RESUMEN
We examined rs2201841 within IL-23R gene in Serbian patients with psoriasis and healthy controls. G allele frequency was significantly increased in the group of patients with psoriatic arthritis compared with controls (0.481 vs 0.308). Carriage of G allele increases risk to develop psoriatic arthritis (P = 0.009, OR = 3.311, 95% CI 1.29-8.70).
Asunto(s)
Artritis Psoriásica/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Alelos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Factores de Riesgo , SerbiaRESUMEN
Intrinsic characteristics of melanoma cells such as expression of inducible nitric oxide synthase (iNOS), redox status, and activity of signaling pathways involved in proliferation, differentiation and cell death define the response of the cells to the diverse treatments. In this context we compared the effectiveness of herbal antaquinone aloe emodin (AE) against mouse B16 melanoma and human A375, different in initial activity of ERK1/2, constitutive iNOS expression and basal level of reactive oxygen species (ROS). Both cell lines are sensitive to AE treatment. However, while the agent induces differentiation of B16 cells toward melanocytes, in A375 cells promoted massive apoptosis. Differentiation of B16 cells, characterized by enhanced melanin production and tyrosinase activity, was mediated by H(2)O(2) production synchronized with rapid p53 accumulation and enhanced expression of cyclins D1 and D3. Caspase mediated apoptosis triggered in A375 cells was accompanied with Bcl-2 but not iNOS down-regulation. In addition, opposite regulation of Akt-ERK1/2 axis in AE treated B16 and A375 cells correlated with different outcome of the treatment. However, AE in a dose-dependent manner rescued both B16 and A375 cells from doxorubicin- or paclitaxel-induced killing. These data indicate that caution is warranted when AE is administrated to the patients with conventional chemotherapy.
Asunto(s)
Antraquinonas/farmacología , Melanoma Experimental/patología , Animales , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Humanos , Sistema de Señalización de MAP Quinasas , Melanoma Experimental/enzimología , Melanoma Experimental/metabolismo , Ratones , Óxido Nítrico Sintasa de Tipo II/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Vitamin A and D analogues play an important role in epidermal homeostasis and are used in the treatment of various skin diseases. The failure of retinoid and vitamin D treatments is sometimes difficult to explain. METHODS: We analyzed the effect of all-trans retinoic acid (all-trans RA), 13-cis retinoic acid (13-cis RA), ergocalciferol and cholecalciferol in keratinocyte cultures established from adult donors, on the cell proliferation by means of [(3)H]thymidine incorporation and apoptosis after fluorescein diacetate/trypan blue staining. RESULTS: All tested agents exerted a dose-dependent inhibition of keratinocyte proliferation in the concentration range of 1.25-5 microM. Based on IC(50) values, the antiproliferative efficiency was as follows: cholecalciferol > ergocalciferol = all-trans RA > 13-cis RA. The observed effect of cholecalciferol and ergocalciferol, but not retinoids, involved the induction of apoptotic cell death. Combining vitamins A and D did not further increase the proliferation block and even displayed an antagonistic effect. CONCLUSION: The susceptibility of keratinocytes to the antiproliferative action of vitamins A and D was markedly different in cell cultures derived from different donors, indicating a possible predictive value of the in vitro testing for the efficiency of the clinical response to these agents.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Vitamina A/análogos & derivados , Vitamina A/farmacología , Vitamina D/análogos & derivados , Vitamina D/farmacología , Apoptosis/efectos de los fármacos , Células Cultivadas , Colecalciferol/farmacología , Relación Dosis-Respuesta a Droga , Ergocalciferoles/farmacología , Humanos , Isotretinoína/farmacología , Queratinocitos/metabolismo , Tretinoina/farmacologíaRESUMEN
We report two unusual patients with Rothmund-Thomson syndrome (RTS), a rare genodermatosis. The first patient is a 5-year-old girl with congenital poikiloderma, photosensitivity, plantar punctate keratoderma, stunted growth and severe mental retardation. Plantar keratoderma associated with RTS has been reported only once. The second patient is a 21-year-old female presenting with rounded "moon" face, trunk obesity, coeliac disease, short stature and mild mental retardation. This is the first case of RTS associated with coeliac disease.
Asunto(s)
Enfermedad Celíaca/complicaciones , Queratodermia Palmoplantar/complicaciones , Síndrome Rothmund-Thomson/complicaciones , Síndrome Rothmund-Thomson/diagnóstico , Adulto , Preescolar , Femenino , Humanos , Síndrome Rothmund-Thomson/terapiaRESUMEN
Chloramphenicol (CAP) is a broad-spectrum antibacterial drug that is widely used for topical application in ophthalmology and dermatology. In the present study we investigated the influence of CAP on human keratinocyte proliferation and apoptosis in vitro. CAP significantly inhibited proliferation and induced apoptosis of cultivated human keratinocytes, as revealed by incorporation of radioactive thymidine and flow cytometry analysis of intracellular esterase activity in fluorescein diacetate-stained cells, respectively. CAP-induced keratinocyte apoptosis was associated with activation of caspases and increased production of reactive oxygen species. The pro-apoptotic action of CAP was antagonized by the antioxidant agent N-acetylcysteine, the protein synthesis inhibitor cycloheximide, and PD98059, a selective inhibitor of extracellular signal-regulated kinase (ERK) activation. Taken together, these data indicate that CAP inhibits keratinocyte proliferation through induction of oxidative stress and ERK-mediated caspase-dependent apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Cloranfenicol/farmacología , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Caspasas/metabolismo , Proliferación Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Humanos , L-Lactato Deshidrogenasa/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
UNLABELLED: The Aim of the paper was to give a review of an early diagnosis, therapy, follow-up and survival rate of patients with thyroid malignancy (TM). The paper presented the algorithm of early diagnosis: clinical, scintigraphic and ultrasonographic examination together with fine needle biopsy, cytologic analysis of the smear and biopsy ex tempore of the clear and suspected thyroid node to malignancy. Therapy of all TM forms was mainly surgical: postsurgical treatment was dependent on the type of malignancy: radioiodine 131-I, radiologic treatment, chemotherapy and radioimmunotherapy, (the latest one being in the phase of a clinical research). Follow-up was in accordance with the protocol and it was necessary because it contributes to the survival rate. In the presentation of survival rate for differentiated and medullar carcinomas we gave our results and literature data, while for the other malignancies only data from literature were presented. CONCLUSION: Only an early diagnosis of the nodular goiter together with an up-to-date treatment can cure TM patients in a high percentage and prevent development of a terminal stage of the disease which is extremely severe in all forms of this malignancy.