RESUMO
Keratoacanthoma formation after skin grafting is rare. We report the third case in the literature of multiple keratoacanthomas developed at both split-thickness skin graft donor and recipient sites. We provide possible explanations for this poorly understood phenomenon and highlight its implications on treatment options.
Assuntos
Ceratoacantoma/etiologia , Ceratoacantoma/terapia , Transplante de Pele/efeitos adversos , Acitretina/uso terapêutico , Idoso de 80 Anos ou mais , Curetagem , Feminino , Humanos , Ceratoacantoma/patologia , Ceratolíticos/uso terapêutico , Sítio Doador de Transplante/patologiaRESUMO
Complex aphthosis, the occurrence of recurrent oral and genital aphthous ulceration without manifestations of systemic disease, is relatively uncommon and of unknown aetiology. We describe a case of complex aphthosis which began within weeks of stopping smoking. After failing to respond to conventional agents, the patient was successfully treated with nicotine lozenges. Recurrent aphthous stomatitis (RAS) is known to be less common in smokers and there have been previous reports of nicotine being used as successful treatments for RAS and Behçet's disease. We discuss the mechanisms of action of nicotine whereby nicotine could influence the natural history of aphthous ulceration. We recommend considering its use when conventional management has failed, particularly in ex-smokers.
Assuntos
Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Estomatite Aftosa/tratamento farmacológico , Doenças da Vulva/tratamento farmacológico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Recidiva , Estomatite Aftosa/diagnóstico , Tabagismo/tratamento farmacológico , Resultado do Tratamento , Doenças da Vulva/diagnósticoRESUMO
Granuloma faciale (GF) is a benign chronic condition characterized by recurrent plaques and nodules most commonly found on the face. We report a man with a 6-month history of plaques on his forehead and preauricular area consistent with GF that responded to twice-daily application of topical tacrolimus ointment, and who remains in remission 1 year later. This case supports previous reports of the successful use of topical tacrolimus in treating GF.
Assuntos
Dermatoses Faciais/tratamento farmacológico , Granuloma/tratamento farmacológico , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Administração Tópica , Relação Dose-Resposta a Droga , Esquema de Medicação , Dermatoses Faciais/patologia , Seguimentos , Granuloma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Dipeptide-based sulfonium peptidylmethylketones derived from 6-diazo-5-oxo-L-norleucine (DON) have been investigated as potential water-soluble inhibitors of extracellular transglutaminase. The lead compounds were prepared in four steps and exhibited potent activity against tissue transglutaminase.
Assuntos
Diazo-Oxo-Norleucina/química , Proteínas de Ligação ao GTP/antagonistas & inibidores , Transglutaminases/antagonistas & inibidores , Água/química , Domínio Catalítico , Química Farmacêutica/métodos , Desenho de Fármacos , Etanol/química , Humanos , Concentração Inibidora 50 , Cetonas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas/métodos , Peptídeos/química , Proteína 2 Glutamina gama-Glutamiltransferase , Solubilidade , Espectrofotometria/métodosRESUMO
Sub-lethal concentrations of the organophosphate phenyl saligenin phosphate (PSP) inhibited the outgrowth of axon-like processes in differentiating mouse N2a neuroblastoma cells (IC(50) 2.5 microM). A transient rise in the phosphorylation state of neurofilament heavy chain (NFH) was detected on Western blots of cell extracts treated with 2.5 microM PSP for 4 h compared to untreated controls, as determined by a relative increase in reactivity with monoclonal antibody Ta51 (anti-phosphorylated NFH) compared to N52 (anti-total NFH). However, cross-reactivity of PSP-treated cell extracts was lower than that of untreated controls after 24 h exposure, as indicated by decreased reactivity with both antibodies. Indirect immunofluorescence analysis with these antibodies revealed the appearance of neurofilament aggregates in the cell bodies of treated cells and reduced axonal staining compared to controls. By contrast, there was no significant change in reactivity with anti-alpha-tubulin antibody B512 at either time point. The activation state of the MAP kinase ERK 1/2 increased significantly after PSP treatment compared to controls, particularly at 4 h, as indicated by increased reactivity with monoclonal antibody E-4 (anti-phosphorylated MAP kinase) but not with polyclonal antibody K-23 (anti-total MAP kinase). The observed early changes were concomitant with almost complete inhibition of the activity of neuropathy target esterase (NTE), one of the proposed early molecular targets in organophosphate-induced delayed neuropathy (OPIDN).
Assuntos
Hidrolases de Éster Carboxílico/metabolismo , Diferenciação Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neuritos/efeitos dos fármacos , Proteínas de Neurofilamentos/metabolismo , Compostos Organofosforados/farmacologia , Animais , Western Blotting , Linhagem Celular Tumoral , Camundongos , Neuritos/enzimologia , Neuritos/patologia , Neuroblastoma/patologia , FosforilaçãoRESUMO
Diabetic nephropathy affects 30-40% of diabetics leading to end-stage kidney failure through progressive scarring and fibrosis. Previous evidence suggests that tissue transglutaminase (tTg) and its protein cross-link product epsilon(gamma-glutamyl)lysine contribute to the expanding renal tubulointerstitial and glomerular basement membranes in this disease. Using an in vitro cell culture model of renal proximal tubular epithelial cells we determined the link between elevated glucose levels with changes in expression and activity of tTg and then, by using a highly specific site directed inhibitor of tTg (1,3-dimethyl-2[(oxopropyl)thio]imidazolium), determined the contribution of tTg to glucose-induced matrix accumulation. Exposure of cells to 36 mm glucose over 96 h caused an mRNA-dependent increase in tTg activity with a 25% increase in extracellular matrix (ECM)-associated tTg and a 150% increase in ECM epsilon(gamma-glutamyl)lysine cross-linking. This was paralleled by an elevation in total deposited ECM resulting from higher levels of deposited collagen and fibronectin. These were associated with raised mRNA for collagens III, IV, and fibronectin. The specific site-directed inhibitor of tTg normalized both tTg activity and ECM-associated epsilon(gamma-glutamyl)lysine. Levels of ECM per cell returned to near control levels with non-transcriptional reductions in deposited collagen and fibronectin. No changes in transforming growth factor beta1 (expression or biological activity) occurred that could account for our observations, whereas incubation of tTg with collagen III indicated that cross-linking could directly increase the rate of collagen fibril/gel formation. We conclude that Tg inhibition reduces glucose-induced deposition of ECM proteins independently of changes in ECM and transforming growth factor beta1 synthesis thus opening up its possible application in the treatment other fibrotic and scarring diseases where tTg has been implicated.