Rationale The small molecule Kartogenin (KGN) promotes cartilage regeneration in osteoarthritis (OA) by activating stem cells differentiation, but its pharmacological mode-of-action remains unclear. KGN can be cleaved into 4-aminobiphenyl (4-ABP) and phthalic acid (PA) following enzymolysis of an amide bond. Therefore, this study investigated whether 4-ABP or PA exerted the same action as KGN.Methods KGN, 4-ABP and PA were analyzed in cartilage of mice after oral, intravenous or intra-articular administration of KGN by liquid chromatography-mass spectrometry method. Their effect on proliferation and chondrogenic differentiation of mesenchymal stem cells (MSC) was evaluated in vitro. Furthermore, their effect on cartilage preservation was tested in mice OA model induced by destabilization of medial meniscus. OA severity was quantified using OARSI histological scoring. Transcriptional analysis was used to find the possible targets of the chemicals, which were further validated.Results We demonstrated that while oral or intra-articular KGN delivery effectively ameliorated OA phenotypes in mice, only 4-ABP was detectable in cartilage. 4-ABP could induce chondrogenic differentiation and proliferation of MSC in vitro and promote cartilage repair in OA mouse models mainly by increasing the number of CD44+/CD105+ stem-cell and prevention of matrix loss. These effect of 4-ABP was stronger than that of KGN. Transcriptional profiling of 4-ABP-stimulated MSC suggested that RPS6KA2 and the PI3K-Akt pathway were 4-ABP targets; 4-ABP could activate the PI3K-Akt pathway to promote MSC proliferation and repair OA injury, which was blocked in RPS6KA2-knockdown MSC or RPS6KA2-deficient mice.Conclusion 4-ABP bio-distribution in cartilage promotes proliferation and chondrogenic differentiation of MSC, and repairs osteoarthritic lesions via PI3K-Akt pathway activation.
Arachnoid cyst of the brain is common in children but its association with spontaneous subdural hygroma is rare. A case of a nine-year-old boy, without any preceding history of trauma, is presented here who came to the emergency department of a tertiary care hospital with complaints of headache, nausea, and vomiting for the last two weeks but more for the last two days. Examination showed a young, fully conscious oriented boy with positive Cushing's reflex and papilledema of left eye. MRI (magnetic resonance imaging) of the brain showed left temporal extra-axial cystic lesion of 5.40 × 4.10 cm in size, representing arachnoid cyst, with bilateral frontoparietal subdural hygromas. Cyst was partially drained through left temporal craniectomy and subdural hygromas were drained through bilateral frontal burr holes. Postoperatively the child recovered uneventfully and was discharged on the seventh postoperative day. Histopathology proves it to be arachnoid cyst of the brain with subdural CSF (cerebrospinal fluid) collection or hygroma.
Purpose. To determine association between apparent diffusion coefficient value on diffusion-weighted imaging and Gleason score in patients with prostate cancer. Methods. This retrospective case series was conducted at Radiology Department of Aga Khan University between June 2009 and June 2011. 28 patients with biopsy-proven prostate cancer were included who underwent ultrasound guided sextant prostate biopsy and MRI. MRI images were analyzed on diagnostic console and regions of interest were drawn. Data were entered and analyzed on SPSS 20.0. ADC values were compared with Gleason score using one-way ANOVA test. Results. In 28 patients, 168 quadrants were biopsied and 106 quadrants were positive for malignancy. 89 lesions with proven malignancy showed diffusion restriction. The mean ADC value for disease with a Gleason score of 6 was 935 mm2/s (SD = 248.4 mm2/s); Gleason score of 7 was 837 mm2/s (SD = 208.5 mm2/s); Gleason score of 8 was 614 mm2/s (SD = 108 mm2/s); and Gleason score of 9 was 571 mm2/s (SD = 82 mm2/s). Inverse relationship was observed between Gleason score and mean ADC values. Conclusion. DWI and specifically quantitative ADC values may help differentiate between low-risk (Gleason score, 6), intermediate-risk (Gleason score, 7), and high-risk (Gleason score 8 and 9) prostate cancers, indirectly determining the aggressiveness of the disease.
abstract:Objectives: This study aimed to assess the technical success, safety and immediate and delayed complications of double-lumen tunnelled cuffed central venous catheters (TVCs) at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman. Methods: This retrospective study took place between January 2012 and October 2013. The clinical records and radiological data of all patients who underwent ultrasound-and fluoroscopy-guided TVC placement at SQUH during the study period were reviewed. Demographic data and information regarding catheter placement, technical success and peri-and post-procedure complications (such as catheter-related infections or thrombosis) were collected. Results: A total of 204 TVCs were placed in 161 patients. Of these, 68 were female (42.2%) and 93 were male (57.8%). The mean age of the patients was 54.4 ± 17.3 years. The most common reason for catheter placement was the initiation of dialysis (63.4%). A total of 203 procedures were technically successful (99.5%). The right internal jugular vein was the most common site of catheter placement (74.9%). Mild haemorrhage which resolved spontaneously occurred in 11 cases (5.4%). No other complications were observed. Subsequent follow-up data was available for 132 catheters (65.0%); of these, thrombosis-related catheter malfunction was observed in 22 cases (16.7%) and catheter-related infection in 29 cases (22.0%). Conclusion: Radiological-guided placement of tunnelled haemodialysis catheters can be performed safely with excellent technical success. The success rate of catheter insertion at SQUH was favourable in comparison with other studies reported in the literature.
A young child presented to the emergency department of a tertiary care hospital with on and off headache, focal seizures involving the left side of the body, weakness of left upper and lower limbs and vomiting for 2 weeks. Examination showed an alert child with grade 4/5 powers in left upper and lower limbs. Blood investigations were normal. An urgent CT of the brain showed intra-axial mass in the right frontal cerebral cortex, superolateral to the right lateral ventricle. MRI of the brain showed supratentorial extraventricular mass of 5.20 × 3.70 × 3.80 cm, in the right frontal cortex, emitting heterogeneous signals on T1, T2 and fluid-attenuated inversion recovery sequences and impression of astrocytoma, ependymoma or choroid plexus papilloma was made. Complete surgical resection of mass was performed. Histopathology of the mass proved it as WHO grade III anaplastic ependymoma. The child made an uneventful postoperative recovery and radiotherapy was followed.
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