Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 717
Filtrar
1.
Biochim Biophys Acta Rev Cancer ; 1873(2): 188355, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32135169

RESUMO

The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K+ channel protein mainly expressed in heart and brain tissue. HERG plays critical role in cardiac repolarization, and mutations in HERG can cause long QT syndrome. More recently, evidence has emerged that HERG channels are aberrantly expressed in many kinds of cancer cells and play important roles in cancer progression. HERG could therefore be a potential biomarker for cancer and a possible molecular target for anticancer drug design. HERG affects a number of cellular processes, including cell proliferation, apoptosis, angiogenesis and migration, any of which could be affected by dysregulation of HERG. This review provides an overview of available information on HERG channel as it relates to cancer, with focus on the mechanism by which HERG influences cancer progression. Molecular docking attempts suggest two possible protein-protein interactions of HERG with the ß1-integrin receptor and the transcription factor STAT-1 as novel HERG-directed therapeutic targeting which avoids possible cardiotoxicity. The role of epigenetics in regulating HERG channel expression and activity in cancer will also be discussed. Finally, given its inherent extracellular accessibility as an ion channel, we discuss regulatory roles of this molecule in cancer physiology and therapeutic potential. Future research should be directed to explore the possibilities of therapeutic interventions targeting HERG channels while minding possible complications.


Assuntos
Carcinogênese/patologia , Canal de Potássio ERG1/metabolismo , Integrina beta1/metabolismo , Neoplasias/patologia , Fator de Transcrição STAT1/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Carcinogênese/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Canal de Potássio ERG1/antagonistas & inibidores , Canal de Potássio ERG1/química , Canal de Potássio ERG1/genética , Epigênese Genética/efeitos dos fármacos , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Síndrome do QT Longo/genética , Potenciais da Membrana/efeitos dos fármacos , Simulação de Acoplamento Molecular , Mutação , Miócitos Cardíacos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Conformação Proteica em alfa-Hélice , Mapeamento de Interação de Proteínas , Estrutura Quaternária de Proteína , Piridinas/farmacologia , Piridinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Sulfanilamidas/farmacologia , Sulfanilamidas/uso terapêutico
2.
J Cardiovasc Pharmacol ; 73(6): 365-372, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31162245

RESUMO

A long-acting loop diuretic, azosemide, has been shown to improve long-term prognosis in patients with heart failure compared with a short-acting loop diuretic, furosemide. However, the therapeutic advantages of azosemide over furosemide have not been clearly established. In this study, we retrospectively analyzed clinical outcomes and laboratory data in patients with congestive heart failure treated with furosemide or azosemide, and the efficacy of these agents was compared. First, we screened 1900 patients and selected 124 (furosemide group: n = 40; azosemide group: n = 84) as the total study population. From these patients, we next selected 72 patients for the propensity score-matched analysis (furosemide group: n = 36; azosemide group: n = 36). The incidence of all-cause death and rehospitalization due to worsening heart failure during 24 months of follow-up was similar between the furosemide and azosemide groups in both the total study population and the propensity score-matched population. However, in the propensity score-matched analysis, the estimated glomerular filtration rate time-dependently decreased during 36 months of follow-up in the furosemide group (56.5 ± 19.5-43.2 ± 16.3 mL/min/1.73 m), whereas it did not change in the azosemide group (58.6 ± 22.0-50.3 ± 17.8 mL/min/1.73 m) (P = 0.032). Azosemide might have some potential advantage for renal protection over furosemide in patients with congestive heart failure.


Assuntos
Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Sulfanilamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Furosemida/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Pontuação de Propensão , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Sulfanilamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos
3.
BMC Res Notes ; 12(1): 244, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31036061

RESUMO

OBJECTIVES: Diabetic foot ulcers (DFUs) often lead to hospital admissions, amputations and deaths; however, there is no up-to-date information on microbial isolates from DFUs and no mention of utilization of molecular techniques in Sub-Saharan Africa. We conducted a cross-sectional study among 83 adult patients at a tertiary hospital in Kenya over 12 months. The study aimed to isolate, identify bacteria, their antibiotic susceptibility patterns in active DFUs, and to compare standard microbiological methods versus a real-time PCR commercial kit in the detection of Staphylococcus aureus DNA and methicillin-resistant S. aureus (MRSA) DNA. RESULTS: Eighty swabs (94%) were culture-positive; 29% were Gram-positive and 65% were Gram-negative. The main organisms isolated were S. aureus (16%), Escherichia coli (15%), Proteus mirabilis (11%), Klebsiella pneumoniae (7%) and Pseudomonas aeruginosa (7%). The bacterial isolates showed resistance to commonly used antibiotics such as ampicillin, amoxicillin, cefepime, ceftazidime, cefuroxime, clindamycin, erythromycin, piperacillin-tazobactam, tetracycline and trimethoprim-sulphamethoxazole (TMPSMX). Thirty-one percent of the S. aureus isolated and 40% of the Gram-negatives were multi-drug resistant organisms (MDROs). There was a high prevalence of nosocomial bacteria. MRSA were not identified using culture methods but were identified using PCR. PCR was more sensitive but less specific than culture-based methods to identify S. aureus.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Pé Diabético/diagnóstico , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Técnicas de Tipagem Bacteriana , Cefalosporinas/uso terapêutico , Clindamicina/uso terapêutico , Estudos Transversais , Pé Diabético/tratamento farmacológico , Pé Diabético/epidemiologia , Pé Diabético/microbiologia , Escherichia coli/classificação , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/isolamento & purificação , Humanos , Quênia/epidemiologia , Klebsiella pneumoniae/classificação , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/isolamento & purificação , Macrolídeos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Penicilinas/uso terapêutico , Proteus mirabilis/classificação , Proteus mirabilis/efeitos dos fármacos , Proteus mirabilis/genética , Proteus mirabilis/isolamento & purificação , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Staphylococcus aureus/classificação , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Sulfanilamidas/uso terapêutico
4.
Bioorg Med Chem Lett ; 27(21): 4914-4919, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28958623

RESUMO

A series of potent, selective and long-acting quinoline-based sulfonamide human H1 histamine receptor antagonists, designed for once-daily intranasal administration for the treatment of rhinitis were developed. Sulfonamide 33b had a slightly lower affinity for the H1 receptor than azelastine, had low oral bioavailability in the rat and dog, and was turned over to five major metabolites. Furthermore, 33b had longer duration of action than azelastine in guinea pigs, lower rat brain-penetration, and did not cause time dependent inhibition of CYP2D6 or CYP3A4. The clinical dose in humans is expected to be low (approximately 0.5mg per day) based on the clinical dose used for azelastine and a comparison of efficacy data from animal models for 33b and azelastine.


Assuntos
Antagonistas dos Receptores Histamínicos H1/química , Quinolinas/química , Receptores Histamínicos H1/metabolismo , Rinite Alérgica/tratamento farmacológico , Sulfanilamidas/química , Sulfonamidas/química , Sulfonas/química , Administração Intranasal , Animais , Encéfalo/metabolismo , Cães , Cobaias , Meia-Vida , Antagonistas dos Receptores Histamínicos H1/farmacocinética , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Concentração Inibidora 50 , Quinolinas/farmacocinética , Quinolinas/uso terapêutico , Ratos , Receptores Histamínicos H1/química , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Relação Estrutura-Atividade , Sulfanilamida , Sulfanilamidas/farmacocinética , Sulfanilamidas/uso terapêutico , Sulfonamidas/farmacocinética , Sulfonamidas/uso terapêutico , Sulfonas/farmacocinética , Sulfonas/uso terapêutico
6.
Neurochem Res ; 42(7): 1972-1982, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28275953

RESUMO

Epilepsy is one of the most common neurological diseases, with between 34 and 76 per 100,000 people developing epilepsy annually. Epilepsy therapy for the past 100+ years is based on the use of antiepileptic drugs (AEDs). Despite the availability of more than twenty old and new AEDs, approximately 30% of patients with epilepsy are not seizure-free with the existing medications. In addition, the clinical use of the existing AEDs is restricted by their side-effects, including the teratogenicity associated with valproic acid that restricts its use in women of child-bearing age. Thus, there is an unmet clinical need to develop new, effective AEDs. In the present study, a novel class of carbamates incorporating phenethyl or branched aliphatic chains with 6-9 carbons in their side-chain, and 4-benzenesulfonamide-carbamate moieties were synthesized and evaluated for their anticonvulsant activity, teratogenicity and carbonic anhydrase (CA) inhibition. Three of the ten newly synthesized carbamates showed anticonvulsant activity in the maximal-electroshock (MES) and 6 Hz tests in rodents. In mice, 3-methyl-2-propylpentyl(4-sulfamoylphenyl)carbamate(1), 3-methyl-pentan-2-yl-(4-sulfamoylphenyl)carbamate (9) and 3-methylpentyl, (4-sulfamoylphenyl)carbamate (10) had ED50 values of 136, 31 and 14 mg/kg (MES) and 74, 53, and 80 mg/kg (6 Hz), respectively. Compound (10) had rat-MES-ED50 = 13 mg/kg and ED50 of 59 mg/kg at the mouse-corneal-kindling test. These potent carbamates (1,9,10) induced neural tube defects only at doses markedly exceeding their anticonvuslnat-ED50 values. None of these compounds were potent inhibitors of CA IV, but inhibited CA isoforms I, II and VII. The anticonvulsant properties of these compounds and particularly compound 10 make them potential candidates for further evaluation and development as new AEDs.


Assuntos
Anticonvulsivantes/uso terapêutico , Carbamatos/uso terapêutico , Anidrases Carbônicas/uso terapêutico , Ácidos Carboxílicos/uso terapêutico , Convulsões/tratamento farmacológico , Sulfanilamidas/uso terapêutico , Animais , Anticonvulsivantes/química , Anticonvulsivantes/toxicidade , Carbamatos/química , Carbamatos/toxicidade , Anidrases Carbônicas/química , Anidrases Carbônicas/toxicidade , Ácidos Carboxílicos/química , Ácidos Carboxílicos/toxicidade , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Excitação Neurológica/efeitos dos fármacos , Excitação Neurológica/fisiologia , Masculino , Camundongos , Defeitos do Tubo Neural/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Convulsões/induzido quimicamente , Relação Estrutura-Atividade , Sulfanilamida , Sulfanilamidas/química , Sulfanilamidas/toxicidade , Teratogênios/química , Teratogênios/toxicidade
7.
Heart Vessels ; 32(7): 865-871, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28105515

RESUMO

We have previously reported that a long-acting loop diuretic, azosemide, reduces cardiovascular risks in patients with chronic heart failure (CHF) as compared with a short-acting one, furosemide, in Japanese Multicenter Evaluation of LOng- versus short-acting Diuretics In Congestive heart failure (J-MELODIC). However, the mechanisms of the difference have not been elucidated. This study aimed to examine whether there is a difference in the reduction in plasma brain natriuretic peptide (BNP) level and in left ventricular (LV) functional recovery between the CHF patients treated with the long-acting diuretic (the azosemide group) and the short-acting diuretic (the furosemide group). We reviewed changes in plasma BNP level and echo-assessed LV functional parameters from baseline to a year after the entry in 288 CHF patients with New York Heart Association class II or III symptoms that joined J-MELODIC. The decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group (p < 0.01). The changes in echocardiographic parameters were not more favorable in the azosemide group than in the furosemide group. In conclusion, the decrease in plasma BNP levels was larger in the azosemide group than in the furosemide group. These findings may account for the better prognosis in CHF patients treated with azosemide than those with furosemide in J-MELODIC.


Assuntos
Furosemida/uso terapêutico , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Sulfanilamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doença Crônica , Ecocardiografia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos
8.
Expert Opin Drug Metab Toxicol ; 12(4): 423-31, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26878088

RESUMO

INTRODUCTION: Carbonic anhydrase inhibitors (CAIs) of the sulfonamide and sulfamate type are clinically used drugs as diuretics, antiglaucoma, antiepileptic, antiobesity and anti-high altitude disease agents. Anticancer agents based on CAIs are also in clinical development for the management of hypoxic, metastatic tumors. Acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide are mainly used as antiglaucoma drugs, sulthiame, topiramate and zonisamide as antiepileptic/antiobesity agents, celecoxib and polmacoxib are dual carbonic anhydrase/cycloxygenase inhibitors. Girentuximab, a monoclonal antibody and SLC-0111, a sulfonamide inhibitor, are in clinical trials as anticancer agents. AREAS COVERED: The drug interactions with many classes of pharmacological agents are reviewed. Some of these drugs, such as acetazolamide, topiramate and celecoxib show a large number of interactions with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, antiepileptics, immunosupressants, anticholinesterase drugs, ß-blockers, anesthetics, oral contraceptives, anticancer agents, antifungals, anti-mycobacterials, lithium, metformin and clopidogrel. EXPERT OPINION: The multiple drug interactions in which CAIs are involved should be carefully considered when such drugs are used in combination with the drug classes mentioned above, as the risks of developing toxicity and serious side effects if the dosages are not adjusted are high. There are also synergistic effects between CAIs and some NSAIDs, anticancer agents and benzodiazepines for the management of cystoid macular edema, some tumor types and neuropathic pain, respectively.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Acetazolamida/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Fármacos Antiobesidade/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antineoplásicos/uso terapêutico , Benzodiazepinas/uso terapêutico , Celecoxib/uso terapêutico , Ensaios Clínicos como Assunto , Contraindicações , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Isoxazóis/uso terapêutico , Metazolamida/uso terapêutico , Fenobarbital/análogos & derivados , Fenobarbital/uso terapêutico , Sulfanilamida , Sulfanilamidas/uso terapêutico , Sulfonamidas/uso terapêutico , Ácidos Sulfônicos/uso terapêutico , Tiazinas/uso terapêutico , Tiofenos/uso terapêutico , Topiramato , Zonisamida
9.
Antimicrob Agents Chemother ; 59(12): 7593-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26416859

RESUMO

The emergence of multidrug-resistant (MDR) uropathogens is making the treatment of urinary tract infections (UTIs) more challenging. We sought to evaluate the accuracy of empiric therapy for MDR UTIs and the utility of prior culture data in improving the accuracy of the therapy chosen. The electronic health records from three U.S. Department of Veterans Affairs facilities were retrospectively reviewed for the treatments used for MDR UTIs over 4 years. An MDR UTI was defined as an infection caused by a uropathogen resistant to three or more classes of drugs and identified by a clinician to require therapy. Previous data on culture results, antimicrobial use, and outcomes were captured from records from inpatient and outpatient settings. Among 126 patient episodes of MDR UTIs, the choices of empiric therapy against the index pathogen were accurate in 66 (52%) episodes. For the 95 patient episodes for which prior microbiologic data were available, when empiric therapy was concordant with the prior microbiologic data, the rate of accuracy of the treatment against the uropathogen improved from 32% to 76% (odds ratio, 6.9; 95% confidence interval, 2.7 to 17.1; P < 0.001). Genitourinary tract (GU)-directed agents (nitrofurantoin or sulfa agents) were equally as likely as broad-spectrum agents to be accurate (P = 0.3). Choosing an agent concordant with previous microbiologic data significantly increased the chance of accuracy of therapy for MDR UTIs, even if the previous uropathogen was a different species. Also, GU-directed or broad-spectrum therapy choices were equally likely to be accurate. The accuracy of empiric therapy could be improved by the use of these simple rules.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Nitrofurantoína/uso terapêutico , Sulfanilamidas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Sistema Urinário/efeitos dos fármacos , Bases de Dados Factuais , Pesquisa Empírica , Humanos , Testes de Sensibilidade Microbiana , Resultado do Tratamento , Estados Unidos , United States Department of Veterans Affairs , Sistema Urinário/microbiologia , Sistema Urinário/fisiopatologia , Infecções Urinárias/diagnóstico , Infecções Urinárias/microbiologia , Infecções Urinárias/fisiopatologia
10.
Lik Sprava ; (1-2): 102-8, 2015.
Artigo em Ucraniano | MEDLINE | ID: mdl-26118037

RESUMO

The efficacy and tolerability of combined chondroprotectors Teraflex® in patients with diabetes mellitus type 1 and 2, complicated by arthropathy were investigated. It was established, that Tera- flex® therapy positively influences on the development of diabetic arthropathy (reducing intensity of pain, increasing the range of movements and reduced volume of the affected joints, increasing the functionality of the patient). In addition, an analysis of the impact of chondroprotectors on the level of sugar among patients.It was found, that it is necessary to control blood sugar while taking chondroprotectors and if needed, increasing the dose of hypoglycohaemic drugs during this period.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Dor/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Adulto , Artrite Reumatoide/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/fisiopatologia , Glicemia/metabolismo , Sulfatos de Condroitina/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Seguimentos , Glucosamina/uso terapêutico , Humanos , Masculino , Dor/sangue , Dor/complicações , Dor/fisiopatologia , Amplitude de Movimento Articular/efeitos dos fármacos , Sulfanilamidas/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Resultado do Tratamento
11.
Clin Exp Nephrol ; 19(2): 247-53, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24821289

RESUMO

BACKGROUND/AIMS: Type 2 diabetic kidney disease (DKD) is frequently accompanied by uncontrollable hypertension due to the sodium sensitivity inherent in DKD and to diuretic-resistant edema. In general, diuretics are effective in treating this condition, but thiazide diuretics are thought to be innocuous in advanced chronic kidney disease (CKD). We examined the renoprotective effects of combination therapy with thiazides and loop diuretics in type 2 DKD patients with CKD stage G4 or G5. METHODS: This study included 11 patients with type 2 DKD and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m(2) who were suffering from severe edema even with loop diuretics. Each patient received additional hydrochlorothiazide (HCTZ) therapy, which was continued for more than 12 months. We examined clinical parameters including blood pressure (BP), proteinuria, and eGFR before and after the addition of HCTZ. RESULTS: Patients received a 13.6 ± 3.8 mg/day dose of HCTZ in addition to loop diuretics (azosemide: 120 mg/day in 6 cases, 60 mg/day in 3 cases and furosemide: 80 mg/day in 1 case, 120 mg/day in 1 case). Side effects of HCTZ were not observed in all patients. After the addition of HCTZ therapy, systolic and diastolic blood pressures (S-BP, D-BP) as well as proteinuria significantly decreased (S-BP: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month, D-BP: at 12 months, p < 0.05 vs. 0 month, proteinuria: at 6 months, p < 0.05 and 12 months, p < 0.01 vs. 0 month). The annual decline in eGFR was not significantly different before and after HCTZ therapy (-7.7 ± 8.5 and -8.4 ± 4.8 mL/min/1.73 m(2)/year, respectively). CONCLUSION: Our findings suggest that the combination of HCTZ and loop diuretics improves BP levels, and decreases proteinuria even in advanced stage type 2 DKD patients with severe edema. The addition of HCTZ therapy was not found to negatively affect the change in eGFR in the present study.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/complicações , Diuréticos/uso terapêutico , Edema/etiologia , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Fármacos Renais/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Nefropatias Diabéticas/fisiopatologia , Quimioterapia Combinada , Feminino , Furosemida/uso terapêutico , Taxa de Filtração Glomerular , Humanos , Hipertensão/etiologia , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Estudos Retrospectivos , Sulfanilamidas/uso terapêutico
12.
Exp Parasitol ; 136: 59-62, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24211419

RESUMO

In the current study, we identified five sheep flocks with fasciolosis in the province of León (northwestern Spain) in order to determine the anthelmintic resistance status to three commonly used anthelmintics, namely albendazole (ABZ), triclabendazole (TCBZ) and clorsulon (CLOR). The identification of one flock resistant to ABZ and CLOR was shown after the faecal egg count reduction test (FECRT). The reductions in eggs per gram values were -17.6% and -68% against immature and adult flukes, respectively, after ABZ treatment; 85.15% and 44.91% against immature and adult flukes, respectively, after CLOR treatment; and 97.06% against both stages, after the administration of TCBZ. As an alternative to control the infection, two combinations of ABZ and CLOR were tested. In the first, both drugs were administered at the recommended dose of each; in this case, the efficiency reached values above 95% against both immature and adult flukes. However, when the combined drugs were administered at half the recommended dose of each, the efficiency of the combination was very low, i.e. 16.67% and -11.11% against mature and immature flukes, respectively. In conclusion, this preliminary report suggests a possible interaction between ABZ and CLOR after their joint administration. However, these results should be confirmed in other flocks.


Assuntos
Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Fasciola hepatica/efeitos dos fármacos , Fasciolíase/veterinária , Doenças dos Ovinos/tratamento farmacológico , Sulfanilamidas/uso terapêutico , Administração Oral , Albendazol/administração & dosagem , Albendazol/farmacologia , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/farmacologia , Benzimidazóis/administração & dosagem , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Resistência a Múltiplos Medicamentos , Quimioterapia Combinada , Fasciolíase/tratamento farmacológico , Fezes/parasitologia , Feminino , Injeções Subcutâneas/veterinária , Contagem de Ovos de Parasitas/veterinária , Ovinos , Doenças dos Ovinos/parasitologia , Sulfanilamidas/administração & dosagem , Sulfanilamidas/farmacologia , Triclabendazol
13.
Subcell Biochem ; 75: 349-59, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24146387

RESUMO

Inhibition of carbonic anhydrase (CA, EC 4.2.1.1) has pharmacologic applications in the treatment of glaucoma, a disease affecting a large number of people and characterized by an elevated intraocular pressure (IOP). At least three isoforms, CA II, IV and XII are targeted by the sulfonamide inhibitors, some of which are clinically used drugs. Acetazolamide, methazolamide and dichlorophenamide are first generation CA inhibitors (CAIs) still used as systemic drugs for the management of this disease. Dorzolamide and brinzolamide represent the second generation inhibitors, being used topically, as eye drops, with less side effects compared to the first generation drugs. Third generation inhibitors have been developed by using the tail approach, but they did not reach the clinics yet. The most promising such derivatives are the sulfonamides incorporating either tails with nitric oxide releasing moieties or hybrid drugs possessing prostaglandin (PG) F agonist moieties in their molecules. Recently, the dithiocarbamates have also been described as CAIs possessing IOP lowering effects in animal models of glaucoma. CAIs are used alone or in combination with other drugs such as adrenergic agonist/antagonists, or PG analogs, being an important component of the antiglaucoma drugs armamentarium.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Glaucoma/tratamento farmacológico , Relação Estrutura-Atividade , Sulfanilamidas/uso terapêutico , Acetazolamida/uso terapêutico , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/química , Anidrase Carbônica IV/antagonistas & inibidores , Anidrase Carbônica IV/química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/química , Anidrases Carbônicas/metabolismo , Glaucoma/patologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Óxido Nítrico/química , Sulfanilamida , Sulfonamidas/uso terapêutico , Tiazinas/uso terapêutico
14.
Future Med Chem ; 5(11): 1331-40, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23859210

RESUMO

More research effort needs to be invested in antimicrobial drug development to address the increasing threat of multidrug-resistant organisms. The enzyme DHPS has been a validated drug target for over 70 years as the target for the highly successful sulfa drugs. The use of sulfa drugs has been compromised by the widespread presence of resistant organisms and the adverse side effects associated with their use. Despite the large amount of structural information available for DHPS, few recent publications address the possibility of using this knowledge for novel drug design. This article reviews the relevant papers and patents that report promising new small-molecule inhibitors of DHPS, and discuss these data in light of new insights into the DHPS catalytic mechanism and recently determined crystal structures of DHPS bound to potent small-molecule inhibitors. This new functional understanding confirms that DHPS deserves further consideration as an antimicrobial drug target.


Assuntos
Álcool Desidrogenase/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Sulfanilamidas/química , Álcool Desidrogenase/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Proteínas de Bactérias/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Sulfanilamida , Sulfanilamidas/farmacologia , Sulfanilamidas/uso terapêutico
15.
Berl Munch Tierarztl Wochenschr ; 126(5-6): 197-201, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23758033

RESUMO

Efflux transporters belonging to the family of ABC transporters have an important functional role in the maintenance of the intestinal barrier. As efflux transporters they prevent the absorption of toxic substances from feed, while at the same time facilitating the excretion of metabolic waste products as well as drugs from the circulation into the intestinal lumen. As Eimeria tenella infection significantly affects the integrity of caecum, the effects of experimental E. tenella infection on the levels of expression of ABCB1 mRNAs in the intestines and livers of broilers were evaluated. ABCB1 mRNA expression was quantified by qRT-PCR. Its expression levels were significantly down-regulated in the caecum of infected animals. The levels of ABCB1 mRNA were not changed in the duodenum and the liver. After treatment of the animals with sulfapyrazine for three days, not only a significant improvement of the clinical appearance but also a normalization of the P-gp expression was noticed. Although the current study cannot distinguish between the direct effect of the drug on the host and the drug action on the parasite, these results suggest that the treatment of coccidiosis with sulfachlorpyrazine also restored the expression of the investigated efflux transporter in the caecum. This is of clinical significance as P-glycoproteins contribute to the integrity of intestines and their function as important biological barriers, protecting poultry from pathogens and toxic compounds in animal feeds.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Galinhas/parasitologia , Coccidiose/veterinária , Eimeria tenella/fisiologia , Doenças das Aves Domésticas/parasitologia , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Anti-Infecciosos/uso terapêutico , Ceco/metabolismo , Ceco/patologia , Galinhas/genética , Coccidiose/genética , Coccidiose/patologia , Regulação para Baixo , Duodeno/metabolismo , Feminino , Fígado/metabolismo , Masculino , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/patologia , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Sulfanilamidas/uso terapêutico
16.
Vet Parasitol ; 196(1-2): 245-9, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23384580

RESUMO

Bot fly larvae (Philornis genus) are obligate subcutaneous blood-feeding parasites of Neotropical birds including psittacines. We analyze twelve years of data on scarlet macaw (Ara macao) nestlings in natural and artificial nests in the lowland forests of southeastern Peru and report prevalence and intensity of Philornis parasitism. Bot fly prevalence was 28.9% while mean intensity was 5.0 larvae per infected chick. Prevalence in natural nests (11%, N=90 nestlings) was lower than in wooden nest-boxes (39%, N=57) and PVC boxes (39%, N=109). We describe a new technique of removing Philornis larvae using a reverse syringe design snake bite extractor. We compare this new technique to two other methods for removing bots from macaw chicks and find the new method the most suitable.


Assuntos
Doenças das Aves/parasitologia , Dípteros/fisiologia , Miíase/veterinária , Papagaios , Envelhecimento , Animais , Animais Selvagens , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Doenças das Aves/terapia , Cumafos/administração & dosagem , Cumafos/uso terapêutico , Combinação de Medicamentos , Inseticidas/administração & dosagem , Inseticidas/uso terapêutico , Larva/fisiologia , Miíase/terapia , Propoxur/administração & dosagem , Propoxur/uso terapêutico , Sulfanilamida , Sulfanilamidas/administração & dosagem , Sulfanilamidas/uso terapêutico
17.
Exp Parasitol ; 132(3): 378-82, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22981889

RESUMO

Interleukin (IL)-12 and IL-10 are immunoregulatory cytokines with an antagonistic effect on the T-helper (Th)1/Th2 cytokine balance and they provide a functional link between innate resistance and the adaptive immune response. This investigation was conducted to determine the expression of IL-10 and IL-12B mRNA levels in chickens' gut mucosa infected with Eimeria tenella and in sulfachlorpyrazine-sodium treated animals after infection. Broiler chickens were randomly allocated in three groups: healthy untreated control; infected untreated animals and infected, treated with sulfachlorpyrazine sodium chickens 6 days after the challenge with an E. tenella. Quantitative real time PCR analysis was performed using specific primer pairs and probes for IL-10 and IL-12B. The expression of IL-10 mRNA was greater in the duodenum then in the caecum and the liver of healthy chickens. E. tenella infection led to significant up-regulation of IL-10 mRNA in the caecum, followed by mRNA in the liver. A significant down regulation was observed mainly in the caecum after the treatment with sulfachlorpyrazine. In contrast, IL-12B expression in all investigated tissues remained insignificantly affected in the studied groups of animals. Distinct up-regulation of IL-10 mRNA, after the challenge with E. tenella, in the caecum can be attributed to the tissue tropism of Eimeria spp. The production of IL-12 is regulated by negative feedback through IL-10 which explains lack of increase in IL-12B mRNA. Sulfonamide treatment resulted in clinical improvement and restoration of IL-10 mRNA to the levels observed in healthy chickens.


Assuntos
Galinhas/parasitologia , Coccidiose/veterinária , Eimeria tenella/imunologia , Interleucina-10/biossíntese , Interleucina-12/biossíntese , Doenças das Aves Domésticas/imunologia , Animais , Ceco/imunologia , Ceco/parasitologia , Coccidiose/tratamento farmacológico , Coccidiose/imunologia , Coccidiostáticos/uso terapêutico , Duodeno/imunologia , Duodeno/parasitologia , Feminino , Expressão Gênica , Interleucina-10/genética , Interleucina-12/genética , Fígado/imunologia , Fígado/parasitologia , Masculino , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/parasitologia , RNA Mensageiro/isolamento & purificação , RNA Mensageiro/metabolismo , RNA de Protozoário/isolamento & purificação , RNA de Protozoário/metabolismo , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Sulfanilamidas/uso terapêutico , Regulação para Cima
18.
Vet Parasitol ; 189(2-4): 227-32, 2012 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-22579500

RESUMO

The objective of this study was to evaluate the efficacy of a pour-on solution containing moxidectin plus triclabendazole (MOX plus TCBZ) against immature and adult stages of the liver fluke in cattle and compare the efficacy with other commercially available preparations. To this end, 104 male Holstein-Friesian calves aged between 3 and 4 months, were randomly allocated to 13 groups of eight animals each, and infected with approximately 500 Fasciola hepatica metacercariae. One group remained untreated, four groups were treated with MOX plus TCBZ at a dose rate of 0.1 mL/kg, four other groups were treated with ivermectin (IVM) plus clorsulon injectable at a dose rate of 0.02 mL/kg, and the remaining four groups were treated with IVM plus closantel pour-on at a dose rate of 0.1 mL/kg. Each treatment was applied to one of the groups at 4 weeks, 6 weeks, 8 weeks and 12 weeks after the experimental infection. At necropsy (99-102 days after infection), all untreated animals were infected with a minimum of 30 flukes. The MOX plus TCBZ treated animals had significantly (P<0.0001) lower fluke counts compared to the untreated control animals at all time points after treatment. Efficacy against 8-week old and adult flukes was >99.5%. For 6-week old immature fluke, the efficacy was 98.0% and for 4-week old immature fluke the efficacy was 90.9%. The IVM plus closantel pour-on treated animals had significantly lower fluke counts compared to the untreated control animals for adult and 8-week old flukes (P<0.0001), and for 6-week old flukes (P=0.002). The efficacy was 26.8%, 68.2%, 90.6% and 99.3% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. The IVM plus clorsulon treated animals had significantly lower fluke counts compared to the untreated control animals for adult (P<0.0001) and 8-week old (P<0.05) flukes. The efficacy was 29.7%, 43.4%, 53.2% and 99.2% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. For treatments at 4, 6 and 8 weeks after infection, the fluke counts were significantly (P<0.0001) lower for the MOX plus TCBZ treatment than for IVM plus closantel or IVM plus clorsulon. The results confirm the high efficacy (>90%) of the MOX plus TCBZ pour-on combination against 4-week old to adult liver fluke in cattle. The IVM plus closantel pour-on combination was effective (>90%) against 8-week old and adult flukes, but had low efficacy against 4- and 6-week old fluke. The IVM plus clorsulon injectable combination was effective (>90%) against adult fluke only.


Assuntos
Anti-Helmínticos/uso terapêutico , Benzimidazóis/uso terapêutico , Fasciola hepatica/efeitos dos fármacos , Fasciolíase/veterinária , Macrolídeos/uso terapêutico , Animais , Anti-Helmínticos/administração & dosagem , Benzimidazóis/administração & dosagem , Bovinos , Combinação de Medicamentos , Fasciolíase/tratamento farmacológico , Feminino , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Macrolídeos/administração & dosagem , Masculino , Sulfanilamidas/administração & dosagem , Sulfanilamidas/uso terapêutico , Triclabendazol
19.
Circ J ; 76(4): 833-42, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22451450

RESUMO

BACKGROUND: Diuretics are the most prescribed drug in heart failure (HF) patients. However, clinical evidence about their long-term effects is lacking. The purpose of this study was to compare the therapeutic effects of furosemide and azosemide, a short- and long-acting loop diuretic, respectively, in patients with chronic heart failure (CHF). METHODS AND RESULTS: In this multicenter, prospective, randomized, open, blinded endpoint trial, we compared the effects of azosemide and furosemide in patients with CHF and New York Heart Association class II or III symptoms. 320 patients (160 patients in each group, mean age 71 years) were followed up for a minimum of 2 years. The primary endpoint was a composite of cardiovascular death or unplanned admission to hospital for congestive HF. During a median follow-up of 35.2 months, the primary endpoint occurred in 23 patients in the azosemide group and in 34 patients in the furosemide group (hazard ratio [HR], 0.55, 95% confidence interval [CI] 0.32-0.95: P=0.03). Among the secondary endpoints, unplanned admission to hospital for congestive HF or a need for modification of the treatment for HF were also reduced in the azosemide group compared with the furosemide group (HR, 0.60, 95%CI 0.36-0.99: P=0.048). CONCLUSIONS: Azosemide, compared with furosemide, reduced the risk of cardiovascular death or unplanned admission to hospital for congestive HF.


Assuntos
Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Sulfanilamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Doença Crônica , Intervalo Livre de Doença , Feminino , Furosemida/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Sulfanilamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
20.
J Cardiol ; 59(3): 352-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22365947

RESUMO

BACKGROUND: Loop diuretics have two different classes with different duration of activity: short-acting such as furosemide (duration of activity, 6h) and long-acting such as azosemide (duration of activity, 10-12h). We conducted a multicenter, randomized, controlled trial in order to compare the therapeutic effects of azosemide, a long-acting loop diuretic, and furosemide, a short-acting one, on neurohumoral factors and cardiac function in outpatients with chronic heart failure (CHF). METHODS: We enrolled 98 patients with CHF who were receiving furosemide and an angiotensin-converting enzyme inhibitor, and they were randomly divided into furosemide (n=49) and azosemide (n=49) groups. The furosemide group continued furosemide at the same dosage, and the azosemide group switched from furosemide to azosemide. At baseline and after 3 months, we measured body weight, and levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), norepinephrine, active renin, creatinine, blood urea nitrogen, sodium, potassium, and hematocrit. Chest X-ray and echocardiography were also performed. RESULTS: Body weight and plasma levels of BNP and ANP significantly decreased after 3 months in the azosemide group compared to the furosemide group. There were no significant differences in changes of levels of creatinine, blood urea nitrogen, sodium, potassium, hematocrit, norepinephrine, and active renin after 3 months between the furosemide and azosemide groups. Echocardiography and chest X-ray did not demonstrate significant differences between the two groups. CONCLUSIONS: Long-acting azosemide is suggested to be useful for the improvement of neurohumoral factors compared with short-acting furosemide in patients with CHF.


Assuntos
Furosemida/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Sulfanilamidas/uso terapêutico , Idoso , Fator Natriurético Atrial/sangue , Biomarcadores/sangue , Doença Crônica , Preparações de Ação Retardada , Ecocardiografia , Feminino , Furosemida/administração & dosagem , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Humanos , Masculino , Peptídeo Natriurético Encefálico/sangue , Pacientes Ambulatoriais , Inibidores de Simportadores de Cloreto de Sódio e Potássio/classificação , Sulfanilamidas/administração & dosagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA