35 research outputs found
Elicitation of gymnemic acid production in cell suspension cultures of Gymnema sylvestre R.Br. through endophytic fungi
Asiatic Acid Inhibits Pro-Angiogenic Effects of VEGF and Human Gliomas in Endothelial Cell Culture Models
Malignant gliomas are one of the most devastating and incurable tumors. Sustained excessive angiogenesis by glioma cells is the major reason for their uncontrolled growth and resistance toward conventional therapies resulting in high mortality. Therefore, targeting angiogenesis should be a logical strategy to prevent or control glioma cell growth. Earlier studies have shown that Asiatic Acid (AsA), a pentacyclic triterpenoid, is effective against glioma and other cancer cells; however, its efficacy against angiogenesis remains unknown. In the present study, we examined the anti-angiogenic efficacy of AsA using human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC). Our results showed that AsA (5–20 µM) inhibits HUVEC growth and induces apoptotic cell death by activating caspases (3 and 9) and modulating the expression of apoptosis regulators Bad, survivin and pAkt-ser473. Further, AsA showed a dose-dependent inhibition of HUVEC migration, invasion and capillary tube formation, and disintegrated preformed capillary network. AsA also inhibited the VEGF-stimulated growth and capillary tube formation by HUVEC and HBMEC. Next, we analyzed the angiogenic potential of conditioned media collected from human glioma LN18 and U87-MG cells treated with either DMSO (control conditioned media, CCM) or AsA 20 µM (AsA20 conditioned media, AsA20CM). CCM from glioma cells significantly enhanced the capillary tube formation in both HUVEC and HBMEC, while capillary tube formation in both endothelial cell lines was greatly compromised in the presence of AsA20CM. Consistent with these results, VEGF expression was lesser in AsA20CM compared to CCM, and indeed AsA strongly inhibited VEGF level (both cellular and secreted) in glioma cells. AsA also showed dose-dependent anti-angiogenic efficacy in Matrigel plug assay, and inhibited the glioma cells potential to attract HUVEC/HBMEC. Overall, the present study clearly showed the strong anti-angiogenic potential of AsA and suggests its usefulness against malignant gliomas
Estimation of the burden of cardiovascular disease attributable to modifiable risk factors and cost-effectiveness analysis of preventative interventions to reduce this burden in Argentina
Background. Cardiovascular disease (CVD) is the primary cause of mortality and morbidity in Argentina representing 34.2% of deaths and 12.6% of potential years of life lost (PYLL). The aim of the study was to estimate the burden of acute coronary heart disease (CHD) and stroke and the cost-effectiveness of preventative population-based and clinical interventions. Methods. An epidemiological model was built incorporating prevalence and distribution of high blood pressure, high cholesterol, hyperglycemia, overweight and obesity, smoking, and physical inactivity, obtained from the Argentine Survey of Risk Factors dataset. Population Attributable Fraction (PAF) of each risk factor was estimated using relative risks from international sources. Total fatal and non-fatal events, PYLL and Disability Adjusted Life Years (DALY) were estimated. Costs of event were calculated from local utilization databases and expressed in international dollars (I 2,908 per DALY saved), mass media campaign to promote tobacco cessation amongst smokers (I 14,432 per DALY saved); and one intervention was not found to be cost-effective: tobacco cessation with bupropion (I$ 59,433 per DALY saved). Conclusions. Most of the interventions selected were cost-saving or very cost-effective. This study aims to inform policy makers on resource-allocation decisions to reduce the burden of CVD in Argentina.Centro de Endocrinología Experimental y Aplicada (CENEXA
Extracting residues from stone tools for optical analysis: towards an experiment-based protocol
The identification of residues is traditionally based
on the distinctive morphologies of the residue fragments by
means of light microscopy. Most residue fragments are amorphous,
in the sense that they lack distinguishing shapes or
easily visible structures under reflected light microscopy.
Amorphous residues can only be identified by using transmitted
light microscopy, which requires the extraction of residues
from the tool’s surface. Residues are usually extracted with a
pipette or an ultrasonic bath in combination with distilled water.
However, a number of researchers avoid residue extraction
because it is unclear whether current extraction techniques are
representative for the use-related residue that adheres to a
flaked stone tool. In this paper, we aim at resolving these
methodological uncertainties by critically evaluating current
extraction methodologies. Attention is focused on the variation
in residue types, their causes of deposition and their adhesion
and on the most successful technique for extracting a
range of residue types from the stone tool surface. Based on an
experimental reference sample in flint, we argue that a stepwise
extraction protocol is most successful in providing rep-
resentative residue extractions and in preventing damage, destruction
or loss of residue.Evohaf