RESUMO
Despite many endeavors to treat malignant gliomas in the last decades, the median survival of patients has not significantly improved. The infiltrative nature of high-grade gliomas and the impermeability of the blood-brain barrier to the most therapeutic agents remain major hurdles, impeding an efficacious treatment. Theranostic platforms bridging diagnosis and therapeutic modalities aim to surmount the current limitations in diagnosis and therapy of glioma. Gold nanoparticles (AuNPs) due to their biocompatibility and tunable optical properties have widely been utilized for an assortment of theranostic purposes. In this Review, applications of AuNPs as imaging probes, drug/gene delivery systems, radiosensitizers, photothermal transducers, and multimodal theranostic agents in malignant gliomas are discussed. This Review also aims to provide a perspective on cancer theranostic applications of AuNPs in future clinical trials.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Glioma/diagnóstico por imagem , Glioma/terapia , Compostos de Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Nanomedicina Teranóstica , Animais , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/patologia , Portadores de Fármacos , Técnicas de Transferência de Genes , Terapia Genética , Glioma/patologia , Compostos de Ouro/efeitos adversos , Humanos , Imunoterapia , Nanopartículas Metálicas/efeitos adversos , Imagem Molecular , Fotoquimioterapia , Terapia Fototérmica , Valor Preditivo dos TestesRESUMO
Cutaneous chrysiasis is gold deposition in the dermis, described after parenteral administration of gold salts or after topical exposure to gold-containing materials. Gold microparticles (GMPs) have versatile therapeutic effects and are increasingly used in medicine. This case report describes the development of a blue-gray macule following the facial application of GMPs and laser treatment of acne vulgaris. Dermoscopy showed a nonspecific homogenous blue-gray pattern, gradually fading over an 8-month-period. Reflectance confocal microscopy (RCM) detected hyperreflective, subcellular particles in the papillary dermis, localized around hair follicles, eccrine glands, and inside macrophages. Histopathological evaluation, darkfield illumination with hyperspectral imaging, and neutron activation analysis confirmed the presence of GMPs in the dermis. RCM allowed non-invasive fast visualization of aggregates of hyperreflective particles in the dermis and can potentially be used for monitoring localized cutaneous chrysiasis and other metal deposition conditions over time. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Assuntos
Acne Vulgar/terapia , Compostos de Ouro/efeitos adversos , Terapia Fototérmica/efeitos adversos , Transtornos da Pigmentação/etiologia , Acne Vulgar/diagnóstico por imagem , Adolescente , Dermoscopia , Feminino , Humanos , Microscopia Confocal , Transtornos da Pigmentação/diagnóstico por imagemRESUMO
Lichenoid drug reactions are rare compared to typical morbilliform drug exanthema or urticaria. They are associated with specific drugs or drug families like gold, antimalarial drugs, ßblockers and angiotensin-converting-enzyme inhibitors. Recent observations included associations with novel drugs such as biologics (e.â¯g. tumour necrosis factor antagonists) and immune checkpoint inhibitors (anti-programme cell death protein 1 antibodies). Lichenoid drug reactions most often resemble lichen planus mainly in areas of ultraviolet-light exposed skin, but also mucosal lichen planus and even bullous lesions may occur.
Assuntos
Toxidermias/diagnóstico , Erupções Liquenoides/induzido quimicamente , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anticorpos/efeitos adversos , Anticorpos/uso terapêutico , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Produtos Biológicos/efeitos adversos , Produtos Biológicos/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Compostos de Ouro/efeitos adversos , Compostos de Ouro/uso terapêutico , Humanos , Interferons/efeitos adversos , Interferons/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The behavior and fate of intravenously (i.v.) injected nanoparticles (NPs) can be controlled by several physicochemical factors including size, shape and surface charge. To evaluate the role of surface charge on distribution of NPs, we used neutral-charged 15-nm-sized polyethylene glycol-coated gold nanoparticles (AuNP(PEG)) as a core NP and carboxyl or amine groups were conjugated to AuNP(PEG) to generate negative (AuNP(COOH)) or positive AuNP (AuNP(NH2)), respectively. Each type of AuNP was i.v. injected into mice (1 mg kg(-1)) and the concentration of Au was measured in different organs at 30 min, 4, 24 h, 7, 14 days, 1, 3 and 6 months post-injection. The organ distribution also showed the higher deposition rate depending on their functional groups: AuNP(PEG) for mesenteric lymph node, kidney, brain and testis; AuNP(COOH) for liver; AuNP(NH2) for spleen, lung and heart. The blood circulation time and the major excretion route were different depending on their functional groups. In conclusion, functional groups conjugated on the surface of AuNPs produce differences in blood kinetics, organ distribution and elimination pattern which can be important information for directing NPs to specific organs or improving the kinetic properties.
Assuntos
Compostos de Ouro/farmacocinética , Nanopartículas Metálicas/efeitos adversos , Animais , Compostos de Ouro/efeitos adversos , Compostos de Ouro/análise , Injeções Intravenosas , Masculino , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/análise , Camundongos , Camundongos Endogâmicos BALB C , Espectrofotometria Atômica/métodos , Propriedades de Superfície , Distribuição TecidualRESUMO
The recognition and treatment of allergy is a great challenge for all fields of medicine. The high prevalence of allergic reactions to dental materials and the related financial burden of their treatment make investigation of this disease very important. Our investigation was carried out on patients assigned to our outpatient department for dental allergy test between 1996 and 1998. We determined the distribution of gender and age among the allergic patients in the examined population. We also studied the prevalence of allergic reactions to different dental allergens and the distribution of dental allergens. In a follow-up study we determined the proportion of those patients, who were retreated in conformity with the results of epicutan tests and we followed up the positive effects of these treatments. We have found that dental allergy occurred five times more frequently in women (84%) than in men (16%) and the most affected age group was between 20 to 39 and 40-49 years (31%). Seventy-five percent of the patients suffered from a combination of metal and polymer allergy. The most frequent metal allergen was TEGDMA (triethylene glycol dimethacrylate) (49.7%). The suggested treatment plan was carried out in 63% of the allergic patients. The applied treatment was successful in 48% of these cases. We experienced that 48% of these patients got rid of their earlier signs and symptoms.
Assuntos
Alérgenos/efeitos adversos , Materiais Dentários/efeitos adversos , Hipersensibilidade/diagnóstico , Hipersensibilidade/terapia , Metais/efeitos adversos , Polímeros/efeitos adversos , Adulto , Distribuição por Idade , Idoso , Alérgenos/imunologia , Cloretos/efeitos adversos , Cobalto/efeitos adversos , Sulfato de Cobre/efeitos adversos , Feminino , Seguimentos , Compostos de Ouro/efeitos adversos , Humanos , Hungria/epidemiologia , Hipersensibilidade/epidemiologia , Hipersensibilidade/prevenção & controle , Incidência , Masculino , Metais/imunologia , Pessoa de Meia-Idade , Níquel/efeitos adversos , Pacientes Ambulatoriais , Paládio/efeitos adversos , Compostos de Platina/efeitos adversos , Polietilenoglicóis/efeitos adversos , Ácidos Polimetacrílicos/efeitos adversos , Dicromato de Potássio/efeitos adversos , Distribuição por Sexo , Compostos de Prata/efeitos adversosRESUMO
Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth--inhibitory effects, generally achieved by exploiting non-cisplatin-like mechanisms of action. The rationale of our research work is to combine the antitumor properties of the gold(III) metal center with the potential chemoprotective function of coordinated dithiocarbamates in order to reduce toxic side effects (in particular nephrotoxicity) induced by clinically established platinum-based drugs. In this context, [Au(III) Br(2) (ESDT)] (AUL12) was proved to exert promising and outstanding antitumor activity in vitro and to overcome both acquired and intrinsic resistance showed by some types of tumors toward cisplatin. As a subsequent extension of our previous work, we here report on detailed in vivo studies in rodents, including antitumor activity toward three transplantable murine tumor models, toxicity, nephrotoxicity and histopathological investigations. Remarkably, the gold(III) complex AUL12 stands out for higher anticancer activity than cisplatin toward all the murine tumor models examined, inducing up to 80% inhibition of tumor growth. In addition, it shows low acute toxicity levels (lethal dose, LD(50) = 30 mg kg(-1) ) and reduced nephrotoxicity. Altogether, these results confirm the reliability of our drug design strategy and support the validation of this gold(III)-dithiocarbamato derivative as a suitable candidate for clinical trials.
Assuntos
Antineoplásicos/farmacologia , Compostos de Ouro/farmacologia , Neoplasias/prevenção & controle , Tiocarbamatos/farmacologia , Animais , Antineoplásicos/efeitos adversos , Compostos de Ouro/efeitos adversos , Masculino , Camundongos , Neoplasias/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Tiocarbamatos/efeitos adversosRESUMO
The high frequency of contact allergy to gold in patients with dermatitis was established after exhaustive skin testing, determining the right test agent, the best concentration, and repeated test readings. Metallic gold in contact with skin is slowly ionized, permitting absorption and haptenisation. Contact allergy to gold is statistically correlated to the presence of dental gold. But in many case reports it has also been attributed to wearing gold jewellery, albeit not statistically demonstrated. Epicutaneous testing with gold salts increases the blood gold level, and by intramuscular injection systemic contact dermatitis is provoked in an allergic individual. In coronary heart disease, gold-coated intravascular stents have been shown to be correlated to contact allergy and even to an increased risk of restenosis. Gold is far from inert.
Assuntos
Dermatite Alérgica de Contato/etiologia , Ouro/efeitos adversos , Prótese Dentária , Dermatite Alérgica de Contato/sangue , Dermatite Alérgica de Contato/imunologia , Ouro/sangue , Ouro/imunologia , Compostos de Ouro/efeitos adversos , Compostos de Ouro/sangue , Compostos de Ouro/imunologia , Humanos , Joias , Testes do Emplastro , Absorção Cutânea , StentsRESUMO
Gold nanoparticles (GNPs) are an emerging area of interest in radiation therapy due to their unique radio-sensitizing properties. In the literature, the enhancing capability of GNPs is usually quantified using the metric dose enhancement ratio (DER). Traditionally, the focus of the vast majority of studies has always been on intravenous administration of GNPs. However, recent work showed the potential of using GNP inhalation, rather than intravenous injection, to enhance the dose to the lung. Yet, some of these studies are employing simplistic analytical methods to calculate DER and, thus far, there are no detailed computations of the enhancement profiles therein. Moreover, the coating on the GNP surface can be adversely affected by the large gradient of the radiation dose in the immediate vicinity of GNPs, leading to the rupture of ligands and detachment of GNPs from the surface of the membrane, and hence the loss of its efficacy. In this study, a next-generation deterministic code was used to resolve the DER profile at the interface between the septum, air, and surface of GNPs when they are attached and detached. The results show that the large values of DER in conjunction with the developed hot spots are very effective in lung treatment; on the other hand, coating rupture can lead to significant reduction in DER that may reach 64%. Thus, GNPs can be beneficial in inhalational medicine to treat lung cancer, provided that more comprehensive studies on the characteristics of the coating are addressed to maximize the radio-therapeutic benefit of GNPs.
Assuntos
Compostos de Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Administração por Inalação , Simulação por Computador , Sistemas de Liberação de Medicamentos/efeitos adversos , Elétrons , Estudos de Viabilidade , Compostos de Ouro/efeitos adversos , Compostos de Ouro/química , Humanos , Neoplasias Pulmonares/radioterapia , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/química , Modelos Teóricos , Nanomedicina/métodos , Radiossensibilizantes/efeitos adversos , Radiossensibilizantes/química , Radioterapia/métodos , Raios XRESUMO
Lichen planus is one of the most common mucocutaneous conditions seen in dental practice. A variety of other conditions known as lichenoid reactions can simulate lichen planus either clinically or histologically. This paper will discuss the more common lichenoid reactions seen in clinical practice and review the diagnosis and management of these conditions.
Assuntos
Erupções Liquenoides/diagnóstico , Erupções Liquenoides/etiologia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Cinnamomum zeylanicum/efeitos adversos , Amálgama Dentário/efeitos adversos , Diagnóstico Diferencial , Compostos de Ouro/efeitos adversos , Humanos , Líquen Plano Bucal/diagnóstico , Lesões Pré-Cancerosas/complicaçõesAssuntos
Cloretos/uso terapêutico , Compostos de Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Nanomedicina , Neoplasias/terapia , Terapia Fototérmica , Animais , Cloretos/efeitos adversos , Compostos de Ouro/efeitos adversos , Humanos , Nanopartículas Metálicas/efeitos adversos , Terapia Fototérmica/efeitos adversosRESUMO
Cases of contact dermatitis due to nickel and gold especially in pierced earlobes, are increasing in number the world over. However, the presence of these metal fragments has not been demonstrated in the skin lesions. The aim of this study was to demonstrate nickel and gold in contact dermatitis lesions in pierced earlobes. Skin specimens taken from such earlobe lesions were examined using scanning electron microscopy and x-ray microanalysis. The pierced earrings worn when the lesions appeared were examined by the same techniques, and their analysis confirmed. In nickel dermatitis, small, electron-dense fragments were seen in the specimens examined by scanning electron microscopy, and nickel was detected in locations corresponding to these fragments by x-ray microanalysis. In contact dermatitis due to gold, small dense fragments containing gold were observed. It is suggested that small fragments of nickel and gold remain in the skin lesions of pierced earlobes for a long time, even after the studs have been removed, and cause prolonged irritation and various cutaneous reactions.
Assuntos
Dermatite Alérgica de Contato/patologia , Orelha Externa/patologia , Orelha Externa/cirurgia , Compostos de Ouro/efeitos adversos , Níquel/efeitos adversos , Adulto , Dermatite Alérgica de Contato/etiologia , Microanálise por Sonda Eletrônica , Feminino , Humanos , Microscopia Eletrônica de Varredura , PunçõesRESUMO
Three cases of linear lichen planus on the lower extremities unaccompanied by mucous lesions are described. Dental metal compounds were thought to be the precipitating factor in all cases. Skin lesions did not respond to topical steroid ointment or antihistamines. Two cases showed a positive patch test reaction to gold (HAuCl4) and a positive lymphocyte stimulation test to gold compound (Gold sodium thiomalate). One case showed a positive patch test reaction to mercury (HgCl2), but a negative lymphocyte stimulation test. Suspected metal compounds were demonstrated in their dental materials. Removal of gold materials in one case gradually improved the lesions within 6 months with a transient erythematous swelling of the face shortly after removal of the metal. Both of these cases responded to oral disodium chromoglycate therapy. These results suggest that metal compound specific T cells might be responsible for the development of linear lichen planus.
Assuntos
Materiais Dentários/efeitos adversos , Compostos de Ouro/efeitos adversos , Líquen Plano/etiologia , Líquen Plano/imunologia , Adulto , Biópsia por Agulha , Feminino , Seguimentos , Humanos , Líquen Plano/tratamento farmacológico , Líquen Plano/patologia , Masculino , Pessoa de Meia-Idade , Testes do EmplastroRESUMO
MU-Gold, tetrakis (trishydroxymethyl) phosphine gold(I) chloride, a novel gold compound, has cytotoxic effects against human androgen-dependent and -independent prostatic, gastric, and colonic carcinoma in cell culture and against malignant lymphoma in rodent models. A pilot study was conducted to evaluate the tolerance and pharmacokinetic properties of MU-Gold in normal dogs in anticipation of clinical trials in cancer-bearing dogs. MU-Gold (10 mg/kg) was administered by i.v. injection to three purpose-bred dogs. Serum was collected from all dogs for measurement of gold levels via atomic absorption spectrometry. In addition, complete blood counts and biochemical profiles were monitored for Dogs 2 and 3 every 7 days for 30 days. A two-compartment i.v. bolus model with first-order kinetics, mean elimination half-life of approximately 40 hours, and mean volume of distribution of 0.6 L/kg was established. Serum gold concentrations ranging from 10 to 50 mcg/ml were sustained for 2 to 3 days with no clinically significant toxicities observed. Based on in vitro results in earlier studies and preliminary pharmacokinetic data collected in the present study, Phase I clinical trials should be conducted to define the optimal dosage, dose-limiting toxicities, and other characteristics of MU-Gold that will be used to design Phase II clinical trials.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Compostos de Ouro/efeitos adversos , Compostos de Ouro/farmacocinética , Compostos Organometálicos , Fosfinas , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Cães , Compostos de Ouro/administração & dosagem , Compostos de Ouro/química , Meia-Vida , Injeções Intravenosas , Masculino , Estrutura Molecular , Compostos OrganoáuricosAssuntos
Trombocitopenia/induzido quimicamente , Abciximab , Anticorpos Monoclonais/efeitos adversos , Carbamazepina/efeitos adversos , Compostos de Ouro/efeitos adversos , Heparina/efeitos adversos , Humanos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Procainamida/efeitos adversos , Quinidina/efeitos adversos , Quinina/efeitos adversos , Rifampina/efeitos adversos , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Trombocitopenia/terapia , Fatores de TempoAssuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antirreumáticos/efeitos adversos , Síndrome Nefrótica/induzido quimicamente , Antidepressivos/efeitos adversos , Antineoplásicos/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Cisteína/efeitos adversos , Cisteína/análogos & derivados , Difosfonatos/efeitos adversos , Compostos de Ouro/efeitos adversos , Humanos , Interferons/efeitos adversos , Compostos de Lítio/efeitos adversos , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/terapia , Pamidronato , Penicilamina/efeitos adversosAssuntos
Adjuvantes Imunológicos/fisiologia , Dermatite Alérgica de Contato/imunologia , Tolerância Imunológica , Metais Pesados/imunologia , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/farmacologia , Animais , Dermatite Alérgica de Contato/etiologia , Modelos Animais de Doenças , Compostos de Ouro/efeitos adversos , Compostos de Ouro/farmacologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/fisiopatologia , Tolerância Imunológica/efeitos dos fármacos , Mercúrio/efeitos adversos , Mercúrio/farmacologia , Metais Pesados/efeitos adversos , Metais Pesados/farmacologia , Camundongos , Paládio/efeitos adversos , Paládio/farmacologia , Platina/efeitos adversos , Platina/farmacologia , Ratos , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaAssuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Compostos de Ouro/administração & dosagem , Antirreumáticos/efeitos adversos , Substituição de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicina Baseada em Evidências , Compostos de Ouro/efeitos adversos , Humanos , Infusões Intravenosas , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Indução de Remissão , Resultado do TratamentoAssuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Compostos de Ouro/administração & dosagem , Administração Oral , Antirreumáticos/efeitos adversos , Auranofina/administração & dosagem , Auranofina/efeitos adversos , Produtos Biológicos/administração & dosagem , Produtos Biológicos/efeitos adversos , Substituição de Medicamentos , Medicina Baseada em Evidências , Compostos de Ouro/efeitos adversos , Tiomalato Sódico de Ouro/administração & dosagem , Tiomalato Sódico de Ouro/efeitos adversos , Humanos , Infusões Intravenosas , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Resultado do TratamentoRESUMO
Until recently, gold allergy was considered to be extremely rare. Gold has been used and worshipped for thousands of years without any obvious complaints of skin problems, either in those participating in mining and other ways of prospecting, or in those wearing jewellery. When studies on contact allergy to gold sodium thiosulfate were published at the beginning of the 1990s, the allergic nature of the reported positive patch test reactions to gold was questioned. The major argument for such questioning was the lack of demonstrable clinical relevance in most positive reactors. A major reason for the questioning may have been confusion in differentiating between contact allergy and allergic contact dermatitis. To arrive at a diagnosis of allergic contact dermatitis, 3 steps have, in principle, to be fulfilled: (i) establishment of contact allergy; (ii) demonstration of present exposure; (iii) assessment of clinical relevance, i.e., causing or aggravating a contact dermatitis. In this paper, these steps are discussed with regard to gold. With our present knowledge of contact allergy-allergic contact dermatitis, we do not recommend including gold sodium thiosulfate in the standard series. It should be applied for scientific purposes and when allergic contact dermatitis from gold is suspected.