Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Quinolonas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Combinação Fluticasona-Salmeterol/uso terapêutico , Glucocorticoides/uso terapêutico , Glicopirrolato/uso terapêutico , Indanos/uso terapêutico , Administração por Inalação , Ensaios Clínicos Controlados Aleatórios como Assunto , Quinolonas/efeitos adversos , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Combinação de Medicamentos , Combinação Fluticasona-Salmeterol/efeitos adversos , Glicopirrolato/efeitos adversos , Indanos/efeitos adversosRESUMO
OBJECTIVE: To characterize pediatric exposures to the antidementia drugs donepezil, memantine, rivastigmine, and galantamine by reviewing a poison control system's database. STUDY DESIGN: A retrospective review of a statewide poison control system's database identified cases of pediatric (less than 19 years of age) exposures to antidementia drugs over an 11-year period. Data collected included age, sex, drug(s) involved, route of exposure, reason for exposure, symptoms, and interventions. RESULTS: There were 189 cases identified (53% male, median age: 2.3 years, 99% unintentional exposures). Donepezil was the most commonly reported exposure (106 cases), followed by memantine (57), galantamine (18), oral rivastigmine (16), and transdermal rivastigmine (3). Coingestants were reported in 68 (36%) cases. Symptoms were reported in 38 (20%) cases. Gastrointestinal symptoms were most common (n = 21) followed by central nervous system depression (n = 15). Oral rivastigmine was associated with higher rates of symptoms. No bradycardia, seizures, or fasciculations were reported. Eighty-nine cases (47%) were evaluated at a health care facility, and 13 (7%) were admitted to a hospital. Oral rivastigmine exposures were associated with increased rate of health care facility evaluation. Activated charcoal was administered in 28 cases. Atropine was given only once, for drooling. There were no serious outcomes or deaths in this series. CONCLUSIONS: Reported pediatric exposures to antidementia drugs resulted in minimal morbidity and no mortality. Oral rivastigmine exposures were found to be associated with more symptoms and health care facility evaluations.
Assuntos
Demência/tratamento farmacológico , Galantamina/efeitos adversos , Indanos/efeitos adversos , Memantina/efeitos adversos , Nootrópicos/efeitos adversos , Piperidinas/efeitos adversos , Centros de Controle de Intoxicações/estatística & dados numéricos , Rivastigmina/efeitos adversos , Criança , Pré-Escolar , Donepezila , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
The results of our previous study demonstrated that ptaquiloside, the main toxic agent found in Pteridium aquilinum, suppresses natural killer (NK) cell-mediated cytotoxicity. However, the ability of ptaquiloside to suppress the cytotoxicity of NK cells was prevented by selenium supplementation. NK cells play an important role in the innate immune response and have the ability to kill tumor cells. Therefore, we hypothesized that selenium may prevent the higher susceptibility to urethane-induced lung carcinogenesis that has been observed in mice treated with P. aquilinum. The immunosuppressive effects of ptaquiloside have been associated with a higher number of urethane-induced lung nodules in mice. Hence, we assessed the effects of P. aquilinum-induced immunosuppression on urethane-induced lung carcinogenesis in C57BL/6 mice that had been supplemented with selenium. For these experiments, mice were treated with both an aqueous extract of P. aquilinum (20 g/kg/day) and selenium (1.3 mg/kg) by gavage once daily for 14 days followed by a once-weekly intraperitoneal injection of urethane (1 g/kg) for 10 weeks that was accompanied by gavage 5 days a week. Lung adenomas in mice that had been treated with P. aquilinum plus urethane occurred with a frequency that was 44% higher than that in mice that had been treated with only urethane. In mice that had been supplemented with selenium and treated with P. aquilinum plus urethane, the occurrence of lung adenomas was reduced to 26%. These results suggest that selenium prevents the immunosuppressive effects of P. aquilinum on urethane-induced lung carcinogenesis.
Assuntos
Adenoma/prevenção & controle , Carcinógenos/farmacologia , Suplementos Nutricionais , Indanos , Neoplasias Pulmonares/prevenção & controle , Pteridium/química , Selênio/farmacologia , Sesquiterpenos , Uretana , Adenoma/induzido quimicamente , Adenoma/patologia , Animais , Feminino , Indanos/efeitos adversos , Indanos/farmacologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/patologia , Camundongos , Sesquiterpenos/efeitos adversos , Sesquiterpenos/farmacologia , Uretana/efeitos adversos , Uretana/farmacologiaRESUMO
INTRODUCTION/OBJECTIVES: Previous publications have shown beneficial effects of cholinergic medication on obstructive sleep apnea (OSA) in Alzheimer's disease (AD) patients. We hypothesized that cholinergic medication could also improve OSA in non-AD patients. The present study evaluated the effects of donepezil on OSA in non-AD patients. METHODS: A randomized, double-blind, placebo-controlled study was conducted. The final sample consisted of 21 male patients with mild to severe OSA and AHI >10 divided into two groups, a donepezil-treated group (n=11) and a placebo-treated group (n=10). The dosage was one tablet/day (5 mg) for the first two weeks and two tablets/day (10 mg) for the last two weeks. Polysomnography and sleepiness evaluations were performed at baseline and after one month of treatment. Groups were compared using two-way ANOVA for repeated measures with treatment-group and treatment-time as the main factors and time-treatment as an interaction effect. RESULTS: Considering the effect of the interaction with time-treatment, there was a significant improvement in the obstructive apnea/hypopnea index, desaturation index, percentage of time with O(2) saturation ≤3% lower than baseline, lowest oxygen saturation, and the Epworth Sleepiness Scale (ESS) scores with donepezil treatment (p<0.05). Sleep efficiency significantly decreased (p<0.01). CONCLUSIONS: Donepezil treatment improved obstructive sleep apnea index, oxygen saturation, and sleepiness in parallel with a reduction in sleep efficiency. Our findings support the concept that cholinergic transmission may influence breathing regulation in OSA patients.
Assuntos
Inibidores da Colinesterase/administração & dosagem , Indanos/administração & dosagem , Piperidinas/administração & dosagem , Apneia Obstrutiva do Sono/tratamento farmacológico , Fases do Sono/efeitos dos fármacos , Adulto , Idoso , Inibidores da Colinesterase/efeitos adversos , Donepezila , Método Duplo-Cego , Humanos , Indanos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Piperidinas/efeitos adversos , Placebos , Polissonografia , Apneia Obstrutiva do Sono/diagnóstico , Resultado do TratamentoRESUMO
INTRODUCTION: Patients with diabetes complicated by hypertension and microalbuminuria have elevated cardiovascular risk, and controlling blood pressure in these patients is an urgent clinical priority. The present study aimed to examine the effects of a fixed-dose combination of antihypertensives on blood pressure and microalbuminuria. METHODS: Patients with type 2 diabetes, mild-to-moderate hypertension (diastolic blood pressure 85-105 mmHg, systolic blood pressure <160 mmHg, and 24-hour mean systolic blood pressure >130 mmHg), and microalbuminuria were randomized to 1 year of doubleblind treatment with fixed-dose manidipine/delapril (n=54) or losartan/hydrochlorothiazide (HCTZ) (n=56). RESULTS: Blood pressure was significantly reduced at 1 year in both groups (-22.2/-14.6 mmHg and -19.5/-14.3 mmHg, for systolic and diastolic blood pressure respectively, P<0.001 for each), with no significant between-group difference. Reductions in microalbuminuria occurred in both groups, with mean changes at 1 year of -3.9 mg/mmol creatinine (95% CI -5.3, -2.5) for manidipine/delapril (P<0.001 vs. baseline) and -2.7 mg/mmol creatinine (95% CI -4.0, -1.3) for losartan/HCTZ (P<0.001 vs. baseline and P=0.199 between groups). Glycemia over the 1-year study was largely unaffected; the blood glucose concentration was reduced from baseline with manidipine/delapril, although not statistically significant (mean change -0.2 mmol/L, P=0.064). Both treatments were well tolerated, with discontinuation for adverse events for one (1.9%) patient in the manidipine/delapril group and two (3.6%) in the losartan/HCTZ group. CONCLUSIONS: A fixed-dose manidipine/delapril combination represents a useful addition to the treatment options available to control hypertension complicated by diabetes and microalbuminuria.
Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Indanos/uso terapêutico , Losartan/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Albuminúria/complicações , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , Diabetes Mellitus Tipo 2/complicações , Di-Hidropiridinas/administração & dosagem , Di-Hidropiridinas/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Hipertensão/complicações , Indanos/administração & dosagem , Indanos/efeitos adversos , Losartan/administração & dosagem , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nitrobenzenos , PiperazinasRESUMO
The complex taxon embraced in the Pteridium genus, popularly known as bracken fern and notorious weeds in many parts of the world, is one of the few vascular plants known to induce cancer naturally in animals. It has been known for long to be acutely toxic to livestock and sublethal chronic oral feeding of bracken fronds leads to cancerous lesions in the urinary bladder, or bovine enzootic haematuria (BEH) and ileum of cattle. Bracken poisoning has been attributed chiefly to ptaquiloside, a norsesqui-terpene which is also a potent carcinogen inducing various malignancies in laboratory animals. It is capable of alkylating uncoiled DNAbases at key proto-oncogenes of selected organs. Some human populations also eat young bracken shoots and epidemiological studies in Japan and Brazil have shown a close association between bracken consumption and cancers of the upper alimentary tract. In addition, other studies reveal that the mere presence of bracken swards represents a greater risk to die of gastric adenocarcinoma for people who live more than 20 years in such areas or are exposed in childhood. This work reviews the bracken-cancer connections established by in vitro and in vivo experiments and epidemiological studies in various parts of the world, and provides insights into the possible bridges for bracken carcinogens to reach the human diet. Also, specific points where more research is needed are highlighted.