Both P-gp and MRP2 mediate transport of Lopinavir, a protease inhibitor

Polarized epithelial non-human (canine) cell lines stably transfected with human or murine complementary DNA (cDNA) encoding for various efflux transporters (P-gp/MDR1, MRP1, MRP2, and Bcrp1) were used to study transepithelial transport of Lopinavir (LVR) and compare results with the MDCKII-Wild type cells. These transmembrane proteins cause multidrug resistance by decreasing the total intracellular accumulation of drugs. Lopinavir efflux was directional and was completely inhibited by MK-571, a selective MRP family inhibitor in the MDCKII-MRP2 cell line. Similarly, LVR efflux was also inhibited by P-gp inhibitors P-gp 4008 and GF120918 in the MDCKII-MDR1 cell line. The efflux ratios (Efflux rate/ Influx rate) of LVR in the absence of any efflux inhibitors in the MDCK-Wild type, MDCKII-MDR1, MDCKII-MRP1, MDCKII-MRP2 and MDCKII-Bcrp1 cell monolayers were 1.32, 4.91, 1.26 and 2.89 respectively. The MDCKII-MDR1 and MDCKII-MRP2 cells have significantly increased LVR efflux ratio relative to the parental cells due to the apically directed transport by MDR1 and MRP2 respectively. The efflux ratios in MRP2 and MDR1 transfected cell lines were close to unity in the presence of MK-571 and P-gp 4008 respectively; indicating that LVR efflux by MRP2 and P-gp was completely inhibited by their selective inhibitors. MDCKII-MRP1 cells did not exhibit a significant reduction in the LVR efflux relative to the parental cells, indicating that LVR is not a good substrate for MRP1. Transport studies across MDCKII-Bcrp1 cells indicated that LVR is not transported by Bcrp1 and is not a substrate for this efflux protein. In conclusion, this study presents direct evidence that LVR is effluxed by both P-gp and MRP2 which may contribute to its poor oral bioavailability and limited penetration into the CNS

Process intensification for the small footprint compact heat transfer device

Process intensification for the development of compact heat exchanger with small footprint is greatest challenge of the heat exchanger technology today. In the present study, a heat transfer device, coiled flow inverter (CFI) is revamped for the better heat transfer efficiency with a smaller footprint. The proposed small foot-print coiled flow inverter (SFCFI) is fabricated by bending of helical coil at 90° with equal arm lengths before and after the bend with variable curvature radius. In integration to the improved centrifugal force due to variable curvature, the SFCFI additionally offers a complete 90 flow inversion caused by each 90 bend, which results in higher radial mixing and heat transfer. The velocity and temperature flow fields depict the improved radial mixing under the laminar flow regime for the Dean number ranges from 8 to 1581. The performance of existing CFI of same heat transfer area (0.17 m2) was studied and compared with the novel SFCFI device. The results suggest, the proposed SFCFI device provides three-fold heat transfer enhancement as compared to the straight tube of same heat transfer area at Dean number 400. Additionally, heat transfer coefficient in SFCFI enhanced by 48 % as compared to helical coil. Furthermore, SFCFI provides 18 % higher value of Nusselt number as compared to the CFI. The reason for improved heat transfer may be the enhanced centrifugal force due to additional curvature effect provided in each arm of SFCFI in the plane of vortex formation. It was interesting to note that the proposed device provides 11 % lower pressure drop as compared to the CFI. The present study may aids to the development of a novel design of compact coiled and small footprint heat transfer device.Papers presented at the 13th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Portoroz, Slovenia on 17-19 July 2017 .International centre for heat and mass transfer.American society of thermal and fluids engineers

Removal of phenol in aqueous solution by adsorption onto green synthesized coinage nanoparticles beads

The adsorption of phenol from aqueous solution was carried out by using alginate-stabilized silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) beads as adsorbents. The resulting AgNPs and AuNPs were characterized by scanning electron microscope, UV-visible spectroscopy and Fourier transform infrared spectroscopy. Batch adsorption studies have shown that removal is dependent upon process parameters like initial concentration, contact time, pH and adsorbent dosage. The adsorption data obtained from batch studies at optimized conditions have been subjected to Freundlich and Langmuir isotherm studies. The pseudo-first-order and pseudo-second-order kinetic models were also applied to the experimental data. Phenol was effectively (90.0 +/- A 0.8 %) removed from the aqueous solution using alginate-stabilized AuNPs beads as the adsorption process. Desorption studies were made to elucidate recovery of the adsorbate and adsorbent for the economic competitiveness of the removal system. The alginate-stabilized AgNPs and AuNPs beads were found to be good adsorbents for adsorption of phenol from the aqueous solution

Физика сознания и ее модели как руководство к решению многих научных проблем, включая квантовую загадку

Consciousness model assuming TCP (thought-carrying particle) and TRP (thought retaining particle) may provide guidelines to solve many scientific problems including quantum enigma.Модель сознания, включающая TCP (переносящие мысль частицы) и TRP (удерживающие мысль частицы), может предоставить новые возможности для решения многих научных проблем, включая квантовую загадку

Octreotide-Targeted Lcn2 siRNA PEGylated Liposomes as a Treatment for Metastatic Breast Cancer

Lcn2 overexpression in metastatic breast cancer (MBC) can lead to cancer progression by inducing the epithelial-to-mesenchymal transition and enhancing tumor angiogenesis. In this study, we engineered a PEGylated liposomal system encapsulating lipocalin 2 (Lcn2) small interfering RNA (Lcn2 siRNA) for selective targeting MBC cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. The PEGylated liposomes were decorated with octreotide (OCT) peptide. OCT is an octapeptide analog of somatostatin growth hormone, having affinity for somatostatin receptors, overexpressed on breast cancer cells. Optimized OCT-targeted Lcn2 siRNA encapsulated PEGylated liposomes (OCT-Lcn2-Lipo) had a mean size of 152.00 nm, PDI, 0.13, zeta potential 4.10 mV and entrapment and loading efficiencies of 69.5% and 7.8%, respectively. In vitro uptake and intracellular distribution of OCT-Lcn2-Lipo in MCF-7 and MDA-MB-231 and MCF-12A cells demonstrated higher uptake for the OCT-targeted liposomes at 6 h by flow cytometry and confocal microscopy. OCT-Lcn2-lipo could achieve approximately 55−60% silencing of Lcn2 mRNA in MCF-7 and MDA-MB-231 cells. OCT-Lcn2-Lipo also demonstrated in vitro anti-angiogenic effects in MCF-7 and MDA-MB-231 cells by reducing VEGF-A and reducing the endothelial cells (HUVEC) migration levels. This approach may be useful in inhibiting angiogenesis in MBC

Effect of vitamin C on adrenomedullary hormones in gonadectomised juvenile pigeons

Administration of vitamin C to juvenile castrated pigeons leads to a fall in the adrenal epinephrine level, but no significant change in the norepinephrine level is noted. Since the role of vitamin C in converting dopamine to norepinephrine is anticipated, it has been surmised that the bursa of Fabricius (thymolymphatic organ) might be responsible for the inability of these young birds to respond to vitamin C treatment

Hyaluronic Acid-Targeted Stimuli-Sensitive Nanomicelles Co-Encapsulating Paclitaxel and Ritonavir to Overcome Multi-Drug Resistance in Metastatic Breast Cancer and Triple-Negative Breast Cancer Cells

Active targeting and overcoming multi-drug resistance (MDR) can be some of the important attributes of targeted therapy for metastatic breast cancer (MBC) and triple-negative breast cancer (TNBC) treatment. In this study, we constructed a hyaluronic acid (HA)-decorated mixed nanomicelles-encapsulating chemotherapeutic agent paclitaxel (PTX) and P-glycoprotein inhibitor ritonavir (RTV). HA was conjugated to poly (lactide) co-(glycolide) (PLGA) polymer by disulfide bonds (HA-ss-PLGA). HA is a natural ligand for CD44 receptors overexpressed in breast cancer cells. Disulfide bonds undergo rapid reduction in the presence of glutathione, present in breast cancer cells. The addition of RTV can inhibit the P-gp and CYP3A4-mediated metabolism of PTX, thus aiding in reversing MDR and sensitizing the cells toward PTX. An in vitro uptake and cytotoxicity study in MBC MCF-7 and TNBC MDA-MB-231 cell lines demonstrated the effective uptake of the nanomicelles and drug PTX compared to non-neoplastic breast epithelium MCF-12A cells. Interestingly, in vitro potency determination showed a reduction in mitochondrial membrane potential and reactive oxygen species in breast cancer cell lines, indicating effective apoptosis of cancer cells. Thus, stimuli-sensitive nanomicelles along with HA targeting and RTV addition can effectively serve as a chemotherapeutic drug delivery agent for MBC and TNBC

Effect of stress on the catecholamine content of the adrenal gland of intact and bursectomized chicks

1. Bursa-intact and bursectomized chicks were exposed to cold-wet immobilization (CWI) stress for 1.5 min. The catecholamines (CA) from the adrenal gland were measured spectrofluorometrically 5, 15, 30 and 60 min after stress. 2. In bursa-intact chicks, the CWI stress caused decrease of both norepinephrine and epinephrine from the adrenal glands 5 min after stress. Resynthesis of epinephrine exceeded the control value 30 and 60 min after stress. 3. In bursectomized chicks, the CWI stress brought about a decrease of norepinephrine 15 and 30 min and of epinephrine 30 and 60 min after stress. 4. The findings suggest that bursa facilitates early (5 min) release of CA and also helps in quick resynthesis of epinephrine during stress