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Biomedical subjects

M Cirillo

Publications and source records attributed to M Cirillo.

At least 109 records · Page 6Linked to original sources

Calmodulin reduces ouabain-sensitive ATPase of cardiac sarcolemmal membranes: high reduction in spontaneously hypertensive rats.

Calmodulin and calcium effects on cardiac ouabain-sensitive adenosine triphosphatase (ATPase) activity were studied in young spontaneously hypertensive rats (SHR) and in their normotensive control Wistar-Kyoto rats (WKY). Cardiac sarcolemmal membranes from SHR showed significantly higher ouabain-sensitive ATPase activity than membranes from WKY rats. This activity was unaffected by calmodulin or calcium alone. However, when both calmodulin and calcium were added, ouabain-sensitive activity was significantly reduced without changes in the total ATPase activity. The calcium-dependent calmodulin effect was dose-dependent and greater in SHR than in WKY membranes. An altered interaction between the calcium-calmodulin system and sodium handling by the plasma membrane in SHR may play a role in the pathogenesis of hypertension.

Adenosine Triphosphatases↗

Basal parathyroid activity and renal calcium handling during an intravenous calcium load.

Urinary excretion of calcium and urinary cyclic AMP (cAMP), plasma parathyroid hormone (PTH) and ionized serum calcium concentration, and creatinine clearance were measured in 15 healthy humans. In the same subjects, renal tubular reabsorption of calcium was evaluated by analyzing the regression line of urinary calcium excretion rate on rising the level of serum calcium during an intravenous calcium infusion. The regression line intercept on the y-axis, which has been proposed to depend on the calcium reabsorption in the renal distal tubule, was found to be significantly related to both urinary cAMP and PTH levels. The theoretical renal threshold for calcium excretion was directly related to the y-axis intercept and thus also to the index of parathyroid activity. No relationship was found between urinary cAMP or plasma PTH levels and the regression line slope of urinary calcium to serum calcium. In healthy subjects, parathyroid activity significantly affects the extrapolated regression line of urinary calcium to serum calcium by changing the intercept, but not the slope.

Adult↗

[Active calcium and sodium transport by cardiac plasma membranes in the genetically hypertensive rat].

Active Na+ and Ca2+ transports by sarcolemmal vesicles from young spontaneously hypertensive rats (SHR) and their normotensive controls (WKY) were compared. The effects of the calmodulin and the calcium antagonist nifedipine on Ca2+ binding ATP-dependent accumulation of Ca2+ were studied at free Ca2+ concentrations of 2.10(-8)M and 4.10(-7)M. 2.10(-7)M calmodulin stimulated Ca2+ binding to SHR membranes up to a level equivalent to that in WKY, whereas it enhanced active Ca2+ transport more in WKY than in SHR, thus suppressing the difference between the two substrains. At a 2.10(-8)M free Ca2+ concentration low concentrations of nifedipine (10(-7) to 10(-6)M) induced an increases in ATP-dependent Ca2+ transport by SHR vesicles. Inhibition of NA+, K+-adenosine triphosphatase activity by ouabain was also studied. Na+, K+ATPase activity in SHR membranes was double that in membranes from WKY (22.1 +/- 2.8 v.s. 11.3 +/- 1.1. mumole Pi/h/mg protein). These differences, observed on 3 week-old rats, before a significant rise blood pressure, may reflect genetic characteristics of these hypertensive-prone rats.

Animals↗

Altered active sodium and calcium transport by heart sarcolemmal membranes from young spontaneously hypertensive rats: modulation by calmodulin.

Active transport of Na+,K+ and Ca2+ was compared in heart plasma membranes from 3-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). ATP-dependent Ca2+ accumulation, which reflects Ca2+, Mg2+-ATPase activity, was higher in SHR than in WKY membranes. At a free calcium concentration of 4 X 10(-7)M, the addition of 2 X 10(-7)M calmodulin enhanced the active Ca2+-transport more in WKY than in SHR vesicles. Na+- and K+-dependent ATPase activity was two fold higher in SHR than in WKY. From ouabain binding studies this seemed to be due to an increased density of enzyme units. Physiological concentrations of calmodulin and calcium ions reduced Na+,K+-ATPase activity in the two strains but more in SHR than in WKY. This study demonstrates that active Na+ and Ca2+ transport is enhanced in young SHR; the Ca2+-calmodulin complex may regulate Na+,K+-ATPase activity and sensitivity of Na+,K+-ATPase and Ca2+,Mg2+-ATPase activities to Ca2+-calmodulin differs between SHR and WKY.

Aging↗

Altered kinetics of an intravenous calcium load in hypertensive patients.

Essential hypertensive (EH) patients have a higher rate of urinary calcium excretion and, according to some reports, somewhat lower levels of serum ionized calcium. The aim of this study was to investigate the kinetics of an i.v. calcium load in EH patients and in normotensive controls. Fifteen EH patients and twelve sex-and weight-matched controls received a constant ionized rate i.v. calcium infusion (0.1 mmol Ca2+/kg body weight/h) for 2 h. Serum ionized calcium and urinary calcium excretion were determined at regular intervals during the infusion and, in two subgroups of seven hypertensives and seven controls, for up to 4 hours later. EH patients had significantly higher excretion rates (P less than (P less than 0.001) and slightly, but not significantly, lower serum ionized calcium compared to controls. The serum ionized calcium concentration attained at 60 and 120 min of the Ca2+ infusion was significantly lower in EH (P less than 0.01) and it remained appreciably lower for up to 220 min from the beginning of the test. The area under the curve of serum ionized calcium calculated at different time points was significantly reduced in the hypertensives. The mean renal calcium clearance of the patients during the infusion and the elimination phase was somewhat higher, but the difference from controls did not reach statistical significance. These data indicate an abnormal handling of a calcium load by patients with EH and raise the possibility that such abnormality may not be due simply to a renal defect but perhaps to an altered calcium distribution among different compartments in the body.

Adult↗

Abnormalities of calcium metabolism in essential hypertension.

Calcium metabolism has been investigated in patients with essential hypertension and normal renal function to evaluate the renal calcium handling and the reported increase in renal calcium loss. In 55 hypertensive and 55 sex- and age-matched healthy normotensive subjects creatinine clearance, serum total and ionized calcium, plasma parathyroid hormone and 24 h urinary excretion of calcium, sodium and cAMP were measured. In a subgroup of 20 hypertensive patients and 20 controls the fasting calcium excretion rate was also measured. Both 24 h and fasting calcium excretion rates were higher in the hypertensive group; so also were plasma parathyroid hormone and urinary cAMP. Serum total and ionized calcium levels were not different in the two groups. After intravenous calcium infusion (15 mg 3 h-1 kg-1) in seven hypertensive patients and controls, the hypertensive patients excreted more calcium at all serum calcium concentrations. These results support the hypothesis of primary renal calcium leak in essential hypertension. Enhanced urinary calcium excretion rate may cause compensatory parathyroid overactivity.

Adult↗

Body impedance studies in end-stage heart failure.

This study adds another category of patients to those amenable to body impedance analysis (BIA). BIA measurements were obtained for the first time in 23 male patients with end-stage heart failure who were waiting for heart transplantation, and the data were compared with those obtained in 69 healthy controls matched for age, sex, height and weight. The data indicate that in end-stage heart failure there is an increased reactance (p<0.01) and an altered intracellular water/extracellular water ratio (p<0.03) due to the increased intracellular water (p<0.01) and decreased extracellular water (p<0.01).

Adult↗

Systolic hypertension: the nephrologist's point of view.

The elevation of systolic blood pressure associated with aging has been considered for years a physiologic phenomenon. This idea was based on the repeated observation that, also after middle age, a large majority of individuals in industrialized countries experience a continuous and progressive increase over time in systolic blood pressure, not in diastolic blood pressure. However, some individuals in industrialized countries and most individuals in nonindustrialized countries do not acquire an increased systolic blood pressure over time proving that the age-associated rise in systolic blood pressure is not an inevitable phenomenon. The change in systolic blood pressure over time strongly reflects lifestyles. Diet-dependent factors such as body weight, alcohol intake, and balance between dietary salt and potassium, are important in favoring the age-associated increase in systolic blood pressure, independently of several confounders. Epidemiologic studies suggest that elevation of systolic blood pressure is a risk factor for cardiovascular diseases: it relates to high incidence of lethal and nonlethal cardiovascular events also in the presence of diastolic blood pressure in the nonhypertensive range. Controlled clinical trials show that the treatment of isolated systolic hypertension reduces the number of cardiovascular events. In addition to cardiovascular disease, systolic blood pressure relates also to microalbuminuria, an index of early glomerular damage, to long-term incidence of end-stage renal disease, and, in hemodialyzed patients, to premature death. Thus, high systolic blood pressure appears an unhealthy condition also for patients with or at risk for kidney diseases.

Aging↗

[Microalbuminuria in nondiabetic adults].

This paper deals with the clinical relevance of moderate increase in urinary albumin excretion, commonly known as microalbuminuria, in non-diabetic adults. Presently there are several definitions of microalbuminuria. When measuring excretion rates, microalbuminuria is defined by thresholds of 30 mg/day or 20 g/min with urine collections shorter than 24 hours whereas macroalbuminuria is defined by rates higher than 300 mg/day or micro 200 g/min, respectively. Clinical and epidemiological data indicate the presence of a correlation between blood pressure and microalbuminuria. Microalbuminuria is progressively more frequent with higher blood pressure (systolic or diastolic) also in non-hypertensive persons. Antihypertensive drugs lower urinary albumin excretion, the effect is modest or absent for dihydropyridinic calcium-channel blockers, strong for inhibitors of the renin-angiotensin system. In addition to blood pressure, other factors directly related to urinary excretion of albumin are cigarette smoking, blood lipids, body mass and dietary protein. In non-diabetics, microalbuminuria anticipates lethal and non-lethal cardiovascular events. This correlation can also be observed in the range of urinary albumin excretion below the thresholds that define microalbuminuria. Present data are not consistent on the possible correlation between microalbuminuria and renal function in non-diabetics.

Albuminuria↗

Primary gastrointestinal lymphoma: a clinicopathological study of 58 cases.

BACKGROUND: Primary non Hodgkin's lymphoma (NHL) of the gastrointestinal tract (GI) is the most frequent extranodal lymphoma accounting for approximately 40% of all extranodal primary NHL. The role of surgery and other treatment modalities in the management of these patients is still controversial. PATIENTS AND METHODS: We reviewed the records of 68 patients with primary GI-NHL. Ten patients had incomplete records and were excluded from further evaluation. The records of 58 patients were considered, and all were available for analysis and follow-up. RESULTS: The most frequent site of involvement was the stomach (47 patients), followed by ileum (7 patients), large bowel (3 patients) and duodenum (1 patient). Malignant lymphomas of follicular center cell origin represented the most prevalent histologic types, accounting for 58% (34 of 58) of all cases. Stage, evaluated according to the criteria of Musshoff, was Ie in 15 cases, IIe in 16, IIIe in 7, and IV in the remaining 20 cases. The median survival for the entire group of 58 patients was 54 months, with 46% of patients surviving at 5 years. The median survival was 71 months for patients in stage I-II, 60 for patients in stage III, and 25 for patients in stage IV (p = 0.016). Moreover, we found significantly improved survival in patients undergoing surgical tumor resection (p = 0.003). CONCLUSIONS: Even if at the present time the optimal management of primary GI-NHL is difficult to assess, our data suggest that it is prudent to advise resection followed by adjuvant CT in most patients, whereas CT alone should be considered only when surgery cannot be performed.

Adolescent↗

[Urinary albumin excretion and coronary artery disease].

The moderate elevation in urinary albumin excretion defined as microalbuminuria is common in the population and associated with cardiovascular (CV) risk factors. Microalbuminuria prevalence is low in the absence of CV risk factors and progressively increases with the number of the individual's CV risk factors. The main correlate of microalbuminuria is blood pressure (BP). The relationship between BP and microalbuminuria is continuous and graded since the prevalence of microalbuminuria increases with the severity of hypertension. Among hypertensives receiving treatment, BP control is associated with a low prevalence of microalbuminuria. Therefore, BP appears as a determinant of microalbuminuria rather than a mere correlate. For hypercholesterolemia, smoking and diabetes, the data are less strong, but point to an independent positive association with microalbuminuria. Altogether, data indicate that microalbuminuria in the population reflects the presence of CV risk factors. Data concerning microalbuminuria and coronary heart disease (CHD) support this idea. There is a continuous and graded relationship between urinary albumin excretion and CHD prevalence. High urinary albumin excretion is a likely sign of vascular damage existing both at renal and cardiac levels and induced by one or more uncontrolled CV risk factors.

Albuminuria↗

Sevelamer worsens metabolic acidosis in hemodialysis patients.

BACKGROUND: Sevelamer hydrochloride, a major phosphate binder for patients on maintenance hemodialysis (MHD) is associated with reduced serum bicarbonate concentration due to hydrochloric acid release in the gut and to the binding of short chain fatty acids in the large intestine. Since metabolic acidosis can be deleterious, a study was devised to compare the time course of serum bicarbonate concentration during treatment with sevelamer hydrochloride or calcium carbonate. METHODS: Sixteen well nourished patients on MHD who were in excellent clinical conditions and achieving target levels for blood pressure (BP) and hemoglobin (Hb), while on a protein intake of 1.1g/kg body weight (bw), were enrolled in the study. After a 2-week washout period, the patients were divided into two groups, each consisting of eight patients, and randomized either to 24 weeks of sevelamer followed by 24 weeks of calcium carbonate (group A) or to 24 weeks of calcium carbonate followed by 24 weeks of sevelamer (group B). Protein intake, n-protein catabolic rate (nPCR), serum concentrations of calcium, phosphate, calcium x phosphate (Ca x P) product, bicarbonate, intact parathyroid hormone (iPTH) and albumin were monitored. Time course changes in serum bicarbonate concentrations in relation to short and long dialytic intervals (48 vs. 72 hr) were also investigated. RESULTS: Both sevelamer and calcium carbonate effectively controlled serum phosphate and the Ca x P product. During calcium carbonate treatment plasma phosphate concentrations were significantly below those of patients on sevelamer. Plasma bicarbonate concentration fell within target DOQI values during calcium carbonate administration both in group A and in group B, a goal which was not achieved under sevelamer administration. After a long dialytic interval in patients on sevelamer, serum bicarbonate concentration averaged 17.3 +/- 1.1 mEq/L, whereas it averaged 21.1 +/- 0.7 mEq/L in patients on calcium carbonate (p<0.01). Finally, a 24-week sevelamer administration caused a statistically significant (p<0.05) reduction (0.8 g/dL) in serum albumin concentration, without affecting iPTH. Taken together, these results indicate that sevelamer worsens metabolic acidosis, which needs to be corrected.

Acidosis↗