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L Sacca

Publications and source records attributed to L Sacca.

At least 19 recordsLinked to original sources
PubMed2000

Responses of markers of bone and collagen turnover to exercise, growth hormone (GH) administration, and GH withdrawal in trained adult males.

To examine the interactions between acute exercise and GH on markers of bone and collagen turnover and to assess the potential for detecting GH abuse in athletes using these markers, we studied 17 aerobically trained males (age, 26.9+/-1.5 yr). Sequential studies of exercise, GH administration, and GH withdrawal were undertaken. A randomized, controlled study of rest vs. exercise showed that exercise did not change serum osteocalcin; other markers of formation increased transiently (each P<0.001): bone-specific alkaline phosphatase (+16.1%), carboxyterminal propeptide of type I procollagen (+14.1%), and procollagen III N-terminal extension peptide (+5.0%). The carboxyterminal cross-linked telopeptide of type I collagen, a bone resorption marker, increased 9.7% (P = 0.018) in response to exercise. A randomized, double blind, placebo-controlled, parallel study of recombinant human GH treatment (0.15 IU/kg x day) for 1 week increased serum osteocalcin (net increase preexercise, +/-10.0%; P = 0.017), carboxyterminal propeptide of type I procollagen (+17.6%; P = 0.002), procollagen III N-terminal extension peptide (+48.4%; P = 0.001), and carboxyterminal cross-linked telopeptide of type I collagen (53.3%; P = 0.009). Disappearance half-times after cessation of recombinant human GH for pre- and postexercise markers ranged from 248-770 h. We conclude 1) endurance exercise transiently activates bone and collagen turnover; 2) brief GH administration results in similar but quantitatively greater augmentation; and 3) these data will assist in designing a GH detection strategy.

Adolescent↗
PubMed2000

The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group.

Measurements of serum insulin-like growth factor I (IGF-I) and related markers are routinely used in the diagnosis and treatment of GH deficiency and excess. The validity of these markers for assessment of exogenous GH exposure in healthy adults is, however, unknown. We therefore conducted a double blind, placebo-controlled GH treatment trial in 99 healthy subjects [49 women and 50 men; mean +/- SE age, 25.6+/-0.6 (women)/25.7+/-0.6 yr (men)]. Blood was collected weekly during a 4-week treatment period (days 1-28), and the subjects were subsequently followed for additional 8 weeks (days 29-84). The treatment arms included: I) 0.1 IU/kg x day GH (n = 30; GH 0.1), II) 0.2 IU/kg x day GH (n = 29; GH 0.2), and III) placebo (n = 40). At baseline no gender-specific differences existed, except that the acid-labile subunit (ALS) levels were higher in females. Serum insulin-like growth factor I (IGF-I) levels in males receiving GH increased significantly through day 42 with no significant difference between the 2 doses. The absolute IGF-I response was significantly lower in females, and there was a clear dose-response relationship. ALS levels in males increased through day 30 (P < 0.001). In females ALS levels were only modestly increased on day 28 compared with those in the placebo group (P < 0.02). IGF-binding protein-3 (IGFBP-3) levels in males increased significantly in the GH 0.1 and the GH 0.2 groups on day 30 (P < 0.03), whereas no solid IGFBP-3 increase was detected in females. IGFBP-2 levels decreased insignificantly during GH exposure in both genders. A gender-specific upper normal range for each analyte was arbitrarily defined as 4 SD above the mean level at baseline. On the basis of IGF-I levels alone, GH exposure in the GH 0.2 group was detected in 86% of the males and in 50% of the females on day 21. On day 42 GH exposure was only weakly detectable in males and was not detectable in females. We conclude that 1) males are significantly more responsive than females to exogenous GH; 2) the increase in IGF-I is more robust compared with those in IGFBP-3 and ALS; 3) IGFBP-2 changes very little during GH treatment; and 4) among IGF-related substances, IGF-I is the most specific marker of supraphysiological GH exposure.

Adolescent↗
PubMed1999

Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult males: a potential test for GH abuse in sport.

GH abuse by elite athletes is currently undetectable. To define suitable markers of GH doping, we assessed the effects of acute exercise, GH administration, and GH withdrawal on the GH/insulin-like growth factor (IGF) axis in athletic adult males. Acute endurance-type exercise increased serum GH, GH-binding protein (GHBP), total IGF-I, IGF-binding protein (IGFBP)-3, and acid-labile subunit (ALS), each peaking at the end of exercise. IGFBP-1 increased after exercise was completed. Free IGF-I did not change with exercise. Recombinant human GH treatment (0.15 IU/kg x day) for 1 week increased serum total IGF-I, IGFBP-3, and ALS, exaggerating the responses to exercise. IGFBP-2 and IGFBP-1 were trivially suppressed. After GH withdrawal, the GH response to identical exercise was suppressed. Total IGF-I, IGFBP-3, and ALS returned to baseline over 3-4 days. In summary, 1) acute exercise transiently increased all components of the IGF-I ternary complex, possibly due to mobilization of preformed intact complexes; 2) GH pretreatment augmented the exercise-induced changes in ternary complexes; 3) postexercise IGFBP-1 increments may protect against delayed onset hypoglycemia; 4) serum total IGF-I, IGFBP-3, and ALS may be suitable markers of GH abuse; and 5) differences in disappearance times altered the sensitivity of each marker for detecting GH abuse.

Adult↗
PubMed1996

Cardiovascular aspects in acromegaly: effects of treatment.

Patients with acromegaly have significant morbidity and mortality, associated with cardiovascular disease. Acromegaly is often complicated by other diseases such as diabetes mellitus, hypertension, and coronary artery disease, so the existence of acromegalic cardiomyopathy remains uncertain. Cardiac performance was investigated in patients with uncomplicated acromegaly. A subgroup of hypertensive acromegalics was also studied. In addition, the effects of chronic octreotide therapy or surgery on cardiac structure and function in acromegaly were studied. Twenty-six patients and 15 healthy controls underwent gated blood-pool cardiac scintigraphy and echocardiography at rest and during exercise. Echocardiography was repeated after 6 months of octreotide therapy (n = 11). Cardiac scintigraphy was repeated after 12 and 24 months of octreotide therapy (n = 10) or 12 to 24 months after surgery (n = 8). ECG, blood pressure, and heart rate were monitored during cardiac scintigraphy. Left ventricular mass (LVM) was calculated from the findings of the echocardiography. Serum growth hormone (GH) levels and plasma insulin-like growth factor-1 (IGF-1) levels were monitored. LVM index was significantly higher (P < .003) in acromegalics than controls and in hypertensive acromegalics than normotensives, but all other indices of cardiac function were similar. Chronic octreotide decreased GH and IGF-1 levels and improved the structural abnormalities as measured by echocardiography. Chronic octreotide or surgery did not alter cardiac function parameters. Thus, important changes in cardiac structure and function occur in uncomplicated acromegaly, and improvements can be demonstrated after chronic octreotide therapy. Heart disease in acromegaly appears to be secondary to high circulating GH levels.

Acromegaly↗
PubMed1995

Effects of epinephrine on human muscle glucose and protein metabolism.

Systemic epinephrine infusion causes hypoaminoacidemia and inhibits whole body leucine flux (proteolysis) in humans. Its specific action on muscle protein is not known and is difficult to assess during systemic epinephrine infusions, which affect plasma insulin, amino acid, and free fatty acid concentrations. During a steady-state infusion of L-[ring-2,6-3H]phenylalanine, we examined the effect of locally infused epinephrine on the metabolism of protein and glucose in forearm muscle of 10 healthy human volunteers. During local epinephrine infusion, systemic concentrations of glucose, phenylalanine, insulin, and epinephrine were unchanged and lactate declined (P < 0.02). Compared with baseline, epinephrine induced significant increases in forearm blood flow (P < 0.01) and net lactate release (P < 0.001) and a decrease in glucose uptake (P < 0.01) at both 2 and 4 h. At 2 and 4 h phenylalanine release from muscle proteolysis was suppressed (P < 0.01), and at 4 h the net phenylalanine balance was less negative than baseline (P < 0.02), indicating an anticatabolic effect on muscle protein. We conclude that in human forearm muscle epinephrine, at physiological concentrations, has a catabolic effect on muscle glycogen but an anticatabolic action on muscle protein. The mechanism of this latter effect is not known.

Adult↗
PubMed1994

Kinetic analysis of glycogen synthase and PDC in cirrhotic rat liver and skeletal muscle.

Glycogen synthase (GS) and pyruvate dehydrogenase complex (PDC) were kinetically analyzed in the liver and skeletal muscle of fasted and refed rats with thioacetamide-induced cirrhosis of the liver. In control rats, refeeding induced a 54% decrease in the A0.5 for glucose 6-phosphate (G-6-P) of hepatic GS (P < 0.001), reflecting allosteric activation of the enzyme. In skeletal muscle the A0.5 for G-6-P did not change after refeeding, whereas the activity ratio increased by 56% (P < 0.01), indicating a greater percentage of the active G-6-P-independent form of the enzyme. In cirrhotic rats, neither the A0.5 for G-6-P of liver GS nor the activity ratio of muscle GS was influenced by refeeding. Consequently, glycogen replenishment was significantly impaired both in the liver (2.56 +/- 0.2 vs. 5.11 +/- 0.4 g/100 g; P < 0.001) and skeletal muscle (0.45 +/- 0.01 vs. 0.52 +/- 0.02 g/100 g; P < 0.01). Refeeding increased the percentage of the active form of hepatic PDC both in control (+88%; P < 0.01) and cirrhotic rats (+91%; P < 0.001). In the latter, however, the rates of total and active PDC were significantly lower than in controls [-44% and -40% in fasted (P < 0.005) and refed (P < 0.005) rats, respectively]. Muscle PDC kinetics (both maximal velocity and Michaelis constant) and the percent active form were identical in cirrhotic and control rats, regardless of the nutritional state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Platelet aggregability in patients with a VVI pacemaker.

Several studies have suggested an increased incidence of thromboembolic events in patients with VVI pacemaker (VVI patients); furthermore, other authors have demonstrated that a treatment with anticoagulants or antiplatelet drugs may be effective in reducing thromboembolic events, thus suggesting an increased formation of platelet thrombi in these patients. In this respect, platelet aggregability was investigated in ten VVI patients and ten age- and sex-matched subjects. beta-thromboglobulin (beta-Tg) and platelet factor 4 (PF4) plasma levels were determined as well as platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid. Plasma beta-Tg levels were increased in the patient group (86 +/- 24 vs 24 +/- 13 ng/mL; P < 0.001) in presence of normal PF4 values (14 +/- 11 vs 13 +/- 6 ng/mL; NS). Aggregation curves showed abnormal values of maximal amplitude, slope, and lag time. In particular, maximal amplitude was significantly higher in VVI patients as compared with controls (ADP P < 0.01, collagen P < 0.001, adrenaline P < 0.01, arachidonic acid P < 0.05). These findings strongly suggest an increase of platelet activity in VVI patients.

Adenosine Diphosphate↗
PubMed1991

Efficacy of ticlopidine in the prevention of thromboembolic events in patients with VVI pacemakers.

This study was designed to evaluate whether long-term treatment with ticlopidine reduces the incidence of thromboembolic episodes in patients with a VVI pacemaker. One hundred eleven patients with a VVI pacemaker were randomly assigned to two groups: group A (52 patients) was treated with ticlopidine at the dose of 250 mg a day; and group B (59 patients) was not treated and served as a control group. The primary analysis of efficacy of ticlopidine was based on the occurrence of thromboembolic episodes and of cardiovascular and cerebrovascular deaths. The mean follow-up period was 66 months. In group A, there was a significant reduction in the incidence of thromboembolic episodes (P less than 0.05) with a smaller incidence of total cardiovascular and cerebrovascular deaths (8 in group A and 18 in group B; P = 0.05) as compared with group B. Twelve percent of patients had moderate side effects with 1 dropout (epistaxis). Our data confirm the high incidence of thromboembolic events in patients with a VVI pacemaker and demonstrate the efficacy of ticlopidine in preventing them.

Aged↗
PubMed1988

Quantitation of forearm glucose and free fatty acid (FFA) disposal in normal subjects and type II diabetic patients: evidence against an essential role for FFA in the pathogenesis of insulin resistance.

This study was designed to quantitate glucose and FFA disposal by muscle tissue in patients with type II diabetes and to investigate the relationship between FFA metabolism and insulin resistance. The forearm perfusion technique was used in six normal subjects and two groups of normal weight diabetic patients, i.e. untreated (n = 8) and insulin-treated (n = 6). The latter received 2 weeks of intensive insulin therapy before the study. Plasma insulin levels were raised acutely [950-1110 pmol/L) (130-150 microU/mL)], while the blood glucose concentration was clamped at its basal value [4.9 +/- 0.1 (+/- SE) mmol/L in the normal subjects, 5.7 +/- 0.5 in the insulin-treated diabetic patients, and 5.5 +/- 0.3 in the untreated diabetic patients] by a variable glucose infusion. During the control period, arterial FFA concentrations were similar in the three groups, and they decreased to a comparable extent (less than 0.1 mmol/L) in response to insulin infusion. During the control period, the mean forearm FFA uptake was 2.5 +/- 0.5 mumol/L.min in the normal subjects, 2.9 +/- 0.5 in the insulin-treated patients, and 2.1 +/- 0.5 in the untreated diabetic patients. During the insulin infusion, FFA uptake was profoundly suppressed to similar levels in the normal subjects (0.9 +/- 0.1 mumol/L.min), the insulin-treated diabetic patients (1.1 +/- 0.3), and the untreated diabetic patients (0.9 +/- 0.1; P less than 0.001). Forearm glucose uptake was similar in the three groups during the control period. It increased during the insulin infusion, but the response in both diabetic groups was less than that in the normal subjects. The total amounts of glucose taken up by the forearm during the study period were 5.2 +/- 0.7, 2.6 +/- 0.5, and 2.1 +/- 0.6 mmol/L.min in the normal subjects, the insulin-treated diabetic patients, and the untreated diabetic patients, respectively (P less than 0.01). We conclude that 1) insulin-mediated glucose uptake by forearm skeletal muscle is markedly impaired in type II diabetes and improves only marginally after 2 weeks of intensive insulin therapy; 2) in contrast, no appreciable abnormality in forearm FFA metabolism is demonstrable in insulin-treated type II diabetic patients; and 3) FFA do not contribute to the insulin-treated skeletal muscle insulin resistance that occurs in patients with type II diabetes mellitus.

Adult↗
PubMed1988

Abnormalities of glucose metabolism induced by liver cirrhosis and glycosylated hemoglobin levels in chronic liver disease.

UNLABELLED: The prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (DM) such as defined by National Diabetes Data Group criteria, and glycosylated hemoglobin levels were assessed in a series of consecutive patients who had chronic active hepatitis (CAH) or cirrhosis in the absence of any known diabetogenic risk factors and who had normal fasting glycemic levels. Based on oral glucose tolerance test, the prevalence of IGT (15%) and DM (27%) in cirrhosis was significantly higher (p less than 0.005) than that observed in CAH (0%) and controls (0%). In contrast, HbA1 levels were not statistically different in cirrhotic patients (with normal or altered glucose tolerance) as compared with CAH and control subjects. IN CONCLUSION: (a) HbA1 is an unsatisfactory test in the diagnosis of altered glucose tolerance in patients with cirrhosis, and (b) Cirrhosis (but not CAH) represents itself a risk factor for the development of glucose metabolism alterations. Therefore, routine oral glucose tolerance testing is warranted in these patients.

Adult↗
PubMed1985

Glycogen depletion during prolonged exercise: influence of glucose, fructose, or placebo.

We examined the influence of various carbohydrates of fuel homeostasis and glycogen utilization during prolonged exercise. Seventy-five grams of glucose, fructose, or placebo were given orally to eight healthy males 45 min before ergometer exercise performed for 2 h at 55% of maximal aerobic power (VO2max). After glucose ingestion, the rises in plasma glucose (P less than 0.01) and insulin (P less than 0.001) were 2.4- and 5.8-fold greater than when fructose was consumed. After 30 min of exercise following glucose ingestion, the plasma glucose concentration had declined to a nadir of 3.9 +/- 0.3 mmol/l, and plasma insulin had returned to basal levels. The fall in plasma glucose was closely related to the preexercise glucose (r = 0.98, P less than 0.001) and insulin (r = 0.66, P less than 0.05) levels. The rate of endogenous glucose production and utilization rose similarly by 2.8-fold during exercise in fructose group and were 10-15% higher than in placebo group (P less than 0.05). Serum free fatty acid levels were 1.5- to 2-fold higher (P less than 0.01) after placebo than carbohydrate ingestion. Muscle glycogen concentration in the quadriceps femoris fell in all three groups by 60-65% (P less than 0.001) during exercise. These data indicate that fructose ingestion, though causing smaller perturbations in plasma glucose, insulin, and gastrointestinal polypeptide (GIP) levels than glucose ingestion, was no more effective than glucose or placebo in sparing glycogen during a long-term exercise.

Adult↗
PubMed1984

Role of plasma vasopressin in the impairment of water excretion in nephrotic syndrome.

To verify whether or not an increased secretion of ADH may cause the water retention commonly observed in nephrotic syndrome, 16 nephrotic patients and 13 normal control subjects were studied in basal conditions and following a water load or an iso-osmotic blood volume expansion by 20% albumin infusion. In the basal condition there were no differences in plasma ADH, urine output, urinary osmolality (UOsm), and plasma renin activity between nephrotic patients and control subjects; POsm, PNa+, UNaV, and blood volume (BV) instead, were significantly lower in nephrotic patients than in control subjects. Following the water load control subjects reached a minimal UOsm of 82 +/- 12 mOsm/kg at 60 min and excreted completely the ingested water in 150 min; nephrotic patients reached a minimal UOsm of 160 +/- 111 mOsm/kg at 120 min, and the water was eliminated completely in 240 min. Plasma ADH decreased significantly in the first hour following water load only in control subjects. A significant direct correlation was observed between plasma ADH and POsm in control subjects (ADH = -85 + 0.30 POsm, P less than 0.001) but not in nephrotic patients. Plasma ADH was inversely correlated with BV in nephrotic patients (ADH = 15.47 -0.17 BV, P less than 0.001) but not in normal control subjects. In nephrotic patients with reduced BV the expansion of BV with 20% albumin was effective in reducing the plasma levels of ADH and promoting a water diuresis. Our results demonstrate a sustained volume mediated secretion of ADH in the nephrotic syndrome, which is responsible for the impairment in water excretion.

Adolescent↗
PubMed1982

Effects of oral salt loading on beta-adrenergic receptor responsiveness in normal and hypertensive subjects.

The effect of oral salt loading (400 mmol per day of NaCl for 7 days) on cardiac and pancreatic beta-receptor responsiveness has been evaluated in 12 patients with established essential hypertension and in seven age-matched control subjects. Cardiac beta-receptor responsiveness was evaluated by assessing the dose of isoprenaline which increased a stable heart rate by 25% (chronotropic dose 25%, CD 25%). Pancreatic beta-receptor responsiveness was measured by the incremental areas of insulin secretion induced by iv infusion of increasing amounts of isoprenaline. Before salt load, CD 25% was significantly higher in hypertensives compared with controls (7.84 +/- 1.34 micrograms vs 3.9 +/- 0.48 micrograms, P less than 0.05) while there was no difference in the isoprenaline-induced insulin secretion between the two groups of subjects. After salt loading, CD 25% was significantly reduced in hypertensive patients but was not modified in normal subjects. Therefore, the difference in CD 25% was no longer detectable between the two groups (5.5 +/- 1.42 micrograms vs 3.2 +/- 0.48 micrograms in normal subjects and in hypertensives, respectively, NS). Furthermore, salt loading failed to induce any change in isoprenaline-induced insulin secretion in either groups. These results support the existence of a relationship between sodium intake and adrenergic beta-receptor responsiveness in human hypertension.

Adolescent↗
PubMed1982

Renal function in borderline hypertensive first-degree relatives of essential hypertensives. Effects of sodium load.

Renal function in the basal state and after sodium load has been investigated in 21 borderline, hypertensive, first-degree relatives of established hypertensives and in 21 age- and sex-matched, normal subjects with no family history of hypertension. During intravenous infusion of inulin and p-aminohippurate in saline, both groups showed a decrease in plasma aldosterone levels (p less than 0.05) but renal plasma flow (595 +/- 48 vs. 750 +/- 59 ml/min, p less than 0.05), diuresis (1.4 +/- 0.2 vs. 2.2 +/- 0.5 ml/min, p less than 0.05), natriuresis (0.21 +/- 0.02 vs. 0.3 +/- 0.02 mEq/min, p less than 0.05) and sodium clearance (1.05 +/- 0.1 vs. 2.4 +/- 0.4 ml/min, p less than 0.05) in borderline hypertensives were higher than in the control group. After the salt load (NaCl, 1.35% i.v., 5 ml/min for 2 h) there was an increase in blood pressure and a decrease in plasma aldosterone and potassium levels in both groups. However, borderline hypertensives showed higher diuresis, natriuresis, sodium clearance and also kaliuresis compared to normotensives. These results suggest that borderline hypertensives already present the changes in renal function which are characteristics of established hypertensives.

Adolescent↗
PubMed1982

Influence of acetylsalicylic acid on glucose turnover in normal man.

This study was designed to evaluate the influence of intravenous infusion (72 mg min-1) of lysine acetylsalicylate (LAS), an inhibitor of endogenous prostaglandin synthesis, on glucose homeostasis in normal man. LAS infusion produced a transient decrease of both hepatic glucose production (Ra, p less than 0.01) and peripheral glucose uptake (Rd, p less than 0.01). Since Ra fell more than Rd, a slight but significant decrease of plasma glucose concentration occurred. Glucose metabolic clearance rate also showed a rapid, although transient, decrease after the start of LAS infusion. Plasma insulin rose twofold in response to LAS, while plasma glucagon remained unchanged. The failure of the glucose clearance to increase as a consequence of the augmented insulin levels suggests that salicylate compounds may cause a state of insulin resistance.

Adult↗
PubMed1981

Baroreflex responsiveness in borderline hypertensives: a study with neostigmine.

The baroreflex response to changes in transmural pressure throughout the arterial tree or limited to the carotid sinus was evaluated in ten borderline hypertensives and compared with that observed in ten normal subjects and in ten established hypertensives. Baroreceptor sensitivity was tested by evaluating both heart rate response to phenylephrine-induced increase in arterial pressure and heart rate and blood pressure changes induced by increased neck tissue pressure by means of a neck chamber. The heart rate response to phenylephrine (evaluated by the regression of the R-R interval versus the systolic blood pressure) was depressed both in borderline and established hypertensives as compared with controls. Similarly, the heart rate and the pressor response to increased neck tissue pressure were depressed in both groups of hypertensives. In borderline, but not in established hypertensives, neostigmine administration improved consistently the pressor baroreflex response to increased neck tissue pressure and the heart rate reflex response to both the employed stimuli. These findings indicate that a reduced parasympathetic activity is one of the components involved in the altered baroreflex sensitivity in borderline hypertensives.

Adult↗