Role of Farnesoid Receptors and Nrf2-mediated Genes in Gentamicin-induced Nephrotoxicity in Rat: A Time-course Study.

INTRODUCTION: Farnesoid-X-activated receptor (FXR) is considered as an upstream controller which could influence the other key regulatory genes encoding cellular antioxidant defense system. METHODS: Thirty-five male Wistar rats (240 ± 20 g) were randomly allocated into five groups: 1) control, 2) received gentamicin (100 mg/kg/d) for three days (GM-3d), 3) seven days (GM-7d), 4) 10 days (GM-10d), and 5) 14 consecutive days (GM-14d). Biochemical measurements of BUN and serum creatinine (SCr), histological assessment of renal samples as well as molecular analysis using real-time qRT-PCR were used to investigate the pattern of changes in different levels. RESULTS: Administration of gentamicin was associated with a significant increase in the BUN and SCr until the 10th day, which then suddenly dropped at the day 14. Meantime, the maximum histological distortion was also seen on the 10th day but in a similar pattern, 14th day was associated with clear improvement. Compared to the control value, the maximum reduction in the mRNA expression of Farnesoid X-activated receptor (FXR), nuclear factor erythroid 2-related factor 2 (Nrf2) and Glutathione cysteine ligase-modulatory subunit (GCLM), occurred at the 3rd and 7th days, respectively. Compared to the control, the mRNA expression of the mentioned genes significantly increased up to day 14. Apart from the 3rd day, the mRNA expression of alpha-glutathione S-transferase (α-GST) and superoxide dismutase (SOD) showed a similar descending and ascending pattern at 7th and 10th days, respectively. CONCLUSION: The expression of FXR, as an upstream controller gene and its downstream pathways mediated by Nrf2, could play a role in gentamicin-induced nephrotoxicity but the pattern of expression was rather biphasic at the acute phase or the subacute ones.  DOI: 10.52547/ijkd.7523.

A rare case of floated talar head accompanying medial subtalar dislocation.

INTRODUCTION AND IMPORTANCE: Concomitant medial subtalar dislocation and a rotated displaced talar neck fracture may result in poor outcomes. This study aimed to explain this extremely rare injury and assess the clinical outcomes following surgical treatment. CASE PRESENTATION: A 22-year-old Iranian man referred to the emergency department with a gross deformity and pain in his right foot and ankle after a falling from 2 m. Plain radiographs showed a rotated free talar head accompanying medial subtalar dislocation. Closed reduction was performed in the emergency department under sedation. Prompt open reduction and internal fixation of talar fracture was done, after removal of free osseocartilaginous fragments in the subtalar and talonavicular joints. At 25 months postoperatively, the clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale and visual analogue scale for pain which were 73 and 3, respectively. In exam, the patient had a stiffed subtalar joint without talar osteonecrosis or collapse. CLINICAL DISCUSSION: Several osseous and soft tissue barriers could prevent a successful closed reduction of a subtalar dislocation. Associated cartilage injuries or fractures may result in poor clinical outcomes such as persistent pain, limping, osteoarthritis, and osteonecrosis. Immediate open reduction and rigid fixation of associated fractures and resection of small free osseocartilaginous fragments may prevent further soft tissue damages and preserve clinical functions. CONCLUSIONS: Satisfactory clinical outcome could be expected following proper on-time approach to a subtalar dislocation associated with a rotated displaced talar neck fracture.

Total Knee Arthroplasty with Non-Stemmed Tibial Components among Obese Patients: Clinical and Radiologic Evaluation and Review of Literature.

Objective: This study aimed to evaluate the radiologic and clinical outcomes of TKA with non-stemmed tibial components in relation to their body mass index (BMI). Methods: In this retrospective cohort study, the outcome of TKA with non-stemmed tibial components based on their BMI was evaluated (BMI<30 vs. BMI≥30). The patients' function was assessed using the International Knee Documentation Committee (IKDC) and Lysholm knee questionnaires. Radiologic evaluation for probable signs of loosening was performed using two quantitative scoring systems by Ewald and Bach et al. Moreover, we reviewed the current literature on the application of non-stemmed tibial components in obese patients. Results: Twenty-one patients (two men and 19 women) with BMI≥30 and a mean age of 65.1±9.5 years, and 22 patients (three men and 19 women) with BMI<30 and a mean age of 63.6±8.5 years were studied. The mean follow-up periods with BMI≥30 (47.0±19.8 months) and BMI<30 (49.2±18.7 months) were comparable (p=0.618). No patients in either group experienced clinical loosening. Besides, none of the patients had any kind of revision surgery. The patients in both BMI groups had comparable IKDC scores (both the total score and its sub-scores; p>0.05). Furthermore, the total Lysholm knee scores were similar in both groups (p=0.122). Using both scoring systems, the peri-prosthetic bone radiolucency near the tibial components was similar in both groups (p>0.999). Conclusion: The present study found no significant difference in the radiologic or clinical outcome of non-stemmed TKA in patients with BMIs under and over 30.

Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines.

OBJECTIVE: Inhibition of lipid metabolism in breast cancer has been suggested as an effective approach for cancer therapy. Saffron-derived crocetin (Crt) and crocin (Cro) with the known anticancer activity, have shown hypolipidemic effect in diabetes and atherosclerosis. Here, we investigated the effect of Crt/Cro on lipid content in breast cancer. MATERIALS AND METHODS: A multi-model approach involving in vivo, in vitro and in silico studies was applied. The 4T1-induced breast cancer in mice was used to investigate the effect of Crt/Cro on cholesterol (Chl) and triglyceride (TG) levels in serum and tumor tissues. The Chl/TG levels were also assessed in the cytosol of MDA-MB-231 and MCF-7 breast cancer cell lines 6, 12 and 24 hr after Crt/Cro treatment. The interaction between Crt/Cro and hydroxymethylglutaryl coenzyme A reductase (HMGCR) was also computed by docking analysis. RESULTS: Crt reduced both serum (p=0.003) and tumor (p=0.011) Chl and TG (p=0.001) levels in mice. Cro reduced TG levels in tumor (p=0.014) and serum (p=0.002) and Chl level in tumor (p=0.013) tissues. Crt reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Cro reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Crt binds to the active site of HMGCR with higher affinity (ΔG0=-6.6 kcal/mol) than simvastatin (ΔG0 =-6.0 kcal/mol). CONCLUSION: Crt and Cro effectively decreased Chl/TG content in the sera of tumor bearing mice, in breast tumors and breast cancer cell lines. Crt showed a higher hypolipidemic potential than Cro. In silico analysis indicated Crt binding in the HMGCR active site.

Comparison of Accuracy in Expert Clinical Examination versus Magnetic Resonance Imaging and Arthroscopic Exam in Diagnosis of Meniscal Tear.

BACKGROUND: Many clinical tests and diagnostic studies have been developed to increase the clinician's ability to accurately diagnose disorders of the knee. Torn menisci or ligamentous structures within the knee cause significant pain and disability and thus require expeditious management. This study was conducted to evaluate the accuracy of clinical examination in comparison with MRI examination and with the help of arthroscopic examination as the gold standard in the diagnosis of meniscal tears. METHOD: All of the arthroscopic surgery candidates, presenting symptoms of meniscal or cruciate ligament lesions, referring to Namazi and Chamran hospitals, Shiraz, Iran, were included in this study. Clinical examination (including McMurray test, Apley test, and 20 Thessaly test) was performed before the arthroscopy, and the results were recorded in special forms. Magnetic resonance imaging (MRI) results were also added. Then, arthroscopy was performed, declaring the definite diagnosis, and the results were compared to the results obtained from both tests and MRI. Statistical analysis was performed using SPSS software. RESULTS: 86 patients with a mean age of 27 years old, including 63 (73%) male and 23 (27%) female, were studied. 57 (66%), 19 (22%), and 10 (12%) injuries were caused by sports, twisting, or trauma, respectively. Arthroscopic results showed 32 meniscal tears, of which 28 (87%) and 4 (13%) were in medial and lateral menisci, respectively, including 10 bucket handle, 17 longitudinal, and 5 of other types (transverse, oblique, radial) of injuries. Comparing MRI results to arthroscopic results, we had 2 false-positive and 2 false-negative cases. 62 cases of McMurray test results were accurate; 15 and 9 cases were reported false positive and false negative, respectively. 60 cases of Apley test results were accurate; 16 and 10 cases were reported false positive and false negative, respectively. 78 cases of Thessaly test results were accurate; 5 and 3 cases were reported false positive and false negative, respectively. Comparing Thessaly test results to McMurray and Apley showed statistical significance (P < 0.05). Comparing Thessaly test results to MRI showed no statistical significance (P = 0.151), while comparing McMurray and Apley test results to MRI showed statistical significance (P < 0.01). CONCLUSION: Clinical examination, performed by an experienced examiner, can have equal or even more diagnostic accuracy compared to MRI to evaluate meniscal lesions. In this study, the Thessaly test has been approved as a reliable clinical test in the diagnosis of meniscal tears.

Cosmeceutical effect of ethyl acetate fraction of Kombucha tea by intradermal administration in the skin of aged mice.

BACKGROUND/PURPOSE: Natural ingredients have been always an interesting approach to prolong youthful appearance of skin. One of the natural compounds is Kombucha tea (KT), which has been mainly used as an energy drink in Asian countries for a long time. Previous reports indicated that it has pharmaceutical and favorable wound repairing effects. The beneficial properties of KT are thought to be mainly due to the presence of fermentation products such as flavonoids and other polyphenols with inhibition of hydrolytic and oxidative enzymes and anti-inflammatory effects. These properties prompted us to study the anti-aging potential of KT and investigate its effective fraction in aged mice, METHODS: Kombucha tea was fractionated into chloroform, butanol, and ethyl acetate, and flavonoid content was determined. Young and old mice were used as control. KT ethyl acetate fraction (KEAf), which had the highest flavonoid content, was intradermally administered to old mice. RESULTS: Administration of KEAf significantly increased the collagen content, NAD+ /NADH level, and concomitantly improved skin connective tissue abnormalities in the aged skin. No sensitivity or irritation was observed. CONCLUSION: This finding suggested that KEAf can be a suitable candidate as a cosmetic product to improve aging-related skin abnormalities and regeneration of aged skin.

Hip abductors pyomyositis: a case report and review of the literature.

Pyomyositis, an acute hematogenous intramuscular bacterial infection, is an unusual disease in temperate climates. We present the case of a 15-year-old girl who was referred to our centre with pain, fever, and limping.  Magnetic resonance imaging and surgery showed diffuse pus collection in the hip abductor muscles. With increased incidence of this disease in immunocompromised patients in temperate areas, physicians must become familiar with its signs and symptoms to facilitate early diagnosis.