Ventilation and metabolism among rat strains

Strohl, Kingman P., Agnes J. Thomas, Pamela St. Jean, EvelynH. Schlenker, Richard J. Koletsky, and Nicholas J. Schork. Ventilation and metabolism among rat strains. J. Appl. Physiol. 82(1): 317-323, 1997.We examinedventilation and metabolism in four rat strains with variation in traitsfor body weight and/or blood pressure regulation.Sprague-Dawley [SD; 8 males (M), 8 females (F)], BrownNorway (BN; 10 M, 11 F), and Zucker (Z; 11 M, 12 F) rats were comparedwith Koletsky (K; 11 M, 11 F) rats. With the use of noninvasiveplethysmography, frequency, tidal volume, minute ventilation(E),O₂ consumption, andCO₂ production were derived atrest during normoxia (room air) and during the 5th minute of exposureto each of the following: hyperoxia (100% O₂), hypoxia (10%O₂-balanceN₂), and hypercapnia (7%CO₂-balance O₂). Statistical methods probedfor strain and sex effects, with covariant analysis by body weight,length, and body mass. During resting breathing, strain effects werefound with respect to both frequency (BN, Z > K, SD) and tidal volume(SD > BN, Z) but not to E. Sexinfluenced frequency (F > M) alone. Z rats had higher values forO₂ consumption,CO₂ production, and respiratoryquotient than the other three strains, with no independent effect bysex. During hyperoxia, frequency was greater in BN and Z than in SD orK rats; SD rats had a larger tidal volume than BN or Z rats; Z rats hada greater E than K rats; and M had alarger tidal volume than F. Strain differences persisted duringhypercapnia, with Z rats exhibiting the highest frequency andE values. During hypoxic exposure,strain effects were found to influenceE (SD > K, Z), frequency (BN > K), and tidal volume (SD > BN, K, Z). Body mass was only amodest predictor of E during normoxia, of both E and tidal volume withhypoxia, hypercapnia, or hyperoxia, and of frequency duringhypercapnia. We conclude that strain of rats, more than their body massor sex, has major and different influences on metabolism, the patternand level of ventilation during air breathing, and ventilation duringacute exposure to hypercapnia or hypoxia.

     

Modification of sodium inactivation in myelinated nerve by Anemonia toxin II and iodate. Analysis of current fluctuations and current relaxations

(1) Na+ currents and Na+ current fluctuations were measured in single myelinated nerve fibres of Rana esculenta under voltage-clamp conditions. The process of Na+ inactivation was modified by external treatment with 7 microM Anemonia Toxin II or by internal application of 20 or 40 mM IO3(-). (2) At depolarization of 24 and 32 mV the spectral density of Na+ current fluctuations could be described as the sum of two contributions, Sh(f) and Sm(f), representing the spectrum from fluctuations of the inactivation (h) and activation (m) gates, respectively. At higher depolarizations of 40 and 48 mV the low frequency (h) fluctuations could be better fitted by the sum, Sh1(f)+Sh2(f), of two separate Lorentzian functions. (3) The Na+ current and the variance of Na+ current fluctuations between 150 and 450 ms after depolarization are increased by one order of magnitude after application of Anemonia Toxin II or IO3(-). (4) The kinetics of Na+ current inactivation were described as A1 x exp(-t/tau h1) + A2 x exp(-t/tau h2) + B. The constant, tau h1, of fast Na+ inactivation was the same in normal and modified nerve fibres. The slow inactivation time constant, tau h2, increased with increasing depolarizations in modified fibres but decreased under control conditions. In all cases tau h2 showed a similar voltage dependence as the time constant found by fitting the low frequency fluctuations of Na+ current with one Lorentzian function, Sh(f). (5) It is concluded that Anemonia Toxin II and IO3(-) modify a fraction of Na+ channels in an all-or-none manner. A lower limit of the number of modified Na+ channels is estimated from the Na+ current and the variance Na+ current fluctuations. 7 microM external Anemonia Toxin II modifies more than 17% and 20 or 40 mM internal IO3(-) more than 8% of all Na+ channels. The inactivation gates in modified channels experience an electric field different from that in normal fibres.     

Chemical and biological consequences of β-decay

Summary Radioactive decay in a labelled molecule leads to specific chemical and biological consequences which are due to local transmutation effects such as recoil, electronic excitation, build-up of charge states and change of chemical identity, as well as to internal radiolytic effects. In the present paper these effects are reviewed emphasizing the relation of the chemical alterations on a molecular level to the biological manifestation. Potential importance of this type of research for biomedical applications is pointed out. In part 1 we review the underlying physical and chemical principles and consequences of -decay of³H,¹⁴C,³²P,³³P,³⁵S and¹²⁵I for gaseous and simple condensed organic systems. Part 2 which will appear in the next issue will include the discussion of biological effects associated with -decay.     

Cholelithiasis in a male rhesus monkey (Macaca mulatta) fed a cholesterol-containing diet.

In this report we describe the development of cholelithiasis in a male rhesus monkey fed a cholesterol-containing diet for 24 months. This represents the only case of cholelithiasis in this species of nonhuman primate that we have observed out of a population of over 500 rhesus monkeys fed similar cholesterol-containing diets. Associated with the appearance of gallstones was the production of bile saturated with cholesterol, and the excretion of bile with an abnormal bile acid composition.     

Seminars in Virology: A Biological Perspective of Slow Virus Infection and Chronic Disease

Sequential events characterize the interaction of viruses with parenchymal cells, and acute lytic infections of tissues and organs have broad biological attributes. A knowledge of these permits a keener understanding of persistent, intermittent herpesvirus infections and persistent, continuous respiratory virus infections. In addition to unique biochemical mechanisms which may permit the latter chronic infections to evolve, the roles of defective and mutant strains of virus, viral interference, and the genetic, developmental and immunological expressions of the host are of considerable and provocative importance.The traditional view of viral infections embraces a broad spectrum of acute pathological and inflammatory events. The relationship of measles virus to subacute sclerosing panencephalitis, the elucidation of the latency of herpes simplex virus, and the slow unmasking of the pathogenesis of multiple sclerosis have illustrated the subtle elements of persistent viral infections of the human being. These chronic neurological diseases have provided the opportunity and stimulus for sharp dissection of the biological and biochemical processes which embellish the logical link of viral infections to other forms of chronic human illness.     

The isolation of Saumarez Reef virus, a new flavivirus, from bird ticks Ornithodoros capensis and Ixodes eudyptidis in Australia.

Strains of a new flavivirus, for which the name Saumarez Reef Virus is proposed, were isolated from seabird ticks collected from four localities. Two strains were isolated from ticks of the species Ornithodoros capensis Neumann 1901 collected from the nests of Sooty Terns, Sterna fuscata Linnaeus 1766 on coral cays off the east coast of Queensland, Australia. The other three strains were isolated from ticks of the species Ixodes eudyptidis Maskell 1885 taken from two dead Silver Gulls Larus novaehollandiae Stephens 1826 in northern Tasmania. The new virus was compared serologically with 50 other flaviviruses at the Yale Arbovirus Research Unit and was found to be most closely related to Tyuleniy virus.     

Inhibitors of sterol synthesis. Characterization of trimethylsilyl dienol ethers of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one. Applications in the analysis of mitochondrial metabolites of the 15-ketosterol by gas chromatography-mass spectrometry.

Derivatization of delta 8(14)-15-ketosterols as bis-TMS dienol ethers facilitates their analysis by gas chromatography-mass spectrometry (GC-MS). Conditions are presented for the preparation of each of the three possible bis-TMS dienol ethers of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (1), a potent regulator of cholesterol metabolism. Treatment of 1 with N,O-bis(tri-methylsilyl)-trifluoroacetamide (BSTFA) and pyridine for 20 h at 100 degrees C produced primarily 3 beta,15-bis(trimethylsilyloxy)-5 alpha-cholesta-7,14-diene. Treatment of 1 with BSTFA-pyridine in the presence of 0.1% perchloric acid for 20 h at 22 degrees C gave mainly the delta 8(14)15, dienol ether. Heating this reaction mixture at 100 degrees C for 4 days gave mainly the delta 8,14 ether. The structures of the three dienol ethers were established by GC-MS and 1H and 13C nuclear magnetic resonance spectroscopy. The three TMS dienol ethers of 1 were resolved by capillary GC and gave very simple mass spectra upon electron impact with fragmentation limited almost exclusively to the elimination of trimethylsilanol, methyl, and the side chain. The TMS dienol ethers showed reduced artefact formation, improved chromatographic resolution, and increased sensitivity relative to the delta 8(14)-15-ketosterols, properties that improve the detection and identification of minor components in analyses of complex biological mixtures. The utility of this derivatization is illustrated for the delta 7,14 TMS dienol ethers of the 3-deoxy, 3-keto, 3 alpha-hydroxy, and 3 beta-methoxy analogs of 1 and for delta 8(14)-15-ketosterols in mixtures obtained from incubations of 1 with rat liver mitochondria in the presence of NADPH.     

Semi-automated solid-phase DNA sequencing.

Increasing the efficiency of DNA sequencing necessitates the development of systems which reduce the need for manual operations by integrating template preparation, sequencing reactions, product separation and detection. A semi-automated system, whereby PCR-amplified biotinylated genomic or plasmid DNA is immobilized on streptavidin-coated magnetic beads, has been developed.     

In vivo clearance of low-density lipoproteins and beta-very-low-density lipoproteins in normal and hypercholesterolemic White Carneau pigeons

Low-density lipoproteins (hLDL) and beta-migrating-very-low-density lipoproteins (beta-VLDL) were isolated from the plasma of cholesterol-fed White Carneau (WC) pigeons and low-density lipoproteins (nLDL) were isolated from the plasma of grain-fed WC pigeons. The lipoproteins were radiolabeled with 125I or 131I and injected into normocholesterolemic or hypercholesterolemic WC pigeons to determine their rate of clearance from the plasma. The fractional catabolic rate (FCR) of nLDL and hLDL in normocholesterolemic pigeons averaged 0.202 and 0.206 pools/h.respectively. beta-VLDL was cleared at a significantly slower rate of 0.155 pools/h. The FCR of the same lipoproteins injected into hypercholesterolemic pigeons was reduced by 17% for nLDL, 50% for hLDL and 57% for beta-VLDL, indicating that the effect of hypercholesterolemia on clearance in vivo was different for the three lipoproteins. The FCR of reductively methylated pigeon LDL (MeLDL), which gives a measure of receptor-independent clearance of LDL, was shown previously to be 0.037 pools/h. These studies suggest therefore that LDL and beta-VLDL are cleared from the plasma of normocholesterolemic and hypercholesterolemic pigeons at a rate substantially greater than that predicted for non-specific processes. Despite the reduction in the clearance rate of hLDL and beta-VLDL due to cholesterol feeding, the absolute amount of cholesterol that was cleared from the plasma by these lipoproteins was increased from approx. 200 mg/kg body weight per day in the normocholesterolemic pigeons to greater than 1000 mg/kg body weight per day in the hypercholesterolemic pigeons. This is due principally to the enrichment in cholesterol relative to protein of the lipoproteins isolated from cholesterol-fed pigeons and the failure of hypercholesterolemia to completely inhibit receptor-dependent clearance of LDL and beta-VLDL. The lower rate of clearance of beta-VLDL relative to LDL is in marked contrast to mammalian beta-VLDL, which is cleared much faster than LDL, but is consistent with the lack of apo E on pigeon lipoproteins. Apo E is the apoprotein that is thought to be responsible for the rapid clearance of beta-VLDL in normocholesterolemic mammals. The low rate of beta-VLDL clearance in pigeons also suggests that pigeons lack an apolipoprotein that function like mammalian apo E.