In-vitro antioxidant and in-vivo anti-inflammatory activities of aerial parts of Cassia species

AbstractCassia species are native to Southeast Asia and sub-Saharan Africa and are commonly used as food and in a broad variety of medicinal applications. Cassia species are widely used in India, but there are few reports in the literature of studies on its chemical compositions and biological properties. In this study, the antioxidant and anti-inflammatory activities of two plants of Cassia species namely Cassia siamea (Lam.) and Cassia javanica (Linn.) were evaluated and the total phenolic compounds and flavonoid contents were determined.The antioxidant activity of the extracts was measured using scavenging of 2,2′-Diphenyl-1-picrylhydrazyl hydrate (DPPH), bleaching of β-carotene and % inhibition of H2O2. The anti-inflammatory activity was evaluated using carrageenan induced paw edema method on Wistar albino rats. The etahnolic extracts of aerial parts of C. siamea and C. javanica were evaluated for in vivo anti-inflammatory activity against the animal model of female Wistar albino rats. Ethanol extracts showed significant and dose-dependent anti-inflammatory effects. The contents of flavonoids and total phenolic compounds could be correlated with the antioxidant and anti-inflammatory activities observed for C. siamea and C. javanica. Our findings suggest that aerial parts of C. siamea and C. javanica contain potential antioxidant and anti-inflammatory compounds, which could be tested as drug candidates against oxidative and inflammation-related pathological processes in medicinal chemistry studies

Influence of clinical history on MRI interpretation of optic neuropathy

Background and purpose: Clinical history is known to influence interpretation of a wide range of radiologic examinations. We sought to evaluate the influence of the clinical history on MRI interpretation of optic neuropathy. Materials and methods: 107 consecutive orbital MRI scans were retrospectively reviewed by three neuroradiologists. The readers independently evaluated the coronal STIR sequence for optic nerve hyperintensity and/or atrophy (yes/no) and the coronal post-contrast T1WI for optic nerve enhancement (yes/no). Readers initially evaluated the cases blinded to the clinical history. Following a two week washout period, readers again evaluated the cases with the clinical history provided. Inter-reader and reader-clinical radiologist agreement was assessed using Cohen's simple kappa coefficient. Results: Intra-reader agreement, without and with provision of clinical history, was 0.564–0.716 on STIR and 0.270–0.495 on post-contrast T1WI. Inter-reader agreement was overall fair-moderate. On post-contrast T1WI, inter-reader agreement was significantly higher when the clinical history was provided (p = 0.001). Reader-clinical radiologist agreement improved with provision of the clinical history to the readers on both the STIR and post-contrast T1WI sequences. Conclusions: In the MRI assessment of optic neuropathy, only modest levels of inter-reader agreement were achieved, even after provision of clinical history. Provision of clinical history improved inter-reader agreement, especially when assessing for optic nerve enhancement. These findings confirm the subjective nature of orbital MRI interpretation in cases of optic neuropathy, and point to the importance of an accurate clinical history. Of note, the accuracy of orbital MRI in the context of optic neuropathy was not assessed, and would require further investigation

MR imaging phenotype correlates with extent of genome-wide copy number abundance in IDH mutant gliomas

PURPOSE: There is variability in survival within IDH mutant gliomas determined by chromosomal events. Copy number variation (CNV) abundance associated with survival in low-grade and IDH mutant astrocytoma has been reported. Our purpose was to correlate the extent of genome-wide CNV abundance in IDH mutant astrocytomas with MRI features. METHODS: Presurgical MRI and CNV plots derived from Illumina 850k EPIC DNA methylation arrays of 18 cases of WHO grade II-IV IDH mutant astrocytomas were reviewed. IDH mutant astrocytomas were divided into CNV stable group (CNV-S) with ≤ 3 chromosomal gains or losses and lack of focal gene amplifications and CNV unstable group (CNV-U) with \u3e 3 large chromosomal gains/losses and/or focal amplifications. The associations between MR features, relative cerebral blood volume (rCBV), CNV abundance, and time to progression were assessed. Tumor rCBV estimates were obtained using DSC T2* perfusion analysis. RESULTS: There were nine (50%) CNV-S and nine (50%) CNV-U IDH mutant astrocytomas. CNV-U tumors showed larger mean tumor size (P = 0.004) and maximum diameter on FLAIR (P = 0.004) and also demonstrated significantly higher median rCBV than CNV-S tumors (2.62 vs 0.78, P = 0.019). CNV-U tumors tended to have shorter time to progression although without statistical significance (P = 0.393). CONCLUSIONS: Larger size/diameter and higher rCBVs were seen associated CNV-U astrocytomas, suggesting a correlation of aggressive imaging phenotype with unstable and aggressive genotype in IDH mutant astrocytomas

Correlation between IDH mutation status, patient survival, and blood volume estimates in diffuse gliomas: A TCGA/TCIA project

PURPOSE: Prior studies have shown correlation between relative cerebral blood volume (rCBV) and patient survival as well as with tumor genomics. The purpose of this study was to determine whether rCBV values correlate with isocitrate dehydrogenase (IDH) mutation status and patient overall survival in diffuse gliomas. MATERIALS & METHODS: 96 treatment naive gliomas (62 patients from TCGA/TCIA dataset and 34 patients from our institute) (WHO grades II=26, grade III=30, grade IV=40) with DSC T2∗ perfusion data were included. IDH mutation status (IDHmut-codel, IDHmutnon- codel, and IDHwt) and survival data were assayed by the TCGA, and pre-surgical imaging collected by the TCIA (The Cancer Imaging Archive). rCBV was obtained from 4 regions of interests within the highest perfusion areas including enhancing and non-enhancing segments of each tumor, utilizing Olea Sphere software (Olea Medical, LaCiotat). Mean differences in rCBV are compared by ANOVA and t-test. Associations with overall survival, defined as the time from diagnosis to death or last follow-up, are estimated by Cox regression models and Kaplan-Meier methods. RESULTS: IDHwt gliomas (n=40) demonstrated higher rCBV (rCBV=6.36 ± 3.05) values than IDHmut gliomas (n=46) (rCBV=2.07 ± 1.83; t-test p\u3c0.0001). Gliomas with rCBV \u3c2.0 showed better survival (n=14, median 117.3 months) than gliomas with rCBV \u3e2.0 (n=48, median 15.4 months; log-rank (p\u3c0.0001). Among the IDH mutated tumors, the group with rCBV values \u3e2.0 (n=8) showed poorer survival (36.5% surviving at 3 years) than IDHmut gliomas (n=11) with lower rCBV (87.5% surviving at 3 years; log-rank p=0.0299). CONCLUSION: IDHwt gliomas have higher rCBV than IDHmut gliomas irrespective of the glioma grade. Higher CBV measurements are associated with poor survival in the entire cohort, and rCBV higher than 2.0 within IDHmut gliomas may identify a subset of IDHmut patients with decreased survival

Fluid attenuation in non-contrast-enhancing tumor (nCET): an MRI Marker for Isocitrate Dehydrogenase (IDH) mutation in Glioblastoma

The WHO 2016 update classifies glioblastomas (WHO grade IV) according to isocitrate dehydrogenase (IDH) gene mutation status. We aimed to determine MRI-based metrics for predicting IDH mutation in glioblastoma. This retrospective study included glioblastoma cases (n = 199) with known IDH mutation status and pre-operative MRI (T1WI, T2WI, FLAIR, contrast-enhanced T1W1 at minimum). Two neuroradiologists determined the following MRI metrics: (1) primary lobe of involvement (frontal or non-frontal); (2) presence/absence of contrast-enhancement; (3) presence/absence of necrosis; (4) presence/absence of fluid attenuation in the non-contrast-enhancing tumor (nCET); (5) maximum width of peritumoral edema (cm); (6) presence/absence of multifocal disease. Inter-reader agreement was determined. After resolving discordant measurements, multivariate association between consensus MRI metrics/patient age and IDH mutation status was determined. Among 199 glioblastomas, 16 were IDH-mutant. Inter-reader agreement was calculated for contrast-enhancement (ĸ = 0.49 [- 0.11-1.00]), necrosis (ĸ = 0.55 [0.34-0.76]), fluid attenuation in nCET (ĸ = 0.83 [0.68-0.99]), multifocal disease (ĸ = 0.55 [0.39-0.70]), and primary lobe (ĸ = 0.85 [0.80-0.91]). Mean difference for peritumoral edema width between readers was 0.3 cm [0.2-0.5], p < 0.001. Multivariate analysis uncovered significant associations between IDH-mutation and fluid attenuation in nCET (OR 82.9 [19.22, ∞], p < 0.001), younger age (OR 0.93 [0.86, 0.98], p = 0.009), frontal lobe location (OR 11.08 [1.14, 352.97], p = 0.037), and less peritumoral edema (OR 0.15 [0, 0.65], p = 0.044). Conventional MRI metrics and patient age predict IDH-mutation status in glioblastoma. Among MRI markers, fluid attenuation in nCET represents a novel marker with high inter-reader agreement that is strongly associated with Glioblastoma, IDH-mutant

The landscape of brain tumor mimics in neuro-oncology practice.

BACKGROUND AND OBJECTIVE: Differentiating neoplastic and non-neoplastic brain lesions is essential to make management recommendations and convey prognosis, but the distinction between brain tumors and their mimics in practice may prove challenging. The aim of this study is to provide the incidence of brain tumor mimics in the neuro-oncology setting and describe this patient subset. METHODS: Retrospective study of adult patients referred to the Division of Neuro-oncology for a presumed diagnosis of brain tumor from January 1, 2005 through December 31, 2017, who later satisfied the diagnosis of a non-neoplastic entity based on neuroimaging, clinical course, and/or histopathology evaluation. We classified tumor mimic entities according to clinical, radiologic, and laboratory characteristics that correlated with the diagnosis. RESULTS: The incidence of brain tumor mimics was 3.4% (132/3897). The etiologies of the non-neoplastic entities were vascular (35%), inflammatory non-demyelinating (26%), demyelinating (15%), cysts (10%), infectious (9%), and miscellaneous (5%). In our study, 38% of patients underwent biopsy to determine diagnosis, but in 26%, the biopsy was inconclusive. DISCUSSION: Brain tumor mimics represent a small but important subset of the neuro-oncology referrals. Vascular, inflammatory, and demyelinating etiologies represent two-thirds of cases. Recognizing the clinical, radiologic and laboratory characteristics of such entities may improve resource utilization and prevent unnecessary as well as potentially harmful diagnostic and therapeutic interventions