Exploration of molecular interactions between scoparone and associated compounds with Constitutive androstane receptor (CAR) leading to gallstone prevention: an in silico investigation.

Scoparone (6, 7 dimethylesculetin) is a biologically active compound derived from the herb Artemisia capillaris having anti-inflammatory, anti-lipemic, and anti-allergic roles. Activation of the constitutive androstane receptor (CAR) in primary hepatocytes of both wild-type and humanized CAR mice by scoparone, accelerates bilirubin and cholesterol clearance in vivo. This can prevent gallstones which is a dreaded gastrointestinal disease. To date, surgery is regarded as the gold standard for treating gallstones. The molecular interactions between scoparone and CAR leading to gallstone prevention are not yet explored. In this study, we have analyzed these interactions through an insilico approach. After extracting the CAR structures (mice and human) from the protein databank and 6, 7-dimethylesuletin from PubChem, energy minimization of both the receptors was done to make them stable followed by docking. Next, a simulation was performed to stabilize the docked complexes. Through docking, H-bonds and pi-pi interactions were found in the complexes, which imply a stable interaction, thus activating the CAR. A similarity search for scoparone was performed and the selected compounds were docked with the CAR receptors. Esculentin acetate and scopoletin acetate interacted with human CAR through pi-alkyl and H-bond respectively. While Fraxidin methyl ether, fraxinol methyl ether, and 6, 7 diethoxycoumarin interacted with mice CAR through H-bond and Pi-Pi T-shaped bonds. The selected complexes were simulated further. Our results are in accordance with the hypothesis in the literature. We have also analyzed the drug likeliness, absorption, non-carcinogenicity, and other properties of scoparone which can support further in vivo studies.Communicated by Ramaswamy H. Sarma.

Extensive Multifocal Emphysematous Osteomyelitis of Spine: A Rare Case and a Review of Literature.

BACKGROUND: Emphysematous osteomyelitis (EO) is an extremely rare form of osteomyelitis which is complicated mainly by infection with gas-forming organisms. The common causative agents of this disease are mainly members of Enterobacteriaceae family, the most common are Escherichia coli and Klebsiella pneumoniae along with anaerobes. A total of 48 cases of EO have been reported in the literature till now globally and none have documented the isolation of Corynebacterium amycolatum. CASE PRESENTATION: We report a rare case of emphysematous osteomyelitis of the spine and pelvis due to Escherichia coli along with the isolation of Corynebacterium amycolatum from the same pus samples on two consecutive occasions in a 50-year-old female with uncontrolled diabetes mellitus, who was successively treated with antibiotics and drainage of pus. We also did a brief review of the literature of all cases reported till now. CONCLUSION: The role of Corynebacterium amycolatum in the etiology of emphysematous osteomyelitis needs to be evaluated further in future studies as we cannot completely ignore its isolation in two consecutive samples as a mere contaminant.

The role of diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the diagnosis of diabetic foot osteomyelitis: a preliminary report.

Purpose: To assess the role of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusionweighted imaging (DWI) in diagnosing diabetic foot osteomyelitis (DFO). Material and methods: Twenty-five participants with suspected osteomyelitis were included, who underwent MRI including DCE-MRI and DWI sequences. It was subsequently followed by bone biopsy and microbiological analysis (gold standard). The participants were divided into 2 groups based on biopsy results: DFO-positive or DFO-negative. The semi-quantitative DCE-MRI parameters (SI0, SImax, SIrel, wash-in rate [WIR], and type of curve) and apparent diffusion coefficient (ADC) values were subsequently compared between the 2 groups. Results: Out of the 25 cases, 19 were DFO-positive and 6 were DFO-negative on bone biopsy. The SI0, SImax, and WIR were significantly higher in DFO-positive cases (p-value 0.050, 0.023, and 0.004, respectively). No difference was seen in SIrel. 100% negative cases revealed type-I curve, and 94% of positive cases showed type-II curve. SI0 > 143.4 revealed a sensitivity of 94.7% and specificity of 83.3%. SImax had a sensitivity of 89.5% but lower specificity of 67.7% at a cut-off value of 408.35. The most significant difference was seen with WIR; p-value ~0.004. At the cut-off value of > 1.280, it had a specificity and sensitivity of 100% and 76%, respectively. Also, ADC values below 1.57 × 10-3 had a sensitivity of 88.2% and specificity of 80% for diagnosing DFO. Conclusions: DWI and DCE-MRI provide non-invasive sequences, which can help to increase the overall specificity and sensitivity of conventional MRI for the diagnosis of osteomyelitis, differentiating it from acute Charcot's arthropathy.

Comparative Evaluation of Diffusion Kurtosis Imaging and Diffusion Tensor Imaging in Detecting Cerebral Microstructural Changes in Alzheimer Disease.

OBJECTIVE: Comparative evaluation of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) using a whole-brain atlas to comprehensively evaluate microstructural changes in the brain of Alzheimer disease (AzD) patients. METHODS: Twenty-seven AzD patients and 25 age-matched controls were included. MRI data was analyzed using a whole-brain atlas with inclusion of 98 region of interests. White matter (WM) microstructural changes were assessed by Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), Kurtosis fractional anisotropy (KFA), mean kurtosis (MK), axial kurtosis (AK) and radial kurtosis (RK). Gray matter (GM) integrity was evaluated using KFA, MK, RK, AK and MD. Comparison of the DKI and DTI metrics were done using student t-test (p ≤ 0.001). RESULTS: In AzD patients widespread increase in MD, AD and RD were found in various WM and GM region of interests. The extent of abnormality for DKI parameters was more limited in both GM and WM regions and revealed reduced kurtosis values except in lentiform nuclei. Both DKI and DTI parameters were sensitive to detect abnormality in WM areas with coherent and complex fiber arrangement. Receiver operating characteristic curve analysis for hippocampal values revealed the highest specificity of 88% for AK <0.6965 and highest sensitivity of 95.2% for MD >1.2659. CONCLUSION: AzD patients have microstructural changes in both WM and GM and are well-depicted by both DKI and DTI. The alterations in kurtosis parameters, however, are more limited and correlate with areas in the brain primarily involved in cognition.

MR vessel wall imaging in tubercular meningitis.

PURPOSE: Tubercular meningitis (TBM) has the propensity to cause secondary vasculitis through various mechanisms leading to development of cerebrovascular complications. These vascular involvements can be detected by vessel wall imaging (VWI). In this study, we aimed to study detailed findings of vessel wall imaging in cases of tubercular meningitis. METHODS: All consecutive patients of suspected tubercular meningitis in whom diagnosis of TBM could be made according to diagnostic criteria given by Ahuja et al. were included in the study. High-resolution MR VWI and time of flight (TOF) magnetic resonance angiography (MRA) were done along with routine MRI sequences. Arteries up to second-order branches were studied, and statistical analyses were done with respect to stage of tubercular meningitis, infarctions and TOF MRA findings. RESULTS: Out of all 101 cases of TBM, infarctions were found in 49 cases (48.5%), and vessel wall enhancement was seen in 67 cases (66.3%). With increasing severity of disease, more severe vascular involvement was seen on VWI. There was significant association between enhancement of individual arteries and infarctions in their territories. VWI had better sensitivity than the MRA, while MRA had better specificity than VWI for detection of vascular complications. CONCLUSION: Tubercular vasculitis can be detected by VWI in the form of nodular or smooth segmental enhancement of vessel wall with or without stenosis. Incorporation of VWI in routine MR imaging can play a greater role in early detection and management of cerebrovascular complications which can help to improve prognosis of the disease.