Search results for "porter"
showing 10 items of 920 documents
Does P-glycoprotein-170 expression predict for chemoresistance in transitional cell carcinoma of the bladder?
2003
Introduction: The glycoprotein P-170, causing drug efflux from the cells, may represent at least one cause of resistance to most drugs used in intravesical chemotherapy of superficial bladder cancer. Materials and Methods: GP-170 was retrospectively assessed in 60 patients affected by superficial transitional cell tumours of the bladder. It was assessed by immunohistochemistry in a semiquantitative way by the intensity of staining and by the percentage of positive cells. Correlation of GP-170 expression with G-grade, T-category, multiplicity, recurrence rate and treatment was investigated. In 44 patients recurrence was analysed in relation to GP-170 basal expression and to its variations. T…
Gene therapy with iNOS enhances regional contractility and reduces delayed contrast enhancement in a model of postischemic congestive heart failure
2012
Aims: The purpose of this study was to evaluate the effect of transient local myocardial gene transfer of iNOS on cardiac function in a large mammal animal model of heart failure induced by chronic ischemia. Methods: Chronic myocardial ischemia was induced using a minimally invasive model in 16 landrace pigs. Upon demonstration of heart failure, eight animals were treated with liposome-mediated iNOS-gene-transfer by local intramyocardial injection; eight animals received a sham procedure to serve as control. Results: The transmurality of late enhancement (control: 46.4%, iNOS: 35.9%; p < 0.05) was significantly decreased in the ischemic area in the iNOS-treated group. Wall thickness at end-…
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron
2012
Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins tha…
Kinetics of zinc transport in vitro in rat small intestine and colon: interaction with copper.
2002
The present study was planned to investigate the kinetic transport of zinc, in the intact intestine of the rat, in order to establish if more than one transporter is involved as well as the existence of a preferent sector in the cation uptake. Using an in vitro technique, the influx of zinc across the brush border membrane in three sectors of the small intestine (proximal, mid and distal) and in the colon of the rat was measured at six different concentrations (from 0.0007 to 11 mM). The kinetic study showed that intestinal transport of zinc occurs by a saturable process in the small intestine. The K(m) value obtained in the proximal segment (10.78+/-4.40 mM) is clearly higher than those ob…
Unique pharmacology of KAR-2, a potential anti-cancer agent: absorption modelling and selective mitotic spindle targeting.
2008
Abstract Bis-indols are a large group of the anti-cancer agents, which effectively arrest the uncontrolled division of the cancerous cells. Their use in clinical chemotherapy is still limited because of: (i) the non-specific targeting of the mitotic cells; (ii) low bioavailability of the drugs. KAR-2 has been identified as a tubulin binding agent which displays significantly lower cytotoxicity but favourable anti-cancer potency than its mother molecule, vinblastine. The objective of this paper, on one hand, was to show that the human intestinal epithelial Caco-2 cells, used for pharmacokinetic studies display distinct sensitivity against KAR-2 and vinblastine due to their distinct targeting…
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.
2001
The expression of P-glycoprotein is induced in cell cultures upon exposure to various inducers. Therefore, the aim of the present study was to evaluate the in-vivo relevance of this observation, i.e. the influence of chronic pretreatments with selected drugs -- all of which are ligands to P-glycoprotein (P-gp) as demonstrated in radioligand binding studies and all of which have some or a considerable effect on P-gp expression in Caco-2 cells -- on the effective intestinal permeabilities of the model compound talinolol in rats employing in-situ single-pass intestinal perfusion of three different gut segments. Talinolol was selected, because it shows high selectivity for one of the exsorptive…
Identical T-cell expansions in the colon mucosa and the synovium of a patient with enterogenic spondyloarthropathy.
2000
Abstract Intestinal T lymphocytes activated by antigen are suspected to play a key role in enterogenic spondyloarthropathies (SpA). Therefore, we aimed to identify and functionally characterize T-cell clones that are coexpanded in the intestinal mucosa and the synovium. Colon, peripheral blood, and synovium of a patient with enterogenic SpA were screened for clonal T-cell expansions by TCRB-CDR3 length analysis and sequencing. T-cell clones expanded in vivo were isolated from archived synovial cells by targeted T-cell cloning and characterized for phenotype, cytokine production, and antigen specificity. The synovial TCRBV18 + T-cell repertoire of the patient was dominated by 2 CD8 + T-cell …
Cannabidiol prevents priming- and stress-induced reinstatement of the conditioned place preference induced by cocaine in mice
2021
[Background]: Cocaine dependence is an important problem without any effective pharmacological treatment. Some preclinical studies have suggested that cannabidiol (CBD), a component of the Cannabis sativa plant, could be useful for the treatment of cocaine use disorders.
Delayed post-ischemic administration of CDP-choline increases EAAT2 association to lipid rafts and affords neuroprotection in experimental stroke
2007
Glutamate transport is the only mechanism for maintaining extracellular glutamate concentrations below excitotoxic levels. Among glutamate transporters, EAAT2 is responsible for up to 90% of all glutamate transport and has been reported to be associated to lipid rafts. In this context, we have recently shown that CDP-choline induces EAAT2 translocation to the membrane. Since CDP-choline preserves membrane stability by recovering levels of sphingomyelin, a glycosphingolipid present in lipid rafts, we have decided to investigate whether CDP-choline increases association of EAAT2 transporter to lipid rafts. Flotillin-1 was used as a marker of lipid rafts due to its known association to these m…
Human cationic amino acid transporter hCAT-3 is preferentially expressed in peripheral tissues.
2001
At least five distinct carrier proteins form the family of mammalian cationic amino acid transporters (CATs). We have cloned a cDNA containing the complete coding region of human CAT-3. hCAT-3 is glycosylated and localized to the plasma membrane. Transport studies in Xenopus laevis oocytes revealed that hCAT-3 is selective for cationic L-amino acids and exhibits a maximal transport activity similar to other CAT proteins. The apparent substrate affinity and sensitivity to trans-stimulation of hCAT-3 resembles most closely hCAT-2B. This is in contrast to rat and murine CAT-3 proteins that have been reported to display a very low activity and to be inhibited by neutral and anionic L-amino acid…