p53 and clock genes play an important role in memory and learning ability depression due to long-term ultraviolet A eye irradiation.

BACKGROUND: Long-term ultraviolet A (UVA) eye irradiation decreases memory and learning ability in mice. However, the underlying mechanism is still unclear. OBJECTIVES: In this study, ICR mice were used to study the effects of long-term UVA eye irradiation. METHODS: The eyes of mice were exposed to UVA from an FL20SBLB-A lamp three times a week for 1 year. Then, we analyzed memory and learning ability in the mice using water maze and step-through passive avoidance tests, and measured the levels of p53, Period2 (Per2), Clock, brain and muscle Arnt-like protein-1 (Bmal1), nicotinamide mononucleotide adenylyltransferase (NMNAT) activity, nicotinamide phosphoribosyltransferase (NAMPT) activity, nicotinamide adenine dinucleotide (NAD+), and sirtuin 1 (Sirt1) in the brains of treated and control animals. RESULTS: The results showed that the p53 level increased significantly following long-term UVA eye irradiation, whereas the levels of Period2, Bmal1, Clock, NMNAT and NAMPT activities, NAD+, and Sirt1 decreased significantly. Furthermore, we found that p53 inhibition ameliorated the UVA eye irradiation-induced depression of memory and learning ability. CONCLUSION: These results indicate that long-term UVA eye irradiation stimulates p53, inhibits the clock gene, and reduces Sirt1 production in the NAD+ constructional system, resulting in reduced memory and learning ability.

Preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil for oral squamous cell carcinoma.

The objectives of this study were to evaluate survival in 141 patients with stage II-IV oral squamous cell carcinoma (OSCC) treated with preoperative intra-arterial chemotherapy with docetaxel, cisplatin, and peplomycin combined with intravenous chemotherapy using 5-fluorouracil (IADCPIVF) via the superficial temporal artery, and to clarify the prognostic factors. The study population included 59 patients with stage II OSCC, 34 with stage III, and 48 with stage IV. After IADCPIVF, 139 patients underwent surgery; minimally invasive surgeries (MIS) including excisional biopsy were performed on 96 patients with a remarkably good response to IADCPIVF. The primary tumour response rate was 99.3% (complete response rate 56.7%, good partial response rate 17.0%, fair partial response rate 25.5%). Additionally, there were no serious adverse events associated with IADCPIVF. The 5-year overall survival rate was 74.6% (stage II 83.6%, stage III 72.7%, stage IV 64.8%). In the multivariate analysis of survival, T classification and clinical tumour response were significant prognostic factors. Eight (8.3%) of the patients who received MIS had primary recurrence and six were salvaged. In conclusion, IADCPIVF is safe and efficacious for treating OSCC, and MIS could reduce the extent of primary tumour resection in the case of a remarkably good response.

Factors predictive of serious infections over time in systemic lupus erythematosus patients: data from a multi-ethnic, multi-national, Latin American lupus cohort.

AIM: The aim of this study was to identify factors predictive of serious infections over time in patients with systemic lupus erythematosus (SLE). METHODS: A multi-ethnic, multi-national Latin American SLE cohort was studied. Serious infection was defined as one that required hospitalization, occurred during a hospitalization or led to death. Potential predictors included were sociodemographic factors, clinical manifestations (per organ involved, lymphopenia and leukopenia, independently) and previous infections at baseline. Disease activity (SLEDAI), damage (SLICC/ACR Damage Index), non-serious infections, glucocorticoids, antimalarials (users and non-users), and immunosuppressive drugs use; the last six variables were examined as time-dependent covariates. Cox regression models were used to evaluate the predictors of serious infections using a backward elimination procedure. Univariable and multivariable analyses were performed. RESULTS: Of the 1243 patients included, 1116 (89.8%) were female. The median (interquartile range) age at diagnosis and follow-up time were 27 (20-37) years and 47.8 (17.9-68.6) months, respectively. The incidence rate of serious infections was 3.8 cases per 100 person-years. Antimalarial use (hazard ratio: 0.69; 95% confidence interval (CI): 0.48-0.99; p = 0.0440) was protective, while doses of prednisone >15 and ≤60 mg/day (hazard ratio: 4.18; 95 %CI: 1.69-10.31; p = 0.0019) and >60 mg/day (hazard ratio: 4.71; 95% CI: 1.35-16.49; p = 0.0153), use of methylprednisolone pulses (hazard ratio: 1.53; 95% CI: 1.10-2.13; p = 0.0124), increase in disease activity (hazard ratio: 1.03; 95% CI: 1.01-1.04; p = 0.0016) and damage accrual (hazard ratio: 1.22; 95% CI: 1.11-1.34; p < 0.0001) were predictive factors of serious infections. CONCLUSIONS: Over time, prednisone doses higher than 15 mg/day, use of methylprednisolone pulses, increase in disease activity and damage accrual were predictive of infections, whereas antimalarial use was protective against them in SLE patients.

First-principles calculations of Raman vibrational modes in the fingerprint region for connective tissue.

Vibrational spectroscopy has been widely employed to unravel the physical-chemical properties of biological systems. Due to its high sensitivity to monitoring real time "in situ" changes, Raman spectroscopy has been successfully employed, e.g., in biomedicine, metabolomics, and biomedical engineering. The interpretation of Raman spectra in these cases is based on the isolated macromolecules constituent vibrational assignment. Due to this, probing the anharmonic or the mutual interactions among specific moieties/side chains is a challenge. We present a complete vibrational modes calculation for connective tissue in the fingerprint region (800 - 1800 cm-1) using first-principles density functional theory. Our calculations accounted for the inherent complexity of the spectral features of this region and useful spectral markers for biological processes were unambiguously identified. Our results indicated that important spectral features correlated to molecular characteristics have been ignored in the current tissue spectral bands assignments. In particular, we found that the presence of confined water is mainly responsible for the observed spectral complexity.

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

Flicker electroretinograms recorded with mydriasis-free RETeval system before and after cataract surgery.

PurposeThe purpose of this study is to compare the amplitudes and peak times of the flicker electroretinograms (ERGs) recorded before and after cataract surgery with the RETeval system (LKC Technologies, Gaithersburg, MD, USA) from eyes without dilation.Patients and methodsThirty-two eyes of 32 patients (77.3±6.5 years) that had grade 2 Emery-Little nuclear or cortical cataract without any other abnormalities were studied. Flicker ERGs were recorded with the RETeval system under mydriatic-free conditions. Skin electrodes were used to pick-up the ERGs that were elicited by white light delivered at a rate of 28.3 Hz and intensity of 2, 8, and 32 Td-s. The amplitudes and peak times of the flicker ERGs before and after cataract surgery were compared.ResultsThe mean amplitudes were significantly increased after the removal of the cataractous lenses at the three stimulus intensities (2 Td-s, P<0.0001; 8 Td-s, P<0.0001; and 32 Td-s, P<0.0001). The mean peak times of the flicker ERGs elicited by 2 and 8 Td-s were significantly shortened after the surgery (2 td-s, P<0.0001 and 8 td-s, P=0.0127) but not at 32 td-s (P=0.595).ConclusionsThese results indicate that the presence of cataracts will affect both the amplitudes and the peak times of the flicker ERGs even if the cataract is mild. In addition, the results indicate that as stimulus intensity increases, the peak times is less affected by a cataract. The clarity of the crystalline lens should be considered when interpreting the flicker ERGs recorded with the RETeval system.

Early discoid lupus erythematosus protects against renal disease in patients with systemic lupus erythematosus: longitudinal data from a large Latin American cohort.

OBJECTIVES: The objective of this study was to examine whether early discoid lupus erythematosus (DLE) would be a protective factor for further lupus nephritis in patients with systemic lupus erythematosus (SLE). METHODS: We studied SLE patients from GLADEL, an inception longitudinal cohort from nine Latin American countries. The main predictor was DLE onset, which was defined as physician-documented DLE at SLE diagnosis. The outcome was time from the diagnosis of SLE to new lupus nephritis. Univariate and multivariate survival analyses were conducted to examine the association of DLE onset with time to lupus nephritis. RESULTS: Among 845 GLADEL patients, 204 (24.1%) developed lupus nephritis after SLE diagnosis. Of them, 10 (4.9%) had DLE onset, compared to 83 (12.9%) in the group of 641 patients that remained free of lupus nephritis (hazard ratio 0.39; P = 0.0033). The cumulative proportion of lupus nephritis at 1 and 5 years since SLE diagnosis was 6% and 14%, respectively, in the DLE onset group, compared to 14% and 29% in those without DLE (P = 0.0023). DLE onset was independently associated with a lower risk of lupus nephritis, after controlling for sociodemographic factors and disease severity at diagnosis (hazard ratio 0.38; 95% confidence interval 0.20-0.71). CONCLUSIONS: Our data indicate that DLE onset reduces the risk of further lupus nephritis in patients with SLE, independently of other factors such as age, ethnicity, disease activity, and organ damage. These findings have relevant prognosis implications for SLE patients and their clinicians. Further studies are warranted to unravel the biological and environmental pathways associated with the protective role of DLE against renal disease in patients with SLE.

Non-Hodgkin lymphoma of the female genital tract mimicking primary gynecological tumors: a single-center series of 3 cases.

INTRODUCTION: Malignant lymphoma of the female genital tract is quite rare and its presentation may resemble that of other, more common tumors, causing confusion for clinicians. CASE HISTORY: The authors report three patients with a non-Hodgkin lymphoma (NHL) involving the female genital tract: two cases involved the ovary and one involved the uterus. In all patients, the genital tract was the initial site of clinical presentation of a B cell lymphoma. One patient was diagnosed postoperatively and subsequently received chemotherapy; the other two patients were diagnosed by imaging-guided biopsy and were successfully managed by chemotherapy without resection surgery. Two patients were alive, without evidence of disease, and one patient was alive with disease at their most recent follow-up visit. CONCLUSION: The authors' experience emphasizes that lymphoma should be in the differential diagnosis of pelvic gynecological malignancies, and its clinical, biological, and radiological signs must be actively sought. Imaging-guided biopsy should be performed to avoid unnecessary surgery.

An examination of factors related to aspiration and silent aspiration in older adults requiring long-term care in rural Japan.

Swallowing disorders are a growing problem among the elderly in long-term care (LTC), and they can cause aspiration pneumonia. In order to detect swallowing disorders early, simple tools are needed to assess aspiration and silent aspiration (SA). To compile a sample of elderly people requiring LTC, and categorise them as having suspected aspiration and/or SA using simple screening tools. In addition, oral ability, severity of dementia, vital functions and nutritional status were compared in these groups. A total of 393 elderly people in LTC (89 men and 304 women; age ranging from 65 to 100 years) were included in the study. The modified water swallow test, cervical auscultation and cough test were used to assess swallowing function. The participants were categorised as having suspected aspiration and/or SA, and the following assessments were performed: (i) oral ability (lips function, tongue function, rinsing and gargling ability), (ii) dementia severity, (iii) vital functions and (iv) nutritional status. Suspected aspiration was apparent in 50.5% of patients, of which 24.0% had suspected SA. Those with suspected aspiration showed worsened oral ability, dementia severity, vital functions and nutritional status. Similarly, those with suspected SA showed worsened dementia severity, vital functions and nutritional status. Logistic regression analysis revealed that lip closure, lingual movement and rinsing ability were significantly associated with suspected aspiration. Dementia severity was the best predictor of suspected SA. Simple screening tools can be used to identify suspected aspiration and SA, which may facilitate early detection of aspiration pneumonia or swallowing disorder risk.

Psychological distress in corticosteroid-naive patients with systemic lupus erythematosus: A prospective cross-sectional study.

OBJECTIVE: Psychological distress, such as depression and anxiety, has been intensively studied in patients with systemic lupus erythematosus (SLE). However, those studies have mostly included patients who were treated with corticosteroids, which might themselves induce mood disturbances. We investigated psychological distress in corticosteroid-naive patients with SLE who did not exhibit any overt neuropsychiatric manifestations. METHODS: Forty-three SLE in-patients with no current or past abnormal neuropsychiatric history participated in the study. Patients and 30 healthy control subjects with similar demographic and personality characteristics were administered a comprehensive battery of psychological/neuropsychological tests. The Profile of Mood States (POMS) was used to assess depression and anxiety. Results of clinical, laboratory, and neurological tests were compared with regard to their presence. RESULTS: Prevalence of depression was higher in patients (n = 11, 25.6%) than in controls (n = 2, 6.7%; p = 0.035), although prevalence of anxiety did not differ across groups (patients: 34.9%, n = 15; controls: 16.7%, n = 5; p = 0.147). Using multiple logistic regression analysis, we identified avoidance coping methods (OR, 1.3; 95% CI 1.030-1.644; p = 0.027) as an independent risk factor for depression. CONCLUSION: Our results indicate that depression presents more frequently in corticosteroid-naive patients with early-stage, active SLE than in the normal population, but anxiety does not. Depression may be related to psychological reactions to suffering from the disease.

Liquid marbles as a micro-reactor for efficient radical alternating copolymerization of diene monomer and oxygen.

Liquid marbles have been shown to be a novel micro-reactor to synthesize polyperoxides by the radical alternating copolymerization of the 1,3-diene monomer with oxygen in a good yield. Oxygen gas is effectively absorbed as a comonomer by the large and permeable gas-liquid interface of the liquid marbles.

Lupus in Latin-American patients: lessons from the GLADEL cohort.

The need for comprehensive published epidemiologic and clinical data from Latin American systemic lupus erythematosus (SLE) patients motivated the late Dr Alarcón-Segovia and other Latin American professionals taking care of these patients to spearhead the creation of the G: rupo L: atino A: mericano D: e E: studio del L: upus (GLADEL) cohort in 1997. This inception cohort recruited a total of 1480 multiethnic (Mestizo, African-Latin American (ALA), Caucasian and other) SLE patients diagnosed within two years from the time of enrollment from 34 Latin American centers with expertise in the diagnosis and management of this disease. In addition to the initial 2004 description of the cohort, GLADEL has contributed to improving our knowledge about the course and outcome of lupus in patients from this part of the Americas. The major findings from this cohort are highlighted in this review. They have had important clinical implications for the adequate care of SLE patients both in Latin America and worldwide where these patients may have emigrated.

Long-term persistence of anti-ß2 glycoprotein I in treated leprosy patients.

ß2 glycoprotein I (ß2GPI) is a phospholipid binding protein that plays an important role in endothelial stability, blood coagulation, clearance of apoptotic debris and other physiologic processes. Anti-ß2GPI antibodies occur in normal individuals and transiently during the course of infections, but are also associated with thrombotic events in autoimmune disease: the antiphospholipid syndrome (APS). A total of 31 out of 37 treated leprosy patients previously found to present high titers of IgM anti-ß2GPI and/or anticardiolipin antibodies (aCL) remained positive for IgM antiphospholipid antibodies (aPL), and exhibited high titers of anti-ß2GPI. The 37 patients were part of the 77 aPL-positive patients from a previous study that evaluated 158 leprosy patients. The median time elapsed between the first and second sample was 66 months. None of the 37 patients had any thrombotic event and 24 had a reactional state and were still requiring the use of prednisone, thalidomide or both. None of them fulfilled World Health Organization criteria for leprosy recurrence.

The effect of acute physical exercise on cytokine levels in patients with systemic lupus erythematosus.

BACKGROUND: Acute exercise increases IL-6, IL-10 and TNF-α levels in healthy subjects. There is no study evaluating the effect of exercise on cytokines level in systemic lupus erythematosus (SLE) patients. OBJECTIVE: Our aim was to assess IL-10, IL-6 and TNF-α levels at baseline and after acute physical exercise in patients with SLE. METHODS: In total, 27 female SLE patients and 30 healthy controls were evaluated. Serum levels of IL-10, IL-6 and TNF-α at baseline and soon after the ergospirometric test were measured by ELISA test. Student's t-tests and Mann-Whitney test were used for intra- and inter-group comparisons; p values <0.05 were considered significant. RESULTS: Patients with SLE presented worse ergospirometric parameters compared with controls: VO2max (25.78 ± 5.51 vs. 32.74 ± 5.85 ml/kg/min, p < 0.001); maximum heart rate (174.18 ± 12.36 vs. 185.15 ± 2.07 bpm, p = 0.001); maximum ventilation (65.51 ± 15.68 vs. 80.48 ± 18.98 l/min, p = 0.001) and maximum speed (7.70 ± 1.24 vs. 9.40 ± 1.22 km/h, p < 0.001). At baseline, SLE patients presented higher levels of IL-6 (2.38 ± 1.70 vs. 1.71 ± 0.29 pg/ml, p = 0.035) and IL-10 (1.09 ± 1.55 vs. 0.30 ± 0.11 pg/ml, p = 0.037) than controls. Acute exercise in controls increased IL-6 level (1.71 ± 0.29 vs. 2.01 ± 0.27 pg/ml, p = 0.003) without change in IL-10 and TNF-α levels. However, no significant change in cytokine levels was observed in SLE patients after acute exercise. CONCLUSION: This is the first study evaluating the effect of acute exercise on cytokine levels in patients with SLE. In contrast to healthy controls, acute physical exercise did not increase the levels of IL-6 in patients with SLE, and seems to be safe in those patients with inactive or mild active disease.

Ultraviolet B irradiation of the mouse eye induces pigmentation of the skin more strongly than does stress loading, by increasing the levels of prohormone convertase 2 and α-melanocyte-stimulating hormone.

BACKGROUND: In previous studies, we made the unexpected finding that in mice, ultraviolet (UV)B irradiation of the eye increased the concentration of α-melanocyte-stimulating hormone (α-MSH) in plasma, and systemically stimulated epidermal melanocytes. AIMS: To compare the extent of the pigmentation induced by social and restraint stress (which activate the hippocampus-pituitary system) with that induced by UVB irradiation. METHODS: DBA/2 and sham-operated or hypophysectomized DBA/2 mice were subjected to local UVB exposure using a sunlamp directed at the eye, and two types of stress (social and restraint) were imposed. RESULTS: UVB irradiation of the eye or exposure to stress loading both increased the number of Dopa-positive melanocytes in the epidermis, and hypophysectomy strongly inhibited the UVB-induced and stress-induced stimulation of melanocytes. Irradiation of the eye caused a much greater increase in dopamine than did the stress load. Both UVB eye irradiation and stress increased the blood levels of α-MSH and adrenocorticotropic hormone (ACTH). In addition, the increase in plasma α-MSH was greater in animals subjected to UVB eye irradiation than in those subjected to stress loading, whereas the reverse occurred for plasma ACTH. UVB irradiation to the eye and stress loading increased the expression of prohormone convertase (PC)1/3 and PC2 in the pituitary gland. The increase in expression of pituitary PC2 was greater in animals subjected to UVB eye irradiation than to stress, whereas no difference was seen between the two groups for the increase in PC1/3. CONCLUSIONS: UVB eye irradiation exerts a stronger effect on pigmentation than stress loading, and is related to increased levels of α-MSH and PC2.

Reduction of thickness of ganglion cell complex after internal limiting membrane peeling during vitrectomy for idiopathic macular hole.

BACKGROUND/AIM: The aim of this study is to report a reduction in the thickness of the ganglion cell complex (GCC) after vitrectomy with internal limiting membrane (ILM) peeling in eyes with idiopathic macular hole (MH). METHODS: Twenty-eight consecutive eyes with an idiopathic MH treated by vitrectomy with ILM peeling were studied. All eyes had an intravitreal injection of indocyanine green to make the ILM more visible. The best-corrected visual acuity (BCVA), GCC thickness measured by spectral domain optical coherence tomography, and retinal sensitivity measured by microperimetry were determined before and at 3 and 6 months after the vitrectomy. RESULTS: The MH in all eyes was closed after the initial surgery. The BCVA was significantly improved at 3 and 6 months (P<0.001 and P<0.001, respectively). The thickness of the GCC was significantly reduced at 3 and 6 months postoperatively (P<0.001 and P<0.001, respectively). The GCC thickness was significantly correlated with the retinal sensitivity in the central 10 degrees at 6 months (r=0.55, P=0.004). CONCLUSION: A reduction of the GCC thickness was observed after vitrectomy with ILM peeling for idiopathic MH.

Ezetimibe reduces urinary albumin excretion in hypercholesterolaemic type 2 diabetes patients with microalbuminuria.

OBJECTIVE: This study investigated the effects of ezetimibe, an inhibitor of intestinal cholesterol absorption, on early phase diabetic nephropathy. METHODS: A total of 32 hypercholesterolaemic type 2 diabetes patients with microalbuminuria, defined as a urinary albumin excretion (UAE) 30 but < 300 mg/g creatinine, were enrolled. Various clinical and laboratory parameters were determined at baseline and after 6 months of treatment with 10 mg/day ezetimibe. RESULTS: Ezetimibe treatment significantly decreased glycated haemoglobin (HbA(1c)), low-density lipoprotein-cholesterol (LDL-C), triglycerides and UAE, and significantly increased high-density lipoprotein-cholesterol and albumin. It also decreased the serum level of monocyte chemoattractant protein-1 (MCP-1), but this difference was not statistically significant. Univariate analyses showed a correlation between UAE and body mass index, systolic and diastolic blood pressures, HbA(1c), LDL-C, estimated glomerular filtration rate (inverse), creatinine and MCP-1. Since these parameters may be closely correlated with each other, multiple stepwise regression analysis was performed and demonstrated that HbA(1c) and MCP-1 were independent determinants of UAE. CONCLUSIONS: Ezetimibe may be a promising therapeutic strategy for improving albumin excretion, partly through its anti-inflammatory properties, and for reducing LDL-C in hypercholesterolaemic type 2 diabetes patients with microalbuminuria.

Anharmonic transitions in nearly dry L-cysteine I.

Two special dynamical transitions of universal character have recently been observed in macromolecules (lysozyme, myoglobin, bacteriorhodopsin, DNA and RNA) at T* ~100-150 K and T(D) ~180-220 K. The underlying mechanisms governing these transitions have been the subject of debate. In the present work, a survey is reported on the temperature dependence of structural, vibrational and thermodynamical properties of a nearly anhydrous amino acid (orthorhombic polymorph of the amino acid l-cysteine at a hydration level of 3.5%). The temperature dependence of x-ray powder diffraction patterns, Raman spectra and specific heat revealed these two transitions at T* = 70 K and T(D) = 230 K for this sample. The data were analyzed considering amino acid-amino acid, amino acid-water, water-water phonon-phonon interactions and molecular rotor activation. Our results indicated that the two referred temperatures define the triggering of very simple and particular events that govern all the interactions of the biomolecular: activation of CH(2) rigid rotors (T < T* ), phonon-phonon interactions between specific amino acid and water dimer vibrational modes (T* < T < T(D)), and water rotational barriers surpassing (T > T(D)).

Short-term effect of leflunomide in patients with Takayasu arteritis: an observational study.

OBJECTIVES: To evaluate the efficacy of leflunomide in controlling disease activity in patients with Takayasu arteritis (TA) refractory or intolerant to conventional treatment. METHODS: We conducted a prospective open-label study of 15 TA patients (mean age 36.2 years) with active disease based on clinical assessment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and magnetic resonance angiography (MRA). Patients received leflunomide 20 mg/day for at least 6 months and were followed up for a mean of 9.1 months. Adverse events attributable to leflunomide were recorded. RESULTS: At baseline, 14 TA patients had active disease despite therapy with corticosteroids and immunosuppressive agents, while one patient had intolerance to current treatment. In the follow-up visit, we found a significant decrease in the frequency of patients with active TA (93% vs. 20%, p = 0.002), in the mean daily dose of prednisone (34.2 vs. 13.9 mg, p < 0.001) and in the median values of ESR (29.0 vs. 27.0 mm/h, p = 0.012) and CRP (10.3 vs. 5.3 mg/L, p = 0.012). Two patients (13.3%) developed new angiographic lesions in the follow-up MRA. Three patients (20%) experienced mild adverse events during the study and none discontinued therapy. CONCLUSIONS: This is the first open-label study to demonstrate improvement in disease activity and acute phase reactants with 20 mg/day of leflunomide in TA patients who were refractory or intolerant to conventional therapy with corticosteroids and immunosuppressive agents. Leflunomide was safe and a steroid-sparing effect was observed. A double-blind controlled study is desirable to confirm this finding.

Oral microbial colonization in patients with systemic lupus erythematous: correlation with treatment and disease activity.

Treating patients with systemic lupus erythematosus (SLE) with steroids and immunosuppressive drugs may interfere in the presence of potentially opportunistic microorganisms in the oral cavity. The aim of this study was to evaluate the presence of Candida spp., Staphylococcus spp., Enterobacteria and Pseudomonas spp. in the oral cavity of SLE patients, compared with healthy controls. A group of 40 patients who had received therapy for at least 60 days was selected (19-53 years). For the control group, 40 healthy individuals matched for age, gender and use of partial prosthesis were selected. Oral rinse samples were collected and plated on specific culture media. After incubation, the number of colony forming units (CFU) was obtained and the isolates were identified at species level. Microbial counts were compared between SLE and control by analysis of variance (ANOVA) and Mann-Whitney (p < 0.05 significant). Microorganism counts in patients with and without immunosuppressive drugs, as well with active and inactive disease (according to SLEDAI score) were also compared. No significant differences in CFU/mL between SLE and control patients were observed (yeasts, p = 0.55; Staphylococci, p = 0.24; Enterobacteria/Pseudomonas spp., p = 0.26). No differences in microbial counts were observed regarding clinical parameters tested. The most frequent species isolated in the SLE group were Candida albicans, Staphylococcus epidermidis and Klebsiella oxytoca. In conclusion, no differences in frequency and microorganism levels were found between SLE patients and healthy individuals.