Vitiligo surgical, laser, and alternative therapies: a review and case series.

INTRODUCTION: Vitiligo is a condition caused by the destruction of melanocytes, resulting in areas of skin without pigmentation. While many topical therapies exist for its treatment, not all patients respond to such treatments. Various surgical, laser and other alternative therapies are available for use as well. OBJECTIVE: The objective of this review was to describe the various surgical, laser, and alternative therapies available for vitiligo. A literature review was conducted through Pubmed and Ovid using the search terms "Vitiligo treatment", "Vitiligo surgery", "Vitiligo laser". Since no articles were available about needling on both Pubmed and Ovid using the search criteria, individual articles were sought out through Google. RESULTS: The literature review yielded many possible surgical interventions including autologous mini-punch grafting, suction epidermal blister grafting, split-thickness grafting, and cultured and noncultured melanocyte keratinocyte transfer. Laser options included the helium-neon and xenon-chloride lasers, with tattooing and needling serving as other options. While all the above techniques can provide improvement to pigmentation in vitiliginous patches, physician comfort and experience are important factors with regards to outcome. Our case series of four patients treated with the needling method yielded favorable results, with repigmentation rates ranging from 25-50%, with one patient having 90% repigmentation. CONCLUSION: There are many surgical, laser, and alternative treatment options available for vitiligo when conventional medical therapy fails or for use in conjunction with medical therapies. Autologous mini punch grafting and needling both have minimal equipment requirements and are easy to learn. Physician experience and comfort play a large role in outcome and availability of services.

Adalimumab for the treatment of pityriasis rubra pilaris: a case report.

Pityriasis rubra pilaris (PRP) is a chronic papulosquamous eruption of the skin characterized by follicular hyperkeratosis, salmon pink scaly plaques with islands of unaffected skin, and palmoplantar keratoderma. Widely used oral systemic and topical treatments are not greatly effective. We present a 62-year-old man with PRP of 2 years' duration who used routine topical treatments, oral retinoids, and UV therapy without improvement, but his symptoms greatly improved with the initiation of adalimumab.

Racial disparities in the management of skin ulcers: an analysis of the National Ambulatory Medical Care Survey, 2012-2018.

PURPOSE: Racial/ethnic differences in health care are pervasive in the USA, but the literature is limited with regards to racial disparities in the treatment of dermatologic diseases. MATERIALS AND METHODS: Data on the management of skin ulcers was analyzed from the National Ambulatory Medical Care Survey (NAMCS) from 2012 to 2018. Data distributions between Blacks and Whites, chi-squared statistics, and Fisher Exact Tests were computed to identify significant differences in demographic factors, patient encounter characteristics, and medication prescribed, as a function of race. RESULTS: Blacks were less likely than Whites to receive: care by a physician (p = .0389), a skin examination (p < .0001), or cryotherapy (p < .0175). Blacks were more likely to be seen by a nurse practitioner (p = .0359). Whites were 6.698 times more likely than Blacks to have a follow up visit scheduled after 2 months or more. CONCLUSIONS: Our data suggests that among outpatient visits for skin ulcers in the USA, racial disparities exist in the probability of seeing a physician, receiving treatment, and follow-up care. Further research must be conducted and interventions implemented in order to combat racial disparities in Black patients' access to dermatologic treatment for skin ulcers.

Characterization of human adult stem-cell populations isolated from visceral and subcutaneous adipose tissue.

Adipose tissue is a dynamic endocrine organ with a central role in metabolism regulation. Functional differences in adipose tissue seem associated with the regional distribution of fat depots, in particular in subcutaneous and visceral omental pads. Here, we report for the first time the isolation of human adipose-derived adult stem cells from visceral omental and subcutaneous fat (V-ASCs and S-ASCs, respectively) from the same subject. Immunophenotyping shows that plastic culturing selects homogeneous cell populations of V-ASCs and S-ASCs from the corresponding stromal vascular fractions (SVFs), sharing typical markers of mesenchymal stem cells. Electron microscopy and electrophysiological and real-time RT-PCR analyses confirm the mesenchymal stem nature of both V-ASCs and S-ASCs, while no significant differences in a limited pattern of cytokine/chemokine expression can be detected. Similar to S-ASCs, V-ASCs can differentiate in vitro toward adipogenic, osteogenic, chondrogenic, muscular, and neuronal lineages, as demonstrated by histochemical, immunofluorescence, real-time RT-PCR, and electrophysiological analyses, suggesting the multipotency of such adult stem cells. Our data demonstrate that both visceral and subcutaneous adipose tissues are a source of pluripotent stem cells with multigermline potential. However, the visceral rather than the subcutaneous ASC could represent a more appropriate in vitro cell model for investigating the molecular mechanisms implicated in the pathophysiology of metabolic disorders such as obesity.

A new mechanism involving ERK contributes to rosiglitazone inhibition of tumor necrosis factor-alpha and interferon-gamma inflammatory effects in human endothelial cells.

OBJECTIVE: Microvascular endothelium is one of the main targets of the inflammatory response. On specific activation, endothelial cells recruit Th1-lymphocytes at the inflammatory site. We investigated the intracellular signaling mediating tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma inflammatory response in human microvascular endothelial cells (HMEC-1) and the interfering effects of the peroxisome-proliferator-activated-receptor (PPARgamma) agonist, rosiglitazone (RGZ). METHODS AND RESULTS: TNFalpha and IFNgamma, mainly when combined, stimulate IFNgamma-inducible protein of 10 kDa (IP10) and fractalkine production evaluated by ELISA and TaqMan analyses. This effect is not only mediated by activation of the NFkB and Stat1 classic pathways, but also involves a rapid increase in phosphorylation and activation of extracellular signal-regulated kinases (ERK1/2) as measured by Western blot. RGZ interferes with TNFalpha and IFNgamma stimulation of IP10, fractalkine, and adhesion molecule through a novel rapid mechanism which involves the blocking of ERK activation. CONCLUSIONS: Our findings shed new light on the mechanisms underlying the inflammatory response of microvascular endothelium and on the possible therapeutic use of RGZ in vasculopathies involving Th1-responses.

Telemedicine: current status in developed and developing countries.

BACKGROUND: Many developed countries, including the United States, have made it a priority to incorporate telemedicine into their healthcare systems. Worldwide, this concept has been adopted by countries in effort to provide better healthcare for those in rural areas where hospitals may be at a distance and specialists may be even farther. Previous studies and reports have shown that the use of telemedicine, especially tele-dermatology, has proven to be an inexpensive method for providing care to those whose countries face financial, social, and environmental barriers to adequate healthcare. OBJECTIVE: To assess the current status of, and address the potential for, improving healthcare by using telemedicine with emphasis on tele-dermatology in developed and developing countries. METHODS: Current literature on telemedicine/tele-dermatology was reviewed and its efficiency critiqued in an attempt to improve dermatological care in developing areas. CONCLUSION: The U.S., while significantly incorporating telemedicine on a national basis, faces various issues from state to state regarding reimbursement and other legality concerns. Although current efforts using telemedicine have demonstrated positive effects in countries in need, they have not substantially reduced or compensated for a fundamental lack of healthcare. Countries with inadequate healthcare must incorporate telemedicine into their healthcare system through volunteer efforts of doctors in countries worldwide.

Src activation triggers capacitation and acrosome reaction but not motility in human spermatozoa.

BACKGROUND: Protein tyrosine phosphorylation is one of the main processes associated with sperm activation. Although this process and its targets have been well characterized, only few tyrosine kinases have been identified so far and their roles in spermatozoa are still largely unknown. In this study, we report the presence and localization of Src kinase in ejaculated human spermatozoa and investigate its role in regulating the processes underlying sperm activation. METHODS AND RESULTS: Specific anti-Src antibodies, against different epitopes of the protein, identified a single band of approximately 70 kDa relating to a protein which is mainly localized in the post-acrosomal region of the head, neck and midpiece. By immunoprecipitation and immunofluorescence techniques performed with antibodies against Src phosphorylated at Tyr416, which identifies the active kinase, we showed an increased phosphorylation during sperm capacitation. Blocking Src activity with SU6656 resulted in a significant reduction in the protein tyrosine phosphorylation. Moreover, this inhibitor also blocked the progesterone-induced acrosome reaction and interfered with the calcium response to progesterone evaluated in fura-2-loaded spermatozoa. No effect on sperm motility and hyperactivation resulted from incubation with SU6656. CONCLUSIONS: We identified a novel Src isoform in human spermatozoa, which appears to be involved in regulating sperm capacitation, calcium fluxes, tyrosine phosphorylation and acrosome reaction.

Peroxisome-proliferator-activated receptor gamma (PPARgamma) is required for modulating endothelial inflammatory response through a nongenomic mechanism.

Besides their well-known anti-diabetic effects, the peroxisome-proliferator-activated receptor gamma (PPARgamma) thiazolidinedione ligands (TZD) have been suggested to also display anti-inflammatory properties. The receptor role in mediating such effects is far from being elucidated. Here, we demonstrated that PPARgamma is necessary for TZD to interfere with TNFalpha and IFNgamma inflammatory activity in human endothelial cells. Different PPARgamma ligands similarly inhibit cytokinic stimulation of IFNgamma-inducible-protein-of-10-kDa (IP10) secretion in a dose-dependent manner and prevent the induced phosphorylation/activation of extracellular-signaling-regulated-kinases (ERK1/2). To further confirm the PPARgamma role in mediating both rapid and long term anti-inflammatory effects of its ligands, we evaluated RGZ inhibitory action in PPARgamma-silenced and -overexpressing cells. PPARgamma-silencing results in a reversion of RGZ inhibitory activity on cyto/chemokine secretions and rapid ERK phosphorylation. Conversely, receptor overexpression significantly increases RGZ inhibitory activity. Finally, PPARgamma-overexpression results in a reduction of ERK1/2 phosphorylation and inflammatory secretions in response to TNFalpha and IFNgamma even in the absence of RGZ, suggesting a restraining effect controlled by endogenous ligands. In conclusion, our data provide the first evidence that PPARgamma is involved in the anti-inflammatory action of TZD in endothelial cells, not only by modulating cyto/chemokine secretions but also by restraining ERK activation through a novel rapid nongenomic mechanism.

Rosiglitazone impairs proliferation of human adrenocortical cancer: preclinical study in a xenograft mouse model.

Adrenocortical carcinoma (ACC) is a rare aggressive tumor with a poor prognosis. The lack of a specific and effective medical treatment is due to the poor knowledge of the mechanisms underlying tumor growth. Research on potential drugs able to specifically interfere with tumor proliferation is essential to develop more efficacious therapies. We evaluated for the first time the in vivo effect of rosiglitazone (RGZ), an anti-diabetic drug with in vitro anti-tumor properties, on ACC proliferation in a xenograft model obtained by s.c. injection of human ACC H295R cells in athymic mice. When the tumor size reached 5 mm, animals were allocated to 5 mg/kg RGZ- or water-treated groups. Tumor volume was measured twice a week. A significant reduction of tumor growth in RGZ versus control (control) group was observed and was already maximal following 17 day treatment (1-T/C=75.4% (43.7-93.8%)). After 31 days of treatment, mice were killed and tumor analyzed. Tumor histological evaluation revealed characteristics of invasiveness, richness in small vessels and mitotic figures in control group, while RGZ group tumors presented non infiltrating borders, few vessels, and many apoptotic bodies. Tumor immunohistochemistry showed that Ki-67 was reduced in RGZ versus control group. Quantitative real-time RT-PCR demonstrated a significant reduction in the expression of angiogenic (VEGF), vascular (CD31), proliferation (BMI-1), and anti-apoptotic (Bcl-2) genes in RGZ versus control group tumors. The same inhibitory effects were confirmed in in vitro RGZ-treated H295R. Our findings support and expand the role of RGZ in controlling ACC proliferation and angiogenesis in vivo and in vitro.

Molecular mechanisms underlying the pro-inflammatory synergistic effect of tumor necrosis factor alpha and interferon gamma in human microvascular endothelium.

Tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) are among the most potent cytokines involved in orchestrating the inflammation response. The molecular mechanisms implicated in the synergism between cytokines are still poorly characterized. We demonstrate that both cytokines dose-dependently stimulate IFNgamma-inducible-protein-of-10-kDa (IP-10) secretion in human microvascular endothelial cells (HMEC-1), showing a potent synergism which is not restricted to IP-10, but is also evident for monokine-induced-by-IFNgamma (MIG) and IL-6 secretion. Immunofluorescence analysis reveals that TNFalpha and IFNgamma converge on a rapid phosphorylation of ERK, which however results in a different subcellular compartmentalization of the activated enzyme in response to the two cytokines. Differences in the subcellular recruitment of ERK in response to IFNgamma and TNFalpha are responsible for generating different ERK downstream signaling, which can thus synergize on the secretion of IP-10 as well as of other cytokines/chemokines. The importance of ERK activation in mediating the synergism of the two cytokines is further confirmed by the inhibitory effect of the anti-diabetic drug rosiglitazone and ERK blockers on IP-10, MIG and IL-6 secretion. A further mechanism of synergism involving the reciprocal upregulation of TNFalpha-RII and of IFNgamma-R, in response to IFNgamma and TNFalpha, respectively, was revealed by flow cytometry and quantitative real time RT-PCR analysis.

Rosiglitazone inhibits adrenocortical cancer cell proliferation by interfering with the IGF-IR intracellular signaling.

Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-gamma, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R) of human adrenocortical carcinoma (ACC) and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR). We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K)-Akt, and extracellular signal-regulated kinase (ERK1/2) cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR.

Avaliação da transferência de imunidade passiva em cordeiros com até 30 dias de idade / Passive transfer immunity valuation in lambs with until 30 days of life

O objetivo deste estudo foi determinar as concentrações séricas de imunoglobulina G, PT e de sua fração eletroforética gama globulina, assim como a atividade enzimática de GGT e ALP. Estabeleceu-se a possibilidade da atividade destas enzimas ser utilizada indiretamente como indicadoras de um adequado nível de proteção humoral e/ou como falha de transferência de imunidade passiva em cordeiros. Foi pesquisada a correlação entre as variáveis em quatro grupos de idade divididos em até 30 dias de vida. Para tanto, foram coletadas 191 amostras de sangue de cordeiros em 21 propriedades da região de Araçatuba - São Paulo. Realizaram-se os testes de imunodifusão radial, espectrofotometria e eletroforese para obtenção dos valores de IgG, PT e γ globulina, respectivamente. Para os valores da atividade de GGT e ALP, foram utilizados kits comerciais. Notou-se correlação significativa entre ALP e GGT, fato observado também com PT, IgG e GGT. A gama-globulina mostrou-se correlacionada com GGT, IgG e PT. A atividade de FA não deve ser utilizada como indicadora de transferência de imunidade passiva em cordeiros.

The aim of this study was to determine the serum concentrations of immunoglobulin G, TP and the gamma globulin electrophoretic fraction, as well as the enzymatic activities of GGT and ALP. This was done in order to explore the possibility of using changes in activities of these enzymes as indirect indicators of adequate humoral immunity and/ or failure of immune passive transfer in lambs. Pearson correlation was performed between variable of four groups of age during the first 30 days of life. Blood samples (191) from lambs from 21 different farms in Araçatuba region- São Paulo. The following tests were perfomed: radial immunodiffusion, spectrophotometry and electrophoresis to stain the amount of IgG, TP and gamma globulin, respectively. GGT and ALP values were determinate using commercial kits. There was a statistically significant correlation between ALP and GGT. The same correlation was observed from TP, IgG and GGT. A positive gamma globulin correlation was found between GGT, IgG and TP. ALP activity cannot be used as an indicator of immune passive transfer.