Independent component analysis applied to raman spectra for classification of in vitro human coronary arteries

Optical diagnostic methods, such as near-infrared Raman spectroscopy allow quantification and evaluation of human affecting diseases, which could be useful in identifying and diagnosing atherosclerosis in coronary arteries. The goal of the present work is to apply Independent Component Analysis (ICA) for data reduction and feature extraction of Raman spectra and to perform the Mahalanobis distance for group classification according to histopathology, obtaining feasible diagnostic information to detect atheromatous plaque. An 830nm Ti:sapphire laser pumped by an argon laser provides near-infrared excitation. A spectrograph disperses light scattered from arterial tissues over a liquid-nitrogen cooled CCD to detect the Raman spectra. A total of 111 spectra from arterial fragments were utilized.

Mechanisms underlying the biphasic effect of vitamin K-1 (phylloquinone) on arterial blood pressure

Phylloquinone (vitamin K-1, VK1) is widely used therapeutically and intravenous administration of this quinone can induce hypotension. We aimed to investigate the mechanisms underlying the effects induced by VK1 on arterial blood pressure. With this purpose a catheter was inserted into the abdominal aorta of male Wistar rats for blood pressure and heart rate recording. Bolus intravenous injection of VK1 (0.5-20 mg kg(-1)) produced a transient increase in blood pressure followed by a fall. Both the pressor and depressor response induced by VK1 were dose-dependent. On the other hand, intravenous injection of VK1 did not alter heart rate. The nitric oxide synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 10 and 20 mg kg(-1)) reduced both the increase and decrease in blood pressure induced by VK1 (5 mgkg(-1)). On the other hand, indometacin (10 mg kg(-1)), a non-selective cyclooxygenase inhibitor, did not alter the increase in mean arterial pressure (MAP) induced by VK1. However, VK1-induced fall in MAP was significantly attenuated by indometacin. We concluded that VK1 induces a dose-dependent effect on blood pressure that consists of an acute increase followed by a more sustained decrease in MAP. The hypotension induced by VK1 involves the activation of the nitric oxide (NO) pathway and the release of vasodilator prostanoid(s).

Properties and function of KCNQ1 K+ channels isolated from the rectal gland of Squalus acanthias

KCNQ1 (K(V)LQT1) K+ channels play an important role during electrolyte secretion in airways and colon. KCNQ1 was cloned recently from NaCl-secreting shark rectal glands. Here we study. the properties and regulation of the cloned sK(V)LQT1 expressed in Xenopus oocytes and Chinese hamster ovary (CHO) cells and compare the results with those obtained from in vitro perfused rectal gland tubules (RGT). The expression of sKCNQ1 induced voltage-dependent, delayed activated K+ currents, which were augmented by an increase in intracellular cAMP and Ca2+. The chromanol derivatives 293B and 526B potently inhibited sKCNQ1 expressed in oocytes and CHO cells, but had little effect on RGT electrolyte transport. Short-circuit currents in RGT were activated by alkalinization and were decreased by acidification. In CHO cells an alkaline pH activated and an acidic pH inhibited 293B-sensitive KCNQ1 currents. Noise analysis of the cell-attached basolateral membrane of RGT indicated the presence of low-conductance (

Regulation and properties of KCNQ1 (K(v)LQT1) and impact of the cystic fibrosis transmembrane conductance regulator

The K+ channel KCNQ1 (K(V)LQT1) is a voltage-gated K+ channel, coexpressed with regulatory subunits such as KCNE1 (IsK, mink) or KCNE3, depending on the tissue examined. Here, we investigate regulation and properties of human and rat KCNQ1 and the impact of regulators such as KCNE1 and KCNE3. Because the cystic fibrosis transmembrane conductance regulator (CFTR) has also been suggested to regulate KCNQ1 channels we studied the effects of CFTR on KCNQ1 in Xenopus oocytes, Expression of both human and rat KCNQ1 induced time dependent K+ currents that were sensitive to Ba2+ and 293B. Coexpression with KCNE1 delayed voltage activation, while coexpression with KCNE3 accelerated current activation. KCNQ1 currents were activated by an increase in intracellular cAMP, independent of coexpression with KCNE1 or KCNE3. cAMP dependent activation was abolished in N-terminal truncated hKCNQ1 but was still detectable after deletion of a single PKA phosphorylation motif. In the presence but not in the absence of KCNE1 or KCNE3, K+ currents were activated by the Ca2+ ionophore ionomycin. Coexpression of CFTR with either human or rat KCNQ1 had no impact on regulation of KCNQ1 K+ currents by cAMP but slightly shifted the concentration response curve for 293B. Thus, KCNQ1 expressed in Xenopus oocytes is regulated by cAMP and Ca2+ but is not affected by CFTR.

Distribution of C-14 Cylindrospermopsin in vivo in the mouse

Radiolabelled C-14 cylindrospermopsin (CYN) has been prepared and used to investigate the distribution and excretion of CYN in vivo in male Quackenbush mice. At a dose of 0.2 mg/kg (i.e., approx. median lethal dose) the following mean (SID) urinary and faecal recoveries (cumulative) were obtained, respectively: (0-6 hours, n = 4) 48.2 (29.3)%, 11.9 (21.4)%; (0-12 hours, n = 12) 66.0 (27.1)%, 5.7 (5.6)%; (0-24 hours, n = 12) 68.4 (26.7)%, 8.5 (8.1)%. Mean (SD) recoveries from livers at 6 hours were 20.6 (6.4)% (n = 4), at 48 hours 13.1 (7.7)% (n = 8), and 5-7 days were 2.1 (2.1)% (n = 8). A substantial amount (up to 23%) can be retained in the liver for up to 48 hours with a lesser amount retained in the kidneys. The excretion patterns show substantial interindividual variability between predominantly faecal or urinary excretion, but these patterns are not related in any simple manner to the outcome in terms of toxicity. There is at least one methanol-extractable metabolite as well as a nonmethanol-extractable metabolite in the liver. The methanol-extractable metabolite was not found in the kidney and is more hydrophilic than CYN itself on reverse phase. (C) 2001 by John Wiley & Sons, Inc.

A classification of subantarctic Heard Island vegetation

The vascular and bryophyte floras of subantarctic Heard Island were classified using cluster analysis into six vegetation communities: Open Cushion Carpet, Mossy Feldmark, Wet Mixed Herbfield, Coastal Biotic Vegetation, Saltspray Vegetation, and Closed Cushion Carpet. Multidimensional scaling indicated that the vegetation communities were not well delineated but were continua. Discriminant analysis and a classification tree identified altitude, wind, peat depth, bryophyte cover and extent of bare ground, and particle size as discriminating variables. The combination of small area, glaciation, and harsh climate has resulted in reduced vegetation variety in comparison to those subantarctic islands north of the Antarctic Polar Front Zone. Some of the functional groups and vegetation communities found on warmer subantarctic islands are not present on Heard Island, notably ferns and sedges and fernbrakes and extensive mires, respectively.

Linear ketenimines. Variable structures of C,C-dicyanoketenimines and C,C-bis-sulfonylketenimines

C,C-Dicyanoketenimines 10a-c were generated by flash vacuum thermolysis of ketene NS-acetals 9a-c or by thermal or photochemical decomposition of alpha-azido-,beta-cyanocinnamonitrile 11. In the latter reaction, 3,3-dicyano-2-phenyl-1-azirine 12 is also formed. IR spectroscopy of the keteniminines isolated in Ar matrixes or as neat films, NMR spectroscopy of 10c, and theoretical calculations (B3LYP/6-31G*) demonstrate that these ketenimines have variable geometry, being essentially linear along the CCN-R framework in polar media (neat films and solution), but in the gas phase or Ar matrix they are bent, as is usual for ketenimines. Experiments and calculations agree that a single CN substituent as in 13 is not enough to enforce linearity, and sulfonyl groups are less effective that cyano groups in causing linearity. C,C-Bis(methylsulfonyl)ketenimines 4-5 and a C-cyano-C-(methylsulfonyl)ketenimine 15 are not linear. The compound p-O2NC6H4N=C= C(COOMe)2 previously reported in the literature is probably somewhat linearized along the CCNR moiety. A computational survey (B3LYP/6-31G*) of the inversion barrier at nitrogen indicates that electronegative C-substituents dramatically lower the barrier; this is also true of N-acyl substituents. Increasing polarity causes lower barriers. Although N-alkylbis(methylsulfonyl)ketenimines are not calculated to be linear, the barriers are so low that crystal lattice forces can induce planarity in N-methylbis(methylsulfonyl)ketenimine 3.

Electrolyte transport in the mouse trachea: No evidence for a contribution of luminal K+ conductance

Recent studies on frog skin acini have challenged the question whether Cl- secretion or Na+ absorption in the airways is driven by luminal K+ channels in series to a basolateral K+ conductance. We examined the possible role of luminal K+ channels in electrolyte transport in mouse trachea in Ussing-chamber experiments. Tracheas of both normal and CFTR (-/-) mice showed a dominant amiloride-sensitive Na+ absorption under both, control conditions and after cAMP-dependent stimulation. The lumen-negative transepithelial voltage was enhanced after application of IBMX and forskolin and Cl- secretion was activated. Electrolyte secretion induced by IBMX and forskolin was inhibited by luminal glibenclamide and the blocker of basolateral Na(+)2Cl(-)K(+) cotransporter azosemide. Similarly, the compound 29313, a blocker of basolateral KCNQ1/KCNE3 K+ channels effectively blocked Cl- secretion when applied to either the luminal or basolateral side of the epithelium. RT-PCR analysis suggested expression of additional K+ channels in tracheal epithelial cells such as Slo1 and Kir6.2. However, we did not detect any functional evidence for expression of luminal K+ channels in mouse airways, using luminal 29313, clotrimazole and Ba2+ or different K+ channel toxins such as charybdotoxin, apamin and alpha-dendrotoxin. Thus, the present study demonstrates Cl- secretion in mouse airways, which depends on basolateral Na(+)2Cl(-)K(+) cotransport and luminal CFTR and non-CFTR Cl- channels. Cl- secretion is maintained by the activity of basolateral K+ channels, while no clear evidence was found for the presence of a luminal K+ conductance.