Tuning the transdermal transport by application of external continuous electric field: a coarse-grained molecular dynamics study.

The control of skin permeability to specific substances (e.g., medications, vitamins, and nutrients) through stratum corneum is a challenge. Iontophoresis is an option in spite of the lack of a detailed understanding of the underlying molecular mechanism. In the present work, the simulations concerning application of an external continuous electric field to stratum corneum, in a range of low intensity (0-24 mV nm-1), were carried out using the coarse-grained molecular dynamics approach. Using a set of random seed replicas of the starting configuration, we observed that in the range of electric field intensity of 22-23 mV nm-1, water-rich lipid vesicles were formed in 20% of cases. Pores appeared in the remaining 80%. We argue that lipids undergo fast re-orientations under electric field inducing mechanical instability, which originates the pores. We presented a simple electrostatic model to interpret the results where the mismatch between electrical permittivities of the membrane and external media and the gradient of the local electric field in the membrane surface, govern the time scales and electric fields for vesicle formation. Our results indicate that just 10% difference between electrical permittivities of the membrane and external media decreases 1/6 the minimal time required for vesicle formation. The minimal electric field required decreases 10 times. The control and tunning of formation of biologically compatible vesicles, capable of transporting substances under low-intensity electric fields, has a promising application in fields such as drug therapy and dermo-cosmetics allowing the use of hydrophilic substances in dermal applications.

Molluscum contagiosum: immunomorphological aspects of keratinocytes markers of differentiation and adhesion.

BACKGROUND: Molluscum contagiosum (MC) is a Molluscipox virus infection of keratinocytes with hyperplasia and intracytoplasmic inclusions - the molluscum bodies (MBs). Few papers address cytokeratins (K) profile in MC, mainly focusing terminal keratinization process. METHODS: Forty-one MC lesions were subjected to immunohistochemical technique to verify K1, K10, K14, K16, involucrin, filaggrin, E-cadherin and p63 expression. MC immunolabeling pattern was compared to adjacent normal appearing epidermis (ANAE). RESULTS: In MC and ANAE, K1/K10 were expressed in suprabasal layers, K14 was expressed in basal and suprabasal layers and K16 was expressed through all spinous layer. Involucrin and filaggrin were observed in granular, spinous and in basal layer of ANAE and MC. E-cadherin was present up to the first layers of MC while ANAE exhibited E-cadherin labeling at basal and spinous layers. Basal and spinous layers keratinocytes nuclei, in both MC and ANAE, express p63. CONCLUSION: Infection by Molluscipox virus alters keratinocyte differentiation status. The presence of K14 and p63 in spinous layer, as well as early expression of involucrin and filaggrin, associated to a hyperproliferative state disclosed by K16 expression, may be a result of disruption in keratinocytes maturation process. The changes observed at ANAE may represent early events in keratinization disturbance.

[Thyroid disorders in diabetic patients]. / Associação de tireopatias em uma população de pacientes com diabetes.

OBJECTIVE: To evaluate thyroid function and morphology in all diabetic outpatients from our institution. METHODS: From 1996 to 1998, all diabetic patients were submitted to thyroid ultrasonography (US) and serum measurement of free T4, TSH, TPOAB, and TRAb. The control group, encompassing outpatients of the same hospital without diabetes and thyroid diseases, was submitted to the same evaluation. A patient was shown to have thyroid disorder when two or more measurements were altered, or when the US was abnormal. RESULTS: The diabetic patients (n= 256) differed from controls (n= 75) by presenting a greater frequency of thyroid disorders (51.6% vs. 38.7%; P<0.05). In patients with thyroid disorders, both groups did not differ regarding thyroid function. In diabetic patients with thyroid disorders there was a higher frequency of women, type 2 diabetes, and family history of thyroid disorders. CONCLUSIONS: The high prevalence of thyroid disorders in the diabetic population leads us to recommend thyroid evaluations in all diabetic patients.

Associacão de tireopatias em uma populacão de pacientes com diabetes / Thyroid disorders in diabetic patients

OBJETIVO: Avaliar morfológica e funcionalmente a tireóide de pacientes com diabetes mellitus (DM) acompanhados ambulatorialmente no Hospital das Clínicas de Botucatu. MÉTODOS: No período de 1996 a 1998, a todo paciente com DM, exceto os com tireopatia prévia, era solicitada dosagem sérica de T4L, TSH, anti-TPO e TRAb e ultra-sonografia (US) da tireóide. Diagnosticou-se tireopatia quando havia dois ou mais parâmetros séricos ou a US alterados. Procedeu-se igualmente com pacientes ambulatoriais da mesma Instituicão, sem DM e não-tireopatas prévios (controle). RESULTADOS: Os 256 pacientes com DM apresentaram maior freqüência de tireopatias que os 75 controles (51,6 por cento vs. 38,7 por cento; P<0,05). Entre os com tireopatias, ambos os grupos não diferiram quanto ao estado funcional da tireóide. Entre os pacientes com DM com e sem tireopatias, os primeiros apresentaram maior freqüência de mulheres, de DM tipo 2 e de história familiar de tireopatia. CONCLUSÕES: A elevada prevalência de tireopatias na populacão com DM conduz à recomendacão de avaliacão tireoidiana em todo paciente com DM.