The potential role of cobalt ions released from metal prosthesis on the inhibition of Hv1 proton channels and the decrease in Staphyloccocus epidermidis killing by human neutrophils

Infection by Staphylococcus epidermidis is a devastating complication of metal-on-metal (MM) total hip arthroplasty (THA). Neutrophils are the first line of defense against infection, and these innate immune cells are potentially exposed to Co(2+) ions released in the peri-prosthetic tissue by the wear of MM THA. The toxicity of Co(2+) is still debated, but Co(2+) is a potential inhibitor of the Hv1 proton channel that sustains the production of superoxide by neutrophils. In this study, we show that the Co(2+) concentration in peri-prosthetic tissue from patients with MM THA averages 53 μM and that such high concentrations of Co(2+) alter the antibacterial activity of human neutrophils in vitro by inhibiting Hv1 proton channels. We show that submillimolar concentrations of Co(2+) inhibit proton currents, impair the extrusion of cytosolic acid, and decrease the production of superoxide in human neutrophils. As a result, Co(2+) reduces the ability of human neutrophils to kill two strains of Staphyloccocus epidermidis by up to 7-fold at the maximal concentration tested of 100 μM Co(2+). By inhibiting proton channels, the Co(2+) ions released by metal prostheses might therefore promote bacterial infections in patients with metal-on-metal total hip arthroplasty.     

Performance of OSEM and depth-dependent resolution recovery algorithms for the evaluation of global left ventricular function in 201Tl gated myocardial perfusion SPECT.

It is unknown whether the use of ordered-subsets expectation maximization (OSEM) and depth-dependent resolution recovery (RR) will increase the accuracy of (201)Tl electrocardiogram-gated SPECT (GSPECT) for the measurement of global left ventricular (LV) function. METHODS: Fifty-six patients having both rest (201)Tl GSPECT and planar equilibrium radionuclide angiography (planar(RNA)) on the same day were studied. Twenty-nine patients also had LV conventional contrast angiography (Rx). LV ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) were calculated with the quantitative gated SPECT software (QGS) using 4 different processing methods: filtered backprojection (FBP), OSEM, RR + FBP, and RR + OSEM. LVEF calculated with planar(RNA) and LV EDV and ESV calculated with Rx were considered gold standards. LVEF and volumes provided with the GSPECT methods were compared with the gold standard methods. RESULTS: LVEF calculated with GSPECT methods (FBP, OSEM, RR + FBP, and RR + OSEM) were similar (not statistically significant) and correlated well with planar(RNA). On Bland-Altman analysis, the mean +/- SD of absolute difference in LVEF with GSPECT FBP, OSEM, RR + FBP, and RR + OSEM methods versus planar(RNA) were similar, with relatively large limits of agreement. LV volumes calculated with the 4 GSPECT methods were significantly lower but correlated well with Rx LV volumes. LV volumes calculated with FBP and OSEM were lower than those calculated with RR + FBP and RR + OSEM (P < 0.01). On Bland-Altman analysis, the mean +/- SD of absolute difference in LV volumes with FBP, OSEM, RR + FBP, and RR + OSEM versus Rx was, respectively, 56 +/- 45 mL (P < 0.01 vs. the other 3 methods), 57 +/- 45 mL (P < 0.01 vs. the other 3 methods), 43 +/- 48 mL, and 46 +/- 47 mL, with correspondingly large limits of agreement. The variance of random error did not differ between FBP, OSEM, RR + FBP, and RR + OSEM for either LVEF or volumes. CONCLUSION: OSEM and FBP presented similar accuracy for LVEF and volume measured with the QGS software. Their combination with depth-dependent RR provided similar LVEF but more accurate LV volumes.     

Impact of IMCI training and language used by provider on quality of counseling provided to parents of sick children in Bougouni District, Mali

This study evaluates the impact of the Integrated Management Of Childhood Illness (IMCI) training on quality of counseling provided to caregivers about administration of antimalarials to their children. Ten community health centers in southern Mali were randomized to either training or comparison arms of the study, and health providers' consultations with caregivers were observed. Out of a 10-point counseling scale (Cronbach's alpha=0.77), IMCI-trained providers completed an average of 1.47 (95% CI, -0.25, 3.2) more tasks than did providers who had not received IMCI training in a linear regression analysis that accounted for intra-provider correlations. Drug consultations done in both French and the local language, Bambara, had higher scores than those conducted exclusively in Bambara. The effect of providers receiving IMCI training was more pronounced in bilingual consultations, with an average increase of 2.49 (95% CI, 0.76, 4.22) in IMCI, bilingual consultations, and average increase of 0.87 (95% CI, -0.95, 2.69) in IMCI monolingual (Bambara) consultations as compared to non-IMCI-trained providers in monolingual consultations. IMCI training showed a non-significant trend overall in improving drug counseling provided to caregivers, with significant improvements in bilingual consultations. The IMCI program in Mali should consider strategies such as role-playing of counseling in Bambara or other local languages during training to improve patient-provider communication. Similar problems related to counseling by health workers in local languages are likely to be present throughout Africa, and warrant further study.     

Novel functional interactions between Trk kinase and p75 neurotrophin receptor in neuroblastoma cells

To understand the functional interactions between the TrkA and p75 nerve growth factor (NGF) receptors, we stably transfected LAN5 neuroblastoma cells with an expression vector for ET-R, a chimeric receptor with the extracellular domain of the epidermal growth factor receptor (EGFR), and the TrkA transmembrane and intracellular domains. EGF activated the ET-R kinase and induced partial differentiation. NGF, which can bind to endogenous p75, did not induce differentiation but enhanced the EGF-induced response, leading to differentiation of almost all cells. A mutated NGF, 3T-NGF, that binds to TrkA but not to p75 did not synergize with EGF. Enhancement of EGF-induced differentiation required at least nanomolar concentrations of NGF, consistent with the low-affinity p75 binding site. EGF may induce a limited number of neuronal cells because it also enhanced apoptosis. Both NGF and a caspase inhibitor reduced apoptosis and, thereby, enhanced differentiation. NGF seems to enhance survival through the phosphatidylinositol-3 kinase (PI3K) pathway. Consistent with this hypothesis, Akt, a downstream effector of the PI3K pathway, was hyperphosphorylated in the presence of EGF+NGF. These results demonstrate that TrkA kinase initiates differentiation, and p75 enhances differentiation by rescuing differentiating cells from apoptosis via the PI3K pathway. Even though both EGF and NGF are required for differentiation of LAN5/ET-R cells, only NGF is required for survival of the differentiated cells. In the absence of NGF, the cells die by an apoptotic mechanism, involving caspase-3. An anti-p75 antibody blocked the survival effect of NGF. Brain-derived neurotrophic factor also enhanced cell survival, indicating that in differentiated cells, NGF acts through the p75 receptor to prevent apoptosis.     

Synovial chondromatosis of the hip

The authors report a case of synovial chondromatosis of the hip in physically active male adult operated on three years ago and apparently cured. Review of the literature shows that the diagnosis, essentially based on X-ray examination, bonescan and arthrography, needs to be confirmed by histological examination. Treatment must be surgical and must be carried out as soon as possible to prevent arthrosis. Surgery should include thorough excision of the synovial membrane and a curettage of the acetabular fossa to avoid recurrence. Under these conditions, prognosis appears to be excellent.     

Aflatoxin B1 Occurrence in Children under the Age of Five’s Food Products and Aflatoxin M1 Exposure Assessment and Risk Characterization of Arab Infants through Consumption of Infant Powdered Formula: A Lebanese Experience

Aflatoxin M1 (AFM1) is a salient metabolite that can be used to assess Aflatoxin B₁ (AFB1) exposure in humans and animals. The carcinogenic potency of AFB1 and AFM1 was severely reported. The aims of this study were (1) to survey the contamination level of AFM1 in the most traded infant powdered formula brands (IPF) (n = 42) along with the AFB1 level in under 5’s children food brands (biscuits, cornflakes, and cereals) (n = 42) and (2) to assess the estimated daily intake (EDI), the hazard quotient (HQ) and the margin of exposure (MOE) of AFM1 among infants (0–12 months) in Lebanon. All of the samples were analyzed using ELISA technique. AFB1 was below detection limit in all of the children’s food brands samples. Out of 42 IPF samples 9.5% were AFM1-positive in the range of 29.54–140.16 ng/L and exceeded the maximum tolerable limit (MTL) set by the European commission (25 ng/kg). The overall average contamination level was 5.72 ± 0.014 ng/L. The EDI of AMF1 for male was in the range of 0.37–0.78 ng/kg/b.w./day and 0.40–0.87 ng/kg/b.w./day for females. Similarly, the HQ calculation resulted in an average of 3.05 for males and 3.28 for females. MOE calculations were far lower from 10,000 in both genders which indicates a high risk of genotoxicity and carcinogenicity. Our findings show that AFM1’s EDI, HQ and MOE scored high among Lebanese infants. As infants consume more IPF relative to their body weight, the persistence of IPF with high AFM1 levels threatens their health. Thus, infant’s exposure risk to AFM1 in IPF should be a continuous focus of attention.