The infiltrates of intracerebrally inoculated DBLA-6 leukemia cells of the rat were used as an experimental model of meningeal leukemia in acute leukemia. Systemic administration of an antileukemic agent (daunomycin) started at the early stage of the leukemic involvement in the arachnoid, when the blood-brain barrier (blood-cerebrospinal fluid barrier) was not yet broken in the pial microcirculation. In those animals in which the antileukemic agent alone was administered, leukemic infiltration was decreased in the dura while it was clearly observed in the subarachnoid space. In those animals in which the blood-brain barrier was damaged by acute angiotensin-induced hypertension, the chemotherapeutic effect on leukemic infiltration was markedly enhanced in the arachnoid and other parts of the brain. The blood-brain barrier dysfunction was analysed using the technique of fluorescein cine-angiography. The results indicated that the chemotherapeutic effect of the agent given systemically was impeded by the barrier, particularly in early arachnoidal infiltration of leukemic cells. Also, this in vivo experiment showed the importance of drug delivery to tumor cells growing outside blood vessels in cancer chemotherapy.

Angiotensin II↗

PubMedDate not supplied

Haemodynamic and humoral consequences of chronic infusion of vasopressin in conscious rats.

1. To determine the long-term haemodynamic and humoral effects of arginine vasopressin (AVP), a chronic intravenous infusion of AVP was performed in conscious Wistar normotensive rats. 2. AVP (1, 10, 50 or 100 ng/h) or saline as a vehicle control was infused continuously into the right jugular vein at a rate of 1 microL/h using an osmotic minipump for 7 days. 3. As a result, significant elevations of systolic blood pressure were observed in association with increases in plasma AVP concentration. Significant decreases in heart rate were observed during infusion of 100 ng/h of AVP. Mean arterial pressures measured directly on the sixth day of infusion were significantly higher in the rats given 50 ng/h (125 +/- 3 mmHg) or 100 ng/h (125 +/- 2 mmHg) compared with control rats (117 +/- 2 mmHg). Intravenous injection of the V1 antagonist, d(CH2)5Tyr(Me)AVP, significantly reduced the elevated mean arterial pressure induced by 50 or 100 ng/h of AVP (-7 +/- 4 and -11 +/- 2 mmHg, respectively). Plasma renin and norepinephrine concentrations were not affected by AVP infusion, while plasma epinephrine concentration was lower in the rats given 100 ng/h of AVP. Intravenous infusion of AVP did not alter bodyweight, serum electrolytes or osmolality. 4. These results suggest that AVP has a long-term pressor effect which is attributable to its vasoconstrictor action in conscious rats.

Animals↗

PubMedDate not supplied

Aminoglutethimide effect on circadian rhythms in urinary variables in a patient with idiopathic hyperaldosteronism.

Aminoglutethimide (AG: 750 mg/day) was administered to a patient with idiopathic hyperaldosteronism (IHA) and circadian rhythms in urinary excretion of sodium (UNaV), potassium (UKV), aldosterone (AER) and 17-OHCS were analyzed by the single cosinor method. Urine was collected every 4h for 24h on the day before and on the 1st, 3rd and 7th day of AG administration, and above variables in each sample were determined. Circadian rhythms of 14 patients with primary aldosteronism (PA) who served as controls were also analyzed. In the present case, circadian acrophases in UNaV and AER studied before AG administration occurred at 22(19) and 07(05), respectively. They were similar to those of preoperative PA-patients. Circadian acrophase in UNaV occurred earlier with AG administration and on the 7th day it was at 14(05), a value similar to that of postoperative PA-patients. Circadian mesor in AER decreased remarkably from 4.1 to 0.6 micrograms/4h with AG administration, as did circadian mesor in UKV, whereas circadian mesor and acrophase in 17-OHCS did not change. Thus, the circadian characteristics in urinary variables in the present IHA-case were pathophysiologically similar to those of PA.

17-Hydroxycorticosteroids↗