or no difference to fasting blood glucose (2 studies, 120 participants; low certainty evidence), and medication discontinuation due to adverse events (1 study, 62 participants; low certainty evidence). No studies of DPP-4 inhibitors, or glitazones reported effects on transplant or graft survival, delayed graft function or death (any cause). AUTHORS' CONCLUSIONS: The efficacy and safety of glucose-lowering agents in the treatment of pre-existing and new-onset diabetes in kidney transplant recipients is questionable. Evidence from existing studies examining the effect of intensive insulin therapy, DPP-4 inhibitors, SGLT inhibitors and glitazones is mostly of low to very low certainty. Appropriately blinded, larger, and higher quality RCTs are needed to evaluate and compare the safety and efficacy of contemporary glucose-lowering agents in the kidney transplant population.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adamantano/efeitos adversos , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Viés , Causas de Morte , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Jejum/sangue , Hemoglobina A Glicada/metabolismo , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Insulina Glargina/efeitos adversos , Insulina Glargina/uso terapêutico , Nitrilos/efeitos adversos , Nitrilos/uso terapêutico , Pioglitazona , Complicações Pós-Operatórias/etiologia , Pirrolidinas/efeitos adversos , Pirrolidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fosfato de Sitagliptina/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiazolidinedionas/efeitos adversos , Tiazolidinedionas/uso terapêutico , Transplantados , Vildagliptina
3.
Clin Drug Investig ; 40(9): 847-859, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32621143

RESUMO

BACKGROUND AND OBJECTIVES: Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used for the management of hyperuricemic patients with or without gout in Japan. Accumulating evidence has demonstrated the efficacy of topiroxostat for the treatment of hyperuricemia with or without gout. However, the safety and efficacy of topiroxostat in the clinical setting remain unclear, and there is little large-scale clinical evidence. We conducted a post-marketing observational study over 54 weeks. PATIENTS AND METHODS: Patients were centrally enrolled, and case report forms of 4491 patients were collected between April 2014 and March 2019 from 825 medical sites. RESULTS: Overall, 4329 patients were assessed for safety and 4253 patients for effectiveness. The overall incidence of adverse drug reactions was 6.95%, and the incidence rates of adverse drug reactions of gouty arthritis, hepatic dysfunction, and skin disorders, which are of special interest in this study, were 0.79%, 1.73%, and 0.95%, respectively. No case of serious gouty arthritis was observed. Serum urate levels decreased stably over time and showed a significant reduction rate at 54 weeks (21.19% ± 22.07%) and on the final visit (19.91% ± 23.35%) compared to the baseline. The rates for subjects who achieved serum uric acid levels ≤ 6.0 mg/dL at 18 and 54 weeks after administration were 43.80% and 48.28%, respectively. CONCLUSIONS: This study suggests that there is no particular concern about adverse drug reactions or the efficacy of topiroxostat for hyperuricemic patients with or without gout in a post-marketing setting in Japan.


Assuntos
Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Nitrilos/uso terapêutico , Vigilância de Produtos Comercializados , Piridinas/uso terapêutico , Xantina Desidrogenase/antagonistas & inibidores , Adulto , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Supressores da Gota/efeitos adversos , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Piridinas/efeitos adversos , Resultado do Tratamento , Ácido Úrico/sangue
4.
Leukemia ; 34(8): 2125-2137, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32572189

RESUMO

Bosutinib is approved for newly diagnosed Philadelphia chromosome-positive (Ph+) chronic phase (CP) chronic myeloid leukemia (CML) and for Ph+ CP, accelerated (AP), or blast (BP) phase CML after prior treatment with tyrosine kinase inhibitors (TKIs). In the ongoing phase 4 BYOND study (NCT02228382), 163 CML patients resistant/intolerant to prior TKIs (n = 156 Ph+ CP CML, n = 4 Ph+ AP CML, n = 3 Ph-negative/BCR-ABL1+ CML) received bosutinib 500 mg once daily (starting dose). As of ≥1 year after last enrolled patient (median treatment duration 23.7 months), 56.4% of Ph+ CP CML patients remained on bosutinib. Primary endpoint of cumulative confirmed major cytogenetic response (MCyR) rate by 1 year was 75.8% in Ph+ CP CML patients after one or two prior TKIs and 62.2% after three prior TKIs. Cumulative complete cytogenetic response (CCyR) and major molecular response (MMR) rates by 1 year were 80.6% and 70.5%, respectively, in Ph+ CP CML patients overall. No patient progressed to AP/BP on treatment. Across all patients, the most common treatment-emergent adverse events were diarrhea (87.7%), nausea (39.9%), and vomiting (32.5%). The majority of patients had confirmed MCyR by 1 year and MMR by 1 year, further supporting bosutinib use for Ph+ CP CML patients resistant/intolerant to prior TKIs.


Assuntos
Compostos de Anilina/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Nitrilos/uso terapêutico , Quinolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/efeitos adversos , Feminino , Humanos , Leucemia Mieloide de Fase Crônica/genética , Leucemia Mieloide de Fase Crônica/psicologia , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Cromossomo Filadélfia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Qualidade de Vida , Quinolinas/efeitos adversos
5.
Cochrane Database Syst Rev ; 5: CD002309, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32356609

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life expectancy. Apart from smoking cessation, no other treatments that slow lung function decline are available. Roflumilast and cilomilast are oral phosphodiesterase-4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This Cochrane Review was first published in 2011, and was updated in 2017 and 2020. OBJECTIVES: To evaluate the efficacy and safety of oral PDE4 inhibitors for management of stable COPD. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 9 March 2020). We found other trials at web-based clinical trials registers. SELECTION CRITERIA: We included RCTs if they compared oral PDE4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were change in lung function (minimally important difference (MID) = 100 mL) and quality of life (scale 0 to 100; higher score indicates more limitations). MAIN RESULTS: We found 42 RCTs that met the inclusion criteria and were included in the analyses for roflumilast (28 trials with 18,046 participants) or cilomilast (14 trials with 6457 participants) or tetomilast (1 trial with 84 participants), with a duration between six weeks and one year or longer. These trials included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II to IV), with mean age of 64 years. We judged risks of selection bias, performance bias, and attrition bias as low overall amongst the 39 published and unpublished trials. Lung function Treatment with a PDE4 inhibitor was associated with a small, clinically insignificant improvement in forced expiratory volume in one second (FEV1) over a mean of 40 weeks compared with placebo (mean difference (MD) 49.33 mL, 95% confidence interval (CI) 44.17 to 54.49; participants = 20,815; studies = 29; moderate-certainty evidence). Forced vital capacity (FVC) and peak expiratory flow (PEF) were also improved over 40 weeks (FVC: MD 86.98 mL, 95% CI 74.65 to 99.31; participants = 22,108; studies = 17; high-certainty evidence; PEF: MD 6.54 L/min, 95% CI 3.95 to 9.13; participants = 4245; studies = 6; low-certainty evidence). Quality of life Trials reported improvements in quality of life over a mean of 33 weeks (St George's Respiratory Questionnaire (SGRQ) MD -1.06 units, 95% CI -1.68 to -0.43; participants = 7645 ; moderate-certainty evidence). Incidence of exacerbations Treatment with a PDE4 inhibitor was associated with a reduced likelihood of COPD exacerbation over a mean of 40 weeks (odds ratio (OR) 0.78, 95% CI 0.73 to 0.84; participants = 20,382; studies = 27; high-certainty evidence), that is, for every 100 people treated with PDE4 inhibitors, five more remained exacerbation-free during the study period compared with those given placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 27). No change in COPD-related symptoms nor in exercise tolerance was found. Adverse events More participants in the treatment groups experienced an adverse effect compared with control participants over a mean of 39 weeks (OR 1.30, 95% CI 1.22 to 1.38; participants = 21,310; studies = 30; low-certainty evidence). Participants experienced a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting, or dyspepsia. Diarrhoea was more commonly reported with PDE4 inhibitor treatment (OR 3.20, 95% CI 2.74 to 3.50; participants = 20,623; studies = 29; high-certainty evidence), that is, for every 100 people treated with PDE4 inhibitors, seven more suffered from diarrhoea during the study period compared with those given placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). The likelihood of psychiatric adverse events was higher with roflumilast 500 µg than with placebo (OR 2.13, 95% CI 1.79 to 2.54; participants = 11,168; studies = 15 (COPD pool data); moderate-certainty evidence). Roflumilast in particular was associated with weight loss during the trial period and with an increase in insomnia and depressive mood symptoms. Participants treated with PDE4 inhibitors were more likely to withdraw from trial participation; on average, 14% in the treatment groups withdrew compared with 8% in the control groups. Mortality No effect on mortality was found (OR 0.98, 95% CI 0.77 to 1.24; participants = 19,786; studies = 27; moderate-certainty evidence), although mortality was a rare event during these trials. AUTHORS' CONCLUSIONS: For this current update, five new studies from the 2020 search contributed to existing findings but made little impact on outcomes described in earlier versions of this review. PDE4 inhibitors offered a small benefit over placebo in improving lung function and reducing the likelihood of exacerbations in people with COPD; however, they had little impact on quality of life or on symptoms. Gastrointestinal adverse effects and weight loss were common, and the likelihood of psychiatric symptoms was higher, with roflumilast 500 µg. The findings of this review provide cautious support for the use of PDE4 inhibitors in COPD. In accordance with GOLD 2020 guidelines, they may have a place as add-on therapy for a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management (e.g. people whose condition is not controlled by fixed-dose long-acting beta2-agonist (LABA) and inhaled corticosteroid (ICS) combinations). More longer-term trials are needed to determine whether or not PDE4 inhibitors modify FEV1 decline, hospitalisation, or mortality in COPD.


Assuntos
Aminopiridinas/administração & dosagem , Benzamidas/administração & dosagem , Ácidos Cicloexanocarboxílicos/administração & dosagem , Nitrilos/administração & dosagem , Inibidores da Fosfodiesterase 4/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tiazóis/administração & dosagem , Administração Oral , Aminopiridinas/efeitos adversos , Benzamidas/efeitos adversos , Ácidos Cicloexanocarboxílicos/efeitos adversos , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Diarreia/induzido quimicamente , Progressão da Doença , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Pico do Fluxo Expiratório/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiazóis/efeitos adversos , Capacidade Vital/efeitos dos fármacos
6.
Int J Hematol ; 112(1): 24-32, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32279228

RESUMO

This open-label, single-arm, phase 2 study (ClinicalTrials.gov, NCT03128411) evaluated the efficacy, safety, and pharmacokinetics of bosutinib at a starting dose of 400 mg once daily (QD) in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). The primary endpoint was major molecular response (MMR) at Month 12 in the modified as-treated population (Philadelphia chromosome-positive [Ph+] patients with e13a2/e14a2 transcripts). Sixty Japanese patients with CP CML were treated with bosutinib; median age was 55 years (range 20-83), 60.0% were males, and all were Ph+ and had e13a2/e14a2 transcripts. After median follow-up of 16.6 months (range 11.1-21.9), 41 (68.3%) patients remained on bosutinib. The MMR rate at Month 12 was 55.0% (2-sided 90% confidence interval: 44.4-65.6). There were no on-treatment transformations to accelerated/blast phase, and no patient died on treatment or within 28 days of the last bosutinib dose. The most common treatment-emergent adverse events were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). The primary objective of this phase 2 study was met, and there were no new safety signals for bosutinib. These data suggest bosutinib is an effective first-line treatment option for Japanese patients with newly diagnosed CP CML.


Assuntos
Compostos de Anilina/administração & dosagem , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Nitrilos/administração & dosagem , Quinolinas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Compostos de Anilina/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Aspartato Aminotransferases/sangue , Diarreia , Feminino , Seguimentos , Humanos , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Cromossomo Filadélfia , Quinolinas/efeitos adversos , Transcrição Genética , Resultado do Tratamento , Adulto Jovem
7.
J Pediatr Hematol Oncol ; 42(4): 261-265, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32218096

RESUMO

PURPOSE: Primary objective is to evaluate safety of isavuconazonium sulfate (ISA) in pediatrics below 18 years old. Exploratory endpoint includes mortality due to probable and proven invasive fungal infection (IFI) and overall morality in this population. PATIENTS AND METHODS: Retrospective review of patients below 18 years receiving ISA for ≥7 days for possible, probable, or proven IFI or prophylaxis between June 2015 and March 2018. Descriptive analysis performed to calculate median, frequency, and percentages. RESULTS: Safety analysis included 18 patients and a subgroup of 11/18 patients were assessed for efficacy. Median age 12.5 years (4 to 17 y), median weight 50.25 kg (19 to 118 kg), 50% male, 77% acute leukemias, 94% hematopoietic cell transplant recipients, 50% matched unrelated donors and 78% in remission. Elevated alanine aminotransferase 3 times baseline within 30 days of ISA occurred in 22% (4/18). No patients had elevated bilirubin or increase in serum creatinine. All-cause mortality at 90 days was 22% (4/18) and 27% (3/11) in patients with probable or proven IFI. Clinical response rates: 14-day: 45% (5/11) partial, 27% (3/11) stable; 30-day: 45% (5/11) partial, 36% (4/11) stable; 90-day: 54% (6/11) had either partial (n=3) or complete (n=3) response to ISA. CONCLUSIONS: ISA is safe in pediatric patients for the treatment of IFI. Prospective, randomized controlled trials are warranted to determine efficacy and safety of ISA in pediatric patients with hematologic malignancies and hematopoietic cell transplant.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Infecções Fúngicas Invasivas , Nitrilos/administração & dosagem , Piridinas/administração & dosagem , Triazóis/administração & dosagem , Adolescente , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/terapia , Humanos , Infecções Fúngicas Invasivas/sangue , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/etiologia , Masculino , Nitrilos/efeitos adversos , Piridinas/efeitos adversos , Estudos Retrospectivos , Triazóis/efeitos adversos
9.
ACS Appl Mater Interfaces ; 11(51): 47739-47749, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31774643

RESUMO

Polymeric carbon nitride (PCN), which demonstrates unique properties, has been widely explored, mostly in photocatalysis; however, the evaluation of its biocompatibility is still needed. Herein, the cytocompatibility of PCN with different lateral size distributions (A-PCN with 160 nm, B-PCN with 20 nm, and C-PCN with 10 nm dominating lateral sizes) was investigated. The viability of three cell lines (L929, MCF-7, and HepG2) has been determined using cell counting kit-8 (CCK-8), neutral red uptake (NRU), and lactate dehydrogenase (LDH) leakage assays. It was found that the highest cytotoxicity of PCN was observed for flakes with a lateral size of ∼20 nm (B-PCN) in three cell lines after 48 h of exposition. The uptake process of B-PCN sheets labeled with fluorescein isothiocyanate (FITC) by cells was also the most effective. Confocal laser scanning microscopy and atomic force microscopy revealed the nanomaterial distribution throughout the cytoplasm and perinuclear region. The results demonstrated the correlation among size, internalization process, and cytocompatibility of the tested polymeric carbon nitride structures.


Assuntos
Nanoestruturas/química , Nitrilos/química , Polímeros/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , L-Lactato Desidrogenase/metabolismo , Células MCF-7 , Microscopia Confocal , Nitrilos/efeitos adversos , Polímeros/efeitos adversos , Sincalida/metabolismo
10.
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
11.
Pediatr Infect Dis J ; 38(10): 1035-1037, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31568141

RESUMO

Isavuconazole is a new azole approved for adults with invasive aspergillosis and mucormycosis, with a favorable hepatic tolerability reported in Phase III trials. Here, we report on a case of drug-induced liver failure related to isavuconazole in a pediatric patient treated for invasive aspergillosis after bone marrow transplant.


Assuntos
Antifúngicos/efeitos adversos , Aspergilose Pulmonar Invasiva/complicações , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Nitrilos/efeitos adversos , Piridinas/efeitos adversos , Triazóis/efeitos adversos , Adolescente , Antifúngicos/administração & dosagem , Transplante de Medula Óssea/efeitos adversos , Humanos , Masculino , Nitrilos/administração & dosagem , Piridinas/administração & dosagem , Triazóis/administração & dosagem
13.
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
14.
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
15.
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
16.
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
17.
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
18.
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
19.
JAMA Oncol ; 5(5): 623-632, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30703190

RESUMO

Importance: Androgen-deprivation therapy (ADT) plus docetaxel is the standard of care in hormone-naive metastatic prostate cancer but is of uncertain benefit in a nonmetastatic, high-risk prostate cancer setting. Objective: To assess the benefit of ADT plus docetaxel in patients presenting with rising prostate-specific antigen (PSA) levels after primary local therapy and high-risk factors but no evidence of metastatic disease. Design, Setting, and Participants: This open-label, phase 3, randomized superiority trial comparing ADT plus docetaxel vs ADT alone enrolled patients from 28 centers in France between June 4, 2003, and September 25, 2007; final follow-up was conducted April 12, 2017, and analysis was performed May 2 to July 31, 2017. Patients had undergone primary local therapy for prostate cancer, were experiencing rising PSA levels, and were considered to be at high risk of metastatic disease. Stratification was by prior local therapy and PSA-level doubling time (≤6 vs >6 months), and intention-to-treat analysis was used. Interventions: Patients were randomly assigned to receive ADT (1 year) plus docetaxel, 70 mg/m2 (every 3 weeks [6 cycles]), or ADT alone (1 year). Main Outcomes and Measures: The primary outcome was PSA progression-free survival (PSA-PFS). Secondary end points were PSA response, radiologic PFS, overall survival, safety, and quality of life. Results: Overall, 254 patients were randomized (1:1) to the trial; median age, 64 years in the ADT plus docetaxel arm, 66 years in the ADT alone arm. At a median follow-up of 30.0 months, the median PSA-PFS was 20.3 (95% CI, 19.0-21.6) months in the ADT plus docetaxel arm vs 19.3 (95% CI, 18.2-20.8) months in the ADT alone arm (hazard ratio [HR], 0.85; 95% CI, 0.62-1.16; P = .31). At a median follow-up of 10.5 years, there was no significant between-arm difference in radiologic PFS (HR, 1.03; 95% CI, 0.74-1.43; P = .88). Overall survival data were not mature. The most common grade 3 or 4 hematologic toxic effects in the ADT plus docetaxel arm were neutropenia (60 of 125 patients [48.0%]), febrile neutropenia (10 [8.0%]), and thrombocytopenia (4 [3.0%]). There was no significant between-arm difference in overall quality of life. Conclusions and Relevance: Compared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA-PFS in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease. Trial Registration: French Health Products Safety Agency identifier: 030591; ClinicalTrials.gov identifier: NCT00764166.


Assuntos
Antagonistas de Androgênios/administração & dosagem , Anilidas/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel/administração & dosagem , Nitrilos/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Compostos de Tosil/administração & dosagem , Pamoato de Triptorrelina/administração & dosagem , Idoso , Antagonistas de Androgênios/efeitos adversos , Anilidas/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Docetaxel/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Nitrilos/efeitos adversos , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Qualidade de Vida , Risco , Compostos de Tosil/efeitos adversos , Pamoato de Triptorrelina/efeitos adversos
20.
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
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