RESUMO
Pathogenic mutations in genes COL4A3/COL4A4 are responsible for autosomal Alport syndrome (AS) and thin basement membrane nephropathy (TBMN). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3/COL4A4, in 40 unrelated Portuguese probands with clinical suspicion of AS/TBMN. To assess genotype-phenotype correlations, we compared clinically relevant phenotypes/outcomes between homozygous/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3/COL4A4 mutations were identified in 62.5% (25/40) of the probands. Regardless of the mutated gene, all patients with ARAS manifested chronic renal failure (CRF) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF or extrarenal symptoms. CRF was diagnosed at a significantly younger age in patients with ARAS. In our families, the occurrence of COL4A3/COL4A4 mutations was higher, while the prevalence of XLAS was lower than expected. Overall, a pathogenic COL4A3/COL4A4/COL4A5 mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS. With such a population background, simultaneous next-generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV-related glomerular basement membrane nephropathies.
Assuntos
Autoantígenos/genética , Colágeno Tipo IV/genética , Hematúria/genética , Mutação , Nefrite Hereditária/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Mutacional de DNA , Exoma , Feminino , Estudos de Associação Genética , Hematúria/diagnóstico , Hematúria/metabolismo , Humanos , Falência Renal Crônica/genética , Falência Renal Crônica/metabolismo , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/metabolismo , Portugal , Adulto JovemRESUMO
Alport syndrome (AS) is caused by pathogenic mutations in the genes encoding α3, α4 or α5 chains of collagen IV (COL4A3/COL4A4/COL4A5), resulting in hematuria, chronic renal failure (CRF), sensorineural hearing loss (SNHL) and ocular abnormalities. Mutations in the X-linked COL4A5 gene have been identified in 85% of the families (XLAS). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS and no evidence of autosomal inheritance, had pathogenic COL4A5 mutations detected by Sanger sequencing and/or multiplex-ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL in males, and with higher risk of CRF and SNHL in females. Pathogenic COL4A3 or COL4A4 mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5. The lower than expected prevalence of XLAS in Portuguese families warrants the use of next-generation sequencing for simultaneous COL4A3/COL4A4/COL4A5 analysis, as first-tier approach to the genetic diagnosis of collagen type IV-related nephropathies.
Assuntos
Colágeno Tipo IV/genética , Mutação , Nefrite Hereditária/diagnóstico , Nefrite Hereditária/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Análise Mutacional de DNA , Exoma , Feminino , Estudos de Associação Genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Nefrite Hereditária/metabolismo , Portugal , Adulto JovemRESUMO
The objective of present study was to estimate the efficiency of lysine utilization by meat quail of 21 to 35 d of age. A total of 500 meat quails were distributed in a completely randomized design in a 2 × 5 factorial arrangement, with 2 sexes (male and female) and 5 digestible lysine levels (0.714, 0.816, 0.918, 1.020, and 1.122%) and 5 replications of 10 birds each. The variables studied were feather-free body weight (FFBW), feed intake (FI), lysine intake (LysI), feather-free body protein deposition (FFBPD), feather-free body lysine deposition (FFBLysD), feather-free body fat deposition (FFBFatD), feather weight (FW), feather protein deposition, feather lysine deposition, and feather fat deposition. The FFBW, FFBPD, FFBLysD, and FFBFatD were regressed as a function of LysI for each sex to estimate the efficiency of lysine utilization in the feather-free body (ELysFFB), and the individual equations were compared. In addition, a multiple regression without intercept was also used to estimate the ELysFFB and in feathers (ELysF) individually. To compare the ELysFFB obtained by the different methods, the t-statistic was used. There was no effect on sex × lysine level interactions for any variable. The females showed higher FFBW (5.07%) and FFBFatD (26.23%) than males. All variables increased with the level of dietary lysine, with the exception of FI, FW, and the deposition of nutrients within them. The ELysFFB values obtained by simple linear regression and multiple linear regression were 48.0 and 44.6%, respectively. As there was no difference in the efficiencies estimated by the different methodologies, the best estimate of ELysFFB was 46.3%, that is, the average. The best estimate of ELysF was 18.1%, obtained by multiple linear regression.
Assuntos
Galinhas , Lisina , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Masculino , Carne/análise , CodornizRESUMO
Beagle dogs between 7.6 and 8.8 years of age administered a twice daily supplement of alpha-lipoic acid (LA) and acetyl-L-carnitine (ALC) over approximately 2 months made significantly fewer errors in reaching the learning criterion on two landmark discrimination tasks compared to controls administered a methylcellulose placebo. Testing started after a 5 day wash-in. The dogs were also tested on a variable delay version of a previously acquired spatial memory task; results were not significant. The improved performance on the landmark task of dogs supplemented with LA + ALC provides evidence of the effectiveness of this supplement in improving discrimination and allocentric spatial learning. We suggest that long-term maintenance on LA and ALC may be effective in attenuating age-associated cognitive decline by slowing the rate of mitochondrial decay and cellular aging.
Assuntos
Acetilcarnitina/administração & dosagem , Ácido Tióctico/administração & dosagem , Acetilcarnitina/farmacologia , Animais , Cães , Aprendizagem , Placebos , Ácido Tióctico/farmacologiaRESUMO
Two outbreaks of Hypochaeris radicata-induced Australian stringhalt involving two farms and seven horses from southern Brazil are reported here. Subsequently, the disease was experimentally reproduced in a feeding trial with one colt fed H. radicata from the suspect paddocks. Fresh H. radicata was fed to the experimental animal for 50 days at an average daily dosage of 9.8 kg. Initially, the plant was collected from the paddock where the clinical disease occurred and was fed for 19 consecutive days producing mild clinical signs. However, on days 20-23 fresh plant was collected from a neighboring farm where the disease had not been reported and fed to the colt at which time the colt appeared to recover. Therefore, plant collections from the original suspect paddock resumed and feeding trials continued with clinical signs reoccurring by day 36, and increasing in intensity from days 43-50 after which plant administration was stopped. Within 15 days after ending the feeding trial with H. radicata, the colt appeared to have recovered. This experimental reproduction of stringhalt in a single colt fed H. radicata demonstrated that the two outbreaks of the disease resulted from this plant. Interestingly, the change in location for collection of plant material 19 days into the treatment, and the subsequent recovery of the colt, would suggest that plant material may differ in toxicity depending on location.
Assuntos
Asteraceae/intoxicação , Surtos de Doenças/veterinária , Doenças dos Cavalos/etiologia , Doenças Neuromusculares/veterinária , Animais , Doenças dos Cavalos/epidemiologia , Cavalos , Doenças Neuromusculares/epidemiologia , Doenças Neuromusculares/etiologiaRESUMO
In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS effects in apolipoprotein E knockout (ApoE-/-) mice exposed to two levels of concentrated ultrafine particulate matter in central Los Angeles. Mice were euthanized 24h after the last exposure and brain, liver, heart, lung and spleen tissues were collected and frozen for subsequent bioassays. There was clear evidence of aberrant immune activation in the brains of exposed animals as judged by a dose-related increase in nuclear translocation of two key transcription factors, NF-kappaB and AP-1. These factors are involved in the promotion of inflammation. Increased levels of glial fibrillary acidic protein (GFAP) were also found consequent to particulate inhalation suggesting that glial activation was taking place. In order to determine the mechanism by which these events occurred, levels of several MAP kinases involved in activation of these transcription factors were assayed by Western blotting. There were no significant changes in the proportion of active (phosphorylated) forms of ERK-1, IkB and p38. However, the fraction of JNK in the active form was significantly increased in animals receiving the lower concentration of concentrated ambient particles (CAPs). This suggests that the signaling pathway by which these transcription factors are activated involves the activation of JNK.
Assuntos
Doenças do Sistema Nervoso Central/induzido quimicamente , Doenças do Sistema Nervoso Central/patologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Material Particulado/toxicidade , Transdução de Sinais/efeitos dos fármacos , Animais , Apolipoproteínas E/genética , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Doenças do Sistema Nervoso Central/enzimologia , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Proteína Glial Fibrilar Ácida/metabolismo , Inflamação/enzimologia , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/fisiologia , Neuroglia/metabolismo , Neuroglia/patologia , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Transcrição AP-1/metabolismoRESUMO
Cellular oxidative damage is thought to be one of the key mechanisms underlying age-related cognitive impairment in dogs. Several nutritional interventions to limit cognitive decline are reported in the literature. To our knowledge, the association of grape and blueberry extracts has never been tested in aged dogs. Our objective was to evaluate the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on oxidative status and cognitive performances in aged dogs. A total of thirty-five beagle dogs (aged 8·0-14·5 years) were fed a basal diet with PEGB at either 0 parts per million (ppm) (n 11; control), 240 ppm (n 12; PEGB1) or 480 ppm (n 12; PEGB2) for 75 d. To investigate the effects of PEGB supplementation on cognition and oxidative status, a delayed non-matching to position (DNMP) test and RT-PCR on genes involved in oxidative stress were evaluated. The dogs fed PEGB1 showed a higher superoxide dismutase mRNA expression compared with dogs fed PEGB2 (P = 0·042) and with the control group (P = 0·014). Moreover, the dogs fed PEGB2 showed higher nuclear factor-like 2 (Nrf2) mRNA expression compared with the dogs fed PEGB1 (P = 0·027). Concerning the DNMP test, the proportion of dogs showing cognitive improvements relative to their baseline level was significantly higher in dogs fed the PEGB, regardless of the dosage, than in dogs receiving no supplementation (P = 0·030). The results obtained in the DNMP test suggested a potential benefit of the PEGB on working memory. However, this hypothesis should be further investigated to confirm this cognitive effect.
RESUMO
The objective of the study was to assess the effects of a dog-appeasing pheromone (DAP) collar in reducing sound-induced fear and anxiety in a laboratory model of thunderstorm simulation. Twenty-four beagle dogs naïve to the current test were divided into two treatment groups (DAP and placebo) balanced on their fear score in response to a thunderstorm recording. Each group was then exposed to two additional thunderstorm simulation tests on consecutive days. Dogs were video-assessed by a trained observer on a 6-point scale for active, passive and global fear and anxiety (combined). Both global and active fear and anxiety scores were significantly improved during and following thunder compared with placebo on both test days. DAP significantly decreased global fear and anxiety across 'during' and 'post' thunder times when compared with baseline. There was no significant improvement in the placebo group from baseline on the test days. In addition, the DAP group showed significantly greater use of the hide box at any time with increased exposure compared with the placebo group. The DAP collar reduced the scores of fear and anxiety, and increased hide use in response to a thunder recording, possibly by counteracting noise-related increased reactivity.
Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Cães/psicologia , Medo/efeitos dos fármacos , Ruído/efeitos adversos , Feromônios/farmacologia , Animais , Ansiedade/etiologia , Método Duplo-Cego , Feminino , Masculino , Gravação em Vídeo , Tempo (Meteorologia)RESUMO
RATIONALE: The cholinergic system is linked extensively to memory, but its exact role remains controversial. In particular, scopolamine-induced impairment in rodents is not task specific, which may be due to difficulty in developing rodent protocols to assess deficits in recent memory, in which the remembered event is brief and distinct, and/or to non-specific behavioral impairment. OBJECTIVES: The present study sought to determine whether scopolamine-induced deficits in recent memory, using a working memory task, could be dose-specifically dissociated from deficits in associative memory in dogs. METHODS: A Latin-square design was used to determine the effect of scopolamine (5, 10 and 15 microg/kg; SC) on a variable delayed-non-matching-to-position (DNMP) task, which assesses visuospatial working memory. Subsequently, the minimal effective dose (15 microg/kg; SC) was administered prior to testing on a landmark discrimination task, which provides a measure of allocentric spatial ability, a black-white discrimination task, an oddity discrimination task and tests of exploratory behavior. We also investigated the effects of a 30 microg/kg dose (SC) on tests of oddity discrimination and behavioral activity. RESULTS: A 15 microg/kg dose produced significant impairment on the DNMP task, but did not affect performance of any discrimination task and did not alter behavior on tests of open field or curiosity. A 30 microg/kg dose caused disruption on discrimination performance and on open field measures. CONCLUSIONS: Working memory performance is most sensitive to scopolamine-induced impairment and can be dissociated from scopolamine-induced deficits in discrimination performance and non-cognitive behaviors. The present results indicate that scopolamine-induced impairments of working memory in the dog can serve as a model of age-related cholinergic dysfunction.
Assuntos
Aprendizagem por Discriminação/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Antagonistas Muscarínicos , Escopolamina , Transtornos da Visão/induzido quimicamente , Envelhecimento/psicologia , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Feminino , Masculino , Transtornos da Memória/psicologia , Antagonistas Muscarínicos/administração & dosagem , Recompensa , Escopolamina/administração & dosagem , Transtornos da Visão/psicologiaRESUMO
Assessment of canine palatability is important for both the pet food and pharmaceutical industries; however, the current palatability assessment protocols are limited in their utility. The most common technique, the two-pan test, does not control for the satiating effects of food and may not be useful for long-term palatability analysis because nutritional or caloric characteristics of the diets may interfere with the results. Furthermore, the large quantities of foods consumed may be detrimental to the health of animals that do not self-limit their food intake. The purpose of this study was to determine whether a cognitive protocol could be used to determine food palatability in dogs. Five beagle dogs were trained on a three-choice object-discrimination learning task. After establishing object preferences, the preferred object was associated with no reward, a second object was associated with the dog's normal laboratory diet (Purina Agribrands Canine Lab Chow No. 5006; Agribrands Purina Canada, Inc., Woodstock, ON, Canada), and the third object was associated with a commercial (Hill's P/D; Hill's Pet Nutrition Inc., Topeka, KS) diet. In the discrimination-training phase, dogs were trained until they learned to avoid the no-reward object. They were subsequently given an additional 20 test sessions, which were used to determine food preference. In the reversal phase, which involved reversal learning, the object-food associations were modified, such that the object that was previously associated with Hill's P/D diet was now associated with the normal laboratory diet and vice versa. Once the dogs learned to avoid the no-reward object, they were tested for an additional 20 sessions. All subjects learned to avoid the no-reward object during the initial learning, and the number of choices to the object associated with the Hill's P/D diet was greater than the number of choices to the objects associated with the dry laboratory diet (P < 0.05) and no reward (P < 0.05), indicating a strong preference for the Hill's P/D diet. The object preferences were reversed in only three of five dogs when the food-choice associations were reversed, although the two phases did not differ significantly from one another. The protocol in the present study provides a robust measure of food palatability and circumvents many of the limitations associated with other palatability assessment techniques. The present protocol should be useful as a replacement or adjunct to other tests of palatability, but requires further validation by comparing the assessment of more similar and novel foods directly with other palatability tests.
Assuntos
Ração Animal/normas , Aprendizagem por Discriminação/fisiologia , Cães/fisiologia , Preferências Alimentares/fisiologia , Paladar , Animais , Comportamento de Escolha , Feminino , Masculino , Análise e Desempenho de Tarefas , Paladar/efeitos dos fármacos , Paladar/fisiologiaRESUMO
This study lists 32 species of sand flies, 1 of them belonging to the genus Brumptomyia and 31 to the genus Lutzomyia, distributed among the following subgenera: Psychodopygus (6), Nyssomyia (5), Pressatia (3), Evandromyia (2), Psathyromyia (2), Sciopemyia (2), Lutzomyia (1), Micropygomyia (1), Viannamyia (1), and the groups Oswaldoi (5) and Migonei (3). The sand flies were captured in the wild (forest) and in peridomicile (pigpen, hen house and stable) and intradomicile (bedroom) areas from 06:00 PM to 06:00 AM, once a month, for 4 years on the Island of São Luis, Maranhão. All species sampled were present in the forest. Among them, 16 were found in the peridomicile, while 11 were found inside the houses. A total of 22,581 specimens were captured, 65.1% of them in the peridomicile, 17.5% in the forest and 17.4% in the intradomicile. The most common species was Lutzomyia longipalpis (66.4% of the captured specimens), followed by Lutzomyia whitmani (24%) and Lutzomyia evandroi (5.9%). The remaining 29 species represented 3.7% of the total sample.
Assuntos
Psychodidae , Animais , Brasil , Psychodidae/classificação , Saúde da População RuralRESUMO
OBJECTIVE: The aim of this study was to analyse different ultrasound parameters for the assessment of isolated left ventricular diastolic dysfunction (LVDD) in patients with chronic renal failure (CRF) on periodic hemodialysis (HD), comparing pulsed wave Doppler with pulsed tissue Doppler. MATERIALS AND METHODS: Forty-seven patients with CRF on HD (61% were male; mean age was 51.0 +/- 16.5 years, mean HD time--3.7 +/- 3.8 years, 38% had hypertension, 17% had diabetes) were studied by echocardiography (bidimensional, M-Mode, flow pulsed Doppler and tissue Doppler imaging). All patients had symptoms of left heart failure-class II NYHA, were in sinus rhythm and had no symptoms of ischemic heart disease. The presence of abnormal LV regional contractility was the exclusion criteria. According to their mitral inflow profile Doppler characteristics, patients were included in two groups: Group A (E/A > 1; n = 21) and B (E/A < 1; n = 26). We compared: LV dimensions and function, left atrial (LA) dimension. Gaasch index, LV mass index. E and A wave velocities (in flow pulsatile Doppler and tissue Doppler). E/N ratio in tissue Doppler, isovolumetric relaxation time (IVRT) and deceleration time (DT). RESULTS: There were no significant differences in the prevalence of age > or = 65 years male sex, hypertension or diabetes between group A and B patients, and almost all patients were on hemodialytic treatment for more than one year (81% vs 85%: NS). LV hypertrophy was present in almost all group A and B patients (A--95% vs B--85.5%; NS). Group A, compared with group B, had a difference in the Gaasch index (2.45 +/- 0.3 vs 2.08 +/- 0.4; p < 0.05), E wave velocity in flow pulsatile Doppler and tissue Doppler (cm/sec) (110 +/- 27 vs 62 +/- 20; p < 0.001 and 41 +/- 15 vs 28.5 +/- 16; p < 0.05), E/A ratio in tissue Doppler (1.3 +/- 0.4 vs 0.8 +/- 0.3; p < 0.001). IVRT (msec) (80.7 +/- 15.2 vs 113.5 +/- 28.3; p < 0.001) and DT (msec) (189.7 +/- 24 vs 278.2 +/- 17.9; p < 0.001). According to the E'/A' ratio in tissue Doppler, group A patients were divided in another two groups: E'/A' > 1 (13/21--62%) and < 1 (8/21--38%) and a significantly longer IVRT (75.8 +/- 9.3 vs 100.9 +/- 3.2; p < 0.001) and DT (178 +/- 15 vs 240 +/- 20; p < 0.001) and a greater LA dimension (37.6 +/- 6.9 vs 44.6 +/- 6.9; p < 0.05) were found. CONCLUSIONS: Pulsed wave Doppler is the most useful non invasive method for assessment of global diastolic dysfunction. In our study, 17% of the patients had E/A < 1 only in the tissue Doppler study. These patients probably had a pseudonormal mitral pattern.
Assuntos
Falência Renal Crônica/diagnóstico por imagem , Diálise Renal , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Diástole , Ecocardiografia Doppler/métodos , Ecocardiografia Doppler/estatística & dados numéricos , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Disfunção Ventricular Esquerda/etiologiaRESUMO
PURPOSE: In the current study we analyzed clinical evolution and therapeutic aspects of malignant diphtheric myocarditis. METHODS: Fourteen patients with primary diagnosis of diphtheria were prospectively evaluated. Cardiac involvement was detected after 11.5 (mean) days. The diagnosis of diphtheric myocarditis was done in clinical basis. RESULTS: Seven (50%) patients died. Cardiac failure was a common finding in all cases. Complete A-V block was identified in eight (57%) patients. Temporary pacemaker was implanted in 10 cases, six of them died due to myocardial failure. Definitive pacemaker was necessary in two patients with persistent complete A-V block after one-month follow-up. One patient with atrial fibrillation died with sepsis. Respiratory infection was the commonest extracardiac complication (six cases) and two patients developed Guillain-Barré syndrome. We also identified neurologic, renal and adrenal complications. CONCLUSION: Cardiac rhythm disturbances in diphtheric myocarditis are associated with high probability of necessity of temporary pacemaker and high mortality. Definitive pacemaker can be implanted in persistent complete A-V block.
Assuntos
Difteria/complicações , Miocardite/etiologia , Adolescente , Criança , Pré-Escolar , Eletrocardiografia , Feminino , Bloqueio Cardíaco/etiologia , Bloqueio Cardíaco/terapia , Humanos , Masculino , Miocardite/mortalidade , Marca-Passo ArtificialRESUMO
A multicentric, non-comparative study was made to evaluate the efficacy and safety of diltiazem 180 mg in the elderly, with dose titration in subjects above the age of 60 years. The blood pressure measurements were done by ambulatory blood pressure monitoring (ABPM). We achieved a reduction of at least 10 mmHg in systolic blood pressure in 52.2% and in diastolic blood pressure in 42.5% of the patients. The estimated differences between the initial values and those after treatment are 30% (CI95%: 22-38%) for diurnal blood pressure load, 22% (CI95%: 14-29%) for nocturnal blood pressure load, 13 mmHg (CI95%: 10-16 mmHg) for median systolic BP, and 8 mmHg (CI95%: 6-10 mmHg) for median diastolic BP. In 62.5% of the subjects the daily dose of diltiazem was increased to 240 mg (180 mg in the morning and 60 mg at night). All the cardiovascular parameters evaluated showed a significant decrease at the end of the study. A significant change was not recorded in the laboratory parameters and the adverse event average was minimal. The results showed that diltiazem in monotherapy is effective in the control of hypertension in the elderly and can improve compliance to the treatment.
Assuntos
Anti-Hipertensivos/uso terapêutico , Diltiazem/uso terapêutico , Hipertensão/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Regulatory T (TREG) cells play an important role in maintaining immune tolerance and avoiding autoimmunity. We analyzed the expression of membrane molecules in TREG and effector T cells in systemic lupus erythematosus (SLE). TREG and effector T cells were analyzed for the expression of CTLA-4, PD1, CD28, CD95, GITR, HLA-DR, OX40, CD40L, and CD45RO in 26 patients with active disease, 31 with inactive disease, and 26 healthy controls. TREG cells were defined as CD25+/high CD127 Ø/low FoxP3+, and effector T cells were defined as CD25+CD127+FoxP3 Ø. The ratio of TREG to effector T cells expressing GITR, PD1, HLA-DR, OX40, CD40L, and CD45RO was determined in the three groups. The frequency of TREG cells was similar in patients with SLE and controls. However, SLE patients had a decreased frequency of CTLA-4+TREG and CD28+TREG cells and an increased frequency of CD40L+TREG cells. There was a decrease in the TREG/effector-T ratio for GITR+, HLA-DR+, OX40+, and CD45RO+ cells, and an increased ratio of TREG/effector-T CD40L+ cells in patients with SLE. In addition, CD40L+TREG cell frequency correlated with the SLE disease activity index (P=0.0163). In conclusion, our findings showed several abnormalities in the expression of functionally critical surface molecules in TREG and effector T cells in SLE that may be relevant to the pathogenesis of this disease.