Hormones and liver cytoplasm. 4. Ribonucleotides, ribonucleic acid synthesis and protein synthesis after adrenalectomy.
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Heat-killed cells of Group A streptococci caused death of the adrenalectomized rat. While the adrenalectomized rat readily succumbed to intraperitoneal infection with living cells, death was due primarily to toxicity. The normal rat was highly resistant under either condition. For studies on the toxic materials, the cells of numerous serological types of group A streptococci, and of a Group B and a Group D streptococcus, were extracted with 0.1 N HCl at 100 degrees C. or by sonic oscillation. The extracts, containing macromolecular components, were subjected to chemical fractionation and purification. C substance and M protein of Group A streptococci released from the cell by sonic oscillation were toxic to the adrenalectomized rat in quantities of 1 mg./100 gm. rat. Death usually occurred within 2 hours. On the other hand, C substance and M protein released from the cell with HCl at 100 degrees C. were relatively non-toxic to the adrenalectomized rat. The sonic-extracted C substance of streptococcal Groups B, C, and D was also toxic. The toxic property of the C and M preparations was neutralized in vitro in each case by group and type-specific rabbit antiserum. Heterologous antiserum was without effect. Adrenalectomized rats which received homologous antiserum 18 hours before challenge were also resistant to the toxicity of the C and M preparations. Trypsin destroyed the toxic effect of the M protein preparations and was without effect on the toxicity of the C substance. The R antigen and a nucleoprotein component of Group A streptococci, preparations of protein from Groups B and D streptococci, and coagulase from Staphylococcus aureus were all found to be essentially non-toxicic for the adrenalectomized rat. Large quantities of peptone, crystalline albumin, and rabbit serum were also without effect.
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The intravenous administration of the antiadrenaline drug phenoxybenzamine (Dibenzyline) markedly raised the arterial adrenaline and noradrenaline concentration in dogs lightly anaesthetized with thiopentone. Graded haemorrhage led to a further rise in the amounts of amine. In adrenalectomized dogs, phenoxybenzamine moderately increased the plasma noradrenaline concentration. During haemorrhagic hypotension, previous treatment of adrenalectomized animals with phenoxybenzamine led to a significantly greater rise in plasma noradrenaline compared with that of adrenalectomized animals subjected to haemorrhage without treatment with phenoxybenzamine. Thus, phenoxybenzamine (1) raised plasma amine concentration largely due to adrenal medullary stimulation, and (2) led to increased plasma noradrenaline concentrations during sympathetic stimulation in adrenalectomized animals. The previous administration of phenoxybenzamine reduced the amount of blood which could be withdrawn before final circulatory collapse in both normal and adrenalectomized dogs.
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Changes in serous and encephalic serotonin in hypophysectomized or adrenalectomized rats have been observed. Adrenalectomy produces a decrease of serous serotonin and an increase of the serotonin of hemispheres, base, and medulla oblongata; with hypophysectomy, serotonin is also reduced in serum and increased only in the base and medulla oblongata.
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