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Biomedical subjects

F Sangalli

Publications and source records attributed to F Sangalli.

16 recordsLinked to original sources
PubMed2006

ACE inhibition reduces glomerulosclerosis and regenerates glomerular tissue in a model of progressive renal disease.

Today angiotensin II inhibition is primarily used to slow the rate of progression of kidney diseases. There is evidence that these therapies can induce a partial regression of glomerular lesions. However, we do not know yet the extent of sclerotic lesion regression and whether new glomerular tissue is formed to help support the renal function. We used male Munich Wistar Fromter (MWF) rats, an experimental model for progressive kidney disease, to quantify kidney structural lesions upon angiotensin-converting enzyme (ACE) inhibition therapy. Animals were studied at 50 weeks of age, when renal function and structure are severely altered, and after a 10-week observation period, without or with treatment with lisinopril (80 mg/l in drinking water). A group of untreated Wistar rats was used as controls. With age, proteinuria, and serum creatinine worsen, but lisinopril almost normalized proteinuria and stabilized serum creatinine. Serial section analysis of whole glomerular tufts showed that at baseline, glomerulosclerosis affected the entire glomerular population, and that these changes further increased with age. Lisinopril significantly reduced incidence and extent of glomerulosclerosis, with the presence of glomerular tufts not affected by sclerosis (23% of glomeruli). Glomerular volume was not significantly affected by treatment, and glomerular mass spared from sclerosis increased from 46.9 to 65.5% upon treatment, indicating consistent regeneration of glomerular tissue. Lisinopril normalized baseline glomerular transforming growth factor-beta and alpha-smooth muscle actin overexpression, and prevented worsening of interstitial changes. Hence, ACE inhibition, which is widely used in human kidney disease, may not only halt the progression of renal failure, but also actually induce the regeneration of new renal tissue.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Post-transplant renal artery stenosis: the hemodynamic response to revascularization.

BACKGROUND: Percutaneous transluminal angioplasty and stenting are relatively noninvasive approaches to treat post-transplant renal artery stenosis. However, the real impact of this procedure on renal function recovery has never been quantitated precisely to date. METHODS: In eight consecutive renal transplant patients with renal graft artery stenosis, blood pressure, body weight, and anatomical, functional, and Doppler ultrasound parameters were evaluated before and one month after renal artery transluminal angioplasty and stenting. On both occasions, glomerular filtration rate and renal plasma flow were evaluated by inulin and paraaminohippuric acid renal clearances, and glomerular size-selective function was evaluated by the fractional clearances of neutral dextran macromolecules. RESULTS: The correction of renal artery stenosis, by normalizing renal vascular resistances, fully restored kidney perfusion and decreased arterial blood pressure, relieved water and sodium retention, restored an almost laminar arterial blood flow, and normalized vascular shear stress without appreciable effects on glomerular barrier size-selective function and proteinuria. Preangioplasty and postangioplasty renal resistive indices and peak systolic blood velocity estimated by Doppler ultrasounds were significantly correlated with the effective renal plasma flow and the blood velocity calculated at the site of stenosis. All patients were discharged without sequelae one or two days after angioplasty. CONCLUSIONS: Percutaneous transluminal angioplasty and stenting are safe and effective procedures to normalize the functional changes sustained by hemodynamically significant artery stenosis after renal transplantation. Doppler ultrasound scanning is a reliable and reproducible technique to monitor the renal functional response to vascular reperfusion.

Adult↗
PubMed2001

Permissive hypercapnia.

The term permissive hypercapnia defines a ventilatory strategy for acute respiratory failure in which the lungs are ventilated with a low inspiratory volume and pressure. The aim of permissive hypercapnia is to minimize lung damage during mechanical ventilation; its limitation is the resulting hypoventilation and carbon dioxide (CO2) retention. In this article we discuss the rationale, physiologic implications, and implementation of permissive hypercapnia. We then review recent clinical studies that tested the effect of various approaches to permissive hypercapnia on the outcome of patients with acute respiratory failure.

Adult↗
PubMed2000

ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome.

Patients with idiopathic membranous nephropathy (IMN) and persistent nephrotic-range proteinuria are at risk for progression to end-stage renal failure. Whether angiotensin-converting enzyme (ACE) inhibitors are also renoprotective in these patients remains elusive. In 14 patients with IMN (patients) and persistent proteinuria (protein > 3 g/24 h for >6 months), we studied mean arterial pressure (MAP), urinary protein excretion, glomerular filtration rate (GFR), renal plasma flow (RPF), and albumin and neutral dextran fractional clearance after 2 months washout from previous antihypertensive treatment (basal), after 2 months of enalapril (2.5 to 20 mg/d) therapy (posttreatment), and 2 months after enalapril withdrawal (recovery). MAP, proteinuria, and GFR were also measured at the same time points in 6 patients with IMN and persistent overt proteinuria maintained on conventional treatment throughout the study period (controls). Basal MAP, proteinuria, and GFR were similar in the two study groups. However, in patients at the end of the treatment period, MAP (posttreatment, 99.6 +/- 11.2 versus basal, 103.3 +/- 12.1 mm Hg; P < 0.05), proteinuria (posttreatment protein, 5.0 +/- 2.9 versus basal, 7.1 +/- 4.9 g/24 h; P < 0.05), albumin fractional clearance (posttreatment median, 1.7 x 10(-3); range, 0.2 to 22.7 x 10(-3) versus basal median, 4.1 x 10(-3); range, 0.4 to 22. 1 x 10(-3); P < 0.05), and fractional clearance of largest neutral dextrans (radii from 62 to 66 A) were significantly less than basal values. At recovery, MAP significantly increased to 106.6 +/- 11.7 mm Hg (P < 0.001 versus enalapril), but all other parameters remained less than basal values. GFR and RPF were similar at each evaluation. Changes in proteinuria after treatment withdrawal positively correlated (r = 0.72; P < 0.01) with baseline GFR. Theoretical analysis of dextran-sieving data indicated that ACE inhibitor treatment significantly improved glomerular membrane size-selective dysfunction. This effect persisted more than 2 months after treatment withdrawal. No patient had symptomatic hypotension, acute renal function deterioration, or hyperkalemia during enalapril treatment. Thus, in patients with IMN and long-term nephrotic syndrome, ACE inhibitor treatment, but not conventional therapy, improves glomerular barrier size selectivity. The antiproteinuric effect of ACE inhibition is long lasting, especially in patients with more severe renal insufficiency. This is the premise of a long-term renoprotective effect that may limit the need for treatment with more toxic drugs.

Adult↗
PubMed2000

Reverse-thrust ventilation in hypercapnic patients with acute respiratory distress syndrome. Acute physiological effects.

Techniques of tracheal gas insufflation (TGI) have been shown to enhance CO(2) clearance efficiency in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). Clinical studies have explored the effects of such techniques only at moderate intratracheal gas flow rates, with TGI superimposed to mechanical ventilation in a continuous fashion, or synchronized to the expiratory phase of the duty cycle. We examined the effects of intratracheal pulmonary ventilation (ITPV), delivering the entire tidal volume (VT) in the proximity of the tracheal carina, with all the gas flow supplied continuously through a reverse-thrust catheter (RTC). A potential limitation in the application of TGI is dynamic hyperinflation. Therefore, in a subgroup of patients, we also evaluated the effects of ITPV on end-expiratory lung volume (EELV) by respiratory inductive plethysmography (RIP). Eleven patients with ARDS under volume-cycled mechanical ventilation were subsequently switched to ITPV at the same baseline respiratory rate, I:E ratio, and VT. At the same minute volume, Pa(CO(2)) decreased from 70 +/- 12.3 to 59 +/- 9.5 mm Hg, with a percent reduction of 15 +/- 4% (range from 10 to 20%). The CO(2) decrease was greater in patients with higher baseline Pa(CO(2)) levels (DeltaPa(CO(2)) = 0.29 x Pa(CO(2)) - 9.48, r = 0.95). During transition from mechanical ventilation to ITPV, tracheal positive end-expiratory pressure (PEEP(tr)) decreased with a correspondent decrease in EELV. Both were restored by increasing the PEEP at the ventilator by 3.6 +/- 2.0 cm H(2)O. These data suggest that in patients with ARDS ITPV effectively reduces dead space ventilation and the employment of the RTC may limit or avoid dynamic hyperinflation.

Adult↗
PubMed1999

Beneficial effects of calcium channel blockade on acute glomerular hemodynamic changes induced by cyclosporine.

Experimental and human studies have documented that cyclosporine (CsA) acutely reduces glomerular filtration rate (GFR). It has been reported that this effect can be partially prevented by calcium (Ca) channel blockade; however, the mechanisms by which this combination exerts its beneficial effects are unknown. We evaluated glomerular ultrafiltration determinants during acute CsA administration in the rat. First, we determined that maximal whole-kidney functional changes occur between 120 and 150 minutes after CsA administration and confirmed that pretreatment of MWF rats with the Ca channel blocker lacidipine effectively prevents a reduction in GFR. Micropuncture measurements in CsA-treated animals showed that a reduction in GFR (0.49 +/- 0.24 v 0.88 +/- 0.26 mL/min; P < 0.05; CsA-treated v untreated rats) is associated with a significant increase in glomerular capillary pressure (Pgc; 63.1 +/- 2.1 v 52.8 +/- 2.8 mm Hg; P < 0.01) and efferent arteriolar resistance, whereas single-nephron (SN) GFR and ultrafiltration coefficient (Kf) are both importantly reduced (34.0 +/- 11.7 v 68.9 +/- 23.8 nL/min; P < 0.05 and 1.04 +/- 0.33 v 4.40 +/- 2.36 nL/min/mm Hg; P < 0.01, respectively). Lacidipine partially prevented SNGFR (43.1 +/- 14.3 nL/min) and Kf decline (2.08 +/- 1.10 nl/min/mm Hg) despite the presence of elevated Pgc. This study further documents that Ca channel blockade has favorable effects on CsA-induced acute renal dysfunction. The mechanism of protection includes the prevention of glomerular hemodynamic changes induced by CsA, mainly GFR decline and reduction in glomerular Kf.

Acute Disease↗
PubMed1999

Glomerular size-selective dysfunction in NIDDM is not ameliorated by ACE inhibition or by calcium channel blockade.

BACKGROUND: In patients with insulin-dependent diabetes mellitus (IDDM) and overt nephropathy glomerular barrier size-selectivity progressively deteriorates with time and is effectively improved by angiotensin converting enzyme (ACE) inhibition. Whether similar glomerular functional changes develop in proteinuric patients with non-insulin-dependent diabetes mellitus (NIDDM), and whether antihypertensive agents can favorably affect glomerular filtration of macromolecules in these patients, has not been documented yet. METHODS: We investigated renal hemodynamics and fractional clearance of neutral dextrans of graded sizes, in nine proteinuric patients with NIDDM and renal biopsy findings of typical diabetic glomerulopathy. Six healthy volunteers served as controls. We also investigated the effects of an ACE inhibitor and of a calcium channel blocker, both given in doses targeted to achieve a comparable level of systemic blood pressure control, on glomerular hemodynamics and sieving function. Theoretical analysis of glomerular macromolecule transport was adopted to evaluate intrinsic glomerular membrane permeability properties. RESULTS: Fractional clearance of large macromolecules (42 to 66 A in radius) was significantly higher in diabetic patients than in controls, and the distribution of membrane pore radii was calculated to be shifted towards larger pore sizes in diabetics (mean radius increased from 55 to 60 A). Despite effective blood pressure control, neither antihypertensive affected glomerular hemodynamics to any significant extent. Fractional clearance of dextrans, as well as of albumin and IgG, and total urinary proteins were not modified by either treatments. CONCLUSIONS: These data indicate that patients with NIDDM and overt nephropathy develop abnormalities in size-selective function of the glomerular barrier and, at variance to IDDM, such changes were not ameliorated either by ACE inhibition or calcium channel blockade.

Adult↗
PubMed1999

ACE inhibition and ANG II receptor blockade improve glomerular size-selectivity in IgA nephropathy.

Protein trafficking across the glomerular capillary has a pathogenic role in subsequent renal damage. Despite evidence that angiotensin-converting enzyme (ACE) inhibitors improve glomerular size-selectivity, whether this effect is solely due to ANG II blocking or if other mediators also play a contributory role is not clear yet. We studied 20 proteinuric patients with IgA nephropathy, who received either enalapril (20 mg/day) or the ANG II receptor blocker irbesartan (100 mg/day) for 28 days in a randomized double-blind study. Measurements of blood pressure, renal hemodynamics, and fractional clearance of neutral dextran of graded sizes were performed before and after 28 days of treatment. Both enalapril and irbesartan significantly reduced blood pressure over baseline. This reduction reached the maximum effect 4-6 h after drug administration but did not last for the entire 24-h period. Despite transient antihypertensive effect, proteinuria was effectively reduced by both treatments to comparable extents. Neither enalapril nor irbesartan modified the sieving coefficients of small dextran molecules, but both effectively reduced transglomerular passage of large test macromolecules. Theoretical analysis of sieving coefficients showed that neither drug affected significantly the mean pore radius or the spread of the pore-size distribution, but both importantly and comparably reduced the importance of a nonselective shunt pathway. These data suggest that antagonism of ANG II is the key mechanism by which ACE inhibitors exert their beneficial effect on glomerular size-selective function and consequently on glomerular filtration and urinary output of plasma proteins.

Adult↗
PubMed1998

The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indomethacin.

Evidence is available from animal and human studies that protein traffic through the glomerular capillary has a pathogenetic role in subsequent renal damage and that angiotensin-converting enzyme (ACE) inhibitors appear superior to other drugs in lowering proteinuria and the rate of renal function decline. This study compares the effect of ACE inhibition or angiotensin II (AngII) receptor blockade on urinary protein excretion and renal hemodynamics in 20 patients with IgA glomerulonephritis randomized to receive enalapril (20 mg/d) or irbesartan (100 mg/d) for 28 d in a double-blind study with two parallel groups. This study also evaluated whether addition of indomethacin (75 mg twice a day) to each of the two treatments resulted in a more potent antiproteinuric effect. Enalapril alone reduced total protein excretion (61% change from baseline) and fractional clearance of albumin without changes in GFR and minor elevation in renal plasma flow. Also, patients randomized to receive the AngII receptor antagonist irbesartan for 28 d had lower proteinuria (55% change from baseline) and fractional clearance of albumin at the end of the treatment period with similar renal hemodynamic changes. When indomethacin was added to enalapril treatment, a further significant reduction in urinary proteins and fractional albumin clearance was observed. In patients given irbesartan, the addition of indomethacin further reduced proteinuria and fractional clearance of albumin. The combined therapy with enalapril or irbesartan and indomethacin did not significantly affect GFR and renal plasma flow compared with baseline. These findings indicate that in patients with IgA glomerulonephritis the antiproteinuric effect of blocking AngII activity by either ACE inhibitors or AngII receptor antagonists is potentiated by indomethacin, an effect that occurred without impairment of renal function.

Adult↗
PubMed1998

Progressive glomerular injury in the MWF rat is predicted by inborn nephron deficit.

It has been suggested that a reduced number of nephrons may predispose to systemic hypertension and glomerular injury. Compensatory hemodynamic changes, due to a low number of glomeruli, might be responsible for glomerular functional and structural changes. It is difficult to evaluate this hypothesis in humans because of limitations in estimating the number of nephrons in the living kidney. The aim of the present study was to estimate nephron number, single glomerular hemodynamics, and glomerular volume in male and female MWF rats, a strain that spontaneously develops systemic hypertension, proteinuria, and glomerulosclerosis. Male and female Wistar rats were used as controls. At 12 to 14 wk of age, male MWF rats developed proteinuria, whereas female MWF and Wistar rats showed normal urinary protein excretion rate. Glomerular number was significantly reduced in male and female MWF rats (13,690+/-1,489 and 12,855+/-1,781 gl/ kidney, respectively) compared with Wistar rats (26,955+/-2,171 and 27,166+/-1,754 gl/kidney, respectively). The mean number of nephrons per unit of body weight was also lower in MWF males (88+/-10) compared with MWF females (139+/-20) and compared with male and female Wistar animals (142+/-14 and 221+/-22 gl/g body wt). Whole-kidney hemodynamic parameters and the number of nephrons were used to calculate single-nephron filtration rate and plasma flow. Both measures were markedly elevated in male MWF rats relative to values obtained in the other three groups. Similarly, glomerular volume was significantly greater in MWF males than in other animals. These results suggest that an inborn deficit of nephrons may be responsible for spontaneous development of later-in-life hypertension and renal dysfunction. The data also indicate the need to investigate the role of this potential pathogenetic factor for human hypertension and kidney disease in humans.

Animals↗
PubMed1996

Angiotensin II modulates glomerular capillary permselectivity in rat isolated perfused kidney.

Studies in experimental animals and humans have documented that inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitors reduces urinary protein excretion rate and retards the development of renal injury. Here we sought to investigate whether angiotensin II (All) modified the size-selective properties to macromolecules of the glomerular capillary barrier in isolated perfused rat kidney preparation. Compared with basal values, continuous All infusion into the renal artery at the rate of 3 or 8 ng/min, but not at 0.6 ng/min, induced a progressive and significant increase in urinary protein excretion rate. Evaluation of the sieving properties of the glomerular barrier by fractional clearance of polydisperse Ficoll showed that All significantly enhanced the filtration of tracer molecules of radil > or = 34A. All-induced changes in urinary protein excretion rate and in Ficoll fractional clearance were completely prevented by pretreatment with the specific All Type 1 receptor antagonist SR 47436.

Angiotensin II↗
PubMed1996

[The unique trans-fronto-nasal approach. A new approach to benign expansive bone tumors of the anterior floor of the skull base].

We report our experience with a new access route for benign expansive bone tumors of the anterior floor of the skull. From 1991, we used a unique transfrontonasal route, adapted from Raveh's technique for trauma surgery of the anterior floor, to access all tumors in this region. The images presented here show the advantages of this technique: overall vision allows permanent intraoperative control. In addition, the absence functional or esthetic sequelae favor this route for benign tumors.

Adolescent↗
PubMed1989

[Craniofacial injuries and cerebral tomographic scintigraphy using N-isopropyl-iodo-amphetamine 123 I-AMP].

An investigation was done with N.-isopropyl-iodoamphetamine (123I AMP) in 20 patients: 10 patients with craniofacial injury and 10 patients without brain dysfunction or injury. Brain X ray computerized Tomography was normal. SPECT 123 I AMP detected functional defects related with traumatic impacts. Sensitivity is higher with SPECT than with CT Scan. The indications for the initial evaluation of head injury, and the relations with later sequelae i.e. post traumatic epilepsia and subjective syndrome are discussed.

Adolescent↗
PubMedDate not supplied

Unexpected lower prevalence of HBsAg in diabetics than in controls. (A study on 2,465 patients).

Serum samples from 2,465 diabetics were examined by radioimmunoassay for HBsAg, anti-HBs and anti-HBc at the Centro Antidiabetico of the Ospedale Maggiore di Lodi; during the same period, the same tests were carried out on serum samples from 2,176 control subjects, who had been admitted to the surgical, casualty and obstetrical departments for reasons that had nothing whatsoever to do with any form of liver disease. The ages of the two groups ranged from 6 to 90 years. The diabetics were divided into three groups; insulin-dependent, non-insulin-dependent and diabetics treated with insulin for diabetic complications. The overall frequency of HBsAg in the various groups of diabetics was 3.5%, while in the controls it was 6.1% (p less than 0.001). In the group of young insulin-dependent diabetics, the frequency was 1.7%, as compared to 6.9% for the controls in the same age group (p less than 0.05). In the group of patients treated with insulin for diabetic complications, the frequency increased to 11.5%, while for the controls in the same age group it was 5.5%. The levels of HBsAg were practically the same in the diabetics and in the controls, whereas the level of anti-HBc was higher in the diabetics: 55.6% compared to 50% (p less than 0.005). This last result indicates that the chances of hepatitis B virus infection were greater for the diabetics than for the controls. Diabetics, and especially those insulin-dependent are, therefore, believed to possess a greater capacity of resistance through their T cell-mediated immune response to the hepatitis B virus.

Adolescent↗
PubMedDate not supplied

Prevention of renal injury in diabetic MWF rats by angiotensin II antagonism.

We studied the effect of the combination of streptozotocin-induced diabetes and spontaneous renal injury in male MWF rats. Renal hemodynamics was studied by micropuncture 1 month after streptozotocin administration, and kidney morphological evaluation was performed after 4 months of diabetes. We also studied the effect of angiotensin II antagonism on development of renal lesions. Untreated animals developed mild hypertension, proteinuria, and glomerulosclerosis. Induction of diabetes, and maintenance of a moderate hyperglycemic state, was associated with slight but significant elevation in systemic and glomerular capillary blood pressure. Development of proteinuria was not accelerated or exacerbated by diabetes. Glomerular and tubular structural changes were also not worsened by diabetes. Antihypertensive treatment with an ACE inhibitor (benazepril) or with an AII receptor antagonist (valsartan) almost completely prevented systemic and glomerular capillary hypertension, proteinuria and renal structural changes. No significant differences in glomerular volume were observed among the four groups. That induction of experimental diabetes, although associated with glomerular capillary hypertension, did not aggravate the rate of progression of renal dysfunction would suggest that glomerular injury is not directly influenced by glomerular hemodynamic conditions in these animals. Prevention of renal functional and structural abnormalities by antagonism of AII activity in diabetic MWF rats suggests a pathogenetic role for angiotensin in inducing the renal disease in these animals.

Angiotensin II↗