Estudo clínico-laboratorial das articulações de cães naturalmente infectados com leishmaniose visceral e experimentalmente inoculados com Leishmania chagasi por via intra-articular

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Impacto do uso droga imunomoduladora no tratamento da artrite séptica por Staphylococcus aureus

Pós-graduação em Doenças Tropicais - FMB

Avaliação do efeito trombogênico da perfusão regional intravenosa com gentamicina em equinos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differential arthritogenicity of Staphylococcus aureus strains isolated from biological samples

Background Staphylococcus aureus is the most common agent of septic arthritis that is a severe, rapidly progressive and destructive joint disease. Superantigens produced by S. aureus are considered the major arthritogenic factors. In this study, we compared the arthritogenic potential of five superantigen-producing staphylococcal strains. Methods Male C57BL/6 mice were intravenously infected with ATCC 19095 SEC+, N315 ST5 TSST-1+, S-70 TSST-1+, ATCC 51650 TSST-1+ and ATCC 13565 SEA+ strains. Clinical parameters as body weight, arthritis incidence and clinical score were daily evaluated. Joint histopathological analysis and spleen cytokine production were evaluated at the 14th day after infection. Results Weight loss was observed in all infected mice. ATCC 19095 SEC+, N315 ST5 TSST-1+ and S-70 TSST-1+ were arthritogenic, being the highest scores observed in ATCC 19095 SEC+ infected mice. Intermediate and lower clinical scores were observed in N315 ST5 TSST-1+ and S-70 TSST-1+ infected mice, respectively. The ATCC 13565 SEA+ strain caused death of 85% of the animals after 48 h. Arthritis triggered by the ATCC 19095 SEC+ strain was characterized by accentuated synovial hyperplasia, inflammation, pannus formation, cartilage destruction and bone erosion. Similar joint alterations were found in N315 ST5 TSST-1+ infected mice, however they were strikingly more discrete. Only minor synovial proliferation and inflammation were triggered by the S-70 TSST-1+ strain. The lowest levels of TNF-α, IL-6 and IL-17 production in response to S. aureus stimulation were found in cultures from mice infected with the less arthritogenic strains (S-70 TSST-1+ and ATCC 51650 TSST-1+). The highest production of IL-17 was detected in mice infected with the most arthritogenic strains (ATCC 19095 SEC+ and N315 ST5 TSST-1+). Conclusions Together these results demonstrated that S. aureus strains, isolated from biological samples, were able to induce a typical septic arthritis in mice. These results also suggest that the variable arthritogenicity of these strains was, at least in part, related to their differential ability to induce IL-17 production.

Failure of ceftriaxone in an intravenous drug user with invasive infection due to Ralstonia pickettii

We report a case of septic arthritis due to Ralstonia pickettii in an intravenous drug user with unfavorable clinical course under antibiotic therapy with ceftriaxone despite in vitro susceptibility to the drug. The treatment failure may have been due to a discrepancy between in vitro and in vivo susceptibility of R. pickettii, or to resistance development mediated by a recently described inducible beta-lactamase.

Arthroscopic approaches to the fetlock joint of adult cattle: a cadaver study

The objective of the present study was to describe the arthroscopic anatomy of the bovine fetlock joint using one palmar/plantar and three dorsal joint approaches. A comparative anatomic, ultrasonographic and arthroscopic study using 20 cadaveric feet from 13 non-lame adult dairy cows was performed. Arthroscopy was accomplished using a rigid arthroscope to view the synovial cavities with their synovial villi and parts of the following structures: the distal ends of the metacarpal/metatarsal III/IV bones with their trochleae and sagittal ridges, synovial grooves, the articular surfaces of the proximal sesamoid bones, the proximal aspects of the first phalanges, the lateral and medial collateral ligaments, the suspensory ligament and the interdigital ligaments as parts of the interosseus muscle, the cruciate sesamoidean ligaments, the communication site between the lateral and medial pouch in the palmar/plantar area, and dorsally the septum between the lateral and the medial pouch. The technique allowed a good overall view of most relevant structures in the sound cadaver joint. Further investigations are warranted to evaluate the diagnostic, therapeutic and prognostic applications of these techniques in the treatment of septic arthritis.

Continuous infusion of ticarcillin-clavulanate for home treatment of serious infections: clinical efficacy, safety, pharmacokinetics and pharmacodynamics

Continuous infusion (CI) ticarcillin-clavulanate is a potential therapeutic improvement over conventional intermittent dosing because the major pharmacodynamic (PD) predictor of efficacy of beta-lactams is the time that free drug levels exceed the MIC. This study incorporated a 6-year retrospective arm evaluating efficacy and safety of CI ticarcillin-clavulanate in the home treatment of serious infections and a prospective arm additionally evaluating pharmacokinetics (PK) and PD. In the prospective arm, steady-state serum ticarcillin and clavulanate levels and MIC testing of significant pathogens were performed. One hundred and twelve patients (median age, 56 years) were treated with a CI dose of 9.3-12.4 g/day and mean CI duration of 18.0 days. Infections treated included osteomyelitis (50 patients), septic arthritis (6), cellulitis (17), pulmonary infections (12), febrile neutropenia (7), vascular infections (7), intra-abdominal infections (2), and Gram-negative endocarditis (2); 91/112 (81%) of patients were cured, 14 (13%) had partial response and 7 (6%) failed therapy. Nine patients had PICC line complications and five patients had drug adverse events. Eighteen patients had prospective PK/PD assessment although only four patients had sufficient data for a full PK/PD evaluation (both serum steady-state drug levels and ticarcillin and clavulanate MICs from a bacteriological isolate), as this was difficult to obtain in home-based patients, particularly as serum clavulanate levels were found to deteriorate rapidly on storage. Three of four patients with matched PK/PD assessment had free drug levels exceeding the MIC of the pathogen. Home Cl of ticarcillin-clavulanate is a safe, effective, convenient and practical therapy and is a therapeutic advance over traditional intermittent dosing when used in the home setting. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Genetic and Molecular Basis of Encapsulation and Capsule Diversity in Kingella kingae

Kingella kingae is a bacterial pathogen that is increasingly recognized as an etiology of septic arthritis, osteomyelitis, bacteremia, and endocarditis in young children. The pathogenesis of K. kingae disease starts with bacterial adherence to the respiratory epithelium of the posterior pharynx. Previous work has identified type IV pili and a trimeric autotransporter protein called Knh (Kingella NhhA homolog) as critical factors for adherence to human epithelial cells. Additional studies established that the presence of a polysaccharide capsule interferes with Knh-mediated adherence. Given the inhibitory role of capsule during adherence we sought to uncover the genes involved in capsule expression to understand how capsule is elaborated on the cell surface. Additionally, this work aimed to further characterize capsule diversity among K. kingae clinical isolates and to investigate the relationship between capsule type and site of isolation.

We first set out to identify the carbohydrates present in the K. kingae capsule present in the prototype strain 269-492. Glycosyl composition and NMR analysis of surface extractable polysaccharides demonstrated two distinct polysaccharides, one consisting of GalNAc and Kdo with the structure →3)-β-GalpNAc-(1→5)-β-Kdop-(2→ and the other containing galactose alone with the structure →5)-β-Galf-(1→.

To discern the two polysaccharides we disrupted the ctrA gene required for surface localization of the K. kingae polysaccharide capsule and observed a loss of GalNAc and Kdo but no effect on the presence of Gal in bacterial surface extracts. In contrast, deletion of the pamABCDE locus involved in production of a reported galactan exopolysaccharide eliminated Gal but had no effect on the presence of GalNAc and Kdo in surface extracts. These results established that K. kingae strain KK01 produces a polysaccharide capsule with the structure →3)-β-GalpNAc-(1→5)-β-Kdop-(2→ and a separate exopolysaccharide with the structure →5)-β-Galf-(1→.

Having established that K. kingae produces a capsule comprised of GalNAc and Kdo, we next set out to identify the genetic determinants of capsule through a transposon mutagenesis screen. In addition to the previously identified ctrABCD operon, lipA, lipB, and a putative glycosyltransferase termed csaA (capsule synthesis region A gene A) were found to be essential for the production of surface-localized capsule. The ctr operon, lipA, lipB, and csaA were found to be present at unlinked locations throughout the genome, which is atypical for gram-negative organisms that elaborate a capsule dependent on an ABC-type transporter for surface localization. Through examining capsule localization in the ctrA, lipA, lipB, and csaA mutant strains, we determined that the ctrABCD, lipA/lipB, and csaA gene products respectively function in capsule export, assembly, and synthesis, respectively. The GalNAc transferase and Kdo transferase domains found in CsaA further support its role in catalyzing the synthesis of the GalNAc-Kdo capsule in the K. kingae prototype strain.

To investigate the capsule diversity that exists in K. kingae we screened a panel of strains isolated from patients with invasive disease or healthy carriers for the csaA capsule synthesis locus. We discovered that Kingella kingae expresses one of 4 capsule synthesis loci (csa, csb, csc, or csd) associated with a capsule consisting of Kdo and GalNAc (type a), Kdo and GlcNAc (type b), Kdo and ribose (type c), and GlcNAc and galactose (type d), respectively. Cloning of the csa, csb, csc, or csd locus into the empty flanking gene region in a non-encapsulated mutant (creation of an isogenic capsule swap) was sufficient to produce either the type a, type b, or type c capsule, respectively, further supporting the role of these loci in expression of a specific polysaccharide linkage. Capsule type a and capsule type b accounted for 96% of invasive strains. Conversely, capsule type c and capsule type d were found disproportionately among carrier isolates, suggesting that capsule type is important in promoting invasion and dissemination.

In conclusion, we discovered that Kingella kingae expresses a polysaccharide capsule and an exopolysaccharide on its surface that require distinct genetic loci for surface localization. Further investigation into genetic determinants of encapsulation revealed the loci ctrABCD, lipA/lipB, and a putative glycosyltransferase are required for capsule expression, with the gene products having roles in capsule export, assembly, and synthesis, respectively. The putative glycosyltransferase CsaA was determined to be a bifunctional enzyme with both GalNAc-transferase and Kdo-transferase activity. Furthermore, we discovered a total of 4 capsule types expressed in clinical isolates of K. kingae, each with a distinct capsule synthesis locus. The variation in the proportion of capsule types found between invasive strains and carriage strains suggest that capsule type is important in promoting invasion and dissemination. Taken together, this work expands our knowledge of the capsule types expressed among K. kingae carrier and invasive isolates and provides insights into the common genetic determinants of capsule expression. These contributions may lead to selecting clinically relevant capsule types to develop into a capsule based vaccine to prevent K. kingae colonization.

Artritis séptica de hombro

Hombre de 66 años de edad, con dolor en hombro derecho, malestar general y fiebre de una semana de evolución. Al exámen físico presenta edema, rubor y calor del hombro derecho. Los paraclínicos evidenciaron leucocitosis con neutrofilia. La resonancia magnética y el aislamiento de Staphylococcus aureus en sangre confirmaron la sospecha de artritis séptica de hombro. El paciente requirió manejo en unidad de cuidado intensivo, antibioticoterapia y drenaje quirúrgico.

Infection and immune-mediated meningococcal-associated arthritis: combination features in the same patient

We present a case of a 16-year-old male patient with sudden-onset, rash, arthritis and meningitis by Neisseria meningitidis one week after an acute upper respiratory infection. On the 10th day of treatment followed by neurological and arthritis clinical improvement, he presented once again a tender and swollen left knee with a moderate effusion, and active and passive range of motion was severely limited secondary to pain, and when he was submitted to surgical drainage and synovial fluid analysis he showed inflammatory characteristics. A non-steroidal anti-inflammatory drug was taken for five days with complete improvement of symptoms. The case is notable for its combination of features of septic and immune-mediated arthritis, which has rarely been reported in the same patient.

Infection and immune-mediated meningococcal-associated arthritis: combination features in the same patient

We present a case of a 16-year-old male patient with sudden-onset, rash, arthritis and meningitis by Neisseria meningitidis one week after an acute upper respiratory infection. On the 10th day of treatment followed by neurological and arthritis clinical improvement, he presented once again a tender and swollen left knee with a moderate effusion, and active and passive range of motion was severely limited secondary to pain, and when he was submitted to surgical drainage and synovial fluid analysis he showed inflammatory characteristics. A non-steroidal anti-inflammatory drug was taken for five days with complete improvement of symptoms. The case is notable for its combination of features of septic and immune-mediated arthritis, which has rarely been reported in the same patient.

15-deoxy-Δ12,14-prostaglandin J2 Reduces Albumin-induced Arthritis In Temporomandibular Joint Of Rats.

The aim of this study was to evaluate the peripheral effect of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in albumin-induced arthritis in temporomandibular joint (TMJ) of rats. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund׳s adjuvant. Pretreatment with an intra-articular injection of 15d-PGJ2 (100 ng/TMJ) before mBSA intra-articular injection (10 µg/TMJ) (challenge) in immunized rats significantly reduced the albumin-induced arthritis inflammation. The results demonstrated that 15d-PGJ2 was able to inhibit plasma extravasation, leukocyte migration and the release of inflammatory cytokines IL-6, IL-12, IL-18 and the chemokine CINC-1 in the TMJ tissues. In addition, 15d-PGJ2 was able to increase the expression of the anti-adhesive molecule CD55 and the anti-inflammatory cytokine IL-10. Taken together, it is possible to suggest that 15d-PGJ2 inhibit leukocyte infiltration and subsequently inflammatory process, through a shift in the balance of the pro- and anti-adhesive properties. Thus, 15d-PGJ2 might be used as a potential anti-inflammatory drug to treat arthritis-induced inflammation of the temporomandibular joint.

Cervical Spine Involvement In Rheumatoid Arthritis--a Systematic Review.

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disorder that can compromise the cervical spine in up to 80% of the cases. The most common radiological presentations of cervical involvement are atlantoaxial subluxation (AAS), cranial settling and subaxial subluxation (SAS). We performed a systematic review in the PubMed Database of articles published later 2005 to evaluate the prevalence, progression and risk factors for cervical spine involvement in RA patients. Articles were classified according to their level of evidence. Our literature review reported a wide range in the prevalence of cervical spine disease, probably explained by the different studied populations and disease characteristics. Uncontrolled RA is probably the main risk factor for developing a spinal instability. Adequate treatment with DMARD and BA can prevent development of cervical instabilities but did not avoid progression of a pre-existing injury. MRI is the best radiological method for diagnosis cervical spine involvement. AAS is the most common form of RA. Long term radiological follow-up is necessary to diagnosis patients with late instabilities and monitoring progression of diagnosed injuries.

[the Modified Us7 Score In The Assessment Of Synovitis In Early Rheumatoid Arthritis].

To evaluate the modified US7 score (MUS7 score SYN) in the assessment of patients with early rheumatoid arthritis (ERA). In addition, dorsal and palmar recesses of the wrists as well as of small joints of the hands and feet were examined for the presence of synovitis by means of a global assessment of joints. The study sample comprised 32 patients treated for arthritis, with an average disease duration of 13 months. An ultrasound machine with high frequency transducer was used. Hands were also X-rayed and analysed by Larsen score. Out of the 832 examined joints, synovitis was detected in 173 (20,79%), tenosynovitis in 22 (4,91%), and erosions in 3 (1,56%). Synovitis was predominantly detected in the dorsal recess (73,38%) of MCP and PIP joints, when compared with palmar recess (26%). The presence of synovitis in the joints evaluated correlated with clinical (HAQ-DI, DAS28), laboratory (ACPA, RF, CRP), and ultrasound results (r = 0,37 to r = 0,42; p = 0,04 to p = 0,003). We found correlation of the MUS7 score SYN of the gray scale US or of the power Doppler US with DAS28 (PCR) values (r = 0,38; p = 0,0332), and with CRP results (r = 0,39; p = 0,0280), respectively. The dorsal recess, the wrist, and small joints can be considered as important sites to detect synovitis by the MUS7 score SYN in patients with ERA.

[demographic And Clinical Features Of Patients With Rheumatoid Arthritis In Piauí, Brazil--evaluation Of 98 Patients].

Brazilian epidemiological studies on rheumatoid arthritis are scarce, mainly in the northeast; thus many data currently available originate from the international literature. To describe demographic, clinical and serological characteristics of patients with rheumatoid arthritis (RA) followed-up by the same physician, in state of Piauí, Brazil. Data were collected between August 2010 and March 2013, in three health services of Piauí that provided health care in Rheumatology: a university-affiliated hospital, a public outpatient clinic and a private clinic. The numbers represent mean ± SD or percentage: 47.5±11.03 years-old non-Caucasian woman, non-smoker (59.2%), low educational level, mean disease duration of 7.7 years ± 7.6, and major extra-articular manifestations were rheumatoid nodules (19.4%) and sicca syndrome (46.9%). Features of rheumatoid arthritis obtained in this study are similar to those found in some national and international studies, but we observed higher female preponderance and illiteracy rate, in addition to a moderately severe erosive disease on average, with frequent sicca and other extra-articular manifestations.