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1.
Expert Opin Drug Metab Toxicol ; 15(5): 407-415, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30991855

RESUMO

INTRODUCTION: About 40% of patients with epilepsy are associated with drug-resistant seizures, therefore there has been a continuous search for novel treatment approaches. In experimental studies, natural and synthetic cannabimimetic compounds alone or combined with antiepileptic drugs (AEDs) have been extensively studied and cannabidiol, a naturally occurring compound, has been involved in a number of clinical trials. Areas covered: The authors have performed a literature search (PubMed database up to December 2018) for studies evaluating interactions between AEDs and cannabinoid receptor ligands in experimental models of seizures. Clinical data relate to the add-on treatment with cannabidiol. Expert opinion: WIN55,212-2 mesylate (WIN, a non-selective agonist of CB1 and CB2 receptors) significantly potentiated the anticonvulsant activity of various  AEDs in mice. Profound neurotoxic effects accompanied combinations of WIN with conventional AEDs. Among conventional and newer AEDs, ACEA (a selective CB1 receptor agonist) enhanced the protective action of phenobarbital and levetiracetam without accompanying adverse effects or pharmacokinetic interactions. Cannabidiol proved effective in clinical trials, reducing seizure frequency and the most frequently observed adverse effects were diarrhea, somnolence, and poor appetite. The retention rate was within 14-24% (12-14 weeks - 1 year) but it reached the level of 35% after 2 years.


Assuntos
Anticonvulsivantes/administração & dosagem , Canabinoides/administração & dosagem , Epilepsia/tratamento farmacológico , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacologia , Benzoxazinas/administração & dosagem , Benzoxazinas/efeitos adversos , Benzoxazinas/farmacologia , Canabinoides/efeitos adversos , Canabinoides/farmacologia , Modelos Animais de Doenças , Interações Medicamentosas , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Humanos , Camundongos , Morfolinas/administração & dosagem , Morfolinas/efeitos adversos , Morfolinas/farmacologia , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/farmacologia
2.
PLoS One ; 14(1): e0211346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30703155

RESUMO

Nicotine and cannabis use during adolescence has the potential to induce long lasting changes on affective and cognitive function. Here, we examined whether adolescent exposure to nicotine, the cannabinoid agonist WIN55-212,2 (WIN), or co-exposure to both would alter operant learning, locomotion, and anxiety- and reward-related behaviors in male and female mice during adulthood. Males exposed to a moderate dose of WIN (2 mg/kg) or co-exposed to nicotine and the moderate dose of WIN exhibited decreased anxiety-associated behaviors and increased cognitive flexibility, but did not differ in operant learning or generalized locomotion. In contrast, differences were not found among the females in these measures at the moderate WIN dose or in both sexes with exposure to a low WIN dose (0.2 mg/kg). Furthermore, a sex-dependent dissociative effect was found in natural reward consumption. Males exposed to the moderate dose of WIN or co-exposed to nicotine and the moderate dose of WIN demonstrated increased sucrose consumption. In contrast, females exposed to the moderate dose of WIN exhibited a decrease in sucrose consumption, which was ameliorated with co-administration of nicotine. Together, these novel findings demonstrate that adolescent exposure to cannabinoids in the presence or absence of nicotine results in altered affective and reward-related behaviors during adulthood.


Assuntos
Ansiedade/tratamento farmacológico , Benzoxazinas/efeitos adversos , Morfolinas/efeitos adversos , Naftalenos/efeitos adversos , Nicotina/efeitos adversos , Animais , Condicionamento Operante/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Recompensa , Caracteres Sexuais , Sacarose/metabolismo
3.
Sci Total Environ ; 656: 1365-1372, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30625665

RESUMO

Echinochloa crus-galli is one of the most noxious weeds in the world and causes yield losses in a variety of different field crops. Napropamide and acetochlor are herbicides commonly employed to control this weed. Both compounds are chiral, with enantiomers displaying different activities. However, it is unclear how the enantiomers of these two chiral herbicides act on different tissues of E. crus-galli. The objective of this paper is to investigate the action mechanism of napropamide and acetochlor in the roots and shoots of E. crus-galli. R­enantiomers were found to be more active than either the racemates or S-enantiomers on the weed. The content of chlorophyll was not significantly affected by treatment with either enantiomer. The impacts on the activity for the oxidative stress enzymes, except catalase (CAT), showed that both napropamide and acetochlor enantiomers could induce oxidative stress. Furthermore, R­enantiomers caused greater oxidative damage. Enhanced glutathione-S-transferase (GST) activity and expression of GST genes suggested both EcGSTF1 and EcGSTZ1 were present in the roots and shoots, and this will be helpful for detoxification. The changes in both the roots and shoots revealed the two herbicides displayed tissue selectivity in E. crus-galli. These results enable a better understanding on the mechanism of action for napropamide and acetochlor enantiomers on different tissues, including the shoots and roots in E. crus-galli.


Assuntos
Echinochloa/efeitos dos fármacos , Herbicidas/efeitos adversos , Naftalenos/efeitos adversos , Toluidinas/efeitos adversos , Transcrição Genética/efeitos dos fármacos , Echinochloa/genética , Echinochloa/fisiologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Brotos de Planta/efeitos dos fármacos , Brotos de Planta/genética , Brotos de Planta/fisiologia , Estereoisomerismo
4.
Toxicol Lett ; 300: 31-39, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30352267

RESUMO

Cholestasis is one of the most challenging diseases to be treated in current hepatology. However little is known about the adaptation difference and the underlying mechanism between acute and chronic cholestasis. In this study, wild-type and Pparα-null mice were orally administered diet containing 0.05% ANIT to induce chronic cholestasis. Biochemistry, histopathology and serum metabolome analysis exhibited the similar toxic phenotype between wild-type and Pparα-null mice. Bile acid metabolism was strongly adapted in Pparα-null mice but not in wild-type mice. The Shp and Fxr mRNA was found to be doubled in cholestatic Pparα-null mice compared with the control group. Western blot confirmed the up-regulated expression of FXR in Pparα-null mice treated with ANIT. Inflammation was found to be stronger in Pparα-null mice than those in wild-type mice in chronic cholestasis. These data chain indicated that bile acid metabolism and inflammation signaling were different between wild-type and Pparα-null mice developing chronic cholestasis, although their toxic phenotypes could not be discriminated. So basal PPARα cross-talked with FXR and inhibited bile acid metabolism adaptation in chronic cholestasis.


Assuntos
Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Colestase/induzido quimicamente , Colestase/fisiopatologia , Isocianatos/efeitos adversos , Fígado/metabolismo , Camundongos Knockout/genética , Naftalenos/efeitos adversos , Animais , Doença Crônica , Variação Genética , Masculino , Camundongos , Fenótipo
5.
Mod Rheumatol ; 29(6): 1042-1052, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30334639

RESUMO

Objective: Evaluate efficacy/safety of verinurad monotherapy in patients with gout (Japan/US) or asymptomatic hyperuricemia (Japan).Methods: Two randomized, placebo-controlled, phase II studies were conducted (NCT01927198/NCT02078219). Patients were randomized to once-daily doses of placebo or escalating doses of verinurad (study 1: 5-12.5 mg; study 2: 2.5-15 mg). Primary endpoint was percentage change from baseline in serum urate (sUA) at week 12 (study 1)/week 16 (study 2). Safety was also assessed.Results: Most patients in study 1 (n = 171) were white (74.9%); all patients were Japanese in study 2 (n = 204). Least squares means (±SE) estimate of percentage change in sUA levels from baseline in study 1 was 1.2 ± 2.9 for placebo, and -17.5 ± 2.8, -29.1 ± 2.8, -34.4 ± 2.9 for verinurad 5, 10, 12.5 mg, respectively. In study 2, results were -2.4 ± 2.5 and -31.7 ± 2.5, -51.7 ± 2.6,-55.8 ± 2.5, respectively. Difference from placebo was significant for each verinurad dose (p<.0001). The proportion of patients with treatment-emergent adverse events (TEAEs) was similar across all groups. Renal-related TEAEs were more common with verinurad than placebo.Conclusion: Verinurad monotherapy resulted in sustained reductions in sUA in Japanese/US patients but renal AEs occurred, so verinurad alone is not recommended for treatment of hyperuricemia or gout. The renal consequences of excessive uric acid excretion deserve study.


Assuntos
Supressores da Gota/efeitos adversos , Gota/tratamento farmacológico , Hiperuricemia/tratamento farmacológico , Naftalenos/efeitos adversos , Propionatos/efeitos adversos , Piridinas/efeitos adversos , Uricosúricos/efeitos adversos , Adulto , Feminino , Supressores da Gota/uso terapêutico , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Naftalenos/uso terapêutico , Propionatos/uso terapêutico , Piridinas/uso terapêutico , Estados Unidos , Uricosúricos/uso terapêutico
6.
Clin Exp Nephrol ; 23(2): 258-267, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30159688

RESUMO

BACKGROUND: This study investigated the pharmacokinetics, pharmacodynamics, and safety of multiple doses of evocalcet in Japanese secondary hyperparathyroidism (SHPT) patients receiving hemodialysis. METHODS: In this multicenter, open-label study, conducted between August 2013 and March 2014, 27 patients received multiple doses of 1 and 4 mg evocalcet for 14 days, followed by an extension period of multiple doses of 8 and 12 mg evocalcet for 7 days using an intra-patient dose escalation protocol. Pharmacodynamic parameters consisted of measurement of intact parathyroid hormone (PTH), serum-corrected calcium, serum phosphorus and intact fibroblast growth factor 23 concentrations. Safety was assessed by analysis of adverse events. RESULTS: Plasma evocalcet levels reached steady state 3 days after the first day of administration. Pharmacodynamic analyses showed that evocalcet effectively reduced intact PTH and serum-corrected calcium levels. Adverse events (AEs) occurred in 29.6 and 62.5% of patients receiving multiple doses of 1 or 4 mg, respectively. The AE 'blood calcium decreased' occurred in eight patients (33.0%) after multiple doses of 4 mg. All events were mild, except for one patient with a moderate AE (abnormal liver function) and one patient with a severe adverse drug reaction (blood calcium decreased). CONCLUSION: Multiple doses of evocalcet reduced intact PTH levels with a concomitant decrease in serum calcium levels. Evocalcet was well tolerated in SHPT patients receiving hemodialysis.


Assuntos
Calcimiméticos , Hiperparatireoidismo Secundário/tratamento farmacológico , Naftalenos , Pirrolidinas , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Calcimiméticos/administração & dosagem , Calcimiméticos/efeitos adversos , Calcimiméticos/farmacocinética , Calcimiméticos/farmacologia , Cálcio/sangue , Esquema de Medicação , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/diagnóstico , Hiperparatireoidismo Secundário/etiologia , Japão , Masculino , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/farmacologia , Hormônio Paratireóideo/sangue , Fósforo/sangue , Pirrolidinas/administração & dosagem , Pirrolidinas/efeitos adversos , Pirrolidinas/farmacologia , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Resultado do Tratamento , Adulto Jovem
7.
Vet Dermatol ; 30(2): 167-e50, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30556631

RESUMO

BACKGROUND: Ectoparasitism of ornamental birds, including captive species kept in zoos, represents a serious health problem. Up to 13 different species of lice have been reported to affect peacocks worldwide and heavy infestation may cause anaemia. Because of this, alternatives to the prevailing treatments have been sought including use of isoxazolines. This class of drugs has been used successfully in poultry without adverse effects on health or production. OBJECTIVE: To evaluate the effect of afoxolaner on the peacock louse (Goniodes pavonis). ANIMALS: Twenty-three peacocks (Pavo cristatus) with naturally occurring infestation with G. pavonis. METHODS AND MATERIALS: The peacocks were divided in two groups; one was treated once orally with 2.5 mg/kg afoxolaner and the other group received no treatment. Samples were collected using the acetate tape technique, for identification of lice by microscopy. Concomitantly, blood samples were taken to evaluate the haematocrit before and after the intervention. RESULTS: Treatment with afoxolaner significantly decreased the number of peacocks positive for lice (P = 0.02) compared to the control group, in which the number of positive birds did not decrease. The haematocrit improved in the afoxolaner-treated group from a baseline of 46.4%-54.7% at 35 days post-treatment, whereas it decreased in untreated birds (44.6%-40.7%). No adverse effects attributed to afoxolaner treatment were observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Oral administration of afoxolaner is an effective treatment for G. pavonis infestation of peacocks.


Assuntos
Doenças das Aves/tratamento farmacológico , Galliformes/parasitologia , Isoxazóis/uso terapêutico , Infestações por Ácaros/veterinária , Naftalenos/uso terapêutico , Ftirápteros/efeitos dos fármacos , Administração Oral , Animais , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Infestações por Ácaros/tratamento farmacológico , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Distribuição Aleatória , Comprimidos/administração & dosagem , Comprimidos/uso terapêutico
8.
Int J Occup Med Environ Health ; 31(6): 763-770, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30568313

RESUMO

OBJECTIVES: 1-Methylnaphthalene (1-MN) is a constituent of polycyclic aromatic hydrocarbons, the chemicals that have become ubiquitous in the environment as result of natural and industrial process. This paper reports a study on the distribution and excretion of 1-MN in rats after single and repeated inhalation exposure to 1-MN vapor. MATERIAL AND METHODS: Male Wistar rats were exposed to 1-MN vapor at nominal concentrations of 50 mg/m3 or 200 mg/m3 in the dynamic inhalation chambers (TSE Systems Head Nose Only Exposure) for 6 h (single exposure) or 5 days (6 h/day, repeated exposure). Blood, urine and tissue samples were collected during and after the exposure. Blood, urine and tissue concentrations of 1-MN were estimated by gas chromatography using the headspace technique. RESULTS: The elimination of 1-MN from blood followed an open 2-compartment model. The concentration in rat tissues was dependent on the magnitude and time of exposure. After repeated exposure, the concentration 1-MN in tissue decreased in comparison to single exposure. The elimination of 1-MN with urine after single and repeated exposure to 1-MN occurred mainly in the samples collected during the first day of collection. CONCLUSIONS: 1-Methylnaphthalene was rapidly eliminated from the blood and tissues of animals exposed by inhalation to 1-MN. In repeated exposure, there was probably a significant increase of 1-MN metabolism in rats exposed to low and high 1-MN doses. Under conditions of repeated 1-MN exposure, no significant systemic 1-MN accumulation could be observed. Int J Occup Med Environ Health 2018;31(6):763-770.


Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/metabolismo , Exposição por Inalação/efeitos adversos , Naftalenos/efeitos adversos , Naftalenos/metabolismo , Toxicocinética , Animais , Relação Dose-Resposta a Droga , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Masculino , Naftalenos/sangue , Naftalenos/urina , Ratos , Ratos Wistar
9.
Environ Health ; 17(1): 91, 2018 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-30572877

RESUMO

BACKGROUND: Naphthalene is the simplest polycyclic aromatic hydrocarbon (PAH). It is easily emitted into the atmosphere, posing a significant risk to human health. However, limited studies have described the impact of naphthalene exposure on birth outcomes. In this study, we investigated the association between the maternal urinary metabolites of naphthalene, 2-hydroxynaphthalene (2-OH NAP), and birth outcomes. METHOD: In the present study, four urinary PAH metabolites were measured in 263 pregnant women during late pregnancy. Multiple linear regression analysis was used to analyze the relationship between the concentrations of 2-OH NAP and birth outcomes, and restricted cubic spline models were further used to examine the shapes of the dose-response association. RESULT: General linear models showed that prenatal urinary 2-OH NAP was associated with lower birth weight (BW) (- 4.38% for the high vs. low exposure group of 2-OH NAP; p for trend = 0.049) and higher cephalization index (CI) (4.30% for the high vs. low exposure group of 2-OH NAP; p for trend = 0.038). These associations were linear and significant when 2-OH NAP was modeled as a continuous variable in restricted cubic spline models (P linear = 0.0293 for 2-OH NAP and BW; P linear = 0.0326 for 2-OH NAP and CI). Multiple linear regression data indicated that each 1 ln-unit increase in 2-OH NAP was significantly associated with a 2.09 g/cm increase in the CI. The associations among 2-OH NAP, BW, and CI were also observed in a subset of participants residing close to arterial traffic. CONCLUSION: Our data indicated that prenatal exposure to naphthalene had an adverse effect on fetal birth outcomes, especially the brain development index. Reduced exposure to naphthalene may improve newborn health outcomes. In Taiyuan, naphthalene may result from traffic pollution.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Recém-Nascido de Baixo Peso , Exposição Materna/efeitos adversos , Naftalenos/efeitos adversos , Naftóis/urina , Gravidez/urina , Adulto , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , China , Monitoramento Ambiental , Feminino , Humanos , Recém-Nascido , Masculino , Troca Materno-Fetal , Adulto Jovem
10.
Parasite ; 25: 63, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30516132

RESUMO

The efficacy of NexGard® and NexGard Spectra® against sarcoptic mange in dogs was evaluated in a clinical field study. Skin scrapings from dogs presenting signs suggestive of sarcoptic mange were examined to confirm infestation. A total of 106 dogs were screened at eight sites in Portugal and Germany. In all, 80 dogs that had demonstrated ≥5 live Sarcoptes mites in five skin scrapings were enrolled, scored for specific clinical signs (pruritus; papules and crusts; alopecia), and allocated at random to receive either NexGard® or NexGard Spectra® twice, one month apart per label instructions. To determine efficacy, live Sarcoptes mites in five skin scrapings per dog were counted, and clinical signs were scored one month and two months after first treatment and compared to pre-treatment (baseline) values. Based on compliance, 65 dogs were determined to be evaluable cases at the end of the study. The efficacy, in terms of reduction of geometric mean live Sarcoptes mite counts, was 98.9% and 99.7% for NexGard®-treated (n = 38) and 99.6% and 100% for NexGard Spectra®-treated dogs (n = 27) at one month and two months after treatment initiation (p < 0.001, both treatments). Both treatments resulted in a significant improvement in pruritus, papules and crusts, and alopecia one month and two months after treatment initiation (p = 0.0001, both treatments). In conclusion, this field study confirms that both NexGard® and NexGard Spectra® administered twice one month apart provide an effective and safe treatment against sarcoptic mange in dogs.


Assuntos
Acaricidas/uso terapêutico , Doenças do Cão/tratamento farmacológico , Isoxazóis/uso terapêutico , Macrolídeos/uso terapêutico , Naftalenos/uso terapêutico , Escabiose/veterinária , Acaricidas/administração & dosagem , Acaricidas/efeitos adversos , Animais , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Feminino , Alemanha/epidemiologia , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Macrolídeos/administração & dosagem , Macrolídeos/efeitos adversos , Masculino , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Portugal/epidemiologia , Distribuição Aleatória , Escabiose/tratamento farmacológico , Escabiose/epidemiologia , Escabiose/parasitologia , Comprimidos/administração & dosagem , Resultado do Tratamento
11.
Cochrane Database Syst Rev ; 10: CD007360, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30306544

RESUMO

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition in ageing men that may cause lower urinary tract symptoms (LUTS). Treatment aims are to relieve symptoms and prevent disease-related complications. Naftopidil is an alpha-blocker (AB) that has a high affinity for the A1d receptor that may have advantages in treating LUTS in this setting. This is an update of a Cochrane Review first published in 2009. Since that time, several large randomised controlled trials (RCTs) have been reported, making this update relevant. OBJECTIVES: To evaluate the effects of naftopidil for the treatment of LUTS associated with BPH. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, LILAC, and Web of Science), trials registries, other sources of grey literature, and conference proceedings with no restrictions on the language of publication or publication status up to 31 May 2018 SELECTION CRITERIA: We included all parallel RCTs. We also included cross-over design trials. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. We performed statistical analyses using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. Primary outcomes were urological symptom scores, quality of life (QoL) and treatment withdrawals for any reason; secondary outcomes were treatment withdrawals due to adverse events, acute urinary retention, surgical intervention for BPH, and cardiovascular and sexual adverse events. We considered outcomes measured up to 12 months after randomisation as short term, and later than 12 months as long term. We rated the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included 22 RCTs with 2223 randomised participants across four comparisons for short-term follow-up. This abstract focuses on only two of four comparisons for which we found data since two comparators (i.e. propiverine and Eviprostat (phytotherapy)) are rarely used. One study comparing naftopidil to placebo did not report any relevant outcomes and was therefore excluded. There were no trials that compared to combination therapy with naftopidil or any 5-alpha reductase inhibitors (5-ARIs) to combination therapy with other ABs and any 5-ARIs.All included studies were conducted in Asian countries. Study duration ranged from four to 12 weeks. Mean age was 67.8 years, prostate volume was 35.4 mL, and International Prostate Symptom Score was 18.3. We were unable to perform any of the preplanned subgroup analyses based on age and baseline symptom score.Naftopidil versus tamsulosinBased on 12 studies with 965 randomised participants, naftopidil may have resulted in little or no difference in urological symptom score (mean difference (MD) 0.47, 95% confidence interval (CI) -0.09 to 1.04 measured on a scale from 0 to 35 with higher score representing increased symptoms), QoL (MD 0.11, 95% CI -0.09 to 0.30; measured on a scale from 0 to 6 with higher scores representing worse QoL), and treatment withdrawals for any reason (risk ratio (RR) 0.92, 95% CI 0.64 to 1.34; corresponding to 7 fewer per 1000 participants, 95% CI 32 fewer to 31 more). Naftopidil may have resulted in little to no difference in sexual adverse events (RR 0.54, 95% CI 0.24 to 1.22); this would result in 26 fewer sexual adverse events per 1000 participants (95% CI 43 fewer to 13 more). We rated the certainty of evidence as moderate for urological symptom score and low for the other outcomes.Naftopidil versus silodosinBased on five studies with 652 randomised participants, naftopidil may have resulted in little or no difference in the urological symptom scores (MD 1.04, 95% CI -0.78 to 2.85), QoL (MD 0.21, 95% CI -0.23 to 0.66), and treatment withdrawals for any reason (RR 0.80, 95% CI 0.52 to 1.23; corresponding to 26 fewer per 1000 participants, 95% CI 62 fewer to 32 more). We rated the certainty of evidence as low for all these outcomes. Naftopidil likely reduced sexual adverse events (RR 0.15, 95% CI 0.06 to 0.42; corresponding to 126 fewer sexual adverse events per 1000 participants, 95% CI 139 fewer to 86 fewer). We rated the certainty of evidence as moderate for sexual adverse events. AUTHORS' CONCLUSIONS: Naftopidil appears to have similar effects in the urological symptom scores and QoL compared to tamsulosin and silodosin. Naftopidil has similar sexual adverse events compared to tamsulosin but has fewer compared to silodosin.


Assuntos
Antagonistas Adrenérgicos alfa/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Naftalenos/uso terapêutico , Piperazinas/uso terapêutico , Hiperplasia Prostática/complicações , Prostatismo/tratamento farmacológico , Agentes Urológicos/uso terapêutico , Antagonistas Adrenérgicos alfa/efeitos adversos , Benzilatos/efeitos adversos , Benzilatos/uso terapêutico , Combinação de Medicamentos , Etamsilato/efeitos adversos , Etamsilato/uso terapêutico , Humanos , Indóis/efeitos adversos , Indóis/uso terapêutico , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Naftalenos/efeitos adversos , Piperazinas/efeitos adversos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/uso terapêutico , Prostatismo/etiologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Tansulosina/efeitos adversos , Tansulosina/uso terapêutico , Agentes Urológicos/efeitos adversos
12.
Ann Saudi Med ; 38(5): 366-375, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30284992

RESUMO

BACKGROUND: The safety and efficacy of dapoxetine for the treatment of premature ejaculation (PE) is still controversial. Thus, we decided to conduct a meta-analysis using trial sequential analysis (TSA) to determine the sufficiency of conclusions. OBJECTIVE: Evaluate the efficacy and safety of dapoxetine in the treatment of patients with PE and assess the reliability of the findings. DESIGN: Meta-analysis of randomized controlled trials (RCTs). METHODS: Electronic databases including PUBMED, EMBASE, Cochrane Library, CNKI and Wanfang data were reviewed up to July 2017. RCTs evaluating the efficacy of dapoxetine in patients with PE and reporting intravaginal ejaculatory latency time (IELT), patient global impression of change (PGIC) and/or adverse events (AEs) were included. MAIN OUTCOME MEASURES: Mean differences between trials in efficacy for IELT, and risk ratios for PGIC and treatment-emergent AEs. SAMPLE: 8 RCTs. RESULTS: For IELT and PGIC, significant effects were found for all doses of dapoxetine versus placebo, and similar results were obtained in subgroups of the 30-mg dose versus 60-mg dose. There were also statistically different dose-related effects on AEs. Trial sequential analysis showed that the result of our meta-analysis was confirmed and further trials are unnecessary. CONCLUSIONS: The evidence suggests that dapoxetine may be a safe and effective drug for patients with PE. REGISTRATION: Not registered, no published protocol. CONFLICT OF INTEREST: No relationship with manufacturer of drug.


Assuntos
Benzilaminas/uso terapêutico , Naftalenos/uso terapêutico , Ejaculação Precoce/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Benzilaminas/efeitos adversos , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Naftalenos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Captação de Serotonina/efeitos adversos , Fatores de Tempo
13.
Drug Alcohol Depend ; 191: 14-24, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071445

RESUMO

BACKGROUND: A subset of cannabis users develop some degree of Cannabis Use Disorder (CUD). Although behavioral therapy has some success in treating CUD, many users relapse, often citing altered sleep, mood, and irritability. Preclinical animal tests of cannabinoid withdrawal focus primarily on somatic-related behaviors precipitated by a cannabinoid receptor antagonist. The goal of the present study was to develop novel cannabinoid withdrawal assays that are either antagonist-precipitated or spontaneously induced by abstinence. METHODS: C57BL/6 J mice were repeatedly administered the phytocannabinoid Δ9-tetrahydrocannabinol (THC; 1, 10 or 50 mg/kg, s.c.), the synthetic cannabinoid receptor agonist JWH-018 (1 mg/kg, s.c.), or vehicle (1:1:18 parts ethanol:Kolliphor EL:saline, s.c.) for 6 days. Withdrawal was precipitated with the cannabinoid receptor inverse agonist rimonabant (3 mg/kg, i.p.) or elicited via abstinence (i.e., spontaneous withdrawal), and putative stress-related behavior was scored. Classic somatic signs of cannabinoid withdrawal were also quantified. RESULTS: Precipitated THC withdrawal significantly increased plasma corticosterone. Precipitated withdrawal from either THC or JWH-018 suppressed marble burying, increased struggling in the tail suspension test, and elicited somatic withdrawal behaviors. The monoacylglycerol lipase inhibitor JZL184 attenuated somatic precipitated withdrawal but had no effect on marble burying or struggling. Spontaneous THC or JWH-018 withdrawal-induced paw tremors, head twitches, and struggled in the tail suspension test after 24-48 h abstinence. JZL184 or THC attenuated these spontaneous withdrawal-induced behaviors. CONCLUSION: Outcomes from tail suspension and marble burying tests reveal that THC withdrawal is multifaceted, eliciting and suppressing behaviors in these tests, in addition to inducing well-documented somatic signs of withdrawal.


Assuntos
Comportamento Animal/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/efeitos adversos , Abuso de Maconha/etiologia , Síndrome de Abstinência a Substâncias/etiologia , Animais , Benzodioxóis/efeitos adversos , Dronabinol/efeitos adversos , Indóis/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naftalenos/efeitos adversos , Piperidinas/efeitos adversos , Pirazóis/efeitos adversos , Rimonabanto
14.
Kidney Int ; 94(4): 818-825, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30049473

RESUMO

Secondary hyperparathyroidism (SHPT) leads to cardiovascular calcification, which affects survival and quality of life in patients with chronic kidney disease. Cinacalcet is used to control SHPT, but it may induce gastrointestinal symptoms, resulting in lower adherence and insufficient dosages. Therefore, a need exists to develop new calcimimetics that cause fewer gastrointestinal symptoms. Here we conducted a phase 3, randomized, double-blind, double-dummy trial for a head-to-head comparison of the efficacy and safety of evocalcet, a new oral calcimimetic, to the established cinacalcet. Japanese patients with SHPT on hemodialysis were randomized to receive evocalcet or cinacalcet (317 patients each) for 30 weeks. The primary efficacy endpoint was non-inferiority of evocalcet to cinacalcet in the proportion of patients achieving a mean intact parathyroid hormone level of 60 to 240 pg/mL from week 28 to 30 (non-inferiority margin, -15%, per protocol set analyses). In the evocalcet and cinacalcet groups, 72.7% and 76.7%, respectively, achieved the target intact parathyroid hormone level (between-group difference: -4.0% [95% confidence interval -11.4%, 3.5%], for non-inferiority). The incidence of gastrointestinal-related adverse events was 18.6% and 32.8%, respectively (between-group difference: -14.2% [-20.9%, -7.5%], significant for superiority). Thus, the non-inferiority of evocalcet to cinacalcet in suppressing intact parathyroid hormone with fewer gastrointestinal-related adverse events was demonstrated. Hence, evocalcet may be a favorable alternative to existing calcimimetics for management of SHPT.


Assuntos
Calcimiméticos/uso terapêutico , Cinacalcete/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Naftalenos/uso terapêutico , Pirrolidinas/uso terapêutico , Idoso , Calcimiméticos/efeitos adversos , Cinacalcete/efeitos adversos , Método Duplo-Cego , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Hiperparatireoidismo Secundário/sangue , Japão , Masculino , Pessoa de Meia-Idade , Naftalenos/efeitos adversos , Hormônio Paratireóideo/sangue , Pirrolidinas/efeitos adversos , Diálise Renal , Insuficiência Renal Crônica/terapia
15.
Toxicol Lett ; 298: 91-98, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29990563

RESUMO

Naphthalene occurs together with polycyclic aromatic hydrocarbons (PAHs) at industrial workplaces and is ubiquitous in the environment. For biological monitoring of naphthalene exposures, up to now mainly 1- and 2-naphthol in urine have been used. Recently, we proposed 1,2-dihydroxynaphthalene (1,2-DHN) and the 1- and 2-naphthylmercapturic acid (1- and 2-NMA) as new urinary biomarkers to characterise a naphthalene exposure. In this study, in a collective of nine occupationally exposed workers handling with creosote the naphthalene metabolites 1,2-DHN, 1- and 2-NMA as well as 1- and 2-naphthol were analysed in order to evaluate the suitability of the different parameters for their application in biomonitoring studies. Additionally, air sampling was conducted to characterise the exposure in task related exposure situations at different workplaces. In the analysed 51 urine samples, 1,2-DHN was the main metabolite with concentrations ranging from 2.3 to 886 µg/g creatinine (crea) (median 34 µg/g crea). For the sum of 1- and 2-naphthol, concentrations in the range of 2.6-174 µg/g crea (median 15 µg/g crea) were observed. 1-NMA concentrations were in the range of < LOD-2.4 µg/g crea (61% > LOD), while 2-NMA was not detected in the analysed urine samples. The biomarkers 1,2-DHN, 1- and 2-naphthol as well as 1-NMA showed significant correlations, which pointed out to naphthalene as the common exposure source. The poor correlations between naphthalene in the air and the biomarkers in urine may be a result of the varying exposure situations and may indicate not solely inhalative, but additional dermal uptake. 1,2-DHN was the most sensitive and, together with 1-NMA, the most specific parameter of the biological monitoring of naphthalene exposure at workplaces. Further studies with this parameter are needed for individuals at different workplaces as well as for persons of the general population without occupational PAH exposure to characterise 1,2-DHN levels as well as to establish their relationship with the naphthalene exposure.


Assuntos
Poluentes Ocupacionais do Ar/urina , Creosoto/urina , Monitoramento Ambiental/métodos , Exposição por Inalação , Naftalenos/urina , Exposição Ocupacional , Acetilcisteína/análogos & derivados , Acetilcisteína/urina , Poluentes Ocupacionais do Ar/efeitos adversos , Biotransformação , Creosoto/efeitos adversos , Biomarcadores Ambientais , Humanos , Exposição por Inalação/efeitos adversos , Masculino , Naftalenos/efeitos adversos , Naftóis/urina , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Reprodutibilidade dos Testes , Medição de Risco , Urinálise
16.
Parasit Vectors ; 11(1): 425, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012179

RESUMO

BACKGROUND: Safety and efficacy of the combined monthly use of spot-on fipronil 6.76% w/v / permethrin 50.48% w/v (Frontline Tri-Act®) and chewable tablets of afoxolaner 1.9% w/w / milbemycin oxime 0.4% w/w (NexGard Spectra®) in dogs was evaluated in a field study over a period of 6 months. METHODS: Forty-one healthy dogs living in highly endemic area for canine leishmaniosis and other canine vector borne diseases (VBD) were included in the study at the beginning of the Leishmania transmission season. Sixteen dogs were pet dogs living each in a single household; twenty-five dogs were hunting dogs living in three kennels. At inclusion, the dogs were ELISA (rapid test) negative for antibodies to Anaplasma, Borrelia, Ehrlichia, and for antigens of Dirofilaria. The dogs were also negative for blood microfilariae at the Knott's test, and no clinical or haematological abnormalities were observed. Of the included dogs, six hunting, apparently healthy, dogs were ELISA (rapid test) positive to Leishmania, and some were naturally infected by gastrointestinal nematodes (58.5%) and/or infested by fleas (58.5%) and ticks (9.8%). All the included dogs were treated at Days 0, 28, 56, 84, 112 and 140, and followed-up for efficacy until the study end (Day 168). RESULTS: No adverse events related to the two products, nor skin reactions, general signs, or changes in the haematological profile, were observed during the study. At Day 14, anthelminthic efficacy was 100% for Toxocara canis, Toxascaris leonina and Capillaria aerophila, while few hunting dogs were still shedding eggs of Trichuris vulpis (1/25 hunting dog) and Ancylostomatidae (9/25 hunting dogs). All pet dogs were nematode free at the end of the study. Hunting dogs were free of roundworms and whipworms. Twenty-four hours after the first treatment, 95.8% of the ectoparasite infested dogs were free from fleas and ticks. Ectoparasites were significantly controlled during the 6-month study period, with 100% efficacy on both fleas and ticks from Day 56 to Day 168. Blood and serum samples collected on Day 168 were tested for vector-borne pathogens using same methods of the inclusion and no new seroconversions or circulating blood microfilariae were observed. CONCLUSIONS: Concomitant use of Frontline Tri-Act® and NexGard Spectra® in dogs for six months was well tolerated. The combination was effective in controlling fleas, ticks, gastro-intestinal nematodes, and neither new seroconversion to the tested vector-borne pathogens nor blood microfilariae were detected in treated dogs at the end of the study.


Assuntos
Doenças do Cão/prevenção & controle , Insetos Vetores/efeitos dos fármacos , Inseticidas/farmacologia , Doenças Parasitárias em Animais/prevenção & controle , Animais , Doenças do Cão/parasitologia , Cães , Combinação de Medicamentos , Feminino , Inseticidas/administração & dosagem , Isoxazóis/administração & dosagem , Isoxazóis/efeitos adversos , Isoxazóis/farmacologia , Macrolídeos/administração & dosagem , Macrolídeos/efeitos adversos , Macrolídeos/farmacologia , Masculino , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/farmacologia , Doenças Parasitárias em Animais/parasitologia , Permetrina/administração & dosagem , Permetrina/efeitos adversos , Permetrina/farmacologia , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/farmacologia
17.
Drug Des Devel Ther ; 12: 1799-1807, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29950814

RESUMO

Purpose: Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for treatment of gout and asymptomatic hyperuricemia. This study evaluated verinurad pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese and non-Asian adult male subjects. Methods: This was a Phase I, randomized, single-blind, placebo-controlled study. Panels of 8 Japanese subjects were randomized to receive oral verinurad (2.5-15 mg) or placebo administered as a single dose in a fasted and fed state and as once-daily doses for 7 days in a fed state. Eight non-Asian subjects received verinurad 10 mg as a single dose (fasted and fed) and multiple doses in the fed state. Serial plasma/serum and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse events and laboratory data. Results: Of 48 randomized subjects, 46 (Japanese, 39; non-Asian, 7) completed the study. Following single or multiple doses in Japanese subjects, maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) increased in a near dose-proportional manner. Time to Cmax (Tmax) was ~1.25-2.0 hours with fasting. A moderate-fat meal delayed Tmax (range 3.0-5.0 hours) and had a variable effect on AUC (0%-97% increase) and Cmax (0%-26% increase) across the dose groups. Following multiple verinurad 10 mg doses, Cmax and AUC were 38% and 23% higher, respectively, in Japanese vs non-Asian subjects, largely due to body weight differences. Mean reduction of serum urate following multiple verinurad 10 mg doses was 46% and 44% after 24 hours in Japanese and non-Asian subjects, respectively. Verinurad was well tolerated at all doses. Conclusion: Verinurad monotherapy lowered serum urate and was well tolerated in both healthy Japanese and non-Asian males, while small differences in plasma pharmacokinetics were observed. These data support further evaluation of once-daily verinurad as a treatment for gout and asymptomatic hyperuricemia.


Assuntos
Grupo com Ancestrais do Continente Asiático , Túbulos Renais/efeitos dos fármacos , Naftalenos , Propionatos , Piridinas , Eliminação Renal/efeitos dos fármacos , Reabsorção Renal/efeitos dos fármacos , Ácido Úrico/metabolismo , Uricosúricos/farmacocinética , Administração Oral , Adulto , Área Sob a Curva , Esquema de Medicação , Meia-Vida , Voluntários Saudáveis , Humanos , Túbulos Renais/metabolismo , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/farmacocinética , Naftalenos/farmacologia , Propionatos/administração & dosagem , Propionatos/efeitos adversos , Propionatos/farmacocinética , Propionatos/farmacologia , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/farmacocinética , Piridinas/farmacologia , Método Simples-Cego , Ácido Úrico/sangue , Ácido Úrico/urina , Uricosúricos/administração & dosagem , Uricosúricos/sangue , Adulto Jovem
18.
J Clin Pharmacol ; 58(9): 1214-1222, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29733447

RESUMO

Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for treatment of hyperuricemia and gout. This phase 1b, multiple-dose, drug-drug interaction study evaluated the pharmacokinetics, pharmacodynamics, and tolerability of verinurad in combination with allopurinol. Adult males with gout were randomized to receive once-daily oral doses of allopurinol 300 mg or verinurad 10 mg alone for 7 days, allopurinol 300 mg + verinurad 10 mg on days 8 to 14, and the alternative single agent on days 15 to 21. Colchicine 0.6 mg was taken prophylactically for gout flares. Plasma/serum and urine samples were assayed for verinurad, allopurinol, oxypurinol (allopurinol active metabolite), colchicine (plasma only), and uric acid. Safety was assessed by adverse events (AEs) and laboratory tests. Verinurad plasma exposure was unaffected by allopurinol. Verinurad increased the maximum observed plasma concentration (Cmax ) for allopurinol by 33%; the area under the plasma concentration-time curve (AUC) was unaffected. Oxypurinol Cmax and AUC were reduced 32% and 38%, respectively, by verinurad. Colchicine plasma exposure was unaltered by verinurad. The maximum decrease in serum urate was greater with verinurad + allopurinol (65%) than with verinurad (51%) or allopurinol (43%) alone. Compared with the baseline rate, the maximum rate of uric acid excreted in urine was +56% with verinurad, -46% with allopurinol, and unchanged with verinurad + allopurinol. No serious AEs, discontinuations due to AEs, or clinically significant laboratory abnormalities were noted. Despite decreased systemic exposure of allopurinol and oxypurinol in the presence of verinurad, the combination resulted in greater serum urate reduction compared with either drug alone and was well tolerated at the studied doses.


Assuntos
Supressores da Gota/farmacocinética , Supressores da Gota/uso terapêutico , Gota/tratamento farmacológico , Naftalenos/farmacocinética , Naftalenos/uso terapêutico , Propionatos/farmacocinética , Propionatos/uso terapêutico , Piridinas/farmacocinética , Piridinas/uso terapêutico , Adolescente , Adulto , Idoso , Alopurinol/metabolismo , Alopurinol/farmacocinética , Alopurinol/uso terapêutico , Área Sob a Curva , Esquema de Medicação , Supressores da Gota/administração & dosagem , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Oxipurinol/metabolismo , Oxipurinol/farmacocinética , Propionatos/administração & dosagem , Propionatos/efeitos adversos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Ácido Úrico/sangue , Adulto Jovem
19.
Neuropharmacology ; 137: 268-274, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29778010

RESUMO

The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence. In addition, cannabinoid receptor 2 has been found expressed also in the central nervous system at postsynaptic level. In order to analyze the participation of the eCB system on ethanol (EtOH) preference, mice were exposed to cannabinoid agonist WIN 55,212-2 (WIN) for 5 consecutive days during early adolescence. Anxiety tests were performed the day after WIN treatment withdrawal, and EtOH preference was measured throughout adolescence. Mice exposed to WIN during early adolescence exhibited a significant increase in EtOH intake and preference after treatment. Moreover, WIN exposure during early adolescence induced an anxiogenic effect. Morphometric analysis revealed higher dendritic ramifications and fewer dendritic spines in neurons of the substantia nigra pars compacta in WIN-treated mice. On the other hand, immunohistochemical analysis revealed an increase in the number of tryptophan hydroxylase-expressing neurons in the dorsal raphe nucleus but no differences were found in the ventral tegmental area or substantia nigra pars compacta for tyrosine hydroxylase-expressing neurons. These results demonstrate that exposure to WIN in early adolescence can affect neural development and induce alcohol preference and anxiety-like behavior during late adolescence.


Assuntos
Consumo de Bebidas Alcoólicas , Ansiedade/etiologia , Benzoxazinas/efeitos adversos , Agonistas de Receptores de Canabinoides/efeitos adversos , Morfolinas/efeitos adversos , Naftalenos/efeitos adversos , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/patologia , Animais , Ansiedade/metabolismo , Ansiedade/patologia , Depressores do Sistema Nervoso Central/administração & dosagem , Núcleo Dorsal da Rafe/efeitos dos fármacos , Núcleo Dorsal da Rafe/crescimento & desenvolvimento , Núcleo Dorsal da Rafe/metabolismo , Núcleo Dorsal da Rafe/patologia , Etanol/administração & dosagem , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Parte Compacta da Substância Negra/efeitos dos fármacos , Parte Compacta da Substância Negra/crescimento & desenvolvimento , Parte Compacta da Substância Negra/metabolismo , Parte Compacta da Substância Negra/patologia , Distribuição Aleatória , Receptores de Canabinoides/metabolismo , Serotonina/metabolismo , Maturidade Sexual , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/crescimento & desenvolvimento , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/patologia
20.
Contact Dermatitis ; 79(3): 123-126, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29845618

RESUMO

BACKGROUND: Solvent Orange (SO) 60 is a perinone-type dye that is often used in plastic materials such as spectacle frames and has been shown to cause contact allergy. The first case of SO 60 allergic contact dermatitis caused by spectacle frames was reported in 1999, and the second in 2011. We have recently seen 10 patients, of whom 6 developed dermatitis in the retroauricular/temporal area after wearing plastic spectacles. OBJECTIVES: To report the cause of the dermatitis in the 10 patients and to describe our first case with occupational SO 60 contact allergy. METHODS: In this retrospective study, patch test results of 10 patients, tested with the Swedish baseline series and our specific spectacle and/or plastic series, including SO 60 1.0% pet., in 2011-2017 were analysed. RESULTS: Ten patients, 2 males and 8 females, aged 43 to 71 years, reacted positively to SO 60 1.0% pet., namely, 4 pensioners, 2 nurses, 1 office worker, 1 teacher, 1 shop assistant, and 1 unemployed person. Four of the patients had an atopic history. Patch test reactions varied from + to +++; some had spread >20 cm outside the test area in terms of erythematous, infiltrated skin with papules. Retesting of patient no. 1 with serial dilutions of SO 60 in acetone showed positive reactions down to 1 ppm. Three patients reacted to the extracts of their earpieces. Gas chromatography-mass spectrometry was used to confirm the presence of SO 60 in 2 earpieces. CONCLUSIONS: SO 60 should be included in any spectacle patch test series that may be used. If there is a strong suspicion of contact allergy to SO 60 before patch testing, lowering the test concentration from 1.0% to 0.01% should be considered.


Assuntos
Corantes/efeitos adversos , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/etiologia , Óculos/efeitos adversos , Naftalenos/efeitos adversos , Adulto , Idoso , Corantes/administração & dosagem , Dermatite Alérgica de Contato/diagnóstico , Dermatite Ocupacional/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Naftalenos/administração & dosagem , Testes do Emplastro , Estudos Retrospectivos
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