Search results for "Specificity."

Automated determination of clozapine and major metabolites in serum and urine.

1997

Clozapine is an atypical neuroleptic that is increasingly used for the treatment of schizophrenia. An automated method was developed for the routine quantification of clozapine and its major metabolites, N-desmethylclozapine and clozapine N-oxide, in human serum and urine by column switching and online high-performance liquid chromatography with ultraviolet detection. The method included adsorption of clozapine and its metabolites on a cyanopropyl-coated clean-up column (10 microns; 10 mm x 4.0 mm ID), washing interfering serum constituents to waste by deionized water, and, after column switching, separation on C18 ODS Hypersil reversed-phase material (5 microns; 250 mm x 4.6 mm ID). The co…

Mono- and diglucuronide formation from benzo[a]pyrene and chrysene diphenols by AHH-1 cell-expressed UDP-glucuronosyltransferase UGT1A7

1999

Polycyclic aromatic hydrocarbon (PAH)-type compounds induce at least two rat UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT1A7. Among the glucuronidation reactions of PAH metabolites studied, mono- and diglucuronide formation of benzo[a]pyrene and chrysene-3,6-diphenol showed the highest induction factors in rat liver microsomes. Availability of AHH-1 cells stably expressing UGT1A7 allowed us to study whether this PAH-inducible isoform could catalyze benzo[a]pyrene and chrysene-3,6-diphenol glucuronidation. It was found that UGT1A7 indeed catalyzed mono- and diglucuronide formation of both benzo[a]pyrene and chrysene 3,6-diphenols. V79 cell-expressed rat UGT1A6 also catalyzed these re…

Genetics of the variable expression of CYP3A in humans.

2004

CYP3A isozymes participate in the metabolism of 45-60% of currently used drugs and of a variety of other compounds such as steroid hormones, toxins, and carcinogens. The CYP3A expression status is a major determinant of drug efficacy and safety, and it may also affect an individual's predisposition to certain cancers. The inter- and intraindividual expression of CYP3A is variable because of a complex interplay between genetic and environmental factors. Markers predictive of the individual CYP3A activity could improve therapies with CYP3A substrates by personalised dose adjustments, but their development has been slower than for other drug-metabolizing enzymes. Here we summarize the recent p…

Organic carbonates as alternative solvents for asymmetric hydrogenation

2009

Organic carbonates like propylene carbonate (PC) or butylene carbonate (BC) belong to the class of aprotic, highly dipolar solvents (AHD). Interestingly, their potential as solvents for asymmetric catalysis has been overlooked for a long time. The aim of this work is to evaluate organic carbonates and other organic solvents like THF, CH2Cl2, and acetonitrile as well as members of the AHD-family (DMF, DMSO, etc.) as media for homogeneous asymmetric hydrogenation. For this reason cationic Rh-complexes based on chiral phosphine ligands were tested in the hydrogenation of typical benchmark substrates. In several trials, significant advantages of organic carbonates were found. In contrast to DMS…

Substrate Specificity of Vinorine Hydroxylase, a Novel Membrane-bound Key Enzyme of Rauwolfia Indole Alkaloid Biosynthesis

1995

SPECIES-DEPENDENT STEREOSPECIFIC SERUM PROTEIN BINDING OF PHENPROCOUMON

1978

Role of Redox Signaling, Protein Phosphatases and Histone Acetylation in the Inflammatory Cascade in Acute Pancreatitis: Therapeutic Implications

2010

Acute pancreatitis starts as a local inflammation of the pancreatic tissue but often leads to the systemic inflammatory response syndrome and death by multiple organ failure. Pro-inflammatory cytokines, particularly TNF-alpha and Il-1beta, play a pivotal role together with oxidative stress and glutathione depletion in the inflammatory response in this disease. Most inflammatory mediators act through mitogen activated protein kinases and nuclear factor kB. Nevertheless, elucidation of the precise mechanisms involved in activation and attenuation phases of the inflammatory cascade is still underway. Redox signaling mediated by inactivation of protein phosphatases and histone acetylation trigg…

The ability of soil-borne fungi to degrade organophosphonate carbon-to-phosphorus bonds

1997

The ability of a wide variety of soil-borne fungal strains to degrade four structurally different compounds containing P-C bonds, namely the naturally occurring amino acid ciliatine, the popular herbicide glyphosate, phosphonoacetic acid and 2-amino-3-phosphonopropionic acid, was studied in order to show that soil fungi may play an important role in the biodegradation of organophosphonates. Most of the strains appeared to utilize ciliatine as the sole source of phosphorus for growth. Only a limited number of strains were able to grow on the other phosphonates used in this work. The strains of Trichoderma harzianum, Scopulariopsis sp. and Aspergillus niger chosen for more detailed study show…

Phosphorylation of GAP-43 (growth-associated protein of 43 kDa) by conventional, novel and atypical isotypes of the protein kinase C gene family: dif…

1996

GAP-43 (growth-associated protein of 43 kDa; also known as neuromodulin, P-57, B-50 and F-1) is a neuronal calmodulin binding protein and a major protein kinase C (PKC) substrate in mammalian brain. Here we describe the phosphorylation by and the site specificity of different PKC isotypes. The conventional PKC beta 1 and the novel PKCs delta and epsilon effectively phosphorylated recombinant GAP-43 in vitro; atypical PKC zeta did not. The K(m) values (between 0.6 and 2.3 microM) were very low, demonstrating a high-affinity interaction between kinase and substrate. All PKC isotypes were shown to phosphorylate serine-41 in GAP-43. When using a 19-amino-acid oligopeptide based on the GAP-43 ph…

Power saturation of ESR signal in ammonium tartrate exposed to 60Co gamma-ray photons, electrons and protons.

2006

Abstract Marrale, M., Brai, M., Triolo, A., Bartolotta, A. and D'Oca, M. C. Power Saturation of ESR Signal in Ammonium Tartrate Exposed to 60Co γ-Ray Photons, Electrons and Protons. Radiat. Res. 166, 802–809 (2006). In this paper we present an investigation of the electron spin resonance (ESR) line shape of ammonium tartrate (AT) dosimeters exposed to radiation with different linear energy transfer (LET). We exposed our dosimeters to γ-ray photons (60Co), 7 MeV and 14 MeV initial energy electrons, and 19.3 MeV initial energy protons. The differences in the power saturation behavior of ESR spectra of AT irradiated with photons, electrons and protons could be correlated to the effective LET o…