Background : The MDR1 (multidrug resistance) gene (also known as PGY1), which encodes the transmembrane efflux pump P-glycoprotein (Pgp), confers resistance to Pgp-transported cytotoxic drugs in tissue culture. The increase in MDR1 expression in tumors after chemotherapy is usually attributed to selection of pre-existing multidrug-resistant cells by Pgp-transported drugs. MDR1 expression in tissue culture can be increased by several types of stress-inducing treatment, including agents that activate protein kinase C (PKC). Previous studies, however, failed to demonstrate that short-term exposure to any chemotherapeutic drug can induce the expression of the resident MDR1 gene in drug-sensitive human cells. Purpose : This study was designed to utilize highly sensitive assays to determine if transient exposure to chemotherapeutic drugs would have an effect on MDR1 expression in human cells and to assess if PKC inhibitors would influence such an effect Methods : We analyzed the MDR1 gene expression in several human cell lines derived from leukemias or solid tumors, after treatment with different cytotoxic drugs, in the presence or absence of PKC inhibitors. Pgp function and expression were studied by flow cytometric assays, and MDR1 messenger RNA (mRNA) was assayed by polymerase chain reaction. Results : Transient exposure to chemotherapeutic drugs, including agents that are not transported by Pgp, induced Pgp and MDR1 mRNA expression in subpopulations of treated cells in most of the tested cell lines. This induction was observed along with microscopically detectable cell damage. The drug-induced MDR1 expression and the associated twofold to threefold increase in resistance to vinblastine were sustained in K562 leukemia cells for at least several weeks after the removal of the drug. Drug-mediated MDR1 induction was blocked by nonspecific protein kinase inhibitors that are active against PKC, but not by a protein kinase inhibitor ineffective against PKC. Conclusions : Expression of the human MDR1 mRNA and Pgp can be induced in response to cellular damage by cytotoxic drugs regardless of whether the drugs are transported by Pgp. This induction can be prevented by protein kinase inhibitors. Implications : Induction of MDR1 expression in response to cellular damage may account for increased MDR1 expression in treated human tumors. Protein kinase inhibitors may be useful in preventing the emergence of multidrug resistance during cancer chemotherapy. [J Natl Cancer Inst 85:632-639, 1993]
Artemisinin (ART) resistance in Plasmodium is threatening the artemisinin combination therapies-the first line of defence against malaria. ART resistance has been established to be mediated by the Plasmodium Kelch13 (PfK13) protein. For the crucial role of PfK13 in multiple pathways of the Plasmodium life cycle and ART resistance, it is imperative that we investigate its interacting partners.
Transplant renal vein stenosis (TRVS) is a rare vascular complication of renal transplant that can masquerade findings of rejection and infection. We report a case who presented 2 years 9 months post-transplant with localized non-tender heaviness and fullness at the graft site with renal dysfunction. Initial ultrasonogram (USG) was suggestive of graft pyelonephritis with perinephric collection, though, there were no clinical features of infection and cultures came as sterile. Doppler revealed findings of TRVS, which was confirmed with a CT angiogram. Graft vein angioplasty restored the hemodynamics, but the patient again presented after 4 months with incidentally detected graft dysfunction. USG Doppler showed graft vein stenosis at the same site, which was managed with an elective renal vein angioplasty with stent placement.
Sialic acid-conjugated nanocarriers have emerged as attractive biomarkers with promising biomedical applications. The translation of these nanocarriers into clinical applications requires in-depth assessment in animal models. However, due to the complexity, ethical concerns, and cost of the high-order animal system, there is an immediate need of information-rich simple animal models to decipher the biological significance. Herein, we performed in vivo head-to-head comparison of Neu5Acα(2-6) and α(2-3)Gal conjugated quantum dots (QDs) toxicity, biodistribution, and sequestration in wild-type zebrafish ( Danio rerio) and mouse model (C57BL). The fluorescent properties and cadmium composition of quantum dots were used to map the blood clearance, biodistribution, and sequestration of the sialylated QDs in major organs of both models. We observed that α(2-6) sialylated QDs preferentially have prolonged circulating half-life and broader biodistribution in both models. On the contrary, α(2-3) sialic acid and galactose-conjugated QDs have shortened blood circulation time and are sequestered in the liver, and cleared after several hours in both models. These results demonstrate the applicability of the zebrafish and sialylated QDs to target specific organs, as well as drug delivery and biomedical diagnostics.
Hepatitis B and C are considered as an important health hazard among health care workers (HCWs).These blood borne infections can be transmitted either from HCW to a patient or vice-versa.Both viruses are known to cause hepatitis, cirrhosis and hepatocellular carcinoma.Among these two blood borne infections, HBV is usually more stable in the external environment and is more infectious as compared to HCV.HBV is associated with an average risk of 30% after having a potential exposure to the infected blood as compared to HCV, which is associated with a lower risk of 3%.Though, universal precautions should be undertaken at different clinical setups but still occupational exposure to these blood borne viruses does occur.However, due to the availability of effective vaccination and post exposure prophylaxis against HBV, incidence has decreased tremendously over the past few years.Among different categories of health workers, surgeons, nurses and dentists are at a higher risk as they tend to come in intact with patient's blood and body fluid during various interventions and surgeries.The present chapter describes in detail about the current situation of HBV and HCV as a potential health hazard along with management and treatment guidelines.The Centers for Disease Control (CDC) estimates that about 600,000 to one million needle stick injuries occur each year.Unfortunately, about half of these needle stick injuries go unreported (CDC, 2007) [1,2].HHBV, HCV and HIV are the potential well recognized blood borne viruses.Worldwide they are also the leading cause for chronic hepatitis, cirrhosis and hepato-cellular carcinoma (HCC) [3,4] which draws the attention to take steps for establishing
The data was generated for 24 microsatellite in 3 buffalo populations/breeds viz; Bhadawari, Tarui and local buffaloes of Kerala. Both qualitative, as well as quantitative tests were conducted for testing the population for mutation-drift equilibrium.The data was analysed for heterozygosity excess and allelic distribution. Standardized difference test and Wilcoxon rank test being parametric were utilized in all the 3 mutation models to draw inferences. The TPM revealed Kerala buffaloes and Tarai buffaloes to have experienced populotion bottlenecks in the last 100-250.generation.The qualitative (graphical) test, however, did not exhibit and 'mode shift' distortion in all the 3 population of buffaloes and gave normal L-shaped curve.
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