Skeletal muscle major histocompatibility complex class I and II expression differences in adult and juvenile dermatomyositis

OBJECTIVE: To analyze major histocompatibility complex expression in the muscle fibers of juvenile and adult dermatomyositis. METHOD: In total, 28 untreated adult dermatomyositis patients, 28 juvenile dermatomyositis patients (Bohan and Peter's criteria) and a control group consisting of four dystrophic and five Pompe's disease patients were analyzed. Routine histological and immunohistochemical (major histocompatibility complex I and II, StreptoABComplex/HRP, Dakopatts) analyses were performed on serial frozen muscle sections. Inflammatory cells, fiber damage, perifascicular atrophy and increased connective tissue were analyzed relative to the expression of major histocompatibility complexes I and II, which were assessed as negatively or positively stained fibers in 10 fields (200X). RESULTS: The mean ages at disease onset were 42.0 +/- 15.9 and 7.3 +/- 3.4 years in adult and juvenile dermatomyositis, respectively, and the symptom durations before muscle biopsy were similar in both groups. No significant differences were observed regarding gender, ethnicity and frequency of organ involvement, except for higher creatine kinase and lactate dehydrogenase levels in adult dermatomyositis (p<0.050). Moreover, a significantly higher frequency of major histocompatibility complex I (96.4% vs. 50.0%, p<0.001) compared with major histocompatibility complex II expression (14.3% vs. 53.6%, p = 0.004) was observed in juvenile dermatomyositis. Fiber damage (p = 0.006) and increased connective tissue (p<0.001) were significantly higher in adult dermatomyositis compared with the presence of perifascicular atrophy (p<0.001). The results of the histochemical and histological data did not correlate with the demographic data or with the clinical and laboratory features. CONCLUSION: The overexpression of major histocompatibility complex I was an important finding for the diagnosis of both groups, particularly for juvenile dermatomyositis, whereas there was lower levels of expression of major histocompatibility complex II than major histocompatibility complex I. This finding was particularly apparent in juvenile dermatomyositis.

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 +/- 163.4 IU/ml (range 3.5- 9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 +/- 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels ( r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

JUVENILE RECRUITMENT, EARLY GROWTH, AND MORPHOLOGICAL VARIATION IN THE ENDANGERED SANTA CATALINA ISLAND RATTLESNAKE, CROTALUS CATALINENSIS

Life-history information constitutes the raw data for building population models used in species conservation. We provide life-history data for the endangered Santa Catalina Island Rattlesnake, Crotalus catalinensis. We use data from 277 observations of C. catalinensis made between 2002 and 2011 on the island. Mean snout-vent length (SVL) of adult C. catalinensis was 643 mm for males and 631 mm for females; the difference was not significant. The degree of sexual size dimorphism (SSD; using SVL) was -0.02. However, sexes were dimorphic in total length ( SVL + tail length), relative tail length, and stoutness. Juvenile recruitment occurs during late-summer. In their first year of life, juveniles seem to grow at a rate of about 1.7 cm/mo. Females seem to become mature around 570 mm SVL, probably in the year when they become 2 y old. Scattered literature data corroborates the time of juvenile recruitment described herein. Growth in C. catalinensis seems to be slower than that of C. ruber, its sister taxa, but similar to other rattlesnakes.

Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: microbiological profile

The aim of this trial was to investigate changes occurring in the subgingival microbiological composition of subjects with aggressive periodontitis, treated with antimicrobial photodynamic therapy (aPDT), in a single episode, or scaling and root planing (SRP), in a split-mouth design on -7, 0, and +90 days. Ten patients were randomly assigned to either aPDT using a laser source in conjunction with a photosensitizer or SRP with hand instruments. Subgingival plaque samples were collected and the counts of 40 subgingival species were determined using checkerboard DNA-DNA hybridization. The data were analyzed using the method of generalized estimating equations (GEE) to test the associations between treatments, evaluated parameters, and experimental times (alpha = .05). The results indicated that aPDT and SRP affects different bacterial species, with aPDT being effective in reducing numbers of A. actinomycetemcomitans than SRP. On the other hand, SRP was more efficient than aPDT in reducing the presence of periodontal pathogens of the Red Complex. Additionally, a recolonization in the sites treated by aPDT was observed, especially for T. forsythia and P. gingivalis. Under our experimental conditions, this trial demonstrates that aPDT and SRP affected different groups of bacteria, suggesting that their association may be beneficial for the non-surgical treatment of aggressive periodontitis.

Juvenile systemic lupus erythematosus and dermatomyositis associated with urticarial vasculitis syndrome: a unique presentation

To report a case of triple association of juvenile systemic lupus erythematosus (SLE), juvenile dermatomyositis and urticarial vasculitis as well as a review of the relevant literature. A 12-year-old male patient diagnosed with overlap syndrome between SLE and juvenile dermatomyositis since 2004 evolved with erythematous plaques, which were compatible with an urticarial rash. Clinical, laboratory and histopathological findings indicated a diagnosis of urticarial vasculitis. The patient previously had a C1q deficiency. Using the established treatment with methylprednisolone (1 g/day for 3 days), increasing doses of deflazacort and introduction of a dapsone, as well as mycophenolate mofetil regimen, with the suspension of azathioprine resulted in complete resolution of skin lesions. Urticarial vasculitis can present in various diseases. In SLE, presentation of urticarial vasculitis in children is rarely found. The triple association of juvenile-onset SLE, juvenile dermatomyositis and urticarial vasculitis is unusual, and this is the first case described in literature.

MMP3 and TIMP1 variants contribute to chronic periodontitis and may be implicated in disease progression

Aim Matrix metalloproteinases (MMPs) play a key role in the tissue destruction characteristic of chronic periodontitis. The purpose of this study was to investigate the association of MMP and TIMP polymorphisms with chronic periodontitis in two populations. Material and Methods A total of 34 polymorphisms spanning 12 MMP and 2 TIMP genes were genotyped in 401 individuals from Brazil (99 cases with chronic periodontitis and 302 controls), and 274 individuals from the US (70 cases and 204 controls). Individuals were considered cases if presenting at least three teeth exhibiting sites of clinical attachment loss =5 mm in two different quadrants. Controls were characterized by absence of clinical attachment loss and no sites with probing depth >3 mm. MMP3 and TIMP1 mRNA expression was evaluated in healthy and diseased periodontal tissues. Results TIMP1 showed association with chronic periodontitis in the Brazilian population (for rs5906435, p = 0.0004), whereas MMP3 showed association in the US population (for rs679620, p = 0.0003; and rs650108, p = 0.002) and in the Brazilian population (for rs639752, p = 0.005). MMP3 and TIMP1 mRNA expression was significantly higher in diseased tissues when compared to control tissues. Conclusions Our results further support a role for variations in MMP3 in chronic periodontitis and report a novel association with TIMP1. These genes may be considered additional candidate genes for chronic periodontitis.

Experimental arthritis exacerbates Aggregatibacter actinomycetemcomitans-induced periodontitis in mice

Aim This study aimed to investigate whether chronic antigen-induced arthritis (AIA) influences infection-induced periodontitis (PD) in mice and whether PD modifies the clinical course of AIA. The contribution of anti-TNF-a therapy was also evaluated. Materials and methods The PD was induced in C57BL/6 mice by oral infection with Aggregatibacter actinomycetemcomitans. AIA was induced after infection. Anti-TNF-a and chlorhexidine therapies were used to investigate the role of TNF-a and oral infection on PD and AIA interaction. Maxillae, knee joints, lymph nodes and serum samples were used for histomorphometric, immunoenzymatic and/or real time-PCR analyses. Results Antigen-induced arthritis exacerbated alveolar bone loss triggered by PD infection. In contrast, PD did not influence AIA in the evaluated time-points. PD exacerbation was associated with enhanced production of IFN-? in maxillae and expression of the Th1 transcription factor tBET in submandibular lymph nodes. Increased serum levels of IL-6 and C-reactive protein were also detected. Anti-TNF-a and antiseptic therapies prevented the development and exacerbation of infectious-PD. Anti-TNF-a therapy also resulted in reduced expression of IFN-?, TNF-a and IL-17 in maxillae. Conclusions Altogether, the current results indicate that the exacerbation of infection-induced PD by arthritis is associated with an alteration in lymphocyte polarization pattern and increased systemic immunoreactivity. This process was ameliorated by anti-TNF-a and antiseptic therapies.

Invasive aspergillosis: a severe infection in juvenile systemic lupus erythematosus patients

Infections are an important cause of morbidity and mortality in juvenile systemic lupus erythematosus (JSLE). Among them, invasive aspergillosis (IA), which is usually related to immunosuppressed patients, has been rarely reported in JSLE. From 1983 to 2011, 5604 patients were followed at our institution and 283 (5%) met the American College of Rheumatology (ACR) classification criteria for SLE. Six (2.1%) of our JSLE patients had IA. One of them was previously reported and five will be described herein. Four of them were female. The median age at JSLE diagnosis was 12 years (8-16) and the median interval between diagnosis of JSLE and IA was 6 months (1-38). All had pulmonary involvement and three of them had systemic involvement. The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was 19 (7-22). Diagnosis of IA was performed by isolation of Aspergillus spp., two in bronchoalveolar lavage culture and by way of autopsy in the others. All of them were treated with corticosteroids and/or immunosuppressive drugs at IA diagnosis (azathioprine and/or intravenous cyclophosphamide). They all required treatment in the pediatric intensive care unit with mechanical ventilation and antifungal therapy (fluconazole, amphotericin B, itraconazole and/or voriconazole); nonetheless, none of them survived. In conclusion, this was the first report that evaluated the prevalence of IA in a large population of JSLE patients from a tertiary pediatric hospital, and clearly showed the severity of the outcome, especially in patients with active disease and treated with immunosuppressive agents. This study reinforces the importance of early diagnosis and treatment with certain antifungals, especially in critically ill patients. Lupus (2012) 21, 1011-1016.

Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus

We compared outcomes of alveolar hemorrhage (AH) in juvenile (JSLE) and adult onset SLE (ASLE). From 263 JSLE and 1522 ASLE, the AH occurred in 13 (4.9%) and 15 (1.0%) patients, respectively (p < .001). Both groups had comparable disease duration (2.6 +/- 3.0 vs. 5.6 +/- 7.0 years, p = .151) and median SLEDAI scores [17.5 (2 to 32) vs. 17.5 (3 to 28), p = 1.000]. At AH onset, a higher frequency of JSLE were already on a high prednisone dose ( > 0.5 mg/kg/day) compared to ASLE (54% vs. 15%, p = .042). The mean drop of hemoglobin was significantly lower in JSLE (2.9 +/- 0.9 vs. 5.5 +/- 2.9 g/dL, p = .006). Although treatments with methylprednisolone, plasmapheresis, intravenous immunoglobulin and cyclophosphamide were similar in both groups (p > .050), regarding outcomes, there was a trend in high frequency of mechanical ventilation use (85% vs. 47%, p = .055) and also significant mortality (69% vs. 13%, p = .006) in JSLE compared to ASLE. The sepsis frequency was comparable in both groups (50% vs. 27%, p = .433). We have identified that AH in JSLE has a worse outcome most likely related to respiratory failure. The AH onset in JSLE already treated with high-dose steroids raises the concern of inadequate response to this treatment and reinforces the recommendation of early aggressive alternative therapies in this group of patients. Lupus (2012) 21, 872-877.

Reduced occurrence of programmed cell death and gliosis in the retinas of juvenile rabbits after short-term treatment with intravitreous bevacizumab

OBJECTIVE: Bevacizumab has been widely used as a vascular endothelial growth factor antagonist in the treatment of retinal vasoproliferative disorders in adults and, more recently, in infants with retinopathy of prematurity. Recently, it has been proposed that vascular endothelial growth factor acts as a protective factor for neurons and glial cells, particularly in developing nervous tissue. The purpose of this study was to investigate the effects of bevacizumab on the developing retinas of juvenile rabbits. METHODS: Juvenile rabbits received bevacizumab intravitreously in one eye; the other eye acted as an untreated control. Slit-lamp and fundoscopic examinations were performed both prior to and seven days after treatment. At the same time, retina samples were analyzed using immunohistochemistry to detect autophagy and apoptosis as well as proliferation and glial reactivity. Morphometric analyses were performed, and the data were analyzed using the Mann-Whitney U test. RESULTS: No clinical abnormalities were observed in either treated or untreated eyes. However, immunohistochemical analyses revealed a reduction in the occurrence of programmed cell death and increases in both proliferation and reactivity in the bevacizumab-treated group compared with the untreated group. CONCLUSIONS: Bevacizumab appears to alter programmed cell death patterns and promote gliosis in the developing retinas of rabbits; therefore, it should be used with caution in developing eyes.

Occurrence and antimicrobial susceptibility of Porphyromonas spp. and Fusobacterium spp. in dogs with and without periodontitis

The occurrence of Porphyromonas gulae, Porphyromonas macacae, Fusobacterium nucleatum and Fusobacterium canifelinum in subgingival plaque from dogs with and without periodontitis as well as their antimicrobial susceptibility were evaluated. From 50 dogs with periodontitis were identified 38 P. gulae, 8 P. macacae, 26 F. nucleatum and 15 F. canifelinum, and from 50 dogs without periodontitis were identified 15 P. gulae, 12 F. nucleatum and 11 F. canifelinum. All strains were susceptible to most of the antibiotics tested, however, different resistance rates to clarithromycin, erythromycin and metronidazole among strains were observed. The role of P. gulae, P. macacae, F. nucleatum and F. canifelinum in periodontal disease of household pets needs to be defined to a better prevention and treatment of the canine periodontitis. (c) 2012 Elsevier Ltd. All rights reserved.

Levels of Selenomonas species in generalized aggressive periodontitis

Goncalves LFH, Fermiano D, Feres M, Figueiredo LC, Teles FRP, Mayer MPA, Faveri M. Levels of Selenomonas species in generalized aggressive periodontitis. J Periodont Res 2012; 47: 711718. (c) 2012 John Wiley & Sons A/S Background and Objective: To compare the levels of Selenomonas sputigena and uncultivated/unrecognized Selenomonas species in subgingival biofilms from periodontally healthy subjects and from subjects with generalized aggressive periodontitis. Material and Methods: Fifteen periodontally healthy subjects and 15 subjects with generalized aggressive periodontitis were recruited and their clinical periodontal parameters were evaluated. Nine subgingival plaque samples were collected from each subject and all were individually analyzed for the levels of 10 bacterial taxa, including cultured and uncultivated/unrecognized microorganisms, using the RNA-oligonucleotide quantification technique. Between-group differences in the levels of the test taxa were determined using the MannWhitney U-test. Results: Subjects with generalized aggressive periodontitis showed significantly higher mean counts of Porphyromonas gingivalis, S. sputigena and the Mitsuokella sp. Human Oral Taxon (HOT) 131 (previously described as Selenomonas sp. oral clone CS002), while higher mean counts of Actinomyces gerencseriae and Streptococcus sanguinis were found in periodontally healthy subjects (p < 0.01). Selenomonas sp. HOT 146 was only detected in the generalized aggressive periodontitis group. In the generalized aggressive periodontitis group, the levels of P.gingivalis and S.sputigena were higher in deep sites (probing depth = 5 mm) than in shallow sites (probing depth = 3 mm) (p < 0.01). Furthermore, in subjects with generalized aggressive periodontitis, sites with probing depth of = 3 mm harbored higher levels of these two species than sites with the same probing depth in periodontally healthy subjects. There were positive correlations between probing depth and the levels of P.gingivalis (r = 0.77; p < 0.01), S.sputigena (r = 0.60; p < 0.01) and Selenomonas dianae (previously described as Selenomonas sp. oral clone EW076) (r = 0.42, p < 0.05). Conclusion: S. sputigena and Mitsuokella sp. HOT 131 may be associated with the pathogenesis of generalized aggressive periodontitis, and their role in the onset and progression of this infection should be investigated further.

Exercise training in juvenile dermatomyositis

Objective. To investigate the effects of a supervised exercise training program on health parameters, physical capacity, and health-related quality of life in patients with mild and chronic juvenile dermatomyositis (DM). Methods. This was a prospective longitudinal study following 10 children with mild and chronic juvenile DM (disease duration >1 year). The exercise program consisted of twice-a-week aerobic and resistance training. At baseline and after the 12-week intervention, we assessed muscle strength and function, aerobic conditioning, body composition, juvenile DM scores, and health-related quality of life. Results. Child self-report and parent proxy-report Pediatric Quality of Life Inventory scores were improved after the intervention (-40.3%; P = 0.001 and -48.2%; P = 0.049, respectively). Importantly, after exercise, the Disease Activity Score was reduced (-26.9%; P = 0.026) and the Childhood Muscle Assessment Scale was improved (+2.5%; P = 0.009), whereas the Manual Muscle Test presented a trend toward statistical significance (+2.2%; P = 0.081). The peak oxygen consumption and time-to-exhaustion were increased by 13.3% (P = 0.001) and 18.2% (P = 0.003), respectively, whereas resting heart rate was decreased by 14.7% (P = 0.006), indicating important cardiovascular adaptations to the exercise program. Upper and lower extremity muscle strength and muscle function were also significantly improved after the exercise training (P < 0.05). Both the whole-body and the lumbar spine bone mineral apparent density were significantly increased after training (1.44%; P = 0.044 and 2.85%; P = 0.008, respectively). Conclusion. We showed for the first time that a 12-week supervised exercise program is safe and can improve muscle strength and function, aerobic conditioning, bone mass, disease activity, and health-related quality of life in patients with active and nonactive mild and chronic juvenile DM with near normal physical function and quality of life.

Clinical and Microbiologic Evaluation, by Real-Time Polymerase Chain Reaction, of Non-Surgical Treatment of Aggressive Periodontitis Associated With Amoxicillin and Metronidazole

Background: The aim of the present study is to evaluate the clinical and microbiologic changes resulting from non-surgical periodontal treatment associated with amoxicillin and metronidazole in individuals with aggressive periodontitis. Methods: Fifteen individuals with aggressive periodontitis received non-surgical periodontal treatment and 45 days after completion of treatment were treated with antibiotics. Clinical data and samples of subgingival plaque were collected at baseline, 45 days after the non-surgical periodontal treatment, and 1 month after the use of antimicrobial agents. After 3 and 6 months, only clinical data were collected. The presence and quantification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema denticola (Td), and Dialister pneumosintes were determined by real-time polymerase chain reaction. Results: All clinical parameters, with the exception of clinical attachment level (CAL), had significantly (P<0.05) improved at the end of the third month after non-surgical therapy associated with antibiotics. There was significant (P<0.05) reduction in the quantities of Td and Tf. After 1 month, there were significant (P<0.05) reductions in the frequencies of Pg and Tf. Conclusion: Non-surgical mechanical treatment associated with the use of amoxicillin and metronidazole led to an improvement in all clinical parameters studied, except for CAL, and significantly reduced the amount of subgingival Tf and Td. J Periodontal 2012;83:744-752.

GENETIC VARIABILITY FOR JUVENILE CHARACTERS OF Cedrela fissilis VELL. PROGENIES: A SUBSIDY FOR DEFINITION OF SEED COLLECTION ZONE

The objective of this study was to evaluate the genetic differences among three matrix groups of Cedrela fissilis based on quantitative juvenile variables on a progeny test to define seed collecting zones and use of seeds of this species in the study region as well as to evaluate genetic variability of the sampled material. A progeny test was established in a nursery with seeds from 48 seed trees collected in the municipalities of Rio Negrinho, Mafra and Sao Bento do Sul, state of Santa Catarina, and in the municipalities of Lapa, Rio Negro, Campo do Tenente and Antonio Olinto, state of Parana. Of the collected seed trees, 33 sampled trees were distributed in three sites and 15 trees were dispersed in the studied region. It was used a complete random block design, with 8 replicates and 20 plants per plot. Evaluated data included: emergency rate; seedling base diameter and height (61, 102 and 145 days after the seeds were sowed); seedling survival; number of leaves per seedling; aerial section dry mass and root dry mass; and the foliar area of the third fully expanded leaf measured from the apical meristem. The Maximum Restricted Likelihood Method (REML) was used, using the software SELEGEN for analysis. It was found that the juvenile characters are strongly genetically controlled and they can be used to estimate genetic variability of population samples of Cedrela fissilis. The three groups of trees spatially limited did not significantly differ among each other, allowing to conclude that the three areas are part of the same tree seed transfer zone.