Positive and negative contractile effects of somatostatin-14 on rat ventricular cardiomyocytes.

Somatostatin-14 elicits negative inotropic and chronotropic actions in atrial myocardium. Less is known about the effects of somatostatin-14 in ventricular myocardium. The direct contractile effects of somatostatin-14 were assessed using ventricular cardiomyocytes isolated from the hearts of adult rats. Cells were stimulated at 0.5 Hz with CaCl2 (2 mM) under basal conditions and in the presence of the -adrenoceptor agonist, isoprenaline (1 nM), or the selective inhibitor of the transient outward current (Ito), 4-aminopyridine (500 M). Somatostatin-14 did not alter basal contractile response but it did inhibit (IC50 13 nM) the response to isoprenaline (1 nM). In the presence of 4-aminopyridine (500 M), somatostatin-14 stimulated a positive contractile response (EC50 118 fM) that was attenuated markedly by diltiazem (100 nM). These data indicate that somatostatin-14 exerts dual effects directly in rat ventricular cardiomyocytes: (1) a negative contractile effect, observed in the presence of isoprenaline (1 nM), coupled to activation of Ito; and (2) a previously unreported and very potent positive contractile effect, unmasked by 4-aminopyridine (500 M), coupled to the influx of calcium ions via L-type calcium channels. The greater potency of somatostatin-14 for producing the positive contractile effect indicates that the peptide may exert a predominantly stimulatory influence on the resting contractility of ventricular myocardium in vivo, whereas the negative contractile effect, observed at much higher concentrations, could indicate that localized elevations in the concentration of the peptide may serve as a negative regulatory influence to limit the detrimental effects of excessive stimulation of cardiomyocyte contractility.

Optical spectroscopy of the M 15 intermediate velocity cloud

We present echelle spectrograph observations in the Na D lines, at resolutions of 6.2-8.5 km s(-1), for 11 stars located in the line-of-sight to the M15 intermediate velocity cloud (IVC), which has a radial velocity of similar to +70 km s(-1) in the Local Standard of Rest. This cloud is a part of IVC Complex gp. The targets range in magnitude from m(V) = 13.3-14.8. Seven of the observed stars are in the M15 globular cluster, the remaining four being field stars. Three of the observed cluster stars are located near a peak in intensity of the IVC Hi column density as observed at a resolution of similar to 1 arcmin. Intermediate velocity gas is detected in absorption towards 7 stars, with equivalent widths in NaD2 ranging from similar to0.09-0.20 Angstrom, corresponding to log(10)(N-Na cm(-2)) similar to 11.8-12.5, and Na I/H I column density ratios (neglecting the HII component) ranging from similar to(1-3) x 10(-8). Over scales ranging from 30 arcsec to 1 arcmin, the Na i column density and the Na i/H i ratio varies by upto 70 per cent and a factor of similar to 2, respectively. Combining the current sightlines with previously obtained Nai data from Kennedy et al. (1998b), the Na i/H i column density ratio over cluster sightlines varies by upto a factor of similar to 25, when using Hi data of resolution similar to 2 x 1 arcmin. One cluster star, M15 ZNG-1, was also observed in the Ca i (lambda(air) = 4226.728 Angstrom) and Ca ii (lambda(air) = 3933.663 Angstrom) lines. A column density ratio N(Ca i)/N(Ca ii) <0.03 was found, typical of values seen in the warm ionised interstellar medium. Towards this sightline, the IVC has a Nai/Ca ii column density ratio of &SIM; 0.25, similar to that observed in the local interstellar medium. Finally, we detect tentative evidence for IV absorption in Ki (?(air) = 7698:974 &ANGS) towards 3 cluster stars, which have N(K i)/N(H i) ratios of &SIM;0.5-3 x 10(-9).

Shifting of the electron-capture-to-the-continuum peak in proton-helium collisions at 10 and 20 keV

A refined theoretical approach has been developed to study the double-differential cross sections (DDCS's) in proton-helium collisions as a function of the ratio of ionized electron velocity to the incident proton velocity. The refinement is done in the present coupled-channel calculation by introducing a continuum distorted wave in the final state coupled with discrete states including direct as well as charge transfer channels. It is confirmed that the electron-capture-to-the-continuum (ECC) peak is slightly shifted to a lower electron velocity than the equivelocity position. Comparing measurements and classical trajectory Monte Carlo (CTMC) calculations at 10 and 20 keV proton energies, excellent agreement of the ECC peak heights is achieved at both energies. However, a minor disagreement in the peak positions between the present calculation and the CTMC results is noted. A smooth behavior of the DDCS is found in the present calculation on both sides of the peak whereas the CTMC results show some oscillatory behavior particularly to the left of the peak, associated with the statistical nature of CTMC calculations.

Collision mechanisms in one-electron capture by slow H and He- like ions of C, N and O in H and H-2

Translational energy spectroscopy (TES) has been used to study state-selective one-electron capture by H and He-like ions of C, N and O in both H and H-2 within the range 250-900 eV amu(- 1). The main collision mechanisms leading to state-selective electron capture have been identified, their relative importance assessed and compared, where possible, with theoretical predictions and with any previous measurements based on photon emission spectroscopy. For one-electron capture in H-2, the relative importance of contributions from non- dissociative and dissociative capture as well as from two- electron capture into autoionizing states is found to be strikingly different for the cases considered. Our TES measurements in atomic hydrogen provide an important extension of previous measurements to energies below 1000 eV amu(-1) and show that, as the impact energy decreases, electron capture becomes more selective until only a single n product channel is significant. These product main channels are well described by reaction windows calculated using a Landau-Zener approach. However, the same approach applied to the more complex energy- change spectra observed in H-2 is found to be less successful.

Quantitative analysis of MRP-8 in gingival crevicular fluid in periodontal health and disease using microbore HPLC.

BACKGROUND:

The protein components of GCF can be separated by reverse-phase microbore HPLC on a C18 column with detection on the basis of 214 nm absorbance. A single major symmetrical protein peak eluting with a retention time of 26 min (50% acetonitrile) was evident in gingival crevicular fluid (GCF) from periodontitis patients but not in healthy GCF. This protein was identified as human MRP-8 by N-terminal amino acid sequencing and liquid chromatography quadropole mass spectrometry.

AIMS:

To quantify the amount of MRP-8 detectable in GCF from individual healthy, gingivitis and periodontitis affected sites and to study the relationship, if any, between the levels of this responsive protein and periodontal health and disease.

METHODS:

GCF was sampled (30 s) from healthy, gingivitis, and periodontitis sites in peridontitis subjects (n=15) and from controls (n=5) with clinically healthy gingiva and no periodontitis. Purified MRP-8 was sequenced by Edmann degradation and the phenylthiohydantoin (PTH) amino acid yield determined (by comparison of peak area with external PTH amino acid standards). This value was subsequently used to calculate the relative amount of protein in the peak eluting with a retention time of 26.0 min (MRP-8) in individual GCF chromatograms.

RESULTS:

Higher levels of MRP-8 were detected in inflammatory sites: periodontitis 457.0 (281.0) ng; gingivitis 413.5 (394.5) ng compared with periodontally healthy sites in diseased subjects 14.6 (14.3) ng and in controls 18.6 (18.5) ng, p=0.003. There was at least 20-fold more MRP-8 in the inflammatory compared with the healthy sites studied.

CONCLUSIONS:

The preliminary data indicate that MRP-8 is present in GCF, with significantly greater amounts present at diseased than healthy sites. A systematic study of the relationship of this protein to periodontal disease could prove useful in further clarifying whether MRP-8 could be a reliable GCF biomarker of gingivitis and periodontitis.

Dielectronic recombination of He-like to C-like iodine ions

KLL dielectronic recombination resonances, where a free electron is captured into the L shell and at the same time a K shell electron is excited into the L shell, have been measured for open shell iodine ions by measuring the detected yield of escaping ions of various charge states and modeling the charge balance in an electron beam ion trap. In the modeling, the escape from the trap and multiple charge exchange were considered. Extracted ions were used to measure the charge balance in the trap. The different charge states were clearly separated, which along with the correction for artifacts connected with ion escape and multiple charge exchange made the open shell highly charged ion measurements of this type possible for the first time. From the measured spectra resonant strengths were obtained. The results were 4.27(39)x10(-19) cm(2) eV, 2.91(26)x10(-19) cm(2) eV, 2.39(22)x10(-19) cm(2) eV, 1.49(14)x10(-19) cm(2) eV and 7.64(76)x10(-20) cm(2) eV for the iodine ions from He-like to C-like, respectively.

A Holocene record of human induced and natural environmental change from Lake Forsyth (Te Wairewa), New Zealand

A 1.2 m sediment core from Lake Forsyth, Canterbury, New Zealand, records the development of the catchment/lake system over the last 7000 years, and its response to anthropogenic disturbance following European settlement c. 1840 AD. Pollen was used to reconstruct catchment vegetation history, while foraminifera, chironomids, Trichoptera, and the abundance of Pediastrum simplex colonies were used to infer past environmental conditions within the lake. The basal 30 cm of core records the transition of the Lake Forsyth Basin from a tidal embayment to a brackish coastal lake. Timing of closure of the lake mouth could not be accurately determined, but it appears that Lake Forsyth had stabilised as a slightly brackish, oligo mesotrophic shallow lake by about 500 years BP. Major deforestation occurred on Banks Peninsula between 1860 AD and 1890 AD. This deforestation is marked by the rapid decline in the main canopy trees (Prumnopitys taxifolia (matai) and Podocarpus totara/hallii (totara/mountain totara), an increase in charcoal, and the appearance of grasses. At around 1895 AD, pine appears in the record while a willow (Salix spp.) appears somewhat later. Redundancy analysis (RDA) of the pollen and aquatic species data revealed a significant relationship between regional vegetation and the abundance of aquatic taxa, with the percentage if disturbance pollen explaining most (14.8%) of the constrained variation in the aquatic species data. Principle components analysis (PCA) of aquatic species data revealed that the most significant period of rapid biological change in the lakes history corresponded to the main period of human disturbance in the catchment. Deforestation led to increased sediment and nutrient input into the lake which was accompanied by a major reduction in salinity. These changes are inferred from the appearance and proliferation of freshwater algae (Pediastrum simplex), an increase in abundance and diversity of chironomids, and the abundance of cases and remains from the larvae of the caddisfly, Oecetis unicolor. Eutrophication accompanied by increasing salinity of the lake is inferred from a significant peak and then decline of P. simplex, and a reduction in the abundance and diversity of aquatic invertebrates. The artificial opening of the lake to the Pacific Ocean, which began in the late 1800s, is the likely cause of the recent increase in salinity. An increase in salinity may have also encouraged blooms of the halotolerant and hepatotoxic cyanobacteria Nodularia spumigena.

Electron collisions with iron peak elements: a computational grand challenge

This paper discusses the calculation of electron impact collision strengths and effective collision strengths for iron peak elements of importance in the analysis of many astronomical and laboratory spectra. It commences with a brief overview of R-matrix theory which is the basis of computer programs which have been widely used to calculate the relevant atomic data used in this analysis. A summary is then given of calculations carried out over the last 20 y for electron collisions with Fe II. The grand challenge, represented by the calculation of accurate collision strengths and effective collision strengths for this ion, is then discussed. A new parallel R-matrix program PRMAT, which is being developed to meet this challenge, is then described and results of recent calculations, using this program to determine optically forbidden transitions in e- – Ni IV on a Cray T3E-1200 parallel supercomputer, are presented. The implications of this e- – Ni IV calculation for the determination of accurate data from an isoelectronic e- – Fe II calculation are discussed and finally some future directions of research are reviewed.

Absolute single and multiple charge exchange cross sections for highly charged C, O, and Ne ions on H2O, CO, and CO2

Reported herein are measured absolute single, double, and triple charge exchange (CE) cross sections for the highly charged ions (HCIs) Cq+ (q=5,6), Oq+ (q=6,7,8), and Neq+ (q=7,8) colliding with the molecular species H2O, CO, and CO2. Present data can be applied to interpreting observations of x-ray emissions from comets as they interact with the solar wind. As such, the ion impact energies of 7.0q keV (1.62–3.06 keV/amu) are representative of the fast solar wind, and data at 1.5q keV for O6+ (0.56 keV/amu) on CO and CO2 and 3.5q keV for O5+ (1.09 keV/amu) on CO provide checks of the energy dependence of the cross sections at intermediate and typical slow solar wind velocities. The HCIs are generated within a 14 GHz electron cyclotron resonance ion source. Absolute CE measurements are made using a retarding potential energy analyzer, with measurement of the target gas cell pressure and incident and final ion currents. Trends in the cross sections are discussed in light of the classical overbarrier model (OBM), extended OBM, and with recent results of the classical trajectory Monte Carlo theory.

Structure-activity studies on position 14 of human alpha-calcitonin gene-related peptide

A structure-activity study was performed to examine the role of position 14 of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) in activating the CGRP receptor. Interestingly, position 14 of h-alpha-CGRP contains a glycyl residue and is part of an alpha-helix spanning residues 8-18. Analogues [Ala(14)]-h-alpha-CGRP, [Aib(14)]-h-alpha-CGRP, [Asp(14)]-h-alpha-CGRP, [Asn(14)]-h-alpha-CGRP, and [Pro(14)]-h-alpha-CGRP were synthesized by solid phase peptide methodology and purified by RP-HPLC. Secondary structure was measured by circular dichroism spectroscopy. Agonist activities were determined as the analogues' ability to stimulate amylase secretion from guinea pig pancreatic acini and to relax precontracted porcine coronary arteries. Analogues [Ala(1)4]-h-alpha-CGRP, [Aib(14)]-h-alpha-CGRP, [Asp(14)]-h-alpha-CGRP, and [Asn(14)]-h-alpha-CGRP, all containing residues with a high helical propensity in position 14, were potent full agonists compared to h-alpha-CGRP in both tissues. Interestingly, replacement of Gly(14) of h-alpha-CGRP with these residues did not substantially increase the helical content of these analogues. [Pro(14)]-h-alpha-CGRP, predictably, has significantly lower helical content and is a 20-fold less potent agonist on coronary artery, known to contain CGRP-1 receptor subtypes, and an antagonist on pancreatic acini, known to contain CGRP-2 receptor subtypes. In conclusion, the residue in position 14 plays a structural role in stabilizing the alpha-helix spanning residues 8-18. The alpha-helix is crucial for maintaining highly potent agonist effects of h-alpha-CGRP at CGRP receptors. The wide variety of functional groups that can be tolerated in position 14 with no substantial modification of agonist effects suggests the residue in this position is not in contact with the CGRP receptor. [Pro(14)]-h-alpha-CGRP may be a useful pharmacological tool to distinguish between CGRP-1 and CGRP-2 receptor subtypes.