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PubMed2002

Gas chromatographic determination of 2-hydroxy-4-methoxybenzophenone and octyldimethyl-p-aminobenzoic acid sunscreen agents in swimming pool and bathing waters by solid-phase microextraction.

A method has been developed for the trace determination of two sunscreen constituents (2-hydroxy-4-methoxybenzophenone and octyldimethyl-p-aminobenzoic acid) in water samples, which are commonly used in commercial formulations. The method employs solid-phase microextraction (SPME) and gas chromatography with flame ionization and mass spectrometric detection. The technique was developed with headspace and direct sampling in order to demonstrate the applicability of these SPME extraction modes for the identification of these two UV absorbing compounds in waters. The main parameters affecting the SPME process, such as desorption time, extraction time profile, salt additives, pH, and temperature, were investigated. The poly(dimethylsiloxane) 100-microm and polyacrylate 85-microm fiber coatings were found to be the most efficient for the extraction of these compounds from aqueous matrices. Linear calibration curves in the wide range of 10-500 microg/l were obtained for both compounds yielding typical RSD values of 5-9% for both extraction modes. The recoveries were relatively high, 82-98%, with quantitation limits below 1 microg/l. A comparison between the proposed methods and the conventional multiresidue solid-phase extraction revealed that the proposed technique(s) can be reliably used for sunscreen residue measurement in water samples with satisfactory results.

4-Aminobenzoic Acid↗
PubMed1999

Molecularly imprinted adsorbents for positional isomer separation.

2,4-Dihydroxybenzophenone (2,4-DHB) imprinted polymers were synthesized by surface imprinting technique, using allyl alcohol as the functional monomer. The polymers showed a very high selectivity for 2,4-DHB when compared with various positional isomers such as 2-HB, 2,2'-DHB, 4,4'-DHIB and 4,4'-DMB. Solvents were found to affect the selectivity as well as sorption capacity in the case of surface imprinted polymers. The selectivities decreased drastically when the imprint cavity was blocked. This validated the importance of the cavity and the rebinding interactions in governing the selectivity in the case of MIPs. The surface imprinted polymers also showed a high selectivity under non-equilibrium conditions thereby making them suitable adsorbents for industrial separations.

Benzophenones↗
PubMed1998

An improved method for the production of antibodies to lipophilic carboxylic hapten using small amount of hapten-carrier conjugate.

A rapid, simple and low cost procedure for preparing minute amount of hapten-protein conjugates was developed using 4-acetyl benzoic acid (ABA) and two other closely related small chromophoric haptens. The amide bond-generating mixed anhydride method of Erlanger was modified to promote conjugation to various proteins (bovine serum albumin, ovalbumin, casein and hemocyanin) or to a synthetic homopolymer (Poly-DL-lysine). The key process in this synthesis is the use of a reversed micellar medium allowing strong carrier haptenization as determined by spectrophotometric measurement at characteristic hapten absorption peaks. This coupling procedure is applicable to as little hapten material as 0.2 micromol and is disclosed to be most valuable for other rare lipid haptens which pose analytical problem in biological fluids and matrices. Specific mice polyclonal antibodies were produced following multiple intraperitoneal injections of (ABA)23-BSA conjugate as revealed by indirect and competitive ELISA. Calculated KD for the interaction of the antibodies with free ABA was found to be 5 X 10(-5)M.

Animals↗
PubMed2003

Effect of a gastrin/cholecystokinin B receptor antagonist, S-0509, on the omeprazole-induced proliferation of gastric mucosa in rats.

Hypergastrinemia is known to cause hyperplasia of the gastric mucosa, especially in gastric enterochromaffinlike (ECL) cells. In some clinical conditions causing hypergastrinemia, such as long-term gastric-acid inhibition and gastric-mucosa atrophy, hyperplastic ECL cells may develop into gastric carcinoid tumors. A newly developed gastrin-receptor antagonist, S-0509, has been reported to block gastrin-induced stimulation of gastric-acid secretion. We therefore investigated whether S-0509 inhibits the omeprazole- and gastrin-stimulated hyperproliferation of gastric mucosa, especially of ECL cells. Daily administration of omeprazole and gastrin in male Sprague-Dawley rats induced marked hypergastrinemia and increased proliferation of gastric-mucosa cells. The numbers of ECL cells and of ECL cells producing messenger RNA for regenerating gene, a potent growth factor for gastric-mucosa cells, were also augmented by long-term administration of omeprazole and gastrin. Coadministration of S-0509 with omeprazole or gastrin almost completely inhibited the omeprazole- and gastrin-induced changes in gastric mucosa, including mucosal thickening and ECL hyperplasia. S-0509 did not induce gastric-mucosa atrophy, even when administered for as long as 4 weeks. In summary, we have found that a newly developed gastrin receptor antagonist, S-0509, inhibits omeprazole- and gastrin-induced mucosal hyperplasia, especially ECL-cell hyperplasia, in rats.

Animals↗
PubMed1997

Effects of the K+ channel opener, ZD6169, on volume and PGE2-stimulated bladder activity in conscious rats.

PURPOSE: To investigate the effects of the new K(ATP) channel opener, ZD6169, shown to have an in vivo selectivity for the bladder, on bladder activity in rats. MATERIALS AND METHODS: ZD6169 was given intra-arterially (i.a., 0.1 and 1 mg./kg.) or orally (3 mg./kg.) to conscious Sprague-Dawley rats undergoing continuous cystometry. Investigations were also performed before and after stimulation of bladder activity by intravesical prostaglandin (PG) E2. RESULTS: Intra-arterial ZD6169 increased residual volume, but caused no changes in other cystometric parameters. In rats receiving oral ZD6169, cystometric parameters were compared (every hour up to five hours) to those recorded in rats receiving oral vehicle. No differences were found, except in threshold pressure, which was significantly increased. Intravesical PGE2 20 microM increased micturition and basal pressures, and decreased bladder capacity and micturition volume. ZD6169 1 mg./kg., given i.a., reduced or completely prevented the activity induced by intravesical PGE2. Three hours after orally administered ZD6169 (3 mg./kg.), intravesical PGE2 20 microM had no effect. Three hours after oral administration of vehicle, the effects of PGE2 were attenuated, but still statistically significant. CONCLUSIONS: ZD6169, given i.a. or orally, increased threshold pressure, but had otherwise little effect on volume-induced micturition. However, the drug markedly reduced or prevented PGE2-induced bladder activity when given i.a.; it was also effective when given orally. If ZD6169 has inhibiting effects on bladder contraction in man without any cardiovascular actions, the drug may represent a novel, promising way of treating bladder overactivity.

Administration, Intravesical↗
PubMed2002

Intravesical adenosine triphosphate stimulates the micturition reflex in awake, freely moving rats.

PURPOSE: Adenosine triphosphate (ATP) (Sigma Chemical Co., St. Louis, Missouri) is known to contract animal as well as human detrusor muscle and recent investigations have shown an involvement of ligand gated purinergic-1 receptors in detrusor contraction. In addition, ligand gated purinergic-3 receptors have been demonstrated on suburothelial sensory nerves (C-fibers) and may be involved in distention induced initiation of the micturition reflex. We tested the hypothesis that ATP given intravesically can stimulate afferent nerves and initiate the micturition reflex. MATERIALS AND METHODS: Continuous cystometry was performed in conscious, freely moving, normal female Sprague-Dawley rats. Cystometric parameters were evaluated before and after drug administration. RESULTS: Instilled intravesically ATP (10 mM.) induced bladder overactivity in 6 animals with a mean increase in voiding pressure plus or minus standard error of 73 +/- 9 to 107 +/- 9 cm. water (p <0.01), mean baseline pressure increase of 5.32 +/- 0.58 to 12.71 +/- 1.01 cm. water (p <0.01) and mean bladder capacity decrease of 1.13 +/- 0.25 to 0.75 +/- 021 ml. (p <0.01). Lower concentrations had no significant effect. The effects of ATP were abolished by pretreatment with the ganglion blocker hexamethonium (40 mg./kg. ), nitric oxide synthase substrate L-arginine (Sigma Chemical Co.) (200 mg./kg. ) and neurokinin-2 receptor antagonist 123 (S)-N-methyl-N 123 4-(acetylamino-4-phenyl piperidone)-2-(3,4-dichlorophenyl) butyl 125 benzamide (Molecular Probes, Leiden, The Netherlands) (4 nmol.) given intravenously, the ligand gated purinergic-3 antagonist 2'-(or 3')-O-(trinitrophyl)adenosine 5'-triphosphate (50 microM./kg.) given intravenously and the k channel opener ZD6169 given intravesically.(ATP). CONCLUSIONS: ATP given intravesically can induce bladder overactivity, probably by stimulating suburothelial C-fibers. The data suggest that several mediators and mechanisms are involved in mechano-afferent transduction in the bladder.

Adenosine Triphosphate↗
PubMed2003

K-ATP opener-mediated attenuation of spontaneous bladder contractions in ligature-intact, partial bladder outlet obstructed rats.

Symptoms of urinary frequency and urgency secondary to benign prostatic obstruction are common in elderly men. In many patients, these symptoms correspond to the urodynamic finding of involuntary detrusor contractions during filling cystometry (i.e., detrusor instability). Spontaneous non-voiding contractions during filling can be modeled in animals by subchronic, partial urethral obstruction. However, many investigators remove the obstructive ligature a few days prior to cystometrical evaluation (which may not be an ideal representation of the clinical situation where obstruction is still present), and all perform cystometry within 3 days post-bladder catheterization surgery (i.e., while considerable wound healing is present). In the current study, we evaluated the effects, after oral dosing, of three structurally diverse ATP-sensitive potassium channel openers (KCOs) on spontaneous contractions secondary to obstruction in rats with an intact obstructive ligature at the time of testing and 2 weeks post-bladder catheterization. ZD6169, WAY-133537 and a novel dihydropyridine KCO, A-278637, all significantly decreased spontaneous bladder contractions at 30 min post-dosing (p.o.). However, only ZD6169 (10 micromol/kg) and A-278637 (3 micromol/kg) attenuated such bladder contractions at doses that did not concurrently, significantly affect mean arterial blood pressure and heart rate. These data confirm the efficacy of KCOs to inhibit unstable contractions in obstructed rats, and they further demonstrate the positive effect of a novel, bladder-selective KCO, A-278637, in an animal model with potentially less artifact than in previous such models.

ATP-Binding Cassette Transporters↗
PubMed1999

Monoamine oxidase and catechol-O-methyltransferase inhibitors.

Despite advances in the treatment of PD, there remain significant unmet therapeutic needs. This is particularly true at the later stages of the disease when dopaminergic therapy is complicated by motor fluctuations and dyskinesias. Inhibition of dopamine metabolism is a valuable adjunct to exogenous dopaminergic replacement. Inhibitors of MAO-B have been used to treat early and advanced PD for a number of years. Although controversy remains, existing evidence still raises the possibility that MAO-B inhibition may confer a protective effect in PD, delaying the progression of the underlying pathology. More recently, clinically useful inhibitors of COMT have become available. These medications largely act peripherally to increase the pool of available dopamine precursor and prolong the duration of effect of L-dopa. They are indicated primarily for control of motor fluctuations.

Benzophenones↗
PubMed1997

Effects of catechol-O-methyltransferase inhibition on the rates of uptake and reversibility of 6-fluoro-L-Dopa trapping in MPTP-induced parkinsonism in monkeys.

The uptake rate constant and the loss rate constant that expresses the reversibility of the uptake process of 6-[18F]fluoro-L-Dopa (FDOPA) were measured by positron emission tomography in the striatum of normal rhesus monkeys and in monkeys with unilateral lesions of the dopaminergic nigro-striatal pathway, induced by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Each animal was studied twice: with and without pretreatment of the catechol-O-methyltransferase (COMT) inhibitor Ro 40-7592, tolcapone. After pretreatment with tolcapone, there was a very significant increase in plasma FDOPA throughout the course of the study, accompanied by a significant decrease in its main metabolite, 3-O-methylfluorodopa. Tolcapone did not induce a significant change in the uptake rate constant in either the normal or the MPTP-treated striatum. However, after tolcapone pretreatment, there was a significant decrease in the loss rate constant in the MPTP-treated striatum (25%) and a smaller, non-significant decrease in the normal striatum (13%). It is concluded that the COMT inhibitor tolcapone exhibits clear peripheral and central activity. As compared to peripheral COMT inhibitors, this central effect may help preserve and stabilize the synaptic levels of DA and, thus, further improve the effects of L-DOPA therapy in parkinsonian patients.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2001

Nemorosone, the major constituent of floral resins of Clusia rosea.

Nemorosone, the major constituent of the floral resin of Clusia rosea was isolated after exhaustive chromatography. This compound was fully characterized as it is in the nature, without methylation as reported before. A keto-enol equilibrium was observed and both isomers were totally characterized by NMR spectroscopic techniques. The previously announced structure for methylnemorosone was corrected on the basis of application of chemical methylation, high field 2D NMR techniques and NOE difference spectroscopy experiments on the natural product. Our studies concluded that an interchange occurred in the assignment of the benzoyl moiety position with an isoprenyl group in that structure.

Benzophenones↗
PubMed1999

Interference by plastics additives in the HPLC determination of microcystin-LR and -YR.

Plastics devices used for the field collection of water samples may contain plastics additives which will interfere with the HPLC determination of the cyanobacterial toxins microcystins. The presence of the additives resorcinol monobenzoate or 2,4-dihydroxybenzophenone can interfere with the determination of microcystin-LR. The presence of bisphenol A in plastics can interfere with the determination of microcystin-YR.

Bacterial Toxins↗
PubMed2001

Clad polymer buffer rods for polymer process monitoring.

Clad polymer buffer rods consisting of a polyetheretherketone (PEEK) core and a cladding made of a heat resistance epoxy aluminum composite are presented. The core has a uniform diameter or a taper shape. Ultrasonic measurement results indicate that the ultrasonic signal strength and signal to noise ratio of these clad rods are better than those of the non-clad PEEK rods for both longitudinal and shear waves because of the improved ultrasonic wave guidance in the core. Comparisons of these rods with those made of polymide and high-density polyethylene are given. Applications of these buffer rods for ultrasonic monitoring of polymer extrusion at temperatures up to 200 degrees C and pressures up to 180 psi are demonstrated. The monitoring results also reveal that within certain operating temperature and pressure range, clad polymer buffer rods show advantages over clad steel buffer rods.

Benzophenones↗
PubMed2000

Organochlorine and heavy metal residues in the water/sediment system of the Southeast Regional Park in Madrid, Spain.

A study into levels of contamination by organochlorine compounds (insecticides and PCBs) and heavy metals (Cd and Pb) in the water/sediment system of the Southeast Regional Park (SERP) in Madrid, Spain, has been carried out. Residue levels of xenobiotics were determined in surface and underground waters and sediments from selected sites throughout the protected area. The results showed these contaminants to be widespread throughout the studied area. p,p'-DDT concentration levels were consistently higher than its metabolite p,p'-DDE, indicating a recent use of this organochlorine insecticide in the area. PCB levels exceeded, in the majority of the cases, the levels taken as the maximum (100 ng/microl) for highly polluted waters. Cd and Pb levels found in water samples were under the detection limits of the methodology used. Pb levels found in sediment samples were higher than Cd.

Benzophenones↗