Ulcerative colitis (UC) is an idiopathic, chronic and relapsing colonic inflammatory disease. Despite the involvement of diverse intricate mechanisms, COX mediated inflammatory pathway is crucial in ...the pathophysiology of colitis. Thus, COX inhibition is imperative for managing colitis-associated inflammation. However, the use of COX inhibitory classical non-steroidal anti-inflammatory drugs (NSAIDs) for inflammation resolution has been linked to sudden increased flare-ups. Therefore, considering the anti-inflammatory and pro-resolution effects of antioxidant and essential trace element Selenium (Se), a Seleno-derivative of Celecoxib called Selenocoxib-3 was characterized and evaluated for its favourable pharmacokinetics, safety margins and anti-inflammatory therapeutic potential in DSS-induced experimental colitis. The serum pharmacokinetic profiling elimination rate constant (K) and clearance (Cl) and toxicity profiling suggested enhanced efficacy, therapeutic potential and lesser toxicity of Selenocoxib-3 as compared to its parent NSAID Celecoxib. In vivo studies demonstrated that Selenocoxib-3 efficiently resolves the gross morphological signs of DSS-induced colitis such as diarrhoea, bloody stools, weight loss and colon shortening. Further, intestinal damage evaluated by H & E staining and MPO activity suggested of histopathological disruptions, such as neutrophil infiltration, mucodepletion and cryptitis, by Selenocoxib-3. The expression profiles of COX-1/2 demonstrated mitigation of pro-inflammatory mediators thereby promoting anti-inflammatory efficacy of Selenocoxib-3 when compared with Celecoxib. The current study suggests translational applicability of Se-containing novel class of COX inhibitors for efficiently managing inflammatory disorders such as UC.
Modern-day epidemiologic data on the risk and shifting landscape of occurrence of cardiovascular events in cannabis users remain inadequate and rather conflicting, especially amongst the young adult ...population. Furthermore, the problem of polysubstance use among youth is challenging for healthcare professionals and policy-makers. Previous studies report higher risk of concomitant use of tobacco, alcohol, cocaine, and amphetamine in young cannabis users. However, most of these studies did not eliminate the confounding effects of concomitant other substance abuse while assessing the incidence and outcome of cardiovascular events in cannabis users.
Using weighted discharge records from the National Inpatient Sample (NIS) from 2007-2014, we assessed the national trends in hospitalizations for major cardiovascular events including acute myocardial infarction (AMI), arrhythmia, stroke, and venous thromboembolic events (VTE) among young cannabis users (18-39 years), excluding cases with concomitant substance abuse with alcohol, tobacco, cocaine, and amphetamine.
Of 52.3 million hospitalizations without other substance abuse, 0.7 million (1.3%) young adults were current/former cannabis users. Among young adults without concomitant substance abuse, the frequency of admissions for AMI (0.23% vs. 0.14%), arrhythmia (4.02% vs. 2.84%), and stroke (0.33% vs. 0.26%) was higher in cannabis users as compared to non-users (
< 0.001). However, the frequency of admissions for VTE (0.53% vs. 0.84%) was lower among cannabis users as compared non-users. Between 2007 and 2014, we observed 50%, 79%, 300%, and 75% relative increases in hospitalizations for AMI, arrhythmias, stroke, and VTE, respectively, among young cannabis users as compared to non-users, showing relatively inferior or no ascent in the rates (
< 0.001).
The rising trends in hospitalizations for acute cardiovascular events among young cannabis users without concomitant other substance abuse call for future prospective well-designed studies to assess cannabis-related short-and long-term cardiovascular implications while simultaneously developing focused interventions towards raising awareness among the young population regarding the potential deleterious effects of cannabis use.
In this study, Soda Lime Glass (SLG) and Stainless Steel (SS316L) substrata coated with Titanium oxide (TiOx) were tested for their efficacy in the laboratory microcosms and in field against micro- ...and macrofouling. Laboratory microcosm studies were conducted for five days using natural biofilms, single-species diatom (
sp.), and bacterial biofilms, whereas field observations were conducted for 30 days. The TiOx-coating induced change in the mean contact angle of the substratum and rendered SS316L more hydrophilic and SLG hydrophobic, which influenced the
sp. biofilm, and bacterial community structure of the biofilm. Overall, the TiOx-coated SS316L showed minimal microfouling, whereas non-coated SLG exhibited greater efficacy in deterring/preventing macrofouling organisms. Moreover, the reduction in macrofouling could be attributed to high abundance of Actinobacteria. Unraveling the mechanism of action needs future studies emphasizing biochemical processes and pathways.
In this study, Soda Lime Glass (SLG) and Stainless Steel (SS316L) substrata coated with Titanium oxide (TiOx) were tested for their efficacy in the laboratory microcosms and in field against micro- ...and macrofouling. Laboratory microcosm studies were conducted for five days using natural biofilms, single-species diatom (Navicula sp.), and bacterial biofilms, whereas field observations were conducted for 30 days. The TiOx-coating induced change in the mean contact angle of the substratum and rendered SS316L more hydrophilic and SLG hydrophobic, which influenced the Navicula sp. biofilm, and bacterial community structure of the biofilm. Overall, the TiOx-coated SS316L showed minimal microfouling, whereas non-coated SLG exhibited greater efficacy in deterring/preventing macrofouling organisms. Moreover, the reduction in macrofouling could be attributed to high abundance of Actinobacteria. Unraveling the mechanism of action needs future studies emphasizing biochemical processes and pathways.
Colorectal cancer (CRC), one of the leading causes of cancer related deaths worldwide is an outcome of both genetic and epigenetic changes in colonic epithelia leading to the formation of ...adenocarcinomas. Histone deacetylases (HDACs) through their key roles in regulation of cellular processes, are associated with the development and progression of cancer. Thus, in this regard, HDAC inhibitors have become promising therapeutic targets. These inhibitors induce cell cycle arrest, differentiation, autophagy and apoptotic cell death by inhibiting multiple signaling pathways. Suberoylanilide hydroxamic acid (SAHA), a second generation HDAC inhibitor has been approved by US‐FDA for the treatment of cutaneous T‐Cell lymphoma, however its anti‐cancerous effects against colorectal cancer is still unknown. Also, essential dietary element Selenium (Se) has been found to have an important role in CRC prevention via modulating redox sensitive molecular pathways. Therefore, the present study aimed to explore the anti‐tumorigenic role of SAHA and its Se analog namely, SelSA‐1 (25 mg/kg) in DMH induced experimental colon cancer model in Balb/c mice. The toxicity studies and pharmacokinetic characterization of SelSA‐1 exhibited better tolerance, absorption and elimination rate than SAHA. Further, histological and morphological analyses showed that SelSA‐1 has better/comparable chemotherapeutic potential compared to SAHA at lower doses than SAHA. Further, the positive redox modulatory effects of SelSA‐1 and SAHA in CRC associated oxidative stress were also noteworthy, projecting the plausible use of similar analogs as compounds of choice for cancer treatments based on their safety profiles, efficacy and specificity in terms of chemotherapeutic potential.
Support or Funding Information
Department of Science and Technology (DST), Govt. of India, New Delhi; University Grant Commission (UGC), Govt. of India, New Delhi
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Objectives: Epilepsy is one of the common neurological conditions worldwide.
Methods: The observational, continuous, prospective, and single-center study was carried out to evaluate prescribing ...pattern of antiepileptic drugs (AEDs) in pediatric patients at a tertiary care teaching hospital of Gujarat for a total duration of 18 months. Patients were followed up monthly for the period of 3 months to evaluate seizure freedom, breakthrough seizure, and change in the AEDs, add-on therapy, treatment adherence and ADRs. Rationality was assessed for selection of drug and selection of the right dose according to recent guidelines.
Results: Majority of patients in the age group of 7–9 years with mean age of 6.83 ± 3.09 years. Male-to-female ratio was 1.3:1. Total 73 AEDs were prescribed to pediatric epilepsy patients after diagnosis. Thirty-seven (69.80%) patients were prescribed AED on visit as monotherapy and 16 (30.20%) patients were prescribed polytherapy. Sodium valproate (77.36%) was most commonly prescribed AED followed by levetiracetam and carbamazepine. Most of AEDs were prescribed according to NICE guideline and by generic name.
Conclusion: Conventional AEDs are still used as first line of treatment for pediatric epilepsy patients, although newer AEDs also frequently prescribed as add on or primary drug. Low birth weight, NICU admission, and non-compliance to treatment are associated with breakthrough seizures.
Background: Frozen section (FS) diagnosis is one of the promising applications of digital pathology (DP). However, the implementation of an appropriate and economically viable DP solution for FS in ...routine practice is challenging. The objective of this study was to establish the non-inferiority of whole-slide imaging (WSI) versus optical microscopy (OM) for FS diagnosis using a low cost and portable DP system. Materials and Methods: A validation study to investigate the technical performance and diagnostic accuracy of WSI versus OM for FS diagnosis was performed using 60 FS cases120 slides i.e, 60 hematoxylin and eosin (H & E) and 60 toluidine blue (TOLB). The diagnostic concordance, inter- and intra-observer agreement for FS diagnosis by WSI versus OM were recorded. Results: The first time successful scanning rate was 89.1% (107/120). Mean scanning time per slide for H and E and TOLB slide was 1:47 min (range; 0:22–3: 21 min) and 1:46 min (range; 0:21–3: 20 min), respectively. Mean storage space per slide for H and E and TOLB slide was 0.83 GB (range: 0.12–1.73 GB) and 0.71 GB (range: 0.11–1.66 GB), respectively. Considering major discrepancies, the overall diagnostic concordance for OM and WSI, when compared with the reference standard, was 95.42% and 95.83%, respectively. There was almost perfect intra as well as inter-observer agreement (k ≥ 0.8) among 4 pathologists between WSI and OM for FS diagnosis. Mean turnaround time (TAT) of 14:58 min was observed using WSI for FS diagnosis, which was within the College of American Pathologists recommended range for FS reporting. The image quality was average to best quality in most of the cases. Conclusion: WSI was noninferior to OM for FS diagnosis across various specimen types. This portable WSI system can be safely adopted for routine FS diagnosis and provides an economically viable alternative to high-end scanners.
Recent reports suggest a link between increased cannabis (marijuana) use and stress-cardiomyopathy (Takotsubo Syndrome, TTS) and related complications. Amidst recent trends in cannabis legalization ...and a paucity of data, it remains essential to evaluate the prevalence, trends and outcomes of TTS in cannabis users on a large-scale.
We studied prevalence and trends in TTS among adult cannabis users vs. non-users using the National Inpatient Sample (2007–2014). Baseline characteristics, comorbidities, and in-hospital outcomes of TTS were compared between cannabis users vs. non-users. Weighted logistic regression was performed adjusting for confounders to estimate the inpatient outcomes of TTS with vs. without cannabis use.
The overall prevalence of TTS in cannabis users (47/100,000) was lower as compared to non-users (62/100,000). Rising trends in TTS among cannabis users (<11 to 82, ~8-fold) were more pronounced as compared to non-users (19 to 108, ~6 fold) per 100,000 hospitalizations from 2007 to 2014 (ptrend<0.001). Of all inpatient encounters for TTS (n=156,506), 1565 (0.1%) reported cannabis use. Polysubstance use including alcohol (4.1% vs. 24.4%), cocaine (0.4% vs. 8.5%), amphetamine (0.2% vs. 8.0%), and smoking (31.2% vs. 64.8%) was significantly higher in TTS-cannabis cohort. Although cardiovascular comorbidities were lower in TTS-cannabis cohort, the adjusted odds of all-cause mortality (aOR1.50, p<.05) were 50% higher in cannabis users compared to non-users without statistically significant difference in cardiac complications.
Cannabis users showed lower prevalence but a more pronounced rising trend of TTS and subsequent risk of in-hospital mortality compared to non-users.
•Overall prevalence of TTS was lower in cannabis users (47/100,000) vs. non-users (62/100,000).•Increasing trends of TTS in cannabis users (8-fold) vs. non-users (6-fold) from 2007 to 2014.•1565 (0.1%) had reported using cannabis of all TTS-related admissions (n=156,506).•Cardiovascular comorbidities were lower in the TTS-cannabis cohort.•The odds of all-cause mortality were 50% higher in cannabis users compared to non-users.
Abstract
Glioblastoma Multiforme (GBM) is a deadly brain cancer and represents the most common central nervous system (CNS) tumors in adults. Although GBM does not metastasize, its aggressive growth ...and invasive nature are responsible for poor patient prognosis. The current standard therapy for newly diagnosed GBM patients involves surgical resection, followed by radiation and chemotherapy with Temozolomide. However, its rapid rate of infiltration into normal brain tissue ultimately renders the therapy ineffective. Epidemiological studies on dietary isoflavones (e.g., genistein, biochanin A) have shown their anti-cancer potential in different cancers. Though primarily used in management of hyperlipidemia and cardiovascular diseases, statins are known to exert anti-proliferative effects. We therefore hypothesized that a combination treatment of biochanin A & statins (e.g., Atorvastatin, Lovastatin, Simvastatin, Fluvastatin and Pravastatin) exerts enhanced anticancer effects on GBM U-87 MG and T98 G cells. Our studies showed statins induced differential effects on viability of GBM cells in combination with biochanin A, with U-87 MG being more susceptible than T98 G cells. The combination treatment of biochanin A and atorvastatin also decreased invasion in U-87 MG cells. Additionally, cell metabolism studies using seahorse XFp analyzer showed a switch in their metabolic phenotype with an increase in mitochondrial respiration and a decrease in glycolytic activity with the combination treatment. We also performed metabolite extraction on GBM cells for a global unbiased profiling of metabolites using a single extraction procedure and dual separation analysis by LCMS. A differential analysis of alternative GBM treatment indicated statistically significant changes in carbohydrate and amino acid metabolism as well as alterations to various degradation pathway intermediates. Together, the combination treatment-induced effects on GBM cell lines are differential and our results may have potential implications in developing combination therapies with biochanin A in vivo and support the design of new and better therapies for the treatment of a lethal cancer like GBM.
Citation Format: Vilas S. Desai, Eric Buchhalter, Max Cabanzo, Arushi Tiwari, Gagan Kaushal, James C. Lai, Alok Bhushan. Differential effects of combination treatment of biochanin A and statins on glioblastoma multiforme cell proliferation and cell metabolism abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 243.
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