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1.
G Ital Dermatol Venereol ; 153(3): 316-325, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27627098

RESUMO

BACKGROUND: Clinical or quality of life assessments are currently available for psoriasis severity evaluation and therapeutic response. Laboratory scores focused to measure and follow treatment efficacy are lacking at present. METHODS: A microscopic and biomolecular score was designed to monitor skin disease severity and clinical response to anti-psoriatic treatments. A susceptibility gene analysis on cellular retinoic acid binding protein-II (CRABP-II), acting on keratinocyte differentiation, was also performed. A Molecular Index of Therapeutic Efficacy (MITE) was defined by assembling morphometric/semiquantitative measurement of epidermal thickness, immunohistochemical Ki-67, keratin 17 and CRABP-II expression of lesional and non-lesional psoriatic skin biopsies before and after anti-tumor necrosis factor (TNF) α therapies. A 0-12 MITE score was correlated with Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI) scores and inflammation. Three CRABP-II SNPs were analyzed by TaqMan assay. RESULTS: All parameters were highly expressed in psoriatic lesions and reduced after 12 weeks of anti-TNF-α treatments. MITE score strongly correlated with PASI and PDI values either before or after therapies (P<0.001 and P<0.001, respectively). Conversely, MITE values did not change after treatments of non-responder patients. CRABP-II did not result in a psoriatic susceptibility gene for the SNPs probes analyzed. CONCLUSIONS: MITE score variations corresponded to the patients' clinical improvement following anti-TNF-α treatments, with significant statistical correlation among MITE, PASI and PDI scores. If confirmed in a larger series and/or in different hyperproliferative and inflammatory dermatoses, MITE score could be proposed as additional monitoring system to evaluate treatment protocols in skin disorders and targeted biomolecular pathways supporting clinical efficacy.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Qualidade de Vida , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Biópsia , Diferenciação Celular , Fármacos Dermatológicos/farmacologia , Feminino , Humanos , Queratinócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Psoríase/fisiopatologia , Receptores do Ácido Retinoico/genética , Índice de Gravidade de Doença , Resultado do Tratamento
2.
J Neurovirol ; 23(1): 147-151, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27431677

RESUMO

In this retrospective case-control study, we compared the number of circulating lymphocyte subsets among 31 healthy controls, 18 naïve and 40 antiretroviral-treated HIV patients, 28 untreated and 18 treated relapsing-remitting multiple sclerosis (MS) patients. Lymphocyte subsets were no different between untreated MS patients and controls. Untreated and treated MS had a lower CD8+ count and a higher CD4+ number compared to untreated and treated HIV patients except similar CD4+ number between treated MS and HIV patients. CD4/CD8 ratio was lower in female HIV non-responders and in relapsing MS women compared, respectively, to female HIV responders and remitting MS women, and there were no differences in men.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/diagnóstico , Fatores Imunológicos/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Adulto , Terapia Antirretroviral de Alta Atividade , Biomarcadores/análise , Contagem de Linfócito CD4 , Relação CD4-CD8 , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Estudos de Casos e Controles , Feminino , Acetato de Glatiramer/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Imunofenotipagem , Interferon beta/uso terapêutico , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/virologia , Prognóstico , Estudos Retrospectivos , Fatores Sexuais , Carga Viral/efeitos dos fármacos
3.
J Exp Clin Cancer Res ; 35(1): 118, 2016 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-27448598

RESUMO

BACKGROUND: Human T-cell leukemia virus (HTLV-1) is a lymphotropic retrovirus associated to adult T cell leukemia (ATL) and to non-neoplastic inflammatory conditions affecting the central nervous system, lung or skin. The inflammatory disorders associated to HTLV-1 are mediated by different proinflammatory cytokines as IL-1α, IL-6, TNF-α. The release and the role of IL-17 is still debated. Aims of this study were to analyze IL-17 induction by HTLV-1 infection and to determine whether resveratrol (RES) is able to down regulate the pathway of cytokines production either in HTLV-1 chronically infected MT-2 cell line or in human CD4+ cells infected in vitro with HTLV-1. METHODS: MT-2 and HTLV-1 infected CD4+ cells were analyzed for proinflammatory cytokine production before or after RES treatment. The concentrations of IL-17, IL-1α, IL-6, and TNF-α were measured in cell culture supernatants by ELISA and SearchLight™ technology. The IL-17 mRNA expression was evaluated by RT-PCR. NF-kB activation was detected by non-radioactive, Electro Mobility Shift Assay (EMSA). HTLV-1 RNA expression was detected by Real-time-PCR (RQ-PCR). RESULTS: We found that RES is capable of inducing a dose-dependent inhibition of IL-1α, IL-6 and TNF-α production in vitro and can down regulate the expression of IL-17 at both mRNA and protein levels in HTLV-1 infected cells. This effect was associated with a dose-dependent inhibition of the of the nuclear factor kappa-B (NF-kB) activity. Conversely, RES did not apparently affect HTLV-1 proliferation. CONCLUSIONS: These results support the anti-inflammatory properties of RES, suggesting that it might be a useful therapeutic agent for the treatment of HTLV-1 related inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Linfócitos T CD4-Positivos/virologia , Regulação para Baixo , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Interleucina-17/metabolismo , Estilbenos/farmacologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-17/genética , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Resveratrol , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
4.
Int J Mol Sci ; 17(6)2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27258263

RESUMO

The human herpes virus 8 (HHV-8), also known as Kaposi sarcoma-associated herpes virus (KSHV), can infect endothelial cells often leading to cell transformation and to the development of tumors, namely Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and the plasmablastic variant of multicentric Castleman's disease. KSHV is prevalent in areas such as sub-Saharan Africa and the Mediterranean region presenting distinct genotypes, which appear to be associated with differences in disease manifestation, according to geographical areas. In infected cells, KSHV persists in a latent episomal form. However, in a limited number of cells, it undergoes spontaneous lytic reactivation to ensure the production of new virions. During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. This review will focus on the interplay between the KSHV and the DDR response pathway throughout the viral lifecycle, exploring the putative molecular mechanism/s that may contribute to malignant transformation of host cells.


Assuntos
Dano ao DNA , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/fisiologia , Animais , Transformação Celular Viral/genética , Infecções por Herpesviridae/metabolismo , Humanos , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/metabolismo , Sarcoma de Kaposi/virologia , Transdução de Sinais , Ativação Viral/genética , Latência Viral/genética , Replicação Viral
5.
BMC Immunol ; 16: 4, 2015 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-25651756

RESUMO

BACKGROUND: Para-phenylenediamine (PPD) is the main allergen causing adverse reactions to hair dyes and a frequent cause of occupational-related skin sensitization among hairdressers and beauticians. The immunologic mechanism of the disease relies on the production of inflammatory cytokines by allergen-specific T cells, while regulatory T cells are thought to down-modulate the allergic response. This study was aimed at investigating the expression of effector or regulatory cytokines in exposed subjects in order to verify whether different cytokine profiles might predict distinct clinical outcomes. Peripheral blood mononuclear cells (PBMC) from 21 subjects occupationally exposed or not (10) to PPD were kept in short term cultures in the presence of optimized concentrations of NiSO4 × 6H2O or PPD. The production of IFN-γ and IL-10 elicited by antigens were analyzed by the ELISpot assay. RESULTS: The presence of IFN-γ responses toward PPD was significantly correlated with a positive patch test (P = 0.002) and allergic symptoms, while IL10 responses were invariably found in PPD-exposed but clinically asymptomatic subjects with negative patch testing. We found concordance between the different cytokine profiles and patch test results. No false-positive results were found for the different cytokine profiles induced by PPD, resulting in 100% specificity. The sensitivity of the test was 87.5% (95% CI 65.9-100.0) with an overall test accuracy of 93.3%. Although larger prospective-retrospective studies are necessary to validate the predictive potential of the test, the negative and positive predicted values for PPD in this study were NPV = 87.5% and PPV = 100%, respectively. CONCLUSIONS: These data indicate that distinct cytokine profiles are associated with different clinical manifestations. The test, which is based on a simple and rapid profiling of cytokine responses by T lymphocytes against allergens, has proven to be a promising laboratory tool, useful for both the identification of previous contact with allergens and the etiologic diagnosis of contact allergies as well as capable of predicting the clinical outcome (development of an allergic or tolerant response).


Assuntos
Técnicas de Laboratório Clínico/métodos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Ocupacional/diagnóstico , Níquel/metabolismo , Fenilenodiaminas/metabolismo , Linfócitos T/imunologia , Adulto , Alérgenos/imunologia , Células Cultivadas , Dermatite Alérgica de Contato/imunologia , Dermatite Ocupacional/imunologia , ELISPOT , Feminino , Tinturas para Cabelo/metabolismo , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Fenilenodiaminas/imunologia , Valor Preditivo dos Testes , Prognóstico , Sensibilidade e Especificidade , Adulto Jovem
6.
J Exp Clin Cancer Res ; 34: 1, 2015 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-25592960

RESUMO

BACKGROUND: Classical Kaposi's Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with cKS or in HHV-8 infected subjects either asymptomatic or with cKS-unrelated cutaneous lymphoproliferative disorders. METHODS: The VR1 and VR2 regions of the ORF K1 sequence were analyzed in samples (peripheral blood and/or lesional tissue) collected between 2000 and 2010 from 27 subjects with HHV-8 infection, established by the presence of anti-HHV-8 antibodies. On the basis of viral genotyping, a phylogenetic analysis and a time-scaled evaluation were performed. RESULTS: Two main clades of HHV-8, corresponding to A and C subtypes, were identified. Moreover, for each subtype, two main clusters were found distinctively associated to cKS or non-cKS subjects. Selective pressure analysis showed twelve sites of the K1 coding gene (VR1 and VR2 regions) under positive selective pressure and one site under negative pressure. CONCLUSION: Thus, present data suggest that HHV-8 genetic variants may influence the susceptibility to cKS in individuals with HHV-8 infection.


Assuntos
Variação Genética , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/classificação , Herpesvirus Humano 8/genética , Proteínas de Membrana/genética , Sarcoma de Kaposi/genética , Proteínas do Envelope Viral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia
8.
Neurol Sci ; 35(11): 1737-41, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24847961

RESUMO

The exact prevalence and pathogenic role of antiphospholipid antibodies (aPL) in multiple sclerosis (MS) remain unclear. This observational laboratory-blinded study evaluated the rate of aPL positivity in healthy controls and MS patients in different disease phases to recognize their frequency and possible pathogenic meaning. Reactivity for anti-cardiolipin, anti-ß2 glycoprotein I, anti-prothrombin, anti-annexin V (IgG and IgM) was studied by enzyme immunoassays in 60 healthy controls and 100 consecutive MS patients [58 relapsing-remitting (RR) patients in remission, 26 RR patients in relapse, and 16 secondary progressive patients]. The overall rate of positivity for at least one aPL was significantly higher in MS patients compared to controls (32 % vs. 7 %, respectively, p < 0.0001), and in relapsing phase compared to those remitting or secondary progressive (53.8, 20.7 and 37.5 %, respectively, p = 0.002). In the single aPL analysis, the rate of positivity was significantly higher in MS patients compared to controls for anti-prothrombin IgM (7 % vs. 0, p = 0.05), and in relapsing phase compared to remitting and secondary progressive phases for anti-ß2 glycoprotein I IgM (26.9, 1.7, 6.3 %, respectively, p < 0.0001), anti-prothrombin IgM (15.4, 3.4, 6.3 %, respectively, p = 0.05) and IgG (19.2, 5.2, 0 %, respectively, p = 0.05). We showed a significant aPL increase in MS patients compared to healthy controls, particularly during disease relapse which was also associated with significantly higher values of anti-ß2 glycoprotein I and anti-prothrombin. These data suggest that antiphospholipid antibody occurrence in multiple sclerosis could be related to modification of structure and function of proteins involved in the inflammatory-thrombotic processes during disease re-activation.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Esclerose Múltipla/patologia , Adulto , Autoanticorpos/sangue , Autoantígenos/imunologia , Feminino , Humanos , Imunoensaio , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla/imunologia , Protrombina/imunologia , Recidiva , Trombose/patologia , beta 2-Glicoproteína I/imunologia
9.
Dermatol Ther ; 26(5): 424-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24099075

RESUMO

Radiation recall dermatitis is an acute, rare skin reaction confined to previously irradiated areas that can be triggered by chemotherapeutic drugs (generally doxorubicin and taxanes), which are administrated after radiotherapy. We describe this case report to discuss the timing of the different choice of treatments of progressive Kaposis's sarcoma (KS) disease. KS, the neoplastic disease associated with HHV-8 infection, is still the most commonly diagnosed malignancy in HIV-1 patients, even if its incidence dramatically declined in the highly active antiretroviral therapy (HAART) era. The cutaneous form of disease generally improves with HAART alone or in association with local treatment (cryotherapy, radiotherapy, intralesion chemotherapy), whereas disseminated and/or progressive disease needs to be treated with systemic chemotherapy. In selected patients with progressive disease, systemic and local therapeutic options should be associated. We report a case of a 30-year-old HIV-1-positive man, affected by epidemic cutaneous and mucosal KS, who received several cycles of chemotherapy in succession with radiotherapy and other chemotherapy treatments for disease progression. After 7 months, the end of the last rechallenge with chemotherapy, the patient presented cutaneous painful and ulcerated lesions on the same skin areas previously irradiated.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/terapia , Infecções por HIV/complicações , Radiodermite/patologia , Sarcoma de Kaposi/terapia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Progressão da Doença , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 8/isolamento & purificação , Humanos , Incidência , Masculino , Sarcoma de Kaposi/patologia , Fatores de Tempo
10.
Clin Dev Immunol ; 2013: 390563, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23818915

RESUMO

In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc) and undifferentiated connective tissue disease (UCTD), we have explored the setting of peripheral T regulatory (T reg) cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc) or diffuse (dcSSc) disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.


Assuntos
Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Doença Mista do Tecido Conjuntivo/sangue , Escleroderma Sistêmico/sangue , Linfócitos T Reguladores/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Hormônio Liberador da Corticotropina/sangue , Hormônio Liberador da Corticotropina/imunologia , Estudos Transversais , DNA Topoisomerases Tipo I/sangue , DNA Topoisomerases Tipo I/imunologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/imunologia , Doença Mista do Tecido Conjuntivo/patologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Índice de Gravidade de Doença , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Urocortinas/sangue , Urocortinas/imunologia
11.
J Exp Clin Cancer Res ; 31: 9, 2012 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-22296726

RESUMO

BACKGROUND: Antigen-specific CD8+ cytotoxic T lymphocytes represent potent effector cells of the adaptive immune response against viruses as well as tumours. Therefore assays capable at exploring the generation and function of cytotoxic T lymphocytes represent an important objective for both clinical and experimental settings. METHODS: Here we show a simple and reproducible assay for the evaluation of antigen-specific CD8+ cytotoxic T lymphocytes based on a LysiSpot technique for the simultaneous determination of antigen-specific IFN-γ production and assessment of tumor cytolysis. The assay was developed within an experimental model of colorectal carcinoma, induced by the colorectal tumor cell line DHD-K12 that induces tumors in BDIX rats and, in turn, elicits a tumor- specific immune response. RESULTS: Using DHD-K12 cells transfected to express Escherichia coli ß-galactosidase as target cells, and by the fine setting of spot colours detection, we have developed an in vitro assay that allows the recognition of cytotoxic T lymphocytes induced in BDIX rats as well as the assessment of anti-tumour cytotoxicity. The method highlighted that in the present experimental model the tumour antigen-specific immune response was bound to killing target cells in the proportion of 55%, while 45% of activated cells were not cytotoxic but released IFN-γ. Moreover in this model by an ELISPOT assay we demonstrated the specific recognition of a nonapeptide epitope called CSH-275 constitutionally express in DHD-K12 cells. CONCLUSIONS: The assay proved to be highly sensitive and specific, detecting even low frequencies of cytotoxic/activated cells and providing the evaluation of cytokine-expressing T cells as well as the extent of cytotoxicity against the target cells as independent functions. This assay may represent an important tool to be adopted in experimental settings including the development of vaccines or immune therapeutic strategies.


Assuntos
Neoplasias Colorretais/imunologia , Epitopos/imunologia , Interferon gama/metabolismo , Neoplasias Experimentais/imunologia , Linfócitos T Citotóxicos/imunologia , Imunidade Adaptativa , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Epitopos/metabolismo , Interferon gama/imunologia , Ratos
12.
Clin Dev Immunol ; 2011: 718708, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22110527

RESUMO

S. aureus represents a critical cofactor in atopic dermatitis (AD). In this paper, the prevalence of S. aureus infection/colonization was evaluated in 117 children as well as in their cohabitants, in order to assess the value of S. aureus characterization in predicting disease onset and severity and in providing indications for prophylaxis. Results showed that children with AD as well as their cohabitants had a significantly greater incidence of S. aureus infection/colonization as compared to controls. The genetic characterization showed a virtual identity of the bacteria strains collected at different sites of the patients with those found in the cohabitants, suggesting both a direct transmission between the nasal reservoir and the lesions in the same atopic subject and a risk for reinfection within family cohabitants. These data stress the need of preliminary laboratory assessment and posttherapy control in both AD patients and their close contacts for effective S. aureus eradication.


Assuntos
Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Criança , Pré-Escolar , DNA Bacteriano/análise , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Transmissão de Doença Infecciosa , Família , Feminino , Seguimentos , Humanos , Incidência , Masculino , Prevalência , Prognóstico , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade
13.
J Exp Clin Cancer Res ; 30: 40, 2011 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-21489270

RESUMO

BACKGROUND: Kaposi Sarcoma (KS) is a malignancy of endothelial skin cells with multifocal localization on the skin, lymph nodes and visceral organs. Although all clinical variants are associated with HHV-8 infection, specific differences in the clinical onset and in the natural history of AIDS-KS and Classic-KS have been described. The present randomised prospective-observational study aimed to investigate whether the ultrasound pattern and color Doppler flow imaging of vascularisation of skin lesions of patients with Classic KS (CKS) or AIDS-KS could provide useful information to the evaluation of clinical activity of the disease. METHODS: Cutaneous lesions of 24 patients with histologically confirmed KS were investigated using very high frequency ultrasound probes; 16 patients had CKS and 8 had AIDS-KS. HHV-8 infection was confirmed in all patients by investigating the specific humoral response to viral antigens. Immunological and virological parameters were also assessed to monitor HIV or HHV-8 viral infection. For each patient, a target skin lesion was selected on the basis of size (diameter from 0.4 to 2 cm). Each lesion was analyzed in terms of size, depth and color Doppler pattern. RESULTS: The B-mode ultrasound patterns of skin lesions did not differ when comparing CKS patients to AIDS-KS patients, whereas the color Doppler signal, which is associated with vascular activity, was detected in the KS lesions of 6/8 AIDS-KS patients (75.0%) and in 2/16 CKS (16,7%); the latter two patients showed a clinically progressive and extensive disease stage (IV B). CONCLUSIONS: Our preliminary results suggest that small cutaneous KS lesions - in both CKS and AIDS-KS patients- display similar B-mode ultrasound patterns ( hypoechoic, well defined, superficial lesions). However, the color Doppler signal, which is associated with endothelial activity and angiogenesis, which play a substantial role in KS progression, could constitute a useful tool for evaluating disease activity.


Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Sarcoma de Kaposi/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Herpesvirus Humano 8 , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neovascularização Patológica , Sarcoma de Kaposi/irrigação sanguínea , Sarcoma de Kaposi/virologia , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/virologia , Ultrassonografia Doppler em Cores
14.
J Am Acad Dermatol ; 63(5): 782-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20619486

RESUMO

BACKGROUND: Postadolescent acne is usually described as an inflammatory, mild-to-moderate dermatosis, frequently involving the lower third of the face, the jawline, and the neck. However, we have also frequently observed a clinical form predominantly characterized by retention lesions (microcomedones and macrocomedones), with few inflammatory lesions (comedonal postadolescent acne [CPAA]), which appears significantly correlated with cigarette smoking. OBJECTIVE: We sought to investigate the clinical features of postadolescent acne in a group of female patients affected by acne and its relationship with cigarette smoking. METHODS: A total of 226 women with acne (25-50 years) attending our department were examined by a team of 3 dermatologists, to assess the age of onset of the disease, and the number, type, and distribution of acne lesions. RESULTS: In all, 192 of 226 patients (85.0%) were classified as having CPAA and 34 as having papulopustular postadolescent acne. A smoking habit was confirmed in 150 of 226 (66.3%). Remarkably, 72.9% of patients with CPAA were smokers as compared with only 29.4% of those with papulopustular postadolescent acne (P < .0001). LIMITATIONS: Possible limitations are related to geographic area or to the prevalence of darker skin types (III and IV) (data about skin types have not been collected). Other possible aggravating factors (ie, stress and diet) have not been investigated. CONCLUSIONS: According to our results, CPAA appears as the most frequent clinical form of postadolescent acne and seems to be strictly correlated with cigarette smoking.


Assuntos
Acne Vulgar/epidemiologia , Acne Vulgar/patologia , Índice de Gravidade de Doença , Fumar/epidemiologia , Fumar/patologia , Adulto , Idade de Início , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Pigmentação da Pele
15.
BMC Immunol ; 9: 19, 2008 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-18482439

RESUMO

BACKGROUND: Recent attempts to diminish nickel use in most industrial products have led to an increasing utilization of alternative metal compounds for destinations such as the alloys used in orthopaedics, jewellery and dentistry. The present study was undertaken with the aim to evaluate the potential for an allergic response to nickel, palladium and rhodium on the basis of antigen-specific induction of inflammatory/regulatory cytokines, and to characterize, according to the cytokine profiles, the nature of simultaneous positive patch tests elicited in vivo. Peripheral blood mononuclear cells (PBMC) from 40 patients with different patch test results were kept in short term cultures in the presence of optimized concentrations of NiSO4 x 6H2O, PdCl2 and Rh(CH3COO)2. The production of IFN-gamma and IL-10 elicited by metal compounds were analyzed by the ELISpot assay. RESULTS: We found a specific IFN-gamma response by PBMC upon in vitro stimulation with nickel or palladium in well recognized allergic individuals. All controls with a negative patch test to a metal salt showed an in vitro IL-10 response and not IFN-gamma production when challenged with the same compound. Interestingly, all subjects with positive patch test to both nickel and palladium (group 3) showed an in vitro response characterized by the release of IFN-gamma after nickel stimulation and production of IL-10 in response to palladium. CONCLUSION: These results strongly suggest that the different cytokine profiles elicited in vitro reflect different immune responses which may lead to the control of the allergic responses or to symptomatic allergic contact dermatitis. The development of sensitive and specific in vitro assays based on the determination of the cytokine profiles in response to contact allergens may have important diagnostic and prognostic implications and may prove extremely useful in complementing the diagnostic limits of traditional patch testing.


Assuntos
Dermatite Alérgica de Contato/imunologia , Interferon gama/metabolismo , Interleucina-10/metabolismo , Níquel/imunologia , Paládio/imunologia , Ródio/imunologia , Adulto , Dermatite Alérgica de Contato/diagnóstico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Imunização , Masculino , Níquel/farmacologia , Paládio/farmacologia , Testes do Emplastro , Ródio/metabolismo , Ródio/farmacologia
16.
BMC Infect Dis ; 7: 143, 2007 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-18053246

RESUMO

BACKGROUND: The occurrence of, and risk factors for, HHV-8 infection have yet to be definitively determined, particularly among heterosexual individuals with at-risk behavior for sexually transmitted infections (STI). The objective of this study was to estimate the incidence and determinants of HHV-8 infection among HIV-uninfected individuals repeatedly attending an urban STI clinic. METHODS: Sera from consecutive HIV-uninfected individuals repeatedly tested for HIV-1 antibodies were additionally tested for HHV-8 antibodies using an immunofluorescence assay. To identify determinants of HHV-8 infection, a nested case-control study and multivariate logistic regression analysis were performed. RESULTS: Sera from 456 HIV-uninfected individuals (224 multiple-partner heterosexuals and 232 men who have sex with men (MSM]) were identified for inclusion in the study. The HHV-8 seroprevalence at enrollment was 9.4% (21/224; 95% C.I.: 6.0-14.2%) among heterosexuals with multiple partners and 22.0% (51/232; 95% C.I.: 16.9-28.0%) among MSM. Among the 203 multiple-partner heterosexuals and 181 MSM who were initially HHV-8-negative, 17 (IR = 3.0/100 p-y, 95% C.I.: 1.9 - 4.8) and 21 (IR = 3.3/100 p-y, 95% C.I:.2.1 - 5.1) seroconversions occurred, respectively. HHV-8 seroconversion tended to be associated with a high number of sexual partners during the follow-up among MSM (> 10 partners: AOR = 3.32 95% CI:0.89-12.46) and among the multiple-partner heterosexuals (> 10 partner; AOR = 3.46, 95% CI:0.42-28.2). Moreover, among MSM, HHV-8 seroconversion tended to be associated with STI (AOR = 1.80 95%CI: 0.52-7.96). During the study period the HIV-1 incidence was lower than that of HHV-8 among both groups (0.89/100 p-y among MSM and 0.95/100 p-y among multiple-partner heterosexuals). CONCLUSION: The large difference between the incidence of HHV-8 and the incidence of HIV-1 and other STIs may suggest that the circulation of HHV-8 is sustained by practices other than classical at-risk sexual behavior.


Assuntos
Infecções por HIV/epidemiologia , HIV-1 , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 8 , Comportamento Sexual , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Feminino , HIV-1/imunologia , HIV-1/isolamento & purificação , Infecções por Herpesviridae/transmissão , Herpesvirus Humano 8/imunologia , Herpesvirus Humano 8/isolamento & purificação , Humanos , Incidência , Itália/epidemiologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia
17.
Ann N Y Acad Sci ; 1110: 578-89, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17911474

RESUMO

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in sustaining the inflammatory process in the skin as well as in the joints of patients with psoriasis and psoriatic arthritis. In fact, biological therapies based on monoclonal antibodies against TNF-alpha have been proven to be effective on both the arthropathy and the cutaneous symptoms of the disease. Among the several effects produced by TNF-alpha on keratinocytes there is the induction of expression of MMP-9, a matrix metalloproteinase (MMP) produced mainly by monocytes and macrophages. In this article we refer to the results of a study on the behavior of MMP-9 in the sera and in the lesional skin in association with effective therapy with infliximab. Measurements of TNF-alpha, MMP-2, vascular endothelial growth factor (VEGF), and E-selectin were also performed in the same samples. Eleven psoriatic patients included in a therapeutic protocol based on the administration of infliximab monotherapy were collected before treatment and after 6 and 12 weeks of therapy. Significant decrease of MMP-9 and MMP-2 levels in the sera was associated with clinical improvement and with the decrease of TNF-alpha, VEGF, and E-selectin, angiogenic molecules already known to be implicated in the clinical expression of psoriasis. The clinical amelioration of the cutaneous expression of psoriasis was significantly associated with the decrease of MMP-9, TNF-alpha, and E-selectin levels, spontaneously released by lesional biopsy samples before and after therapy, measured in the culture supernatants by immunoenzymatic assays. In addition, significant correlations were found between the clinical score and TNF-alpha, MMP-9, and E-selectin lesional production. MMP-9 levels were significantly correlated with those of TNF-alpha. Our findings show the existence of a direct relationship between MMP-9 and TNF-alpha production, strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis, while a different role may be attributed to MMP-2.


Assuntos
Artrite Psoriásica/imunologia , Artrite Psoriásica/terapia , Metaloproteases/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pele/irrigação sanguínea , Pele/enzimologia , Pele/imunologia
18.
J Autoimmune Dis ; 3: 5, 2006 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-17022813

RESUMO

BACKGROUND: Inflammation represents an early and key event in the development of both the cutaneous psoriasis and psoriatic arthritis. Compelling evidences indicate that the production of TNF-alpha plays a central role in psoriasis by sustaining the inflammatory process in the skin as well as in the joints. Among the multiple effects produced by TNF-alpha on keratinocytes, the induction of matrix metalloproteinase-9 (MMP-9), a collagenase implicated in joint inflammatory arthritis which acts as an angiogenesis promoting factor, might represent a key mechanism in the pathogenesis of the disease. Aims of the present study were to investigate a) the role of MMP-9 in the development of psoriasis by assessing the presence of MMP-9 in lesional skin and in sera of psoriatic patients; b) the association of MMP-9 with the activity of the disease; c) the relationship between MMP-9 and TNF-alpha production. METHODS: Eleven psoriatic patients, clinically presenting joint symptoms associated to the cutaneous disease, were included in a therapeutic protocol based on the administration of anti-TNF-alpha monoclonal antibody (Infliximab). Sera and skin biopsies were collected before treatment and after 6 weeks of therapy. Tissues were kept in short term cultures and production soluble mediators such as TNF-alpha, MMP-9, MMP-2, VEGF and E-Selectin, which include angiogenic molecules associated to the development of plaque psoriasis, were measured in the culture supernatants by immunoenzymatic assays (ng/ml or pg/ml per mg of tissue). MMP-9 concentrations were also measured in the sera. The cutaneous activity of disease was evaluated by the Psoriasis Area and Severity Index (PASI). RESULTS: Clinical and laboratory assessment indicated that all but one patients had a significant improvement of the PASI score after three months of therapy. The clinical amelioration was associated to a significant decrease of MMP-9 (P = 0.017), TNF-alpha (P = 0.005) and E-selectin (P = 0.018) levels, spontaneously released by lesional biopsies before and after therapy. In addition, significant correlations were found between the PASI measurements and TNF-alpha (r2 = 0.33, P = 0.005), MMP-9 (r2 = 0.25, P = 0.017), E-selectin (r2 = 0.24, P = 0.018) production. MMP-9 levels were significantly correlated with those of TNF-alpha (r2 = 0.30, P = 0.008). A significant decrease of MMP-9 in the sera, associated to the clinical improvement was also found. CONCLUSION: Our findings show the existence of a direct relationship between MMP-9 and TNF-alpha production strongly suggesting that MMP-9 may play a key role in the skin inflammatory process in psoriasis.

19.
Cancer ; 107(9): 2282-90, 2006 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-16998933

RESUMO

BACKGROUND: Classic Kaposi sarcoma (CKS) is an inflammatory-mediated neoplasm that develops in the presence of KS-associated herpesvirus (KSHV) and immune perturbation. In the current study, the authors compared CKS cases with age-matched and sex-matched KSHV-seropositive controls without human immunodeficiency virus-1 infection and markers of viral control, blood counts, CD4-positive and CD8-positive lymphocytes, and serum beta-2-microglobulin and neopterin levels. METHODS: Viral loads were detected using real-time amplification of the KSHV-K6 and EBV-pol genes, anti-K8.1 (lytic) titers were detected by enzyme-linked immunoadsorbent assay, and antilatent nuclear antigen (LANA) titers were detected using immunofluorescence. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using logistic regression adjusted for sex, age, and study site. RESULTS: Peripheral blood mononuclear cells (PBMC) KSHV DNA detection (P < or = .0001) and high KSHV lytic (>1:1745; P < or = .0001) and latent (>1:102,400; P = .03) antibody titers were found to be positively associated with CKS risk. Antibody titers were higher in cases with lesions compared with cases without lesions (P < or =.05). The detection of Epstein-Barr virus (EBV) DNA in PBMCs was not found to be associated with CKS (P = .95). Independent of PBMC KSHV DNA, CKS risk was found to be positively associated with reduced hematocrit (<37.4%; P = .03), hemoglobin (<12g/dL; P = .04), and lymphocytes (<1000 cells/microL; P = .004), including CD4-positive (+) cells (<457 cells/microL; P = .07) and CD8+ cells (<213cells/microL; P = .04), and with increased monocytes (> or =638 cells/microL; P = .009). Nonsignificant elevations of beta-2-microglobulin and neopterin were observed among cases regardless of disease burden (P > or = .08). In a multivariate model, the CKS risk was found to be associated with PBMC KSHV DNA (OR of 2.7; 95% CI, 1.4-5.3), a high KSHV lytic antibody titer (OR of 3.7; 95% CI, 1.9-7.4), and low lymphocytes, particularly among those patients age <70 years (OR of 8.0; 95% CI, 2.7-23.7). CONCLUSIONS: The findings of the current study appear to corroborate the specificity of KSHV and highlight the hematologic and immunologic correlates involved in the pathogenesis of CKS.


Assuntos
Biomarcadores/sangue , Infecções por HIV/complicações , HIV-1/imunologia , Sarcoma de Kaposi/diagnóstico , Sarcoma de Kaposi/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Infecções por HIV/imunologia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Sarcoma de Kaposi/complicações
20.
Arch Dermatol ; 141(10): 1235-42, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16230560

RESUMO

OBJECTIVE: To investigate the prevalence of human herpesvirus 8 (HHV-8; Kaposi sarcoma-associated herpesvirus) infection in patients with lymphoproliferative skin diseases such as large-plaque parapsoriasis (LPP) and mycosis fungoides compared with inflammatory cutaneous conditions or healthy control subjects. DESIGN: A survey study was undertaken in 123 subjects with various clinical conditions. SETTING: All patients had been seen in the Dermatology Department of the San Gallicano Dermatology Institute, Rome, Italy, in the last 2 years. PATIENTS: Forty-five patients with inflammatory or autoimmune cutaneous diseases, 50 healthy control subjects, 10 patients with LPP, 12 patients with mycosis fungoides, and 6 patients with classic Kaposi sarcoma were included in the study. MAIN OUTCOME MEASURES: The prevalence of HHV-8 infection was investigated with serologic studies using the gold standard assay based on body cavity-based B-cell lymphoma-1 cells latently infected with HHV-8. The presence of HHV-8 conserved sequence, corresponding to open reading frame 26, was also assessed in the peripheral blood and lesion tissue samples from patients with lymphoproliferative cutaneous diseases with nested polymerase chain reaction. The presence and distribution of cell types infected with HHV-8 in the lesion tissues was determined with immunohistochemical staining with the monoclonal antibody directed against the latent nuclear antigen-1 of HHV-8 encoded by open reading frame 73. RESULTS: In healthy control subjects and patients with inflammatory skin diseases, 13.9% were found to have antibody against HHV-8, consistent with the seroprevalence population in Italy. A highly significant association of HHV-8 infection and LPP was found (100%) compared with mycosis fungoides (25%). The peripheral blood mononuclear cells in 8 of 10 patients with LPP were found to harbor viral sequences at nested polymerase chain reaction, whereas none of them had a detectable serum viral load. All LPP lesion tissue samples were positive for HHV-8-encoded open reading frame 26, and the presence of HHV-8-infected cells was confirmed by immunohistochemistry profiles performed on paraffin-embedded tissues from 4 of 10 patients. The positive cell types included endothelial cells and the infiltrating dermal lymphocytes, characteristic hallmarks of LPP. Analysis of T-cell receptor gamma chain rearrangements in lesion tissue from our patients confirmed the lack of a significant association between T-cell clonality and LPP. CONCLUSION: These data suggest that HHV-8 may play a role in the onset of LPP, a disease whose cause and evolution are still undefined and which has often been considered the early stage of mycosis fungoides.


Assuntos
Infecções por Herpesviridae/complicações , Herpesvirus Humano 8 , Transtornos Linfoproliferativos/virologia , Dermatopatias/virologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Estudos de Casos e Controles , Pré-Escolar , Rearranjo Gênico , Genoma Viral , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/imunologia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Transtornos Linfoproliferativos/sangue , Pessoa de Meia-Idade , Micose Fungoide/sangue , Micose Fungoide/genética , Micose Fungoide/virologia , Fases de Leitura Aberta , Prevalência , Psoríase/sangue , Psoríase/genética , Psoríase/virologia , Receptores de Antígenos de Linfócitos T gama-delta/genética , Sarcoma de Kaposi/sangue , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/virologia , Estudos Soroepidemiológicos
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