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2.
Expert Opin Emerg Drugs ; 19(4): 441-58, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25286776

RESUMO

INTRODUCTION: Atopic eczema (AE) is a chronic relapsing inflammatory skin condition and one of the most common, potentially debilitating diseases with increasing incidence. AREAS COVERED: The complex etiology of AE with multiple systemic and local immunologic and inflammatory responses and interactions between susceptibility genes and environmental factors leading to defects in skin barrier function and eczematous skin lesions is presented. Knowledge of pathogenesis is important for understanding the more innovative treatment approaches discussed. EXPERT OPINION: Basic therapy consists of hydrating topical treatment and avoidance of specific and unspecific provocation factors. For acute eczematous skin lesions, anti-inflammatory treatment consists mainly of topical glucocorticoids and topical calcineurin inhibitors. Microbial colonization and superinfection may induce skin exacerbation, which can be treated by either topical or systemic antimicrobial treatment. Systemic anti-inflammatory therapy is limited to severe cases and consists of systemic steroids, cyclosporine A or mycophenolate mofetil. Novel anti-inflammatory concepts that go beyond corticosteroids are in the early phases of development. There are targeted therapeutic approaches, such as cytokine and chemokine modulators, and it remains to be investigated how effective they will be and what side effects they may carry. Existing treatment modalities such as barrier repair therapy, topical immunosuppressive agents, antiseptic treatment as well as systemic treatment options are discussed.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Eczema/tratamento farmacológico , Administração Cutânea , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/fisiopatologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacologia , Desenho de Fármacos , Eczema/fisiopatologia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Terapia de Alvo Molecular
3.
Wien Med Wochenschr ; 163(21-22): 495-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24221053

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by lacking expression of estrogen receptor and progesterone receptor as well as absence of human epidermal growth factor receptor 2 overexpression and is an aggressive clinical phenotype. PATIENTS AND METHODS: We report the case of a 33-year-old woman who has been treated using a targeted approach for TNBC and developed a malignant melanoma metastasis without any primary. RESULTS AND CONCLUSION: Using targeted therapies, tumors can be treated much more effectively, but up to now, we do not know much about potential adverse reactions. Due to the targeted therapy, tumors may be pressurized for transformation. We call for further investigations to rule out the potential risks of targeted therapy in TNBC. This is the first report of a potential transforming of one tumor entity to another by a targeted therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Melanoma/induzido quimicamente , Melanoma/patologia , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Desconhecidas/induzido quimicamente , Neoplasias Primárias Desconhecidas/patologia , Neoplasias da Medula Espinal/induzido quimicamente , Neoplasias da Medula Espinal/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Adulto , Transformação Celular Neoplásica/patologia , Terapia Combinada , Ciclo-Oxigenase 2/genética , Progressão da Doença , Receptores ErbB/genética , Evolução Fatal , Feminino , Humanos , Antígeno Ki-67/genética , Melanoma/genética , Melanoma/secundário , Estadiamento de Neoplasias , Neoplasias Primárias Desconhecidas/genética , Receptor ErbB-2/genética , Neoplasias da Medula Espinal/genética , Neoplasias da Medula Espinal/secundário , Fator A de Crescimento do Endotélio Vascular/genética
4.
Curr Allergy Asthma Rep ; 12(2): 85-98, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22359067

RESUMO

The hypereosinophilic syndromes (HES) are a heterogeneous group of disorders defined as persistent and marked blood eosinophilia of unknown origin with systemic organ involvement. HES is a potentially severe multisystem disease associated with considerable morbidity. Skin involvement and cutaneous findings frequently can be seen in those patients. Skin symptoms consist of angioedema; unusual urticarial lesions; and eczematous, therapy-resistant, pruriginous papules and nodules. They may be the only obvious clinical symptoms. Cutaneous features can give an important hint to the diagnosis of this rare and often severe illness. Based on advances in molecular and genetic diagnostic techniques and on increasing experience with characteristic clinical features and prognostic markers, therapy has changed radically. Current therapies include corticosteroids, hydroxyurea, interferon-α, the tyrosine kinase inhibitor imatinib mesylate, and (in progress) the monoclonal anti-interleukin-5 antibodies. This article provides an overview of current concepts of disease classification, different skin findings, and therapy for HES.


Assuntos
Síndrome Hipereosinofílica/classificação , Síndrome Hipereosinofílica/diagnóstico , Dermatopatias/diagnóstico , Diagnóstico Diferencial , Humanos , Síndrome Hipereosinofílica/genética , Síndrome Hipereosinofílica/terapia , Dermatopatias/patologia , Dermatopatias/terapia
6.
Arch Dermatol ; 147(8): 963-6, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21482864

RESUMO

BACKGROUND: Octopus vulgaris is a common marine animal that can be found in nearly all tropical and semitropical waters around the world. It is a peaceful sea dweller with a parrotlike beak, and its primary defense is to hide through camouflaging adjustments. Bites from animals of the class Cephalopoda are very rare. We describe a boy who was bitten on his forearm by an Octopus vulgaris. OBSERVATION: A 9 -year-old boy was bitten by an Octopus vulgaris while snorkeling. There was no strong bleeding or systemic symptoms; however, 2 days later, a cherry-sized, black, ulcerous lesion developed, surrounded by a red circle that did not heal over months and therefore had to be excised. Histologic examination showed ulceration with extensive necrosis of the dermis and the epidermis. A microbial smear revealed Pseudomonas (formerly known as Flavimonas) oryzihabitans. After excision, the wound healed within 2 weeks, without any complications or signs of infection. CONCLUSIONS: To the best of our knowledge, this case represents the first report of an Octopus vulgaris bite resulting in an ulcerative lesion with slow wound healing owing to P oryzihabitans infection. We recommend greater vigilance regarding bacterial contamination when treating skin lesions caused by marine animals.


Assuntos
Mordeduras e Picadas/complicações , Mordeduras e Picadas/microbiologia , Octopodiformes , Infecções por Pseudomonas/etiologia , Úlcera Cutânea/etiologia , Úlcera Cutânea/microbiologia , Animais , Criança , Humanos , Masculino
8.
Expert Opin Emerg Drugs ; 15(2): 249-67, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20433363

RESUMO

IMPORTANCE OF THE FIELD: Atopic eczema (AE) is a chronic relapsing inflammatory skin condition and one of the most common, potentially debilitating diseases with increasing incidence. AREAS COVERED IN THIS REVIEW: The complex etiology of AE with multiple systemic and local immunologic and inflammatory responses and interactions between susceptibility genes and environmental factors leading to defects in skin barrier function and eczematous skin lesions is presented. Knowledge of pathogenesis is important for understanding the more innovative treatment approaches discussed. WHAT THE READER WILL GAIN: Basic therapy consists of hydrating topical treatment and avoidance of specific and unspecific provocation factors. For acute eczematous skin lesions, anti-inflammatory treatment consists mainly of topical glucocorticoids and topical calcineurin inhibitors (tacrolimus and pimecrolimus). Microbial colonization and superinfection may induce skin exacerbation, which can be treated by either topical or systemic antimicrobial treatment. Systemic anti-inflammatory therapy is limited to severe cases and consists of systemic steroids, cyclosporine A or mycophenolate mofetil. Novel anti-inflammatory concepts that go beyond corticosteroids are in the early phases of development. There are targeted therapeutic approaches, such as cytokine and chemokine modulators and it remains to be investigated how effective they will be and what side effects they may carry. TAKE HOME MESSAGE: Existing treatment modalities such as barrier repair therapy, topical immunosuppressive agents, antiseptic treatment as well as systemic treatment options are discussed. The review aims to summarize the most recent findings of more innovative treatment approaches such as modulation of cytokines or chemokines, modulation of T-cell responses or anti-IgE therapy.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/uso terapêutico , Drogas em Investigação/uso terapêutico , Administração Cutânea , Animais , Anti-Infecciosos Locais/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Produtos Biológicos/uso terapêutico , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Fármacos Dermatológicos/administração & dosagem , Drogas em Investigação/administração & dosagem , Humanos , Imunossupressores/uso terapêutico , Imunoterapia , Resultado do Tratamento
10.
J Allergy Clin Immunol ; 113(6): 1152-60, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15208598

RESUMO

BACKGROUND: Eosinophil accumulation at sites of allergic inflammation is largely regulated by chemokines and lipid mediators released by a variety of cells of the local microenvironment. Recent studies have shown that pollen grains, apart from their function as allergen carriers, are a rich exogenous source of eicosanoid-like lipid mediators that are rapidly released on contact with the aqueous phase and thus may contribute to the generation of local inflammatory responses. OBJECTIVE: Here we analyze the biological activity of pollen-associated lipid mediators (PALMs) on peripheral human blood eosinophils. METHODS: Human eosinophils were coincubated with pollen grains and analyzed by electron microscopy. The lipid mediator composition of aqueous pollen extracts (APEs) was analyzed by HPLC. Human eosinophils were exposed to APEs or lipid fractions from pollen. Effects on eosinophils were tested by transwell migration and surface expression of CD11b. RESULTS: In vitro experiments showed adhesion of eosinophils to Phleum pratense pollen. In chemotaxis assays eosinophils displayed significant directed migration to APEs. HPLC analysis of APEs from Phleum pratense and Betula alba pollen demonstrated the occurrence of linoleic and alpha-linolenic acid as well as their monohydroxylated derivatives. Moreover, total lipid extracts from pollen and RP-HPLC fractions containing monohydroxylated derivatives of linoleic and alpha-linolenic acid induced similar migratory responses, although to a lesser degree than APEs. In addition, APEs and lipid extracts induced up-regulation of CD11b surface expression and secretion of eosinophil cationic protein. APE-induced chemotaxis was blocked by the leukotriene B(4) receptor antagonist LY293111, suggesting that PALMs may serve as ligands for LTB(4) receptors. CONCLUSION: Pollen grains release lipid mediators that recruit and activate eosinophils in vitro. Similar mechanisms may be effective under natural exposure conditions, in which PALMs may play a role in the recruitment of eosinophils to the site of allergic inflammation.


Assuntos
Quimiotaxia de Leucócito , Eosinófilos/imunologia , Lipídeos/farmacologia , Extratos Vegetais/farmacologia , Pólen/imunologia , Benzoatos/farmacologia , Proteínas Sanguíneas/metabolismo , Antígeno CD11b/análise , Adesão Celular , Movimento Celular , Proteínas Granulares de Eosinófilos , Eosinófilos/fisiologia , Humanos , Imunidade Inata , Ribonucleases/metabolismo
12.
Eur J Immunol ; 33(4): 834-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12672048

RESUMO

Patients with hypereosinophilia frequently suffer from eosinophil-mediated damages of the heart, lungs, skin, and other organs, while some do not. The reason(s) for this difference is not known. We observed that eosinophils from most patients with hypereosinophilia express the alpha-chain of the IL-2 receptor (CD25), and that IL-2 enhances platelet-activating factor-stimulated release of eosinophil cationic protein from CD25-expressing but not from CD25-negative eosinophils. Such a "priming" effect has previously been described for eosinophil hematopoietins. These data suggest that patients with increased eosinophil surface CD25 expression are at higher risk of eosinophil degranulation and subsequent tissue damage when IL-2 is present at inflammatory sites.


Assuntos
Degranulação Celular , Eosinofilia/imunologia , Eosinófilos/imunologia , Interleucina-2/farmacologia , Ribonucleases , Asma/imunologia , Proteínas Sanguíneas/metabolismo , Dermatite Atópica/imunologia , Sinergismo Farmacológico , Proteínas Granulares de Eosinófilos , Eosinofilia/tratamento farmacológico , Eosinófilos/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Síndrome Hipereosinofílica/imunologia , Interleucina-5/farmacologia , Fator de Ativação de Plaquetas/farmacologia , Receptores de Interleucina-2/metabolismo , Receptores de Interleucina-2/fisiologia , Síndrome
13.
J Allergy Clin Immunol ; 109(5): 831-8, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11994708

RESUMO

BACKGROUND: Under natural exposure conditions, pollen grains function as allergen carriers that release allergens from internal binding sites on contact with the aqueous phase of mucosa membranes. In addition, we recently demonstrated that pollen are a rich source of eicosanoid-like mediators, which are rapidly released on contact with the aqueous phase. OBJECTIVE: The current study was designed to characterize the biochemical nature of pollen-derived lipid mediators in more detail and to delineate their biologic activity on polymorphonuclear granulocytes (PMNs). METHODS: Aqueous and lipid extracts from Phleum pratense L and Betula alba L pollen were analyzed by means of HPLC. PMNs were exposed to aqueous extracts or lipid fractions from pollen or to HPLC-purified lipid mediators identified in pollen extracts. Effects on PMNs were tested with transwell migration, calcium mobilization, and surface expression of CD11b. RESULTS: Aqueous pollen extracts (APEs) contained predominantly monohydroxylated products derived of linoleic acid and linolenic acid. In chemotaxis assays PMNs displayed significant migration to APEs. Lipid extracts from pollen and the HPLC fraction containing 13-hydroxy-octadecadienoic acid/hydroxy-linoleic acid and 13-hydroxy-octadecatrienoic acid/hydroxy-linolenic acid induced migratory responses, although to a lesser degree than the APEs. In addition, APE, as well as lipid, extracts induced PMN activation, as documented by means of calcium mobilization and upregulation of CD11b. CONCLUSION: Pollen grains release mediators that recruit and activate PMNs in vitro. Similar mechanisms may be effective in vivo, suggesting that pollen-derived lipid mediators may act as adjuvants in the elicitation phase of allergic reactions.


Assuntos
Fatores Quimiotáticos/farmacologia , Lipídeos/farmacologia , Ativação de Neutrófilo , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Pólen/metabolismo , Movimento Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ácidos Graxos Insaturados/farmacologia , Humanos , Ácidos Linoleicos/análise , Ácidos Linoleicos/farmacologia , Lipídeos/análise , Antígeno de Macrófago 1/metabolismo , Extratos Vegetais/farmacologia , Pólen/química , Transdução de Sinais , Regulação para Cima
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