Effect of daptomycin on primary rat muscle cell cultures in vitro

Daptomycin is a lipopeptide antibiotic that has strong bactericidal activity against Gram-positive bacteria and that was previously reported to exhibit minor side effects on skeletal muscle. This study was designed to further characterize the effect of daptomycin on skeletal muscle through the use of primary cultures of muscles from rats. Our investigations demonstrated that daptomycin has a concentration-dependent and time-dependent effect on the plasma membrane of primary cultures of differentiated, spontaneously contracting rat myotubes. No effects were evident in non-differentiated myoblasts or other mononucleated cells present in cultures even at the highest daptomycin concentrations tested (6,000 μg/mL). In cultures treated with daptomycin at a concentration of 2,000 μg/mL, plasma membrane damage was observed in ∼20–30% of differentiated myotubes; no myotube damage was detected at concentrations of 1,000 μg/mL and below. A transient loss of spontaneous myotube contractions was evident at 750 μg/mL, while at 2,000 μg/mL and above, a permanent loss of spontaneous contractility was observed. These results suggest that the putative targets for daptomycin effects on skeletal muscle are structures on the plasma membrane of highly differentiated myotubes.     

The phenotype and genotype of rheumatoid arthritis in the Democratic Republic of Congo

Introduction

Little is known about rheumatoid arthritis in the black, particularly in Congolese, populations. Our objective was to describe the phenotype and genotype of rheumatoid arthritis (RA) in Congolese.

Methods

All consecutive rheumatoid arthritis (RA) patients attending Kinshasa University Hospital in a three-year time period were included. Demographics, clinical features and tobacco consumption were noted. Disease Activity Score (DAS)-28 based on the erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ), anti-citrullinated peptide antibodies (CCP) antibodies and rheumatoid factor (RF) were determined. Radiographs were scored according to Sharp-van der Heijde. On a subset of patients and controls HLA-DRB1 typing was performed.

Results

A total of 114 females and 14 males aged 51.2 ± 14.9 were included. Mean duration of symptoms was four years. Moderate tobacco consumption was reported in a minority of patients. DAS-28 at first visit was >5.1 and HAQ ≥0.5 in all patients. X-rays showed joint erosions and/or joint space narrowing, mostly of a moderate grade in 55.8% of patients. Anti-CCP and/or RF were present in 48.6% of patients with available data (n = 72) and in 3.0% of controls (n = 67). Radiographic changes and nodules were more frequent in RF or anti-CCP positive patients. One copy of the shared epitope was found in 13 patients (35.1%) and 3 controls (12.5%). Two copies were found in one patient (2.7%) and in one control (4.2%).

Conclusion

Congolese patients with RA consult long after disease onset. Despite this delay, the majority presents without major damage and is RF, anti-CCP and SE negative. We put forward the hypothesis that besides different environmental factors there is probably also a particular genetic risk profile in Congolese patients, different from the HLA-DRB1 shared epitope.     

False killer whales and fisheries interactions in Hawaiian waters: Evidence for sex bias and variation among populations and social groups

We assessed scarring patterns as evidence of fisheries interactions for three populations of false killer whales in Hawai‘i. Bycatch of the pelagic population in the tuna longline fishery exceeds their Potential Biological Removal level. Scarring was assessed by seven evaluators as consistent, possibly consistent, or not consistent with fisheries interactions, and average scores computed. Scores were highest for scarred main Hawaiian Island (MHI) false killer whales, followed by pelagic and Northwestern Hawaiian Island (NWHI) individuals. Considering only whales for which the majority of evaluators scored scarring as consistent revealed significant differences among populations in the percentage of individuals scarred; MHI: 7.5%, pelagic: 0%, NWHI: 0%. Assessment by social cluster for the MHI population showed that 4.2% of Cluster 1, 7.1% of Cluster 2, and 12.8% of Cluster 3 individuals had such scarring, although differences between clusters were not statistically significant. There was a significant sex bias; all sexed individuals (n = 7) with injuries consistent with fisheries interactions were female. The higher proportion of MHI individuals with fisheries‐related scarring suggests that fisheries interactions are occurring at a higher rate in this population. The bias towards females suggests that fisheries‐related mortality has a disproportionate impact on population dynamics.