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Biomedical subjects

E Strocchi

Publications and source records attributed to E Strocchi.

At least 73 records · Page 4Linked to original sources

Altered erythrocyte Na-K pump in anorectic patients.

The status of the erythrocyte sodium pump was evaluated in a group of patients suffering from anorexia nervosa and a group of healthy female control subjects. Anorectic patients showed significantly higher mean values of digoxin-binding sites/cell (ie, the number of Na-K-ATPase units) with respect to control subjects while no differences were found in the specific 86Rb uptake (which reflects the Na-K-ATPase activity) between the two groups. A significant correlation was found between relative weight and the number of Na-K-ATPase pump units (r = -0.66; P less than 0.0001). Anorectic patients showed lower serum T3 concentrations (71.3 +/- 53 ng/dL) with respect to control subjects (100.8 +/- 4.7 ng/dL; P less than 0.0005) and a significant negative correlation between T3 levels and the number of pump units (r = -0.52; P less than 0.003) was found. Our study therefore shows that the erythrocyte Na-K pump may be altered in several anorectic patients. We suggest that this feature could be interrelated with the degree of underweight and/or malnutrition.

Adolescent↗

Heterogeneity of the erythrocyte Na-K pump status in human obesity.

The number of Na-K pump units, the Na-K-ATPase activity, the K transport turnover rate per pump unit and the intracellular Na and K concentrations were measured in the erythrocytes of 56 obese patients and 20 normal subjects. No differences were found between the two groups. In obese patients, we failed to observe any influence of dietary habits, age of onset, or family history of obesity on the Na pump status. On the other hand, we found that the number of pump units was not a close reflection of the membrane cation transport and in some patients with an abnormally high number of pump units, an inappropriately low Na-K-ATPase activity was observed. We also identified two small groups of obese patients with, respectively, abnormally high or low K transport turnover rate per pump unit. Our study seems to support the hypothesis that abnormalities in the erythrocyte Na-K pump system are not usual in the obese population but are probably present only in a limited number of selected patients.

Adolescent↗

Comparison of two automatic devices and the standard mercury sphygmomanometer in hypertensive patients.

The standard mercury sphygmomanometer (SMS) and two automatic blood pressure recording devices, Dinamap 845 (D) and Sentron (S), were compared by means of a randomized 3-period cross-over experiment. Both devices recorded diastolic BP lower than SMS, on average and for most individual patients. Systolic BP was similar for SMS and S, and slightly lower for D, with variations for individual patients. A second study failed to detect effects of the physician's presence when BP was measured, whereas the difference between D and SMS was substantially confirmed.

Blood Pressure↗

Analgesic activity of medroxyprogesterone acetate (MAP) in cancer patients: an antiinflammatory mediated activity?

When we initially used high doses of MAP (greater than 500 mg/day/im or greater than 2000 mg/day p.o.) in advanced cases of breast cancer, we noticed that, even before objective remission became apparent, the treatment induced subjective remission and a strong analgesic effect. Overall, our breast cancer patients treated with MAP at high doses (300 patients) showed a 65% incidence of pain relief. The analgesic effect of MAP does not seem to be closely related to its antitumour effect, because the same effect was also observed in patients with hormone-insensitive tumours. Our pharmacokinetic studies have demonstrated that it is important to use high doses in order to obtain high plasma levels. In order to clarify the mode of action of this MAP analgesy, hot-plate, tail-flick, Randall, writhing and carrageenin-oedema tests were carried out on rats. We found no evidence for central or peripheral analgesic activity, but there was evidence for an antiinflammatory activity of MAP.

Animals↗

Epirubicin pharmacokinetics after intrahepatic arterial and intraperitoneal administration.

The high hepatic clearance of the new doxorubicin analogue epirubicin (4'-epidoxorubicin, epiDX) suggests a possible use of this drug in local and regional therapy where a first pass through the liver is required before the drug can reach systemic circulation. EpiDX pharmacokinetics was followed in advanced cancer patients with liver metastases or a primary tumour after single bolus administration in the hepatic artery, through a surgically implanted catheter and subcutaneous access port. The first-pass effect through the liver was appreciable and only a relatively low fraction of the drug reached systemic circulation. Mild leucopenia and alopecia were observed only in a patient with a hepatopulmonary shunt; this subject was actually exposed to higher epiDX plasma levels. Low intraperitoneal doses of epiDX were administered in a weekly schedule to advanced cancer patients with peritoneal metastases and ascites. Drug concentrations were monitored in the ascitic effusion and in plasma. A high concentration gradient was present between the peritoneal cavity and peripheral circulation. No relevant local or systemic toxicity was observed.

Adult↗

Epirubicin plasma and blood pharmacokinetics after single i.v. bolus in advanced cancer patients.

Plasma and whole blood pharmacokinetics of epirubicin (4'-epidoxorubicin, epiDX), a new doxorubicin (DX) analogue with an improved spectrum of activity and lower toxicity, were investigated in advanced cancer patients after i.v. bolus administration. Drug decay is triphasic, with a long terminal half-life. Plasma and blood levels of the C-13 reduced epiDX metabolite, epirubicinol (epiDXol), are lower than those of the parent compound. Glucuronides of epiDX and epiDXol are also present in plasma, bile and urine; similar compounds are not described in the literature among the metabolites of DX. EpiDX plasma clearance is consistently higher and mean residence time lower than the corresponding DX parameters, thus indicating a more efficient disposition of the new drug. This behaviour is also reflected in a faster elimination of epiDXol with respect to the corresponding Dx metabolite, doxorubicinol. After an initial induction period, epiDX concentration is higher in whole blood than in plasma. Blood clearance is lower than plasma clearance; volume of distribution at steady state Vss is lower if blood concentration data are used in the pharmacokinetic analysis. Mean Residence Time is similar in plasma and blood. A statistically significant reduction of clearance parameters is observed in patients with liver metastases, even in the absence of altered bilirubin levels. Drug clearance problems induced by renal dysfunction become relevant only in severe renal failure.

Bile↗

Erythrocyte Na+-ATPase in obese patients.

Na+-K+-ATPase activity, as measured by erythrocytic 86Rb uptake and number Digoxin Binding Sites were evaluated in 34 obese patients and in 39 control subjects. No differences were found in 86Rb uptake and Digoxin Binding Sites between obese and controls. Likewise no differences were found between obese patients on their spontaneous caloric intake and those studied during various hypocaloric regimens. Finally, no relationship between thyroid hormone serum concentrations and ATPase activity was found in the group of obese patients.

Adult↗

Comparison of the effects of prizidilol and propranolol on renal haemodynamics at rest and during exercise.

Effective renal plasma flow and glomerular filtration rate were measured in 22 mild-to-moderate, uncomplicated, essential hypertensive patients during placebo and after 3 months of randomly assigned treatment either with prizidilol (n = 10) or propranolol (n = 12). Measurements were performed at rest and during cycloergometer exercise. For a comparable effect on blood pressure effective renal plasma flow was significantly increased at rest by prizidilol (+9%) and decreased by propranolol (-13.6%); these patterns were maintained during exercise. Glomerular filtration rate was immodified after the treatment with both drugs. It is concluded that prizidilol is an effective hypotensive agent with no deleterious effects on renal haemodynamics.

Adult↗

Digitalis: new aspects of pharmacokinetics and clinical implications.

Any evaluation of the efficacy of digoxin therapy must rely upon a precise index of the digitalization status. As the plasma concentrations bear a rather poor relationship with clinical effects of treatment, the occupied fraction of digoxin receptors (Na-K ATPase) on the erythrocytes membranes is proposed as a new index of digitalization status; preliminary data on the value of this approach are discussed.

Digitalis Glycosides↗

Long-term antihypertensive, metabolic and cellular effects of enalapril.

Fifty-three patients with mild to moderate essential hypertension were treated with enalapril (10-40 mg q.d.) alone, in combination with a fixed dose of hydrochlorothiazide (50 mg/day), or in a randomized cross-over study with varying dosages of hydrochlorothiazide (50, 25, 12.5 mg/day). Normalization of blood pressure was obtained in 47% of the patients after enalapril. In the remaining patients, all except four were normalized by the combination with hydrochlorothiazide. The addition of hydrochlorothiazide was required in six patients who had optimally responded to enalapril during the first three months. In the cross-over study, diastolic blood pressure was maintained below 95 mmHg with all the doses of diuretic used in association with 40 mg enalapril. No adverse metabolic (blood glucose, cholesterol, triglycerides), renal (creatinine clearance, urinary lysozyme and gamma-GT) or haematological (total and differential counts) effects were observed after long-term treatment for one year with enalapril alone or in combination with hydrochlorothiazide. Blood uric acid decreased significantly after enalapril and tended to increase after the combination with hydrochlorothiazide. Enalapril increased Na/K ATPase activity on erythrocyte membranes thus reducing intracellular sodium and increasing potassium.

Adult↗

The effect of high dose medroxyprogesterone acetate on water and salt metabolism in advanced cancer patients.

Ten advanced cancer patients (both with hormone-sensitive and non-hormone sensitive tumors) were treated with high dose medroxyprogesterone acetate (MAP, greater than 500 mg/day). We determined body weight, lean body mass, blood pressure, sodium blood level, urinary excretion, and exchangeable sodium pool by the 22Na method before and after treatment. These data seem to exclude a fluid retentive effect for high-dose MAP.

Antineoplastic Agents↗

[Digoxin-amiodarone interaction].

Digoxin plasma levels and digoxin erythrocytic membrane content have been evaluated in 39 patients treated with digoxin and amiodarone in a fixed dose for more than 3 months. The results were compared with those obtained in a group of patients treated with digoxin alone and matched for age, renal function and digoxin daily dose in micrograms/kg body weight. Digoxin plasma levels and digoxin erythrocytic content were significantly higher in patients treated with amiodarone than in controls, thus confirming the interaction between digoxin and amiodarone. The relation between digoxin plasma levels and digoxin bound to erythrocytic membranes--as a marker of the deep tissue accumulation--was not different in patients treated with digoxin or with digoxin + amiodarone, further indicating that amiodarone may not increase digoxin plasma levels by means of a displacement of the glycoside from tissues. The clinical significance of the interaction is still undefined.

Adult↗

Medroxyprogesterone acetate (MAP) plasma levels after multiple high-dose administration in advanced cancer patients.

Medroxyprogesterone acetate plasma levels were measured in advanced cancer patients after multiple PO or IM administration (500, 1000, 2000, 3000, 4000, and 5000 mg/day PO and 500, 1000, 2000 mg/day IM for 30 days). After PO administration, the plasma concentration rises quickly and plateau level is reached in 4-10 days. Discontinuation of the treatment produces a fast decay (t1/2 = 62.4 h) of the drug levels. When medroxyprogesterone acetate is given IM plasma levels, steadily increase and after drug discontinuation no noticeable decay is observed for at least 6 months; plateau plasma levels are about three times higher than after the corresponding PO treatment. Extremely high interpatient variation in bioavailability is present with both administration routes. These data may well rationalize the results of previous clinical trials and will help in planning treatment schedules.

Administration, Oral↗

The anabolic effect of high dose medroxyprogesterone acetate in oncology.

Ten advanced cancer patients not amendable to conventional therapy were treated with high dose (greater than 500 mg/day, for 30 days) Medroxyprogesterone Acetate (MAP) both orally and intramuscularly, in order to evaluate a possible anabolic effect of this hormone. During the treatment, mean protein intake increased from 37.2 gr/day to 58.8 gr/day (p less than 0.01), nitrogen intake from 5.8 to 9.4 gr/day (p less than 0.01) and caloric intake from 1407.9 to 2075 Kcal/day (p less than 0.01). Nitrogen balance also showed a significant increase (p less than 0.05), as well as elementary strength (p less than 0.02). Lean body mass and body weight did not show significant variations. The above data confirms what was already been documented by us in animals and proposed in man-that MAP has an anabolic effect.

Anabolic Agents↗

Comparison of the antihypertensive activity of cadralazine (ISF 2469) and dihydralazine during chronic treatment.

The antihypertensive activity of a new vasodilating agent (ISF 2469) cadralazine (CD) was compared in a randomized, crossover, intrapatient study with that of hydralazine (HD) in 20 hypertensive patients whose diastolic blood pressure (BP) was greater than 95 mmHg during treatment with atenolol (AT), 100 mg 1 X daily. The initial dose of CD was 15 mg 1 X daily; after 15 days in case of poor response, the dose was increased to 20 mg 1 X daily. HD was given at a dose of 25 mg 3 X daily and was increased to 50 mg 2 X daily in case of poor response. BP values (standing) during AT were 174/108; they fell to 144/88 during CD and to 138/88 during HD. No significant difference was detected between the two drugs for both systolic and diastolic BP (supine and standing). Heart rate increased with both drugs, with a greater increase during CD. The difference was clinically nonsignificant. A total of 24 patients were enrolled, but 4 had to cease treatment because of side effects during HD. The overall prevalence of side effects was much higher during HD, especially during the first days of therapy. Also the severity of side effects was greater during HD. Our data show that CD has the same antihypertensive activity as HD with a lesser incidence of side effects and with a single dose/day administration in contrast with three administrations of HD. This can result in greater patient compliance.

Adult↗

Propranolol and renal hemodynamics at rest and during exercise.

The effects of long-term propranolol treatment on renal hemodynamics at rest and during submaximal physical exercise were evaluated in 15 mild-to-moderate essential hypertensive patients. After 3-month treatment propranolol induced a significant decrease at rest both of effective renal plasma flow (-17.1%) and glomerular filtration rate (-7.4%) and an increase of renal vascular resistances (+11.8%). These changes were irrespective of response to treatment, degree of beta blockade, age, or initial values of hemodynamic parameters. The beta blocker had an additive effect to physical exercise in reducing renal perfusion, but it did not induce any qualitative variation in the response of renal hemodynamics to exercise.

Adult↗