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1.
Anim Genet ; 50(5): 543-545, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31294848

RESUMO

An eight-week old Doberman Pinscher was diagnosed with Ehlers Danlos syndrome based on the dog's hyper-mobile carpal, tarsal and stifle joints and abnormal skin. The skin was loose and hyper-elastic with several wounds and large atrophic scars. The dog was euthanized after a severe degloving injury from minimal trauma. A whole-genome sequence, generated with DNA from the dog's blood, contained a rare, homozygous C-to-T transition at position 2408978 on chromosome 11. This transition is predicted to alter the ADAMTS2 transcript (ADAMTS2:c.769C>T) and encode a nonsense mutation (p.Arg257Ter). Biallelic ADAMTS2 mutations have caused a type of Ehlers Danlos syndrome known as dermatosparaxis in other species.


Assuntos
Proteínas ADAMTS/genética , Doenças do Cão/genética , Síndrome de Ehlers-Danlos/veterinária , Dermatopatias/veterinária , Animais , Cães , Síndrome de Ehlers-Danlos/genética , Dermatopatias/genética
3.
Ann Hematol ; 98(7): 1617-1626, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30923995

RESUMO

Langerhans cell histiocytosis (LCH) is a clonal histiocytic disorder with recurrent mutations of BRAF and MAP2K1, but data on the impact of genetic features on progression and long-term sequelae are sparse. Cases of pediatric LCH with long-term follow-up from our institution were analyzed for mutations in BRAFV600 and MAP2K1 exons 2 and 3 by immunostaining with mutation-specific VE1 antibody, as well as allele-specific PCR and sequencing, respectively. Clinical and follow-up data were obtained from our files and a questionnaire sent to all former patients. Sixteen of 37 (43%) evaluable cases showed BRAFV600E, one case a BRAFV600D and eleven (30%) a MAP2K1 mutation. Nine cases were unmutated for both genes. All cases with risk organ involvement showed either BRAFV600 or MAP2K1 mutation. Patients with BRAFV600 mutation excluding Hashimoto-Pritzker cases had a significantly higher risk for relapses (p = 0.02). Long-term sequelae were present in 19/46 (41%) patients (median follow-up 12.5 years, range 1.0 to 30.8) with a trend for higher rates in mutated cases (mutated = 9/17, 53% versus non-BRAFV600/MAP2K1 mutated = 2/7, 29%). In addition, 8/9 cases with skin involvement including all Hashimoto-Pritzker cases (n = 3) were positive for BRAFV600E. Infants below 2 years more frequently had BRAFV600 mutations (p = 0.013). Despite favorable prognosis, pediatric LCH shows a high frequency of relapses and long-term medical sequelae.


Assuntos
Histiocitose de Células de Langerhans/genética , MAP Quinase Quinase 1/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Histiocitose de Células de Langerhans/epidemiologia , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/terapia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , Dermatopatias/epidemiologia , Dermatopatias/genética , Dermatopatias/patologia , Dermatopatias/terapia
4.
PLoS Genet ; 15(3): e1007984, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30893314

RESUMO

Inorganic arsenic (iAs) is a carcinogen, and exposure to iAs via food and water is a global public health problem. iAs-contaminated drinking water alone affects >100 million people worldwide, including ~50 million in Bangladesh. Once absorbed into the blood stream, most iAs is converted to mono-methylated (MMA) and then di-methylated (DMA) forms, facilitating excretion in urine. Arsenic metabolism efficiency varies among individuals, in part due to genetic variation near AS3MT (arsenite methyltransferase; 10q24.32). To identify additional arsenic metabolism loci, we measured protein-coding variants across the human exome for 1,660 Bangladeshi individuals participating in the Health Effects of Arsenic Longitudinal Study (HEALS). Among the 19,992 coding variants analyzed exome-wide, the minor allele (A) of rs61735836 (p.Val101Met) in exon 3 of FTCD (formiminotransferase cyclodeaminase) was associated with increased urinary iAs% (P = 8x10-13), increased MMA% (P = 2x10-16) and decreased DMA% (P = 6x10-23). Among 2,401 individuals with arsenic-induced skin lesions (an indicator of arsenic toxicity and cancer risk) and 2,472 controls, carrying the low-efficiency A allele (frequency = 7%) was associated with increased skin lesion risk (odds ratio = 1.35; P = 1x10-5). rs61735836 is in weak linkage disequilibrium with all nearby variants. The high-efficiency/major allele (G/Valine) is human-specific and eliminates a start codon at the first 5´-proximal Kozak sequence in FTCD, suggesting selection against an alternative translation start site. FTCD is critical for catabolism of histidine, a process that generates one-carbon units that can enter the one-carbon/folate cycle, which provides methyl groups for arsenic metabolism. In our study population, FTCD and AS3MT SNPs together explain ~10% of the variation in DMA% and support a causal effect of arsenic metabolism efficiency on arsenic toxicity (i.e., skin lesions). In summary, this work identifies a coding variant in FTCD associated with arsenic metabolism efficiency, providing new evidence supporting the established link between one-carbon/folate metabolism and arsenic toxicity.


Assuntos
Amônia-Liases/genética , Arsênico/toxicidade , Glutamato Formimidoiltransferase/genética , Metiltransferases/genética , Adulto , Alelos , Amônia-Liases/fisiologia , Arsênico/metabolismo , Intoxicação por Arsênico , Bangladesh , Exposição Ambiental , Feminino , Ácido Fólico/metabolismo , Frequência do Gene/genética , Glutamato Formimidoiltransferase/fisiologia , Humanos , Masculino , Metilação , Metiltransferases/metabolismo , Mutação de Sentido Incorreto , Razão de Chances , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Dermatopatias/induzido quimicamente , Dermatopatias/genética , Poluentes Químicos da Água
5.
Int J Mol Sci ; 20(3)2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717203

RESUMO

Ozone therapy has been widely used in everyday clinical practice over the last few years, leading to significant clinical results in the treatment of herniated discs and pain management. Nevertheless, further studies have demonstrated its potential efficacy and safety under other clinical and experimental conditions. However, some of these studies showed controversial results regarding the safety and efficacy of ozone therapy, thus mining its potential use in an everyday clinical practice. To this regard, it should be considered that extensive literature review reported the use of ozone in a significant different dose range and with different delivery systems. The aim of the present review is to describe the various pharmacological effects of ozone in different organs and clinical conditions and to provide possible biochemical and molecular insights for ozone biological properties, thus providing a possible explanation for various controversial clinical outcomes described in the scientific literature.


Assuntos
Doenças Cardiovasculares/terapia , Degeneração do Disco Intervertebral/terapia , Deslocamento do Disco Intervertebral/terapia , Ozônio/administração & dosagem , Dor/prevenção & controle , Substâncias Protetoras/administração & dosagem , Dermatopatias/terapia , Doença Aguda , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Quimiotaxia/efeitos dos fármacos , Quimiotaxia/imunologia , Doença Crônica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/imunologia , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/imunologia , Degeneração do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/imunologia , Deslocamento do Disco Intervertebral/patologia , Estresse Oxidativo , Ozônio/efeitos adversos , Dor/genética , Dor/imunologia , Dor/patologia , Manejo da Dor/métodos , Substâncias Protetoras/efeitos adversos , Dermatopatias/genética , Dermatopatias/imunologia , Dermatopatias/patologia
6.
Expert Rev Gastroenterol Hepatol ; 13(4): 307-317, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30791773

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently observed and involve the joints, eyes, hepatobiliary tract, and skin. Areas covered: In this review, we discuss classical EIM focusing on epidemiology, genetics, and pathogenesis, highlighting recent advances in the understanding of EIM. We further discuss treatment-induced immunological phenomena, which are increasingly recognized and might challenge IBD-treating physicians in the era of biological treatment. Expert opinion: EIM considerably contributes to morbidity and mortality. Genetic studies have revealed a common genetic background between EIM and IBD and among specific EIM. Identified protein interactions have been shown to cluster in shared biological pathways. However - despite these recent advances - pathogenesis of EIM is at best partially understood. Several pathogenic mechanisms have been proposed such as upregulation of tumor necrosis factor, aberrant lymphocyte homing, and cross-reactive antigen presentation. It still remains unclear whether EIM is a direct result of the inflammatory process in the gut or rather a consequence of a shared genetic background leading to dysfunctional immune responses to environmental stimuli. Exploration and understanding of EIM genetics and pathophysiology will pave the road for better and more efficacious treatment options in the future.


Assuntos
Doenças do Sistema Digestório , Oftalmopatias , Doenças Inflamatórias Intestinais , Artropatias , Dermatopatias , Doenças do Sistema Digestório/epidemiologia , Doenças do Sistema Digestório/genética , Doenças do Sistema Digestório/imunologia , Doenças do Sistema Digestório/terapia , Oftalmopatias/epidemiologia , Oftalmopatias/genética , Oftalmopatias/imunologia , Oftalmopatias/terapia , Predisposição Genética para Doença , Humanos , Imunossupressores/efeitos adversos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Artropatias/epidemiologia , Artropatias/genética , Artropatias/imunologia , Artropatias/terapia , Fenótipo , Prognóstico , Medição de Risco , Fatores de Risco , Dermatopatias/epidemiologia , Dermatopatias/genética , Dermatopatias/imunologia , Dermatopatias/terapia
7.
J Sci Food Agric ; 99(9): 4200-4210, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30767231

RESUMO

BACKGROUND: Equol is a major isoflavone metabolite, and equol-producing bacteria have been isolated and characterized; however, fermentation has been performed with soybean-based products as substrates. Pueraria lobata has been reported as a plant with higher content of isoflavones. RESULTS: The genome of new equol-producing bacteria, Lactobacillus paracasei JS1, was analyzed. Also, the effect of P. lobata extract fermented with L. paracasei JS1 (FPE) on the skin and intestinal immune response was examined. With gene expression analysis, it was proven that seven skin-related proteins, hyaluronan synthase-1, -2, -3, collagen, elastin, epidermal growth factor, and epidermal growth factor receptor were differentially expressed upon FPE treatment. The messenger RNA expression increased with treatment with the FPE, and a skin moisturizing effect was confirmed by a hematoxylin-eosin staining experiment. In addition, such an experiment showed that proinflammatory cytokines, tumor necrosis factor-α, cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1ß, -4, and -6, were reduced in large intestine when treated with FPE. CONCLUSION: L. paracasei JS1 has the ability to produce equol having beneficial effects on the skin. Moreover, FPE also has an inhibitory effect on inflammation cytokines in the large intestine. Thus, the novel and edible equol-producing L. paracasei JS1 and FPE have thepotential to be developed as nutricosmetic resources. © 2019 Society of Chemical Industry.


Assuntos
Equol/metabolismo , Enteropatias/prevenção & controle , Lactobacillus paracasei/metabolismo , Probióticos/administração & dosagem , Dermatopatias/prevenção & controle , Animais , Colágeno/genética , Colágeno/metabolismo , Elastina/genética , Elastina/metabolismo , Fermentação , Humanos , Hialuronan Sintases/genética , Hialuronan Sintases/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Enteropatias/genética , Enteropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Dermatopatias/genética , Dermatopatias/metabolismo
9.
Seizure ; 65: 25-30, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30599396

RESUMO

PURPOSE: To determine genetic associations between oxcarbazepine (OXC)-induced cutaneous adverse drug reactions (cADRs) and human leukocyte antigen (HLA) variants in the Eastern Han Chinese population. METHODS: A total of 120 patients were enrolled in this study, including 30 subjects with OXC-induced cADRs (case group) and 90 OXC-tolerant patients (control group). High-resolution HLA genotyping was conducted for HLA-A, HLA-B, HLA-C, and HLA-DRB1, and allele frequencies were compared. RESULTS: No patient carried the HLA-B *1502 allele in the case group, the frequency of HLA-B *1502 allele in the control group was 6.1%. HLA-A*3201 allele was detected in 13.3% of 30 patients with OXC-induced cADRs (4/30) and 0% of 90 OXC-tolerant patients (0/90). The difference in HLA-A*3201 frequency between the two groups was statistically significant [P = 0.004, odds ratio (OR) = 15.877, 95% confidence interval (CI) = 1.817-138.720]. CONCLUSIONS: Eastern Han Chinese patients with the HLA-A*3201 allele may be more susceptible to OXC-induced cADRs, while the HLA-B*1502 allele is not correlated with it. The precise association between HLA alleles and OXC-induced cADRs warrants further study.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Antígenos HLA-A/genética , Oxcarbazepina/efeitos adversos , Dermatopatias/induzido quimicamente , Dermatopatias/genética , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Epilepsia/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Antígenos HLA-A/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Genes Dev ; 33(1-2): 55-60, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30567998

RESUMO

Polycomb-repressive complex 1 (PRC1) and PRC2 are critical chromatin regulators of gene expression and tissue development. Here, we show that despite extensive genomic cobinding, PRC1 is essential for epidermal integrity, whereas PRC2 is dispensable. Loss of PRC1 resulted in blistering skin, reminiscent of human skin fragility syndromes. Conversely, PRC1 does not restrict epidermal stratification during skin morphogenesis, whereas PRC2 does. Molecular dissection demonstrated that PRC1 functions with PRC2 to silence/dampen expression of adhesion genes. In contrast, PRC1 promotes expression of critical epidermal adhesion genes independently of PRC2-mediated H3K27me3. Together, we demonstrate a functional link between epigenetic regulation and skin diseases.


Assuntos
Células Epidérmicas/fisiologia , Epiderme/fisiologia , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Complexo Repressor Polycomb 1/metabolismo , Complexo Repressor Polycomb 2/metabolismo , Dermatopatias/genética , Animais , Adesão Celular/genética , Epiderme/crescimento & desenvolvimento , Histonas/metabolismo , Camundongos , Complexo Repressor Polycomb 1/genética , Dermatopatias/fisiopatologia
11.
Clin Exp Dermatol ; 44(1): 47-51, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29845638

RESUMO

BACKGROUND: Mid-dermal elastolysis (MDE) is a rare skin condition, characterized by selective loss of elastic fibres in the mid dermis. The pathogenesis of MDE is still unclear. AIM: To investigate expression of lysyl oxidase-like 2 (LOXL2) in a reasonable sample of patients with MDE and to search for mutations in LOXL2. METHODS: We investigated archived lesional tissue of 13 patients with MDE and skin tissue samples of 10 sex- and age-matched healthy controls (HCs). Gene and protein expression of LOXL2 was investigated using real-time reverse-transcription PCR and immunohistochemistry. Mutation analysis was performed using the Sanger method. RESULTS: We observed decreased LOXL2 mRNA expression in lesional skin of patients with MDE (0.48 ± 0.16) compared with healthy skin of the same patients (1.5 ± 0.51) and normal skin of HCs (1.9 ± 0.13). Compared with healthy patient skin (epidermis 2.38 ± 1.6, dermis 1.2 ± 1), LOXL2 protein expression in lesional patient skin (epidermis 1.1 ± 0.7, dermis 0.3 ± 0.45) was significantly decreased (P < 0.04 and P = 0.02, respectively). Mutation analysis of the entire LOXL2 gene could be performed for five patients, all of whom were found to have at least one mutation in the LOXL2 gene. Three of these had a mutation in the promoter region (c.967 G>C, c.1022 C>T, and c.1025 G>A, respectively), and one of them also had a mutation in the splice region of intron 11/exon 12 (IVS11-1 G>A). Of the remaining two patients, one had a mutation in exon 3 (T1391), and the other had a mutation in exon 11 (C663Y). CONCLUSIONS: Our present data suggest that decreased elastin renewal due to LOXL2 mutations and consecutive reduced LOXL2 expression contribute to the pathogenesis of MDE.


Assuntos
Aminoácido Oxirredutases/genética , Elastina/metabolismo , RNA Mensageiro/metabolismo , Dermatopatias/genética , Pele/patologia , Tecido Elástico/patologia , Tecido Elástico/fisiopatologia , Predisposição Genética para Doença , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Dermatopatias/metabolismo
12.
N Engl J Med ; 379(26): 2540-2546, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30586518

RESUMO

There is evidence that Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling plays a role in the pathogenesis of sarcoidosis. We treated a patient with cutaneous sarcoidosis with the JAK inhibitor tofacitinib; the patient had not previously had a response to medications and had not received systemic glucocorticoids. This treatment resulted in clinical and histologic remission of her skin disease. Sequencing of RNA and immunohistochemical examination of skin-lesion samples obtained from the patient before and during therapy and immunohistochemical testing of lesion samples obtained from other patients with cutaneous sarcoidosis support a role for JAK-STAT signaling in cutaneous sarcoidosis. (Funded by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research and others.).


Assuntos
Janus Quinases/antagonistas & inibidores , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sarcoidose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Pele/patologia , Feminino , Humanos , Imuno-Histoquímica , Janus Quinases/metabolismo , Pessoa de Meia-Idade , Indução de Remissão , Fatores de Transcrição STAT/metabolismo , Sarcoidose/genética , Sarcoidose/patologia , Sarcoidose Pulmonar/tratamento farmacológico , Análise de Sequência de RNA , Transdução de Sinais , Pele/metabolismo , Dermatopatias/genética , Dermatopatias/patologia
13.
Ann Dermatol Venereol ; 145 Suppl 7: VIIS17-VIIS23, 2018 Dec.
Artigo em Francês | MEDLINE | ID: mdl-30583753

RESUMO

A traditional lecture given during the annual meeting of the French Society of Dermatology in Paris summarizes the highlights of the scientific literature over the past year. In the current article the selection of the 2017-2018 period retains the following areas of interest: role of microbiome in the response to anti-PD-1 and in autoimmunity, PI3Kδ inhibitors in autoimmune bullous diseases, diagnostic and therapeutic applications of CRISPR/Cas, arrival of CAR-T cells therapy into clinical practice, gene therapy successes, use of targeted therapies in genodermatoses and integration of genetics in primary care. © 2018 Elsevier Masson SAS. All rights reserved.


Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Microbioma Gastrointestinal/imunologia , Imunoterapia Adotiva , Dermatopatias/terapia , Doenças Autoimunes/microbiologia , Carcinoma Basocelular/genética , DNA Tumoral Circulante/genética , Dermatologia/tendências , Epidermólise Bolhosa/imunologia , Terapia Genética , Humanos , Hipotricose/genética , Imunoterapia , Proteínas dos Microfilamentos/genética , Mutação , Proteínas de Neoplasias/sangue , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Dermatopatias/genética , Neoplasias Cutâneas/genética
14.
Ann Dermatol Venereol ; 145 Suppl 7: VIIS32-VIIS46, 2018 Dec.
Artigo em Francês | MEDLINE | ID: mdl-30583755

RESUMO

In order to describe the latest news in Pediatric dermatology (pathophysiology, clinical aspects and therapy), a literature review was performed from September 2017 to September 2018. This article is not an exhaustive review but present the new data that may infuence the daily practice. The results are presented by disease that may be common or rare. Some references are available as supplements.


Assuntos
Dermatopatias , Malformações Arteriovenosas/terapia , Dermatologia/tendências , Hemangioma/terapia , Humanos , Pediatria/tendências , Propranolol/administração & dosagem , Fatores de Risco , Dermatopatias/diagnóstico , Dermatopatias/genética , Dermatopatias/terapia , Neoplasias Cutâneas/terapia , Vasodilatadores/administração & dosagem
15.
Mol Med Rep ; 18(3): 3153-3158, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30066947

RESUMO

Keratosis pilaris (KP) and nevus comedonicus (NC) are congenital keratinized dermatoses; however, the exact etiology of these two diseases is unclear. The objective of the present study was to identify the disease­causing genes and their association with functional alterations in the development of KP and NC. Peripheral blood samples of one KP family, two NC families and 100 unrelated healthy controls were collected. The genomic sequences of 147 genes associated with 143 genetic skin diseases were initially analyzed from the KP proband using a custom­designed GeneChip. A novel heterozygous missense mutation in the ATP­binding cassette sub­family A member 12 (ABCA12) gene, designated c.6694G>T (p.Asp2232Tyr), was identified in the KP proband and confirmed by Sanger sequencing. The same mutation was also present in the affected family members but not in the healthy family members, the two patients with NC or population­matched controls. The predictions provided by PolyPhen­2 and SIFT analyses suggested that the mutation may produce a damaged protein. The region surrounding the mutation is the extra­membrane domain, which is conserved among particular species, as suggested by ClustalX; however, no ABCA12 mutations were reported in the patients with NC. As observed by immunofluorescence, ABCA12 expression was upregulated in the sebaceous glands of the patients with NC compared with that of normal controls. In summary, ABCA12­associated mutations or alterations in expression may exhibit causative or contributive effects to the development of keratinized dermatoses, including KP and NC.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Anormalidades Múltiplas/genética , Doença de Darier/genética , Sobrancelhas/anormalidades , Mutação de Sentido Incorreto , Dermatopatias/genética , Regulação para Cima , Transportadores de Cassetes de Ligação de ATP/análise , Anormalidades Múltiplas/patologia , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Criança , Doença de Darier/patologia , Sobrancelhas/patologia , Feminino , Humanos , Masculino , Linhagem , Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/patologia , Pele/patologia , Dermatopatias/patologia , Adulto Jovem
16.
Seizure ; 60: 163-171, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30015149

RESUMO

PURPOSE: The aim of this study was to assess the association between human leukocyte antigen (HLA) variants and lamotrigine (LTG)-induced cutaneous adverse drug reactions (cARDs). METHODS: A comprehensive literature search was conducted on the relationship of HLA alleles with LTG-induced cADRs in Asian populations, through PubMed, Embase, and Cochrane Library. The last search was in February 2018. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to access the strength of the association between an HLA allele and LTG-induced cADRs. RESULTS: A total of 11 studies met the inclusion criteria and were enrolled in our meta- analysis, which were based on Chinese, Korean, and Thai populations. Among these populations, we observed that HLA-B*1502 is a risk allele for LTG-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Chinese populations (pooled OR 2.4, 95% CI: 1.20-4.78, P = 0.01), HLA-A*2402 was found to be a significant risk allele for both SJS/TEN (pooled OR 3.50, 95% CI: 1.61-7.59, P = 0.002) and maculopapular eruption (MPE) (pooled OR 2.14, 95% CI: 1.10-4.16, P = 0.03), and HLA-B*3303 was considered to be a protective marker for MPE in Chinese and Korean populations (pooled OR 0.2, 95% CI 0.06-0.64, P = 0.007). CONCLUSIONS: In Asian populations, HLA-B*1502 is a risk factor for LTG-induced bullous lesions such as SJS/TEN in Chinese populations, and HLA-A*2402 is associated with the susceptibility to either SJS/TEN or MPE. HLA-A*3303 is a protective allele against LTG-induced MPE in Chinese and Korean populations.


Assuntos
Anticonvulsivantes/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Antígenos HLA/genética , Dermatopatias/induzido quimicamente , Dermatopatias/genética , Triazinas/efeitos adversos , Humanos , Lamotrigina , Variantes Farmacogenômicos
17.
BioDrugs ; 32(4): 297-309, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29959665

RESUMO

Spherical nucleic acids (SNAs) are highly oriented, well organized, polyvalent structures of nucleic acids conjugated to hollow or solid core nanoparticles. Because they can transfect many tissue and cell types without toxicity, induce minimum immune response, and penetrate various biological barriers (such as the skin, blood-brain barrier, and blood-tumor barrier), they have become versatile tools for the delivery of nucleic acids, drugs, and proteins for various therapeutic purposes. This article describes the unique structures and properties of SNAs and discusses how these properties enable their application in gene regulation, immunomodulation, and drug and protein delivery. It also summarizes current efforts towards clinical translation of SNAs and provides an expert opinion on remaining challenges to be addressed in the path forward to the clinic.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Ácidos Nucleicos/química , Ácidos Nucleicos/uso terapêutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Regulação da Expressão Gênica , Terapia Genética/métodos , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Imunomodulação/efeitos dos fármacos , Imunomodulação/genética , Nanopartículas/administração & dosagem , Nanopartículas/química , Ácidos Nucleicos/administração & dosagem , Proteínas/administração & dosagem , Dermatopatias/genética , Dermatopatias/terapia
18.
Biomed Res Int ; 2018: 7290913, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29888276

RESUMO

Psoriasis is a skin inflammatory disease characterized by an increased body of comorbidities, including parodontopathy. Despite the visibility of skin lesions, prognostic biomarkers, related to disease monitoring and therapeutic effectiveness, are still missing. Although several markers have been studied, none of them has been identified as an independent prognostic factor. This concise review aims to summarize the current knowledge and results in saliva research applied to psoriasis. Combination of different markers could improve the prognostic prediction in patients with psoriasis. Future studies are needed to implement research on salivary biomarkers and their prognostic/therapeutic effects in the management of patients with psoriasis.


Assuntos
Doenças Periodontais/genética , Psoríase/genética , Saliva/metabolismo , Dermatopatias/genética , Biomarcadores/metabolismo , Comorbidade , Humanos , Doenças Periodontais/metabolismo , Doenças Periodontais/patologia , Prognóstico , Psoríase/epidemiologia , Psoríase/metabolismo , Pesquisa , Saliva/química , Dermatopatias/epidemiologia , Dermatopatias/metabolismo
19.
Vet Parasitol ; 252: 9-16, 2018 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-29559159

RESUMO

Cutaneous habronematidosis (CH) is a highly prevalent seasonally recurrent skin disease that affects donkeys as a result from the action of spirurid stomach worm larvae. Carrier flies mistakenly deposit these larvae on previous skin lesions or on the moisture of natural orifices, causing distress and inflicting relapsing wounds to the animals. First, we carried out a meta-analysis of the predisposing factors that could condition the development of CH in Andalusian donkeys. Second, basing on the empirical existence of an inter and intrafamilial variation previously addressed by owners, we isolated the genetic background behind the hypersensibility to this parasitological disease. To this aim, we designed a Bayesian linear model (BLM) to estimate the breeding values and genetic parameters for the hypersensibility to CH as a way to infer the potential selection suitability of this trait, seeking the improvement of donkey conservation programs. We studied the historical record of the cases of CH of 765 donkeys from 1984 to 2017. Fixed effects included birth year, birth season, sex, farm/owner, and husbandry system. Age was included as a linear and quadratic covariate. Although the effects of birth season and birth year were statistically non-significant (P > 0.05), their respective interactions with sex and farm/owner were statistically significant (P < 0.01), what translated into an increase of 40.5% in the specificity and of 0.6% of the sensibility of the model designed, when such interactions were included. Our BLM reported highly accurate genetic parameters as suggested by the low error of around 0.005, and the 95% credible interval for the heritability of ±0.0012. The CH hypersensibility heritability was 0.0346. The value of 0.1232 for additive genetic variance addresses a relatively low genetic variation in the Andalusian donkey breed. Our results suggest that farms managed under extensive husbandry conditions are the most protective ones against developing CH. Furthermore, these results provide evidence of the lack of repercussion of other factors such as age or sex. Potentially considering CH hypersensibility as a negative selection aimed goal in donkey breeding programs, may turn into a measure to improve animal welfare indirectly. However, the low heritability value makes it compulsory to control environmental factors to ensure the effectiveness of the breeding measures implemented to obtain individuals that may genetically be less prone to develop the condition.


Assuntos
Cruzamento , Equidae/genética , Dermatopatias/congênito , Dermatopatias/genética , Criação de Animais Domésticos , Bem-Estar do Animal , Animais , Teorema de Bayes , Fazendas , Feminino , Variação Genética , Modelos Lineares , Masculino , Fenótipo , Reprodução/genética , Fatores de Risco , Estações do Ano , Dermatopatias/epidemiologia , Dermatopatias/parasitologia , Espanha/epidemiologia
20.
Int J Mol Sci ; 19(4)2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29584680

RESUMO

Background: Chronic skin wounds are a growing financial burden for healthcare providers, causing discomfort/immobility to patients. Whilst animal chronic wound models have been developed to allow for mechanistic studies and to develop/test potential therapies, such systems are not good representations of the human chronic wound state. As an alternative, human chronic wound fibroblasts (CWFs) have permitted an insight into the dysfunctional cellular mechanisms that are associated with these wounds. However, such cells strains have a limited replicative lifespan and therefore a limited reproducibility/usefulness. Objectives: To develop/characterise immortalised cell lines of CWF and patient-matched normal fibroblasts (NFs). Methods and Results: Immortalisation with human telomerase resulted in both CWF and NF proliferating well beyond their replicative senescence end-point (respective cell strains senesced as normal). Gene expression analysis demonstrated that, whilst proliferation-associated genes were up-regulated in the cell lines (as would be expected), the immortalisation process did not significantly affect the disease-specific genotype. Immortalised CWF (as compared to NF) also retained a distinct impairment in their wound repopulation potential (in line with CWF cell strains). Conclusions: These novel CWF cell lines are a credible animal alternative and could be a valuable research tool for understanding both the aetiology of chronic skin wounds and for therapeutic pre-screening.


Assuntos
Técnicas de Cultura de Células/métodos , Fibroblastos/citologia , Modelos Biológicos , Dermatopatias/patologia , Telomerase/metabolismo , Experimentação Animal , Proliferação de Células , Células Cultivadas , Senescência Celular , Doença Crônica , Fibroblastos/química , Fibroblastos/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Fenótipo , Dermatopatias/genética , Cicatrização
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