PubMed · 5452133
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I Ansari, G Wallace, C A Clemetson, V R Mallikarjuneswara, C D Clemetson. 1970. Tilt caesarean section.. https://doi.org/10.1111/j.1471-0528.1970.tb03597.x
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We have demonstrated recently that nitrous acid or nitric oxide converts 2'-deoxyguanosine (dGuo) into 2'-deoxyoxanosine (dOxo) [Suzuki, T., Yamaoka, R., Nishi, M., Ide, H., & Makino, K. (1996) J. Am. Chem. Soc. 118, 2515-2516]. In the present study, we have measured susceptibility of the N-glycosidic bond of dOxo to spontaneous hydrolysis and its base-pairing stability to evaluate the biological significance of dOxo as a new lesion in DNA. When oligodeoxynucleotide d(T5OT6) (O = dOxo), isolated from nitrous acid-treated d(T5GT6), was incubated at pH 4.0 and 70 degrees C, hydrolysis of the N-glycosidic bond of dOxo occurred with a first-order rate constant. Comparison of the rate constants with those of dGuo and dXao indicates that the N-glycosidic bond of dOxo was as stable as that of dGuo in d(T5GT6) and hydrolyzed 44-fold more slowly than that of 2'-deoxyxanthosine (dXao), a simultaneously generated damage by nitrous acid and nitric oxide. For the estimation of the base-pairing stability, UV melting curves were measured for the duplexes of d(T5OT6).d(A6NA5) (N = A, G, C, and T) at neutral pH. The Tm values obtained were 15.3, 14.1, 19.3, and 16. 3 degrees C for N = A, G, C, and T, respectively, which are much lower than that of the intact duplex containing a G.C pair at the same position [d(T5GT6).d(A6CA5), Tm = 32.8 degrees C] but comparable with those of d(T5XT6).d(A6NA5) (X = dXao, Tm = 14.8-22.3 degrees C). CD spectra of the four duplexes containing dOxo showed preservation of the structure of the intact duplex at low temperature. UV and NMR pH-titration studies indicated the pKa for the ring-opening and -closing equilibrium to be 9.4, implying that dOxo is in the ring-closed form at physiological pH. This structure appears to be not suitable geometrically for the hydrogen bond formation with a specific counter base, thus causing equally low Tm values for all the counter bases. Consequently, these results imply that dOxo, a novel DNA lesion, may have an important and unique role in mutagenic events in cells.
OBJECTIVE: To examine the effect of participation in a long-distance race on serum electrolyte concentrations, estimated exchangeable cation content, and acid-base status of Alaskan sled dogs. DESIGN: Prospective study. ANIMALS: 9 male and 5 female, sexually intact, physically fit Alaska sled dogs between 18 and 48 months old. PROCEDURE: Body weight was recorded, and blood samples were collected from dogs before, during, and after a 300-mile race. RESULTS: Serum sodium and potassium concentrations decreased during the race, as did serum total protein, albumin, and globulin concentrations and PCV. Effects on acid-base status were minimal. Body weight and estimated total exchangeable cation content in dogs also decreased significantly during the race. CLINICAL IMPLICATIONS: Prolonged running is associated with decreases in serum cation concentration and estimated total exchangeable cation content in dogs, as in human beings and horses. However, the mechanism of the decrease in serum cation concentration likely differs among species. Clinical abnormalities associated with cation depletion were not observed in the dogs in this study.
We investigated the effects of omeprazole and Sch 28080, a more specific and a more potent inhibitor of K+,H+-ATPase than omeprazole, in canine cerebrospinal fluid (CSF) production. CSF production was measured by ventriculocisternal perfusion (VCP) technique in three groups (n = 10 in each group) of anesthetized, paralyzed and mechanically ventilated dogs. Group I served as control, Sch 28080 (10(-4) mol/l of synthetic CSF) was added to VCP in group II, and omeprazole (10(-5) mol/l of synthetic CSF) was added to VCP in group III, after baseline control CSF production had been determined at 15, 30, 45, and 60 min. Comparing the three groups, the mean baseline values for CSF production did not differ significantly. However, the percent decreases in CSF production in the omeprazole treated group were 26 +/- 17 and 24 +/- 13 at 210 and 225 min, which were significantly more than the respective values in the control group. Percent decrease in CSF production in Sch 28080 was not significantly different from that in the control group. We conclude that in the canine model, physiological doses of omeprazole decrease CSF production by about 26%. However, the effect is independent of the K+,H+-ATPase activity, since Sch 28080 which is more potent than omeprazole did not significantly affect CSF production.