Assessment of obestatin and arginine vasopressin (AVP) levels in acute renal failure and acute heart failure.

OBJECTIVE: We conducted this study to assess the clinical application of obestatin and arginine vasopressin (AVP) levels in cases of acute renal failure (ARF) and acute heart failure (AHF). PATIENTS AND METHODS: 30 cases of ARF, 30 cases of AHF, 30 cases of ARF complicated with AHF, and 30 cases of healthy subjects (control group) were successively selected. An ELISA test was conducted to detect levels of obestatin and AVP. Routine biochemistry testing was applied to detect the levels of serum creatinine and calculate the glomerular filtration rate (GFR). Electrochemiluminescence double antibody sandwich fluorescence immune testing was applied to detect NT-proBNP and color Doppler ultrasound diagnostic apparatus was applied to detect renal arterial resistive index (RI) and left ventricular ejection fraction (LVEF). The 30-day mortality was documented. RESULTS: Compared to other groups, the group of patients suffering from ARF complicated with AHF had significantly higher levels of obestatin and AVP, and significantly higher levels of serum creatinine, NT-proBNP and RI; however, their GFR and LVEF levels were the lowest. Differences were statistically significant (p < 0.05). Levels of obestatin and AVP are positively correlated with serum creatinine, NT-proBNP and RI levels, but negatively correlated with GFR and LVEF levels. The mortality rate of the group suffering from ARF complicated with AHF was markedly increased (p = 0.035). The obestatin and AVP levels of the death group were significantly higher than that of the survival group. However, the comparison among levels of serum creatinine, GFR, NT-proBNP, RI and LVEF revealed no statistical significance (p > 0.05). CONCLUSIONS: Obestatin and AVP levels were closely related to the severity of ARF and AHF and survival prognosis, which could be a sensitive indicator for diagnoses and prognoses.

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

Preoperative assessment for pituitary surgery.

Evaluation of pituitary function is essential before pituitary surgery. In hyperprolactinaemic patients with a pituitary macrolesion, tumoral secretion of prolactin must be distinguished from 'disconnection' hyperprolactinaemia; serum prolactin >200 mcg/l is virtually diagnostic of a macroprolactinoma whereas levels <80 mcg/l usually indicate 'disconnection'. The prolactin 'hook effect' should be excluded. A minimum set of pre-operative endocrine tests should include serum electrolytes, cortisol (at 08.00-09.00 h), free-T4, TSH, prolactin, oestradiol/testosterone, LH, FSH and IGF-1. Some clinicians will choose to perform pre-operative Synacthen or insulin tolerance testing to further define ACTH reserve. If basal cortisol, Synacthen or insulin tolerance test results are abnormal, steroid supplementation is indicated for at least the first 48 h after surgery. If pre-operative basal cortisol is <100 nmol/l, replacement steroids should be continued until the time of post-operative pituitary function testing (6-8 weeks after surgery). In patients with pre-operative basal cortisol >450 nmol/l, peri-operative glucocorticoid replacement is unnecessary and further cortisol levels should be checked a few days after surgery. Most clinicians defer detailed evaluation of growth hormone reserve until after surgery. Diabetes insipidus is rarely a problem before surgery in patients with pituitary adenomas but may occur post-operatively. Close co-operation between anesthetic, endocrine and surgical teams is strongly recommended.

Clinical, biochemical, and hygiene assessment of stabled horses provided continuous or intermittent access to drinking water.

OBJECTIVE: To compare health, hydration status, and management of stabled pregnant mares provided drinking water continuously or via 1 of 3 intermittent delivery systems. ANIMALS: 22 Quarter Horse (QH) or QH-crossbred mares and 18 Belgian or Belgian-crossbred mares (study 1); 24 QH or QH-crossbred mares and 18 Belgian or Belgian-crossbred mares (study 2). PROCEDURE: Stabled horses were provided water continuously or via 1 of 3 intermittent water delivery systems in 2 study periods during a 2-year period. Body temperature, attitude, appetite, water intake, and urine output were recorded daily. Hygiene of each horse and the stable were assessed weekly. Clinical and biochemical measures of hydration were determined 3 times during each study. Clinical measures of hydration included skin turgor, gum moisture, capillary refill time, and fecal consistency. Biochemical measures of hydration included PCV, plasma total protein concentration, serum osmolality, plasma vasopressin concentration, urine specific gravity, and urine osmolality. RESULTS: All horses remained healthy. Stable hygiene was worse when horses had continuous access to water. Clinical and biochemical measures of hydration did not differ among water delivery systems. CONCLUSIONS AND CLINICAL RELEVANCE: Various continuous and intermittent water delivery systems provided adequate amounts of water to stabled horses to maintain health and hydration status. Providing intermittent access to water may be preferable on the basis of stable hygiene.

Preclinical assessment of a new transdermal delivery system for clonidine (M-5041T).

The effects of a new transdermal delivery system for clonidine (M-5041T) on hypotensive effect, urine volume, plasma renin activity (PRA) and antidiuretic hormone (ADH) in spontaneously hypertensive rats (SHRs) were compared to the effects of the continuous infusion of clonidine. Both M-5041T (1.5 and 4.5 mg/kg) and the continuous infusion of clonidine (250 micrograms/kg/24 h) elicited hypotensive effects persisting for 12 hours or more. These effects were based on consistent plasma concentrations of clonidine. These two treatments produced diuresis followed by antidiuresis, which was remarkably observed by continuous infusion of clonidine. Single subcutaneous injection of clonidine (50 micrograms/kg) produced diuresis accompanied by increases in electrolytes corresponding to plasma levels of clonidine. M-5041T at 1.5 mg/kg did not affect PRA until 12 h, and produced an increase in PRA at 24 h. M-5041T at 4.5 mg/kg and the continuous infusion of clonidine resulted in a decrease in PRA at 2 and 1 h followed by an increase at 12 and 24 h, respectively. M-5041T at 1.5 mg/kg did not affect plasma levels of ADH. Plasma ADH did increase at 2 and 4 h accompanied by diuresis following M-5041T at 4.5 mg/kg or the continuous infusion of clonidine, respectively. Clonidine-induced diuresis was not at least due to the inhibition of ADH release. The decrease in urine volume observed by continuous infusion of clonidine may be due to decrease in renal blood flow based on stimulation of peripheral adorenoceptors of clonidine. These findings suggest that the increases in ADH and PRA are due to the compensatory effects related to both diuresis and the long-lasting hypotensive effect induced by high plasma concentrations of clonidine. Thus, it can be expected that M-5041T at 1.5 mg/kg showing the minimum effective plasma concentration of clonidine will not result in tolerance to the hypotensive effect of clonidine associated with the retention of sodium in SHRs.

[Neurohormonal assessment in heart failure: from the sophisticated laboratory to practical indications]. / La valutazione neuro-ormonale nell'insufficienza cardiaca: dal laboratorio sofisticato alle indicazioni pratiche.

Heart failure is a syndrome characterized by the activation of neurohumoral mechanisms (sympathoadrenergic, renin-angiotensin, vasopressin) which cause peripheral vasoconstriction, sodium retention and myocardial hypertrophy. In acute myocardial disfunction these systems can play a critical role in patient survival, however, they can directly worsen myocardial function and patient prognosis on a long-term basis. Other neurohumoral systems activated in heart failure (atrial natriuretic factor, prostaglandins, dopamine) tend to counterbalance the vasoconstrictive, sodium retentive mechanisms. Though their secretion is increased in heart failure, it is however not sufficient, and peripheral vasoconstriction and sodium retention prevail. Moreover the role of local factors, such as tissue renin-angiotensin system, EDRF and endothelin secretion has been recently pointed out. Neurohumoral activation is directly related to the severity of the clinical and hemodynamic impairment and prognosis of the patient with heart failure. A thorough evaluation of the neurohumoral mechanisms is therefore of paramount importance for the assessment of patients with heart failure. Neurohumoral activation can be roughly assessed using some simple laboratory measurements: plasma sodium concentration, for example, is inversely related to the degree of activation of many neurohormones such as norepinephrine, angiotensin II, vasopressin and atrial natriuretic factor. The method most commonly used to assess neurohumoral activity relies on the direct measurement of the plasma concentrations. It must be noted, however, that plasma levels are critically dependent on many factors besides hormone secretion and metabolism. For example, 3-4 days on a low sodium diet or standing for at least 2 hours can increase plasma renin activity in a normal subject from 1.5 to 5-10 pg/ml/hr. Plasma concentrations of neurohormones are related to the factors controlling their secretion: for example, "normal" values of plasma renin activity in presence of fluid retention and edema are to be judged as excessively elevated. Autonomic nervous system activity can also be assessed studying reflexes in which this system is involved (orthostasis, cold pressor test, phenylephrine test...). Another method consists in the study of the spontaneous variability of some parameters controlled by this system, such as heart rate and blood pressure. The most reliable method is based on the power spectral analysis of heart rate variability. With this last method, a low frequency component depending mainly on sympathetic activity and an high frequency component depending on vagal activity can be identified in heart rate variability. Thus, complex phenomena such as sympatho-vagal balance can be easily studied through simple noninvasive tools.

Pharmacological assessment of the site of action of opioids on the release of vasopressin and oxytocin in the rat.

Naloxone and its congener, methyl naloxone, were given subcutaneously (s.c.) or centrally (i.c.v.) to 24-h water-deprived male rats 30 min prior to decapitation and the effect on plasma levels of vasopressin (VP) and oxytocin (OT) was studied. The potency of s.c. applied methyl naloxone to increase plasma OT levels did not differ from that of naloxone. Injected i.c.v., neither methyl naloxone nor naloxone had a clear effect and they antagonized i.c.v. co-administered dynorphin A-(1-13) equipotently. Methyl naloxone or naloxone, s.c., antagonized the inhibitory action of simultaneous dynorphin A-(1-13) and beta-endorphin-(1-31) given i.c.v., although higher doses of methyl naloxone were required. The data indicate that the sites of inhibition of neurohypophysial hormone release due to beta-endorphin-(1-31) are more likely to be located mostly within the blood-brain barrier, to which methyl naloxone has less ready access, than are the sites of inhibition due to dynorphin A-(1-13).

Assessment of a plasma ADH radioimmunoassay in experimental and physiologic or pathologic conditions.

A radioimmunoassay of ADH has been applied to the study of plasma ADH levels in various conditions. The validity of the assay has been evaluated by the usual quality control parameters of RIA and by the measure of plasma levels in 12 upright water deprived normal volunteers (mean 9.5 pg/ml, SEM +/- 1.5) in 8 resting and hydrated normal volunteers (1.3 +/- 0.4 pg/ml), in a case of diabetes insipidus (1.6 pg/ml), in 8 cases of SIADH Syndrome (range 13-77 pg/ml) and in 4 anesthetized dogs before (33.7 +/- 9.2 pg/ml) and after acute haemorrhage (66 +/- 9.5 pg/ml, p less than 0.02). The osmotoic challenge to ADH secretion has been studied in 8 patients with no overt endocrine pathology by salt perfusion and showed a significant rise (p less than 0.05) of plasma ADH from 6.3 +/- 3.1 pg/ml before, to 20.6 +/- 7.9 pg/ml during salt infusion corresponding to the significant (p less than 0.0001) rise of plasma osmolality from 273 +/- 2.8 to 288.2 +/- 1.1 m Osm/kg.