Can pirfenidone prevent tendon adhesions? An experimental study in rats.

OBJECTIVES: In this experimental study, we aimed to investigate the effectiveness of oral pirfenidone (PFD) treatment on preventing tendon adhesion and tendon healing in rats. MATERIALS AND METHODS: A total of 21 rats were assigned into three groups including seven rats in each group. In Group 1 (sham group), no surgical procedure was performed. In Group 2 (control group), tendon repair was performed following right achillotomy. In Group 3 (treatment group), the rats also underwent tendon repair after right achillotomy. Additionally, 30 mg/kg of oral PFD was initiated from the postoperative Day 1 and administered via gavage for 28 days. At the end of the study, tendon healing and fibrosis levels in the tendon repair site were compared macroscopically, histopathologically, and immunohistochemically among the groups. RESULTS: Macroscopically, moderate and severe adhesions were observed in four and three rats, respectively in the control group, while no adhesion was found in four rats and filmy adhesions were observed in three rats in the treatment group (p<0.01). Microscopically, there was moderate adhesions in three rats and severe adhesions in four rats in the control group, while three rats had no adhesions and four rats had slight adhesions in the treatment group (p<0.01). Microscopically, tendon healing was good in six rats and fair in one rat in the control group, while five rats showed excellent tendon healing and two rats showed good tendon healing in the treatment group (p<0.01). Immunohistochemically, expressions of collagen I (p<0.01), collagen III (p<0.001), vascular endothelial growth factor (VEGF) (p<0.001), and proliferating cell nuclear antigen (PCNA) (p<0.001) significantly decreased in the treatment group compared to the control group. CONCLUSION: Our study results indicated that PFD decreased collagen synthesis and prevented the formation of peritendinous adhesion in rats; however, it did not impair tendon healing.

Dental follicle mesenchymal stem cells down-regulate Th2-mediated immune response in asthmatic patients mononuclear cells.

BACKGROUND: Asthma is a chronic inflammatory disease in which inflammatory responses have the polarisation of CD4+ T cells to Th2 cells. Dental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells. OBJECTIVE: We investigated the immunomodulatory effects of DFSCs on CD4+ T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals. METHOD: Peripheral blood mononuclear cells (PBMC) were isolated from immunotherapy naïve asthmatics, asthmatics on subcutaneous Der p1 immunotherapy and from healthy individuals. PBMC were pre-conditioned with anti-CD3/anti-CD28 mAbs, Der p1 or IFN-γ in the presence and absence of DFSCs and analysed for T cell viability and proliferation, CD4+ CD25+ FOXP3+ regulatory T cell frequencies, cytokine expression, and GATA3, T bet and FoxP3 expressions. Neutralisation of TGF-ß and blockade of IDO and PGE2 pathways were performed to determine suppressive signalling pathways of DFSCs. RESULTS: Dental follicle mesenchymal stem cells suppressed proliferative responses of CD4+ T lymphocytes and increased the frequency of Treg cells. DFSCs decreased effector and effector memory CD4+ T cell phenotypes in favour of naïve T cell markers. DFSCs decreased IL-4 and GATA3 expression and increased IFN-γ, T-bet and IL-10 expression in asthmatics. Costimulatory molecules were suppressed in monocytes with DFSCs in the cocultures. DFSCs down-regulated inflammatory responses via IDO and TGF-ß pathways in asthmatic patients. CONCLUSION: Dental follicle mesenchymal stem cells suppressed allergen-induced Th2-cell polarisation in favour of Th1 responses and attenuated antigen-presenting cell co-stimulatory activities. These studies suggest that DFSC-based cell therapy may provide pro-tolerogenic immunomodulation relevant to allergic diseases such as asthma.

Do the trace elements play a role in the etiopathogenesis of developmental dysplasia of hip?

OBJECTIVE: Alterations in the connective tissue of the hip joint capsule and ligaments might account for the increased laxity seen in patients with developmental dysplasia of the hip. The tensile features of the connective tissue depend on collagen. A number of prior studies have noted the association between the trace elements and collagen biosynthesis. The aim of this research is to determine whether there exists an association between the trace elements and developmental dysplasia of the hip. PATIENTS AND METHODS: This investigation included 27 patients with developmental dysplasia of the hip (18 females and nine males; mean age 24.3 ± 6.3 months, range 18­36 months) and 26 healthy controls (15 females and 11 males; mean age 23.8 ± 5.4 months, range 18-36 months). The levels of the serum trace elements in the groups were statistically compared. RESULTS: The Cu levels of the patients with developmental dysplasia of hip were statistically higher than those of the control group (p<0.05). The Zn, Fe, Mg, and Mn levels of the patients with developmental dysplasia of hip were statistically lower than those of the control group (p<0.05). CONCLUSIONS: We found an association between developmental dysplasia of the hip and the serum trace element levels. We, therefore, believe that the trace element levels may shed light on the etiopathogenesis of developmental dysplasia of the hip. This work should be supported by future studies concerning the causes of the alterations in the serum trace element levels seen in patients with developmental dysplasia of the hip.

Macrophage Infiltration into Subcutaneous Adipose Tissue is Associated with Local Levels of 11BHSD1.

The present study aimed to evaluate the infiltration of macrophages in form of crown-line structures (CLS) in subcutaneous adipose tissue (SAT) of obese individuals, and to investigate the effect of these on both metabolic parameters and adipose tissue 11-beta-hydroxysteroid dehydrogenase type 1 (11BHSD1) enzyme levels. A total of 53 obese (10 men, 43 woman) enrolled in the study. Body mass index (BMI), waist circumference (WC), hip circumfrence, and systolic (SBP) and diastolic blood pressures (DBP) of all subjects were recorded. Insulin resistance was determined using the homeostasis model assessment (HOMA). The concentration of SAT, tumor necrosis factor (TNF)-α, interleukin (IL)-6, 11BHSD1 were performed by enzyme-linked immunosorbent assay (ELISA) method. The infiltration of macrophages in form of CLS in adipose tissue were determined using cell-specific stains against CD68. There was no significant difference between the CLS+group and the CLS- group in terms of age, gender, BMI, WC, waist-to-hip circumference ratio (WHR), SBP and DBP levels. Fasting plasma glucose (FPG), HOMA-IR, insulin and SAT TNF-α levels were higher in the CLS+group compared to the CLS- group. FPG and SAT TNF-α levels were significantly higher in participants with high CLS density compared to participants with low density CLS. SAT 11BHSD1 levels was significant higher in the CLS+group compare to the CLS- group and in the high CLS density group compared to the low density group. In conclusion, the infiltration of macrophages in the form of CLS in SAT is associated with increased 11BHSD1 levels. It may be an important mechanism in the development of metabolic disorders.

A cyclin D1 (CCND1) gene polymorphism contributes to susceptibility to papillary thyroid cancer in the Turkish population.

Cyclin D1 is an important positive regulator of the G1/S phase of the cell cycle. We investigated the association between the CCND1 G870A polymorphism and susceptibility to papillary thyroid cancer in Turkish people. This study covered 102 patients with papillary thyroid cancer and 174 healthy controls. CCND1 genotyping was determined by the PCR-RFLP method. We found that the A allele frequency was higher in the cases than in the controls (p=0.042). On stratification analysis, papillary thyroid cancer risk was significantly elevated in individuals older than 45 years with the A allele (OR=1.91, 95% CI, 1.09-3.35, p=0.024) and in females with the A allele (OR=1.73, 95% CI, 1.06-2.84, p=0.029), compared to the G allele. According to the subject age, there was an increased papillary thyroid cancer risk for the individuals older than 45 years with the AA genotype (OR=2.28, 95% CI, 1.02-5.13, p=0.046) compared to the AG+GG combined genotypes. In conclusion, it is suggested that the CCND1 G870A polymorphism may contribute to the susceptibility to papillary thyroid cancer, especially in those who were older subjects (45 ≤ years old) and female, in the Turkish population.

Iatrogenic or fracture-related nerve injuries in supracondylar humerus fracture: is treatment necessary for nerve injury?

BACKGROUND: Supracondylar humerus fractures are very common types of elbow fractures in children between the ages of three and ten years. Totally displaced supracondylar humerus fractures can be associated with neurovascular injuries, and treatment can be complicated by iatrogenic neurovascular injury, compartment syndrome, malunion, and elbow stiffness. AIM: The aim of this study was to describe the clinical outcome of nerve injuries associated with supracondylar humerus fractures in children observed over a period of seven years. PATIENTS AND METHODS: Children with displaced supracondylar humerus fracture who were treated with closed reduction and percutaneous cross K-wire fixation were reviewed retrospectively at the Medical School Hospital of Yuzuncu Yil University from May 2004 to October 2012. RESULTS: There were 91 patients available for follow-up. Nerve injury was observed in 11 (12.1%) of 91 patients with supracondylar humerus fractures. In 10 (90.1%) of these 11 cases, nerve functions recovered completely (excellent outcome) and in one (9.9%) case partial recovery was seen (good outcome). CONCLUSIONS: Iatrogenic or fracture-related nerve injury in a supracondylar humerus fracture is a benign condition which may be resolved spontaneously and observation appears to be a good and valuable method for treatment of this complication.

Biomechanical comparison of Achilles tenotomy and achilloplasty techniques in young rats: an experimental study.

BACKGROUND: Tendo Achillis lengthening is performed by means of Z-plasty in the classic treatment of clubfoot. In the Ponseti method for treating clubfoot, Achilles tenotomy is performed percutaneously for residual equine deformity. A randomized study was designed to compare tendon healing after tenotomy versus Z-plasty. METHODS: Thirty-six Sprague-Dawley rats were divided randomly into two groups. On the first day, while the right tendo Achillis of group 1 rats underwent tenotomy, those of group 2 rats underwent Z-plasty. Nine rats from each group were humanely killed on days 21 and 45 postoperatively. The two groups were compared with each other biomechanically and histologically. The Achilles tendons of eight rats in each group were evaluated biomechanically, and the remaining rat in each group underwent histologic evaluation. RESULTS: Mean +/- SD maximum load at rupture of the treated tendons on days 21 and 45 in the tenotomy group was 26.38 +/- 7.31 N and 47.16 +/- 15.36 N, respectively, and in the Z-plasty group was 27.37 +/- 5.20 N and 45.27 +/- 9.59 N, respectively. The biomechanical evaluation revealed no significant difference in terms of breaking forces between the two groups. The difference between breaking forces on days 21 and 45 was statistically significant for both groups. CONCLUSIONS: Tendons in the tenotomy group healed as well as those in the Z-plasty group, and Achilles tenotomy in the rat was similar to Z-plasty for Achilles tendon lengthening. Human correlation may or may not exist, but this study suggests that it should be considered and investigated.

"Ring leg deformity" in Bartsocas-Pappas syndrome.

INTRODUCTION: We reported an extremely rare foot deformity in Bartsocas-Pappas syndrome. This patient family is from Van that is a city in the east part of Turkey and the family is Turkish origin. In literature review we find only two cases resembling to this deformity. CASE PRESENTATION: A 20-day-old infant with an extremely rare type lower extremity anomaly. There was a skin band between the syndactylia 2nd and 3rd toes of the right and left feet. CONCLUSION: This deformity resembles to a ring. We could not find a specific name for this anomaly. Therefore we want to advise a name "ring leg" deformity to describe this deformity.