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1.
BMC Infect Dis ; 20(1): 726, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008333

RESUMO

BACKGROUND: Ivermectin is an excellent microfilaricide against Onchocerca volvulus. However, in some regions, long term use of ivermectin has resulted in sub-optimal responses to the treatment. More data to properly document the phenomenon in various contexts of ivermectin mass drug administration (IVM-MDA) is needed. Also, there is a need to accurately monitor a possible repopulation of skin by microfilariae following treatment. Skin snip microscopy is known to have a low sensitivity in individuals with light infections, which can be the case following treatment. This study was designed with two complementary objectives: (i) to assess the susceptibility of O. volvulus microfilariae to ivermectin in two areas undergoing IVM-MDA for different lengths of time, and (ii) to document the repopulation of skin by the O. volvulus microfilariae following treatment, using 3 independent diagnostic techniques. METHOD: Identified microfilaridermic individuals were treated with ivermectin and re-examined after 1, 3, and 6 months using microscopy, actin real-time PCR (actin-qPCR) and O-150 LAMP assays. Susceptibility to ivermectin and trends in detecting reappearance of skin microfilariae were determined using three techniques. Microscopy was used as an imperfect gold standard to determine the performance of actin-qPCR and LAMP. RESULTS: In Bafia with over 20 years of IVM-MDA, 11/51 (21.6%) direct observe treated microfilaridemic participants were still positive for skin microfilariae after 1 month. In Melong, with 10 years of IVM-MDA, 2/29 (6.9%) treated participants were still positive. The microfilarial density reduction per skin biopsy within one month following treatment was significantly lower in participants from Bafia. In both study sites, the molecular techniques detected higher proportions of infected individuals than microscopy at all monitoring time points. LAMP demonstrated the highest levels of sensitivity and real-time PCR was found to have the highest specificity. CONCLUSION: Patterns in skin mirofilariae clearance and repopulation were established. O. volvulus worms from Bafia with higher number of annual MDA displayed a lower clearance and higher repopulation rate after treatment with ivermectin. Molecular assays displayed higher sensitivity in monitoring O. volvulus microfilaridemia within six months following treatment.


Assuntos
Antiparasitários/uso terapêutico , Ivermectina/uso terapêutico , Onchocerca volvulus/fisiologia , Oncocercose/tratamento farmacológico , Pele/patologia , Adolescente , Animais , Biópsia , Camarões , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Administração Massiva de Medicamentos , Microscopia , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
2.
Medicine (Baltimore) ; 99(40): e22534, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019459

RESUMO

RATIONALE: Foreign bodies are frequently ingested, but only approximately 1% of them cause perforation. Perforations in the lesser curvature of the stomach are exceedingly rare. Here, we report a case of gastric perforation in the lesser curvature caused by a foreign body. The patient presented to the clinic complaining of abdominal skin swelling and reddening with upper abdominal discomfort as the initial symptoms. PATIENT CONCERNS: An 83-year-old female presented with a mass in the middle of the epigastrium for 10 days. Physical examination found an apparent local tenderness and inflammatory mass in the upper abdominal wall. Her body temperature was normal (37.5°C) and the white blood cell count was elevated (8.12 × 10/L [reference value 3.5-9.5 × 10/L]). DIAGNOSES: The ultrasound examination of the abdomen revealed a 4 cm strip-like hyperechoic object entangled in the muscles of the abdominal wall. The computed tomography scan revealed a thin strip of bone-like hyperdense shadow. Intraoperative findings showed a sharp fishbone protruding from the lesser curvature of the stomach into the abdominal cavity, part of which remained in the gastric cavity. The postoperative pathological report revealed chronic suppurative inflammation with abscess and sinus canal formation. INTERVENTIONS & OUTCOMES: The patient underwent a gastric foreign body removal with partial gastrectomy. Anti-inflammatory treatment post-surgery rapidly relieved the patient's symptoms of discomfort in the upper abdomen. At the 1-month follow-up, the patient showed no discomfort in the upper abdomen and the inflammatory mass was no longer present. LESSONS: A foreign body had penetrated through the lesser curvature of the stomach, an area with a flat gastric wall, which occurs infrequently. In such cases, computed tomography is the gold standard for diagnosis of foreign bodies in the digestive tract. Ultrasound can also be used as a supplemental diagnostic technique. It is recommended that people who wear dentures should exercise caution while eating, especially when the food contains bones.


Assuntos
Parede Abdominal/patologia , Corpos Estranhos/cirurgia , Inflamação/etiologia , Pele/patologia , Estômago/cirurgia , Assistência ao Convalescente , Idoso de 80 Anos ou mais , Osso e Ossos , Ingestão de Alimentos , Feminino , Corpos Estranhos/diagnóstico por imagem , Humanos , Alimentos Marinhos , Perfuração Espontânea , Estômago/microbiologia , Estômago/patologia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Ultrassonografia/métodos
3.
Adv Exp Med Biol ; 1268: 387-405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918230

RESUMO

Exposure to sunlight is a major source of vitamin D for most people. Yet public health advice has focused overwhelmingly on avoiding exposure of unprotected skin because of the risks of erythema and skin cancer. Given that there are also health risks associated with low vitamin D status, we explore the possibilities of achieving a range of targets associated with vitamin D and the accompanying erythema risk. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that a recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year, and for all the year at some (low) latitudes. We also show that such daily, sub-erythemal doses at lunchtime during the summer months is sufficient to avoid winter-time vitamin D deficiency for the UK all-weather climate, provided that lower arms and legs are exposed in the warmer months. At the higher proposed vitamin D dose of 1000 IU, lunchtime sun exposure is still a viable route to the vitamin but requires the commitment to expose greater areas of skin and is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.


Assuntos
Eritema/etiologia , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Vitamina D/biossíntese , Humanos , Medição de Risco , Pele/patologia , Deficiência de Vitamina D/prevenção & controle
6.
Clin Imaging ; 67: 214-218, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32871425

RESUMO

This article reports 2 adult patients who had developed an acute allergic reaction to food ingredients or medications, respectively. Both patients presented with concurrent urticaria of the skin and colon. The latter finding appeared as numerous raised plaques of the colonic mucosa on radiographic and computed tomography (CT) of the abdomen. The urticarial lesions affecting the skin and large bowel resembled each other and resolved after treatment with antihistamines. Pertinent clinical data and previously published cases of this unusual entity are briefly reviewed.


Assuntos
Colo/diagnóstico por imagem , Hipersensibilidade , Urticária/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pele/patologia , Urticária/tratamento farmacológico , Urticária/etiologia
7.
Int J Mol Sci ; 21(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971906

RESUMO

In December 2019, physicians reported numerous patients showing pneumonia of unknown origin in the Chinese region of Wuhan. Following the spreading of the infection over the world, The World Health Organization (WHO) on 11 March 2020 declared the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak a global pandemic. The scientific community is exerting an extraordinary effort to elucidate all aspects related to SARS-CoV-2, such as the structure, ultrastructure, invasion mechanisms, replication mechanisms, or drugs for treatment, mainly through in vitro studies. Thus, the clinical in vivo data can provide a test bench for new discoveries in the field of SARS-CoV-2, finding new solutions to fight the current pandemic. During this dramatic situation, the normal scientific protocols for the development of new diagnostic procedures or drugs are frequently not completely applied in order to speed up these processes. In this context, interdisciplinarity is fundamental. Specifically, a great contribution can be provided by the association and interpretation of data derived from medical disciplines based on the study of images, such as radiology, nuclear medicine, and pathology. Therefore, here, we highlighted the most recent histopathological and imaging data concerning the SARS-CoV-2 infection in lung and other human organs such as the kidney, heart, and vascular system. In addition, we evaluated the possible matches among data of radiology, nuclear medicine, and pathology departments in order to support the intense scientific work to address the SARS-CoV-2 pandemic. In this regard, the development of artificial intelligence algorithms that are capable of correlating these clinical data with the new scientific discoveries concerning SARS-CoV-2 might be the keystone to get out of the pandemic.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Inteligência Artificial , Betacoronavirus/isolamento & purificação , Sistema Nervoso Central/patologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Humanos , Rim/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Miocárdio/patologia , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Prognóstico , Pele/patologia
8.
Clin Dermatol ; 38(4): 399-407, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972599

RESUMO

Genodermatoses are heritable skin diseases that can cause significant morbidity and mortality. Most of them show characteristic cutaneous findings. Genodermatoses can be associated with extracutaneous system abnormalities. Diagnosing hereditary skin disorders is still a challenging task due to their rarity and diversity, due to diseases evolving over many years, and the initial manifestations not always being diagnostic; therefore, ongoing evaluation and surveillance is often required to make the accurate diagnosis. The algorithm for the diagnosis depends on a combination of thorough clinical and family history clinical examination, laboratory findings, consultation of multiple medical specialists, and molecular analysis. Diagnostic testing targeted at differentiation of similar genodermatoses may be required. Recognition is crucial for the initiation of the treatment for skin manifestations and detection of other extracutaneous abnormalities, including malignancy. Diagnostic accuracy and molecular diagnosis may help in providing a template for ongoing management, testing, and education and prognostication for families of children with genodermatoses.


Assuntos
Técnicas e Procedimentos Diagnósticos , Doenças Raras , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/patologia , Pele/patologia , Algoritmos , Diagnóstico Precoce , Feminino , Testes Genéticos , Humanos , Masculino , Síndrome
9.
Clin Dermatol ; 38(4): 421-431, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972601

RESUMO

Café au lait spots are common birthmarks seen sporadically and in association with several genetic syndromes. Dermatologists are often asked to evaluate these birthmarks both by other physicians and by parents. In some cases, it is challenging to know when and how to pursue further evaluation. Diagnostic challenges may come in the form of the appearance of the individual lesions, areas and patterns of cutaneous involvement, and associated features (or lack thereof). In this review, we aim to clarify when and how to evaluate the child with multiple or patterned café au lait spots and to explain some emerging concepts in our understanding of the genetics of these lesions.


Assuntos
Manchas Café com Leite/congênito , Manchas Café com Leite/diagnóstico , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Pele/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Manchas Café com Leite/genética , Manchas Café com Leite/patologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Deleção de Genes , Estudos de Associação Genética , Mutação em Linhagem Germinativa , Humanos , Lactente , Recém-Nascido , Masculino , Neurofibromatose 1/patologia , Neurofibromina 1/genética , Dermatopatias Genéticas/patologia , Síndrome
10.
Clin Dermatol ; 38(4): 432-454, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972602

RESUMO

The hereditary nature of some forms of cancer was recognized long ago. Over time, recognition of associated findings led to the delineation of numerous hereditary cancer syndromes. Many of these syndromes also have cutaneous manifestations, the recognition of which can lead to their early identification. Recognition of these syndromes allows vigilant surveillance and preemptive treatment, which can dramatically impact the risks of morbidity and mortality for affected patients. The rise of rapid and accurate genetic testing now allows the early identification of asymptomatic at risk family members so that monitoring can be initiated as early as possible. The dermatologist plays a critical role in early identification of these syndromes and, in many cases, their treatment. This review summarizes many known hereditary cancer syndromes with cutaneous findings, their etiology, identification, evaluation, and management. Importantly, this is an ever evolving topic and new findings and syndromes will continue to be recognized. The dermatologist must be always alert to ensure they are detected.


Assuntos
Síndromes Neoplásicas Hereditárias , Dermatopatias Genéticas , Síndrome do Nevo Basocelular , Síndrome de Birt-Hogg-Dubé , Complexo de Carney , Neoplasias Colorretais Hereditárias sem Polipose , Diagnóstico Precoce , Feminino , Síndrome de Gardner , Testes Genéticos , Síndrome do Hamartoma Múltiplo , Humanos , Masculino , Neoplasia Endócrina Múltipla , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Síndromes Neoplásicas Hereditárias/terapia , Neurofibromatoses , Pele/patologia , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Dermatopatias Genéticas/patologia , Dermatopatias Genéticas/terapia
11.
Clin Dermatol ; 38(4): 467-476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972605

RESUMO

Basal cell nevus syndrome, also known as Gorlin syndrome, is a hereditary cancer syndrome associated with multiple basal cell carcinomas, congenital defects, and nondermatologic tumors. This disease is autosomal dominant with variable expressivity and is caused by abnormalities in the sonic hedgehog signaling pathway. Management requires a multidisciplinary approach and should include the biopsychosocial needs of patients and their families. Genetic testing is necessary to confirm an unclear diagnosis, evaluate at-risk relatives, and assist with family planning.


Assuntos
Síndrome do Nevo Basocelular/genética , Síndrome do Nevo Basocelular/terapia , Terapia de Alvo Molecular , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Adulto , Síndrome do Nevo Basocelular/diagnóstico , Síndrome do Nevo Basocelular/patologia , Feminino , Testes Genéticos , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Comunicação Interdisciplinar , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/patologia , Receptor Patched-1/genética , Receptor Patched-1/metabolismo , Receptor Patched-2/genética , Receptor Patched-2/metabolismo , Equipe de Assistência ao Paciente , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais/genética , Pele/patologia , Adulto Jovem
12.
Nat Commun ; 11(1): 4306, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32855398

RESUMO

Metastatic melanoma carries a poor prognosis despite modern systemic therapies. Understanding the evolution of the disease could help inform patient management. Through whole-genome sequencing of 13 melanoma metastases sampled at autopsy from a treatment naïve patient and by leveraging the analytical power of multi-sample analyses, we reveal evidence of diversification among metastatic lineages. UV-induced mutations dominate the trunk, whereas APOBEC-associated mutations are found in the branches of the evolutionary tree. Multi-sample analyses from a further seven patients confirmed that lineage diversification was pervasive, representing an important mode of melanoma dissemination. Our analyses demonstrate that joint analysis of cancer cell fraction estimates across multiple metastases can uncover previously unrecognised levels of tumour heterogeneity and highlight the limitations of inferring heterogeneity from a single biopsy.


Assuntos
Evolução Clonal , Heterogeneidade Genética , Melanoma/genética , Neoplasias Cutâneas/genética , Idoso , Biópsia , Análise Mutacional de DNA , Humanos , Masculino , Melanoma/secundário , Estudos Prospectivos , Pele/patologia , Neoplasias Cutâneas/patologia , Sequenciamento Completo do Genoma
13.
Medicine (Baltimore) ; 99(34): e21947, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846864

RESUMO

An intermittent closure with silk suture is routinely used for closing different surgical wounds. However, subcuticular closure with absorbable sutures has gained considerable attention due to convenience and better cosmetic appearance.To compare the clinical outcomes and risk of surgical-site infection of subcuticular and intermittent closure after total-knee arthroplasty (TKA), 106 patients that underwent TKA between January 2017 to June 2019 at the Department of Orthopedics in Xiangya Hospital of Centre South University were retrospectively assessed. Forty-three had received running subcuticular closure (group A) and 58 underwent intermittent closure (group B). The Knee Society score was measured before and 6 months after operation. Inflammation markers including the serum levels of procalcitonin, interleukin-6, and C-reactive protein, and the erythrocyte sedimentation rate were evaluated before operation, 1 day after and 1 month after operation. Patient satisfaction with the closure was evaluated using the Likert scale at the last follow-up.No significant difference was seen in the 6-month postoperative Knee Society score, or in the 1-day and 6-month postoperative inflammation marker levels between both groups (P > .05). Likert scores were higher in group A compared to group B (4.0 ±â€Š1.0 vs 3.6 ±â€Š1.2, P < .05).Running subcuticular closure after TKA results in a better appearance compared to intermittent closure, although neither method has an advantage in terms of efficacy and risk of infection.


Assuntos
Artroplastia do Joelho/métodos , Pele/patologia , Suturas/tendências , Técnicas de Fechamento de Ferimentos/tendências , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/análise , China/epidemiologia , Feminino , Humanos , Inflamação/metabolismo , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Pró-Calcitonina/sangue , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do Tratamento
14.
Nat Commun ; 11(1): 3945, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32770028

RESUMO

TP53 missense mutations leading to the expression of mutant p53 oncoproteins are frequent driver events during tumorigenesis. p53 mutants promote tumor growth, metastasis and chemoresistance by affecting fundamental cellular pathways and functions. Here, we demonstrate that p53 mutants modify structure and function of the Golgi apparatus, culminating in the increased release of a pro-malignant secretome by tumor cells and primary fibroblasts from patients with Li-Fraumeni cancer predisposition syndrome. Mechanistically, interacting with the hypoxia responsive factor HIF1α, mutant p53 induces the expression of miR-30d, which in turn causes tubulo-vesiculation of the Golgi apparatus, leading to enhanced vesicular trafficking and secretion. The mut-p53/HIF1α/miR-30d axis potentiates the release of soluble factors and the deposition and remodeling of the ECM, affecting mechano-signaling and stromal cells activation within the tumor microenvironment, thereby enhancing tumor growth and metastatic colonization.


Assuntos
Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Complexo de Golgi/patologia , Síndrome de Li-Fraumeni/genética , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/genética , Animais , Biópsia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Feminino , Fibroblastos , Regulação Neoplásica da Expressão Gênica , Complexo de Golgi/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Síndrome de Li-Fraumeni/patologia , Camundongos , Microtúbulos/metabolismo , Microtúbulos/patologia , Mutação , Cultura Primária de Células , Vesículas Secretórias/metabolismo , Vesículas Secretórias/patologia , Transdução de Sinais/genética , Pele/citologia , Pele/patologia , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Niger J Clin Pract ; 23(8): 1039-1043, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788478

RESUMO

Aim: The aim of this study was to investigate the relationship between the presence of Demodex on the face and within the eyelash follicles in patients with rosacea. Subjects and Methods: This prospective cross-sectional study included 80 participants, 40 patients with rosacea and 40 individuals with no rosacea as controls. The presence of Demodex on the face was assessed by standard superficial skin biopsy. Sixteen eyelashes were epilated from each patient and control. Results: The rate of Demodex infestation and severe infestation on the face in patients with rosacea was significantly higher than the control group. Demodex count within the eyelash follicle was significantly higher in patients with erythematotelangiectatic type rosacea than the control group. There was no increase in blepharitis in rosacea patients but when blepharitis was present, the rate of the presence of Demodex was higher in this group. There was a statistically significant relationship between the presence of Demodex within the eyelashes and itchy eyes in people without blepharitis. Conclusion: When at least one Demodex is found on the face in rosacea patients, the eyelashes should be examined for effective treatment of the mite. Itchy eyes may be an important sign of the presence of Demodex in people without blepharitis.


Assuntos
Infecções Oculares Parasitárias/parasitologia , Pestanas/parasitologia , Infestações por Ácaros/parasitologia , Rosácea/parasitologia , Pele/patologia , Adulto , Animais , Biópsia , Blefarite/diagnóstico , Blefarite/epidemiologia , Blefarite/parasitologia , Estudos de Casos e Controles , Conjuntivite , Estudos Transversais , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/epidemiologia , Face , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infestações por Ácaros/diagnóstico , Infestações por Ácaros/epidemiologia , Ácaros , Estudos Prospectivos , Prurido , Rosácea/diagnóstico , Rosácea/epidemiologia
16.
Nat Commun ; 11(1): 4092, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796837

RESUMO

Single nucleotide polymorphisms (SNPs) in the gene encoding kinesin family member 3A, KIF3A, have been associated with atopic dermatitis (AD), a chronic inflammatory skin disorder. We find that KIF3A SNP rs11740584 and rs2299007 risk alleles create cytosine-phosphate-guanine sites, which are highly methylated and result in lower KIF3A expression, and this methylation is associated with increased transepidermal water loss (TEWL) in risk allele carriers. Kif3aK14∆/∆ mice have increased TEWL, disrupted junctional proteins, and increased susceptibility to develop AD. Thus, KIF3A is required for skin barrier homeostasis whereby decreased KIF3A skin expression causes disrupted skin barrier function and promotes development of AD.


Assuntos
Dermatite Atópica/metabolismo , Cinesina/metabolismo , Pele/metabolismo , Adolescente , Adulto , Alelos , Animais , Criança , Dermatite Atópica/genética , Dermatite Atópica/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cinesina/genética , Masculino , Metilação , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Pele/patologia , Adulto Jovem
17.
Int J Nanomedicine ; 15: 5629-5643, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32801706

RESUMO

Purpose: Lecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein. Methods: Lecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein. Results: The lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation. Conclusion: These results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.


Assuntos
Flavanonas/administração & dosagem , Nanopartículas/administração & dosagem , Fosfolipídeos/química , Administração Cutânea , Animais , Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Flavanonas/farmacocinética , Interações Hidrofóbicas e Hidrofílicas , Lecitinas/química , Masculino , Nanopartículas/efeitos adversos , Nanopartículas/química , Permeabilidade , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
18.
PLoS One ; 15(8): e0238076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857768

RESUMO

Epidermal lineages and injury induced regeneration are controlled by transcriptional programs coordinating cellular signaling and epigenetic regulators, but the mechanism remains unclear. Previous studies showed that conditional deletion of the transcriptional coactivator Mediator 1 (Med1) changes epidermal lineages and accelerates wound re-epithelialization. Here, we studied a molecular mechanism by which Med1 facilitates these processes, in particular, by focusing on TGFß signaling through genome wide transcriptome analysis. The expression of the TGF ligands (Tgfß1/ß2) and their downstream target genes is decreased in both normal and wounded Med1 null skin. Med1 silencing in cultured keratinocytes likewise reduces the expression of the ligands (TGFß1/ß2) and diminishes activity of TGFß signaling as shown by decreased p-Smad2/3. Silencing Med1 increases keratinocyte proliferation and migration in vitro. Epigenetic studies using chromatin immuno-precipitation and next generation DNA sequencing reveals that Med1 regulates transcription of TGFß components by forming large clusters of enhancers called super-enhancers at the regulatory regions of the TGFß ligand and SMAD3 genes. These results demonstrate that Med1 is required for the maintenance of the TGFß signaling pathway. Finally, we show that pharmacological inhibition of TGFß signaling enhances epidermal lineages and accelerates wound re-epithelialization in skin similar to that seen in the Med1 null mice, providing new insights into epidermal regeneration.


Assuntos
Subunidade 1 do Complexo Mediador/genética , Regeneração/fisiologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Animais , Linhagem da Célula , Movimento Celular , Proliferação de Células , Regulação para Baixo , Epiderme/fisiologia , Queratinócitos/citologia , Queratinócitos/metabolismo , Subunidade 1 do Complexo Mediador/antagonistas & inibidores , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Pele/metabolismo , Pele/patologia , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta2/genética , Regulação para Cima
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