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Jpn J Physiol. 2000 Dec;50(6):625-33.
Voltage dependency of the frequency of slow waves in antrum smooth muscle of the guinea-pig stomach.

Nose K, Suzuki H, Kannan H.

Department of Physiology, Nagoya City University Medical School, Nagoya, 467-8601 Japan.

The effects of membrane depolarization on the frequency of spontaneous activities were investigated in circular smooth muscle of the guinea-pig antrum attached with (intact tissue) or without longitudinal muscles (circular tissue). Both types of tissue were spontaneously active; the intact tissues generated slow wave and circular tissues generated regenerative potential. The latter but not the former was abolished by caffeine. Increasing K(+) concentrations depolarized the membrane and reduced the amplitude and interval between spontaneous activities in both tissues; the amplitude was reduced linearly with depolarization and disappeared at about -35 mV; the interval was reduced successively with depolarization and reached a stable value (about 8 s) at about -45 mV. The depolarization and reduction in amplitude and interval of spontaneous activities induced by high K(+) solution were not altered by atropine, nitroarginine, or apamin in either tissue, suggesting that these changes did not involve the effects of neurotransmitters. The depolarization of the membrane by electrical stimulation also reduced the amplitude and interval of spontaneous activities in both tissues, in a potential-dependent way. The absolute refractory period for generation of the evoked regenerative potential was about 8 s, and the relative refractory period was 8--12 s. The results indicate that the frequency of slow waves increases with a depolarization of the membrane up to -45 mV, irrespective of the presence of caffeine-insensitive components. A depolarization of the membrane above -45 mV does not further increase the frequency of slow waves, possibly because of the refractory period for the generation of slow waves.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11173558&dopt=Abstract

Cytogenet Cell Genet. 2000;91(1-4):261-6.
Mutagen sensitivity of human lymphoblastoid cells with a BRCA1 mutation in comparison to ataxia telangiectasia heterozygote cells.

Speit G, Trenz K, Schutz P, Bendix R, Dork T.

Abt. Humangenetik, Universitatsklinikum Ulm, Ulm, Germany. guenter.speiedizin.uni-ulm.de

Our previous results indicated a close relationship between the presence of a BRCA1 mutation in lymphocytes and hypersensitivity for the induction of micronuclei by gamma irradiation and hydrogen peroxide (H(2)O(2)). Comparative investigations with the comet assay (single-cell gel electrophoresis) suggested a normal rate of damage removal and pointed to a disturbed fidelity of DNA repair as a direct or indirect consequence of a BRCA1 mutation. We now wanted to see whether similar results could be obtained with lymphoblastoid cell lines (LCLs) and whether such permanent cells are suitable as a model for the investigation of mechanisms involved in mutagen sensitivity. Our results show that LCLs with a BRCA1 mutation are also hypersensitive to the chromosome-damaging effects of gamma irradiation or H(2)O(2), as revealed by the micronucleus test. Interestingly, LCLs heterozygous for an ataxia telangiectasia (AT) mutation have similar characteristics as BRCA1 cells with respect to the induction and repair of DNA damage induced by either gamma irradiation or H(2)O(2). However, caffeine enhanced the induction of micronuclei by gamma irradiation only in normal and heterozygous AT cells but not in BRCA1 cells, thus indicating a difference in the pathways leading to mutagen sensitivity in cells with a BRCA1 or an AT mutation. Our results suggest that caffeine could be useful in discriminating AT heterozygotes from carriers of a BRCA1 mutation, as well as BRCA1 mutation carriers from normal individuals. 2001 S. Karger AG, Basel.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11173867&dopt=Abstract

Echocardiography. 1998 Aug;15(6):519-526.
Alcohol- and Caffeine-Induced Changes in Mitral Valve Echo Morphology and Auscultation in Healthy Females.

Friedman Kelly L, Bender AM, Lax D, Goldberg SJ.

Department of Pediatrics (Cardiology), 1501 N. Campbell Avenue, Tucson, AZ 85724-5073.

Mitral valve prolapse (MVP) is a common cardiac valve abnormality that affects women more frequently than men. We have shown that mild dehydration induces echocardiographic signs of MVP in healthy females more frequently than in males. The present study investigated whether ethanol and caffeine, two commonly used substances, will induce changes in mitral leaflet morphology in normal subjects and whether these changes are gender dependent. Ten healthy volunteers were examined after ingesting 0.95 g/kg ethanol at breath ethanol values of 0.025% +/- 0.005%, 0.050% +/- 0.005%, and 0.075% (peak) +/- 0.005%, and at decreasing ethanol levels of 0.050% +/- 0.005% and 0.025% +/- 0.005%. Twelve healthy subjects were studied at 1.5, 3, and 4.5 hours after ingesting 5 mg/kg body weight of caffeine in a randomized, double-blind, crossover manner. A significant increase in mitral valve shape index (MVSI) on apical four-chamber view was documented in females following ethanol ingestion at all ethanol levels. These changes were accompanied by auscultatory findings characteristic of MVP. Decreased systemic vascular resistance, and afterload and increased heart rate, also occurred after ethanol ingestion. A significant increase in MVSI occurred on parasternal long axis in females at peak caffeine level; auscultatory findings characteristic of MVP also were documented. MVSI increased slightly on apical four-chamber view in males; however, no male subject developed auscultatory MVP. Body mass index was significantly lower in females (20.8 +/- 0.7 kg/m(2)) versus males (23.7 +/- 0.3 kg/m(2), P < 0.05). All subjects lost weight after caffeine intake; afterload and contractility also were increased. This study documents that ethanol and caffeine, at concentrations similar to those present in social intake, induced significant echo changes in mitral leaflet morphology and auscultation suggestive of MVP in healthy females. These results suggest that in addition to apparent hydration state, recent ethanol or caffeine intake should be taken into consideration before making the diagnosis of MVP.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11175075&dopt=Abstract [PubMed - as supplied by publisher]

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