Suppression of atopic dermatitis in mice model by reducing inflammation utilizing phosphatidylserine-coated biodegradable microparticles

Controlling inflammatory response is important to avoid chronic inflammation in many diseases including atopic dermatitis (AD). In this research, we tried using a phosphatidylserine (PS)-coated microparticles in the AD mouse model for achieving the modulation of the macrophage phenotype to an anti-inflammatory state. Here, we prepared poly (D,L-lactic acid) microparticle coated with PS on the outside shell. We confirmed the cellular uptake of the PS-coated microparticle, which leads to the significant downregulation of the inflammatory cytokine production. In the mouse model of AD, the PS-coated microparticle was injected subcutaneously for a period of 12 days. The mice showed significant reduction in the development of AD symptoms comparing with the mice treated with the PC-coated microparticle.     

Difference in the distribution of tumor-infiltrating CD8+ T cells and FOXP3+ T cells between micronodular thymoma with lymphoid stroma and micronodular thymic carcinoma with lymphoid stroma

Micronodular thymoma with lymphoid stroma (MNT) is a rare thymic epithelial neoplasm subtype characterized by a micronodular tumor cell growth pattern and abundant lymphoid stroma. Micronodular thymic carcinoma with lymphoid stroma (MNCA) is considered as a malignant counterpart of MNT and exhibits a growth pattern similar to that of MNT but has histologic features reminiscent of thymic squamous cell carcinoma, such as cytologic atypia and CD5 and CD117 immunoexpression. Although both MNT and MNCA are characterized by abundant lymphoid stroma, it remains unknown whether there are differences in infiltrating lymphocytes between MNT and MNCA. We analyzed the immune microenvironment profile in eight MNT and three MNCA cases. The cell density of CD8-positive T cells was significantly higher in MNT than in MNCA, whereas that of FOXP3-positive T cells was significantly higher in MNCA than in MNT. There was no significant difference in the cell density of programmed death protein 1-positive T cells and programmed death ligand 1 expression between the MNT and MNCA cases. Our findings indicated that the immune microenvironment of MNCA differed from that of MNT and, compared with the T-cell profile of MNT, that of MNCA was more suppressive to patients′ antitumor immune response.     

Therapeutic Interventions for Increasing Ankle Dorsiflexion After Ankle Sprain: A Systematic Review

Context:

Clinicians perform therapeutic interventions, such as stretching, manual therapy, electrotherapy, ultrasound, and exercises, to increase ankle dorsiflexion. However, authors of previous studies have not determined which intervention or combination of interventions is most effective.

Objective:

To determine the magnitude of therapeutic intervention effects on and the most effective therapeutic interventions for restoring normal ankle dorsiflexion after ankle sprain.

Data Sources:

We performed a comprehensive literature search in Web of Science and EBSCO HOST from 1965 to May 29, 2011, with 19 search terms related to ankle sprain, dorsiflexion, and intervention and by cross-referencing pertinent articles.

Study Selection:

Eligible studies had to be written in English and include the means and standard deviations of both pretreatment and posttreatment in patients with acute, subacute, or chronic ankle sprains. Outcomes of interest included various joint mobilizations, stretching, local vibration, hyperbaric oxygen therapy, electrical stimulation, and mental-relaxation interventions.

Data Extraction:

We extracted data on dorsiflexion improvements among various therapeutic applications by calculating Cohen d effect sizes with associated 95% confidence intervals (CIs) and evaluated the methodologic quality using the Physiotherapy Evidence Database (PEDro) scale.

Data Synthesis:

In total, 9 studies (PEDro score = 5.22 ± 1.92) met the inclusion criteria. Static-stretching interventions with a home exercise program had the strongest effects on increasing dorsiflexion in patients 2 weeks after acute ankle sprains (Cohen d = 1.06; 95% CI = 0.12, 2.42). The range of effect sizes for movement with mobilization on ankle dorsiflexion among individuals with recurrent ankle sprains was small (Cohen d range = 0.14 to 0.39).

Conclusions:

Static-stretching intervention as a part of standardized care yielded the strongest effects on dorsiflexion after acute ankle sprains. The existing evidence suggests that clinicians need to consider what may be the limiting factor of ankle dorsiflexion to select the most appropriate treatments and interventions. Investigators should examine the relationship between improvements in dorsiflexion and patient progress using measures of patient self-reported functional outcome after therapeutic interventions to determine the most appropriate forms of therapeutic interventions to address ankle-dorsiflexion limitation.Key Words: chronic ankle instability, range of motion, stretching, joint mobilization

Key Points

• A static-stretching intervention as part of a standardized home exercise program had the strongest effects on ankle-dorsiflexion improvement after acute ankle sprains.
• Clinicians need to consider what may be the limiting factor of ankle dorsiflexion to select the most appropriate treatments and interventions.
• Investigators should examine the long-term effects of treatments on ankle dorsiflexion and a relationship between an improvement in ankle dorsiflexion and measures of patient self-reported and physical function to determine the most appropriate forms of therapeutic interventions to address limited dorsiflexion.

Lateral ankle sprain has been documented to be the most common lower extremity injury sustained during sport participation.^1–4 Approximately 85% of all ankle sprains result from an inversion mechanism and damage to the lateral ligamentous complex of the ankle.⁵ Injury to the lateral ligamentous complex at the ankle joint results in pain, swelling, and limited osteokinematics.⁶ A loss of normal ankle dorsiflexion usually is observed at the talocrural joint after lateral ankle sprain.^7–12The amount of available ankle dorsiflexion plays a key role in the cause of lower extremity injuries.^7,13–22 Limitation of dorsiflexion may be a predisposition to reinjury of the ankle^11,16 and several future lower limb injuries, including plantar fasciopathy,^13,20,21 lateral ankle sprains,^13,15,17,19 iliotibial band syndrome,¹⁴ patellofemoral pain syndrome,¹⁸ patellar tendinopathy,²² and medial tibial stress syndrome.¹⁴The importance of restoring ankle dorsiflexion after an acute ankle sprain often is emphasized in rehabilitation guidelines,⁹ and proper recovery of ankle dorsiflexion is a vital component of ankle rehabilitation. Inadequate restoration of ankle dorsiflexion may increase the risk of developing recurrent ankle sprain^11,16 and limit functional activities, such as walking, with long-term pain and disability.²³ Limited ankle-dorsiflexion range of motion (ROM) after lateral ankle sprain has been considered a predisposing factor for recurrent ankle sprain because diminished dorsiflexion prevents the ankle from reaching its closed-pack position by holding the ankle in a hypersupinated position. Therefore, ensuring appropriate restoration of ankle dorsiflexion after ankle sprain has important clinical implications for restoring full functional abilities, ultimately leading to reduced risk of recurrent ankle sprain.Clinicians perform several therapeutic interventions, such as stretching, manual therapy, electrotherapy, ultrasound, and exercises, to increase ankle dorsiflexion. However, the intervention or combination of interventions that most effectively improves ankle dorsiflexion has not been established. In previous systematic reviews,^24–26 researchers have examined the effects of specific intervention techniques of manipulative therapy on various outcome variables. In addition, Bleakley et al²⁷ conducted a systematic review with a comprehensive search of various therapeutic interventions to provide evidence for the management of ankle sprains and the prevention of long-term complications; however, the authors focused only on patients with an acute ankle sprain. Therefore, the purpose of this systematic review was to determine the magnitude of therapeutic intervention effects on and the most effective therapeutic interventions for restoring normal ankle dorsiflexion after ankle sprain. In contrast to previous reviews,^24–26 we comprehensively searched the existing literature to determine the effectiveness of various therapeutic intervention techniques in restoring ankle dorsiflexion in patients with acute, subacute, or recurrent ankle sprains. By providing a quantitative estimate of the magnitude of the effect of therapeutic interventions, our review provides a new perspective on the evidence of interventions to restore ankle dorsiflexion in various stages of ankle-sprain conditions.     

Evaluation of bioartificial renal tubule device prepared with human renal proximal tubular epithelial cells cultured in serum-free medium

Bioartificial renal tubule devices (BTD) use cell therapy to improve conditions commonly observed in recipients of artificial kidneys for treatment of kidney diseases. We previously reported significant improvement of the condition of acute kidney injury (AKI) animals after treatment with BTD prepared with lifespan-extended human renal proximal tubular cells (hRPTEC). However, a major obstacle to use of BTD for patients is their biological safety, because hRPTEC are cultured in medium containing fetal calf serum. To establish the biological safety of BTD, we prepared BTD with lifespan-extended hRPTEC cultured in a newly developed serum-free medium and compared these with BTD prepared with hRPTEC cultured in serum-containing conventional medium. Lifespan-extended hRPTEC cultured in serum-free medium (hRPTEC-SFM) can proliferate similar to hRPTEC cultured in serum-containing conventional medium (hRPTEC-CM). Comparison of leakage and of reabsorption of small molecules for BTD prepared with hRPTEC-SFM (BTD-SFM) with those for our previous BTD prepared with hRPTEC-CM (BTD-CM) showed transportation in these two types of BTD was almost identical. When AKI goats were treated with BTD-SFM for 26 h, increase of survival time and reduction of cytokine expression in blood cells were almost same as for AKI goats treated with BTD-CM. Quantification of the expression of some genes of hRPTEC in BTD revealed significant changes during BTD treatment for AKI goats. In conclusion, lifespan-extended hRPTEC-SFM work as well as hRPTEC-CM, and the biological safety of BTD for patients could be elevated without loss of function by preparation from hRPTEC-SFM.     

Low contrast dose protocol involving a 100 kVp tube voltage for hypervascular hepatocellular carcinoma in patients with renal dysfunction

Purpose

To evaluate the feasibility of a 20 % reduced contrast dose hepatic arterial phase (HAP) CT for hypervascular hepatocellular carcinoma (HCC) with 100 kVp.

Materials and methods

The study included 97 patients with hypervascular HCC who underwent dynamic CT, including HAP scanning. The 54 patients had an estimated glomerular filtration rate (eGFR) of ≥60 were scanned with our conventional 120 kVp protocol. The other 43 patients (eGFR < 60) underwent scans using a tube voltage of 100 kVp and a 20 % reduced contrast dose. We compared the estimated effective dose, image noise, tumor-liver contrast (TLC), and contrast-to-noise ratio (CNR) in the hepatic arterial phase between the two groups using the Student’s t test.

Results

Estimated effective dose and image noise were not significantly different between these groups (p = 0.67 and p = 0.20, respectively). The TLC and CNR were significantly higher for the 100 kVp protocol than for the 120 kVp protocol (52.2 HU ± 17.4 vs 40.8 HU ± 18.6, p < 0.01 and 6.8 ± 2.6 vs 5.5 ± 2.4, p = 0.01, respectively).

Conclusion

For hepatic arterial phase CT of hypervascular HCC, 100 kVp scan allows a 20 % reduction in the contrast dose without reduction in image quality compared with a standard 120 kVp CT protocol.

     

Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects

Background

Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically.

Questions/purposes

We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee?

Methods

Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37–80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test.

Results

MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second-look arthroscopy in four patients showed that the cartilage defect appeared to be qualitatively better in all cases. Histologic analyses showed hyaline cartilage in three patients and fibrous cartilage in one at the deep zone. The Lysholm score (median ± 95% CI) was 76 ± 7 before and 95 ± 3 after, and increased after treatment in each patient (p = 0.005). The Tegner Activity Level Scale did not decrease after treatment in each patient.

Conclusions

For this small initial case series, transplantation of synovial MSCs was effective in terms of MRI score, qualitative histology, and Lysholm score. The use of synovial MSCs has an advantage in that the cells can be prepared at passage 0 in only 14 days. Transplantation of synovial MSCs may be less invasive than mosaicplasty and autologous chondrocyte implantation. To conclusively show the effectiveness of this treatment requires comparative studies, especially with more established arthroscopic procedures, such as marrow stimulation techniques.

Level of Evidence

Level IV, therapeutic study.