Acid-base equilibria in aqueous solution of cis-bis(trimethylphosphine)platinum(II) dinitrate at 25 degrees C, 0.2 M ionic strength. A potentiometric study.

Acid-base equilibria in aqueous solutions of cis-bis(trimethylphosphine)platinum(II) dinitrate at 25 degrees C, 0.2 M ionic strength (KNO(3)), have been investigated by potentiometry with a glass electrode. The procedure consisted of multiple addition of the investigated analyte to a supporting electrolyte solution ("multiple sample addition") and subsequent titration with strong base. For the treatment of potentiometric multiple sample addition data, a new linearization procedure, suitable for an acid dissociation equilibrium whose product dimerizes, has been devised and tested. The potentiometric results have been interpreted with the support of NMR data. By dissociation of the first acidic function of the solute diaquo cation, cis-[(PMe(3))(2)Pt(OH(2))(2)](2+), a dimeric ampholite, cis-[(PMe(3))(2)Pt(mu-OH)](2)(2+), is quantitatively formed which, in turn, can be converted into the di-hydroxo derivative cis-(PMe(3))(2)Pt(OH)(2). The two acid dissociation steps involving two molecules of solute and condensation of ampholyte have pK(a1(c)) = 3.89 and pK(a2(c)) = 22.17.

Potentiometric characterization of weak acids by multiple sample addition II. The effect of chemical interferences and the practical performance of linearization methods.

Potentiometric multiple addition of a sample containing a pure weak acid to a solution of supporting electrolyte has been previously shown [C. Maccà and A. Merkoci, Talanta, 41 (1994) 2033] to be formally suitable for the determination of the dissociation constant and concentration of the sample acid. Linear equations have been developed for the treatment of experimental data to yield, simultaneously or separately, the chemical parameters of the acid solution. These equations are now tested on real samples together with analogous equations for titrations, and the results are compared with those obtained with rigorous statistical methods. For the determination of the acidity constant with samples of known concentration, multiple samples addition is comparable with titration. When the sample concentration is unknown and must be determined simultaneously to the acidity constant, the results obtained by linearized multiple sample addition can be seriously affected by impurities present, even at low level, either in the sample or in the supporting solution. Linear equations accounting for the effects of basic or acidic impurities in the sample or in the supporting solution are developed. Sample addition is confirmed to be a useful complement to pH-metric titration for the determination of acidity constants of moderately weak acids by non-linear regression; linearization of data is a convenient technique for screening purposes and a powerful means of detecting and correcting some common pitfalls, interferences and contaminations, whose effects are enhanced in linearized sample addition.

Potentiometric characterization of weak acids by multiple sample addition-I. Linear equations and intrinsic performance of the method.

The suitability of linearized multiple sample-addition for the potentiometric characterization of monoprotic weak acids is examined. Linear equations for the separate or simultaneous determination of the acidity constant and of the sample concentration by treatment of experimental data are introduced. The intrinsic performance of the method and the application range of the different equations are discussed with reference to the theoretical effect of measurement errors on the values of the quantities to be determined.

Effect of the combined administration of galanin and clonidine on serum growth hormone levels in normal subjects and in patients under chronic glucocorticoid treatment.

Aim of our study was to investigate the effect of clonidine and galanin (alone or in combination) on growth hormone (GH) secretion in normal subjects and in adult patients with increased somatostatin tone due to chronic daily immunosuppressive glucocorticoid treatment. We studied 7 adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non endocrine diseases (4F, 3M; age 49.7 +/- 6.3 years). Six normal adult nonobese subjects (3F, 3M; age 34 +/- 2.7 years) served as controls. All subjects underwent the following three tests in random order: 1) iv infusion of clonidine, 150 micrograms in 10 mL of saline, from time 0 to 10 min; 2) iv infusion of synthetic porcine galanin, 500 micrograms in 100 mL of saline from -15 to 30 min; 3) iv infusion of clonidine from 0 to 10 min combined with synthetic porcine galanin iv infusion from -15 to 30 min. Blood samples for GH assay were taken at -15, 0, 15, 30, 45, 60, 90, 120 min. No significant differences in GH absolute values were observed at any time between the three different tests within each group of subjects. Normal subjects showed significantly (p < 0.05) higher GH peaks and GH absolute values from 15 to 90 min after galanin alone, clonidine alone and clonidine+galanin with respect to the glucocorticoid-treated patients. The absence of any either synergistic or at least additive effect on GH secretion of galanin and clonidine in conditions of both normal and increased somatostatin tone suggests that also in man, as well as in the rat, the action of galanin on the GH axis may be mediated through alpha-adrenergic pathways.

Isradipine decreases exercise-induced albuminuria in patients with essential hypertension.

The aim of our study was to investigate the effects of exercise on albuminuria and blood pressure in patients with essential hypertension, and the short-term effect of the calcium channel blocker isradipine on exercise-induced albuminuria (UAE) and blood pressure in the same patients. Ten patients (7 males, 3 females) with essential hypertension were admitted to the study. The mean age was 54 +/- 2.7 years and the mean body mass index was 27 +/- 1 kg/m2. Patients performed two physical exercise tests on a cycloergometer. Workload was increased by 30 watts every 2 min until 90% of the theoretical maximal heart rate was achieved. This workload was maintained for 5 min. Samples for albuminuria assay were collected at the end of exercise and 1 h after exercise. The first physical exercise test was performed after 15 days of placebo washout; the second exercise was performed after 10 days of therapy with isradipine 5 mg once daily p.o. After 10 days of therapy with isradipine, UAE immediately after (31 +/- 8.3 micrograms/min) and 1 h after exercise (31.5 +/- 7.3 micrograms/min) were significantly (p < 0.05) lower as compared to the values found after placebo (37.1 +/- 9.3 micrograms/min; 43.5 +/- 9.9 micrograms/min). Our data show that short-term administration of the calcium channel blocker isradipine is able to cause a concomitant significant decrease in exercise-induced pressor and albuminuric response in patients with essential hypertension. The finding that short-term calcium channel blockade can reduce exercise-induced albuminuria in essential hypertensive patients suggests that progression of nephropathy in this early phase could be slowed by isradipine in these patients.

Comparative effect of galanin and pyridostigmine on the growth hormone response to growth hormone-releasing hormone in normal aged subjects.

The aim of our study was to investigate the effects of aging on the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) alone and in combination with either the neuropeptide galanin or the acetylcholinesterase inhibitor pyridostigmine (PD) in normal subjects. In protocol 1 (GHRH/galanin), 9 old healthy volunteers, ranging in age from 68 to 97 years, and 6 young subjects, ranging in age from 25 to 31 years, received: (a) human GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) porcine galanin, 500 micrograms in 100 ml saline, as an intravenous infusion from -10 to 30 min combined with GHRH, 100 micrograms i.v. at time 0. In protocol 2 (GHRH/PD), 14 old healthy volunteers, ranging in age from 65 to 91 years, and 11 young subjects, ranging in age from 19 to 34 years, received: (a) GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) PD, 120 mg administered per os 60 min before GHRH, 100 micrograms as an intravenous bolus. Blood samples for GH were drawn at -75, -60 (time of PD administration), -45, -30, -15, -10 (time of beginning of galanin infusion), 0 (time of GHRH injection), 15, 30, 45, 60, 90, and 120 min. The GH response to GHRH was significantly (< 0.05) enhanced either by galanin or PD pretreatment both in young and old subjects. However, the GH response to GHRH alone or combined with either galanin or PD was significantly greater in the young subjects as compared to the old subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Linearized multiple standard additions for the potentiometric determination of weak acids.

The feasibility of potentiometric determination of weak monoprotic acids by the multiple standard addition method is examined. A standard solution of pure weak acid is added to the solution containing an unknown amount of the same weak acid, alone or mixed with its conjugate base. The experimental data are processed by Gran-type plots, for which rigorous and approximate equations are obtained. It is shown that weak acids can be determined by multiple standard additions with a precision comparable with that of the usual kinds of potentiometric addition-methods. The validity range of the approximate equations is established. Linear equations similar to those of Hofstee, Scatchard, Lineweaver and Burk, and Scott are also obtained, by which aciditity constants can be determined together with equivalence volumes. The effects of systematic and random measurement errors are examined.

[Salmon calcitonin nasal spray in the treatment of Paget's disease]. / La calcitonina di salmone spray nasale nella terapia del morbo di Paget.

Salmon calcitonin (sCT) is biologically effective when intranasally (i.n.) administered. CT is the treatment of choice for Paget's disease; however, the chronic nature of the disease makes parenteral administration uncomfortable due to the high incidence of adverse reactions occurring after CT injection. The aim of our study was to investigate the efficacy, safety and tolerability of a sCT i.n. spray in the long-term treatment of Paget's disease. Ten pts (4M,6F; age between 58-74 years) with radiological lesions characteristic of Paget's disease, serum alkaline phosphatase (sALP) levels at least 50% above the normal range and never treated for their disease before, were given 200 IU/day of sCT nasal spray for 6 months. sALP levels were measured at month 3 and 6 of therapy; clinical data were recorded every month. sALP levels significantly dropped after 3 months of treatment (72 +/- 6% of basal level, p less than 0.01). After 6 months of therapy sALP levels were similar to the 3 month levels. Pain and functional impairment self-evaluated by the patients decreased after 6 months of therapy: pain index from 5.5 +/- 2.2 to 2.1 +/- 1.1, p less than 0.01; functional impairment index from 2.2 +/- 0.5 to 0.7 +/- 0.5, p less than 0.01. Side-effects were not observed during the entire period of the study. In conclusion, the 200 IU daily regimen of the i.n. spray of sCT without absorption enhancer was, for our patients, effective, safe, and well tolerated in the long-term therapy of Paget's disease.