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1.
Nat Commun ; 11(1): 4527, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913197

RESUMO

Evasion of programmed cell death represents a critical form of oncogene addiction in cancer cells. Understanding the molecular mechanisms underpinning cancer cell survival despite the oncogenic stress could provide a molecular basis for potential therapeutic interventions. Here we explore the role of pro-survival genes in cancer cell integrity during clonal evolution in non-small cell lung cancer (NSCLC). We identify gains of MCL-1 at high frequency in multiple independent NSCLC cohorts, occurring both clonally and subclonally. Clonal loss of functional TP53 is significantly associated with subclonal gains of MCL-1. In mice, tumour progression is delayed upon pharmacologic or genetic inhibition of MCL-1. These findings reveal that MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Evolução Clonal , Variações do Número de Cópias de DNA , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Progressão da Doença , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Transgênicos , Mutação , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Cultura Primária de Células , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , RNA-Seq , Estudos Retrospectivos , Esferoides Celulares , Tiofenos/farmacologia , Tiofenos/uso terapêutico , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Proteína Supressora de Tumor p53/genética , Microtomografia por Raio-X
2.
Int J Nanomedicine ; 15: 4079-4090, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606665

RESUMO

Purpose: The aim of this study is to develop efficient localized therapy of sertaconazole nitrate for the treatment of vaginal candidiasis. Methods: Sertaconazole nitrate-loaded cationic liposomes were prepared by thin-film hydration method and coated with different concentrations of pectin (0.05%, 0.1% and 0.2%) to develop mucoadhesive liposomes. The formulated mucoadhesive vesicles were characterized in terms of morphology, entrapment efficiency, particle size, zeta value, mucoadhesive properties and drug release. The selected formula was incorporated into a gel base and further characterized by an ex vivo permeation study in comparison with conventional sertaconazole gel. Also, the in vivo study was performed to assess the efficacy of sertaconazole mucoadhesive liposomal gel in treating rats with vaginal candidiasis. Results: The mucoadhesive liposomes were spherical. Coating liposomes with pectin results in increased entrapment efficiency and particle size compared with uncoated vesicles. On the contrary, zeta values were reduced upon coating liposomes with pectin indicating efficient coating of liposomes with pectin. Mucoadhesive liposomes showed a more prolonged and sustained drug release compared with uncoated liposomes. Ex vivo study results showed that mucoadhesive liposomal gel increased sertaconazole tissue retention and reduced drug tissue penetration. In the invivo study, the mucoadhesive liposomal gel showed a significant reduction in the microbial count with a subsequent reduction in inflammatory responses with the lowest histopathological change compared with conventional gel. Conclusion: The study confirmed the potentiality of employing mucoadhesive liposomes as a successful carrier for the vaginal delivery of antifungal drugs.


Assuntos
Antifúngicos/uso terapêutico , Candidíase Vulvovaginal/tratamento farmacológico , Imidazóis/uso terapêutico , Muco/química , Tiofenos/uso terapêutico , Adesividade , Animais , Anti-Infecciosos/farmacologia , Biomarcadores/metabolismo , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Feminino , Géis , Humanos , Imidazóis/farmacologia , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Mediadores da Inflamação/metabolismo , Lipossomos/ultraestrutura , Mucinas/metabolismo , Tamanho da Partícula , Ratos Sprague-Dawley , Ovinos , Eletricidade Estática , Tiofenos/farmacologia , Vagina/patologia , beta-Glucanas/metabolismo
3.
Asia Pac J Clin Oncol ; 16(5): e192-e197, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32506805

RESUMO

AIM: To provide guidance for appropriate imaging examinations for diagnosing spinal tumors or tumor-like lesions. METHODS: A total of 121 patients with suspected spinal tumors were included this retrospective study. Each patient underwent ≥2 imaging examinations, including computerized tomography (CT), magnetic resonance (MR), and/or emission computed tomography (ECT). All patients were diagnosed by pathology after core needle or surgical biopsies. The results were compared with those of pathological examinations using paired chi-squared tests, and compared with each other. Statistical indicators that tested the consistency of the results included McNemar's and kappa coefficients, as well as receiver operating characteristic curves. RESULTS: The differences among MR, CT, ECT, and pathology were not significant. The kappa coefficient of MR, CT, and ECT was 46.1%, 36.0%, and 55.9%, respectively. The area under the curve of ECT, MR, and CT scans was 0.809, 0.705, and 0.704, respectively; and the differences among them were significant (P < .05). Post hoc multiple comparisons showed no significant differences among imaging examinations in terms of sensitivity, specificity, misdiagnosis rate, and coincidence rate (P > .05). However, significant differences were noted in the kappa coefficient and missed diagnosis rate (P < .05). CONCLUSIONS: Although ECT was the most accurate imaging method, its high cost and large radiation dosage limit its widespread application. Furthermore, MR verified spinal tumors more effectively; however, CT excluded them more efficiently. In summary, when all factors are considered, MR is still the optimal modality for the diagnosis of spinal tumors, especially during the initial screening.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imagem por Ressonância Magnética/métodos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Diferenciação Celular , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Estudos Retrospectivos , Tiofenos/farmacologia , Tiofenos/uso terapêutico , Adulto Jovem
4.
Cardiovasc Diabetol ; 19(1): 85, 2020 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-32534578

RESUMO

BACKGROUND: Type 2 diabetes (T2D) is associated with renal impairment and vascular endothelial dysfunction. Therefore, this pathological connection is an important therapeutic target. Recent cardiovascular and renal outcome trials demonstrated that sodium glucose cotransporter 2 inhibitors (SGLT2is) consistently reduced the risks of cardiovascular and renal events and mortality in patients with T2D and various other background risks including chronic kidney disease (CKD). However, the precise mechanisms by which SGLT2is accords these therapeutic benefits remain uncertain. It is also unknown whether these SGLT2is-associated benefits are associated with the amelioration of endothelial dysfunction in patients with T2D and CKD. METHODS: The PROCEED trial is an investigator-initiated, prospective, multicenter, open-label, randomized-controlled trial. The target sample size is 110 subjects. After they furnish informed consent and their endothelial dysfunction is confirmed from their decreased reactive hyperemia indices (RHI), eligible participants with T2D (HbA1c, 6.0-9.0%) and established CKD (30 mL/min/1.73 m2 ≤ estimated glomerular filtration ratio [eGFR] < 60 and/or ≥ urine albumin-to-creatinine ratio 30 mg/g Cr) will be randomized (1:1) to receive either 50 mg ipragliflozin daily or continuation of background treatment (non-SGLT2i). The primary endpoint is the change in RHI from baseline after 24 weeks. To compare the treatment effects between groups, the baseline-adjusted means and their 95% confidence intervals will be estimated by analysis of covariance adjusted for HbA1c (< 7.0% or ≥ 7.0%), age (< 70 y or ≥ 70 y), RHI (< 1.67 or ≥ 1.67), eGFR (< 45 mL/min/1.73 m2 or ≥ 45 mL/min/1.73 m2), and smoking status. Prespecified responder analyses will be also conducted to determine the proportions of patients with clinically meaningful changes in RHI at 24 weeks. DISCUSSION: PROCEED is the first trial to examine the effects of ipragliflozin on endothelial dysfunction in patients with T2D and CKD. This ongoing trial will establish whether endothelial dysfunction is a therapeutic target of SGLT2is in this population. It will also provide deep insights into the potential mechanisms by which SGLT2is reduced the risks of cardiovascular and renal events in recent outcome trials. Trial registration Unique Trial Number, jRCTs071190054 (https://jrct.niph.go.jp/en-latest-detail/jRCTs071190054).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiofenos/uso terapêutico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/fisiopatologia , Endotélio Vascular/fisiopatologia , Glucosídeos/efeitos adversos , Humanos , Japão/epidemiologia , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Tiofenos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
5.
Drugs Today (Barc) ; 56(4): 269-286, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32309822

RESUMO

Oliceridine is a next-generation investigational intravenous opioid that is a G protein-selective agonist at the µ-opioid receptor. The G protein selectivity of this compound results in potent analgesia with substantially reduced recruitment of ß-arrestin, a signaling pathway associated with opioid-related adverse events. In randomized, placebo- and active-controlled clinical studies, use of oliceridine for the management of moderate to severe acute pain provided potent analgesic effect superior to that observed with placebo, with lower incidence of adverse events, including respiratory events and gastrointestinal events of nausea and vomiting, compared with morphine. Here, we provide a review of the preclinical and clinical data of intravenous oliceridine, a selective agonist, which has the potential to offer a wider therapeutic window than conventional opioids.


Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Compostos de Espiro/uso terapêutico , Tiofenos/uso terapêutico , Proteínas de Ligação ao GTP/agonistas , Humanos , Morfina , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores Opioides mu
6.
J Med Chem ; 63(7): 3678-3700, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32153186

RESUMO

Bromodomain-containing protein 4 (BRD4) and histone deacetylases (HDAC) are both attractive epigenetic targets in cancer and other chronic diseases. Based on the integrated fragment-based drug design, synthesis, and in vitro and in vivo evaluations, a series of novel thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives are discovered as selective BRD4-HDAC dual inhibitors. Compound 17c is the most potent inhibitor for BRD4 and HDAC with IC50 values at nanomolar levels, as well as the expression level of c-Myc, and increases the acetylation of histone H3. Moreover, 17c presents inhibitory effects on the proliferation of colorectal carcinoma (CRC) cells via inducing autophagic cell death. It also has a good pharmacokinetic profile in rats and oral bioavailability of 40.5%. In the HCT-116 xenograft in vivo models, 17c displays potent inhibitory efficiency on tumor growth by inducing autophagic cell death and suppressing IL6-JAK-STAT signaling pathways. Our results suggest that the BRD4-HDAC dual inhibition might be an attractive therapeutic strategy for CRC.


Assuntos
Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/metabolismo , Histona Desacetilases/metabolismo , Humanos , Ácidos Hidroxâmicos/síntese química , Ácidos Hidroxâmicos/metabolismo , Masculino , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/metabolismo , Pirimidinas/uso terapêutico , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/metabolismo , Tiofenos/uso terapêutico , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
7.
Psychopharmacology (Berl) ; 237(5): 1459-1470, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32002559

RESUMO

RATIONALE: What is the difference between aripiprazole and brexpiprazole? OBJECTIVES: This systematic review, network meta-analysis of randomized trials evaluated the efficacy and safety/tolerability of aripiprazole and brexpiprazole for treating acute schizophrenia. METHODS: We searched Scopus, MEDLINE, and Cochrane Library from inception until May 22, 2019. The response rate was set as the primary outcome. Other outcomes were discontinuation rate and incidence of individual adverse events. The risk ratio (RR) and 95% credible interval (95%CrI) were calculated. RESULTS: Fourteen studies were identified (n = 3925). Response rates of both aripiprazole and brexpiprazole were superior to that of the placebo (RR [95%CrI]: aripiprazole = 0.84 [0.78, 0.92], brexpiprazole = 0.84 [0.77, 0.92]). Aripiprazole and brexpiprazole were associated with a lower incidence of all-cause discontinuation (0.80 [0.71, 0.89], 0.83 [0.72, 0.95]), adverse events (0.67 [0.47, 0.97], 0.64 [0.46, 0.94]), and inefficacy (0.56 [0.40, 0.77], 0.68 [0.48, 0.99]) compared with the placebo. Although brexpiprazole was associated with a lower incidence of schizophrenia as an adverse event compared with the placebo (0.57 [0.37, 0.85]), aripiprazole and brexpiprazole were associated with a higher incidence of weight gain compared with the placebo (2.12 [1.28, 3.68], 2.14 [1.35, 3.42]). No significant differences were found in other individual adverse events, such as somnolence, akathisia, extrapyramidal symptoms, and dizziness between aripiprazole or brexpiprazole and placebo. Any outcome between aripiprazole and brexpiprazole were not different. CONCLUSIONS: Differences in short-term efficacy and safety for acute schizophrenia were not apparent between aripiprazole and brexpiprazole. Future studies are warranted to evaluate whether there are differences in the long-term outcome between treatments.


Assuntos
Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Quinolonas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiofenos/uso terapêutico , Doença Aguda , Acatisia Induzida por Medicamentos/diagnóstico , Antipsicóticos/efeitos adversos , Aripiprazol/efeitos adversos , Humanos , Metanálise em Rede , Quinolonas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Esquizofrenia/diagnóstico , Tiofenos/efeitos adversos , Ganho de Peso/efeitos dos fármacos , Ganho de Peso/fisiologia
8.
Genet Test Mol Biomarkers ; 24(3): 156-164, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32101052

RESUMO

Background: To study the effect of single nucleotide polymorphisms (SNPs) in the thymidylate synthase (TYMS) gene for their value in predicting the efficacy of raltitrexed treatment combined with transcatheter arterial chemoembolization (TACE) for the treatment of primary hepatocellular carcinoma (HCC). Methods: We conducted a genotypic analysis of the TYMS SNPs rs2790, rs8423, rs502396, rs699517, and rs1004474 in150 HCC patients who were subjected to raltitrexed treatment combined with TACE (study group) and another 150 HCC patients who were treated with doxorubicin combined with TACE (control group). After 1 year of follow-up and interventional therapy, the relationship between the TYMS SNPs and survival rate, and the prognosis for survival were analyzed. Results: After interventional therapy, the response rate (RR) and disease control rate (DCR) of the study group were 52.67% and 87.33%, respectively; whereas the RR and DCR of the control group were 54.67% and 84.67%, respectively. No significant differences were detected by comparison of the RRs (p = 0.728) and DCRs (p = 0.506) between the two groups. The HCC patients' TYMS SNPs rs2790, rs8423, rs502396, rs699517, and rs1004474 were associated with the efficacy and prognosis of the raltitrexed-combined TACE intervention (p < 0.05) yet showed no correlation to the efficacy and prognosis of doxorubicin-combined TACE interventional therapy (p > 0.05). Conclusions: The SNPs of the TYMS genes (rs2790, rs8423, rs502396, rs699517, and rs1004474) are associated with the efficacy and prognosis of raltitrexed treatment in HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Quinazolinas/uso terapêutico , Tiofenos/uso terapêutico , Timidilato Sintase/genética , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Farmacológicos/sangue , Carcinoma Hepatocelular/terapia , Estudos de Casos e Controles , Quimioembolização Terapêutica/métodos , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Quinazolinas/administração & dosagem , Taxa de Sobrevida , Tiofenos/administração & dosagem , Timidilato Sintase/metabolismo , Resultado do Tratamento
9.
BMC Infect Dis ; 20(1): 171, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087692

RESUMO

BACKGROUND: Trichophyton benhamiae is a zoophilic dermatophyte that can cause tinea in humans and animals. Lesions caused by T. benhamiae tend to be highly inflammatory, and patients are often infected by animals or other patients infected with T. benhamiae. In this paper, we report the first case of tinea faciei caused by T. benhamiae in a Chinese girl who might be transmitted from a fox. CASE PRESENTATION: A 4-year-old girl from HaiNing city developed an itchy, erythematous, and annular plaque on her right face for the past 2 months. Before the lesion appeared, she was in close contact with the fur of a fox for almost 1 week. Septate hyaline hyphae were detected by direct mycological examination of the scales. Cultures grew on Sabouraud's dextrose agar (SDA) at 26 °C for 2 weeks revealed the presence of T. mentagrophytes. A molecular sequencing test confirmed that the isolate was consistent with reference strains to T. benhamiae. Then, the diagnosis of tinea faciei due to T. benhamiae was made. Treatment with terbinafine (oral 125 mg/d) and sertaconazole nitrate cream (topical, twice daily) for 4 weeks was initiated and achieved significant improvement of the skin lesions. CONCLUSIONS: This rare dermatophytosis case highlights the importance of ITS sequencing in helping to recognize rare pathogenic fungi that can be easily misdiagnosed with a conventional morphological diagnosis.


Assuntos
Arthrodermataceae/genética , Dermatomicoses/diagnóstico , Tinha/diagnóstico , Trichophyton/genética , Administração Oral , Administração Tópica , Animais , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Arthrodermataceae/isolamento & purificação , Pré-Escolar , China , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Face/patologia , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Pele/patologia , Terbinafina/administração & dosagem , Terbinafina/uso terapêutico , Tiofenos/administração & dosagem , Tiofenos/uso terapêutico , Tinha/tratamento farmacológico , Tinha/microbiologia , Resultado do Tratamento , Trichophyton/isolamento & purificação
10.
J Med Chem ; 63(3): 1084-1104, 2020 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-31895562

RESUMO

In our pursuit of developing a novel, potent, and selective cell division cycle 7 (Cdc7) inhibitor, we optimized the previously reported thieno[3,2-d]pyrimidinone analogue I showing time-dependent Cdc7 kinase inhibition and slow dissociation kinetics. These medicinal chemistry efforts led to the identification of compound 3d, which exhibited potent cellular activity, excellent kinase selectivity, and antitumor efficacy in a COLO205 xenograft mouse model. However, the issue of formaldehyde adduct formation emerged during a detailed study of 3d, which was deemed an obstacle to further development. A structure-based approach to circumvent the adduct formation culminated in the discovery of compound 11b (TAK-931) possessing a quinuclidine moiety as a preclinical candidate. In this paper, the design, synthesis, and biological evaluation of this series of compounds will be presented.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/antagonistas & inibidores , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazolonas/uso terapêutico , Pirimidinas/uso terapêutico , Pirimidinonas/uso terapêutico , Quinuclidinas/uso terapêutico , Tiofenos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Sítios de Ligação , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Desenho de Fármacos , Descoberta de Drogas , Formaldeído/química , Humanos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Pirazolonas/farmacologia , Pirimidinas/farmacologia , Pirimidinonas/síntese química , Pirimidinonas/metabolismo , Quinuclidinas/síntese química , Quinuclidinas/metabolismo , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Clin Ther ; 42(1): 77-93, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31928831

RESUMO

PURPOSE: Brexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration-approved OAAs in a real-world setting. METHODS: This retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up. FINDINGS: The final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488-16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05-2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04-2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779-35,353] vs $23,851 [18,907-28,795]; medical, $19,343 [16,294-22,392] vs $12,013 [7488-16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694-11,795; P = 0.009) than in brexpiprazole users. IMPLICATIONS: Patients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.


Assuntos
Antipsicóticos/economia , Hospitalização/economia , Quinolonas/economia , Esquizofrenia/economia , Tiofenos/economia , Administração Oral , Adulto , Antipsicóticos/uso terapêutico , Aripiprazol/economia , Aripiprazol/uso terapêutico , Feminino , Custos de Cuidados de Saúde , Humanos , Cloridrato de Lurasidona/economia , Cloridrato de Lurasidona/uso terapêutico , Masculino , Medicaid/economia , Medicare/economia , Pessoa de Meia-Idade , Olanzapina/economia , Olanzapina/uso terapêutico , Palmitato de Paliperidona/economia , Palmitato de Paliperidona/uso terapêutico , Piperazinas/economia , Piperazinas/uso terapêutico , Fumarato de Quetiapina/economia , Fumarato de Quetiapina/uso terapêutico , Quinolonas/uso terapêutico , Risperidona/economia , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Tiazóis/economia , Tiazóis/uso terapêutico , Tiofenos/uso terapêutico , Estados Unidos
12.
J Cardiovasc Pharmacol ; 75(4): 351-357, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31929323

RESUMO

This study evaluates the cardiovascular risk and safety of a dual peroxisome proliferator-activated receptor alpha and gamma (PPARα&γ), aleglitazar, for the management of type 2 diabetes mellitus. Studies were identified after a literature search in electronic databases and included in the meta-analysis according to eligibility criteria. Meta-analyses of mean differences in the changes from the baseline or odds ratios of selected indices between the aleglitazar- and the placebo/comparator-treated participants were performed. Seven studies {11,832 individuals; age 59.3 years [95% confidence interval (CI) 56.4-61.9]; body mass index 30.8 kg/m [95% CI 30.1-31.7]; sex, 54% males [44-64]} were included. In comparison with the placebo or pioglitazone, the aleglitazar treatment significantly improved %HbA1c, high-density lipoprotein-cholesterol (HDL-chol), and triglycerides. Aleglitazar also significantly decreased fasting plasma glucose and apolipoprotein B compared with the placebo. However, compared with the placebo or pioglitazone, aleglitazar significantly increased serum creatinine levels and significantly decreased the estimated glomerular filtration rate. In addition, the aleglitazar treatment was associated with a significantly increased body weight. Incidence of hypoglycemia, gastrointestinal hemorrhage, bone fractures, heart failure, cardiovascular death, and malignancy was higher in the aleglitazar group. Despite efficacy in glycemic and lipidic control, the aleglitazar treatment was associated with a poor safety profile.


Assuntos
Glicemia/efeitos dos fármacos , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Oxazóis/uso terapêutico , PPAR alfa/agonistas , PPAR gama/agonistas , Tiofenos/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Incidência , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Oxazóis/efeitos adversos , Medição de Risco , Fatores de Risco , Tiofenos/efeitos adversos , Resultado do Tratamento , Ganho de Peso/efeitos dos fármacos
13.
J Pharmacol Exp Ther ; 372(1): 21-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628204

RESUMO

During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by cytochrome P450 2A6 (CYP2A6). Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Male and female mice were trained to self-administer nicotine across daily sessions. Once stable responding was achieved, DLCI-1 or vehicle control was administered prior to nicotine sessions. We found that the lower 25 mg/kg and moderate 50 mg/kg doses of DLCI-1 induced a significant decrease in nicotine intake for both males and females. DLCI-1 was further shown to be more effective than a moderate 1 mg/kg dose of bupropion on reducing nicotine intake and did not exert the adverse behavioral effects found with a high 75 mg/kg dose of bupropion. Although mice treated with DLCI-1 self-administered significantly less nicotine, similar nicotine-mediated behavioral effects on locomotion were observed. Together, along with the analysis of nicotine metabolites during self-administration, these findings support the contention that blocking hepatic nicotine metabolism would allow for similar activation of nicotinic acetylcholine receptors at lower nicotine doses. Moreover, these effects of DLCI-1 were specific to nicotine self-administration, as DLCI-1 did not result in any behavioral changes during food self-administration. Taken together, these studies validate DLCI-1 as a novel compound to decrease nicotine consumption, which may thereby promote tobacco and nicotine product cessation. SIGNIFICANCE STATEMENT: Current pharmacological approaches for nicotine and tobacco cessation have only been able to achieve limited efficaciousness in promoting long-term abstinence. In this work, we characterize the effects of a novel compound, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), which inhibits the main enzyme that metabolizes nicotine, and we report a significant decrease in intravenous nicotine self-administration in male and female mice, supporting the potential of DLCI-1 as a novel tobacco cessation pharmacotherapeutic.


Assuntos
Citocromo P-450 CYP2A6/antagonistas & inibidores , Inibidores Enzimáticos/uso terapêutico , Agentes de Cessação do Hábito de Fumar/uso terapêutico , Tiofenos/uso terapêutico , Tabagismo/tratamento farmacológico , Animais , Citocromo P-450 CYP2A6/metabolismo , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/farmacologia , Feminino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nicotina/metabolismo , Agentes de Cessação do Hábito de Fumar/administração & dosagem , Agentes de Cessação do Hábito de Fumar/efeitos adversos , Agentes de Cessação do Hábito de Fumar/farmacologia , Tiofenos/administração & dosagem , Tiofenos/efeitos adversos , Tiofenos/farmacologia
14.
Int J Chron Obstruct Pulmon Dis ; 14: 2733-2744, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819405

RESUMO

Background: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine - a muco-active antioxidant that modulates bacterial adhesiveness - reduced the rate and duration of exacerbations in moderate and severe COPD with a history of exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear. Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1] 50‒79% predicted) examined exacerbation rate and duration, time to first exacerbation, and exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann-Whitney U-tests, or log rank tests. Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an exacerbation. There was a 47% reduction in the mean exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 exacerbations per-patient per-year, respectively, P=0.003), and a 58.3% reduction in the mild exacerbation rate (0.23 vs 0.53 mild exacerbations per-patient per-year, P=0.001). Mean duration of exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P=0.022), with significant reductions in the duration of mild and moderate-to-severe exacerbations. Mean time to first exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P<0.001) and the mean exacerbation-free time was increased by 51 days (279 days for erdosteine vs 228 days for placebo; P<0.001). Conclusion: These results indicate that adding erdosteine to usual COPD maintenance therapy reduces the number of mild, and duration of all, exacerbations in patients with moderate COPD and a history of exacerbations.


Assuntos
Antioxidantes/uso terapêutico , Expectorantes/uso terapêutico , Pulmão/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Tioglicolatos/uso terapêutico , Tiofenos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Europa (Continente) , Expectorantes/efeitos adversos , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Tioglicolatos/efeitos adversos , Tiofenos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
15.
PLoS One ; 14(11): e0224420, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751384

RESUMO

Within triple negative breast cancer, several molecular subtypes have been identified, underlying the heterogeneity of such an aggressive disease. The basal-like subtype is characterized by mutations in the TP53 gene, and is associated with a low pathologic complete response rate following neoadjuvant chemotherapy. In a genome-scale short hairpin RNA (shRNA) screen of breast cancer cells, polo-like kinase 1 (Plk1) was a frequent and strong hit in the basal breast cancer cell lines indicating its importance for growth and survival of these breast cancer cells. Plk1 regulates progression of cells through the G2-M phase of the cell cycle. We assessed the activity of two ATP-competitive Plk1 inhibitors, GSK461364 and onvansertib, alone and with a taxane in a set of triple negative breast cancer cell lines and in vivo. GSK461364 showed synergism with docetaxel in SUM149 (Combination Index 0.70) and SUM159 (CI, 0.62). GSK461364 in combination with docetaxel decreased the clonogenic potential (interaction test for SUM149 and SUM159, p<0.001 and p = 0.01, respectively) and the tumorsphere formation of SUM149 and SUM159 (interaction test, p = 0.01 and p< 0.001). In the SUM159 xenograft model, onvansertib plus paclitaxel significantly decreased tumor volume compared to single agent paclitaxel (p<0.0001). Inhibition of Plk1 in combination with taxanes shows promising results in a subset of triple negative breast cancer intrinsically resistant to chemotherapy. Onvansertib showed significant tumor volume shrinkage when combined with paclitaxel in vivo and should be considered in clinical trials for the treatment of triple negative cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Piperazinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Linhagem Celular Tumoral , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Camundongos , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Tiofenos/farmacologia , Tiofenos/uso terapêutico , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Biol Pharm Bull ; 42(10): 1707-1712, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582658

RESUMO

Recent clinical studies indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors exhibit a renoprotective effect. While studies at the single nephron level suggest that direct effects of SGLT2 inhibitors on renal hemodynamics may be a possible mechanism underlying their renoprotective effect, few studies have focused on such direct effects at the whole-kidney level. In the present study, we investigated the acute and direct effect of SGLT2 inhibition on creatinine clearance, an index of whole-kidney glomerular filtration rate (GFR), in a rat model of type 2 diabetes. Twelve to fifteen-week-old male Spontaneously Diabetic Torii (SDT) fatty rats and Sprague-Dawley rats were used as diabetic animals and non-diabetic controls, respectively. Under general anesthesia, baseline urine samples were collected from the left and right ureters for 1 h. The selective SGLT2 inhibitor ipragliflozin or vehicle was subsequently administered intravenously and post-drug urine was collected for 1 h. Baseline and post-drug blood samples were collected immediately before baseline urine collection and immediately after post-drug urine collection, respectively. Plasma glucose, urine volume, urinary glucose and albumin excretion were measured, and creatinine clearance was calculated. Blood pressure and heart rate were monitored continuously throughout the experiment. A single intravenous injection of ipragliflozin increased both urine output and glucose excretion, but reduced creatinine clearance without affecting systemic blood pressure. These results suggest that SGLT2 inhibition directly reduced whole-kidney GFR, most likely due to a reduction in intraglomerular pressure, by altering local renal hemodynamics, which may contribute to the renoprotective effects demonstrated in clinical studies.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiofenos/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Cloretos/sangue , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/prevenção & controle , Glucosídeos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos Sprague-Dawley , Sódio/sangue , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Tiofenos/farmacologia
18.
Diabetes Res Clin Pract ; 157: 107867, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31568801

RESUMO

AIM: To evaluate the efficacy, safety and cost-effectiveness of ipragliflozin as an add-on therapy in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, the Cochrane Library, Web of Science and four Chinese databases, as well as the ClinicalTrials.gov website were searched from their inception through Jan 2019. Methodological quality was assessed using the Cochrane risk of bias, and meta-analysis was performed using RevMan5.3. RESULTS: A total of 11 randomized controlled trials with 1766 patients were included. Ipragliflozin administered (50 mg) once daily as an add-on therapy to other glucose-lowering medications (metformin, pioglitazone, sulfonylurea, α-glucosidase inhibitor, sitagliptin, insulin) was associated with reductions in hemoglobin A1c (HbA1c) of -0.74% (95% confidence interval (CI) -1.00 to -0.48), fasting plasma glucose (WMD -25.03 mg/dL; 95% CI -32.89 to -17.16), weight, waist circumference, blood pressure, and triglycerides levels. Neither the incidence of treatment-emergent adverse events (TEAEs) (RR 1.08; 95% CI 1.00 to 1.16) nor drug-related TEAEs (RR 1.19; 95% CI 0.93 to 1.54) was significantly increased. However, it was associated with an increased risk of hypoglycemia when added to insulin (RR 1.71; 95% CI 1.13 to 2.61). Compared with the pioglitazone group and the sitagliptin + metformin group, the incremental cost-effectiveness ratio of ipragliflozin add-on therapy group was $4976.89, $2089.76 per percentage of qualified HbA1c, respectively. CONCLUSION: Ipragliflozin as an add-on therapy is well tolerated and effective. Ipragliflozin as an add-on therapy do not appear cost-effective compared with metformin alone, but may be competitive against pioglitazone group and the sitagliptin + metformin group.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada/métodos , Farmacoeconomia/normas , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tiofenos/uso terapêutico , Feminino , Glucosídeos/farmacologia , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Masculino , Metformina/farmacologia , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Tiofenos/farmacologia
19.
Clin Drug Investig ; 39(12): 1213-1221, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31552641

RESUMO

BACKGROUND AND OBJECTIVE: To avoid insulin-induced hypoglycemia and weight gain, the minimum dose of insulin should be used. In this study, therefore, we examined insulin dose reduction by ipragliflozin add-on therapy in Japanese patients with type 2 diabetes mellitus treated with long-acting basal insulin. METHODS: In this multicenter, open-label study, patients received one ipragliflozin 50-mg tablet once daily in combination with basal insulin for 24 weeks. The primary efficacy endpoint was the change and percent change in insulin dose from baseline to Week 24. Secondary efficacy endpoints included changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), glycoalbumin, cholesterol, leptin, adiponectin, C-peptide, glucagon, body weight, and blood pressure, and number of patients achieving withdrawal of insulin at the end of treatment (EOT). Treatment-emergent adverse events (TEAEs) were evaluated for safety. RESULTS: In total, 114 patients were screened, 103 were registered, and 97 completed the study. The mean age was 59 years and 72.8% of patients were male. The mean change in insulin dose from baseline at Week 24 was - 6.6 ± 4.4 units/day (p < 0.001); the mean percent change was - 29.87%. HbA1c, FPG, glycoalbumin, glucagon levels, body weight, and blood pressure significantly decreased from baseline to EOT (p < 0.05). Cholesterol, leptin, and adiponectin were unaffected. One patient was able to stop insulin treatment at Week 16. The incidence of TEAEs was 60.2%. Hypoglycemia (10.7%) and pollakiuria (13.6%) were the most common drug-related TEAEs. Conclusions Once-daily 50-mg ipragliflozin enabled a 30% dose reduction of insulin by Week 24 compared with baseline. No major safety concerns were raised. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02847091).


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Tiofenos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Feminino , Glucosídeos/efeitos adversos , Humanos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tiofenos/efeitos adversos
20.
Middle East Afr J Ophthalmol ; 26(2): 60-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543661

RESUMO

PURPOSE: The purpose of the study is to evaluate the changes in contrast sensitivity (CS) after using the four different types of antiglaucoma eye drops in patients with primary open-angle glaucoma (POAG) by OPTEC-functional vision analyzer (FVA). METHODS: In this prospective study, eighty patients (80 eyes) with POAG were randomly divided into four groups. The groups were randomly received timolol maleate 0.5%, travoprost 0.004%, dorzolamide 2%, and brimonidine tartrate 0.2%. The medications were used in the eye that was randomly selected. The CS was assessed before and 15 min after the intervention by the FVA. The paired t-test was used to compare the difference between before and after the intervention. P < 0.05 was considered statistically significant. RESULTS: Fifteen minutes after the instillation of timolol maleate (Group A), the CS in three out of twenty patients at the spatial frequencies of 1.5, and 3 cycles per degree (cpd) was significantly decreased (P = 0.015). However, using travoprost (Group B) and dorzolamide (Group C), the CS in one out of twenty patients at low spatial frequencies (1.5 and 3 cpd) was decreased in the two groups, which was not statistically significant for these medications (P > 0.05). In Group D, after applying brimonidine tartrate, the CS in two out of twenty patients at the spatial frequency of 18 cpd was significantly decreased (P = 0.042). CONCLUSION: Our study showed that CS values at low and high spatial frequencies after applying timolol and brimonidine eye drops are temporarily reduced in patients with POAG.


Assuntos
Anti-Hipertensivos/uso terapêutico , Sensibilidades de Contraste/fisiologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Testes Visuais/instrumentação , Adulto , Tartarato de Brimonidina/uso terapêutico , Feminino , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Sulfonamidas/uso terapêutico , Tiofenos/uso terapêutico , Timolol/uso terapêutico , Travoprost/uso terapêutico , Testes de Campo Visual , Campos Visuais/fisiologia
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