Risk of myocardial infarction, heart failure, and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan in patients.

There is a lack of studies comparing the risk of cardio-cerebrovascular disease between angiotensin receptor blockers (ARBs) of different half-lives. We aimed to compare the risks of myocardial infarction (MI), heart failure (HF), and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan with different half-lives in a national claim-based retrospective cohort of patients aged ≥ 40 years with hypertension. To establish a cohort exposed to valsartan, losartan, irbesartan, or telmisartan, we performed propensity score (PS) matching and used an as-treated approach to evaluate exposure. The Cox regression model was employed to calculate hazard ratios, which were based on the incidence rate for each newly occurring event of MI, heart failure, or cerebrovascular disease. These hazard ratios were calculated to compare the risk of MI, heart failure, and cerebrovascular disease associated with valsartan, losartan, and irbesartan in comparison to telmisartan. A PS-matched cohort of 148,229 patients was established for each of valsartan, losartan, irbesartan, or telmisartan. The matched cohort analysis showed that the adjusted hazard ratio (aHRs, 95% confidence interval) for MI was higher for valsartan use (1.39, 1.33-1.45) and losartan use (1.10, 1.05-1.15) but lower for irbesartan use (0.90, 0.86-0.94) compared with the reference (telmisartan). The aHRs for HF were not different among these ARBs (angiotensin receptor blockers). The aHR for cerebrovascular disease was lower for valsartan use (0.85, 0.83-0.87) and losartan use (0.80, 0.78-0.82) but higher for irbesartan use (1.11, 1.09-1.13) compared with the reference. We found differences in the risk of MI and cerebrovascular disease with the use of different ARBs compared to telmisartan use. Valsartan, and losartan with a short half-life, which showed a higher risk of MI, had a lower risk of cerebrovascular disease. Conversely, irbesartan with a long half-life, which showed a lower risk of MI, had a higher risk of cerebrovascular disease.

Potentiation of natural killer (NK) cell activity by methanol extract of cultured cambial meristematic cells of wild ginseng and its mechanism.

AIMS: As an alternative strategy to obtain large amounts of ginseng extract with high yield of ginsenosides, we have utilized culture of cambial meristematic cells (CMCs) from wild ginseng. The anti-tumor effects of methanol extract of ginseng CMCs (MEGC) and their action mechanisms were investigated. MAIN METHODS: Mice were intraperitoneally administered with MEGC, and we explored NK cell activity, suppression of in vivo growth of tumor cells and relevant molecule expression. KEY FINDINGS: MEGC significantly potentiated NK cell activity and suppressed in vivo growth of B16 melanoma cells. However, we observed no increase in NK cell number and unaltered expression of NK cell-activating (NKG2D) and inhibitory (Ly49, CD94/NKG2A) receptors as well as NK cell activation markers (CD25, CD69, CD119, and CD212) in MEGC-treated group compared to the controls. Instead, MEGC significantly enhanced IL-2 responsiveness in the early effector phase and the constitutive expression of granzyme B. SIGNIFICANCE: Our data indicate that culture of CMCs is an attractive alternative method for sustainable production of ginseng extracts and clinical use. In addition, we have unraveled a novel mechanism underlying the potentiation of NK cell activity and antitumor effect of ginseng extract, in which it upregulates the constitutive expression of cytotoxic mediator(s) and IL-2 responsiveness.

Suppression of lipopolysaccharide-induced expression of inflammatory indicators in RAW 264.7 macrophage cells by extract prepared from Ginkgo biloba cambial meristematic cells.

CONTEXT: Ginkgo biloba L. (Ginkgoaceae) leaves have been used as an herbal medicine that has a complex range of biological activities. However, when we consider that biological activity of plant extracts is highly variable according to the source, location, and harvest season, technology to obtain the natural products with homogeneity is extremely important. OBJECTIVE: We established the technology to obtain the cambial meristematic cells (CMCs) of Ginkgo biloba, which were expanded in vitro with homogeneity through a suspension culture and then determined the anti-inflammatory activity of fractionated samples prepared from the ethanol extract of CMCs. MATERIALS AND METHODS: We determined the anti-inflammatory activity of samples using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Especially, influence of sample treatment on the expression of various indicators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein (MAP) kinases, transcription factor, and cytokines, involved in inflammatory activity was assessed. RESULTS: A fractionated sample demonstrated 53.4% inhibition of LPS-induced NO production from the cells. Additionally, when fractionated samples were treated, iNOS and COX-2 expressions were almost completely suppressed. Fractionated samples also inhibited the phosphorylation of LPS-induced extracellular signal-regulated (ERK) and p38 MAP kinases more than 60%. IκB phosphorylation and subsequent nuclear factor (NF)-κB activation were also suppressed by fractionated samples. The expression of pro-inflammatory cytokines, IL-6 and tumor necrosis factor (TNF)-α, was significantly inhibited by the sample treatment. DISCUSSION AND CONCLUSION: Fractionated samples from the ethanol extract of Ginkgo biloba CMCs could potentially be the source of a powerful anti-inflammatory substance.