RESUMO
CONTEXT: The antiproliferative mechanism of mycophenolate acid (MPA) suggests a beneficial effect in patients with Graves' orbitopathy (GO). OBJECTIVE: To systematically analyze for the first time adverse events (AEs) during MPA treatment in GO. DESIGN: Prospective longitudinal study. SETTING: Academic tertiary referral center with a joint thyroid-eye clinic. PATIENTS: Fifty-three consecutive, unselected patients with clinically active and moderate-to-severe GO. METHODS: MPA 0.720 g was given once daily for 24-weeks in GO patients. AEs were documented and coded according to the standardized medical dictionary for regulatory activities (MedDRA). AE were followed up and seriousness as defined by ICH-guideline E6 was documented. All AEs were analyzed regarding a possible underlying cause and if not, graded as side effect (SE). RESULTS: Fifty GO patients (93 %) had Graves' disease, 37 (70 %) and 29 (54.7 %) were female and smoker, respectively. Thirty-six patients (68 %) reported at least one AE. A total of 88 AEs were documented, most frequent AEs were insomnia (N = 6), fatigue (N = 5) and optic neuropathy (N = 5), while other AEs occurred in up to three patients (5.6 %), only. In 12 (23 %) patients, at least one SE occurred. All 17 reported SE, i.e. mild infections and gastrointestinal intolerance were within the known safety profile of MPA. No patient dropped MPA medication because of drug-induced SE. Most AEs showed a recovered (76 %) or recovering (16 %) outcome. Seven (13 %) patients were hospitalized, five (62 %) due to optic neuropathy, none of these events was graded as SE. CONCLUSIONS: MedDRA-coded data documented the good tolerance of a moderate MPA dose in GO patients.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Centros de Atenção Terciária , Adulto JovemRESUMO
CONTEXT: Safety of intravenous (IV) steroid pulses in patients with Graves' orbitopathy (GO) is still controversial while steroid dose and treatment application have not been finalized. Frequency, severity and characterization of adverse events (AE) were prospectively analyzed. SETTING: Academic referral orbital center with a joint thyroid-eye clinic. PATIENTS: Eighty consecutive and unselected patients with active and severe GO. METHODS: During an established treatment with IV methylprednisolone (cumulative dose 4.5 g) occurring AE were prospectively coded according to the standardized and recognized medical dictionary for regulatory activities (MedDRA). Outcome and severity of AE were documented. AEs judged as at least possibly related to drug treatment were graded as side effect (SE). AEs matching a seriousness criteria as defined by the ICH guideline E6 (good clinical practice) were graded as serious. RESULTS: A total of 38.75% (31/80) of the treated GO patients reported at least one AE while 18 patients (22.5%) reported at least one SE. All SE were within the safety profile of IV methylprednisolone; 31/32 SE (96.87%) were mild-moderate and reversible and only 1/80 patient (1.25%) stopped steroid treatment due to exacerbation of her depression. Most AE were accessory symptoms of the underlying disease and a few only were directly related to IV steroids. Most AEs (90.6%) were graded as mild. Only six patients (7.5%) were hospitalized, three of them due to a dysthyroid optic neuropathy. CONCLUSIONS: Prospective and standardized evaluation with MedDRA and the ICH guideline demonstrated the good pharmacological tolerance and low morbidity of this moderate steroid regimen.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/tratamento farmacológico , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Índice de Gravidade de Doença , Administração Intravenosa , Adulto , Idoso , Feminino , Gastroenteropatias/induzido quimicamente , Cardiopatias/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Over the past decade, synthetic cannabinoids have inundated the global market and now form the largest category of new psychoactive substances. Once these chemicals are available on the global market, they can be applied to plant material in a clandestine environment to create an end-product that is smoked by the user. The synthetic cannabinoids AMB-FUBINACA and 5F-ADB were most frequently detected between 2017 and the beginning of 2019. More recently, these two appear to have been replaced by different synthetic cannabinoids. This investigation summarises the recent trends in synthetic cannabinoids detected in New Zealand between 2017 and 2020 and outlines the potential factors influencing these trends.
Assuntos
Canabinoides , Tráfico de Drogas/tendências , Drogas Ilícitas , Medicamentos Sintéticos , Humanos , Nova ZelândiaRESUMO
New psychoactive substances have emerged as a vast and diverse group of illicit drugs over the past decade, with synthetic cannabinoids comprising the largest of the categories. Commonly, a single synthetic cannabinoid is applied to plant material, creating a product that is designed to be smoked by the user. The clandestine preparation process can result in an unevenly distributed product, with varying concentration within and between plant materials. This investigation describes the novel co-detection of the synthetic cannabinoid AMB-FUBINACA, with the piperazine para-fluorophenylpiperazine (pFPP), in a number of plant material samples analysed in New Zealand in 2017. Of 157 samples of plant material containing AMB-FUBINACA, pFPP was detected in 55 of them. A range of pFPP concentrations was observed between the plant material samples, as well as intra-batch variation. The presence of both drugs may be designed to enhance, prolong or balance the psychoactive effects caused from smoking the plant material. However the intended purpose has not been verified. This is the first reported combination of a synthetic cannabinoid and a piperazine in plant material.
Assuntos
Canabinoides/análise , Indazóis/análise , Piperazinas/análise , Plantas/química , Psicotrópicos/análise , Valina/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Drogas Ilícitas/análise , Nova Zelândia , Valina/análiseRESUMO
There has been an explosion of new psychoactive substances (NPS) over the past decade, with synthetic cannabinoids comprising one of the more extensive and chemically diverse groups. Synthetic cannabinoids, like other NPS, are continually evolving with slight alterations in chemical structure, which can lead to unintended and harmful effects for the user. Furthermore, the clandestine preparation of plant material containing one or more synthetic cannabinoid can result in an unevenly distributed product, which poses an additional risk to the user of increased doses. This investigation aimed at providing a snapshot of synthetic cannabinoids in New Zealand in 2017, including the concentrations of synthetic cannabinoids in plant material. Overall, ten different synthetic cannabinoids were detected, with AMB-FUBINACA and 5F-ADB comprising the majority of samples analysed. The synthetic cannabinoid AMB-FUBINACA displayed the greatest range of concentration in plant material, from 5 to over 400 g of synthetic cannabinoid per kilogram of plant material. There was also geographical variation in the synthetic cannabinoids depending on where in New Zealand they were seized from.
RESUMO
Pacific whiting surimi gels heated slowly in a water bath exhibited poor gel quality, while the ohmically heated gels without holding at 55 degrees C showed more than a twofold increase in shear stress and shear strain over conventionally heated gels. Degradation of myosin and actin was minimized by ohmic heating, resulting in a continuous network structure. Ohmic heating with a rapid heating rate was an effective method for maximizing gel functionality of Pacific whiting surimi without enzyme inhibitors. In linear heating, slow heating rates increased proteolysis in Pacific whiting surimi as shown by degradation of myosin heavy chain and low shear stress and shear strain. Proteolysis of whiting surimi was decreased by the presence of beef plasma protein (BPP) to a greater extent at rapid heating rates (20 and 30 degrees C/min) than at slow heating rates (1 and 5 degrees C/min). Shear stress of Alaska pollock surimi gels with or without BPP increased as heating rate decreased, but shear strain was unaffected. An increase in shear stress was accompanied by an increase of cross-linked myosin heavy chain.
Assuntos
Proteínas Alimentares/metabolismo , Peixes , Temperatura Alta , Actinas/química , Actinas/metabolismo , Animais , Proteínas Sanguíneas/química , Bovinos , Reagentes de Ligações Cruzadas , Endopeptidases/metabolismo , Peixes/metabolismo , Manipulação de Alimentos , Géis , Carne/análise , Cadeias Pesadas de Miosina/química , Cadeias Pesadas de Miosina/metabolismo , Estresse MecânicoRESUMO
Since 1982 when secondary poisoning of a red-tailed hawk (Buteo jamaicensis) was documented following the recommended use of famphur applied topically to cattle, the Patuxent Wildlife Research Center has tested dead birds of prey for poisoning by famphur and other pour-on organophosphorus (OP) insecticides. Brain cholinesterase (ChE) activity was first determined, then if ChE was depressed greater than or equal to 50%, stomach and/or crop contents were evaluated for anti-ChE compounds. This report presents the circumstances surrounding the OP-caused deaths of eight bald eagles (Haliaeetus leucocephalus), two red-tailed hawks, and one great horned owl (Bubo virginianus) between March 1984 and March 1985. OP poisoning of raptors by pour-on insecticides in the United States is widespread, but its magnitude is unknown.
Assuntos
Doenças das Aves/induzido quimicamente , Fention/intoxicação , Inseticidas/intoxicação , Intoxicação por Organofosfatos , Compostos Organotiofosforados/intoxicação , Animais , Aves , Bovinos , Organotiofosfatos , SuínosAssuntos
Ração Animal , Doenças das Aves/etiologia , Contaminação de Alimentos , Doenças Transmitidas por Alimentos/veterinária , Inseticidas/intoxicação , Monocrotofós/intoxicação , Acetilcolinesterase/metabolismo , Animais , Doenças das Aves/enzimologia , Aves , Encéfalo/enzimologia , Doenças Transmitidas por Alimentos/enzimologia , Doenças Transmitidas por Alimentos/etiologia , Conteúdo Gastrointestinal/análise , Monocrotofós/análise , Ortópteros/análiseAssuntos
Doenças das Aves/diagnóstico , Inseticidas/intoxicação , Intoxicação por Organofosfatos , Compostos Organotiofosforados/intoxicação , Animais , Aves , Encéfalo/enzimologia , Colinesterases/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Conteúdo Gastrointestinal/análise , Inseticidas/análise , Organotiofosfatos/análiseRESUMO
Organophosphorus pesticides have generally low persistence in the environment, but they may persist in water and accumulate in certain aquatic vertebrates. Frogs are resistant to cholinesterase inhibitors; thus it was suspected that they might accumulate the pesticides. Tadpoles concentrated pesticides from water up to 60 times; those exposed to 1 ppm parathion and 5 ppm fenthion were lethal when they were fed to mallard ducks. Dicrotophos, malathion, and acephate were not accumulated to levels such that they were lethal when consumed in a single meal by ducks. Brain cholinesterase levels were correlated with dose and effect. Metabolites of parathion and fenthion produced by the tadpoles were rapidly excreted and it was concluded that they play a small role in the toxicity of the larvae to ducks. Dangerous levels of some pesticides may be accumulated by amphibians in nature and may adversely affect carnivorous species.
Assuntos
Inseticidas/metabolismo , Compostos Organofosforados , Compostos Organotiofosforados , Animais , Colinesterases/metabolismo , Patos , Inseticidas/análise , Inseticidas/toxicidade , Rana catesbeiana , Distribuição Tecidual , Água/análiseRESUMO
A procedure is described for determining fenvalerate and permethrin residues in grasshoppers and duck tissues. Samples are Soxhlet-extracted with hexane and cleaned up by gel permeation chromatography with an in-line alumina column. Samples are analyzed by gas-liquid chromatography with electron capture detection, and confirmed by gas-liquid chromatography-mass spectrometry. The average recovery from fortified tissues was 97%.
Assuntos
Patos/metabolismo , Gafanhotos/análise , Resíduos de Praguicidas/análise , Fenilbutiratos/análise , Piretrinas/análise , Animais , Cromatografia Gasosa/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Nitrilas , PermetrinaRESUMO
We calculate neutrino-induced fission cross sections for selected nuclei with Z=84-92. We show that these reactions populate the daughter nucleus at excitation energies where shell effects are significantly washed out, effectively reducing the fission barrier. If the r process occurs in the presence of a strong neutrino fluence, and electron neutrino average energies are sufficiently high, perhaps as a result of matter-enhanced neutrino flavor transformation, then neutrino-induced fission could lead to significant alteration in the r-process flow in slow outflow scenarios.
RESUMO
Sixty women with genuine stress incontinence were consecutively assigned to one of four physiotherapy groups who were treated for 6 weeks by either (1) pelvic floor exercises (PFE) in hospital; (2) PFE and faradism; (3) PFE and interferential therapy; (4) PFE at home. Assessment before and after treatment was by 7-day bladder charts, urethral pressure profiles and perineometry. Approximately two-thirds of the hospital-treated patients (groups 1, 2 and 3) experienced marked or moderate subjective improvement and at 6 months, 27% were dry or almost dry. There was little difference in outcome between groups 1, 2 and 3 but hospital-based therapy was more effective than home treatment. Statistical analyses showed that there were significant improvements in the objective indices measured in the 45 hospital-treated patients. Successful treatment was more likely in younger patients, in those with lesser degrees of genuine stress incontinence and those who had had no previous pelvic floor surgery.