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Biomedical subjects

R Burri

Publications and source records attributed to R Burri.

17 recordsLinked to original sources

[Vascular "remodeling"].

Vascular remodeling means a specific organization of the vascular wall around a diminished lumen as to the before existing conditions, with consequent vascular geometry modification. This organization comes from the response of all vascular components (endothelium, muscular cells, connective component, etc.) to physical and chemical stimuli. Particular behaviour of the vascular wall has lately been pointed out, both in long known pathologies (arteriosclerosis, arterial hypertension, diabetes mellitus, arteriosclerotic aneurysms) and in situations involving both physiopathology (ischaemia-reperfusion, angiogenesis) as therapy (angioplasty).

Aneurysm↗

[The concept of quality of life in cardiac failure].

Chronic congestive heart failure is a common yet devastating syndrome and is a leading cause of morbidity and mortality in the industrialised countries. The incidence and prevalence of chronic congestive heart failure is increasing, placing a growing burden on the health care system. Despite many advances in treatment for heart disease, chronic heart failure is a terminal condition with a death rate as high as that for many malignant tumours. Patients suffering from chronic congestive heart failure report a poor quality of life because of physical symptoms, functional disability, emotional and economic burdens, frequent hospitalisations, and poor prognosis. In the context of heart failure, mortality risk (prognosis quoad vitam) can be measured using a variety of physiological variables; left ventricular (LV) dysfunction plays a primary role in the pathogenesis of congestive heart failure and correlates with prognosis, but a strong quantitative relation between exercise performance and indexes of LV function has not been demonstrated. This finding underscores the importance of psychosocial interventions in improving the quality of life and care outcomes for patients with heart failure. For this reason, questionnaires of quality of life, assessed by direct patient self-reports, have recently been imposed in cardiology, they have been used specially for evaluating most treatment of cardiac failure. The refinement of a definition of quality of life improved methods to study quality of life will contribute to a better understanding of this complex concept in heart failure patients.

Activities of Daily Living↗

[Arterial hypertension in an ambulatory population of elderly subjects. Epidemiologic and clinical study in Isonzo].

The authors examine the clinical connotations of arterial hypertension in a geographical population of 1002 patients attending the Cardiological Outpatient Clinic of Unit no.2 in the Isonzo area (Monfalcone) using the most appropriate statistical methods, such as SPSS (Statistical Package for the Social Sciences) implemented on PC IBM AT 286, for multiple linear regression using a stepwise method. 1) Arterial hypertension was the result of a phenomenon which was striking owing to its mean value of 184.7 +/- 20.915 mmHg with equal mode and median of 180 mmHg. In the subgroup of 720 elderly patients this mean value differed slightly, 186.9 +/- 20.648 mmHg, with the same mode and median, whereas in the group of 282 adults the mean was 170.0 +/- 20.540 mmHg with a mode and median of 160 and 175 mmHg respectively. In the overall population 154 cases (15.4%) were affected by slight arterial hypertension with a mean of 158.9 mmHg, and 848 cases (84.8%) presented moderate-severe arterial hypertension with mean values of 189.4 mmHg. In elderly patients the mean rose to 190.4 mmHg whereas it was 186.3 mmHg in adults. 2) Mean age was 65.3 +/- 11.093 years: 70.7 +/- 7.396 years in older patients and 51.7 +/- 6.106 years in adults. Surface ECG showed signs of left ventricular hypertrophy in 292 elderly patients (40.5%) and 85 adults (30.0%), signs of ischemic cardiopathy due to T wave alteration in 246 elderly patients (34.1%) and 101 adults (35.7%), and due to ST tract in 340 (47.2%) and 102 (36.2%) respectively, with equal involvement of the free surface of the left ventricle. The radiographic enlargement of the cardiac shadow in elderly patients was observed in slight form in 153 cases (21.3%) and in moderate and marked form in 222 cases (30.8%), and in adults in 36 (12.8%) and 43 (15.2%) cases respectively. 3) Body weight was normal on average and equivalent to 77.3 +/- 13.578 kg, but of this series 713 cases were overweight and 237 were obese; 504 of elderly patients (70%) were pathological with 346 (48.1%) overweight and 158 (21.9%) obese, and of 209 pathological adults (74.1%), 130 (46.1%) and 79 (28.0%) were respectively overweight and obese. BMI oscillated from 1.70 to 5.60 with a mean of 2.80 +/- 0.409: from 1.70 to 4.21 in elderly patients with a mean of 2.70 +/- 0.379 and in adults from 2.00 to 5.60 with a mean of 2.90 +/- 0.460. 4) Mean cholesterolemia was 237 +/- 48.029 mg% and levels were normal in 203 cases and high in 799 subjects. Elderly patients showed the same mean level with a total of 580 pathological cases (80.5%) divided into 305 (42.3%) cases of slight hypercholesterolemia with a mean of 227.2 mg% and 275 (38.2%) severe cases with levels of 283.7 mg%. Adults presented a mean serum level of 236 +/- 47.588 mg%: 63 (22.3%) cases of normocholesterolemia, 117 (41.5%) cases of slight cholesterolemia with mean serum level of 224.8 mg%, and 102 (36.2%) severe cases with a mean level of 286.2 mg%, resulting in a total of 219 pathological cases (77.7%).

Adult↗

Regional metabolic assessment of human brain during development by proton magnetic resonance spectroscopy in vivo and by high-performance liquid chromatography/gas chromatography in autopsy tissue.

To study the course of regional metabolite concentrations during early brain development, we measured in vivo metabolites [N-acetyl-aspartate (NAA), choline-containing compounds, and myoinositol (M-Ino)] in the precentral area of the cerebrum by short echo-time single volume proton magnetic resonance spectroscopy and compared in vivo established spectroscopic data with classic chromatographic data (HPLC) on age-corresponding autopsy tissue in different regions of the brain. In autopsy tissue, regional (frontal lobe, precentral area, basal ganglia, thalamus) and age-dependent differences of the concentration of creatine, NAA, and M-Ino were determined. In vivo measurement of NAA by proton magnetic resonance spectroscopy shows a significant increase of NAA by increasing postconceptional age. M-Ino shows a weak correlation and a nonsignificant decrease with increasing postconceptional age. Choline shows no age-dependent changes. Creatine concentrations measured by HPLC in different regions of the developing brain at autopsy showed an age-dependent increase that was identical for the left and right side and similar for the precentral area and frontal lobe and more pronounced for the basal ganglia and thalamus. Comparison of the results obtained by the two methods shows agreement for the age-dependent changes and the absolute concentration of M-Ino. NAA determined in autopsy tissue by HPLC is significantly lower than that measured in vivo by proton magnetic resonance spectroscopy. A comparison of the concentrations measured by HPLC in frontal lobe, basal ganglia, and thalamus with the results obtained from the precentral area showed significant regional differences in all measured metabolites. These results define important age-dependent changes detected with both methods and further indicate limitations of both methods that have to be considered when presenting absolute concentration values.

Age Factors↗

Retarded development of neurons and oligodendroglia in rat forebrain produced by hyperphenylalaninemia results in permanent deficits in myelin despite long recovery periods.

The severe hypomyelination seen in the CNS of untreated phenylketonuria (PKU) patients has been suggested to be the result of a defect in the process of myelination itself. Using chronic hyperphenylalaninemia (HPA) in rats as a model of PKU we have previously shown, by immunohistochemistry, that axonal maturation as well as myelination was severely retarded. In the present study we have used image analysis techniques to quantitate changes in myelin basic protein (MBP) and 200-kDa neurofilament protein (NF-H) immunostaining in the corpus callosum and cerebral cortical grey matter of HPA rats. No difference in the density of MBP+ myelin was observed in the corpus callosum after 24 days HPA treatment although the width of the tract was much reduced. In contrast there was a deficit in NF-H immunostaining. Large deficits in both myelin and axonal maturity were seen in the cortical grey matter. Following a 6-week recovery period, despite recovery in the corpus callosum, large deficits in both MBP and NF-H were still seen in all cortical layers. Deficits in NF-H immunostaining were two to three times greater than those for MBP. On increasing the recovery period to 18 weeks significant deficits in myelin remained in layers I-III of the cortical grey matter whereas NF-H immunostaining had returned to normal levels in all layers. Our data suggest a primary effect of HPA on neuronal development, in particular axonal maturation, with a secondary hypomyelination and show that permanent deficits in myelinated axons in outer cortical layers can result when myelination is severely inhibited during a critical developmental period.

Animals↗

Disturbed myelinogenesis and recovery in hyperphenylalaninemia in rats: an immunohistochemical study.

Chronic hyperphenylalaninemia (HPA) in rats has been used as an experimental model of the human inborn error of metabolism phenylketonuria (PKU). Impaired brain development in PKU and HPA is reflected in reduced myelin formation. We have used immunohistochemistry, with antibodies to cell-specific antigenic markers, to investigate the cellular basis of the hypomyelination in the corpus callosum and cerebral cortex of rats made hyperphenylalaninemic from Postnatal Days 3-17. The rats were then allowed to recover until Day 59. No effects were seen on the number and differentiation pattern of ganglioside GD3-expressing glial progenitors. Myelin basic protein and 2'3'-cyclic nucleotide 3'-phosphohydrolase (CNP) immunostaining demonstrated a reduction in myelin formation in the corpus callosum and subcortical white matter at 12 and 17 days postnatal. However, numbers of CNP+ oligodendrocytes appeared normal throughout development. No reactive astrogliosis was seen at any stage. The intensity of axonal neurofilament immunostaining was reduced in the corpus callosum at 17 days. In layers II and III of the cortical gray matter there was an increase in the cell packing density and a concomitant decrease in cell body size. Myelination in the corpus callosum was rapid during the recovery period with no difference noted at Day 59. Axonal neurofilament staining also returned to normal in the corpus callosum. However, recovery became increasingly incomplete away from the corpus callosum into the cortical gray matter. Our data suggest a primary effect of HPA on axonal maturation with hypomyelination consequential upon this.

Animals↗

N-acetyl-L-aspartate is a major source of acetyl groups for lipid synthesis during rat brain development.

The function of N-acetyl-L-aspartate (NAA), a predominant substance in the CNS, has not yet been determined. To investigate the possible function of NAA as a lipid precursor [14C]-N-acetyl-L-aspartate (NAA) or [14C]-acetate (AcA) was injected intracerebrally into 8, 15- and 22-day-old rats. These time points were selected because NAA concentration and the activity of the NAA synthetizing enzyme L-aspartate-N-acetyltransferase (ANAT) were low in 8-day-old rats, intermediate in 15-day-old rats and high in 22-day-old rats. During an incubation period of 4 h the radioactive acetyl group of NAA is incorporated into the lipid fraction in amounts of 42.9 to 65.7% of recovered total radioactivity, increasing with the age of the rats. In contrast, radioactivity incorporated from AcA is constant for all three ages. With NAA as precursor only 7.2-9.4% of the recovered total radioactivity is incorporated into the protein fraction. With AcA as precursor 27.0-18.1% of recovered radioactivity is incorporated into the protein fraction, the amounts decreasing with age. Taking into account that in vivo NAA concentration in the brain is much higher than the AcA concentration, NAA is clearly the more efficient precursor for lipid synthesis than AcA. Further, we compared NAA and AcA as lipid precursors by analyzing the radioactivity in single lipid fractions, expressed as normalized specific incorporation or normalized incorporation. The measured differences between NAA and AcA in normalized specific and normalized incorporation of acetyl groups imply that NAA is not simply degraded to AcA before incorporated into lipids. We conclude that NAA is a major source of acetyl groups for lipid synthesis during rat brain development.

Acetyltransferases↗

Magnetic resonance in preterm and term newborns: 1H-spectroscopy in developing human brain.

Localized proton magnetic resonance spectra were recorded from human cerebellum in vivo with a 1.5-T magnet. The spectra from healthy adults and preterm and term babies showed resonances from N-acetylaspartate, creatine and phosphocreatine, choline-containing compounds such as phosphocholine and glycerophosphocholine, taurine, and inositol. The age-dependent changes of in vivo molar concentrations of N-acetylaspartate, choline, taurine, and inositol were estimated in preterm babies, babies at term, and adults. The range of postconceptional age in the studied babies was 31 to 45 wk. Taking the biochemically measured creatine concentrations in age-corresponding autopsy material as an internal standard, the in vivo concentrations of the other metabolites were calculated from the proton spectra. N-acetylaspartate showed an increase from 1.9 mM in preterm babies to 3.1 mM in term babies and to 6.5 mM in adult brain. Taurine was noted to increase from 1.1 mM in preterm infants to 2.3 mM in term infants and did not decrease significantly in adult brain. Choline and inositol concentrations did not change significantly throughout the studied age groups. These new data on in vivo, localized 1H-spectroscopy show that it is a sensitive method for studying early metabolic brain development in humans.

Adult↗

Brain development: 1H magnetic resonance spectroscopy of rat brain extracts compared with chromatographic methods.

We compared in vitro 1H magnetic resonance spectroscopy (MRS) measurements of rat brain extracts (rats: 2-56 days old) with chromatographic measurements and in a further step also with results of in vitro MRS. The following substances can be reliably measured in brain extracts by in vitro MRS: N-acetylaspartate (NAA), total creatine (Cr), phosphorylethanoloamine (PE), taurine (Tau), glutamate (Glu), glutamine (Gln), gamma-aminobutyrate (GABA) and alanine (Ala). Two different methods of MRS data evaluation compared with chromatographic data on Cr and NAA are shown. During development of the rat from day 2-56 brain concentrations of PE, Tau and Ala decrease, those of NAA, Cr, Glu and Gln increase, while GABA does not change. The developmental patterns of these substances are the same, whether measured by in vitro MRS or by chromatographic methods. Quantification of NAA, Cr, Tau, GABA and PE leads to the same results with both methods, while Glu, Gln and Ala concentrations determined by in vitro MRS are apparently lower than those measured chemically. The NAA/Cr ratios of 7 to 35-day-old rats were determined by in vivo 1H MRS. These results correlate with chromatographic and in vitro data. Using appropriate methods in the in vivo and in vitro MR-technique, the obtained data compare well with the chromatographic results.

Aging↗

Brain damage and recovery in hyperphenylalaninemic rats.

Rats were made hyperphenylalaninemic by injecting a mixture of alpha-methylphenylalanine and phenylalanine. Brain development was measured by biochemical, histological and 31-P nuclear magnetic resonance (NMR) methods. In 17-day-old hyperphenylalaninemic rats, brain myelinogenesis was disturbed. Compared to controls, test animals had lower body weights, brain weights, cerebrosides, sulfatides, myelin basic protein (MBP) and reduced cerebroside sulfotransferase (CST) and 2'3'-cyclic nucleotide-3'-phosphohydrolase (CNP) activities. No changes were found in total proteins, total lipids, total phospholipids, phosphatidylethanolamine and phosphorylethanolamine. In the brain of 17-day-old hyperphenylalaninemic rats no changes in phosphomonoesters, phosphodiester and phosphocreatine were found using in vivo 31-P NMR spectroscopy. Because body weights of hyperphenylalaninemic rats were significantly lower than those of controls, we compared them with undernourished rats. Undernourished rats had lower body weights, brain weights and CNP activity. No other changes were found. Therefore, we conclude that hyperphenylalaninemia per se and not undernutrition affected myelinogenesis in test animals. After treatment was discontinued, test rats recovered completely within 6 weeks with regard to biochemical and histological measurements; at 59 days they had normal body weights, cerebrosides, sulfatides, MBP, total proteins, total lipids, total phospholipids, phosphatidylethanolamine, phosphorylethanolamine and normal CST and CNP activities. Brain weights were significantly reduced.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Correlation between 31P NMR phosphomonoester and biochemically determined phosphorylethanolamine and phosphatidylethanolamine during development of the rat brain.

Phosphomonoesters were measured in the developing rat brain by in vivo and in vitro 31P nuclear magnetic resonance (NMR) spectroscopy and by classical biochemical methods. In vitro NMR showed that the main component of the phosphomonoester peak is phosphorylethanolamine. Phosphomonoesters measured by in vivo NMR decreased during development at the same rate as the biochemically estimated phosphorylethanolamine. Phosphorylethanolamine, a precursor of the membrane lipid phosphatidylethanolamine, decreased during development parallel to an increase of the lipid phosphatidylethanolamine, which was measured biochemically. These studies show that 31P NMR can be used to monitor brain development in vivo.

Aging↗

The effect of vascularization on avian flexor tendon repair. A biochemical study.

Although it has been demonstrated in experimental animals that vascular perfusion functions less effectively than diffusion as a nutrient pathway to the uninjured flexor tendon, it is recognized that the nutritional requirements of an injured flexor tendon may be different. The present study examines several biochemical parameters of avian flexor tendon repair, during a six-week period, in the presence of an intact vinculum longum and with the vinculum longum ligated. Formation of collagen/noncollagen protein, glycosaminoglycan synthesis, and tissue levels of both DNA and hexosamine were quantified. The absence of the vincular blood supply did not affect the levels of total DNA and hexosamine, did not alter the pattern of either protein or glycosaminoglycan formation in the early healing phase, and did not impair the overall synthesis of collagen and noncollagen protein throughout the six-week study period. However, the pattern of collagen and noncollagen protein synthesis differed in lacerated tendons during the period of repair; noncollagen protein synthesis peaked at ten days, while collagen synthesis increased uniformly throughout the 42-day period of study. There was a notable decrease in total matrix hydroxyproline (collagen) during repair, which continued throughout the entire first three weeks after laceration. Thus, the actual percentage of collagen synthesis decreased during the first three weeks of repair and began to return to its normal uninjured level by the sixth week.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of p-chlorophenylalanine on hypothalamic indoleamine levels and the associated changes which occur in catecholamine dynamics and LH surges in estrogen-treated ovariectomized rats.

Recent studies have demonstrated that the serotonergic and noradrenergic systems are functionally and anatomically linked and both systems have been implicated as contributors to the regulation of the phasic release of LH. Consequently, perturbations within the serotonergic system could secondarily affect noradrenergic system activity and result in a loss of phasic LHRH secretion. In the present studies we examined the effects of p-chlorophenylalanine (PCPA) on LH surges and the associated changes which occur in hypothalamic serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations. We also evaluated the effects of this drug on norepinephrine (NE) and dopamine (DA) initial concentrations, rate constants and turnover rates in the medial preoptic area (MPN), suprachiasmatic nuclei (SCN), paraventricular nuclei (PVN) and median eminence (ME). Seven days after ovariectomy, rats received estradiol (E2) capsules (day 0) and on day 1 some animals also received PCPA (250 mg/kg b. wt., i.p.) while the remainder served as controls. LH surges occurred in control animals but not in PCPA-treated rats on days 2, 3 and 4. PCPA produced a significant decline in 5-HT and 5-HIAA concentrations in all microdissected hypothalamic regions at 09.00 and 15.00 h on day 2. In control rats, there were no significant changes in initial concentrations of NE in the MPN, PVN and ME between 09.00 and 15.00 h with the exception of the SCN where a slight decline had occurred by 15.00 h. NE rate constants and turnover rates increased during the afternoon in controls in the MPN, SCN and ME and declined in the PVN concomitant with LH surges. PCPA had variable effects in suppressing NE initial concentrations depending upon the hypothalamic area studied and the time of day. More importantly, the drug abolished the diurnal rhythm in rate constants observed in controls and consequently, neither the MPN, SCN nor ME showed any increase in NE turnover rates in the afternoon of day 2. In contrast, a significant decline in rate constants and turnover rates occurred in the PVN of both control and PCPA-treated rats during the afternoon of day 2. DA initial concentrations declined in controls between 09.00 and 15.00 h in the MPN and ME but not in the SCN or PVN.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

T lymphocytes affect the development of sympathetic innervation of mouse spleen.

We investigated whether the development of sympathetic innervation of the spleen is affected by lymphoid cells. Splenic noradrenaline (NA) levels of athymic nude mice (nu/nu) and normal thymus-bearing littermates (nu/+) were determined at different times during ontogeny. While no differences were detected at birth, higher splenic NA levels were found in 7-, 11-, and 21-day-old athymic mice. Thymus transplantation or thymocyte injection to newborn nude mice resulted in splenic NA levels comparable to those of normal nu/+ mice. Histochemical studies fully confirmed such differences. Taken together with previous studies, these results suggest that T lymphocytes or their products exert an inhibitory influence on sympathetic nerve fibers, thus leading to decreased NA content in the spleen. The data also illustrate the capacity of a nonneuronal cell in a peripheral organ to affect the process of autonomic innervation of this organ.

Aging↗

Determination of neurotransmitter systems in human cerebrospinal fluid and rat nervous tissue by high-performance liquid chromatography with on-line data evaluation.

We describe an improved high-performance liquid chromatographic method for the determination of tyrosine, 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, tryptophan and homovanillic acid in cerebrospinal fluid and nerve tissue, using the new microbore cartridges with 5 micron average particle size. The first four substances are quantified fluorometrically and the last two electrochemically. Both detectors are connected to the same integrator through a relay which can be switched as required. Data are collected in an on-line personal computer and evaluated statistically. An improvement in the method for extraction and separation of catecholamines is also reported.

Animals↗

The immune response evokes changes in brain noradrenergic neurons.

A decreased noradrenaline turnover in the hypothalami of rats was observed at the peak of the immune response to sheep red blood cells. The decrease in noradrenergic neuronal activity was mimicked by injection of soluble r mediators released by immunological cells activated in vitro. Noradrenaline also tended to decrease in the brainstem but not in the residual brain. It is suggested that products released from activated immunological cells during the immune response may induce the previously described autonomic and endocrine mechanisms that contribute to immunoregulation.

Animals↗

Reduced myelinogenesis and recovery in hyperphenylalaninemic rats. Correlation between brain phenylalanine levels, characteristic brain enzymes for myelination, and brain development.

In a previous paper (Burri et al., 1990), we have shown that experimental hyperphenylalaninemia (hyper-Phe) in 3-17 d-old rats leads to reduced myelinogenesis. Such treated rats recover during a 6 w low phenylalanine (Phe) period between days 17 and 59. In order to get more detailed information about the disturbed myelinogenesis and recovery, we measured in hyper-Phe rats the developmental pattern of two brain enzymes typical for myelination, cerebroside sulfotransferase (CST), and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), and other developmental parameters. Further, we correlated brain Phe levels with the brain damage in hyper-Phe rats, and we measured brain acetylcholinesterase (AChE) as a neuronal marker. Experimental hyper-Phe rats, injected between postnatal days 3 and 17 with alpha-methylphenylalanine and phenylalanine, showed a delayed age-dependent increase of CST activity, compared to that of controls. In hyper-Phe rats, CST peak activity was reached 2-4 d later, and was lower than in controls. The age-dependent decrease of the CST activity, however, started in test and control rats at the same time, at day 21. Between days 24 and 59, hyper-Phe rats had normal CST activity. CNP activity in hyper-Phe rats was lower than in controls from day 10 to 35, and recovered to normal values between days 35 and 59. Our results indicate that recovery from reduced myelinogenesis is possible after the period of fast myelination without compensatory increased CST activity. Further, the brain damage in test rats with Phe levels higher than average is more severe than in test rats with Phe levels lower than average; and there is no effect of hyperphenylalaninemia on brain neurons containing AChE.

Acetylcholinesterase↗