Therapeutic effect of finasteride through its antiandrogenic and antioxidant role in a propionic acid-induced autism model: Demonstrated by behavioral tests, histological findings and MR spectroscopy.

BACKGROUND: Autism is a clinically defined neurodevelopmental disorder with unknown origin characterized by significant social, communication and behavioral challenges. Although it can be a lifelong condition, treatments can help alleviate symptoms and enhance a patient's quality of life. PURPOSE: We aimed to assess the therapeutic potential of finasteride in autism with biochemical markers, histopathological evaluation, behavioral tests and radiological imaging. MATERIALS AND METHODS: Propionic acid (PPA) was injected intraperitoneally into 20 out of 30 rats for 5 days to establish an autism model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 10), placebo group (intraperitoneal PPA + 1 ml/kg/day % 0.9 NaCl saline was given via oral gavage for 15 days, n = 10) and treated group (intraperitoneal PPA + 5 mg/kg/day of finasteride was given via oral gavage for 15 days, n = 10). After 4 days of behavioral tests, magnetic resonance spectroscopy (MRS) was performed for measuring creatine and lactate levels. All animals were sacrificed for histopathological examination and biochemical analysis of brain tissue. RESULTS: MDA, NFκB, TNF-α, IL-2, IL-17A and lactate levels in brain homogenates were significantly increased in the placebo group compared to the control group, while Nfr2 levels were decreased; and the levels of all biochemical markers were reversed by finasteride treatment. A significant improvement was observed in autism-like behaviors in rats treated with finasteride compared to the placebo group. Further, the creatine and lactate levels in corpus striatum in MRS, the neuronal counts and glial activity of the hippocampus and cerebellum were closer to the control group in the finasteride-treated group compared to the placebo group. CONCLUSION: Finasteride led significant improvement in autism-like symptoms with its antioxidant effect through Nrf2 modulation in addition to its anti androgen effect.

Protective effect of oxytocin through its anti-inflammatory and antioxidant role in a model of sepsis-induced acute lung injury: Demonstrated by CT and histological findings.

Although several studies demonstrate the anti-inflammatory effect of oxytocin in different pathophysiological processes, there are limited data describing the impact of oxytocin on acute respiratory distress syndrome (ARDS). We aimed to elucidate the protective effect of oxytocin in ARDS with histopathological evaluation and radiological imaging in addition to biochemical markers.Fecal intraperitoneal injection procedure (FIP) was performed on 24 of 32 rats included in the study for creating a sepsis model. Rats were randomly assigned into four groups: control group (no procedure was applied, n = 8), untreated septic group [was operated (FIP) and received no treatment, n = 8], placebo group (FIP, treated with 10 ml/kg of saline at once, n = 8), and treated group (FIP, treated with 0.1 mg/kg of oxytocin at once, n = 8). Chest CT was performed for all rats 20 hours after the procedure and density of the lungs were measured manually by using HU. All animals were sacrificed for histopathological examination of lung damage and blood samples were collected for biochemical analysis.Plasma malondialdehyde (MDA), lactic acid (LA), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL 1-ß) levels were significantly increased in the placebo (FIP + saline) and the untreated (FIP) groups, and plasma levels of all biomarkers were reversed by oxytocin. Further, the density of the lung parenchyma (Hounsfield unit) on CT images and the histopathological lung damage score values were closer to the control group in the oxytocin-treated group compared to the placebo group.Our findings suggested that oxytocin could exert anti-inflammatory, antioxidant and protective effects in FIP-induced ARDS.

Deformity correction with total knee arthroplasty for severe knee osteoarthritis accompanying extra-articular femoral deformity: the results are promising.

PURPOSE: This study aimed to evaluate patients with severe degenerative osteoarthritis of the knee and extra-articular femoral deformities treated with total knee arthroplasty (TKA) and acute deformity correction. METHODS: Ten patients with severe degenerative osteoarthritis of the knee and extra-articular femoral deformities were included, and the median age was 63 years (range 38-67). The etiology was post-traumatic malunion in four patients, rickets sequelae in four patients, and surgical sequelae due to multiple epiphyseal dysplasia in two patients. The severity of degenerative osteoarthritis and deformity analyses were assessed according to the Kellgren-Lawrence and Paley criteria, respectively. The median number of previous operations the patients had undergone was two (range 0-3), and the median Oxford Knee Society score was 9 (range 5-13) before treatment. All patients were treated with primary TKA and deformity correction in the same surgery. The TKA was completed first, followed by an osteotomy at the apex of the deformity. Finally, a retrograde intramedullary nail was inserted. RESULTS: The median follow-up period was 44 (31-60) months. A stable and functional knee joint, a physiological mechanical axis, and solid osseous union were achieved in all patients. Late prosthetic failure was seen in one patient due to deep infection. The median Oxford Knee Society score was 42 (range 37-47) at the final follow-up. CONCLUSIONS: Combining several procedures in single setting for the treatment of severe knee osteoarthritis accompanied by extra-articular deformity may eliminate the need for multiple surgeries. Furthermore, a proper physiological mechanical axis can be obtained without causing substantial bone loss. LEVEL OF EVIDENCE: IV.

Angular deformity development after the distal tibial physeal fractures.

Several clinical and radiological factors can be prognostic in the development of angular deformity following physeal injuries of the distal tibia. One of the radiological parameters, premature physeal closure (PPC), can be detected during postoperative follow-ups. Aim of our study was to identify the prognostic factors in development of angular deformity and its relationship with PPC. One hundred and four patients treated due to physeal injuries of the distal tibia were included in our study. Patients were divided into three groups based on Salter-Harris (SH) classification. The intergroup relationships between sex, age, the amount of energy sustained during injury, premature physeal closure, the amount of residual gap, and deformity were analyzed. Angular deformity developed in 25% (3/12) of SH Type 2, in 60% (9/15) of Type 3 and 30% (3/10) of Type 4 patients with PPC. A residual displacement of more than 2 mm, age and premature physeal closure were specified as significant risk factors for development of angular deformity. 2 mm limit for residual displacement and findings of premature physeal closure in the radiological evaluations during follow-ups are prognostic factors in avoiding malalignment of the distal tibia. LEVEL OF EVIDENCE: Level 3.