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1.
Arthritis Rheum ; 64(1): 285-96, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22031171

RESUMO

OBJECTIVE: Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. METHODS: A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. RESULTS: Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups. CONCLUSION: Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , Ácidos Heptanoicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Pirróis/uso terapêutico , Adolescente , Aterosclerose/complicações , Aterosclerose/diagnóstico , Atorvastatina , Espessura Intima-Media Carotídea , Criança , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Lipídeos/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Masculino , Resultado do Tratamento , Adulto Jovem
2.
J Exp Med ; 180(2): 607-14, 1994 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-8046336

RESUMO

Human interleukin 1 beta (IL-1 beta) is synthesized as an inactive precursor that is cleaved by IL-1 converting enzyme (ICE) between Asp116 and Ala117 to form COOH-terminal mature IL-1 beta and NH2-terminal IL-1 beta propeptide. Little is known about the fate of the NH2-terminal cleavage product. In this study, human recombinant (hr)IL-1 beta propeptide (amino acids 2-116) was produced and used to prepare specific antibodies which do not recognize mature human IL-1 beta. These anti-propeptide antibodies were used for immunoprecipitation of biosynthetically labeled proteins from lipopolysaccharide-stimulated human monocytes. Analysis of immunoprecipitates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography revealed that these antibodies recognize precursor IL-1 beta and two unique proteins: one migrating at 17.5 kD and one at 14 kD. The larger of these two proteins has a migration nearly identical to that of the recombinant IL-1 beta propeptide, and most likely represents naturally derived propeptide. The protein migrating at 14 kD may result from a second cleavage by ICE, between Asp27 and Gly28. These proteins accumulate intracellularly and extracellularly during pulse-chase experiments, and therefore represent stable products of precursor IL-1 beta cleavage.


Assuntos
Interleucina-1/metabolismo , Lipopolissacarídeos/imunologia , Monócitos/imunologia , Especificidade de Anticorpos , Sequência de Bases , Ligação Competitiva , Western Blotting , Cromatografia de Afinidade , DNA , Eletroforese em Gel de Poliacrilamida , Humanos , Dados de Sequência Molecular , Monócitos/metabolismo , Testes de Precipitina , Precursores de Proteínas/metabolismo , Proteínas Recombinantes/imunologia
3.
Lupus ; 19(11): 1315-25, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20861207

RESUMO

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares , Lúpus Eritematoso Sistêmico , Adolescente , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Criança , Colesterol/sangue , Estudos Transversais , Método Duplo-Cego , Feminino , Humanos , Lipoproteína(a)/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Placebos , Fatores de Risco , Triglicerídeos/sangue , Adulto Jovem
4.
JPRAS Open ; 24: 7-11, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32258334

RESUMO

Obstetric brachial plexus injury is reported in 0.42 per 1000 births in UK and Ireland and are associated with a reduction in quality of life for the patient and their carers. In this report we describe the first use of a patient specific, anatomically accurate 3D model as a communication tool in the treatment of a complex case of posterior shoulder subluxation secondary to glenohumeral deformity resulting from obstetric brachial plexus injury. The use of 3D models for surgical planning is associated with decreased operating time and reduction of intra-operative blood loss, whilst their use in patient education increases patient understanding. In this case all surgeons surveyed agreed that it was useful and will use 3D modelling to improve consent processes and to conceptualise novel techniques for complex cases in future. This highly reproducible, low cost technique may be adapted to a variety of upper limb reconstructive surgeries, and as the resolution of image acquisition and additive manufacturing capabilities increase so too do the potential applications of this precise 3D printed surgical adjunct.

7.
Mol Immunol ; 23(2): 97-109, 1986 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2939336

RESUMO

Antigen-specific receptors of B- or T-cells were selectively radiolabeled among the spleen cells from either human gammaglobulin immunized normal or bursectomized agammaglobulinemic chickens. Selective in situ radioiodination was accomplished by employing lactoperoxidase (LPO) covalently linked to antigen (Ag). Ag-specific receptors on B- or T-cells were allowed to bind Ag-LPO conjugates via the Ag portion of the conjugates and then to be selectively catalyzed for iodination by the LPO portion of the bound Ag-LPO conjugates. Radioiodinated cells were either processed for autoradiography to detect Ag-binding cells directly under the microscope or solubilized with detergents for protein analysis with two-dimensional (2-D) gel electrophoresis. On a cellular level, Ag-binding B- and T-cells were selectively radiolabeled and clearly visualized via autoradiography. On a molecular level, selectively radiolabeled Ag-specific membrane immunoglobulin of B-cells was demonstrated on 2-D gel autoradiographs. Furthermore, a unique polypeptide of Ag-specific T-cells with a reduced apparent mol. wt of 27 K and an apparent pI of 5.5-5.7 was demonstrated on 2-D gel autoradiograms. The 27 K molecule appears to be a T-cell receptor component itself, or a closely associated molecule.


Assuntos
Receptores de Antígenos de Linfócitos T/análise , Linfócitos T Reguladores/imunologia , Animais , Linfócitos B/imunologia , Galinhas , Eletroforese em Gel de Poliacrilamida , Radioisótopos do Iodo , Focalização Isoelétrica , Lactoperoxidase , Peptídeos/análise , Receptores de Antígenos de Linfócitos B/análise
10.
Am J Med Sci ; 324(2): 101-3, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12187928

RESUMO

Relapsing polychondritis (RP) is a disease characterized by inflammation and the destruction of cartilage. The detection of antibodies to native type II collagen (CII) in the sera of some patients with relapsing polychondritis suggests that autoimmunity to this cartilage specific protein plays a role in the pathogenesis of the disease. RP is so rare that controlled therapeutic trials have not been carried out. We describe herein a child with RP who had amelioration of symptoms and a deviation in the cellular immune response to CII after being treated with daily oral CII as a toleragen.


Assuntos
Colágeno Tipo II/administração & dosagem , Policondrite Recidivante/tratamento farmacológico , Policondrite Recidivante/imunologia , Pró-Colágeno/administração & dosagem , Administração Oral , Autoimunidade , Criança , Colágeno Tipo II/imunologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pró-Colágeno/imunologia , Linfócitos T/imunologia , Resultado do Tratamento
11.
Br J Pharmacol ; 171(8): 1917-42, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24720258

RESUMO

Diabetic nephropathy (DN) is a progressive microvascular complication arising from diabetes. Within the kidney, the glomeruli, tubules, vessels and interstitium are disrupted, ultimately impairing renal function and leading to end-stage renal disease (ESRD). Current pharmacological therapies used in individuals with DN do not prevent the inevitable progression to ESRD; therefore, new targets of therapy are urgently required. Studies from animal models indicate that disturbances in mitochondrial homeostasis are central to the pathogenesis of DN. Since renal proximal tubule cells rely on oxidative phosphorylation to provide adequate ATP for tubular reabsorption, an impairment of mitochondrial bioenergetics can result in renal functional decline. Defects at the level of the electron transport chain have long been established in DN, promoting electron leakage and formation of superoxide radicals, mediating microinflammation and contributing to the renal lesion. More recent studies suggest that mitochondrial-associated proteins may be directly involved in the pathogenesis of tubulointerstitial fibrosis and glomerulosclerosis. An accumulation of fragmented mitochondria are found in the renal cortex in both humans and animals with DN, suggesting that in tandem with a shift in dynamics, mitochondrial clearance mechanisms may be impaired. The process of mitophagy is the selective targeting of damaged or dysfunctional mitochondria to autophagosomes for degradation through the autophagy pathway. The current review explores the concept that an impairment in the mitophagy system leads to the accelerated progression of renal pathology. A better understanding of the cellular and molecular events that govern mitophagy and dynamics in DN may lead to improved therapeutic strategies.


Assuntos
Nefropatias Diabéticas/fisiopatologia , Doenças Mitocondriais/fisiopatologia , Mitofagia/fisiologia , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Autofagia/fisiologia , Morte Celular/fisiologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/tratamento farmacológico , Fibrose/fisiopatologia , Humanos , Doenças Mitocondriais/complicações , Doenças Mitocondriais/tratamento farmacológico , Mitofagia/efeitos dos fármacos , Modelos Biológicos , Terapia de Alvo Molecular
12.
Rheumatology (Oxford) ; 45(5): 614-20, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16368732

RESUMO

OBJECTIVE: Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. METHODS: A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. RESULTS: Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. CONCLUSION: This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.


Assuntos
Esclerodermia Localizada/diagnóstico , Adolescente , Idade de Início , Autoanticorpos/sangue , Doenças Autoimunes/genética , Criança , Pré-Escolar , Meio Ambiente , Feminino , Predisposição Genética para Doença , Humanos , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Cooperação Internacional , Masculino , Metotrexato/uso terapêutico , Doenças Reumáticas/genética , Fatores de Risco , Esclerodermia Localizada/tratamento farmacológico , Esclerodermia Localizada/epidemiologia , Esclerodermia Localizada/etiologia
13.
J Rheumatol ; 23(6): 965-73, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8782124

RESUMO

OBJECTIVE: To partially purify and characterize a specific inhibitor of interleukin 1 alpha (IL-1 alpha) activity from synovial fluids (SF) of patients with rheumatoid arthritis. METHODS: SF inhibitor of IL-1 alpha (SFI alpha) was partially purified by ammonium sulfate precipitation, gel filtration, anion exchange chromatography, and chromatofocusing. Specificity of inhibition of IL-1 alpha activity was tested in T lymphocyte proliferation assays. The mechanism of this inhibition was investigated by binding assays and mobility shift on gel filtration. RESULTS: The SFI alpha inhibited all in vitro activities of IL-1 alpha tested, but did not inhibit activities of IL-1 beta or IL-2. Inhibitor activity was not diminished by neutralizing antibodies against the IL-1 receptor antagonist, and was not removed by immunoadsorption with antibodies against IL-1 receptors. It was not depleted by monoclonal antibodies against human IgG subclasses, IgA, or IgM. The SFI alpha specifically inhibited binding of IL-1 alpha to cell surface receptors, and appeared to form a high molecular weight complex with IL-1 alpha. CONCLUSION: SFI alpha appeared to block biological activities of IL-1 alpha by specific binding to this cytokine, thereby preventing receptor occupancy. The SFI alpha did not appear to be related to previously described inhibitors of IL-1.


Assuntos
Artrite Reumatoide/metabolismo , Interleucina-1/antagonistas & inibidores , Líquido Sinovial/química , Animais , Anticorpos/análise , Western Blotting , Células Cultivadas , Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Humanos , Imunoensaio , Interleucina-1/imunologia , Interleucina-1/isolamento & purificação , Interleucina-1/metabolismo , Camundongos , Camundongos Endogâmicos , Receptores de Interleucina-1/química
14.
J Biol Chem ; 263(4): 1676-81, 1988 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-2828348

RESUMO

Genomic DNA containing the protein coding region for Drosophila cAMP-dependent protein kinase catalytic subunit has been cloned and sequenced. The probe used to detect and isolate the gene fragment was constructed from two partially complementary synthetic oligonucleotides and contains 60 base pairs that encode (using Drosophila codon preferences) amino acids 195-214 of the beef heart catalytic subunit. In reduced stringency hybridization conditions, the probe recognizes two target sites in fly genomic DNA with 85% homology. One of these sites is in the cAMP-dependent protein kinase catalytic subunit gene, which was isolated as a 3959-base pair HindIII fragment. This fragment contains all of the protein coding portion, 900 base pairs upstream of the initiator ATG, and 2000 base pairs downstream of the termination codon (TAG). The coding portion of the gene contains no introns and yields a protein of 352 amino acids. There is a 2-amino acid insertion near the N terminus of the fly protein relative to the beef and mouse enzymes. Of the remaining 350 amino acids, 273 are invariant in the three species. A probe derived from the coding sequence of the HindIII clone hybridizes strongly to a 5100-base poly(A)+ RNA and weakly to 4100- and 3400-base poly(A)+ RNAs expressed in adult flies. A 2100-base pair EcoRI genomic fragment containing the second site recognized by the 60-base pair probe has also been cloned. DNA sequence analysis demonstrates that this fragment is part of the cGMP-dependent protein kinase gene or a close homolog. The catalytic subunit gene and the cGMP-dependent protein kinase gene have been located in regions 30C and 21D, respectively, of chromosome 2.


Assuntos
Clonagem Molecular , Regulação da Expressão Gênica , Proteínas Quinases/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Enzimas de Restrição do DNA/metabolismo , Desoxirribonuclease HindIII , Drosophila/enzimologia , Drosophila/genética , Dados de Sequência Molecular
15.
J Biol Chem ; 271(38): 23322-8, 1996 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-8798533

RESUMO

The protein encoded by the Drosophila cGMP-dependent protein kinase gene, DG1, was expressed in Sf9 cells. cGMP (10 microM) stimulated histone H2B phosphorylation by the DG1 protein kinase 20-fold. Maximal activity was observed at 40-50 mM Mg2+. The concentrations of cGMP, cAMP, cIMP, 8-bromo-cGMP, and 8-bromo-cAMP that gave 50% activation were 0.19 +/- 0.06, 11.7 +/- 2.8, 5.3 +/- 1.5, 0.04 +/- 0. 01, and 0.62 +/- 0.06 microM, respectively. cGMP activation was cooperative with a Hill coefficient (nH) of 1.28 +/- 0.10, whereas activation by cAMP was not cooperative. DG1 kinase expressed in Sf9 cells was found to be a dimer with an amino-terminal dimerization domain. It also autophosphorylated in a reaction stimulated by cGMP and cAMP. Immunoadsorbed DG1 protein from fly extracts was also capable of autophosphorylation, and this assay was used to quantitate the DG1 kinase in extracts from heads and bodies of adults and whole embryos. Activity was highest in heads of either sex and male bodies, intermediate in female bodies, and lowest in embryos. These results were in accord with DG1 mRNA abundance. Tissue distribution of the DG1 kinase was investigated by immunohistochemistry. In embryos, specific immunoreactivity was observed in large cells scattered along the anterior-posterior axis at stage 13. Prominent staining of adult heads was restricted to the proximal level of the lamina cortex.


Assuntos
Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Drosophila/enzimologia , Fatores Etários , Sequência de Aminoácidos , Animais , Baculoviridae/genética , Proteínas Quinases Dependentes de GMP Cíclico/genética , Proteínas Quinases Dependentes de GMP Cíclico/isolamento & purificação , Drosophila/embriologia , Ativação Enzimática , Feminino , Imuno-Histoquímica , Proteínas de Insetos/genética , Proteínas de Insetos/isolamento & purificação , Proteínas de Insetos/metabolismo , Cinética , Masculino , Dados de Sequência Molecular , Tecido Nervoso/enzimologia , Fosforilação , Conformação Proteica , Proteínas Recombinantes de Fusão/metabolismo , Frações Subcelulares/enzimologia , Distribuição Tecidual
16.
J Immunol ; 163(7): 3969-75, 1999 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-10490999

RESUMO

Cultured dermal fibroblasts from systemic sclerosis patients express higher levels of intracellular IL-1 alpha than fibroblasts from healthy controls. In this study, we found that systemic sclerosis dermal fibroblasts also express higher levels of the intracellular isoform of IL-1 receptor antagonist (icIL-1Ra) than normal fibroblasts after stimulation with IL-1 beta or TNF-alpha. A possible relationship between elevated precursor IL-1 alpha (preIL-1 alpha) and elevated icIL-1Ra was investigated by transducing normal dermal fibroblasts to overexpress preIL-1 alpha, preIL-1 beta, or icIL-1Ra. Fibroblasts that overexpressed icIL-1Ra did not have elevated levels of IL-1 alpha. On the other hand, fibroblasts that overexpressed preIL-1 alpha had at least 4-fold higher basal levels of icIL-1Ra than control fibroblasts and 4-fold higher levels of icIL-1Ra after induction with IL-1 beta or TNF-alpha. Fibroblasts overexpressing preIL-1 beta did not exhibit elevated icIL-1Ra. The differences in icIL-1Ra protein levels were reflected in differences in mRNA. In contrast, IL-1-stimulated levels of MCP-1 and IL-6 were not different in control and preIL-1 alpha-transduced fibroblasts. Addition of neutralizing anti-IL-1 alpha Abs to fibroblast cultures did not diminish basal or stimulated levels of icIL-1Ra in the preIL-1 alpha-transduced cells, supporting an intracellular site of action of preIL-1 alpha. This is the first report of an association between intracellular levels of these IL-1 family members. We hypothesize that intracellular preIL-1 alpha participates in the regulation of icIL-1Ra.


Assuntos
Fibroblastos/metabolismo , Interleucina-1/antagonistas & inibidores , Interleucina-1/biossíntese , Líquido Intracelular/metabolismo , Precursores de Proteínas/antagonistas & inibidores , Precursores de Proteínas/biossíntese , Receptores de Interleucina-1/antagonistas & inibidores , Sialoglicoproteínas/metabolismo , Pele/citologia , Adulto , Idoso , Células Cultivadas , Citocinas/biossíntese , Feminino , Fibroblastos/imunologia , Fibroblastos/patologia , Vetores Genéticos/imunologia , Vetores Genéticos/metabolismo , Humanos , Soros Imunes/farmacologia , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/genética , Interleucina-1/imunologia , Líquido Intracelular/imunologia , Masculino , Pessoa de Meia-Idade , Precursores de Proteínas/genética , Precursores de Proteínas/imunologia , RNA Mensageiro/biossíntese , RNA Mensageiro/metabolismo , Retroviridae/genética , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia , Sialoglicoproteínas/biossíntese , Sialoglicoproteínas/genética , Pele/imunologia , Pele/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
17.
Pediatr Dermatol ; 16(2): 146-50, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10337682

RESUMO

Oral corticosteroids are the main therapeutic choice for systemic lupus erythematosus (SLE). Adverse reactions to systemic corticosteroids rarely occur and the etiology is unclear in most cases. A 14-year-old girl with newly diagnosed SLE developed a pruritic bullous eruption while on prednisone. The patient had been treated successfully in the hospital with intravenous methylprednisolone. In preparation for discharge, the steroid preparation was changed to prednisone to which the patient reacted with a development of new crops of bullous lesions. Skin biopsy specimens of lesional areas showed a bullous eruption consistent with erythema multiforme. The patient underwent immediate and delayed hypersensitivity tests. Intradermal and patch tests to liquid prednisone were positive. The patient was discharged on oral methylprednisolone and has not had recurrence of the skin lesions. In conclusion, a case of prednisone sensitivity in a patient with SLE is presented here. An alternative preparation, methylprednisolone, was used to successfully treat her underlying condition.


Assuntos
Anti-Inflamatórios/efeitos adversos , Toxidermias/etiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Prednisolona/efeitos adversos , Adolescente , Biópsia , Feminino , Humanos , Metilprednisolona/uso terapêutico , Pele/patologia
18.
J Clin Rheumatol ; 7(5): 295-300, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17039159

RESUMO

The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is important to allow for the evaluation of practice patterns for future outcome studies. A survey of nine pediatric rheumatologists was performed between September 1999 and February 2000. Each of the physicians prospectively recorded demographic and treatment information on consecutively sampled JRA patients (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in 35%, and systemic onset JRA in 19% of the children. Naproxen was the most frequently prescribed medication (55% of the patients), followed by methotrexate (MTX), which was used in 39% of the patients. Folic acid supplementation (1 mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used in 11% of the children. Eleven percent of the patients received corticosteroids, and 13% of children on corticosteroids took calcium supplements. Uveitis was present in 8% and had a chronic course in 79% of those cases. Although systemic medications were used in 50% of the children with uveitis to control eye inflammation, severe damage to the eyes developed in 30% of them. Fourteen percent of the patients required gastroprotective medications. Compared with findings of a similar survey performed in 1993, there was no significant change in the frequency of use of naproxen, but nabumetone is now more often prescribed, and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among second-line agents used for JRA have also occurred, although there was no change in the frequency of use of MTX or corticosteroids. JRA continues to be a treatment challenge for the practicing pediatric rheumatologist. Patients often show incomplete response to the currently available medications. Therefore, new therapeutic agents need to be evaluated for their use in JRA, and the treatment of JRA associated uveitis especially needs to be improved.

19.
Arthritis Rheum ; 44(8): 1775-81, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11508428

RESUMO

OBJECTIVE: Joint inflammation in juvenile rheumatoid arthritis (JRA) is sometimes associated with an autoimmune response to type II collagen (CII), a cartilage-specific protein. To test the hypothesis that down-regulation of autoimmunity to CII can be accomplished in JRA by oral administration of CII, an open-label study of CII was performed in 9 patients with JRA. METHODS: Seven rheumatoid factor-negative JRA patients with polyarticular disease and 2 JRA patients with pauciarticular disease (1 with early onset and 1 with late onset) were treated for 3 months with oral bovine CII. Patients were examined for disease activity and underwent routine laboratory testing at monthly intervals. Two of the patients had flares of disease when treatment was discontinued, and these patients were re-treated for an additional 3 months. To test the hypothesis that oral tolerance induces an immune deviation of T cells, peripheral blood mononuclear cells from patients were collected before and after treatment and cultured with CII. Supernatants and RNA were collected and analyzed for the presence of various cytokines. RESULTS: Eight patient trials met the criteria for clinical improvement outlined by Giannini and coworkers in 1997. None of the patients had any side effects from the treatment. In 6 of the 8 patients who improved, interferon-gamma production decreased after oral CII therapy, correlating with clinical improvement, while 6 patients had increases in levels of transforming growth factor beta3. CONCLUSION: These results are encouraging. The possible beneficial effect of oral CII in JRA merits further investigation.


Assuntos
Artrite Juvenil/imunologia , Artrite Juvenil/terapia , Autoimunidade , Colágeno/uso terapêutico , Administração Oral , Adolescente , Autoantígenos/administração & dosagem , Autoantígenos/farmacologia , Autoantígenos/uso terapêutico , Células Cultivadas , Criança , Pré-Escolar , Colágeno/administração & dosagem , Colágeno/farmacologia , Citocinas/biossíntese , Citocinas/genética , Feminino , Humanos , Interferon gama/biossíntese , Interferon gama/genética , Masculino , RNA Mensageiro/biossíntese , Linfócitos T/metabolismo , Fator de Crescimento Transformador beta/biossíntese , Fator de Crescimento Transformador beta/genética , Resultado do Tratamento
20.
Appl Opt ; 11(1): 1, 1972 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-20111447
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