Cerebrolysin induces hair repigmentation associated to MART-1/Melan-A reactivation.

Hair graying, a prototypical sign of human aging, is a progressive loss of pigmentation from growing hair shafts caused by disease and as a side effect of medications. Cerebrolysin is a neuropeptide preparation that mimics the effect of endogenous neurotrophic factors. Cerebrolysin has been widely used in neurologic conditions, such as cerebral stroke, Alzheimer's disease, and dementia, among others. Cerebrolysin treatment has achieved to regain or maintain the cognitive ability of affected patients; however, up to date, there are no reports about the reactivation of hair pigmentation. We describe a previously not described effect occurring on patients receiving Cerebrolysin treatment for neurologic diseases and whether this effect is associated in reactivation of melanocytes and melanin expression. Here, we report five patients (mean age, 70.6 years), who also had age-related hair graying and scalp hair repigmentation during Cerebrolysin treatment. Macroscopic analysis revealed hair repigmentation consisted in diffuse darkening of the scalp hair. Impregnation and immunostaining analysis were performed on scalp biopsies taken before and after Cerebrolysin treatment; the results showed greater melanin and melanocyte marker MART-1/Melan-A staining following Cerebrolysin treatment. We present, to our knowledge, the first report on hair repigmentation is a previously not described effect occurring following Cerebrolysin treatment.

Association between the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants with vitiligo: study on a Mexican population

Abstract Background: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. Objective: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. Methods: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. Results: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). Conclusion: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.

Association between the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants with vitiligo: study on a Mexican population.

BACKGROUND: Vitiligo is characterized by an autoimmune response targeting melanocytes, thus resulting in skin depigmentation. There are several genetic components involved in the development of vitiligo, of which various gene polymorphisms are currently considered as risk factors. For example, the CTLA4 (T-lymphocyte antigen 4) +49A/G (rs231775) and CT60 (rs3087243) gene variants have been associated with a predisposition for autoimmune diseases in different populations; however, their involvement in the development of vitiligo remains controversial. OBJECTIVE: We evaluated the association between vitiligo and the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants in a Mexican population. METHODS: A total of 116 vitiligo patients and 117 control subjects from northeast Mexico were included in the study and analyzed through PCR-RFLP to determine whether there is an association between vitiligo and CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants. RESULTS: No statistical difference was observed for both gene polymorphisms between vitiligo patients and controls (p > 0.05). Otherwise, vitiligo activity, family history of vitiligo, personal history of autoimmune diseases, or sex did not show any difference (p > 0.05). CONCLUSION: As suggested by the analysis of a northeastern Mexican population, the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants do not constitute a risk factor in the development of vitiligo.

Expression of melanocortin 1 receptor before and after narrowband UVB phototherapy treatment in patients with stable vitiligo: A prospective study.

Vitiligo is a disease characterized by skin depigmentation caused by the selective destruction of melanocytes. The melanocortin system participates as a regulator of melanogenesis and skin pigmentation. Narrowband UVB phototherapy (nb-UVB) is currently considered to be the gold standard and first choice treatment method for vitiligo vulgaris. The aim of the present study was to analyze the clinical and biochemical parameters of vitiligo, as well as to determine the expression of proopiomelanocortin (POMC), melanocortin 1 receptor (MC1R) and melanocortin 4 receptor (MC4R) genes in the skin of patients with stable vitiligo receiving nb-UVB phototherapy. Patient clinical and biochemical parameters, and the skin biopsies of 22 patients with stable vitiligo were analyzed. These biopsies were obtained before and after nb-UVB phototherapy. The genetic expression analysis of POMC, MC1R and MC4R genes was performed via RNA-Sequence analysis. A statistical evaluation of the clinical and biochemical parameters, the degree of response to treatment and the expression profiles of the melanocortin system genes were performed to identify their association with treatment response. A two-sided P≤0.05 value was considered to indicate a statistically significant difference. Alterations were observed in the expression profiles of MC1R following nb-UVB phototherapy (P≤0.05). In addition, elevated levels of triiodothyronine were associated with a poor response to nb-UVB phototherapy. In conclusion the current study revealed that nb-UVB phototherapy altered the expression profile of the MC1R gene.

Onychomatricoma of the Nail Bed.

Onychomatricoma is a rare and specific benign tumor of the nail complex, with uncertain etiology. The avulsion of the nail plate reveals cavitations and orifices in its proximal extremity. These are associated with villous tumor formations generating digitiform projections at the nail matrix - typical intraoperative findings. We report a rare case of onychomatricoma in which the nail bed was predominantly affected and show evidence of its clinical, intraoperative, and histopathological presentation. The various descriptions of the disease report that its origin is restricted to the nail matrix, leading to secondary changes in the nail plate.

Evaluation of skin expression profiles of patients with vitiligo treated with narrow-band UVB therapy by targeted RNA-seq

Abstract: Background: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. Objective: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. Methods: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test. Results: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). Study limitations: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. Conclusion: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.

Evaluation of skin expression profiles of patients with vitiligo treated with narrow-band UVB therapy by targeted RNA-seq.

BACKGROUND: Vitiligo is characterized by a lack of pigmentation in the skin. To date, there are no studies that analyze the changes in gene expression in the skin of vitiligo patients in response to narrow-band ultraviolet B (nb-UVB) phototherapy treatment. OBJECTIVE: Explore the usefulness of new generation RNA sequencing in the identification of gene expression changes in the skin of vitiligo patients treated with nb-UVB phototherapy. METHODS: Four skin biopsies (4mm in diameter) were collected from 45 Mexican vitiligo vulgaris patients, 2 specimens before and 2 after treatment with nb-UVB phototherapy, obtained from pigmented and non-pigmented tissue. RNA extracted from the biopsies was analyzed using the Illumina TruSeq Targeted RNA Expression protocol to study the expression of genes that participate in pathways of skin homeostasis. The 2 groups were compared using Student's t-test and the Mann-Whitney U-test. RESULTS: The expression analysis identified differences in 12 genes included in this study after comparing the samples obtained before and after treatment: 5 genes involved in skin pigmentation, 2 genes involved in apoptosis, 2 genes involved in cell survival, 2 genes involved in oxidative stress responses and 1 gene involved in signal transduction mechanisms (p<0.05). STUDY LIMITATIONS: The small size of skin biopsies limits the amount of RNA obtained, the number of genes to be analyzed and the use of conventional techniques such as RT-qPCR. CONCLUSION: We demonstrated usefulness of new generation RNA sequencing in the identification of gene expression changes, in addition to identifying new targets in the study of vitiligo.

Necrose cutânea do tecido enxertado decorrente de tabagismo / Necrosis of skin graft entailed by smoking habits

A cicatrização adequada das feridas cirúrgicas é influenciada pela técnica operatória, pela presença de intercorrências pós-cirúrgicas e pelos hábitos de vida do paciente. Relatamos caso de paciente submetido a exérese de carcinoma basocelular por cirurgia micrográfica de Mohs e reconstrução com enxertia cutânea palpebral. No pós-operatório houve necrose do enxerto devido má perfusão do leito cirúrgico imputada ao tabagismo. O tabagismo interfere na embebição plasmática e neovascularização do enxerto, além de promover estresse oxidativo e disfunção endotelial. O cirurgião deve orientar a suspensão do tabagismo por pelo menos quatro semanas antes do procedimento, a fim de evitar maiores riscos de complicações.

Adequate healing of surgical wounds is influenced by the operative technique, the presence of postoperative complications, and the patient's life style. The authors of the present paper report the case of a patient who underwent excision of a basal cell carcinoma by Mohs micrographic surgery and reconstruction with palpebral skin grafting. The graft necrosed in the postoperative period due to poor perfusion of the surgical bed, correlated to smoking habits. Smoking interferes with plasma perfusion and graft neovascularization, and promotes oxidative stress and endothelial dysfunction. Surgeons should recommend the cessation of smoking for at least 4 weeks prior to the procedure in order to avoid further risks of complications.

CAPN3, DCT, MLANA and TYRP1 are overexpressed in skin of vitiligo vulgaris Mexican patients.

Vitiligo is a disorder causing skin depigmentation, in which several factors have been proposed for its pathogenesis: Environmental, genetic and biological aspects of melanocytes, even those of the surrounding keratinocytes. However, the lack of understanding of the mechanisms has complicated the task of predicting the development and progression. The present study used microarray analysis to characterize the transcriptional profile of skin from Vitiligo Vulgaris (VV) patients and the identified transcripts were validated using targeted high-throughput RNA sequencing in a broader set of patients. For microarrays, mRNA was taken from 20 skin biopsies of 10 patients with VV (pigmented and depigmented skin biopsy of each), and 5 biopsies of healthy subjects matched for age and sex were used as a control. A signature was identified that contains the expression pattern of 722 genes between depigmented vitiligo skin vs. healthy control, 1,108 between the pigmented skin of vitiligo vs. healthy controls and 1,927 between pigmented skin, depigmented vitiligo and healthy controls (P<0.05; false discovery rate, <0.1). When comparing the pigmented and depigmented skin of patients with vitiligo, which reflects the real difference between both skin types, 5 differentially expressed genes were identified and further validated in 45 additional VV patients by RNA sequencing. This analysis showed significantly higher RNA levels of calpain-3, dopachrome tautomerase, melan-A and tyrosinase-related protein-1 genes. The data revealed that the pigmented skin of vitiligo is already affected at the level of gene expression and that the main differences between pigmented and non-pigmented skin are explained by the expression of genes associated with pigment metabolism.

Trichoscopy of Dark Scalp.

Trichoscopy (dermoscopy of the hair and scalp) is a technique that improves diagnostic accuracy and follow-up with hair and scalp disorders. Although several studies of trichoscopy have been made in Caucasian and Asian populations, little has been published regarding trichoscopy findings in skin of color, despite the great prevalence of hair diseases in populations with this kind of skin. The aim of this review was to describe the trichoscopic features of normal scalp and of hair disorders in patients with dark skin phototypes. This will help dermatologists to distinguish between unique trichoscopic features of dark skin, and allow them to provide more accurate diagnoses and treatments for these patients.

Congenital Curved Nail of the Fourth Toe Associated with Oral Disorders.

Congenital curved nail of the fourth toe represents an unusual deformity in which the nail of the fourth toe curves in a plantar direction. It is unknown why only this toe is affected; however, the initial descriptions suggest that this is a mesodermal defect. We describe a case of congenital curved nail of the fourth toe associated with bifid uvula. There are only 2 reports mentioning the association of this nail abnormality with cleft palate and/or lip. In our patient, there was an association with bifid uvula that is considered a minor form of palatine fissure. There seems to be an association of congenital curved nail of the fourth toe with cleft palate to different degrees; however, the pathogenesis of the deformity remains unknown.

Ecthyma gangrenosum: a report of eight cases.

Ecthyma gangrenosum is a rare skin infection classically associated with Pseudomonas aeruginosa. We performed a retrospective study of all cases diagnosed with ecthyma gangrenosum from 2004-2010 in a university hospital in Mexico (8 cases, 5 female patients and 3 male patients, ages between 4 months and 2 years). The most common risk factor for ecthyma gangrenosum is neutropenia in immunocompromised patients. In previously healthy patients, immunological evaluation is important to rule out underlying immunodeficiency. Ecthyma gangrenosum in healthy patients has a high mortality rate and early diagnosis and aggressive antibiotic treatment is imperative as it can improve patients' prognosis.

Macrophage subtypes in recurrent nodular basal cell carcinoma after Mohs micrographic surgery.

BACKGROUND: The macrophages associated with solid tumors are related to the progression or regression of tumors, depending on the differentiation in M1 or M2. M2 subtype promotes angiogenesis, remodeling, and tissue repair (tumor proliferation). In contrast, M1 produces toxic mediators and presents antigens, destroying microorganisms and tumor cells. The microenvironment of most aggressive forms of basal cell carcinoma (BCC) shows an increase in macrophages due to M2 phenotype compared to noninvasive forms. The treatment of nodular BCC by Mohs micrographic surgery (MMS) provides high cure rates, but relapses can occur. AIMS: To compare the total population of macrophages and their subpopulations M1 and M2 in cases of recurrent and nonrecurrent nodular BCC after excision by MMS. MATERIALS & METHODS: Histological sections obtained from paraffin blocks of nine cases of recurrent nodular BCC after MMS and 18 cases of nonrecurrent nodular BCC operated by MMS were immunostained for iNOS, CD204, CD163, and CD68. The expression of these markers was analyzed by image analysis. RESULTS: No significant differences were found between the groups in relation to the average percentage of M1 cells, M2 cells, and total cells. DISCUSSION AND CONCLUSION: A relationship was not seen between tumor-associated macrophages (TAM) and tumor recurrence.

Ecthyma gangrenosum: a report of eight cases

Abstract: Ecthyma gangrenosum is a rare skin infection classically associated with Pseudomonas aeruginosa. We performed a retrospective study of all cases diagnosed with ecthyma gangrenosum from 2004-2010 in a university hospital in Mexico (8 cases, 5 female patients and 3 male patients, ages between 4 months and 2 years). The most common risk factor for ecthyma gangrenosum is neutropenia in immunocompromised patients. In previously healthy patients, immunological evaluation is important to rule out underlying immunodeficiency. Ecthyma gangrenosum in healthy patients has a high mortality rate and early diagnosis and aggressive antibiotic treatment is imperative as it can improve patients' prognosis.