Antidiuretic Response of Kidneys to Different Modes of Vasopressin Administration

The effect of vasopressin given simultaneously with a water load was studied in healthy human volunteers. During maximal water diuresis induced by oral water load of 20 ml water per kilogram body weight, the excreted water fraction was 12.4%, whereas the excretion of osmotically free water was 10.0 ± 1.8 ml/min per 1.73 m² of body surface area. These data suggest that the secretion of arginine vasopressin by the neurohypophysis was almost completely blocked. A water load simultaneously with 8 g sublingual or 0.2 mg oral desmopressin caused a strong and long-lasting antidiuretic response accompanied by a drastic increase in the reabsorption of osmotically free water in the kidneys. It was shown that the magnitude and the time course of the antidiuretic response to therapeutic doses of desmopressin depended on the mode of its administration.     

Evolutionary Advantages of Participation of Vasopressin instead of Vasotocin in Regulation of Water–Salt Balance in Mammals

In experiments on non-anesthetized Wistar white rats there was studied reaction of kidney to an intramuscular injection of arginine vasotocin or arginine vasopressin at doses from 0.001 to 0.05 µg/100 g body mass on the background of a water load. Water (5 ml/100 g body mass) was administered through a catheter into stomach to suppress secretion of endogenous antidiuretic hormone (ADH). In experiments with water administration, diuresis increased due to a decrease of osmotic permeability of renal tubules and to excretion of osmotically free water, with the constant clearance of sodium ions. Injection of 0.05 µg arginine vasopressin led to a marked decrease of diuresis due to a rise of reabsorption of osmotically free water without elevation of excretion of osmotically active substances. Injection of the same dose of arginine vasotocin resulted in no increase of diuresis; however, reabsorption of osmotically free water and excretion of osmotically active substances including sodium ions were more pronounced. Hence, both vasotocin and vasopressin increased osmotic permeability of the tubular epithelium, but vasotocin, unlike vasopressin, promoted reduction of reabsorption of sodium ions and their loss with urine. A suggestion is made that one of the reasons for replacement in mammals of the molecular ADH forms (vasotocin by vasopressin) was the absence of the pronounced natriuretic effect in arginine vasopressin. This was of crucial significance to preserve sodium ions in the organism, to maintain water–salt balance in animals adapted to the terrestrial life, and to provide not only osmo-, but also volumoregulation.     

The effect of glucose on antidiuretic hormone absorption in the rat and frog small intestine

Administration of 5 ml/100 g body weight of 1% glucose solution to stomach produced the same diuretic kidney response in fasted Wistar rats as administration of the same amount of water. Intragastric administration of arginine vasopressin along with the water load evoked an antidiuretic response. Arginine vasopressin in the same volume of glucose induced no kidney response difference as compared with the hormone action in experiments with water load. 0.1 nmol of arginine vasotocin, having been itroduced into the rat isolated ileum, prevented the effect of glucose on the hormone absoption. 0.1 nmol of arginine vasotocin, having been introduced into the frog isolated ileum along with isotonic glucose solution, increased the hormone absorption; fructose did not affect this process whereas mannitol decreased absorption ofarginine vasotocin. This absorption was also reduced by intraileal introduction of arginine vasotocin with the hypotonic Ringer solution. The findings suggest that glucose in the rat gastrointestinal tract does not affect arginine vasopressin absorption in vivo, whereas in the frog ileum glucose increases arginine vasotocin absorption in vitro.     

Biological half-life and organ distribution of [3H]8-arginine vasopressin following administration of vasopressin receptor antagonist OPC-31260

The effects of the antidiuretic (V(2)) non-peptide receptor antagonist OPC-31260 on the plasma vasopressin level and the biological half-life and organ distribution of radiochemically pure, biologically active [(3)H]8-arginine vasopressin [spec. act.: 15.9 mCi/mmol (588 GBq/mmol)] were studied in Wistar rats. The plasma vasopressin level increased significantly throughout the whole experimental period (24 h). There was no change in the fast phase of the curves of total radioactivity disappearance from the plasma after the administration of [(3)H]arginine vasopressin (control: 1.51+/-0.17 min, OPC-31260-treated: 1.42+/-0.12 min, n=10). The fast phase of the disappearance curves of intact [(3)H]arginine vasopressin did not change either following the administration of OPC-31260 in a dose of 30 mg/kg p.o. (control: 1.06+/-0.19 min, OPC-31260-treated: 1.00+/-0.15 min, n=6). The slow phase of the biological half-life, which is characteristic for the examined compound, proved to be significantly longer (total radioactivity control: 9.29+/-0.61 min, OPC-31260-treated: 12.33+/-0.42 min, P<0.05, n=10; [(3)H]arginine vasopressin radioactivity: control: 5.96+/-0.58 min, OPC-31260-treated: 8.90+/-0.37 min, P<0.05, n=6). In the control rats, the radioactivity was accumulated to the greatest extent in the neurohypophysis, adenohypophysis and kidney. Following OPC-31260 administration, significantly more radioactive compounds accumulated in the kidney (control: 0.30+/-0.052 total radioactivity %/100 mg organ weight, OPC-31260-treated: 0.50+/-0.133 total radioactivity %/100 mg organ weight, P<0.05, n=10) and neurohypophysis (control: 0.37+/-0.053 total radioactivity %/100 mg organ weight, OPC-31260-treated: 0.52+/-0.076 total radioactivity %/100 mg organ weight, P<0.05, n=10). Our results permit the conclusion that the antidiuretic antagonist OPC-31260 not only blocks the V(2) receptors, but also increases the biological half-life of vasopressin. The longer biological half-life of vasopressin following OPC-31260 administration may play a role in the elevation of the plasma vasopressin level.     

The effect of glucocorticoids on the diluting capacity of the kidney of a desert rodent: Gerbillus campestris]

The ability to excrete a water load was studied in Wistar rats and in gerbils (Gerbillus campestris). The rat excreted the entire water load in less than 2 h whereas Gerbillus campestris excreted less than 60% of the water load in 4 h. The gerbils which had received a dose of 15 micrograms/100 g body weight dexamethasone improved their rate of excretion which attained 92 +/- 6% in 2 h 30 min. The antidiuretic hormone (ADH) measured by radioimmunoassay at the time of maximum diuresis was undetectable in rats; in contrast, in gerbils the level of ADH remained relatively high (55.4 +/- 6.7 pg/ml). We conclude that the partial inability of the gerbil's kidney to excrete a water load is due to a high ADH level and probably to a low concentration of glucocorticoids.     

Desmopressin, but not vasopressin, decreases activity of the hypothalamo-neurohypophysial system in Brattleboro rats

The pituitary neural lobe of homozygous Brattleboro rats has high rates of glucose utilization not affected by chronic treatment with exogenous vasopressin, despite attenuation of polydipsia and polyuria. We evaluated whether this effect may result from the inability of vasopressin to affect the hypothalamo-neurohypophysial metabolism or from the development of resistance to chronic vasopressin treatment. We used the [14C]deoxyglucose method to compare 28-h effects of vasopressin treatment (5 U/kg, i.m., twice a day) with that of desmopressin (100 micrograms/kg, i.p., once a day), a long-lasting antidiuretic hormone, on glucose utilization of the hypothalamo-neurohypophysial system and related structures in conscious homozygous Brattleboro rats. Vasopressin and desmopressin reduced water intake, plasma osmolality and plasma Na+ concentration similarly. Vasopressin decreased glucose utilization in the supraoptic nucleus, subfornical organ and median preoptic nucleus, but did not alter activity in the paraventricular nucleus and neural lobe. Desmopressin decreased glucose utilization in all these structures. The results indicate that desmopressin has a more potent inhibitory action on the hypothalamo-neurohypophysial system than vasopressin over this short duration of treatment. The lack of response in the neural lobe from chronic treatment with vasopressin seems to be due to its inability to affect the paraventricular nucleus metabolism. The maintenance of metabolic activity in the paraventricular nucleus of vasopressin-treated Brattleboro rats suggests that this structure contributes importantly to the metabolism of neural lobe.     

Renin-Aldosterone System in Osmoregulatory Reactions of Healthy Subjects in Response to Desmopressin

Systemic regulation of osmotic and ionic homeostasis was studied in healthy male volunteers after oral administration of desmopressin. Endogenous secretion of the antidiuretic hormone was inhibited by a water load (WL, 2% of the body mass). Desmopressin exerted an antidiuretic effect. In addition, the WL portion excreted during 4 h decreased and the urine osmolality at peak diuresis increased with the absence of osmotically free water. At maximum diuresis, the ratio between concentrations of osmotically active substances in the urine and in the blood was high, which reflected an intense antidiuretic effect. Desmopressin progressively decreased the rate of sodium excretion owing to a change of sodium reabsorption in the kidneys. The WL increased the level of aldosterone and the activity of renin in blood plasma 1.5 h after its administration. Contrary to the control series, desmopressin stimulated the renin-angiotensin-aldosterone system only by the end of the 4-h observation period. A significant negative correlation between the aldosterone level and the rate of sodium excretion was observed 3 h after the beginning of testing (r = ?0.76). Thus, under conditions of water loading, desmopressin had a specific antidiuretic effect involving systemic mechanisms of ion regulation.     

Prolonged hypobaric hypoxemia attenuates vasopressin secretion and renal response to osmostimulation in men.

Effects of hypobaric hypoxemia on endocrine and renal parameters of body fluid homeostasis were investigated in eight normal men during a sojourn of 8 days at an altitude of 4,559 m. Endocrine and renal responses to an osmotic stimulus (5% hypertonic saline, 3.6 ml/kg over 1 h) were investigated at sea level and on day 6 at altitude. Several days of hypobaric hypoxemia reduced body weight (-2.1 +/- 0.4 kg), increased plasma osmolality (+5.3 +/- 1.4 mosmol/kgH(2)O), elevated blood pressure (+12 +/- 1 mmHg), reduced creatinine clearance (122 +/- 6 to 96 +/- 10 ml/min), inhibited the renin system (19.5 +/- 2.0 to 10.9 +/- 0.9 mU/l) and plasma vasopressin (1.14 +/- 0.16 to 0.38 +/- 0.06 pg/ml), and doubled circulating levels of norepinephrine (103 +/- 16 to 191 +/- 35 pg/ml) and endothelin-1 (3.0 +/- 0.2 to 6.3 +/- 0.6 pg/ml), whereas urodilatin excretion rate decreased from day 2 (all changes P < 0.05 compared with sea level). Plasma arginine vasopressin response and the antidiuretic response to hypertonic saline loading were unchanged, but the natriuretic response was attenuated. In conclusion, chronic hypobaric hypoxemia 1) elevates the set point of plasma osmolality-to-plasma vasopressin relationship, possibly because of concurrent hypertension, thereby causing hypovolemia and hyperosmolality, and 2) blunts the natriuretic response to hypertonic volume expansion, possibly because of elevated circulating levels of norepinephrine and endothelin, reduced urodilatin synthesis, or attenuated inhibition of the renin system.     

Role of V1- and V2-receptors in mechanism of physiological paradox--an increase of reabsorption of the solute free water and simultaneous rise of diuresis

In experiments on non-anesthetized rats with administration into stomach of water (5 ml/100 g body mass) direct correlation has been found between an increase of diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an increase of diuresis and simultaneous rise reabsorption of solute free water (r = 0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to inhibition of sodium re- absorption, with the solute excretion fraction increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological paradox - an increase of diuresis with the simultaneous increase of reabsorption of solute free water - has been revealed at night hours in children with tendency for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this phenomenon consists in a rise of diuresis due to a decrease of sodium ion reabsorption in the ascending Henle loop limb. A problem is discussed of the homeostatic significance of a decrease of sodium reabsorption combined with an increase of solute-free water reabsorption; it is suggested that this phenomenon is based on a redistribution of reabsorption inside the nephron - a decrease of ion and water reabsorption in the initial parts of the nephron distal segment and an increase of solute free water reabsorption with the antidiuretic hormone-stimulated high osmotic permeability of terminal parts of renal tubules. An intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic component of response to arginine-vasotocin, while injection of V2-antagonist (OPC-31260) eliminated the antidiuretic component.     

A bivariate radioimmunoassay for arginine vasopressin and the synthetic antidiuretic agent 1-deamino-8-D-arginine vasopressin (desmopressin)

Pairs of radioimmunoassays, each of which include a two-dimensional matrix of standards, have been previously employed to resolve specificity problems in steroid immunoassay. In this study the bivariate radioimmunoassay principle has been applied to simultaneous measurement of plasma antidiuretic hormone, arginine vasopressin, and the synthetic antidiuretic agent 1-deamino-8-D-arginine vasopressin (desmopressin), by utilizing two arginine vasopressin antisera which show significantly different cross-reactivities with the synthetic analog. Data processing consists of mathematical representation of two curved dose-response surfaces followed by solution of this pair of nonlinear simultaneous equations for the unknown arginine vasopressin and desmopressin concentrations. Details of numerical procedures are given in the Appendix. The assay appears entirely adequate in terms of sensitivity, accuracy, and precision for measurement of these antidiuretic agents in clinical samples. No evidence of significant covariance in estimated concentrations could be detected but precision of estimation is (not unexpectedly) a function of the concentration of both agents. The plasma disappearance half-time of desmopressin (probably the second of a biphasic disappearance) was estimated as 37 min in one normal subject, which is in good agreement with a previously reported value of 30 min.     

Evaluation of synthetic antidiuretic hormone as a corrective substance following a head-down tilt

The effects of the administration of desmopressin, a synthesized analog of antidiuretic hormone, together with a water-salt supplement on the renal function and orthostatic stability were investigated. Six healthy men spent 12 h in the head-down tilt (HDT) position. It was demonstrated that administration of desmopressin led to normalization of salt and water homeostasis; moreover, the tolerance of the standard 20 min passive standing test was improved significantly. These observations indicate that intake of the synthetic vasopressin analog combined with water-salt supplement counteracts hypohydration of the body during HDT and improved orthostatic tolerance.     

Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man.

Corticotrophic secretion of ACTH is stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and suppressed by glucocorticoids. In vitro and preclinical studies suggest that atrial natriuretic factor (ANF) may be a peptidergic inhibitor of pituitary-adrenocortical activity. The aim of this study was to elucidate a possible role of ANF as a modulator of ACTH release in humans. A bolus injection of 100 micrograms human CRH (hCRH) during a 30 min intravenous infusion of 5 micrograms/min human alpha atrial natriuretic factor (h alpha ANF) was administered at 19:00 to six healthy male volunteers. In comparison to saline, a blunted CRH-stimulated secretion of ACTH (mean maximum plasma level +/- SD 45 min after hCRH: saline 46.2 +/- 14.2 pg/ml, h alpha ANF 34.6 +/- 13.8 pg/ml, p-value = 0.007) and a delayed rise (10 min) in cortisol were detected. The maximum plasma cortisol levels remained nearly unchanged between saline and h alpha ANF administration (mean maximum plasma level +/- SD 60 min after hCRH: saline 182 +/- 26 ng/ml, h alpha ANF 166 +/- 54 ng/ml). No effects of h alpha ANF on basal cortisol levels were observed; in contrast, basal ACTH plasma levels were slightly reduced. Basal blood pressure and heart rate remained unaffected. In the control experiment, infusion of 3 IU AVP in the same experimental paradigm increased basal and stimulated ACTH and cortisol levels significantly in comparison to saline. These observations suggest that intravenously administered haANF inhibits the CRH-stimulated release of ACTH in man.     

Role of antidiuretic activity in the inhibition of renin secretion by vasopressin in anesthetized dogs

The nature of the activity of vasopressin which is responsible for the inhibition of renin secretion was studied by comparing the effects of vasopressin (AVP) and analogs of AVP in anesthetized water-loaded dogs. Infusion of AVP (1.0 ng/kg/min) increased mean arterial pressure (MAP) and decreased heart rate (HR) and free water clearance (CH2O). Plasma renin activity (PRA) decreased from 11.9 +/- 4.7 to 3.8 +/- 1.7 ng/ml/3 hr (p less than 0.05). A selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng/kg/min), which had no effect on MAP or HR but was effective as AVP in decreasing CH2O, decreased PRA from 13.5 +/- 4.6 to 7.0 +/- 2.9 ng/ml/3 hr (p less than 0.05). Infusion of a selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng/kg/min), increased MAP and decreased HR but did not decrease CH2O or PRA. A vasoconstrictor antagonist, d(CH2)5Tyr(Me)AVP (10 micrograms/kg), completely blocked the MAP and HR responses to AVP but did not block the decrease in CH2O or PRA (5.9 +/- 1.8 to 2.9 +/- 1.6 ng/ml/3 hr) (p less than 0.001). Infusion of the 0.45% saline vehicle had no significant effect on MAP, HR, CH2O or PRA. These results indicate that the inhibition of renin secretion by vasopressin in anesthetized water-loaded dogs is due to its antidiuretic activity.     

Antidiuretic activity of terlipressin (triglycyl-lysine vasopressin)--role of pressure natriuresis.

Terlipressin (triglycyl-lysine vasopressin TP), a "hormonogen" analogue, was introduced in gastroenterology for its low and protracted vasopressor action, reducing bleeding from gastrointestinal tract. Its antidiuretic activity, estimated originally in ethanol-anaesthetized rats (Sawyer's method) was claimed to be equally low and protracted. We performed several series of antidiuretic tests on conscious rats (Burn's method) with the following results. TP in low doses of 0.05-1.0 micrograms/kg exhibited typical dose-dependent antidiuretic effect. In the dose of 0.2 micrograms/kg, the dynamics of urine and sodium excretion did not differ from that after equivalent dose of lysine vasopressin and equipotent dose of DDAVP. The antidiuretic potency of TP (estimated by parallel line assay) was 175.0 U/mg. TP in doses of 5.0 and 20.0 micrograms/kg exhibited limited diuresis and marked natriuresis. High osmolality and sodium content were present in all portions of excreted urine. The discrepancy between previous and our results concerning antidiuretic activity of TP and the role of pressure natriuresis for overall renal action of TP are discussed.     

Differences in the pregnancy-terminating effectiveness of an LH-RH analogue by subcutaneous, vaginal, rectal, and nasal routes in rats

A long-acting analogue of LH-RH, des-Gly10-[D-Leu6]-LH-RH-ethylamide (TAP-144), was administered once or twice on day 9 of pregnancy by subcutaneous, vaginal, rectal, and nasal routes to rats; the pregnancy-terminating effectiveness of these routes was determined on day 14. When rats were given a single dose of TAP-144, the ED50 value was 1.2 micrograms/100 g body weight by the vaginal route, the effectiveness being 752 and 1,221 times higher than those by the subcutaneous and rectal routes, respectively. Nasal administration was not effective in terminating pregnancy even at a high dose of 2,000 micrograms/100 g body weight. The addition of a surfactant (BL-9) did not increase the effectiveness by the rectal route. When TAP-144 was administered twice a day, the effectiveness was markedly increased by every route. The ED50 values were 0.32 microgram/100 g body weight/time by the subcutaneous route, which was comparable to that of the vaginal route, 14.2 micrograms of the rectal route, and 84.6 micrograms of the nasal route. The addition of the surfactant increased the effectiveness 26 times by the nasal route but not by the rectal route. The pregnancy-terminating effect of TAP-144 was reversed by treatment with progesterone.     

Downward resetting of the osmotic threshold for thirst in patients with SIADH

The syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by euvolemic hyponatremia. Patients with SIADH continue to drink normal amounts of fluid, despite plasma osmolalities well below the physiological osmotic threshold for onset of thirst. The regulation of thirst has not been previously studied in SIADH. We studied the characteristics of osmotically stimulated thirst and arginine vasopressin (AVP) secretion in eight subjects with SIADH and eight healthy controls and the nonosmotic suppression of thirst and AVP during drinking in the same subjects. Subjects underwent a 2-h infusion of hypertonic (855 mmol/l) NaCl solution, followed by 30 min of free access to water. Thirst rose significantly in both SIADH (1.5 +/- 0.6 to 8.0 +/- 1.2 cm, P < 0.0001) and controls (1.8 +/- 0.8 to 8.4 +/- 1.5 cm, P < 0.0001), but the osmotic threshold for thirst was lower in SIADH (264 +/- 5.5 vs. 285.9 +/- 2.8 mosmol/kgH(2)O, P < 0.0001). SIADH subjects drank volumes of water similar to controls after cessation of the infusion (948.8 +/- 207.6 vs. 1,091 +/- 184 ml, P = 0.23). The act of drinking suppressed thirst in both SIADH and controls but did not suppress plasma AVP concentrations in SIADH compared with controls (P = 0.007). We conclude that there is downward resetting of the osmotic threshold for thirst in SIADH but that thirst responds to osmotic stimulation and is suppressed by drinking around the lowered set point. In addition, we demonstrated that drinking does not completely suppress plasma AVP in SIADH.     

Diuretic, natriuretic and hypotensive effects of synthetic atrial natriuretic factor in conscious newborn calves

The effects of synthetic Atrial Natriuretic Factor (ANF) on urine flow rate, sodium excretion, potassium excretion and arterial blood pressure were studied in 10-12 days-old female calves. In four female calves fitted with a Foley catheter, an intravenous administration of ANF (Ile-ANF 26; 1.6 micrograms/kg body wt during 30 min) induced an increase (P less than 0.01) in urine flow rate (from 1.8 +/- 0.2 to 12.8 +/- 1.1 ml/min), sodium excretion (from 0.15 +/- 0.02 to 0.81 +/- 0.06 mmol/min) and free water clearance (from 0.13 +/- 0.9 to 5.16 +/- 0.5 ml/min). It had no significant effect on potassium excretion. In four calves chronically-instrumented with a carotid catheter, an intravenous administration of synthetic ANF alone (1.6 micrograms/kg body wt during 30 min) induced a gradual decrease (P less than 0.01) in systolic, diastolic and mean arterial blood pressure (from 112 +/- 4 to 72, from 72 +/- 2 to 61 +/- 1 and from 90 +/- 2 to 65 +/- 2 mmHg respectively, at the end of ANF infusion). An intravenous administration of angiotensin II (AII) (0.5 micrograms/kg body wt during 45 min) induced a significant increase in systolic, diastolic and mean arterial blood pressure which was antagonized by an i.v. bolus injection of ANF (0.125 micrograms/kg body wt). However, during a simultaneous administration of AII (0.3 micrograms/kg body wt during 30 min) and ANF (1.6 micrograms/kg body wt. during 30 min), the atrial peptide did not influence the pressure action of AII. These findings indicate that the conscious newborn calf is sensitive to diuretic, natriuretic and hypotensive effects of synthetic ANF.     

Effect of arginine on the GHRH-stimulated GH secretion in patients with hyperthyroidism.

Patients with hyperthyroidism have reduced GH responses to pharmacological stimuli and reduced spontaneous nocturnal GH secretion. The stimulatory effect of arginine on GH secretion has been suggested to depend on a decrease in hypothalamic somatostatin tone. The aim of our study was to evaluate the effects of arginine on the GH-releasing hormone (GHRH)-stimulated GH secretion in patients with hyperthyroidism. Six hyperthyroid patients with recent diagnosis of Graves' disease [mean age +/- SEM, 39.2 +/- 1.4 years; body mass index (BMI) 22 +/- 0.4 kg/m2] and 6 healthy nonobese volunteers (4 males, 2 females; mean age +/- SEM, 35 +/- 3.5 years) underwent two experimental trials at no less than 7-day intervals: GHRH (100 micrograms, i.v.)-induced GH secretion was evaluated after 30 min i.v. infusion of saline (100 ml) or arginine (30 g) in 100 ml of saline. Hyperthyroid patients showed blunted GH peaks after GHRH (13.2 +/- 2.9 micrograms/l) as compared with normal subjects (23.8 +/- 3.9 micrograms/l, p < 0.05). GH peaks after GHRH were only slightly enhanced by arginine in hyperthyroid subjects (17.6 +/- 2.9 micrograms/l), whereas, in normal subjects, the enhancement was clear cut (36.6 +/- 4.4 micrograms/l; p < 0.05). GH values after arginine + GHRH were still lower in hyperthyroid patients with respect to normal subjects. Our data demonstrate that arginine enhances but does not normalize the GH response to GHRH in patients with hyperthyroidism when compared with normal subjects. We hypothesize that hyperthyroxinemia may decrease GH secretion, both increasing somatostatin tone and acting directly at the pituitary level.     

Variation in the effects of antidiuretic hormone on the isolated skin of the toad, Scaphiopus couchi.

The rate of active sodium transport as measured by short-circuit current across the isolated skin of the toad, Scaphiopus couchi, was elevated following vasopressin (0.2 units/ml) or arginine vasotocin (0.1 units/ml) treatment of skins from active animals at all times of the year tested. Skins from dormant animals showed no such elevation at any time of the year. The rate of active sodium transport was elevated following treatment with dibutyryl cyclic AMP (2.5mM) plus theophylline (10 mM) in all skins tested. The hydraulic conductivity of isolated skins from both active and dormant animals showed no significant change following treatment with vasopressin (0.2 units/ml) or arginine vasotocin (0.1 units/ml except on the first day following emergence from dormancy in the field. A correlation was, therefore, observed between the occurrence of a hydroosmotic response to antidiuretic hormones and the seasonal exposure of S. couchi to standing water. A small but significant elevation of hydraulic conductivity was observed across the skins of dormant toads following treatment with dibutyryl cyclic AMP (2.5 mM) plus theophylline (10 mM) whereas a substantial elevation was observed with the skins of active animals.     

Ciprofloxacin in the prevention and treatment of surgical infections]

A clinico-laboratory study on ciprofloxacin made by Bayer (Germany) was applied to patients with extended posttraumatic wounds and performed with the aim of preventing postoperative purulent complications in patients operated on the organs of the gastrointestinal tract. In the both groups ciprofloxacin was administered orally in doses of 500 and 1000 mg and intravenously in a dose of 200 mg. The results of the assay on ciprofloxacin sensitivity of the isolates from the wound excretion and urine showed that they were more sensitive to ciprofloxacin than to aminoglycosides and cephalosporins. 15 minutes after the intravenous administration the serum concentration of ciprofloxacin amounted to 7.5 +/- 0.9 micrograms/ml and in 6 hours it was equal to 0.45 +/- 0.45 micrograms/ml, the mean concentrations of ciprofloxacin being attained in the bile (8.7 +/- +/- 3.9 micrograms/ml), gallbladder wall (5.5 +/- 3.8 micrograms/g), liver (0.73 micrograms/g), muscles (1.93 micrograms/g) and tendon (0.15 microgram/g). After the oral administration in a dose of 500 mg ciprofloxacin was detected in the blood serum in an amount of 2.0 +/- 0.7 micrograms/ml in 1 hour and in an amount of 0.9 +/- 0.13 micrograms/ml in 6 hours. After the drug oral administration in a dose of 1000 mg the maximum concentrations were: 6.34 +/- 4.2 micrograms/ml on the average and 2.1 +/- 0.8 micrograms/ml in 6 hours (0.4 micrograms/g in the muscles, 1.4 micrograms/g in the skin and 0.34 micrograms/g in the bones). The study showed that ciprofloxacin was a highly efficient antimicrobial agent in the treatment of the complicated wound infections and the prophylaxis of the purulent complications during the postoperative period in the patients operated on gastrointestinal organs.