Biochemical changes in experimental rat brain tumors induced by ethylnitrosourea and human gliomas after dibutyryl cyclic AMP treatment.
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Biomedical subjects
Publications and source records attributed to J Takezawa.
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Urinary excretion of cyclic AMP, cyclic GMP, inorganic phosphorus, calcium, sodium, potassium and creatinine was measured in 138 healthy male and 104 healthy female humans from 2 to 68 years old. The range of cyclic nucleotide excretion was as follows: cyclic AMP (mumol/day), 1.01-10.89; cyclic GMP (mumol/day), 0.13-2.00; cyclic AMP (mumol/g creatinine), 1.52-8.93; cyclic GMP (mumol/g creatinine), 0.11-1.87. The 242 volunteers were grouped into seven classes according to age: A, 2-9 years old; B, 10-19; C, 20-29; D, 30-39; E, 40-49; F, 50-59 and G, 60-68. Average excretion (mumol/day) of cyclic AMP in class A (2.62 +/- 0.29 for males and 2.30 +/- 0.18 for females) was significantly smaller than that in other classes (4.59 +/- 0.12 for males and 3.90 +/- 0.13 for females) (p less than 0.01). Such a significant difference was not observed in cyclic GMP excretion. In terms of mumol/g creatinine, however, average excretion of both cyclic AMP and cyclic GMP in class A was greater than that in other classes. The amounts of urinary cyclic AMP and cyclic GMP (mumol/day) were correlated with age in the subjects from 2 to 16 years. A reverse correlation between the amounts of both nucleotides (mumol/g creatinine) and age was found in the young subjects. No correlation between the excretion of either urinary cyclic nucleotide and age was found in adults. A significantly positive correlation between cyclic AMP (mumol/day) and inorganic phosphorus (g/day) was found (r = 0.50 for males and 0.56 for females) (p less than 0.01). This correlation suggests that urinary cyclic AMP might reflect the activity of parathyroid hormone in normal humans. There was no significant correlation between cyclic GMP and electrolytes tested. The above results are considered to provide basic data for clinical evaluation of relevant disorders.
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Paraquat intoxication in its initial stage is characterized histologically in the lungs by atelectasis, hyaline membrane formation, alveolar edema and vascular hemorrhage often into the interstitium or air spaces. Information on the functional modification of paraquat-damaged lungs has been lacking. We evaluated lung volumes, single breath diffusing capacity of the lungs for carbon monoxide (DLCO) and static lung compliance (Cst(L)) in rats treated with paraquat or diquat. Measurements were made 12, 24, 48, and 72 h after treatment. Paraquat by intratracheal (i.t.) instillation 0.5 mg/kg or by intraperitoneal injection (i.p.) 27 mg/kg significantly decreased (P less than 0.01) the body weight, total lung capacity (TLC), functional residual capacity (FRC), vital capacity (VC), residual volume (RV), DLCO, apparent alveolar volume (VA) and Cst(L). At a lower dose level (13.5 mg/kg), the effects of paraquat peaked at about 24 h following treatment, causing a significantly decreased (P less than 0.01) VC and TLC. Diquat i.t. or i.p. had little effect on the lungs. However, diquat i.p. decreased body weight (P less than 0.01) and caused a slight increase (P less than 0.05) in VC. The data obtained are consistent with the known pathological changes seen in paraquat-damaged lungs in that, by both routes, paraquat caused severe lung damage associated with decreased elasticity of the lungs and thorax, destruction of gas exchanging alveolar surfaces, and edema. These changes were detected reliably by lung function measurements.
We measured the single-breath diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) in anesthetized male hamsters, rats, guinea pigs, and rabbits whose weights varied from 40 to 3,500 g. TLC (defined as an airway pressure of 25 cmH2O) was calculated by neon dilution. The DLCO was estimated by a modification of the single-breath method. There was a high correlation between body weight and our measurement of both the diffusing capacity and the lung volumes. No significant difference in DLCO was observed in rats when measured in different body positions, at airway pressures of 10 or 20 cmH2O, from FRC or RV, in male or female rats, or following hyperventilation.
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The effects of sympathetic nerve stimulation and administrations of sympathomimetics on the secretion of salivary kallikrein induced by stimulation of Chorda tympani were examined quantitatively and qualitatively in the dog submandibular gland. Both sympathetic stimulation and administrations of sympathomimetics such as norepinephrine, epinephrine, and isoproterenol caused increased secretion of salivary kallikrein. Among these effects, those of the sympathetic stimulation, norepinephrine, and epinephrine were not completely abolished by pretreatment with phenoxybenzamine or propranolol, but the effect of isoproterenol was abolished by pretreatment with propranolol, and was hardly influenced by pretreatment with phenoxybenzamine. From these results, it would appear that secretion of salivary kallikrein may be mediated through adrenergic alpha- and beta-receptors. On the other hand, in contrast with the activities of the salivary kallikrein secreted by Chorda tympani stimulation or administration of isoproterenol which were not inhibited by SBTI, the activities of the salivary kallikrein secreted by sympathetic stimulation as well as administration of norepinephrine or epinephrine were markedly inhibited by SBTI. From these results, it is concluded that secretion of glandular kallikrein is due either to Chorda tympani stimulation or is mediated through adrenergic beta-receptor, while secretion of plasma kallikrein is mediated through adrenergic alpha-receptor.
In the Formalin-induced pulpitis of rats and the electrically stimulated pulps of dogs, a bradykininlike substance developed by the pulps and released into a saline pool on the exposed pulps disappeared after a local application of Apernyl solution. This suggests that the possible pain-reducing or anti-in-flammatory effect of Apernyl is a result of its inhibiting bradykinin production.