Beyond the joints,the extra-articular manifestations in rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease typically affecting the joints, but the systemic inflammatory process may involve other tissues and organs. Many extra-articular manifestations are recognized, which are related to worse long outcomes. Rheumatoid nodules are the most common extra-articular feature, found in about 30% of patients. Secondary Sjögren's syndrome and pulmonary manifestations are observed in almost 10% of patients, also in the early disease. Active RA with high disease activity has been associated with an increased risk of such features. Male gender, smoking habit, severe joint disease, worse function, high pro-inflammatory markers levels, high titer of rheumatoid factor, and HLA-related shared epitope have been reported as clinical predictors of occurrence of these rheumatoid complications. In addition, there is a little evidence deriving from randomized controlled trials in this field, thus the therapeutic strategy is mainly empiric and based on small case series and retrospective studies. However, considering that these extra-articular manifestations are usually related to the more active and severe RA, an aggressive therapeutic strategy is usually employed in view of the poor outcomes of these patients.The extra-articular features of RA remain, despite the improvement of joint damage, a major diagnostic and therapeutic challenge, since these are associated with a poor prognosis and need to be early recognized and promptly managed.     

Effective transfection of cells with multi-shell calcium phosphate-DNA nanoparticles

Coated calcium phosphate nanoparticles were prepared for cell transfection. A calcium phosphate nanoparticle served as core which was then coated with DNA for colloidal stabilisation. The efficiency of transfection could be considerably increased by adding another layer of calcium phosphate on the surface, thereby incorporating DNA into the particle and preventing its degradation within the cell by lysosomes. A subsequent outermost layer of DNA on the calcium phosphate gave a colloidal stabilisation. The efficiency of such multi-shell particles was significantly higher than that of simple DNA-coated calcium phosphate nanoparticles. The transfection efficiency of EGFP-encoding DNA was tested with different cell lines (T-HUVEC, HeLa, and LTK). The dispersions were stable and could be used for transfection after 2 weeks of storage at 4 degrees C without loss of efficiency.     

Latent HBV infection in single blood donors

A total of 14,366 one-time blood donors were examined; 984 (6.8%) donors of them were found to have anti-HBc. All anti-HBc-positive samples were tested for HBsAg, IgM anti-HBc, HBeAg, anti-HBe, and specific DNA-HBV by polymerase chain reaction (sensitivity 400 coplml or higher). Anti-HBc in combinations with HBsAg, anti-HBe, IgM anti-HBc was detected in 29 (2.9%), 3 (0.3%), 5 (0.5%) donors, respectively. Specific HBV DNA was identified in 29 donors with HBs-antigenemia and in 9 anti-HBc positive donors in the absence of serum HBsAg. The activity of AIAt was correlated with neither HBsAg nor HBV DNA. Thus, latent HBV infection is 0.9% of anti-HBc-positive one-time blood donors and tests for anti-HBc may be useful in identifying persons who need a more meticulous study for HBV DNA.     

Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.     

Distinct segregation of the pathogenic m.5667G>A mitochondrial tRNAAsn mutation in extraocular and skeletal muscle in chronic progressive external ophthalmoplegia

Chronic progressive external ophthalmoplegia (CPEO) is a frequent clinical manifestation of disorders caused by pathogenic mitochondrial DNA mutations. However, for diagnostic purposes skeletal muscle tissue is used, since extraocular muscle tissue is usually not available for work-up. In the present study we aimed to identify causative factors that are responsible for extraocular muscle to be primarily affected in CPEO. We performed comparative histochemical and molecular genetic analyses of extraocular muscle and skeletal muscle single fibers in a case of isolated CPEO caused by the heteroplasmic m.5667G>A mutation in the mitochondrial tRNA^Asn gene (MT-TN). Histochemical analyses revealed higher proportion of cytochrome c oxidase deficient fibers in extraocular muscle (41%) compared to skeletal muscle (10%). However, genetic analyses of single fibers revealed no significant difference either in the mutation loads between extraocular muscle and skeletal muscle cytochrome c oxidase deficient single fibers (extraocular muscle 86% ± 4.6%; skeletal muscle 87.8 %± 5.7%, p = 0.246) nor in the mutation threshold (extraocular muscle 74% ± 3%; skeletal muscle 74% ± 4%). We hypothesize that higher proportion of cytochrome c oxidase deficient fibers in extraocular muscle compared to skeletal muscle might be due to facilitated segregation of the m.5667G>A mutation into extraocular muscle, which may explain the preferential ocular manifestation and clinically isolated CPEO.     

Adult nemaline myopathy with trabecular muscle fibers

The term “trabecular myopathy” has been used to designate a syndrome resembling limb‐girdle muscular dystrophy in which the predominant pathological feature is an abundance of lobulated or trabecular muscle fibers. However, the validity of this nosological entity has not been verified. Herein we describe a 63‐year‐old man with a severe, progressive myopathy who exhibited the typical pathological features of both trabecular myopathy and nemaline myopathy in association with a biclonal gammopathy. In this case, adult‐onset nemaline myopathy was probably the primary disease process. The diagnostic significance of trabecular muscle fibers remains uncertain. Muscle Nerve, 2008     

Efficacy of amixine in experimental hantavirus infection

The experimental studies conducted on 2-week suckling mice infected with Hantaan virus, Strain 76-118) treated with oral and subcutaneous amoxine showed its prophylactic, therapeutical-and-prophylactic, and therapeutical efficiencies. Oral amoxine exhibited the highest efficiency when used in a dose of 10 mg/kg-1 96 hours before infection and throughout the incubation period. The protective efficiency was 61%. Subcutaneously, the agent was effective when three schemes for injection in a dose of 1 mg/kg-1. Its maximum effect was observed when amoxine was given by the therapeutical-and-prophylactic scheme. The death protection rate was 65%. The agent is effective in suppressing the reproduction of Hantaan virus in the brain tissue.