3D-Structural Characterization of MicroRNA Expressed in Leprosy / Caracterização Estrutural em 3D de MicroRNAs Expressos na Hanseníase

Introduction: Hansen's disease, or leprosy is caused by Mycobacterium leprae (M. leprae), is a major public health problem in developing countries, and affecting the skin and peripheral nerves. However, M. leprae can also affect bone tissue, mucous membranes, liver, eyes, and testicles, producing a variety of clinical phenotypes. MicroRNAs (miRNAs) have been expressed in the various clinical forms of leprosy and could potentially be used for its diagnosis. Objective: in silico design of the molecular structure of miRNAs expressed in leprosy. Methodology: we performed a nucleotide sequence search of 17 miRNAs expressed in leprosy, designing in silico the molecular structure of the following miRNAs: miRNA-26a, miRNA-27a, miRNA-27b, miRNA-29c, miRNA-34c, miRNA-92a-1, miRNA- 99a-2, miRNA-101-1, miRNA-101-2, miRNA-125b-1, miRNA-196b, miRNA-425-5p, miRNA-452, miRNA-455, miRNA-502, miRNA-539, and miRNA-660. We extracted the nucleotides were from the GenBank of National Center for Biotechnology Information genetic sequence database. We aligned the extracted sequences with the RNA Folding Form, and the three-dimensional molecular structure design was performed with the RNAComposer. Results: we demonstrate the nucleotide sequences, and molecular structure projection of miRNAs expressed in leprosy, and produces a tutorial on the molecular model of the 17 miRNAs expressed in leprosy through in silico projection processing of their molecular structures. Conclusion: we demonstrate in silico design of selected molecular structures of 17 miRNAs expressed in leprosy through computational biology.

Introdução: a doença de Hansen, ou hanseníase é causada pelo Mycobacterium leprae (M. leprae), é um grande problema de saúde pública nos países em desenvolvimento e afeta, a pele e os nervos periféricos. Entretanto, o M. leprae também pode comprometer o tecido ósseo, membranas mucosas, fígado, olhos e testículos, produzindo uma variedade de fenótipos clínicos. MicroRNAs (miRNAs) têm sido expressos nas várias formas clínicas da hanseníase e podem ser potencialmente utilizados para seu diagnóstico. Objetivo: objetivou-se com esse experimento modelar computacionalmente a estrutura molecular dos miRNAs expressos na hanseníase. Metodologia: realizou-se como metodologia uma pesquisa das sequências nucleotídicas de 17 miRNAs expressos na hanseníase, desenhando em modelo computacional a estrutura molecular dos seguintes miRNAs: miRNA-26a, miRNA-27a, miRNA-27b, miRNA- 29c, miRNA-34c, miRNA-92a-1, miRNA-99a-2, miRNA-101-1, miRNA-101-2, miRNA-125b-1, miRNA-196b, miRNA-425-5p, miRNA-452, miRNA-455, miRNA-502, miRNA-539, e miRNA-660. Extraiu-se os nucleotídeos do banco de dados do GenBank of National Center for Biotechnology Information . Alinhou-se as sequências extraídas com o RNA Folding Form, e o projeto da estrutura molecular tridimensional foi realizado com o RNAComposer. Resultados: demonstrou-se como resultados as sequências dos nucleotídeos e a projeção da estrutura molecular dos miRNAs expressos na hanseníase, e produzimos um tutorial sobre o modelo molecular dos 17 miRNAs expressos em hanseníase através do processamento de suas estruturas moleculares em projeção computacional. Conclusão: foi demonstrado computacionalmente o projeto de estruturas moleculares selecionadas de 17 miRNAs expressos em hanseníase através da biologia computacional.

In Silico Prediction of Eye Irritation Using Hansen Solubility Parameters and Predicted pKa Values.

An in silico method has been developed that permits the binary differentiation between pure liquids causing serious eye damage or eye irritation, and pure liquids with no need for such classification, according to the UN GHS system. The method is based on the finding that the Hansen Solubility Parameters (HSP) of a liquid are collectively important predictors for eye irritation. Thus, by applying a two-tier approach in which in silico-predicted pKa values (firstly) and a trained model based solely on in silico-predicted HSP data (secondly) were used, we have developed, and validated, a fully in silico approach for predicting the outcome of a Draize test (in terms of UN GHS Cat. 1/Cat. 2A/Cat. 2B or UN GHS No Cat.) with high validation set performance (sensitivity = 0.846, specificity = 0.818, balanced accuracy = 0.832) using SMILES only. The method is applicable to pure non-ionic liquids with molecular weight below 500 g/mol, fewer than six hydrogen bond donors (e.g. nitrogen-hydrogen or oxygen-hydrogen bonds) and fewer than eleven hydrogen bond acceptors (e.g. nitrogen or oxygen atoms). Due to its fully in silico characteristics, this method can be applied to pure liquids that are still at the desktop design stage and not yet in production.

[Suna no utsuwa (Castle of Sand): A Film Concerning Hansen's Disease].

Hansen's disease (also known as leprosy) is a chronic infection that is caused by Mycobacterium leprae. It predominantly affects the peripheral nerves, skin, eyes, and nasal mucosa, Following the development of effective treatment with diaphenylsulfone followed by rifampicin, and clofazimine since 1940s, Hansen's disease has been eradicated in Japan. However, the longstanding stigma surrounding this disease, exacerbated partly by forced isolation and other regulations introduced in 1930s, has delayed the abrogation of these regulations. The influence of two Japanese films, namely Kojimanoharu (no English title; "Spring in Islets") (1940) and Casle of Sand (1974), inspired by these events and addressing the concerns regarding this disease, are discussed.

Nonsegmental vitiligo follows Blaschko's lines and embryonic pigmentary segments.

BACKGROUND: Pathogenic mechanism that determines the localization of vitiligo patches and thus a patterned distribution in patients with nonsegmental vitiligo has remained poorly elucidated. A distributional similarity of the vitiligo patches with Blaschko's lines has been documented in patients with segmental vitiligo, both isolated segmental vitiligo and mixed vitiligo but never in cases of nonsegmental vitiligo. METHODS: Distribution of nonsegmental vitiligo patches on face and neck regions was assessed and compared with Blaschko's lines and also with embryonic pigmentary segments on the face. RESULTS: This study has documented distributional similarity of the nonsegmental vitiligo patches on face and neck with Blaschko's lines and the "embryonic pigmentary segments" among 154 (58.6%) cases. Patches around the palpebral and other fissures like periorbital, perinasal, perioral, and periaural were more common. In addition to the vitiligo patches, the spared areas were also found to respect the embryonic segmental outlines and follow the Blaschko's lines. CONCLUSION: Distributional pattern of the individual nonsegmental vitiligo patches along the Blaschko's lines and embryonic pigmentary segments suggests that mosaicism might control the susceptibility to the disease process in a patterned manner. LIMITATION: No genetic testing could be performed to confirm the hypothesis. Evaluation of nonsegmental vitiligo was done only on the face and neck areas.

A morphometric and immunohistochemical study of melanocytes in periorbital hyperpigmentation.

BACKGROUND: An increase in number of melanocytes in the basal cell layer of the epidermis is an important feature in many disorders of hyperpigmentation. In this study, we attempted an objective evaluation of the linear density of melanocytes and keratinocytes, along with other epidermal characteristics, in periorbital hyperpigmentation using immunohistochemistry and morphometric techniques. METHODS: Melanocytes and epidermal parameters were assessed by digital morphometry in 30 newly diagnosed cases of periorbital hyperpigmentation and 14 controls from the post-auricular region. Melanocytes were labelled with the immunohistochemical stains, Melan-A and tyrosinase. We studied the linear keratinocyte density, mean linear melanocyte density, ratio of melanocytes to keratinocytes, the ratio between inner and outer epidermal length, maximum epidermal thickness and minimum epidermal thickness. RESULTS: Melan-A expression of melanocytes showed strong positive correlation (r=0.883) with the tyrosinase expression. Mean linear melanocyte density was 24/mm (range: 13-30/mm) in cases and 17/mm (13-21/mm) in controls and this difference was statistically significant (P<0.001). The mean ratio of melanocyte to keratinocyte was 0.22 (0.12-0.29) in cases and 0.16 (0.12-0.21) in controls; again, this difference was statistically significant (P<0.001). There was a mild negative correlation with linear keratinocyte density (r=-0.302) and the ratio between inner and outer epidermal length (r=-0.456). However, there were no differences in epidermal thicknesses. LIMITATIONS: There were fewer control biopsies than optimal, and they were not taken from the uninvolved periorbital region. CONCLUSION: Mean linear melanocyte density and the ratio of melanocytes to keratinocytes is increased in cases with periorbital hyperpigmentation. It is, therefore, likely that increased melanocyte density may be the key factor in the pathogenesis of periorbital hyperpigmentation.

Leproma conjuntival que simula tumor benigno / Conjunctival leproma which simulates benign neoplasm

La lepra es una patología infecto-contagiosa ocasionada por el Mycobacterium leprae, este alcanza el ojo por medio de diseminación hematógena o propagación por lesiones adyacentes. El 21 a 24% de los pacientes con la enfermedad pueden tener compromiso de la visión, el cual es más frecuente en la lepra multibacilar y 5% padecen ceguera. Las complicaciones más frecuentes son hipoestesia corneal (53%), cataratas (12,6%), opacidad corneal (10,5%), precipitados oculares (4,62%), paresia del músculo orbicular (4,62%), lagoftalmos (4,20%), degeneración del nervio corneal (1,68%), triquiasis (0,84%) y ectropión (0,42%), con pocos datos de incidencia de leproma ocular en estos estudios. En la literatura existen escasos reportes de lesiones oculares de presentación que simulan tumor, sin embargo se han reportado algunos casos de leproma ocular en diferentes localizaciones, corneal, escleral, cuerpo ciliar y limbo esclero-corneal; en el presente reporte se describe un caso de leproma conjuntival diagnosticado en Latinoamérica - Colombia. (MÉD.UIS. 2014;27(2):97-103).

Leprosy is an infectious pathology caused by Mycobacterium leprae and this reaches the eyes through haematogenous spread, or via adjacent injuries. Among 21-24% of the patients with the disease might develop visual injuries, which are more frequent in multibacillary leprosy and 5% suffer blindness. The most frequent complications of this condition are corneal hypoesthesia (53%), cataracts (12.6%), corneal opacity (10.5%), keratic precipitates (4.62%), orbicularis oculi weakness (4.62%), lagophthalmos (4.20%), corneal nerve beading (1.68%), trichiasis (0.84%) and ectropion (0.42%), with few data on the incidence of ocular leproma in these studies. There are few reports in ocular injuries that present tumor, nevertheless cases of ocular leproma have been reported in different sites (corneal , scleral, and limbo scleral); provided below a case of ocular leproma is described, this case was diagnose in Colombia in the south American region. (MÉD.UIS. 2014;27(2):97-103).

Lepra Ocular, conceptos actuales / An update in ocular Leproxy

Se cree que la lepra es la enfermedad sistemática con mayor incidencia de repercusión ocular, La afectación ocular se produce sobre todo en las formas lepromatosas. Las manifestaciones oculares son proteiformes y se relacionan con la invasión por el bacilo de las estructuras del segmento anterior y/o anejos, reacción inflamatoria y/o afectación neural de las estructuras oculares. La manifestación extraocular más frecuente es la madarosis de las cejas. La córnea es la parte más afectada del globo presentando una forma de queratitis patognomónica de localización temporal superior. En el iris aparecen también lesiones características como atrofia peripupilar aspecto atigrado y miosis insalvable por denervación. Es además característica la uveítis aguada y crónica. Las lesiones esclerales, son infrecuentes, aunque muy espectaculares. En el fondo de ojo solo se han descrito lesiones de forma esporádica

Leprosy the systemic disease with higher incidence of ocular findings. Eye disease is shown especially in lepromatous disease. Ocular complications are assorted and related to anterior segment and/or extraocular structures invasion by Mcobacterium leprae, inflammatory reaction, and nervous damage of the ocular structures. Superciliary madarosis is the most common extraocular finding. Cornea is the main affected structure of eye. There is a characteristic keratitis located in the superior temporal quadrant. The iris shows typical lesions like peripupilary atrophy, the pupil can be miotic and not responsive to mydriatics because of denervation. The scleral lesions are rare but amazing. Posterior segment lesions have been sporadically described

Pathogenesis of Dry eye in leprosy and tear functions

Seventy-five leprosy patients and an equal number of age- and sex-matched controls were examined for tear functions, using Schirmer's test and tear break up time (BUT). There was no statistically significant difference in the Schirmer's test, but the tear BUT showed a statistically significant lower value of < 10 seconds in multibacillary patients compared to paucibacillary patients. Leprosy patients with lagophthalmos and decreased corneal sensation showed a lower value of tear BUT which was also statistically significant. This study shows that even though the quantity of tears is not affected, proper and prolonged wetting of the cornea is deficient in many leprosy patients.

Pathology of a lepromatous eye.

Histopathological examination of an enucleated eye from a lepromatous leprosy patient showed the cornea, ciliary body, and part of the choroid to be infiltrated by macrophages filled with Mycobacterium leprae. The walls of blood vessels in the sclera, ciliary body and the anterior choroid demonstrated the presence of M. leprae, giving credence to the blood-borne entry of M. leprae into the eye. Unlike the eyes of experimental animals infected with M. leprae, histopathological study of this eye from a lepromatous leprosy patient demonstrated that M. leprae, although demonstrable in the anterior choroid, could not be found in the posterior parts of the eye, substantiating the claim that leprosy does not affect the posterior parts of the eye directly.

Estudo da variação da pressão intra-ocular postural e do tempo do ciclo pupilar na hanseníase / ?

Com o objetivo de estudar a variação da pressão intra-ocular postural e o tempo do ciclo pupilar em hansenianos de controle ambulatorial de um hospital universitário, foram selecionados voluntários sadios e pacientes paucibacilares e multibacilares. As medidas da pressão intra-ocular, realizadas com a tonometria de aplanação, demonstraram que as pressões intra-oculares médias na posição sentada, não apresentaram diferenças estatisticamente significativas entre os grupos estudados. As medidas realizadas na posição sentada e em decúbito dorsal imediato demonstraram que houve tendência à maior variação da pressão intra-ocular postural no grupo multibacilar, não havendo, entretando, significância estatística no achado; as medidas realizadas cinco minutos após a permanência na posição de decúbito dorsal demonstraram aumento siginificativo da pressão intra-ocular no grupo multibacilar. As medidas do tempo do ciclo pupilar, realizadas clinicamante na lâmpada de fenda, apresentaram-se mais prolongadas no grupo multibacilar, seguidas pelo paucibacilar e pelo controle, havendo diferenças estatíticamente significativas entre este e o multibacilar. Os achados podem sugerir comprometimento do sistema nervoso autônomo ocular, mas não foi observada correlação entre a variação da pressão intra-ocular postural e o tempo do ciclo pupilar na hanseníase.

Study of ocular changes in leprosy patients.

In this study, 997 leprosy patients were examined, 528 of them with lepromatous leprosy (53%), 199 with borderline leprosy (20%), 167 with tuberculoid leprosy (16%) and 103 (10.3%) with indeterminate leprosy. Changes in the ocular bulb were noted in 314 patients (31.5%) specially in those with lepromatous leprosy. These alterations were greater with increasing age of the patient and length of disease. Severe ocular lesions were rare, probably due to previous systemic treatment. The "pearls" in the fundus of the eye resulting from leprosy were also studied.