Culture-Expanded Autologous Adipose-Derived Mesenchymal Stem Cell Treatment for Osteonecrosis of the Femoral Head

BackgroudOutcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH.MethodsEighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint.ResultsPreoperatively, the necrotic lesion extent was 63.0% (38.4%–96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI. However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2).ConclusionsOur outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.     

Comparison of static and dynamic models of maternal immunization to prevent infant pertussis in Brazil

BackgroundThis paper compares cost-effectiveness results from two models of maternal immunization to prevent pertussis in infants in Brazil, one static, one dynamic, to explore when static models are adequate for public health decisions and when the extra effort required by dynamic models is worthwhile.MethodsWe defined two scenarios to explore key differences between static and dynamic models, herd immunity and time horizon. Scenario 1 evaluates the incremental cost/DALY of maternal acellular pertussis (aP) immunization as routine infant vaccination coverage ranges from low/moderate up to, and above, the threshold at which herd immunity begins to eliminate pertussis. Scenario 2 compares cost-effectiveness estimates over the models’ different time horizons. Maternal vaccine prices of $9.55/dose (base case) and $1/dose were evaluated.ResultsThe dynamic model shows that maternal immunization could be cost-saving as well as life-saving at low levels of infant vaccination coverage. When infant coverage reaches the threshold range (90–95%), it is expensive: the dynamic model estimates that maternal immunization costs $2 million/DALY at infant coverage > 95% and maternal vaccine price of $9.55/dose; at $1/dose, cost/DALY is $200,000. By contrast, the static model estimates costs/DALY only modestly higher at high than at low infant coverage. When the models’ estimates over their different time horizons are compared at infant coverage < 90–95%, their projections fall in the same range.ConclusionsStatic models may serve to explore an intervention’s cost-effectiveness against infectious disease: the direction and principal drivers of change were the same in both models. When, however, an intervention too small to have significant herd immunity effects itself, such as maternal aP immunization, takes place against a background of vaccination in the rest of the population, a dynamic model is crucial to accurate estimates of cost-effectiveness. This finding is particularly important in the context of widely varying routine infant vaccination rates globally.Clinical Trial registryClinical Trial registry name and registration number: Not applicable.     

Cost-effectiveness of maternal pertussis immunization: Implications of a dynamic transmission model for low- and middle-income countries

ObjectiveThis study evaluates the cost-effectiveness of maternal acellular pertussis (aP) immunization in low- and middle-income countries using a dynamic transmission model.MethodsWe developed a dynamic transmission model to simulate the impact of infant vaccination with whole-cell pertussis (wP) vaccine with and without maternal aP immunization. The model was calibrated to Brazilian surveillance data and then used to project health outcomes and costs under alternative strategies in Brazil, and, after adjusting model parameter values to reflect their conditions, in Nigeria and Bangladesh. The primary measure of cost-effectiveness is incremental cost (2014 USD) per disability-adjusted life-year (DALY).ResultsThe dynamic model shows that maternal aP immunization would be cost-effective in Brazil, a middle-income country, under the base-case assumptions, but would be very expensive at infant vaccination coverage in and above the threshold range necessary to eliminate the disease (90–95%). At 2007 infant coverage (DTP1 90%, DTP3 61% at 1 year of age), maternal immunization would cost < $4,000 per DALY averted. At high infant coverage, such as Brazil in 1996 (DTP1 94%, DTP3 74% at 1 year), cost/DALY increases to $1.27 million. When the model’s time horizon was extended from 2030 to 2100, cost/DALY increased under both infant coverage levels, but more steeply with high coverage. The results were moderately sensitive to discount rate, maternal vaccine price, and maternal aP coverage and were robust using the 100 best-fitting parameter sets. Scenarios representing low-income countries showed that maternal aP immunization could be cost-saving in countries with low infant coverage, such as Nigeria, but very expensive in countries, such as Bangladesh, with high infant coverage.ConclusionA dynamic model, which captures the herd immunity benefits of pertussis vaccination, shows that, in low- and middle-income countries, maternal aP immunization is cost-effective when infant vaccination coverage is moderate, even cost-saving when it is low, but not cost-effective when coverage levels pass 90–95%.     

The establishment of the Korean medical device safety information monitoring center: Reviewing ten years of experience

Medical devices may revolutionize healthcare delivery but can lead to serious adverse events for treated patients and users. While reporting of adverse events related to medical devices is an essential starting point for post-market surveillance, underreporting of medical device adverse events is a global problem. Korea introduced a voluntary medical device adverse event reporting system in 2010, called the Medical Device Safety Information Monitoring Center, which has led to an increase in adverse event reports. For 10 years, the Medical Device Safety Information Monitoring Center has analyzed medical device adverse events systematically and has provided active feedback to the manufacturers and education on safe use. Recently, the Medical Device Safety Information Monitoring Center contributed to harmonization of international medical device vigilance through the sharing of adverse events. This experience of Korea might contribute to improvements in medical device vigilance, which is a critical prerequisite for improving medical device policies and regulations.     

An efficient synthesis of 3-(E)-hydroxypropenyl cephem derivatives, key intermediates for 3-(E)-ammoniopropenylcephalosporin antibiotics

An efficient synthesis of 3-(E)-hydroxy- and 3-(E)-acetoxypropenylcephem derivatives, key intermediates for the synthesis of 3-(E)-propenylcephalosporins was achievedvia Stille coupling reaction of 3-trifloxycephem with 3-(E)-tributylstannylallylic alcohol.     

New flavonoids from the aerial parts of Aconitum chiisanense

The studies were carried out to evaluate the constituents in the aerial part of Aconitum chiisanense (Ranunculaceae). From the butanol fraction of the methanol extract, kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (I), quercetin 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (II), kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-feruloyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (III), kaempferol 3- O-beta-glucopyranoside-7- O-(6-benzoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (IV), kaempferol 7- O-(6-trans)-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (V), and kaempferol 7- O-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (VI) were isolated and identified on the basis of their physicochemical and spectroscopic evidence (UV, IR, FAB(-)MS, (1)H-NMR, (13)C-NMR, (1)H- (1)H COSY, HMQC and HMBC). New compounds I-VI were named chiisanin (I), chiiribanin (II), chiiribaconin (III), chiirin (IV), chiiricanin (V), and chiirirhamnin (VI), respectively.     

Clonazepam release from core-shell type nanoparticlesin vitro

AB-type amphiphilic copolymers (abbreviated as LE) composed of poly (L-leucine) (PLL) as the A component and poly (ethylene oxide) (PEO) as the B component were synthesized by the ring-opening polymerization of L-leucine N-carboxy-anhydride initiated by methoxy polyoxyethylene amine (Me-PEO-NH₂) and characterized. Core-shell type nanoparticles were prepared by the diafiltration method. Particle size distribution obtained by dynamic light scattering was dependent on PLL composition and the size for LE-1, LE-2 and LE-3 was 369.6±267, 523.4±410 and 561.2±364 nm, respectively. Shapes of the nanoparticles observed by transmission electron microscope (TEM) were almostly spherical. The critical micelle concentration (CMC) of the nanoparticles determined by a fluorescence probe technique was dependent on the composition of hydrophobic PLL, and the CMC for LE-1, LE-2 and LE-3 was 2. 0×10⁻⁶, 1.7×10⁻⁶ and 1.5×10⁻⁶ (mol/l), respectively. Clonazepam release from core-shell type nanoparticles in vitro was dependent on PLL composition and drug loading content.     

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of γ-rays (0.01 Gy) 4 or 20 hrs prior to high dose γ-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose γ-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose γ-ray irradiation to high dose γ-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.