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Chlorpropamide (CPM) has been reported to produce impaired water excretion due to the enhancement of renal vasopressin (ADH) action and/or due to centrally enhanced ADH release, but it is still unknown whether CPM gives rise to ADH release with a subsequent hyponatremia in diabetes mellitus (DM), which, in turn, causes an impairment of the central nervous system. In 3 patients with DM, who developed hyponatremia during the treatment with CPM, an acute water load (WL) was carried out in the presence and absence of the drug, and plasma ADH was determined with plasma and urine osmolalities. Moreover, in 2 cases, MRI scans of the brain were taken. In all the patients, acute WL tests failed to suppress completely ADH release in response to changes in plasma osmolality in the presence of CPM, which, in turn, resulted in the impaired water excretion. In the absence of CPM, an acute WL normally suppressed plasma ADH leading to the diuresis. MRI scans illustrated the presence of central pontine myelinolysis. It is likely that CPM might stimulate ADH release in DM with a subsequent hyponatremia and brain damages.

Decreases in blood pressure are well known to increase the release of vasopressin. Studies were carried out to investigate whether vasopressin responses to postural changes in blood pressure are maintained in diabetic patients with orthostatic hypotension [DM-OH(+)] as well as non-diabetic patients with orthostatic hypotension [nonDM-OH(+)] and these responses were compared with those observed in normal subjects and diabetic patients without orthostatic hypotension [DM-OH(-)]. After 30 min in the supine position, the upright posture for 40 min was maintained and then the supine for 10 min. Blood pressure and heart rate (HR) were measured every 5 min and plasma vasopressin levels (plasma AVP) were determined every 10 min. In normal subjects and DM-OH(-), mean arterial blood pressure (MABP) did not change, but HR increased significantly by the upright position. Plasma AVP did not change in these groups. On the other hand, in DM-OH(+) MABP fell abruptly and remained to decrease during the upright posture. The HR responses in this group, however, were similar to those in normal control and DM-OH(-). Plasma AVP in DM-OH(+) significantly increased only at 30 min during upright. These increases were significantly greater than those in normal and DM-OH(-). There were significant correlation in changes in MABP (delta MAP) and plasma AVP (delta AVP) in DM-OH(+) (delta AVP = -0.13 MABP + 1.5, r = -0.32, p < 0.01). Relationship between delta MABP and delta AVP in nonDM-OH(+) was similar to that in DM-OH(+). It is concluded that AVP responses to orthostatic hypotension in diabetic and non-diabetic neuropathies were attenuated, but heart rate responses in these patients ware well reserved.

To assess whether atrial natriuretic peptide (ANP) plays a role in the natriuresis induced by interleukin 1 beta (IL-1 beta), the following experiments were carried out. Experiment (Ex) I: IL-1 beta (7.5 micrograms/kg BW) was given intravenously (i.v.) in conscious hydrated rats (n = 6). Plasma ANP, vasopressin (AVP) osmolality (Posm), Na and K, urine Na (UNa V) and K excretion (UK V), osmolality and flow (UF), and mean arterial blood pressure (MABP) and heart rate were simultaneously determined. In the control group (n = 6), the drug was omitted, and the same protocols were carried out. Ex II: Three mg/kg BW of the specific ANP antagonist, HS-142-1 (HS), was administered i.v. and then, IL-1 beta (7.5 micrograms/kg BW) was given i.v. (n = 6). In the HS alone group (n = 6), IL-1 beta was omitted. The experimental protocols were the same as those in Ex I. IL-1 beta increased significantly plasma ANP and AVP and UNa V, but not UF, accompanied by decreases in Posm and UKV and increases in MABP (ExI). HS inhibited the natriuresis mediated by IL-1 beta, despite increases in plasma ANP and had no influence on plasma AVP and MABP. In the control (ExI) and HS alone (ExII) groups, these parameters did not change, except for decreases in Posm in both groups and increased plasma ANP in the latter. These results suggest that plasma ANP may play an essential role in the IL-1 beta-mediated natriuresis.

To assess whether nitric oxide (NO) formed by IL-1 beta affects vasopressin (AVP) and atrial natriuretic hormone (ANH) release and the regulation of blood pressure and body temperature, intravenous infusion of either N omega-nitro-L-arginine methyl ester (L-NAME) alone (50 micrograms/kg.body weight.min for 135 min), human recombinant interleukin 1 beta (IL-1 beta) alone (750 ng/kg.body weight.min for 120 min), or L-NAME (50 micrograms/kg.body weight.min for 135 min) with IL-1 beta (750 ng/kg.body weight.min for 120 min), was performed following priming doses of L-NAME (2 mg/kg.body weight) and IL-1 beta (7.5 micrograms/kg.body weight) into conscious rats (n = 6 each). In the control group, saline alone was administered. Plasma AVP and ANH, mean arterial blood pressure (MABP), heart rate (HR) and rectal temperature (RT) were determined. In response to L-NAME, plasma AVP significantly increased, but plasma ANH did not change, despite increases in MABP and decreases in HR. In response to IL-1 beta, both plasma AVP and ANH increased with decreases in MABP and RT without any changes in HR. With L-NAME and IL-1 beta, both plasma AVP and ANH increased, and depressor response to IL-1 beta was partly attenuated by L-NAME, without any changes in RT. With saline alone, none of these parameters changed during the study. These results suggest that NO may directly affect the release of AVP and ANH and the regulation of body temperature and blood pressure, but NO formed by IL-1 beta may not have direct effects on the release of these hormones, and the regulation of blood pressure and temperature.

To assess how interleukins (IL) affect the release of vasopressin (AVP), atrial natriuretic hormone (ANH), and ACTH and the regulation of blood pressure (BP), heart rate (HR) and rectal temperature (RT), the 3 doses of 1.73 (low dose, LD), 8.63 (medium dose, MD), and 43.16 pmol/100 gBW (high dose, HD) of human recombinant IL-1 beta were intravenously (iv) administered in conscious rats, and plasma AVP, ANH, and ACTH, BP, HR and RT were determined simultaneously. In the control group (CON), the drug was omitted. Circulatory IL-1 beta levels were determined in each dose, and indomethacin (1 mg/rat, IM) was administered iv in the HD and CON groups. Plasma IL-1 beta increased transiently following IL-1 beta administration in each group. Plasma AVP, ANH, and ACTH increased in the LD, MD, and HD groups, respectively. Mean arterial BP (MABP) and RT increased in the LD group, but HR did not change. In the MD and HD groups, MABP decreased at 30 min followed by its increase at 120 min, but RT in both groups decreased. In the CON group, these parameters did not change. IM attenuated plasma AVP and ACTH responses to HD and also inhibited decreases in MABP and RT. These results suggest that IL-1 beta affects the release of AVP and ACTH, blood pressure and thermogenesis via prostaglandins (PGs), but ANH release related to IL-1 beta may not be mediated by PGs.

The severity of various surgical stresses was classified quantitatively on the basis of degree of adrenocortical stimulation by ACTH-Z. Urinary 17-OHCS (total, free and individual fractions) were dtermined in sixteen patients who underwent various operations and were injected some doses of ACTH-Z. The following quantitative classification of surgical stress was possible. In the group of ureterolithotomy and pyeloithotomy, the severity of operative stress appeared to be equivalent to the adrenocortical stimulation caused by injection of 0.125 mg to 0.25 mg of ACTH-Z. The severity in the group of ureterotomia externa was nearly the same as that in the above group. In the group of nephrectomy by oblique incision, the severity of stress appeared to correspond to the stimulation by injection of 0.25 mg or more of ACTH-Z. The group of total nephroureterectomy with partial cystectomy showed the severity which would correspond to the degree of stimulation by injection of about 0.5 mg ACTH-Z, and the group of transperitoneal nephrectomy, by injection of 0.25 mg to 0.5 mg of ACTH-Z.

In order to detect the bladder tumor specific antigens, the monoclonal antibody (MoAb) No. 10 to human transitional cell carcinoma of the bladder (T.C.C.B.) was obtained. Hybridomas were prepared by cell fusion between the mouse myeloma cell line X 63 Ag 8.653 and the spleen cells of BALB/c mouse hyperimmune to the bladder cancer cells (grade 2) from a patient, and were cloned. Consequently 12 MoAb-producing clones were obtained for the panel screening by enzymeimmunoassay (EIA) and then 3 MoAbs (No. 10, 11 and 14) were selected for the testing of reactivity to bladder cancer cells from patients including normal epithelia. Finally No. 10 was selected as the most appropriate MoAb for this study and was determined IgM with kappa-light chains by EIA.

The mechanism of te development of hemodialysis hyperlipidemia was investigated in uremic patients on maintenance hemodialysis. Hemodialysis treatment lost large amounts of carnitine from blood into the dialysate fluid, resulting in the reduction in serum concentration of carnitine. After the treatments were repeated for more than 12 months, the serum concentration of carnitine reduced markedly and the serum triglyceride level increased significantly. In contrast, in patients who had been supplemented with commercial amino acids solution, the serum concentrations of carnitine and lipid were within normal ranges and remained unchanged even after repeated hemodialysis treatments. Carnitine administration also reduced the serum triglyceride level to or towards normal. The results suggest that carnitine depletion induced by hemodialysis treatments has a probable causal relationship to hyperlipidemia in uremic patients on long-term maintenance hemodialysis and that supplementation of carnitine or amino acids prevents carnitine depletion and improves hemodialysis hyperlipidemia.