Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
1.
Sci Rep ; 11(1): 15816, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349137

RESUMO

We examined a series of structurally related glass-forming liquids in which a phenothiazine-based tricyclic core (PTZ) was modified by attaching n-alkyl chains of different lengths (n = 4, 8, 10). We systematically disentangled the impact of chemical structure modification on the intermolecular organization and molecular dynamics probed by broadband dielectric spectroscopy (BDS). X-ray diffraction (XRD) patterns evidenced that all PTZ-derivatives are not 'ordinary' liquids and form nanoscale clusters. The chain length has a decisive impact on properties, exerting a plasticizing effect on the dynamics. Its elongation decreases glass transition temperature with slight impact on fragility. The increase in the medium-range order was manifested as a broadening of the dielectric loss peak reflected in the lower value of stretching parameter ßKWW. A disagreement with the behavior observed for non-associating liquids was found as a deviation from the anti-correlation between the value of ßKWW and the relaxation strength of the α-process. Besides, to explain the broadening of loss peak in PTZ with the longest (decyl) chain a slow Debye process was postulated. In contrast, the sample with the shortest alkyl chain and a less complex structure with predominant supramolecular assembly through π-π stacking exhibits no clear Debye-mode fingerprints. The possible reasons are also discussed.

2.
J Phys Chem Lett ; 12(1): 245-249, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33331778

RESUMO

In this Letter we report significant differences in the dielectric behavior of four nonpolymeric and sizable glass-forming molecules with related chemical structures. They belong to the recently constituted class of sizable glass-formers [Jedrzejowska et al. Phys. Rev. E: Stat. Phys., Plasmas, Fluids, Relat. Interdiscip. Top. 2020, 101, 010603], for which the pattern of change in dielectric properties with structure has not yet been fully discovered. In the present study we tackle the fundamental problem of the structure-dynamics relationship. It was made possible by judicious choice of investigated systems with the values of dipole moments purposely kept at about the same level, and the only difference is the structure of the terminal substituents applied. The remarkable effect revealed by broadband dielectric spectroscopy is a large difference in the frequency dispersion of the α-relaxation for the systems studied. This interesting finding can be rationalized by the results of X-ray diffraction, clearly indicating the dissimilarities in the local intermolecular structure.

3.
Phys Rev E ; 101(1-1): 010603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32069682

RESUMO

In this Rapid Communication we report the unusual dynamics of planar, rigid, and anisotropy glass-forming molecules of unusually large size by dielectric spectroscopy by using two examples. The size of the molecules is much larger than the dipolar moiety located at the end of the longer axis of each molecule. The observed dynamics deviates strongly from the anticorrelation between ß_{KWW} (fractional exponent of the Kohlrausch-Williams-Watts function) and dielectric strength, Δɛ(T_{g}), established generally for small van der Waals molecular glass formers. Moreover, the dynamics of the two large molecules differ greatly, albeit the difference is the dipole moment being orthogonal or parallel to the longer axis of the molecules. The drastic variation in dielectric response of the two materials coming from different portions of the structural α-relaxation spectrum is probed by the dipole. Thus, the new behavior opens up a new research area of the dynamics and thermodynamics of nonpolymeric sizable molecules, the dielectric response of which can be varied by the design of the dipole moiety.

4.
Mol Pharm ; 13(3): 1111-22, 2016 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-26836258

RESUMO

In this article, we highlight the benefits coming from the application of amorphous protic ionic systems as active pharmaceutical ingredients (APIs). Using the case of the sumatriptan (STR) drug, we show that the conversion of nonionic API to partially ionized amorphous protic succinate salt (STR SUCC) brings a substantial improvement in apparent solubility. Since in general the disordered systems reveal a tendency to self-arrangement during storage, the dominant part of this article is dedicated to the physical stability issue of sumatriptan and its ionic counterpart. To recognize the crystallization tendency of the studied systems, the calorimetric measurements were performed. Additionally, the role of ion dynamics in spontaneous nucleation of amorphous sumatriptan succinate is discussed. The differential scanning calorimetry analysis of ionic and nonionic sumatriptan reveals many similarities in thermal properties of these APIs as well as distinct differences in their resistance against crystallization in the supercooled liquid state. To determine the long-term physical stability of STR SUCC at room temperature conditions, the time scale of structural relaxation below their glass transition temperatures is estimated. We show that in contrast to nonionic materials, τα predictions of STR SUCC are much more complex and require aging experiments.


Assuntos
Estabilidade de Medicamentos , Líquidos Iônicos , Ácido Succínico/química , Sumatriptana/química , Varredura Diferencial de Calorimetria , Cristalização , Solubilidade , Temperatura de Transição , Difração de Raios X
5.
Clin Exp Dermatol ; 40(1): 11-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25223230

RESUMO

INTRODUCTION: Studies have found that the interleukin-23/T helper 17 (IL-23/Th17) pathway plays an important role in the pathogenesis of atopic dermatitis (AD). Inhibition of the IL-23/Th17 pathway with monoclonal antibodies reduces skin inflammation in animal models. AIM: To investigate the association between IL-17A and IL-23R gene single nucleotide polymorphisms (SNPs) and the development of AD in a Polish population. METHODS: Blood samples were collected from 166 patients with AD and 160 controls. We analyzed two SNPs, -152 G/A IL-17A and 1142 G/A IL-23R, using PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: There was no statistically significant difference between the examined IL-17A SNP and the incidence of AD (P > 0.05 for all comparisons). Analysis of the IL-23R gene SNP showed no relationship between AD and the G/A genotype or presence of the A allele. The study did not establish any links between the IL-23R and IL-17A gene SNPs and the likelihood of developing AD resulting from gene-gene interaction. However, there was a significant relationship between the A/A genotype in the -152 G/A IL1-7A SNP and the coexistence of AD and asthma (P < 0.04). Analyzing the association between AD severity and the occurrence of IL-17A SNP, we found that subjects with the A/A genotype were at higher risk of developing moderate or severe AD (P = 0.02). CONCLUSIONS: We found no evidence of any effect of IL-17A or IL-23R SNPs on the occurrence of AD in our Polish population. However, the A/A genotype in IL-17A was found to predispose to increased AD severity and coexistence of AD and asthma.


Assuntos
Asma/complicações , Dermatite Atópica/genética , Predisposição Genética para Doença , Interleucina-17/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Incidência , Lactente , Masculino , Polônia/epidemiologia , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina/genética , Índice de Gravidade de Doença , Adulto Jovem
6.
Lupus ; 23(2): 188-93, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24297641

RESUMO

Despite precise definitions and exclusions for 19 syndromes of neuropsychiatric systemic lupus erythematosus (NPSLE), under some circumstances it appears to be difficult to differentiate whether neuropsychiatric symptoms are caused by SLE or by other reasons such as primary mental disorders or substance-induced mood disorders, especially induced by glucocorticoids or antimalarials. We report the case of a male patient with SLE who presented with an exacerbation of bipolar disorder triggered by chloroquine. Firstly, when the patient was diagnosed with SLE, he underwent six months of therapy with chloroquine without any psychiatric symptoms. Later, the SLE returned and the patient was prescribed chloroquine again, without any mental illness. When the third exacerbation of SLE occurred, it coincided with a severe depressive episode with psychotic features that became aggravated for the first time after the administration of chloroquine. The chloroquine was subsequently replaced with hydroxychloroquine for the next six months without any behavioral problems, following which, the SLE and mood disorder were in remission. Later, a bipolar disorder relapse occurred, manifested by a manic episode, and in the following three months, despite psychiatric treatment, a manic episode with psychotic features developed four days after chloroquine was prescribed for arthritis. It was the second time that the mood disorder was exacerbated by chloroquine. Since that time, chloroquine has been withdrawn. Currently the patient is undergoing treatment with hydroxychloroquine and psychiatric drugs with good response. Our case points out that although chloroquine-induced psychosis is rare, patients presenting with behavioral changes need physicians' attention in order to diagnose early and efficiently treat encountered mood disorders.


Assuntos
Transtorno Bipolar/etiologia , Cloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Cloroquina/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lúpus Eritematoso Sistêmico/psicologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , Vasculite Associada ao Lúpus do Sistema Nervoso Central/tratamento farmacológico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/psicologia , Masculino
7.
Lupus ; 22(14): 1504-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24243911

RESUMO

OBJECTIVE: Recent data indicate that Toll-like receptors (TLRs) participate in various neuropathologic conditions, including ictogenesis, myelin disruptions associated with chronic alcohol abuse, behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage, and activation of microglia to reduce amyloid ß deposits. As seizures and depression are well known neuropsychiatric syndromes in systemic lupus erythematosus (SLE) the aim of the study was to investigate whether TLR4 gene polymorphism 1196C/T (rs4986791, Thr399Ile) was a candidate for susceptibility of development of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: The study covered 60 patients with SLE and 100 healthy individuals. TLR4 1196C/T genotyping was performed by real-time polymerase chain reaction with the SimpleProbe. RESULTS: The SLE group comprised 86.7% of patients with wild-type homozygotes CC and 13.3% heterozygotes CT and no homozygotes TT. The control group consisted of 85% wild-type homozygotes CC, 15% heterozygotes CT and no homozygotes TT. The frequencies of genotype and allele distribution in SLE patients did not differ significantly from those of the control subjects. The probability of describing the possible risk of SLE imputed to genotype did not significantly differ in comparison with the healthy individuals (p = 0.77, odds ratio = 0.87, 95% confidence interval 0.34-2.19). A significant genotype association of genotype CC with arthritis was found in SLE patients (p = 0.02). It was further confirmed by a significant association of a dominant allele C with arthritis (p = 0.02). No association between CC and CT genotypes of TLR4 1196C/T and NPSLE was found. Allele distribution of TLR4 1196C/T also was not associated with NPSLE. No other significant differences were found in genotype and allele frequencies regarding clinical manifestation of SLE patients. CONCLUSION: In the Polish population of SLE patients, 1196C/T polymorphism of TLR4 gene does not increase the risk of development of NPSLE; however, genotype CC and a dominant allele C is associated with arthritis in the course of SLE.


Assuntos
Artrite/genética , Lúpus Eritematoso Sistêmico/genética , Vasculite Associada ao Lúpus do Sistema Nervoso Central/genética , Receptor 4 Toll-Like/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Polimorfismo Genético , Reação em Cadeia da Polimerase em Tempo Real , Risco
10.
Scand J Immunol ; 76(4): 405-10, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22686584

RESUMO

Regulatory T cells (Tregs), toll-like receptors (TLRs) and interleukin-17 (IL-17) play important role in inflammatory diseases; however, their relevance in atopic dermatitis (AD) pathogenesis is not clear. The aim of study was to evaluate the number of circulating Tregs and peripheral blood mononuclear cells (PBMC) expressing TLR2 and TLR4 receptors in patients with AD. PBMC and CD4+/CD25(high) + Tregs were isolated from the whole blood of 32 AD patients and 36 healthy volunteers. Expression of CD4+CD25+, TLR2 and TLR4 receptors and IL 17+ was assessed with the flow cytometry. In the peripheral blood of AD patients, the percentage of Tregs was significantly higher when compared with the controls (P=0.0003). The number of TLR2+PBMC and TLR4+ PBMC in AD patients was significantly lower than in the controls (P=0.035; P=0.001, respectively). Also the percentages of Tregs with expression of both TLR2+ and TLR4+ in AD patients were significantly lower than in the control (3.85 versus 21.6, P<0.0001; 2.2 versus 17.6, P<0.0001, simultaneously). The percentage of CD4+/CD25high+/FOXP3+ Treg lymphocytes with expression of IL-17 was significantly higher in AD group than in healthy subjects (0.3% versus 0.06%; P=0.011). Distinct number of Tregs and various distribution of TLR2 and TLR4 expression on PBMC in AD patients suggest their contribution in the pathogenesis of AD.


Assuntos
Dermatite Atópica/imunologia , Linfócitos T Reguladores/imunologia , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Adulto , Antígenos CD/imunologia , Estudos de Casos e Controles , Dermatite Atópica/sangue , Dermatite Atópica/patologia , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Interleucina-17/biossíntese , Interleucina-17/imunologia , Masculino , Linfócitos T Reguladores/patologia , Receptor 2 Toll-Like/sangue , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/sangue , Receptor 4 Toll-Like/genética
11.
Lupus ; 21(5): 477-84, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22065093

RESUMO

OBJECTIVES: To identify relationships between vitamin D serum levels and the presence of autoantibodies directed against vitamin D and levels of interleukin(IL)-17 and IL-23 in patients with systemic lupus erythematosus (SLE). METHODS: The study included 49 patients with SLE. Serum concentrations of 25(OH)D(3) were measured with electrochemiluminescence immunoassay (ECLIA). Enzyme-linked immunosorbent assays (ELISA) were used to determine antibodies directed against 1,25(OH)(2)D(3) and levels of IL-17 and IL-23 in serum of SLE patients. In evaluation of vitamin D status, the control group consisted of 49 age and gender matched healthy individuals, whereas in assessment of anti-vitamin D antibodies the control group comprised 30 sera from blood donors. RESULTS: Serum concentration of 25(OH)D(3) in SLE patients during the warm season was 18.47 ± 9.14 ng/ml, which was significantly decreased as compared with that of the control group - 31.27 ± 12.65 ng/ml (p = 0.0005). During the cold season a trend toward lower concentration of 25(OH)D(3) in SLE patients was revealed; however, it did not reach statistical significance (11.71 ± 7.21 ng/ml vs. 16.01 ± 8.46 ng/ml; p = 0.054). Results within the recommended range for vitamin D (30-80 ng/ml; 70-200 nmol/l) were observed only in three patients. The 25(OH)D(3) concentration was decreased in SLE patients with renal disease or leucopenia as compared with the levels in patients who did not have either problem (p = 0.006 and p = 0.047, respectively). The cold season was found to be a risk factor for vitamin D deficiency (<20 ng/ml) (odds ratio = 9.25; p = 0.005). Autoantibodies directed against 1,25(OH)(2)D(3) were detected in three SLE patients. No significant difference in 25(OH)D(3) serum concentrations was found between SLE patients with and without these autoantibodies. No link was shown between the existence of autoantibodies against 1,25(OH)(2)D(3) and clinical or laboratory findings, including IL-17 and IL-23 levels. However, serum concentrations of IL-23 were lower in patients with vitamin D deficiency (p = 0.037). CONCLUSIONS: SLE patients, especially those with leucopenia or renal involvement, are at high risk of vitamin D deficiency and require vitamin D supplementation. Some SLE patient sera contained 1,25(OH)(2)D(3) antibodies, but these antibodies do not appear to affect vitamin D levels.


Assuntos
Autoanticorpos/imunologia , Calcifediol/sangue , Lúpus Eritematoso Sistêmico/imunologia , Deficiência de Vitamina D/etiologia , Adulto , Idoso , Calcifediol/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-17/sangue , Interleucina-17/imunologia , Interleucina-23/sangue , Interleucina-23/imunologia , Nefropatias/etiologia , Leucopenia/etiologia , Medições Luminescentes , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estações do Ano , Deficiência de Vitamina D/epidemiologia , Adulto Jovem
12.
Br J Dermatol ; 165(2): 383-90, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21495995

RESUMO

BACKGROUND: Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first-line option in the treatment of moderate to severe acne vulgaris. OBJECTIVES: To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%-BPO 2·5% (A/BPO) fixed-dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. METHODS: A total of 378 subjects were randomized in a double-blind, controlled trial to receive once-daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects 'clear' or 'almost clear'), skin tolerability, adverse events and patients' satisfaction. RESULTS: The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (-74·1%) than in the lymecycline with vehicle group (-56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P < 0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were 'very satisfied' was significantly greater (P = 0·031). CONCLUSION: These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.


Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/administração & dosagem , Peróxido de Benzoíla/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Limeciclina/administração & dosagem , Naftalenos/administração & dosagem , Adapaleno , Administração Oral , Administração Tópica , Adolescente , Adulto , Antibacterianos/efeitos adversos , Peróxido de Benzoíla/efeitos adversos , Criança , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/métodos , Feminino , Géis , Humanos , Limeciclina/efeitos adversos , Masculino , Naftalenos/efeitos adversos , Satisfação do Paciente , Veículos Farmacêuticos , Resultado do Tratamento , Adulto Jovem
13.
Lupus ; 19(6): 683-8, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20064914

RESUMO

Antimalarials are widely used for the treatment of systemic lupus erythematosus. However, their mechanisms of action have not been fully elucidated. Literature data indicate that matrix metalloproteinases may play a role in the immune response and tissue damage that occur in autoimmune skin diseases. The aim of this study was to determine the effect of 3 months of chloroquine treatment on serum levels of MMP-9 and TIMP-1 in patients with systemic lupus erythematosus. The study group consisted of 25 patients with systemic lupus erythematosus and 25 sex- and age-matched healthy volunteers. Before drug administration, serum levels of MMP-9 and TIMP-1 were determined by enzyme-linked immunosorbent assay. The same procedure was performed after chloroquine treatment. We found significantly higher median serum levels of MMP-9 in patients with systemic lupus erythematosus before therapy (57.20 ng/ml) when compared with controls (44.50 ng/ml) (p < 0.001). After chloroquine therapy the median MMP-9 serum level of systemic lupus erythematosus patients decreased significantly (43 ng/ml; p < 0.001). Before treatment the median TIMP-1 serum level in the patients with systemic lupus erythematosus was significantly higher than in the control group (500 vs. 200 ng/ml; p < 0.001), and after therapy it increased significantly (750 ng/ml TIMP-1; p < 0.001). The results suggest that chloroquine treatment may affect the matrix metalloproteinase network, and this effect may contribute to the immunoregulatory and anti-inflammatory properties of antimalarials.


Assuntos
Antimaláricos/uso terapêutico , Cloroquina/análogos & derivados , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Metaloproteinase 9 da Matriz/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Adulto , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Cloroquina/uso terapêutico , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
14.
J Eur Acad Dermatol Venereol ; 24(1): 38-42, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19552717

RESUMO

OBJECTIVE: Systemic lupus erythematosus is an autoimmune disease with uncertain prognosis as to the course. The patients need pharmacotherapy all their life. The main aim of this study was to determinate the impact of therapeutic schedules on patients' quality of life. METHODS: The study was performed on 83 patients who were divided into five groups according to methods of treatment used. Quality of life was measured using MOS SF-36. RESULTS: Obtained results revealed that therapeutic schedules have the highest influence on patients' social functioning. The more medicaments the patients use, the lower their quality of life. CONCLUSIONS: The type of medicaments and therapeutic schemes adopted affect the patients' quality of life. Nevertheless, quality of life and the patients' attitude to it are very subjective and are also influenced by the clinical state of the patients as well as many other factors such as socioeconomic and demographic.


Assuntos
Lúpus Eritematoso Sistêmico/fisiopatologia , Qualidade de Vida , Adulto , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Inquéritos e Questionários
15.
Br J Dermatol ; 161(4): 890-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19709099

RESUMO

BACKGROUND: Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis. OBJECTIVES: To monitor the expression of cell cycle proteins in the epidermis of subjects after repeated exposure to ultraviolet (UV) B radiation, and to test for the development of photoprotection by subsequent irradiation with a single erythemal UVB dose. METHODS: A total of 26 healthy volunteers were divided into four groups: group 1 (n = 9) were given whole-body UVB irradiation for 10 consecutive days with 0.7 minimal erythema dose (MED), group 2 (n = 9) were irradiated as in group 1 followed 24 h later by a single UVB dose of 3 MED on buttock skin, group 3 (n = 4) were irradiated with a UVB dose of 3 MED on buttock skin, and group 4 (n = 4) were not irradiated. Skin biopsies were collected 24 h after the final irradiation and stained for cyclins A, B1, D1, and p16, p18, p21, p27, p53, pRB, Bax and Bcl-2. RESULTS: The expression of cyclin D1, p18 and p21 was significantly higher in groups 1 and 2 compared with the nonirradiated group 4 controls and, in group 2, the expression of pRB, p53 and Bax was also increased. In group 3, only p53 and Bax proteins were significantly elevated compared with group 4. The expression of cyclin D1, p16, p18, p27, pRB and Bcl-2 was higher in group 2 compared with group 3. CONCLUSIONS: Suberythemal UVB radiation was sufficient to cause changes in the expression of several epidermal cell cycle proteins. When tested by irradiation with a single erythemal UVB dose following the repeated exposures, no photoprotection against the UV-induced alteration in cell cycle protein expression was apparent.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Epiderme/efeitos da radiação , Eritema/metabolismo , Raios Ultravioleta/efeitos adversos , Irradiação Corporal Total/efeitos adversos , Adulto , Idoso , Proteínas de Ciclo Celular/genética , Células Cultivadas , Relação Dose-Resposta à Radiação , Epiderme/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Proteção Radiológica , Regulação para Cima/efeitos da radiação
16.
Lupus ; 18(4): 332-41, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19276301

RESUMO

The aim of our study was to assess absolute counts of different subpopulations of circulating endothelial cells (CEC) in patients with active and inactive systemic lupus erythematosus (SLE). We have also investigated a potential correlation of CEC numbers with serum levels of angiogenic proteins as well as with clinical and laboratory symptoms of the disease. For the first time in SLE, CEC were enumerated directly, by the 'single platform' method. Resting (rCEC), activated (aCEC) and progenitor (pCEC) endothelial cells were identified in patients with SLE and healthy volunteers using four-colour flow cytometry. Serum concentrations of angiogenic proteins (vascular endothelial growth factor, placental growth factor (PIGF), soluble vascular cell adhesion molecule and endoglin) were evaluated by ELISA. The SLE activity was scored according to the Systemic Lupus Activity Measure system. We found that total CEC number in patients with SLE was significantly higher (median 14.2/microL) than in the control group (median 3.3/microL) (P < 0.0001). Absolute counts of aCEC, rCEC and pCEC (medians 4.9/microL, 6.8/microL and 2.3/microL, respectively) were also higher in patients with SLE than in healthy persons (medians 0.9/microL, 1.6/microL and 0.1/microL, respectively), with P < 0.0001 for all comparisons. There was no correlation between CEC or their subpopulations and SLE activity. Strong positive correlations were found between CEC, rCEC and pCEC numbers and serum levels of PIGF. Moreover, aCEC, rCEC and pCEC counts were significantly higher in SLE patients with leukopenia. In conclusion, our results show that absolute CEC counts and angiogenic proteins levels are elevated in patients with SLE as compared with healthy controls. These data may suggest that angiogenic process is involved in the pathogenesis of this disease.


Assuntos
Proteínas Angiogênicas/sangue , Células Endoteliais/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Adolescente , Adulto , Idoso , Antígenos CD/sangue , Contagem de Células , Endoglina , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neovascularização Patológica , Receptores de Superfície Celular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
17.
J Eur Acad Dermatol Venereol ; 23(3): 251-5, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19207649

RESUMO

PURPOSE: To determinate satisfaction with life together with positive and negative emotions in SLE patients and correlate them with each other and with activity of the disease, duration of the disease and age of the patient. METHODS: The study was conducted on 83 SLE patients who fulfilled at least 4 out of 11 ACR criteria. Satisfaction with life was measured by the Satisfaction with Life Scale. Positive and negative aspects were assessed by the Positive and Negative Affects Schedule. Other data were collected from the patients at the same time. RESULTS: SLE patients presented reduced satisfaction with life. Duration of the disease, as well as age of the patients had an influence on it. Correlations between patients' quality of life emotions and life's satisfaction were present. CONCLUSIONS: SLE as a chronic, incurable and unpredictable disease has a great influence on patients' life. The awareness of this may lead to better compliance and to develop a new strategy of therapy.


Assuntos
Lúpus Eritematoso Sistêmico/psicologia , Satisfação Pessoal , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polônia
18.
Clin Exp Dermatol ; 34(5): 570-5, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19077101

RESUMO

BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic cutaneous form of lupus erythematosus, characterized by inflammation and scarring skin lesions, with lymphocyte infiltration and vasodilation. Antimalarial drugs have beneficial therapeutic effects in DLE, partially resulting from their immunomodulating and photoprotective properties. The possible influence of these drugs on angiogenesis has not been previously evaluated. AIMS: To investigate the impact of chloroquine (CQ) treatment on the expression of vascular endothelial growth factor (VEGF, a major regulator of angiogenesis) and CD34 (a transmembrane glycoprotein expressed on endothelial cells and involved in tethering lymphocytes) in patients with DLE. METHODS: A 3-mm skin biopsy was taken from typical skin lesions in 10 people with DLE. Another biopsy was taken from the same area after 3 months of treatment with CQ (250 mg/day). Skin sections were stained with monoclonal antibodies directed against VEGF and CD34. The intensity of epidermal VEGF expression, and the number and area of CD34-positive dermal blood vessels were assessed. RESULTS: CQ treatment induced a reduction in epidermal VEGF expression. It also resulted in a significant decrease in the median number of CD34+ dermal blood vessels (from 219 to 125 vessels per mm(2)). Furthermore the median vessel area was significantly lowered from 9.76 x 10(6) to 6.92 x 10(6) mm(2) per mm(2) of the dermis. CONCLUSIONS: These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Cloroquina/uso terapêutico , Lúpus Eritematoso Discoide/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , Pele/irrigação sanguínea , Adulto , Antígenos CD34/metabolismo , Feminino , Humanos , Lúpus Eritematoso Discoide/metabolismo , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Pele/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
20.
Br J Dermatol ; 159(5): 1124-30, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18764842

RESUMO

BACKGROUND: There are very few data addressing the mechanisms of antimalarial treatment benefit locally within the skin of patients with lupus erythematosus, at the level of cytokine messenger RNA (mRNA) expression. OBJECTIVES: The aim of this study was to evaluate whether 3 months of monotherapy with chloroquine influences the mRNA skin expression of interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in nonirradiated and locally ultraviolet B (UVB) irradiated nondiseased skin of patients with systemic lupus erythematosus (SLE). PATIENTS/METHODS: Skin biopsies were collected from 14 patients with SLE 24 h after irradiation at one site and from an adjacent unirradiated site, before and after 3 months of chloroquine treatment. Messenger RNA levels for IL-1beta, IL-6 and TNF-alpha were determined by relative quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: There were no significant differences in the levels of mRNA cytokine expressions in the unirradiated sites before and after 3 months of chloroquine administration. In the irradiated sites, the expression of all three cytokine mRNA levels was significantly higher than in the unirradiated group, approximately 24 h after irradiation, before chloroquine treatment. Significantly lower expression of IL-1beta, IL-6 and TNF-alpha mRNAs was noted in irradiated skin samples after 3 months of chloroquine treatment. CONCLUSIONS: These results demonstrate the local inhibitory effects of chloroquine on UVB-induced upregulation in the mRNA expression of proinflammatory cytokines in irradiated skin of SLE patients, and provide further insight into the apparent immunomodulatory, anti-inflammatory and photoprotective properties of chloroquine.


Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Citocinas/metabolismo , Lúpus Eritematoso Sistêmico/tratamento farmacológico , RNA Mensageiro/análise , Pele/efeitos da radiação , Adulto , Citocinas/genética , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Raios Ultravioleta , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...