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Biomedical subjects

G Sacchi

Publications and source records attributed to G Sacchi.

At least 37 records · Page 2Linked to original sources

Microalbuminuria: a marker of cardiovascular risk and organ damage in essential hypertension.

Microalbuminuria (Mi) is thought to reflect diffuse vascular damage and to predict cardiovascular morbidity and mortality in essential hypertension, although its pathogenesis remains to be fully elucidated. The relationship between microalbuminuria and several cardiovascular risk factors and target organ damage was evaluated in a large cohort of untreated essential hypertensive patients. Albuminuria was measured as the albumin to creatinine ratio in three non consecutive first morning urine samples. Cardiac damage was evaluated by ECG and retinal vascular changes by direct ophtalmoscopy. In a subgroup of 23 patients with Mi and in a control group of 22 normoalbuminurics, selected from the entire cohort of patients and carefully matched for age, gender, body mass index (BMI) and duration of disease, we also measured left ventricular mass index by M-B mode echocardiography, common carotid wall thickness by high resolution US-scan, and renal vascular resistances by US-doppler of interlobar arteries. K-means cluster analysis performed on the entire cohort of patients showed that microalbuminuria is associated with the presence of an unfavorable risk profile and target organ damage. Furthermore, microalbuminuric hypertensive patients have a larger left ventricular mass index, increased intima media thickness of carotid arteries and higher intrarenal vascular resistances as compared to a well matched group of normoalbuminuric patients. We conclude that in essential hypertension increased urinary albumin excretion can be useful to identify patients for whom more aggressive preventive strategies and/or additional treatment measures are advisable.

Albuminuria↗

Glioma cells induce gamma-glutamyl transpeptidase activity in cultured blood but not lymphatic endothelial cells.

Glial cells have been shown to induce enzyme activities, which are characteristically high in brain capillaries, in cerebral and non cerebral endothelial cells in culture. We evaluated the activity of gamma-glutamyl transpeptidase (gamma GT) in freshly isolated (ex vivo) bovine blood (BEC) and lymphatic (LEC) endothelial cells. We also tested the effect of C6 glioma cell conditioned medium (GCM) on gamma GT activity of BEC and LEC in primary culture. Ex vivo BEC had a high gamma GT activity, only 9% of which was retained in culture. After exposure to GCM, however, gamma GT activity of cultured BEC was twofold higher than with control medium. By contrast gamma GT activity was extremely low in ex vivo LEC and did not significantly increase in cultured LEC exposed to GCM. These data show that the basal levels of gamma GT are markedly different in BEC and LEC and also that, unlike BEC, LEC are not capable of producing more gamma GT in response to glial stimulation.

Animals↗

The deletion polymorphism of the angiotensin I-converting enzyme gene is associated with target organ damage in essential hypertension.

The activity of the renin-angiotensin-aldosterone system is thought to play a significant role in the development of target organ damage in essential hypertension. An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been associated with increased risk for left ventricular hypertrophy and coronary heart disease in the general population. The D allele is associated with higher levels of circulating ACE and therefore may predispose to cardiovascular damage. The study presented here was performed to investigate the association between the ACE genotype, microalbuminuria, retinopathy, and left ventricular hypertrophy in 106 patients with essential hypertension. ACE gene polymorphism was determined by polymerase chain reaction technique. Microalbuminuria was evaluated as albumin-to-creatinine ratio (A/C) in three nonconsecutive first morning urine samples (negative urine culture) after a 4-wk washout period. Microalbuminuria was defined as A/C between 2.38 to 19 (men) and 2.96 to 20 (women). Hypertensive retinopathy was evaluated by direct funduscopic examination (keith-Wagener-Barker classification) and left ventricular hypertrophy by M-B mode echocardiography. The distribution of the DD, ID, and II genotypes was 27, 50, and 23%, respectively. The prevalence of microalbuminuria, retinopathy, and left ventricular hypertrophy was 19, 74, and 72% respectively. There were no differences among the three genotypes for age, known duration of disease, body mass index, blood pressure, serum glucose, uric acid, and lipid profile. DD and ID genotypes were significantly associated with the presence of microalbuminuria (odds ratio, 8.51; 95% confidence interval, 1.07 to 67.85; P = 0.019), retinopathy (odds ratio, 5.19; 95% confidence interval, 1.71 to 15.75; P = 0.005) and left ventricular hypertrophy (odds ratio, 5.22; 95% confidence interval, 1.52 to 17.94; P = 0.016). Furthermore, patients with DD and ID genotypes showed higher levels of A/C (3.6 +/- 0.9, DD; 2.6 +/- 0.7, ID; 0.9 +/- 0.2 mg/mmol, II; P = 0.0015 by analysis of variance) and increased left ventricular mass index (152 +/- 4.7, DD + ID versus 133 +/- 5.7 g/m2, II; P = 0.01) compared with II patients. The D allele was significantly more frequent in patients with microalbuminuria (odds ratio, 2.59; 95% confidence interval, 1.24 to 5.41; P = 0.013) and in those with retinopathy (odds ratio, 2.44; 95% confidence interval, 1.21 to 4.90; P = 0.015). Multiple regression analyses performed among the entire cohort of patients demonstrated that ACE genotype significantly and independently influences the presence of retinopathy, left ventricular hypertrophy, and microalbuminuria. In conclusion, the D allele of the ACE gene is associated with microalbuminuria as well as with retinopathy and left ventricular hypertrophy, and seems to be an independent risk factor for target organ damage in essential hypertension.

Adult↗

Cytochemical differentiation between blood and lymphatic endothelium: bovine blood and lymphatic large vessels and endothelial cells in culture.

Cytochemical differentiation between blood and lymphatic endothelium has been studied only in microvessels; 5'-nucleotidase (5'Nase) has been reported to be specific for lymphatic and alkaline phosphatase (ALPase) for blood endothelium. Adenylate and guanylate cyclase (AC and GC) have recently been proposed as lymphatic endothelial markers, but conflicting data exist. This study was designed to verify the presence of these enzymes in the endothelium of large vessels and to determine whether they are retained in endothelial cells (ECs) in culture. Segments of bovine mesenteric arteries, veins, and lymphatic collectors, and EC cultures obtained by collagenase treatment of the same vessels, were assayed for 5'Nase, ALPase, AC, and GC, and were observed by transmission electron microscopy. We found ALPase activity in blood and lymphatic vessels, and this was the only enzyme activity consistently retained under culture conditions. 5'Nase was found in lymphatic but not in blood endothelium, as previously reported for microvessels. AC and GC activity was found in blood but not in lymphatic endothelium. Hence, ALPase is not a useful marker to differentiate blood from lymphatic endothelium in large vessels, whereas 5'Nase is specific for lymphatic and AC and GC for blood endothelium. It is not clear why these enzyme activities are not expressed in culture.

5'-Nucleotidase↗

Subendothelial nerve fibers in bovine mesenteric lymphatics: an ultrastructural and immunohistochemical study.

In the lymphatic vessels of man and most animals the nerve fibers are confined to the adventitia. However, immunohistochemical studies suggest that acetylcholinesterase-positive and monoamine-containing fibers reach as far as the endothelium in bovines. The aim of this study was to verify the presence of subendothelial nerve fibers by transmission electron microscopy (TEM) in bovine mesenteric lymphatics and to determine whether typical sensory neurotransmitters such as Substance P (SP) and calcitonin gene related peptide (CGRP) could be detected in these fibers. TEM revealed numerous unmyelinated nerve fibers in the subendothelial connective environment in close association with endothelial cells. Their axons were devoid of Schwann cell sheath on the endothelial side and contained small clear vesicles and large nerve fibers were demonstrated to be SP and CGRP-immunoreactive with mouse monoclonal antibodies against SP and rabbit polyclonal antibodies against CGRP. It is hypothesized that these fibers act as mechanoceptors capable of detecting intraluminal pressure and vessel wall tension variations and of locally releasing SP and CGRP. Since SP, potentiated by CGRP, is known to be a vasoconstrictor in lymphatics, we propose that the contraction of bovine mesenteric lymphatics may also be neurogenic.

Animals↗

Inhaled mycotoxins lead to acute renal failure.

Mysterious deaths of archeologists after opening Egyptian tombs have been suspected, but never proved, to be secondary to inhalation of mycotoxin. We observed a case of acute renal failure (ARF) due to inhalation of ochratoxin A produced by a mould of the species Aspergillus ochraceus. After working 8 h in a granary closed for several months, a farmer and his wife suffered respiratory distress; the woman developed non-oliguric ARF and biopsy revealed tubulonecrosis. A strain of Aspergillus ochraceus producing ochratoxin was isolated from the wheat.

Acute Kidney Injury↗

Acute renal failure from inhalation of mycotoxins.

Mysterious deaths of archeologists after opening Egyptian tombs have been suspected to be secondary to inhalation of mycotoxin, however, the hypothesis has never been verified. Recently, we observed a case of acute renal failure (ARF) undeniably due to inhalation of ochratoxin of Aspergillus ochraceus. After spending 8 h in a granary which had been closed for several months, a farmer and his wife suffered temporary respiratory distress; 24 h later, the woman developed nonoliguric ARF and biopsy revealed tubulonecrosis which healed in 24 days. Toxic substances were not found, but a strain of A. ochraceus producing ochratoxin was isolated from the wheat.

Acute Kidney Injury↗

Isolation of pig pancreatic islets by a new method with hydraulic shaking: preliminary report.

The limited availability of human pancreas represents a serious problem in islet transplantation. In the past few years many efforts have been made to isolate pancreatic islets from large mammals in order to achieve valid and reproducible isolation methods. For several reasons swine may be considered an ideal source of islet tissue because of the similarity between human and porcine insulin and because of the easy availability of pig pancreata. Some papers have been published recently on this topic with good results. However, some problems, such as islet dissociation into single cells after collagenase digestion, are not completely solved. In this article, an automated method involving a hydraulic shaking system is described for islet isolation from the pig pancreas, developed in our laboratory and derived from Ricordi's model.

Animals↗

Familial occurrence of primary glomerulonephritis: evidence for a role of genetic factors.

Chronic glomerulonephritis was diagnosed in 23 patients born in a small valley in Northern Italy and in five additional patients with one parent or a more remote ancestor born in the same area, all belonging to three potentially related families. Eighteen patients had biopsy-proven glomerulonephritis: 11 IgA nephropathy, 3 IgM nephropathy, 2 membranoproliferative type I, and 2 mesangial proliferative glomerulonephritis with isolated C3 deposits. Ten had clinical glomerulonephritis. A community screening programme discovered six additional related patients. Two underwent renal biopsy (1 IgA nephropathy; 1 focal glomerulosclerosis); four were diagnosed as having clinical glomerulonephritis. Genealogical investigation identified five deceased family members with diagnoses of chronic nephritis recorded on their death certificates. No environmental nephrotoxic factors were identified. Restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta, HLA-DQ alpha and beta genes, and complement typing for C4A, C4B, and Bf polymorphisms were carried out for 29 patients, 168 healthy relatives, and 24 local controls. The frequency of HLA-Dw8.1 specificity, related to DR beta 8, DQ beta 3b, and DQ alpha 1a RFLPs, was significantly increased more in the affected and unaffected pedigree members than in Italian controls.

Adolescent↗

Verotoxin glycolipid receptors determine the localization of microangiopathic process in rabbits given verotoxin-1.

Infection with verotoxin-producing Escherichia coli has been implicated in the cause of hemolytic-uremic syndrome. Cases of thrombotic thrombocytopenic purpura and verotoxin infections have been also described. In this study we sought to determine the following: (1) whether verotoxin induces microvascular lesions in the rabbit, (2) the organ distribution of such lesions, and (3) the distribution of verotoxin glycolipid receptors in the various organs. Rabbits challenged with verotoxin-1 purified from E. coli O157:H7 had anorexia, lethargia, and limb paralysis; renal function, however, was normal. Central nervous system lesions found included pericellular and perivascular edema, focal hemorrhage, vascular lesions, and severe alterations of Purkinje cells. Histologic changes were also seen in the colon, with mucosal and submucosal edema and hemorrhage, and in the lung, with interstitial fibrosis and focal lymphohistiocitic infiltration. No lesions were detected in kidney, heart, liver, and spleen. Screening of various tissues for the presence of the verotoxin receptors revealed galabiosyl ceramide in the central nervous system and globotriosyl ceramide in the gastrointestinal tract, lung, and spleen. No receptors for verotoxin were found in the heart, liver, and kidney. These results indicate that organ localization of the disease in rabbits is dependent on the distribution of verotoxin receptors.

Administration, Oral↗

Renal vascular lesions as a marker of poor prognosis in patients with lupus nephritis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL).

The frequency of renal vascular lesions (RVL) and their relevance in the progression of renal damage were evaluated by the Pathology Group of the "Gruppo Italiano per lo Studio della Nefrite Lupica" (GISNEL). Of 285 patients with lupus nephritis collected from 20 nephrology centers in Italy and classified according to World Health Organization (WHO) criteria, 79 cases (27.7%) with RVL were identified and classified as follows: (1) lupus vasculopathy (n = 27); (2) hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) malignant hypertension-like lesions (n = 24); (3) vasculitis (n = 8); (4) arterio-arteriosclerosis (n = 20). At the time of renal biopsy, patients with RVL had mean serum creatinine levels significantly higher than patients without RVL (201.8 +/- 195.9 mumol/L [2.2 +/- 2.2 mg/dL] v 108.1 +/- 108.0 mumol/L [1.2 +/- 1.2 mg/dL]; P less than 0.01). Hypertension was more frequent in patients with RVL than in those without (68.4% v 30.5%; P less than 0.01). The probability of kidney survival assessed according to the Kaplan-Meier method at 5 and 10 years was, respectively, 74.3% +/- 5.9% and 58.0% +/- 8.9% in patients with RVL, compared with 89.6% +/- 2.7% and 85.9% +/- 3.7% in patients without RVL. However, the two groups did not differ significantly as regards overall survival, the probability of survival at 5 and 10 years being 86.5% +/- 4.5% and 78.8% +/- 6.6% in patients with RVL and 92.2% +/- 2.2% and 83.3% +/- 4.4% in patients without RVL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Autologous peritoneal mesothelial cell implant in rabbits and peritoneal dialysis patients.

Human and rabbit peritoneal mesothelial cells have been successfully cultured and autoimplanted. An original biopsy technique was used to take samples of peritoneal mesothelial cells and after culture they were characterized from the structural and caryological points of view. Staphylococcal peritonitis was induced in 12 rabbits with indwelling peritoneal catheters and after 4 days of antibiotics 6 of them were autoimplanted with cultured autologous mesothelial cells previously marked in 3 cases with thymidine (H3TdR). Direct morphological observation and autoradiography were used to compare the mesothelium of control rabbits and implanted rabbits sacrificed on days 3 and 6 and showed that the cell implants had taken. Four uremic CAPD patients recovering from severe peritonitis were implanted with about 300 million autologous peritoneal mesothelial cells, previously cultured and frozen. Morphological signs of taking were evident from peritoneal laparoscopy biopsies performed 3 and 6 days after implant. The aim of the study was merely to demonstrate that such implants are possible; however, the techniques may have interesting applications not only in peritoneal dialysis, but also in the vaster fields of medicine and surgery.

Adult↗

Plasticity of intercellular junctions of rat liver lymph capillaries in relation to functional conditions.

The junctions between endothelial cells in lymph capillaries may have different degrees of complexity and have been classified as three types: "end to end" (EE), "overlapping" (OVL), and "interdigitating" (ID). Under normal conditions, the more complex junction types (ID and OVL) are more frequent than the simple type (EE). The authors' hypothesis was that not only the folds and digitations of the endothelial profile but also the prevalence of the more complex junction types under normal conditions impart plasticity and distensibility to the endothelial wall. To verify this hypothesis they performed a transmission electron microscope study of lymph capillaries of rat liver under normal conditions and after treatment with histamine, which induces natural filling of lymph vessels. In lymph capillaries of histamine-treated animals they found a significant prevalence of the simplest (EE) junctions (50 +/- 5% versus 20 +/- 4% in controls, p less than 0.001) over the more complex OVL (28 +/- 4% versus 57 +/- 4% in controls, p less than 0.001) and ID junctions (12 +/- 3% versus 19 +/- 4% in controls, NS). The overall trend in junction types showed a highly significant shift toward the simpler types after histamine treatment (p less than .0001). There was also a significant reduction in the mean length of adjoining cell borders from 1.5 +/- 0.1 m in histamine-treated animals (p less than 0.001). These findings indicate the participation of the junctions in variations in capacity of lymph vessels in rat liver. This mobilization of cell junctions may also favor the drainage of interstitial fluids into the absorbing lymph vessels.

Animals↗

Familial IgM mesangial nephropathy: a morphologic and immunogenetic study of three pedigrees.

Eight patients belonging to 3 unrelated families had biopsy-proven IgM mesangial nephropathy. In the first family, the mother and the 2 daughters were affected; in the second, the mother and the son; in the third, 2 sisters and the brother. Two additional sisters of the third family showed a clinical picture consistent with chronic glomerulonephritis. The clinical picture was that of hematuria and/or proteinuria. No patients had nephrotic syndrome. Genealogic investigation enabled us to discover 2 additional affected members in the kindred of the first family (1 with IgA nephropathy, 1 with clinical glomerulonephritis) and 3 other affected members in the pedigree of the third family (1 with IgA nephropathy, 1 with sclerosing glomerulonephritis, 1 with clinical glomerulonephritis). Immunogenetic studies showed the recurrence of an extended haplotype bearing DR beta 11-DQ beta 3B-DQ alpha 2-C4A3-C4B1-BfS in 9 of 10 affected members. Our data suggest that genetic factors may be involved in the mechanism of the disease and support the hypothesis that IgM nephropathy is a distinct disease entity.

Adolescent↗

Pattern of double glomerulopathies. A clinicopathologic study in nine nondiabetic patients.

Nine new cases of double glomerulopathies (GP) were found among 1,715 renal biopsies. Immunofluorescence and electron microscopy were needed to achieve a correct diagnosis and the prevailing relevance of these techniques in single cases was stressed. IgA nephropathy was the most commonly found GP, being associated with membranous glomerulonephritis (GN) (2 patients), minimal change disease (3 patients), and focal segmental glomerulosclerosis (1 patient). In addition, single cases of membranous GN plus crescentic GN and acute GN plus cryoglobulinemic GN were recorded. Possible factors involved in the pathogenesis and clinical significance of double glomerulopathies are discussed.

Adult↗

Histological framework of lymphatic vasa vasorum of major arteries: an experimental study.

We investigated the histological framework of lymphatic vasa vasorum of major arteries in the rabbit and guinea pig combining the "natural filling method" with light and transmission electron microscopy. An absorbing adventitial lymphatic network consisting of large and sparsely distributed vessels with capillary structure occupied a more external arterial wall position than blood capillaries. The latter were smaller, more numerous, densely distributed, and located closer to the arterial lumen at the media-adventitial border. Periarterial lymphatics (with the structure of absorbing lymph vessels) encircled the wall of the major arteries and formed a rich and irregular plexus. The topography and anatomic structure of these absorbing lymph vessels suggest that lymphatic drainage plays a significant role in large arterial wall homeostasis.

Animals↗