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Biomedical subjects

C Catena

Publications and source records attributed to C Catena.

At least 19 recordsLinked to original sources

Lipoprotein(a) and apolipoprotein(a) isoforms and proteinuria in patients with moderate renal failure.

BACKGROUND: Atherosclerotic diseases are a major cause of death in patients with renal failure. Increased serum concentrations of lipoprotein(a) [Lp(a)] have been established as a genetically controlled risk factor for these diseases and have been demonstrated in patients with moderate renal failure, suggesting that this lipoprotein contributes to the increased cardiovascular risk seen in these patients. Variable alleles at the apolipoprotein(a) [apo(a)] gene locus are the main determinants of the serum Lp(a) level in the general population. The purpose of this study was to investigate apo(a) isoforms in patients with moderate renal failure and mild proteinuria (less than 1.0 g/day). METHODS: In 250 consecutive subjects recruited at a hypertension clinic, we assessed the renal function by 24-hour creatinine clearance, proteinuria, and microalbuminuria, as well as the prevalence of atherosclerotic disease, and we also measured apo(a) isoforms, serum albumin, and Lp(a) concentrations. RESULTS: Moderate impairment of renal function (creatinine clearance, 30 to 89 ml/min per 1.73 m2 of body surface area) was found in 97 patients. Lp(a) levels were significantly greater in patients with moderate renal failure (21.7+/-23.9 mg/dl) as compared with patients with normal renal function (15.6+/-16.4 mg/dl, P<0.001), and an inverse correlation was observed between log Lp(a) and creatinine clearance (r = -0.181, P <0.01). However, no difference was found in the frequency of low molecular weight apo(a) isoforms between patients with normal (25.5%) and impaired (27.8%) renal function. Only patients with the smallest size apo(a) isoforms exhibited significantly elevated levels of Lp(a), whereas the large-size isoforms had similar concentrations in patients with normal and impaired renal function. No significant relationship was found between serum Lp(a) and proteinuria. Clinical and laboratory evidence of one or more events attributed to atherosclerosis was found in 9.8% of patients with normal renal function and 25.8% of patients with moderate renal failure (P<0.001). CONCLUSIONS: These results indicate that renal failure per se or other genes beside the apo(a) gene locus are responsible for the elevation of serum Lp(a) levels in patients with moderate impairment of renal function. The elevation of Lp(a) levels occurs independently of the level of proteinuria and may contribute to the risk for atherosclerotic disease in these patients.

Adult

Increased serum lipoprotein(a) levels in patients with early renal failure.

BACKGROUND: Elevated serum lipoprotein(a) levels have been found in patients with end-stage renal disease and in patients undergoing dialysis, suggesting that this lipoprotein contributes to the increased cardiovascular risk seen in these patients. It is not known whether lipoprotein(a) levels are elevated in the early phases of renal disease. OBJECTIVE: To evaluate levels of lipoprotein(a) and other lipids and the prevalence of atherosclerotic disease in patients with early renal failure. DESIGN: Cross-sectional study. SETTING: Hypertension clinic of a university medical center. PATIENTS: 257 patients with normal renal function and 160 patients with early impairment of renal function (creatinine clearance, 30 to 89 mL/min per 1.73 m2 of body surface area). MEASUREMENTS: Renal function was assessed by 24-hour creatinine clearance, proteinuria, and microalbuminuria. Cardiovascular disease status was also assessed. Serum lipoprotein(a), lipids, apolipoproteins, and apolipoprotein(a) isoforms were measured. RESULTS: Age, blood pressure, and serum lipoprotein(a) levels were greater in patients with early renal failure than in those with normal renal function and were independently associated with the presence of decreased creatinine clearance. Serum lipoprotein(a) and creatinine clearance were inversely correlated. The prevalence of coronary artery, cerebrovascular, and peripheral vascular disease was greater in patients with early renal failure than in those with normal renal function. The frequency distribution of apolipoprotein(a) isoforms was similar in patients with normal and those with impaired renal function. CONCLUSIONS: Serum lipoprotein(a) levels are elevated in patients with early impairment of renal function and are associated with greater prevalence of cardiovascular disease. An inverse correlation between serum lipoprotein(a) level and creatinine clearance and a frequency distribution of apolipoprotein(a) isoforms similar to that of normal patients point to decreased renal catabolism as a probable mechanism of lipoprotein(a) elevation in patients with early renal failure.

Adult

Association of serum lipoprotein(a) levels and apolipoprotein(a) size polymorphism with target-organ damage in arterial hypertension.

OBJECTIVE: To investigate the association between lipoprotein(a) [Lp(a)] and other plasma lipids and apolipoproteins and target-organ damage (TOD) in patients with arterial hypertension. DESIGN: Cross-sectional study of a case series. SETTING: University medical center. PARTICIPANTS: Lipoprotein(a) and apolipoproteins were analyzed in 277 untreated patients with mild to moderate essential hypertension and in 102 healthy controls. Apolipoprotein(a) [apo(a)] phenotypes were additionally analyzed in an independent sample set of 106 hypertensive and 105 control subjects. MAIN OUTCOME MEASURES: Staging of TOD obtained according to World Health Organization guidelines by clinical evaluation, and laboratory tests including measurments of creatinine clearance, proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and ultrasound examination of major arteries; levels of lipids, apolipoproteins, Lp(a), fibrinogen, and apo(a) phenotypes. RESULTS: Blood pressure, duration of hypertension, and levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, Lp(a), and fibrinogen were significantly related to the presence and severity of TOD in univariate analysis. Stepwise multivariate analysis showed Lp(a) levels (P<.001) to be the best discriminator of the presence of TOD, followed by systolic blood pressure (P<.001), duration of hypertension (P=.01), and low-density lipoprotein cholesterol (P=.04). The Lp(a) levels were related to TOD independent of the level of blood pressure. We confirmed this association between Lp(a) concentrations and severity of TOD in a second independent sample set and observed a significantly higher frequency of low-molecular-weight apo(a) isoforms with increasing severity of TOD (P=.02). CONCLUSIONS: Lipoprotein(a) and apo(a) phenotype are sensitive indicators of the severity of TOD in patients with essential hypertension, and their evaluation might permit identification of hypertensive subjects liable to the development of organ damage. The higher frequency of low-molecular-weight apo(a) isoforms in patients with TOD demonstrates a genetically determined risk for the development of TOD in hypertensive patients.

Adult

Dose-response of X-irradiated human and equine lymphocytes.

We have investigated and compared DNA damage and cell killing induced in human and equine lymphocytes after in vitro X-irradiation. Our data show that the cytogenetic and the lethality effects are both greater in equine lymphocytes, but that the difference is wider for lethality. The ratios between doses inducing the same effect are 1.3, 1.7 and 9.4 for the number of binucleated cells with micronuclei, micronucleus frequency in binucleated cells and DNA synthesis inhibition, respectively. The very different radiosensitivity observed for the two mammalian species encourages us to use their lymphocytes in cell radiobiology studies.

Animals

Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus.

Exposure to high glucose concentrations increases the mRNA levels of oxygen radical scavenging enzymes in cultured endothelial cells, suggesting a compensatory response to increased free radical production. To test the hypothesis that this response also occurs in vivo, Cu.Zn-superoxide dismutase (Cu.Zn-SOD) and catalase mRNA levels, were measured in the kidneys of Sprague-Dawley rats 17 days after intravenous injection of streptozotocin (60 mg/kg body weight) and compared with those of control rats. Diabetic rats were either left untreated or given differing insulin regimens (2. 3-8, 6-10 IU/day) in two different experiments that were designed to achieve varying degrees of metabolic control. Cu,Zn-SOD and catalase mRNA levels were measured by Northern blot hybridization and standardized by 28S ribosomal RNA determination. Renal Cu,Zn-SOD and catalase mRNA levels were significantly greater in untreated diabetic and in low-dose (2 IU/day) insulin-treated rats than in controls. Treatment with a moderate dose (3-8 IU/day) of insulin normalized catalase but not Cu,Zn-SOD mRNA levels. The highest insulin regimen (6-10 IU/day), in addition to achieving complete metabolic control as evidenced by normal growth and plasma glucose levels, normalized both catalase and Cu,Zn-SOD mRNA levels. Thus, in rats with streptozotocin-induced diabetes Cu,Zn-SOD and catalase renal mRNA levels are greater than in normal rats. This difference is prevented by sufficient insulin dosage to normalize plasma glucose and might be due to an increased production of free radicals.

Animals

Hypertension and abnormalities of carbohydrate metabolism possible role of the sympathetic nervous system.

To investigate the relationships between the sympathetic nervous system (SNS) and parameters of glucose metabolism in arterial hypertension, daily urinary excretion of catecholamines and plasma glucose, insulin, and C-peptide response to an oral glucose load (OGL) have been evaluated in 77 untreated patients with mild-to-moderate essential hypertension and in 31 normotensive controls. Urinary excretion of norepinephrine (UNE) was positively correlated with body mass index and with plasma glucose levels both at fast and after OGL. No correlations were found between urinary excretion of catecholamines and plasma insulin and C-peptide levels both at fast and in response to OGL. Because the frequency distribution of UNE was bimodal, hypertensive subjects were separated into two subgroups using an arbitrary cutoff, and the parameters of glucose metabolism were compared. Subjects with UNE > 205 microg/day had greater levels of fasting glucose and greater glycemic response to OGL than subjects with UNE < 205 microg/day, whereas no significant differences between the groups were found in fasting and stimulated plasma insulin and C-peptide. Thus, activation of SNS is related to glucose tolerance but not hyperinsulinemia and insulin hypersecretion in essential hypertension. Plasma glucose levels, independent of insulin, may contribute to the relationship between SNS activity and blood pressure in essential hypertension.

Carbohydrate Metabolism

Glucose metabolism and insulin receptor binding and mRNA levels in tissues of Dahl hypertensive rats.

Increased insulinemic response to an oral glucose load has been demonstrated in Dahl salt-sensitive hypertensive rats. To determine whether this abnormality is mediated at the level of the insulin receptor, we compared insulin receptor binding and mRNA levels in tissues of Dahl salt-sensitive rats (DS) and in their normotensive controls, Dahl salt-resistant rats (DR). To evaluate possible influences of dietary sodium intake, rats were fed either low (0.07% NaCl) or high salt (7.5% NaCl) chow until the DS became hypertensive, and then were killed by decapitation. Fasting plasma glucose and plasma insulin levels did not differ between DR and DS rats and were not affected by salt intake. In response to an oral glucose load, plasma glucose had a similar increase in DR and DS rats, but the increase in plasma insulin was significantly greater in DS rats. Scatchard analysis of binding was obtained from in situ autoradiographic studies performed in frozen skeletal muscle and kidney sections, and insulin receptor mRNA levels were measured by slot-blot hybridization. Number and affinity of insulin receptors were comparable in skeletal muscle and kidney of DR and DS rats and, in both groups, binding parameters were not affected by dietary sodium chloride. Hepatic and renal insulin receptor mRNA levels were also comparable in DR and DS rats fed either low or high salt chow. Thus, increased plasma insulin response to oral glucose load is associated with normal insulin receptor binding and gene expression in peripheral tissues in rats with Dahl hypertension. A postreceptor defect is likely responsible for the decreased sensitivity to insulin in this model of genetic hypertension.

Animals

Peripheral blood lymphocyte decrease and micronucleus yields during radiotherapy.

PURPOSE: To investigate the relationship between lymphocyte decrease and cytogenetic response in individual patients undergoing radiotherapy. MATERIALS AND METHODS: Peripheral blood lymphocytes obtained from 35 patients with pelvic and from 14 with head and neck tumours before and during radiotherapy were PHA-stimulated in vitro and the cultures prepared for the cytokinesis-block micronucleus test. For some patients only, the micronucleus test was carried out after 2 Gy in vitro X-irradiation, and 3-aminobenzamide (2 mM) was used to calculate the 3AB-index. RESULTS: The initially observed individual variation in the decrease of lymphocytes disappeared with increasing number of radiation exposures, reaching a stable level at about 500/microl lymphocytes in the blood. The slope of the relationship between the reciprocal of the lymphocyte decrease ratio and equivalent dose indicates the radiosensitivity of the lymphocyte pool in individual patients. The micronucleus test performed on lymphocytes obtained from patients during radiotherapy (in vivo) provided a lower cytogenetic response than the in vitro micronucleus yield for the same dose, so it was possible to calculate the cytogenetic recovery factor k. A correlation was found between the 3AB-index calculated before radiotherapy, and the recovery factor k. CONCLUSIONS: The 3AB-index, the micronucleus frequency after 2 Gy in vitro X-irradiation, and the cytogenetic recovery factor are proposed as predictive of individual response to radiotherapy.

Aged

Bone demineralization in cystic fibrosis: evidence of imbalance between bone formation and degradation.

Bone turnover, collagen metabolism, and bone mineral status were investigated in 59 patients with cystic fibrosis and in 72 sex and age-matched control subjects. In all patients and control subjects serum concentrations of osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary values of cross-linked N-telopeptides of type I collagen (NTX), as well as total body bone mineral content (TBBM) were measured. Higher ICTP (microgram/L) and NTX (bone collagen equivalent/urinary creatinine (nmol/mmol) values were found in pre-pubertal, pubertal, and young adult patients than in control subjects (ICTP: 15.4 +/- 2.1 and 13.2 +/- 1.8, p < 0.001; 23.3 +/- 5.3 and 20.1 +/- 4.1, p < 0.02; 4.8 +/- 1.1 and 4.0 +/- 1.0, p < 0.05. respectively; NTX: 1047.5 +/- 528.6 and 227.8 +/- 71.8, p < 0.01; 997.8 +/- 391.7 and 376.3 +/- 91.0, p < 0.01; 993.2 +/- 398.0 and 73.9 +/- 28.5, p < 0.01, respectively). Lower OC and PICP levels (microgram/L) were showed in pubertal patients in comparison with control subjects (OC: 20.2 +/- 12.3 and 39.0 +/- 15.1, p < 0.01; PICP: 305.8 +/- 130.4 and 436.2 +/- 110.1, p < 0.02, respectively). Lower OC and higher PIIINP levels (microgram/L) were found in young adult patients than in control subjects (OC: 4.4 +/- 3.0 and 7.0 +/- 3.1, p < 0.05; PIIINP: 4.8 +/- 1.1 and 3.1 +/- 1.0, p < 0.001, respectively). TBBM (z score) was reduced in prepubertal, pubertal, and young adult patients (-0.8 +/- 0.4, -1.0 +/- 0.4, -1.1 +/- 0.5, respectively). Patients with cystic fibrosis have bone demineralization and imbalance between bone formation and degradation.

Adolescent

Micronuclei in cytokinesis-blocked lymphocytes may predict patient response to radiotherapy.

We have applied the cytokinesis-block micronucleus assay to peripheral blood lymphocytes of patients undergoing radiotherapy in pelvic and pulmonary sites, in order to evaluate the individual cytogenetic response. Our cytogenetic data correlated with the equivalent whole-body dose are homogeneous and compare well with the data presented by other authors. We have used an exponential mathematical formula to calculate the attenuation of the cytogenetic effect with time. The k coefficient (cytogenetic recovery factor) in the formula expresses the degree of attenuation. In lymphocytes from patients after radiotherapy, the trend of the micronucleus frequency observed after 2 Gy of in vitro X-irradiation demonstrates that the cytogenetic effect obtained in vitro is added to that obtained in vivo. The k coefficient is inversely proportional to the micronucleus frequency observed after 2 Gy in vitro. The micronucleus assay and the cytogenetic recovery factor are proposed as suitable diagnostic tools for application in the field of radiotherapy.

Dose-Response Relationship, Radiation

Benign familial macrocytosis.

We have identified a 52-year-old woman and her 27-year-old daughter with macrocytosis, normal haemoglobin and mean corpuscular haemoglobin concentration. Macrocytosis could be demonstrated from the age of 40 and 25 respectively. All blood tests were normal including vitamin B12 and folic acid. Bone marrow investigation showed rare macroblasts without other abnormalities. Endoscopy of the upper gastrointestinal tract and ultrasonography of the abdomen were normal. Thus, persistent macrocytosis was present without evidence of diseases that might account for it. In these subjects, macrocytosis is likely to be related to the presence of a genetic defect.

Adult

Abnormalities of insulin receptors in spontaneously hypertensive rats.

Insulin resistance is present in some strains of rats with genetic hypertension. To determine whether this abnormality is present at the level of the insulin receptor, we compared insulin sensitivity, insulin receptor binding, and mRNA levels in tissues of 10-week-old spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. Because we have previously demonstrated an inverse relationship between dietary sodium intake and renal insulin receptor density and mRNA levels in normal Sprague-Dawley rats, the two rat strains in the current experiment were fed either low salt (0.07% NaCl) or high salt (7.5% NaCl) chow until the SHR became hypertensive. Fasting plasma glucose and plasma insulin levels did not differ between SHR and WKY and were not affected by salt intake. When the rats were maintained on the low salt diet, the rate of glucose infusion required to main euglycemia during a hyperinsulinemic clamp was significantly lower in SHR than WKY. High salt diet decreased the rate of glucose utilization during the hyperinsulinemic clamp in WKY but not SHR. During the low salt diet, insulin infusion decreased sodium excretion in both WKY and SHR. When the rats were maintained on the high salt diet, the antinatriuretic response to insulin was blunted in WKY but not SHR. Both the density and mRNA levels of insulin receptor were comparable in the kidney of WKY and SHR, but only WKY had the previously demonstrated decrease in receptor number and mRNA levels when fed the high salt chow. Hepatic insulin receptor mRNA levels were significantly lower in SHR than WKY fed the low salt diet. High salt diet decreased significantly insulin receptor mRNA levels in the liver of WKY but not of SHR. Thus, SHR appear to have lost the feedback mechanism that normally limits insulin-induced sodium retention when extracellular volume is expanded. A decreased expression of insulin receptor in the liver of SHR provides a possible explanation for the insulin resistance and decreased insulin clearance present in this strain.

Animals

Micronuclei and 3AB index in X-irradiated human lymphocytes in G0 and G1 phases.

We applied the cytokines-block micronucleus assay to observe the radiobiological response of human lymphocytes after X-ray treatment in the G0 and G1 phases. In addition, we used 3-aminobenzamide (3AB) to measure the 3AB index in the two phases. The experimental results show that at 2 Gy the MN yield and the 3AB index are dependent on the cell phase and show considerable inter-individual variability. The radiation-induced MN frequency obtained for 33 subjects is 0.470 +/- 0.063 for the G0 phase and 0.689 +/- 0.139 for the G1 phase; the 3AB index values are 0.326 +/- 0.144 and 0.067 +/- 0.058 for G0 and G1 phases, respectively. At the individual level, the 3AB index for the G1 phase correlates inversely with the cytogenetic effects observed in that phase. We discuss the possibility of applying the MN test combined with the 3AB index to lymphocytes at different phases to study the individual response to radiation (individual radiosensitivity).

Adult

Micronuclei and 3AB index in human and canine lymphocytes after in vitro X-irradiation.

The comparative study of different species could be of interest, both applied and pure, to the field of cytogenetic damage induced by genotoxic agents. For as accurate as possible an evaluation of the inter-species response differences to radiation, we have carried out a comparison between the behaviors of human and canine lymphocytes, using the micronucleus assay (MN test) according to the cytokinesis-block method. Up to 4 Gy doses, canine lymphocytes have been found to be about three times more radiosensitive than human lymphocytes, due to blastization inhibition (binucleation failure), and, for 1 and 2 Gy doses, about 1.3 times more radiosensitive, due to MN yields. We discuss whether the differing chromosome number (dog 78 and man 46) could have any effect on the cytogenetic response. 3-Aminobenzamide, which inhibits poly(ADP-ribose)polymerase activity, is able to increase the genotoxic effect of X-rays in human lymphocytes, with a different response at the individual level. The same phenomenon with the same characteristics is also found in canine lymphocytes at the inter-individual level. Our in vitro radiobiological study confirms that the cytogenetic response obtained in blood from selected breeds of mammalian species can be utilized for applications in environmental studies.

Animals

Lack of effect of inhibitors of DNA synthesis/repair on the ionizing radiation-induced chromosomal damage in G2 stage of ataxia telangiectasia cells.

The relationship between the repair processes occuring at the G2 phase of the cell cycle and cytogenetic damage in ataxia telangiectasia (AT) cells was studied. Lymphoblastoid cells derived from normal, heterozygote AT (HzAT) and three AT patients were exposed to X-rays or fission neutrons and post-treated with inhibitors of DNA synthesis/repair, such as inhibitors of DNA polymerases alpha, delta and epsilon (cytosine arabinoside, ara-C; aphidicolin, APC; buthylphenylen-guanine, BuPdG) or ribonucleotide reductase (hydroxyurea, HU). A strong increase of radiation-induced chromosomal aberrations was observed in normal and HzAT cells post-treated with ara-C, APC and HU, but not in the presence of BuPdG. No enhancing effect was observed in cells derived from AT patients, except for HU post-irradiation treatment. These results suggest that the enzymes that can be inhibited by these agents are not directly involved in the repair of radiation damage induced in G2 cells from AT patients, indicating that probably the AT cells that we used lack the capability to transform the primary DNA lesions into reparable products, or that AT cells might contain a mutated form of DNA polymerase resistant to the inhibitors.

Ataxia Telangiectasia