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.

Clinical Results of Decortication with Bone Grafting Method versus Extracorporeal Shock Wave Treatment in Long-Bone Pseudoarthrosis.

BACKGROUND Despite advanced treatment methods, the treatment of pseudoarthrosis still poses a significant challenge for orthopedists. In this study, we aimed to assess the clinical results of decortication and bone grafting and extracorporeal shock wave treatment (ESWT) in long-bone pseudoarthrosis. MATERIAL AND METHODS Between 2007 and 2015, 68 fractures of 66 patients treated for long-bone pseudoarthrosis were evaluated retrospectively. ESWT was used in 36 extremities and decortication and iliac bone grafting was used in 32. The treatment results of these patients were evaluated and compared with rates in the literature. RESULTS The mean patient age was 43.9 years (range, 21-69). The mean interval between the occurrence of the fracture and treatment with bone grafting or ESWT was 8.6 months and the mean interval between the procedure and achievement of union was 6.9 months. The patients were followed up for a mean period of 25.2 months. After the mean follow-up period, bone union had occurred in all 32 patients (100%) in the decortication and bone grafting group and in 28 (78%) of the 36 patients in the ESWT group (P=0.023). CONCLUSIONS This study shows that extracorporeal shock wave treatment should be considered the first option in treatment of pseudoarthrosis as it is a non-invasive method and also provides good rates of union. In patients that do not heal with ESWT, decortication and bone grafting remains the criterion standard therapy.

The effect of theranekron on femur fracture healing in an experimental rat model.

OBJECTIVES: The aim of this study was to investigate the radiological, biomechanical, histopathological and immunohistochemical effects of theranekron on fracture healing in an experimental rat model. MATERIALS AND METHODS: Forty-eight male albino Wistar rats were used. Four groups were formed, with 12 rats in each of theranekron groups 1 and 2, and control groups 1 and 2. After a fracture was created in the right femur of the rats included in the study, fixation was performed with an intramedullary Kirschner wire. Theranekron was administered subcutaneously to theranekron groups 1 and 2 at a dose of 0.3 mg/kg on days 0, 5 and 10. After radiographic analysis of the femurs of theranekron group 1 and control group 1 rats at four weeks of the study was performed, both groups were divided into two equal subgroups (six femurs in each group). Histopathological and immunohistochemical examinations were performed in one subgroup and biomechanical examination in the other subgroup. At the end of six weeks, the rats in theranekron group 2 and control group 2 were evaluated after applying the same procedure as in the fourth week. RESULTS: When the mean radiological scores of the theranekron and control groups were compared, a statistically significant difference was found in favor of the theranekron group at four and six weeks (p=0.028 and p=0.006, respectively). At four weeks, statistically significant higher biomechanical forces were obtained in the theranekron group compared to the control group (p=0.030). In the histopathological evaluation, the inflammation value of the control group at four weeks was statistically significantly higher than the theranekron group (p=0.027). The angiogenesis, osteoblast proliferation, and bone formation values of the theranekron group were significantly higher than the control group (p=0.014, p=0.014, and p=0.005, respectively). At six weeks, the bone formation values of the theranekron group were statistically significantly higher than the control group (p=0.021). The difference between the theranekron group and the control group scores of the immunohistochemical evaluation were statistically significantly different at four and six weeks (p=0.006 and p=0.011, respectively). CONCLUSION: Theranekron may play a role in accelerating fracture healing by reducing acute inflammation process in the early period of fracture union, increasing fracture strength, angiogenesis, osteoblast proliferation, and bone formation.

Insall-Salvati index is associated with anterior cruciate ligament tears in men: A Case-controlled study.

PURPOSE: Many factors in the etiology of anterior cruciate ligament (ACL) tears, predisposing factors related to knee morphology have also been reported. This study aimed to determine whether the Insall-Salvati (IS) index, which measures patella height, is a predisposing risk factor for ACL tears. METHODS: The IS index, patellar length (PL), and patellar tendon length (PTL) values of patients (study group) that underwent arthroscopic reconstruction for ACL tears obtained by preoperative magnetic resonance imaging (MRI) were compared with the index values in the preoperative MRIs of patients that underwent knee arthroscopy for reasons besides ACL tears. In addition, the anterior tibial translation (ATT) of both groups was also measured and compared on MRI images. The MRI findings of the subjects included in both study groups were arthroscopically confirmed. RESULTS: The mean ages of the study group (n = 120) and control group (n = 90) were 29.1 ± 8.2 years and 31.8 ± 9.8 years, respectively. There was a statistically significant difference between the study and control groups in terms of the PL and PTL values (p = 0.016 and p = 0.001, respectively). The IS index was statistically significantly higher in the study group with ACL tears (p = 0.009). The ATT was 8.61 ± 4.68 mm in the study group and 3.80 ± 1.92 mm in the control group. The ATT results of both groups were evaluated, and it was found that the study group was significantly higher than the control group (p = 0.001). CONCLUSIONS: As a result of our current study, we observed higher IS index values in patients with ACL tears than in patients without ACL tears. It should be kept in mind that patella alta, which is associated with a high IS index as one of the factors of knee morphology associated with ACL tears, may play a role in the etiology of ACL tears.

The Role of Deadlifts in Distal Biceps Brachii Tendon Ruptures: An Alternative Mechanism Described With YouTube Videos.

BACKGROUND: The classic injury mechanism of a distal biceps brachii tendon rupture (DBBTR) is eccentric loading to the flexed elbow when the forearm is supinated. PURPOSE: To determine alternative mechanisms of a DBBTR in powerlifting sports, particularly in deadlift competitions, with the use of YouTube videos. STUDY DESIGN: Descriptive epidemiology study. METHODS: A search on YouTube was performed using the search terms "distal biceps tendon rupture" and "distal biceps tendon injury" combined with "competition," "deadlift," and "powerlifting." The videos underwent an evaluation for accuracy by 3 surgeons according to predetermined criteria. Type of sports activity, participant sex, side of the injury, and arm positions at the time of the injury were recorded. RESULTS: Among the videos reviewed, 35 injuries were found appropriate for an evaluation. All participants were male. The majority of the injuries (n = 25) were observed during the deadlift. Only in 1 deadlift injury were both forearms in supination. In the remaining deadlift injuries (n = 24), all elbows were in extension, with 1 forearm in supination and the other in pronation. Among the deadlift injuries in the mixed-grip position, all ruptures occurred in a supinated extremity: 25% (n = 6) of ruptures occurred on the right side, and 75% (n = 18) of ruptures occurred on the left side; this was a significant difference (P = .014). CONCLUSION: We described an alternative mechanism for a DBBTR, namely, eccentric loading to an extended elbow when the forearm is supinated during the deadlift. As all the ruptures occurred in a supinated extremity, holding the bar with both forearms in pronation may prevent or decrease the risk of ruptures during the deadlift.

Formulation of spray-dried phenytoin loaded poly(epsilon-caprolactone) microcarrier intended for brain delivery to treat epilepsy.

This study evaluates the efficacy of the spray-drying technique in the bioengineering of phenytoin (PHT) containing poly(epsilon-caprolactone) (PCL) microcarrier intended for brain delivery for long-term treatment of epilepsy. Through orthogonally designed experiments, the optimal formulation and process variables for the preparation of PCL-microcarriers containing PHT were obtained. The produced microcarriers were characterized by coulter counter, scanning electron, scanning transmission electron microscopies, differential scanning calorimetry, powder X-ray diffraction, and in vitro release. The results showed that the produced microcarriers have a spherical structure, uniform size distribution, and a particle mean diameter of about 4.0 microm, which is suitable for brain delivery. The PHT was loaded as dispersed microcrystals within the PCL-microcarriers. From this system, PHT was released slowly into a buffer solution for approximately 14 days without any burst effect. These data suggested that PHT containing spray-dried PCL-microcarrier may be a promising drug delivery system for local brain delivery and long-term treatment of pharmacoresistant epilepsy.

Strain-induced disorder, phase transformations, and transformation-induced plasticity in hexagonal boron nitride under compression and shear in a rotational diamond anvil cell: in situ x-ray diffraction study and modeling.

Plastic shear significantly reduces the phase transformation (PT) pressure when compared to hydrostatic conditions. Here, a paradoxical result was obtained: PT of graphitelike hexagonal boron nitride (hBN) to superhard wurtzitic boron nitride under pressure and shear started at about the same pressure ( approximately 10 GPa) as under hydrostatic conditions. In situ x-ray diffraction measurement and modeling of the turbostratic stacking fault concentration (degree of disorder) and PT in hBN were performed. Under hydrostatic pressure, changes in the disorder were negligible. Under a complex compression and shear loading program, a strain-induced disorder was observed and quantitatively characterized. It is found that the strain-induced disorder suppresses PT which compensates the promotion effect of plastic shear. The existence of transformation-induced plasticity (TRIP) was also proved during strain-induced PT. The degree of disorder is proposed to be used as a physical measure of plastic straining. This allows us to quantitatively separate the conventional plasticity and transformation-induced plasticity. Surprisingly, it is found that TRIP exceeds the conventional plasticity by a factor of 20. The cascade structural changes were revealed, defined as the reoccurrence of interacting processes including PTs, disordering, conventional plasticity, and TRIP. In comparison with hydrostatic loading, for the same degree of disorder, plastic shear indeed reduces the PT pressure (by a factor of 3-4) while causing a complete irreversible PT. The analytical results based on coupled strain-controlled kinetic equations for disorder and PT confirm our conclusions.

Preparation and characterization of coenzyme Q10-Eudragit solid dispersion.

A solid dispersion of Coenzyme Q10 and Eudragit L 100-55 was prepared using solvent evaporation method. Solid dispersion, physical mixture, and pure compound were then characterized using differential scanning calorimetry and powder x-ray diffraction. Solubility of CoQ10 in different surfactant media was measured, and a suitable dissolution medium was developed to compare the dissolution patterns of the solid dispersion, physical mixture, and the pure compound. Combining labrasol with different surfactants in dissolution media demonstrated an additive effect on CoQ10 solubility. The solubility of CoQ10 in a 4% Labrasol/2% Cremophor EL solution was 562 microg/ml, which was five times higher than the combined solubility in 5% Labrasol (91 microg/ml) and 5% Cremophor EL (7.8 microg/ml). Moderate change in the crystalline pattern of CoQ10 was observed, which was attributed to solvent displacement rather than the degree of crystallinity change. The dissolution test indicated that the in-vitro release of Coenzyme Q10 from its solid dispersion was much faster than its physical mixture, which in turn was faster than the pure drug. The amount of drug released in 12 hours from solid dispersion, physical mixture, and the pure drug was 100, 26.5 and 12.5% respectively. CoQ10 was photostable throughout the dissolution experiments.