Clinical Management of Hypertriglyceridemia in the Prevention of Cardiovascular Disease and Pancreatitis.

PURPOSE OF REVIEW: Hypertriglyceridemia (HTG) is common and is a significant contributor to atherosclerosis and pancreatitis risk. Specific HTG treatments have had variable success in reducing atherosclerosis risk. Novel therapies for severe HTG treatment and pancreatitis risk reduction are likely to be available soon. These novel therapies are expected to have broader applications for more moderate HTG and atherosclerosis risk reduction as well. RECENT FINDINGS: NHANES 2012 data has confirmed a reduction in average triglyceride (TG) levels in the US population. Dietary modification and weight reduction when needed remain the core treatment elements for all individuals with HTG, while statin therapy is a foundational pharmacologic care for atherosclerotic cardiovascular disease (ASCVD) event risk reduction. In addition, the REDUCE-IT study provides evidence for additional benefit from the use of high-dose icosapent ethyl (IPE) on top of background medical therapy in adults with moderate HTG and ASCVD or type 2 diabetes mellitus (T2D) and additional ASCVD risk factors. However, treatment with eicosapentaenoic acid (EPA) combined with docosahexanoic acid (DHA) did not reduce ASCVD in a similar population studied in the STRENGTH trial. Furthermore, novel therapeutics targeting PPAR-ɑ, as well as ApoC-III and AngPTL3, effectively lower TG levels in individuals with moderate and severe HTG, respectively. These treatments may have applicability for reducing risk from ASCVD among individuals with chylomicronemia; in addition, ApoC-III and AngPTL3 treatments may have a role in treating individuals with the rare monogenic familial chylomicronemia syndrome (FCS) at risk for acute pancreatitis (AP). Residual ASCVD risk in individuals treated with contemporary care may be due in part to non-LDL lipid abnormalities including HTG. The findings from REDUCE-IT, but not STRENGTH, confirm that consumption of high-dose EPA may reduce ASCVD risk, while combination therapy of EPA plus DHA does not reduce ASCVD in a similar population. TG lowering likely reduces ASCVD risk in individuals with HTG, but ASCVD risk is multifactorial; the added benefit of IPE to contemporary preventive therapy is the consequence of differential non-TG biologic properties between the two fatty acids. Acute pancreatitis is more difficult to study prospectively since it is less common; however, TG lowering is likely critical for the care of at-risk individuals. Additional benefit from novel therapy that has an impact on this otherwise refractory condition is anticipated.

Recent Advances in Computed Tomography and MR Imaging.

Numerous advanced MR imaging and computed tomographic techniques have been developed and implemented in clinical practice over the past several years resulting in increased diagnostic accuracy and improved patient care. In this article, the authors highlight recent and emerging imaging techniques in functional and structural MR imaging, perfusion and vascular imaging, standardization of imaging practices, and selected applications of artificial intelligence in clinical practice.

Marijuana Use Among Patients With Glaucoma in a City With Legalized Medical Marijuana Use.

IMPORTANCE: Previous research has shown several limitations associated with the use of marijuana as a treatment for glaucoma. However, little is known regarding patients' perceptions toward using marijuana for glaucoma and their intentions to use this therapeutic alternative. OBJECTIVE: To identify factors among patients with glaucoma that could lead to intentions to use marijuana for treatment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study of 204 patients with glaucoma or suspected to have glaucoma was conducted at an academic-based glaucoma clinic in Washington, DC, between February 1 and July 31, 2013. Patients completed a self-administered survey assessing demographics, perceived severity of glaucoma, prior knowledge about marijuana use in glaucoma, past marijuana use, perceptions toward marijuana use (legality, systemic adverse effects, safety and effectiveness, and false beliefs), satisfaction with current glaucoma management, relevance of treatment costs, and intentions to use marijuana for glaucoma. Medical records were reviewed for disease severity. Data analysis was conducted from September 1, 2013, to September 30, 2015. MAIN OUTCOMES AND MEASURES: The main outcome was patients' intentions to use marijuana for glaucoma. Multiple linear regression analysis was conducted to identify factors associated with patients' intentions to use marijuana for glaucoma. RESULTS: Of the 334 patients who were invited to participate in the study, 204 (61.1%) completed the survey. About half the participants were women (104 [51.0]%), and 82 (40.2%) were white. Regression analysis of 204 respondents indicated that perceptions of legality of marijuana use (ß, 0.378; 95% CI, 0.205 to 0.444; P < .001), false beliefs regarding marijuana (ß, 0.323; 95% CI, 0.236 to 0.504; P < .001), satisfaction with current glaucoma care (ß, -0.222; 95% CI, -0.362 to -0.128; P < .001), and relevance of marijuana and glaucoma treatment costs (ß, 0.127; 95% CI, 0.008 to 0.210; P = .04) were significantly associated with intentions to use marijuana for glaucoma treatment after controlling for demographic variables, disease severity, and previous marijuana use. CONCLUSIONS AND RELEVANCE: This study's findings suggest a need for more education on this topic for ophthalmologists to be able to protect patients with glaucoma against the increased acceptability among the public of using marijuana based on false perceptions of its therapeutic value in glaucoma therapy. Considering the strong influence of perceptions of the legality of marijuana use on intentions to use this substance as a treatment for glaucoma, patient education might be particularly relevant in states in which marijuana use for glaucoma is legal, as in the case of the current study's setting.

Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome.

Curcumin (diferuloylmethane) is the major active component of turmeric and is being actively investigated for its anti-cancer properties. To better understand the biological mechanisms of the chemopreventive potential of curcumin in prostate cancer, we have evaluated curcumin regulated transcriptome in prostate cancer cells. Hierarchical clustering methods and functional classification of the Curcumin-Gene Expression Response (Cu-GER) showed temporal co-regulation of genes involved in oxidative stress response and growth signaling pathways. Interestingly, C4-2B, androgen independent metastatic prostate cancer cells exhibited attenuated Cu-GER response in comparison to parental androgen dependent and less aggressive LNCaP cells. Androgen Receptor (AR) regulated genes which play critical roles in normal growth and differentiation of the prostate gland, as well as in prostate cancer, were also a part of the Cu-GER. Of note, curcumin downregulated transcript encoded by the potentially causal TMPRSS2-ERG gene fusion, a common oncogenic alteration noted in 50-70% of prostate cancer patients. Further more, expression of EGFR and ERBB2 receptor were found to be downregulated in curcumin treated LNCaP and C4-2B cells. This report for the first time establishes novel features of Cu-GER in prostate cancer cells of varying tumorigenic phenotypes and provides potentially novel read-outs for assessing effectiveness of curcumin in prostate cancer and likely in other cancers. Importantly, new gene-networks identified here further delineate molecular mechanism(s) of action of curcumin in prostate cancer cells.

Green tea polyphenol and epigallocatechin gallate induce apoptosis and inhibit invasion in human breast cancer cells.

Currently, there is no effective therapy for estrogen independent breast cancer. MDA-MB-231 is an estrogen receptor negative highly invasive human breast cancer cell line and has been used as a relevant model system to evaluate drugs with chemopreventive potential against highly invasive breast cancer phenotypes. Epidemiological studies though inconclusive have shown that consumption of Green Tea Polyphenols (GTP) reduces the incidence and progression of breast cancer. Green tea is an important source of antioxidants that may be useful for chemoprevention of cancer. Recently published preclinical study from our lab suggested that GTP and EGCG treatment inhibit proliferation and induce apoptosis of MDA-MB-231. In this study, we have evaluated apoptotic and anti-invasive activity of green tea polyphenols (GTP) and its principal constituent Epigallocatechin gallate (EGCG) in MDA-MB-231 human breast cancer cell line. In in vitro human breast cancer model, EGCG and GTP induced apoptosis and significantly decreased invasion of breast cancer cells. Western blotting of MDA-MB-231 cell lysates from EGCG and GTP treated and untreated control revealed an increase in bax, reduction in bcl2 and PARP cleavage. Quantitative fluorescence labeling resulted in a 24-28% reduction in invasion through matrigel by EGCG and 15-23% reduction by GTP in a dose dependent manner. Focussed microarray analysis and reverse transcriptase polymerase chain reaction and zymogram analysis revealed inhibition of MMP-9 expression by polyphenol treatment. Furthermore, AKT was found to be inhibited both at the RNA and protein level by polyphenol treatment. Moreover EGCG and GTP decreased AKT phosphorylation as found out by Western blotting for Phospho-AKT (Ser-473). beta-catenin level was found to be decreased both in cytoplasm and nucleus. For the first time we report the connection of beta-catenin and AKT modulation by GTP and EGCG as a possible mechanism for the induction of apoptosis in human breast cancer cells and also inhibition in their invasive capacity.