Irving Wainer - Academia.edu (original) (raw)

Papers by Irving Wainer

Journal of Medicinal Chemistry, Jun 29, 2004

Journal of Chromatography B: Biomedical Sciences and Applications, Apr 1, 2001

... 69). 6. A. Küpfer, B. Schmid and G. Pfaff. Xenobiotica 16 (1986), p. 421. Full Text via Cross... more ... 69). 6. A. Küpfer, B. Schmid and G. Pfaff. Xenobiotica 16 (1986), p. 421. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (44). 7. P. Dayer, T. Leemann and R. Striberni. Clin. Pharmacol. Ther. 45 (1989), p. 34. ...

The FASEB Journal, Mar 1, 2006

Chromatographia, Oct 1, 1988

A new HPLC stationary phase was synthesized by the covalent immobilization of ~-chymotrypsin on s... more A new HPLC stationary phase was synthesized by the covalent immobilization of ~-chymotrypsin on silica. This increased the stability of the enzyme, without decreasing its activity. The initial chromatographic studies show that this phase can be used for chiral separations of enantiomeric solutes. The stereochemical resolutions of amino acids and amino acid derivatives are reported.

PubMed, 1989

Four hr infusions i.v. of [6RS]5-formyltetrahydrofolate ([6RS]5-CHO-H4PteGlu; 500 mg/m2) and [6RS... more Four hr infusions i.v. of [6RS]5-formyltetrahydrofolate ([6RS]5-CHO-H4PteGlu; 500 mg/m2) and [6RS]5-methyltetrahydrofolate ([6RS]5-CH3-H4PteGlu; 500 mg/m2) were compared for their relative effects on expansion of pools of 5,10-methylenetetrahydrofolates (CH2-H4PteGlun) and tetrahydrofolates (H4PteGlun) in two human colon adenocarcinoma xenografts in mice. Expansion of these pools by 253-661% of control and increase in predominance of di-, tri-, and tetra-glutamate species were observed during [6RS]5-CHO-H4PteGlu infusion. In contrast, only modest pool size expansion (148-164% of control) and limited modulation of polyglutamate species were detected in four tumor lines during infusion with [6RS]5-CH3-H4PteGlu. The data suggest that [6RS]5-CH3-H4PteGlu is less effective than [6RS]5-CHO-H4PteGlu as a precursor for pools of CH2-H4PteGlun and H4PteGlun in colon tumors.

Biochimica Et Biophysica Acta - Biomembranes, Jun 1, 2010

The interaction of 18-methoxycoronaridine (18-MC) with nicotinic acetylcholine receptors (AChRs) ... more The interaction of 18-methoxycoronaridine (18-MC) with nicotinic acetylcholine receptors (AChRs) was compared with that for ibogaine and phencyclidine (PCP). The results established that 18-MC: (a) is more potent than ibogaine and PCP inhibiting (±)-epibatidine-induced AChR Ca 2+ influx. The potency of 18-MC is increased after longer pre-incubation periods, which is in agreement with the enhancement of [ 3 H]cytisine binding to resting but activatable Torpedo AChRs, (b) binds to a single site in the Torpedo AChR with high affinity and inhibits [ 3 H]TCP binding to desensitized AChRs in a steric fashion, suggesting the existence of overlapping sites. This is supported by our docking results indicating that 18-MC interacts with a domain located between the serine (position 6) and valine (position 13) rings, and (c) inhibits [ 3 H]TCP, [ 3 H] ibogaine, and [ 3 H]18-MC binding to desensitized AChRs with higher affinity compared to resting AChRs. This can be partially attributed to a slower dissociation rate from the desensitized AChR compared to that from the resting AChR. The enthalpic contribution is more important than the entropic contribution when 18-MC binds to the desensitized AChR compared to that for the resting AChR, and vice versa. Ibogaine analogs inhibit the AChR by interacting with a luminal domain that is shared with PCP, and by inducing desensitization.

Journal of Biochemical and Biophysical Methods, Mar 1, 2001

Trametes versicolor (TV) cells were embedded in ceramic matrices (TV Biocers) through sol-gel met... more Trametes versicolor (TV) cells were embedded in ceramic matrices (TV Biocers) through sol-gel method using tetraethyl orthosilicate as a silica precursor. The characterization of the free silica and TV Biocers was carried out by using scanning electron microscope, transmission electron microscope, Fourier transform infrared spectrophotometer, nitrogen adsorption-desorption measurement and catalytic activity assay. The performance of the TV Biocers as biocatalysts was evaluated using methylene blue (MB) and malachite green (MG) dyes as model emerging organic micropollutants. It was observed that the dye removal performance g (mmol g-1) of the TV Biocers for MB and MG, respectively, was 7.400 and 5.569 mmol g-1 which was 18 and 128 % higher than the TV Biocers calculated values obtained from the free silica and free TV cells. These results demonstrated that the TV Biocers can offer better dye removal performance through a combination of adsorption and degradation processes. This is the first reported study on the immobilization of the TV cells in silica matrices, and further study is underway to improve their properties toward its applications for removal of emerging organic micropollutants.

Biological Psychiatry, Apr 1, 2017

Journal of Pharmaceutical and Biomedical Analysis, Feb 1, 2014

A validated LC-MS/MS method was developed for the determination of D-Serine in human plasma. The ... more A validated LC-MS/MS method was developed for the determination of D-Serine in human plasma. The method was fully validated for use with human plasma samples and was linear from 0.19 nmol/ml to 25 nmol/ml. The coefficient of variation was ≤ 5% for the high QC standards and ≤ 8% for the low QC standards in plasma. D-Serine and L-Serine were resolved by pre-column derivatization using (R)-1-Boc-2-piperidine carbonyl chloride as the derivatizating agent. The method was used to determine the concentration of D-Serine in plasma samples obtained in patients receiving a continuous 5-day intravenous infusion of (R,S)-ketamine. The changes in D-Ser levels varied in the 6 patients, with circulating D-Ser levels increasing as much as 35% in a patient, while decreasing 20% in a patient. While only preliminary data, the results suggests the potential importance in determining the D-Ser levels in plasma and their potential role in physiological response.

Journal of Pharmaceutical and Biomedical Analysis, 2003

The nicotinic acetylcholine receptor (nAChR) subtypes alpha3beta4-nAChR and alpha4beta2-nAChR hav... more The nicotinic acetylcholine receptor (nAChR) subtypes alpha3beta4-nAChR and alpha4beta2-nAChR have been immobilized and the resulting stationary phases used to determine binding affinities. The alpha3beta4-nAChR column was coupled to a C(18) column and a mixture of 18 compounds was sorted into ligands and non-ligands for the alpha3beta4-nAChR. The results demonstrate that the nAChR stationary phases can be used for on-line high-throughput screening (HTS).

Blackie Academic & Professional eBooks, 1995

Introduction. Efficiency, retention, selectivity and resolution in chromatography. Modes of chrom... more Introduction. Efficiency, retention, selectivity and resolution in chromatography. Modes of chromatography. HPLC stationary phases. Instrumentation: pumps, injectors and column design. Instrumentation: detectors and integrators. Quantitation. Sample preparation. Polymer analysis. HPLC in biomedical and forensic analysis. Environmental analysis. Food, organic and pharmaceutical applications.

Springer eBooks, 1989

If, having assessed the relative merits of all the techniques available for a particular chiral r... more If, having assessed the relative merits of all the techniques available for a particular chiral resolution, it is decided that LC is likely to be the most suitable, it would then be most prudent to take a careful look at the literature. Taking a logical approach to what might work and what might not work is highly commendable, but is no substitute for checking what has been shown to work and what has been shown not to work. A literature search should be carried out for LC enantioseparations, not only of the compound in question but also of other closely related structures. A computer search would be ideal, but for those with no access to such facilities reference to the index of this book would be a more than useful substitute.

(R,R’)-4’-Methoxy-1-naphthylfenoterol ((R,R’)-MNF) and (R,S’)-MNF are GPR55 inhibitors that reduc... more (R,R’)-4’-Methoxy-1-naphthylfenoterol ((R,R’)-MNF) and (R,S’)-MNF are GPR55 inhibitors that reduce proliferation in pancreatic cancer cell lines. The IC50 values for [3H]-thymidine incorporation in PANC-1 cells were 0.11 ± 0.08 µM {(R,S’)-MNF} and 0.65 ± 0.25 µM {(R,R’)-MNF}. (R,R’)-MNF and (R,S’)-MNF attenuate the activities of the β producing decreased expression and nuclear translocation of pyruvate kinase M2, β-catenin and HIF-1α, thereby reducing cyclin D1 expression with concomitant G1/S cell cycle arrest. MNF reduces the expression and function of multidrug exporters in PANC-1 cells and tumor tissues, thereby increasing the sensitivity to other chemotherapeutic agents. The compounds also attenuate expression and function of enzymes and transporters associated with glycolysis including the MCT4 lactate exporter, thereby reducing L-lactate concentration in the tumor microenvironment. We now report the effect of (R,S’)-MNF on the growth of a PANC-1 tumor maintained as a xenograft in mice. Protocol: PANC-1 cells maintained in vitro as monolayer culture were harvested at an exponential growth phase, counted and each mouse inoculated subcutaneously at the right flank region with 5x106 cells in 0.1ml of PBS. On Day 8, mice were weighed and tumor volumes measured (mean tumor size 142mm3), and assigned to groups (n = 10) using randomized block design based on their tumor volumes. The mice received an ip injection (10mL/g) five times per week for 3 weeks of vehicle, 20% hydroxypropyl-beta-cyclodextrin (Control), 20mg/kg (R,S’)-MNF or 40mg/kg (R,S’)-MNF. The animals were checked daily for morbidity and mortality and weight and tumor volume measured twice weekly. On Day 33, the mice were euthanized by cervical extension, body weight, tumor weights and volumes were obtained and the tumors snap frozen. Results: (R,S’)-MNF produced significant dose-dependent inhibition of tumor growth. determined as % change in tumor volume relative to control. In animals treated with 20mg/kg (R,S’)-MNF there was 51.1±5.2% (** p < 0.01) inhibition and a 74.1±2.8% (*** p < 0.005) inhibition in animals receiving 40mg/kg (R,S’)-MNF. No mice were lost to treatment limiting toxicities. There was no significant change in weight between pre-dose and Day 33 for the animals in the control and 20mg/kg (R,S’)-MNF groups while on Day 33 the average weight of the animals receiving 40mg/kg (R,S’)-MNF was significantly lower 9.9±3.7% (*p < 0.05) than their pre-dose weights. The (R,S’)-MNF associated reduction of protein expression in tumor tissues, including pyruvate kinase M2, β-catenin, HIF-1α and MCT4 will be presented as will the changes in tumor/plasma concentrations of L-lactate. Citation Format: Nagendra S. Singh, Irving W. Wainer.{Authors}. GRP55 antagonists alter tumor microenvironment and inhibit tumor growth in a pancreatic tumor xenograft model. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B32.

Journal of Chromatography B, Aug 1, 2013

Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen). A rap... more Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen). A rapid, LC-MS/MS method was developed for the determination of (R,R)-Fen and (R,R ;S,S)-Fen in plasma and urine. The method was fully validated and was linear from 50 pg/ml to 2000 pg/ml for plasma and from 2.500 ng/ml to 160 ng/ml for urine with a lower limit of quantitation of 52.8 pg/ ml in plasma. The coefficient of variation was <15% for the high QC standards and <10% for the low QC standards in plasma and was <15% for the high and low QC standards in urine. The relative concentrations of (R,R)-Fen and (S,S)-Fen were determined using a chirobiotic T chiral stationary phase. The method was used to determine the concentration of (R,R)-Fen in plasma and urine samples obtained in an oral cross-over study of (R,R)-Fen and (R,R ;S,S)-Fen formulations. The results demonstrated a potential pre-systemic enantioselective interaction in which the (S,S)-Fen reduces the sulfation of the active (R,R)-Fen. The data suggests that a non-racemic mixture of the Fen enantiomers may provide better bioavailability of the active

Springer eBooks, 1986

The scope of this article is evident from the section headings. Resolution of enantiomeric drugs ... more The scope of this article is evident from the section headings. Resolution of enantiomeric drugs on HPLC chiral stationary phases (CSP’s). # Resolution of enantiomers as diastereoisomers. # Resolution of enantiomers on CSP’s. Commercially available CSP’s. # Type I CSP’s. # Type II CSP’s. # Type III CSP’s. # Type IV CSP’s. Type I CSP’s in pharmacological studies. # An overview. # Studies of the stereoselectivity of propranolol disposition and clearance. # Stereochemical aspects of the metabolism of ibuprofen. # Glutethv-mide metabolism in glutethimide-intoxicated patients. # Pharmacological studies of the stereoselective metabolism of polycyclic aromatic hydrocarbons. Pharmacokinetic applications using other CSP’s. # An overview. # Determination of (R)- and (S)-disopyramide in human plasma. A look toward the future.

Fundamental & Clinical Pharmacology, Jul 8, 1988

Summary— The 2 stereoisomers of alphamethyldopa (αMD) were separately injected IV at 3 different ... more Summary— The 2 stereoisomers of alphamethyldopa (αMD) were separately injected IV at 3 different doses (3, 10, 30 mg/kg) in anesthetized rabbits. Samples of plasma, aqueous humor (AH), and cerebrospinal fluid (CSF) were collected over a 300‐min period. The concentration of the aminoacid (AA) was determined by liquid chromatography and electrochemical detection. Parameters obtained from kinetic analyses of the plasma concentrations were close to the values reported in other species. Linear elimination kinetics were observed in the dose range studied. A marked dose‐dependent entry of αMD was observed in AH. A stereospecific active transport of αMD was evidenced in the AH since the concentration of the l‐isomer reached values above the plasma levels. CSF entry of the AA was small when compared to AH kinetics. A limited passive diffusion of the AA in the brain could account for this phenomenon. However, greater availability of the l‐stereoisomer was still observed in CSF. These αMD kinetic analyses illustrate the adaptation of AH and CSF removal procedures to the pharmacokinetic studies of the brain and ocular entry of AA isomers.

Chirality, 1996

Enantioselective HPLC methods have been developed for the resolution of (RS)-2-phenylcyclohexanon... more Enantioselective HPLC methods have been developed for the resolution of (RS)-2-phenylcyclohexanone (compound 1) and (RS)-Z-phenyltetrahydropyran-4-one (compound 4) and the diastereoselective and enantioselective separations of their respective cisand trans-alcohols; reduction of compound 1 yields trans-and cis-2-phenyl-l-cyclohexanol (compounds 2 and 3, respectively) and reduction of compound 4 yields trans-and cis-2phenyl-tetrahydropyn-401 (compounds 5 and 6, respectively). Compounds 1, 2, and 3 were stereochemically resolved using a chiral stationary phase (CSP) based upon amylose tris (3,s dimethylphenyl carbamate) coated on 10 p,m silica-gel (Chiralpak AD-CSP). Compounds 4, 5, and 6 were stereochemically resolved on a coupled column system where a column containing a CSP based upon cellulose tris(3,5-dimethylphenyl carbamate) coated on 5 km silica (Chiralcel OD-H-CSP) was coupled in series to the AD-CSP. The strategy employed in the identification of the peaks in the respective chromatograms is also discussed in this presentation.