Muscle mass and composition of the hip, thigh and abdominal muscles in women with and without hip osteoarthritis

The objective of this study was to compare muscle mass and composition between individuals with and without hip osteoarthritis. Twenty-four women with hip osteoarthritis (OA group) and 16 healthy women (healthy group) participated in this study. Muscle thickness (MT) and echo intensity (EI) were measured as indices of muscle mass and composition, respectively, using ultrasound imaging. Seven muscles were examined: gluteus maximus, gluteus medius, quadriceps femoris, rectus abdominis, external oblique, internal oblique and transversus abdominis. MT of only quadriceps femoris in the OA group was significantly thinner than that in the healthy group. EIs of gluteus medius, quadriceps femoris and rectus abdominis were significantly higher in the OA group than those in the healthy group. Thus, actual contractile tissue of gluteus medius and rectus abdominis substantially decreased, although muscle mass was similar, whereas both quantitative and qualitative changes occurred in quadriceps femoris in patients with hip OA.     

Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem particularly in developing countries. The available vaccines have certain limitations regarding their efficacy, and inability to induce an immune response especially in individuals under 2 years of age. Conjugate vaccines which consist of a bacteria-specific polysaccharide chemically bound to a carrier protein overcome these problems by inducing a T-cell dependent immune response characterized by enhanced immunogenicity in all ages. In this study, O-specific polysaccharides (OSP) of S. Typhi were conjugated to diphtheria toxoid (DT) using adipic acid dihydrazide (ADH) as a linker. These conjugates (OSP-AH-DT) were then evaluated for their immunogenicity using mice as a model and showed significantly higher levels of IgG ELISA titers (P = 0.0241 and 0.0245) than lipopolysaccharides alone. Different immunization schedules were compared and it was found that schedule-B (three injections with 4-weeks interval) induced higher immune responses than schedule-A (three injections with 2-weeks interval). We showed that diphtheria toxoid can be successfully employed as a carrier protein for conjugation with Salmonella OSP and play an important role in facilitating adequate immune response.     

The relationship between cognitive and physical function in older adults with rheumatoid arthritis: a literature review

Intact cognitive function is a crucial underpinning for the performance of daily activities in people with chronic diseases, including rheumatoid arthritis (RA). Older adults with RA may have the increased burden of physical function difficulties due to the impact of both age-related cognitive decline and RA-related impairment. Population-based studies reviewed in this article found significant cross-sectional and longitudinal relationships between cognitive function and physical function in older adults with and without comorbid health conditions. Although no study specifically examined this relationship in older adults with RA, interventions designed to enhance functional capacity by minimizing cognitive impairment may benefit older adults with RA. More studies are needed that investigate the relationship between cognitive and physical function in older adults with RA to eventually improve functional status and quality of life.     

Dissemination of multidrug-resistant Escherichia coli in Korean veterinary hospitals

This study was performed to investigate the prevalence of rectal colonization with multidrug-resistant Escherichia coli in dogs hospitalized at veterinary hospitals in Korea and to assess the molecular epidemiologic traits of this organism. A total of 63 unique E. coli isolates obtained from the rectal swabs of hospitalized dogs were analyzed. Genes encoding CTX-M extended-spectrum β-lactamases (ESBLs) and AmpC enzymes were detected in 21 (33.3%) and 15 (23.8%) canine E. coli isolates, respectively. Twelve canine E. coli isolates harbored both the genes encoding the CTX-M and AmpC enzymes. Six ESBL-producing E. coli isolates also carried the rmtB gene. All 24 E. coli isolates producing CTX-M ESBL and/or CMY-2 were resistant to ciprofloxacin. Furthermore, mutations were found in the gyrA and the parC genes. In most cases, the bla genes of the CTX-M ESBL and AmpC enzymes and the rmtB gene were localized to incompatibility group F (IncF) plasmids. Possible small clonal outbreaks are suggested because some E. coli isolates recovered in the same veterinary hospital were identified as identical sequence types and showed identical banding patterns in repetitive sequence-based polymerase chain reaction. The horizontal transfer of IncF plasmids and the clonal transfer of E. coli strains are suggested to play a role in the dissemination of antimicrobial resistance genes, and this transfer may occur across host species (i.e., between humans and dogs).     

AMPK activation reduces vascular permeability and airway inflammation by regulating HIF/VEGFA pathway in a murine model of toluene diisocyanate-induced asthma

Background

Occupational asthma is characterized by airway inflammation and hyperresponsiveness associated with increased vascular permeability. AMP-activated protein kinase (AMPK) has been suggested to be a novel signaling molecule modulating inflammatory responses.

Objective

We sought to evaluate the involvement of AMPK in pathogenesis of occupational asthma and more specifically investigate the effect and molecular mechanisms of AMPK activation in regulating vascular permeability.

Methods

The mechanisms of action and therapeutic potential of an AMPK activator, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) were tested in a murine model of toluene diisocyanate (TDI)-induced asthma.

Results

AICAR attenuated airway inflammation and hyperresponsiveness increased by TDI inhalation. Moreover, TDI-induced increases in levels of hypoxia-inducible factor (HIF)-1α, HIF-2α, vascular endothelial growth factor A (VEGFA), and plasma exudation were substantially decreased by treatment with AICAR. Our results also showed that VEGFA expression was remarkably reduced by inhibition of HIF-1α and HIF-2α with 2-methoxyestradiol (2ME2) and that an inhibitor of VEGFA activity, CBO-P11 as well as 2ME2 significantly suppressed vascular permeability, airway infiltration of inflammatory cells, and airway hyperresponsiveness induced by TDI. In addition, AICAR reduced reactive oxygen species (ROS) generation and levels of malondialdehyde and T-helper type 2 cytokines (IL-4, IL-5, and IL-13), while this agent enhanced expression of an anti-inflammatory cytokine, IL-10.

Conclusions

These results suggest that AMPK activation ameliorates airway inflammatory responses by reducing vascular permeability via HIF/VEGFA pathway as well as by inhibiting ROS production and thus may be a possible therapeutic strategy for TDI-induced asthma and other airway inflammatory diseases.     

Risk Factors for Multidrug Resistance in Nosocomial Bacteremia Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae

Increasing multidrug resistance (MDR) among extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) is of a great concern, because the therapeutic options are severely limited. Thus, we performed a case-control study to evaluate risk factors for MDR among nosocomial bacteremia caused by ESBL-EK. All adult patients with ESBL-EK bacteremia from January 2009 through December 2010 were identified at our institution. MDR was defined as ESBL-EK that demonstrated in vitro resistance to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolone (FQ), and gentamicin. Case patients were those with an MDR ESBL-EK isolate, and control patients were those with a non-MDR ESBL-EK isolate. Among a total of 123 ESBL-EK isolates (74 [60.2%] E. coli and 49 [39.8%] K. pneumoniae) causing nosocomial bacteremia, 33 (26.8%) cases were due to MDR ESBL-EK. In a univariate analysis, the factors significantly associated with acquisition of MDR ESBL-EK were neutropenia, immunosuppressant use, urinary tract infection, and prior use of antibiotics, especially FQ (all p<0.05). A multivariable analysis showed that a prior receipt of FQ (odds ratio [OR]=2.93; 95% confidence interval [CI]=1.07-8.01; p=0.036), percutaneous tube insertion (OR=4.04; 95% CI=1.56-10.75; p=0.005), and neutropenia (OR=4.22; 95% CI=1.56-11.45; p=0.005) were independent risk factors for MDR among ESBL-EK bacteremia in hospitalized patients. The CTX-M-15 enzyme was predominant in both the MDR ESBL-EK and non-MDR ESBL-EK groups (55% [11/20] vs. 55.6% [15/27]). Our data suggest that strategies designed to reduce MDR in ESBL-EK bacteremia should focus on limiting the use of FQ and minimizing invasive procedures such as tube insertion.     

Family based association of GRIN2A and GRIN2B with Korean autism spectrum disorders

N-Methyl-d-aspartate (NMDA) receptor, one of the glutamate receptors, has a role in the regulation of synaptic activity. It functions as an ion channel in the central nervous system and its inappropriate activation has been implicated in several neurological conditions. To test the association between candidate genes related with NMDA receptors and autism spectrum disorders (ASDs), we examined single nucleotide polymorphisms (SNPs) for GRIN2A and GRIN2B by using the family-based association test (FBAT) in 151 Korean trios. There was a statistically significant associations between ASDs and haplotypes in GRIN2B (bi-allelic mode additive model P-value=0.003; FDR P-value=0.012). This study supports a possible role of GRIN2B as a candidate gene for the etiology of ASDs.     

Suppression of autophagy exacerbates Mefloquine-mediated cell death

Mefloquine is an effective treatment drug for malaria. However, it can cause several adverse side effects, and the precise mechanism associated with the adverse neurological effects of Mefloquine is not clearly understood. In this study, we investigated the effect of Mefloquine on autophagy in neuroblastoma cells. Mefloquine treatment highly induced the formation of autophagosomes and the conversion of LC3I into LC3II. Moreover, Mefloquine-induced autophagy was efficiently suppressed by an autophagy inhibitor and by down regulation of ATG6. The autophagy was also completely blocked in ATG5 deficient mouse embryonic fibroblast cells. Moreover, suppression of autophagy significantly intensified Mefloquine-mediated cytotoxicity in SH-SY5Y cells. Our findings suggest that suppression of autophagy may exacerbate Mefloquine toxicity in neuroblastoma cells.