Search results for "kinetics"
showing 10 items of 2224 documents
PHEA-graft-polymethacrylate supramolecular aggregates for protein oral delivery
2013
Abstract Salmon calcitonin (sCT) is characterized by a poor oral availability. A new copolymer, β-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}- d , l -aspartamide (PHEA-IB-p(MANa + )), was designed for the oral administration of sCT through the formation of supramolecular aggregates (SAs) based on electrostatic interactions. Several sCT/PHEA-IB-p(MANa + ) weight ratios were characterized by turbidimetry, DLS, zeta potential, and microscopy analysis. After the incubation of sCT/PHEA-IB-p(MANa + ) complex with digestive enzymes, 10% (w/w) of loaded sCT was released in the native form. In vitro investigation was carried out to determine the copol…
Aqueous two-phase system cold-set gelation using natural and recombinant probiotic lactic acid bacteria as a gelling agent
2016
The present study aimed to entrap probiotic lactic acid bacteria (LAB) in a sodium alginate and sodium caseinate aqueous two-phase gel system. The natural acidifying properties of two therapeutic probiotic LAB were exploited to liberate calcium ions progressively from calcium carbonate (CaCO3), which caused the gelation of the co-existing phases. Bi-biopolymeric matrix gelation of GDL/CaCO3 or LAB/CaCO3 was monitored by dynamic rheological measurements, and the final gels were characterized by frequency dependence measurements and confocal laser scanning microscopy. Weak to strong gels were formed with an elastic modulus G' from 10 to 1.000Pa, respectively. After cold-set gelation of our sy…
Purification and characterization of the ?-β-hydroxybutyrate dehydrogenase from dromedary liver mitochondria
2001
Abstract d -β-Hydroxybutyrate dehydrogenase (BDH) (EC 1.1.1.30), a membrane enzyme, has been purified to homogeneity from dromedary ( Camelus dromedarius ) liver mitochondria. Our new purification method consisted of the solubilization of mitochondrial membranes by Triton X 100 and purification of BDH by two steps: DEAE-Sephacel and Phenyl-Sepharose. The molecular mass of the enzyme subunit size was 67 kDa. The purified enzyme is recognized by anti rat liver mitochondrial BDH antibodies. Furthermore, BDH activity was absolutely dependent upon phospholipids. BDH is also characterized by specific enzymatic parameters: an optimum pH of approximately 8 for the oxidation reaction, and approximat…
Induction of the alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base ex…
1996
Repair of alkylated bases in DNA is performed by O6-methylguanine-DNA methyltransferase (MGMT) and a set of enzymes of the base excision repair pathway involving N-methylpurine-DNA glycosylase (MPG), apurinic endonuclease (APE), DNA polymerase beta (Pol beta) and DNA ligase. The level of expression of these enzymes may exert a profound effect on resistance of cells towards alkylating drugs. We have comparatively analyzed the expression of MGMT and the different base excision repair genes in rat hepatoma cells (line H4IIE) after exposure to alkylating agents, X-rays and the glucocorticoid hormone dexamethasone. Furthermore, the effect of these agents on the activity of the cloned human MGMT …
Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by …
2013
The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profiles. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in…
A new assay for O6-alkylguanine-DNA-alkyltransferase to determine DNA repair capacities using lambda-phage DNA as substrate.
1990
One O6-methylguanine (O6-meG) was introduced into each BamHI site of lambda-phage DNA as a substrate for the determination of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase. A new assay using as the detection group 32P-labeled phosphate introduced at the 3' position of the modified nucleoside by incorporation of 32P-labeled TTP in the 3'-neighboring position proved highly sensitive: 10(-16) mol of the DNA lesion was still easily detectable. This DNA, which has greater than 1000 bp represents a good model for cellular DNA and was used as a substrate to measure the individual repair capacities for O6-meG in human lymphocytes of 20 healthy male and female donors. There were great …
Development and in vitro evaluation of new bifunctional 89Zr-chelators based on the 6-amino-1,4-diazepane scaffold for immuno-PET applications
2021
Abstract Introduction Combination of hydroxamate bearing side chains with the 6-amino-1,4-diazepane scaffold provides a promising strategy for fast and stable 89Zr-labeling of antibodies. Following this approach, we hereby present the development, labeling kinetics and in vitro complex stability of three resulting bifunctional chelator derivatives both stand-alone and coupled to a model protein in comparison to different linear deferoxamine (DFO) derivatives. Methods The novel 89Zr-chelator Hy3ADA5 was prepared via amide-coupling of separately synthesized 6-amino-1,4-diazepane-6-pentanoic acid and hydroxamate-containing side chains. Two further bifunctional derivatives were synthesized by e…
Impact of Undernutrition on the Pharmacokinetics and Pharmacodynamics of Anticancer Drugs: A Literature Review
2017
The etiology of undernourishment in cancer patients is multifactorial: tumor-related mechanisms (such as obstruction, metabolic abnormalities, and functionality changes) in addition to the influence of anticancer therapies, which can induce or worsen undernutrition. The evident role of undernutrition in cancer treatment outcomes suggests the need of considering nutritional status when evaluating anticancer drugs. In order to merge the available data and offer researchers and clinicians a global view of this phenomenon, the present manuscript reviews on a drug-by-drug basis the undernutrition-related pharmacokinetic and pharmacodynamic aspects of anticancer treatments. This review notes inte…
Desferrioxamine as an appropriate chelator for 90Nb: Comparison of its complexation properties for M-Df-Octreotide (M=Nb, Fe, Ga, Zr)
2014
The niobium-90 radioisotope ((90)Nb) holds considerable promise for use in immuno-PET, due to its decay parameters (t½ = 14.6h, positron yield=53%, Eß(+)(mean) = 0.35 MeV and Eß(+)(max) = 1.5 MeV). In particular, (90)Nb appears well suited to detect in vivo the pharmacokinetics of large targeting vectors (50-150 kDa). In order to be useful for immuno-PET chelators are required to both stabilize the radionuclide in terms of coordination chemistry and to facilitate the covalent attachment to the targeting vector. Different chelators were evaluated for this purpose in terms of radiolabelling efficiency and stability of the radiolabelled Nb(V) complex and in order to determine the most suitable…
Abstract B154: A first-in-human trial of GDC-0068: A novel, oral, ATP-competitive Akt inhibitor, demonstrates robust suppression of the Akt pathway i…
2011
Abstract GDC-0068 is a highly selective ATP-competitive small molecule that inhibits all three isoforms of Akt with IC50 values of 5 to 30 nM. GDC-0068 selectively inhibits cancer cells with activated Akt signaling (e.g. via PTEN loss or PIK3CA mutations). Patients with advanced solid tumors were treated with GDC-0068 using a 3+3 escalation design. GDC-0068 was dosed PO QD on a 21-day on, 7-day off schedule; endpoints included safety, pharmacokinetics (PK) and determination of pathway knockdown. Pharmacodynamics (PD) endpoints in surrogate tissue [platelet rich plasma (PRP)] were evaluated in all patients. In addition, at least two patients per cohort had pre- and on-treatment (day 15) tumo…