The effects of hydroxychloroquine-induced oxidative stress on fracture healing in an experimental rat model.

OBJECTIVES: The purpose of this study was to investigate whether hydroxychloroquine (HCQ) sulfate causes oxidative stress (OS) and its effect on fracture healing in an experimental rat model. MATERIALS AND METHODS: In this experimental study, open diaphyseal femur fractures were induced in 24 eight-week-old male rats (mean weight: 225±25 g; range, 200 to 250 g) and then fixed with K-wire. The rats were divided into four groups: HCQ-2, control-2 (C-2), HCQ-4, and control-4 (C-4). During the study period, rats in the HCQ groups received an HCQ solution (160 mg/kg/day), whereas rats in the control groups received saline. The HCQ-2 and C-2 groups were sacrificed on the 14th day, and the HCQ-4 and C-4 groups were sacrificed on the 28th day. After sacrifice, malondialdehyde levels induced by OS were calculated for each rat, and fracture healing was evaluated radiographically, histomorphometrically, histopathologically, and immunohistochemically. RESULTS: Malondialdehyde levels were higher in the HCQ groups than in the control groups (p<0.05). Hydroxychloroquine caused OS in rats. The ratio of total callus diameter to femur bone diameter was lower in HCQ groups compared to control groups (p<0.05). No differences were observed when comparing radiological and histological healing results between the control and HCQ groups. Alkaline phosphatase levels were lower in the HCQ-4 group than the C-4 group at week four (p<0.05), although osteocalcin and osteopontin levels did not differ between groups (p>0.05). Oxidative stress had no adverse effects on histologic healing outcomes and osteoblast functions. Cathepsin K and tartrate-resistant acid phosphatase-5b levels were higher in the HCQ-4 group than in the C-4 group (p<0.05). While the number and function of osteoclasts increased due to OS in callus tissue, a decrease in the number of chondrocytes was observed. CONCLUSION: Hydroxychloroquine-induced OS increases the number and function of osteoclasts and decreases the number of hypertrophic chondrocytes and endochondral ossification but has no significant effect on mid-late osteoblast products and histological fracture healing scores.

The effects of cephalexin on fracture healing in a rat femur fracture model.

OBJECTIVES: The aim of this study was to examine the effects of cephalexin on the fracture union histomorphometrically, radiologically, biomechanically, immunohistochemically, and histopathologically in a rat femur fracture model and to evaluate the effects of the antibiotics to be used in the prophylaxis of fracture infection on the union of the fracture. MATERIALS AND METHODS: A total of 48 male Wistar rats were divided into four groups as two-week control (C2) and cephalexin (CEP2) and four-week control (C4) and cephalexin (CEP4). After establishment of standard fracture model on right femurs, 60 mg/kg/day of cephalexin was applied to CEP2 and CEP4 by oral gavage. Radiological, biomechanical, histopathological, immunohistochemical, and histomorphometric examinations were performed on amputated femurs. RESULTS: Callus volume of CEP4 group significantly increased compared to CEP2 group (p=0.005), while no significant difference was found in the bone mineral density and callus/bone volume among the groups (p>0.05). There was no significant difference in flexural strength between the C4 and CEP4 groups (p=0.093). Histological healing scores increased from Week 2 to Week 4 (p=0.002) and inflammation scores decreased in both control and cephalexin groups (p=0.010 and p=0.008); however, no significant difference was found in healing and inflammation scores (p>0.05). The CD34+ immunoreactivity in the CEP2 group was significantly higher than the C2 group (p=0.029). Collagen type III level was significantly lower in the CEP2 and CEP4 groups compared to the corresponding control groups (p=0.008 and p=0.016, respectively). CONCLUSION: Cephalexin did not exert any radiological, histopathological, histomorphometric, biomechanical, and immunohistochemical adverse effects on the femoral fracture healing model in rats; however, it showed positive effects on CD34 and Collagen type III levels. Based on these findings, antibiotherapy with cephalexin may be considered as a safe treatment for fracture union.

The effects of thymoquinone on steroid-induced femoral head osteonecrosis: An experimental study in rats.

OBJECTIVES: In this study, we aimed to evaluate the antioxidant, anti-apoptotic, osteoblastic and hypolipidemic effects of thymoquinone (TQ) treatment on the steroid-induced osteonecrosis of femoral head (ONFH) model in rats. MATERIALS AND METHODS: A total of 24 rats were randomly divided into four groups: the control group administered saline; the TQ group administered 10 mg/kg/day TQ orally; lipopolysaccharide/methylprednisolone (LPS/MPS) group administered 20 µg/kg intraperitoneally LPS and 40 mg/kg intramuscularly MPS to establish ONFH model; and the LPS/ MPS+TQ group administered both LPS/MPS and, then, TQ once daily for four weeks. All rats were sacrificed after intracardiac blood collection and their right femurs were removed. RESULTS: Micro-computed tomography showed a higher bone mineral density and lower porosity, Tr. Sp and Tr. Sep data were detected in the LPS/MPS+TQ group. In histopathology, osteonecrosis increased significantly in the LPS/MPS group and osteonecrosis decreased in the LPS/MPS+TQ group compared to the LPS/MPS group (p=0.0077). Histomorphometric examination revealed that the percentage of BV/TV in the LPS/MPS group was significantly lower compared to control and other groups (p<0.01 and p<0.05, respectively), while it reached normal rates in the LPS/MPS+TQ group. Immunohistochemically, antioxidant, anti-apoptotic, and angiogenesis indicators (8-hydroxy-20- deoxyguanosine [8-OHdG], malondialdehyde [MDA], B-cell lymphoma [Bcl-2], caspase-3, vascular endothelial growth factor [VEGF]) were significantly improved in tissue and serum with TQ. Furthermore, TQ significantly reduced low- and high-density lipoprotein cholesterol ratio and carboxy-terminal type 1 collagen crosslink (CTX) in serum. CONCLUSION: Vascular and hematopoietic cell damages that occur due to steroid-induced deoxyribonucleic acid (DNA) oxidative and lipid peroxidative damages in an ONFH model can be successfully ameliorated by TQ administration. This antioxidant and anti-apoptotic effects of TQ may be a promising treatment option for early stage of osteonecrosis.

Effects of different vardenafil doses on bone healing in a rat fracture model.

OBJECTIVES: We aimed to investigate the radiological, biomechanical, histopathological, histomorphometric, and immunohistochemical effects of different doses of vardenafil on fracture healing. MATERIALS AND METHODS: Fifty-one rats were divided into three groups. Group V5 was given 5 mg/kg/day of vardenafil; Group V10 was given 10 mg/kg/day of vardenafil; and the control group was given the same volume of saline. Six rats from each group were sacrificed on Day 14 (early period) and the remaining rats were sacrificed on Day 42 (late period). Callus/femoral volume and bone mineral density were measured using micro-computed tomography. Five femurs from each group in the late period were examined by biomechanical tests. In addition to the histopathological and histomorphometric evaluations, immunohistochemical analyses were performed to examine the levels of inducible nitric oxide synthase (iNOS), transforming growth factor-3 (TGF-ß3), and nuclear factor kappa B (NF-κB) proteins. RESULTS: Both doses of vardenafil increased primary bone volume and maximal bone fracture strength in late period, compared to the control group (p<0.05). Histological healing scores of vardenafil groups were significantly higher in early period (p<0.001). While cartilaginous callus/total callus ratio in early period was higher, callus diameter/femoral diameter ratio in late period was lower in vardenafil groups (p<0.01). The NF-κB immunopositivity in V10 group decreased in early period, compared to control group (p<0.001). The TGF-ß3 and iNOS immunopositivity increased in both V5 and V10 groups, compared to the control group in early period, but returned to normal in late period. CONCLUSION: During the first period of fracture healing process in which vasodilation is mostly required with increasing inflammation, vardenafil has ameliorating effects on the bone union and supports fracture healing.

Urine in the thigh, an extraordinary complication of pelvic fracture: Vesicocutaneous fistula.

We present a case of a 67-year-old woman who was initially treated conservatively for pelvic fracture. After 4 weeks, she was admitted to our clinic with swelling and pain in the distal part of her right thigh. Ultrasonography and magnetic resonance imaging showed accumulation of fluid between the subcutaneous adipose tissue and fascia. Urine was detected by a puncture. Bladder injury was detected in the left anterolateral wall using computed tomography. A fistula tract was observed from the right side of the bladder neck in cystogram, which confirmed the diagnosis of vesicocutaneous fistula. Bladder drainage was achieved using a urethral catheter, and the fistula was closed without any complication. The control cystogram showed healing of the bladder. All the patients with pelvic fractures should be evaluated by urine analysis and examined for associated urethral or bladder injury using retrograde urethrography and cystography.

Cyanocobalamin and cholecalciferol synergistically improve functional and histopathological nerve healing in experimental rat model.

BACKGROUND AND PURPOSE: Peripheral nerve injury (PNI) is a frequent problem among young adults. Hopefully, regeneration can occur in PNI unlike central nervous system. If nerve cut is complete, gold standard treatment is surgery, but incomplete cuts have been tried to be treated by medicines. The aim of the study was to evaluate and compare clinical and histopathological outcomes of independent treatment of each of Vitamin B12 (B12) and Vitamin D3 (D3) and their combination on sciatic nerve injury in an experimental rat model. METHODS: Experimental animal study was performed after the approval of BEH Ethics Committee No. 2015/10. 32 rats were grouped into four (n=8) according to treatment procedures, such as Group 1 (controls with no treatment), Group 2 (intraperitoneal 1 mg/kg/day B12), Group 3 (oral 3500 IU/kg/week D3), Group 4 (intraperitoneal 1 mg/kg/day B12+ oral 3500 IU/kg/week D3). Sciatic Functional Index (SFI) and histopathological analysis were performed. RESULTS: SFIs of Group 2, 3, 4 were statistically significantly higher than controls. Group 2 and 3 were statistically not different, however Group 4 was statistically significantly higher than others according to SFI. Axonal degeneration (AD) in all treatment groups were statistically significantly lower than in Group 1. AD in Group 4 was significantly lower than in Group 2 and 3; there was no significant difference between Group 2 and 3. There was no significant difference between Group 1,2 and 3 in Axonolysis (A). But A of Group 4 was significantly very much lower than all others. Oedema- inflammation (OE-I) in all treatment groups were significantly lower than in Group 1; there was no significant difference between Group 2 and group 4. OE-I in Group 2 and 4 were significantly lower than in Group 3. There were no significant differences between Group 1, 2 and 3 in damage level scores; score of Group 4 was significantly lower than of Group 1. CONCLUSION: B12 and D3 were found effective with no statistically significant difference. But combined use of B12 and D3 improve nerve healing synergistically. We recommend combined use of B12 and D3 after PNI as soon as possible.

Factors affecting re-displacement in pediatric forearm fractures and the role of cast indices.

OBJECTIVES: This study aims to investigate the factors affecting the loss of reduction in pediatric diaphyseal forearm fractures and to compare the three-point index (TPI) with the cast index, padding index, Canterbury index, and gap index. PATIENTS AND METHODS: This retrospective study, which was conducted between January 2016 and December 2016, included 159 patients (134 males, 25 females; mean age 8.1±2.8 years; range, 3 to 13 years) with diaphyseal forearm fracture. Patients' age, gender, and the level, displacement, and location of the fractures were recorded. The presence of anatomic reduction, a straight ulnar border, and the cast type (banana or box type) were checked after the reduction. The TPI, cast index, padding index, Canterbury index, and gap index were measured. RESULTS: Fifty-two patients (32.7%) experienced loss of reduction during the follow-up. Displaced fractures of both the radius and the ulna, cast type-banana, anatomical reduction, straight ulnar border, TPI, cast index, padding index, and Canterbury index were found to be associated with re-displacement. CONCLUSION: Although cast indices can be used as a beneficial clinical tool in predicting the loss of reduction in the treatment of pediatric forearm fractures, they may not be sufficient when used alone. Obtaining a more accurate result may be possible by assessing several parameters such as the presence of an anatomic reduction, box-type casting, and TPI together.

Effect of BMI on outcomes of surgical treatment for tibial plateau fractures: A comparative retrospective case series study.

PURPOSE: Tibia plateau fracture (TPF) treatment aims at achieving a stable, aligned, mobile, painless knee and preventing post-traumatic osteoarthritis. To achieve this goal, surgeons consider criteria such as patients' characteristics, severity, risk of complications, fracture displacement/depression, degree of soft tissue injury. However, body mass index (BMI) is not considered as a risk factor in literature. Our study was conducted to find out any possible correlation between BMI and functional scores or radiological score separately. METHODS: Retrospective analysis of case series between 2011 and 2014 was done on the database of a tertiary hospital in Istanbul. There were 67 TPF patients (54 males, 13 females) in the study. Relationship between BMI and functional knee scores or radiological score was compared statistically. Closed fractures with both high-energy and low-energy injury were included in the study. Patients with open fracture, multi-trauma presence, meniscus and/or ligamentous injury, increased co-morbidity, inadequate records (25 cases in all) were excluded. Surgery type, Schatzker classification, injury side, trauma energy, and gender were considered as possible risk factors. Binary regression analysis was done for possible factors affecting functional knee scores and radiologic score. RESULTS: Model summary calculations were done as Nagelkerke R2 test for Knee Society score, Lysholm knee score, and Ahlback and Rydberg radiologic scores, which were 0.648, 0.831, and 0.327 respectively. Homer-Lemeshow test values were 0.976, 0.998, and 0.362, respectively. There is negative correlation between BMI and both knee function scores. There is no correlation between BMI and radiologic score. CONCLUSION: An increase in BMI has a negative effect on functional knee scores after surgical treatment of TPFs. Therefore, BMI should be considered as a risk factor for surgical treatment of TPFs.

Investigation of the biomechanical and histopathological effects of autologous conditioned serum on healing of Achilles tendon.

OBJECTIVE: The aim of this study to evaluate the effects of autologous conditioned serum (ACS) on the healing of transected rat Achilles tendons via the assessment of biomechanical and histological parameters. METHODS: The study was conducted on 45 male Sprague-Dawley rats. Five rats were used as donors for ACS preparation. Animals were randomly assigned to the experimental or control group. In both groups, the Achilles tendon was cut transversally and then sutured. In the placebo control and ACS-treated groups, saline or ACS, respectively, was injected into the repair zone three times after surgery. Ten rats from each group (ACS group, n = 20; control group, n = 20) were euthanized at days 15 and 30 after surgery for histopathological (n = 5) and biomechanical (n = 5) testing. The histopathological findings were interpreted using the Bonar and Movin scales. Tendon remodelling was evaluated via the immunohistochemical staining of collagen type 3. Biomechanical effects were assessed by tensile testing. RESULTS: The Bonar and Movin scale scores were significantly better in the ACS-treated group on both day 15 (p = 0.003 and p = 0.003, respectively) and day 30 (p = 0.005 and p = 0.004, respectively). The immunohistochemical density of collagen type 3 was significantly lower in the ACS-treated group on day 30 (p = 0.018). The type 1/3 collagen ratios of the groups were similar on days 15 and 30, as determined by Sirius Red staining (p = 0.910 and p = 0.133, respectively). In the biomechanical assessment results, the ACS-treated group's maximum load to failure values were significantly higher on day 15 (p = 0.049). CONCLUSION: Injection of ACS had a positive effect on the histopathological healing of rat Achilles tendons on days 15 and 30 and on biomechanical healing on day 15. ACS treatment contributed to lowering the collagen type 3 density by day 30. According to our study, ACS may be favourable for the treatment of human Achilles tendon injuries and tendinopathies.

Volar dislocation of the metacarpophalangeal joint of the thumb: A case report.

We present an 18 year-old patient with a volar dislocation of the metacarpophalangeal joint of the thumb. Open reduction was performed through a dorsal incision. Because of the soft tissue interposition such as dorsal capsule, volar plate, dislocated extensor pollicis longus and brevis tendons, ruptured ulnar collateral ligament; open reduction, soft tissue and ligament repair are recommended for this type of thumb dislocations.

Is intramedullary nailing applicable for distal tibial fractures with ankle joint extension?

OBJECTIVES: This study aims to evaluate the functional and radiographic results and treatment complications of AO/OTA (Arbeitsgemeinschaft fur Osteosynthesefragen/Orthopaedic Trauma Association) type 43C1 and C2 fractures treated with intramedullary nailing. PATIENTS AND METHODS: We retrospectively evaluated 35 AO/OTA type 43C1 and C2 patients (26 males, 9 females; mean age 39.8±16.9 years; range 19 to 82 years) treated with intramedullary nailing. Two interfragmentary screws out of nail were applied in 10 patients (29%), while one interfragmentary screw out of nail was applied in 17 patients (49%). Intramedullary nailing was applied in eight patients (23%) without external screws. Fracture union, union time, alignment problems, and complications were evaluated. Clinical evaluation of patients was conducted using the Olerud and Molander score and by measuring the ankle joint range of motion. RESULT: Union was achieved in all 35 patients. Mean union time was 16.5±2.8 weeks (range 12 to 24 weeks) and mean Olerud and Molander score was 88±8.24. Varus deformity was detected in one patient, valgus deformity was detected in two patients, and rotation deformity was detected in one patient. Superficial infection was detected in three patients (9%). Deep infection was not detected in any patient. CONCLUSION: Intramedullary nailing is not contraindicated for simple intra-articular distal tibial fractures. In these fractures, intramedullary nailing performed in accordance with its technique, with an additional percutaneous screw if necessary, is a successful treatment option with high fracture union rates, high functional results, and low complication rates.

Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer's Disease.

The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals. Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer's disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.

Possible role of antioxidants and nitric oxide inhibitors against carbon monoxide poisoning: Having a clear conscience because of their potential benefits.

Carbon monoxide poisoning is one of the important emergency situations manifested by primarily acute and chronic anoxic central nervous system (CNS) injuries and other organ damages. Current descriptions and therapeutic approaches have been focused on the anoxic pathophysiology. However, this point of view incompletely explains some of the outcomes and needs to be investigated extensively. Considering this, we propose that reactive oxygen species (ROS) including especially nitric oxide (NO) are likely to be a key concept to understand the emergency related to CO poisoning and to discover new therapeutic modalities in CO toxicity. If we consider the hypothesis that ROS is involved greatly in acute and chronic toxic effects of CO on CNS and some other vital organs such as heart, it follows that the antioxidant and anti-NO therapies might give the clinicians more opportunities to prevent deep CNS injury. In support of this, we review the subject in essence and summarize clinical and experimental studies that support a key role of ROS in the explanation of pathophysiology of CO toxicity as well as new treatment modalities after CO poisoning.

The Role of ADAMTS1 and Versican in Human Myocardial Infarction: A Postmortem Study.

OBJECTIVE: To determine the role of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) and fragmented versican in the myocardial infarction (MI) process in humans and to evaluate the diagnostic efficacy of ADAMTS1 for postmortem diagnosis of MI. METHODS: Thirty autopsied individuals were allocated into 2 groups, namely, a study group of individuals who died of myocardial infarction (n = 20), and a control group who died of trauma (n = 10). We performed standard immunohistochemical staining on myocardial tissue specimens, studying anti-ADAMTS1, anti-versican, and anti-versican C terminal peptide sequence (DPEAAE) fragments. RESULTS: Strong, diffuse staining was observed throughout myocardial tissue for ADAMTS1 in the 2 groups. However, in the study group, we observed no expression for ADAMTS1 around fibrotic areas but detected slight staining in coagulative and necrotic zones. CONCLUSION: Similar localizations of ADAMTS and fragmented versican in human heart tissue indicate that versican presumably is cleaved by ADAMTS1. Hence, ADAMTS1 can be regarded as a new marker for postmortem differential diagnosis of MI.

Can propolis and caffeic acid phenethyl ester be promising agents against cyclophosphamide toxicity?

Propolis is a mixture having hundreds of polyphenols including caffeic acid phenethyl ester (CAPE). They have been using in several medical conditions/diseases in both in vitro and in vivo experimental setup. Cyclophosphamide (CP) has been used to treat a broad of malignancies including Hodgkin's and non-Hodgkin's lymphoma, Burkitt's lymphoma, chronic lymphocytic leukemia, Ewing's sarcoma, breast cancer, testicular cancer, etc. It may cause several side effects after treatment. In this mini review, the protective effects of propolis and CAPE were compared each other in terms of effectiveness against CP-induced injuries.

Glomus tumor located in deltoid muscle.

Glomus tumors are benign soft tissue neoplasms arising from the glomus body, which are primarily found under the nail bed of the fingers. They are rarely located in other parts of the body. Only 8 cases of glomus tumors around the shoulder have been published in the literature. The purpose of this study was to present a glomus tumor located in the deltoid muscle in a 68-year-old male patient that was surgically treated by marginal excision. The patient remained asymptomatic, and no recurrence was detected at 2-year follow up.

Melatonin and caffeic acid phenethyl ester in the regulation of mitochondrial function and apoptosis: The basis for future medical approaches.

The aim of this review article is to summarize and compare the effects of melatonin and caffeic acid phenethyl ester (CAPE) on the relationship between mitochondrial functioning and apoptosis. References in this article were selected with an approach based on a comprehensive literature review by using MEDLINE/PubMed and Google Scholar databases which were scanned in the last six months without any restrictions. For each database, the review terms used are 'melatonin', 'caffeic acid phenethyl ester, both together and associated with other key words such as apoptosis and mitochondria. Evidential mitochondrial molecular backgrounds for diseases make these two molecule competitors, since both of them use the same pathways to cope with fundamentals of the diseases such as nuclear factor κ-light-chain-enhancer of activated B (NF-κB inhibition, induction of mitochondrial apoptosis in cancer cells, free radical scavenging effects, and antioxidant activities. The data reviewed in this paper provide a useful background for the understanding of some molecular details of melatonin and CAPE on several medical situation and diseases. Mutual usage of these two tremendous molecules might have a capacity to open new therapeutic approaches in near future.

Effect of platelet-rich plasma for treatment of Achilles tendons in free-moving rats after surgical incision and treatment.

OBJECTIVE: The purpose of this study is to investigate, both histopathologically and biomechanically, the effect of platelet-rich plasma (PRP) on surgically repaired Achilles tendon rupture recovery in rats. METHODS: The study included 25 17-month-old male Sprague-Dawley rats with an average weight of 500-550 g. Five rats were used as donors, while 20 rats were separated as PRP group (n=10) and control group (n=10). The Achilles tendons of the rats were cut transversely, and PRP was administered to the PRP group, while the control group received serum physiologically to create the same surgical effect. In previous studies, it was shown that this serum does not affect tendon recovery. Fifteen and 30 days post-treatment, the rats were sacrificed, and their Achilles tendons were extracted and examined histopathologically and biomechanically. RESULTS: Based on the obtained findings, it was observed that the histopathologic Movin and Bonar scores of PRP group on the 15th and 30th day post-treatment were significantly lower than those of the control group (p=0.019, p=0.017, respectively), while no significant difference was found in maximum force (Fmax) values in biomechanical measures on the 15th and 30th day post-treatment. CONCLUSION: It is thought that PRP use in Achilles tendon ruptures positively affects histopathological recovery in the early period, but that it does not produce the same biomechanical effect. We believe that PRP use for qualified tendon recovery is histopathologically beneficial.