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Biomedical subjects

F Neri

Publications and source records attributed to F Neri.

At least 19 recordsLinked to original sources

Normal neuropsychological development in children with congenital complete heart block who may or may not be exposed to high-dose dexamethasone in utero.

BACKGROUND: Antenatal and postnatal treatment with dexamethasone (DEX) may negatively affect the neuropsychological development in children. Maternal anti-Ro/Sjögren's syndrome A (SSA) antibodies may also be associated with learning disabilities in offspring. OBJECTIVE: To assess neuropsychological development in babies exposed to very high dosages of DEX in utero, whose mothers were anti-Ro/SSA positive. METHODS: 13 children with congenital complete heart block (CHB) (11 exposed and 2 not exposed to DEX) and 3 healthy siblings, all of anti-Ro/SSA-positive women, were evaluated. 11 preschool-aged children (5 boys) were assessed using Griffiths Mental Development Scales. 5 school-aged children (2 boys) were examined using Wechsler Intelligence Scale for Children-Revised to check IQ and reading tests to explore the existence of learning disabilities or dyslexia. None of the children had had major neonatal complications, although those with CHB had to be paced at different intervals from birth. RESULTS: The children had been exposed in utero to a mean total dose of 186.6 mg DEX. IQ levels were always normal (mean IQ 105.1, standard deviation (SD) 9.5). Only one child had a learning disability, of borderline clinical significance, but this child had never been exposed to DEX. CONCLUSION: No negative effects were found on the neuropsychological development in this cohort of children, even if they had been exposed to maternal anti-Ro/SSA antibodies and to very high dosages of DEX (much higher than those used to improve fetal lung maturity). These findings might be of interest in view of the large number of infants exposed in the past to repeated antenatal courses of steroids.

Antibodies, Antinuclear↗

Successful treatment of CCL4-induced acute liver failure with portal vein arterialization in the rat.

INTRODUCTION: Optimization of the conditions for regeneration of the native diseased liver is a major goal in patients with acute liver failure. This study sought to determine whether portal vein arterialization (PVA), which increases the oxygen supply to the liver, was protective in a rat model of liver failure. METHODS: At 24 hours after CCl(4) intoxication, Sprague-Dawley rats (six per group) were assigned to receive PVA or as controls. We determined blood tests, histology, and 10-day survivals. Hepatocyte regeneration was assessed by the mitotic index and bromodeoxyuridine (BrdU) incorporation. RESULTS: Serum transaminases were significantly lower in PVA-treated rats than in control animals: liver necrosis resolved rapidly after PVA. The BrdU staining and mitotic index were severalfold higher among PVA-treated than in untreated rats. Survival was 100% among rats with PVA and 40% in untreated animals (P < .01). CONCLUSIONS: PVA led to resolution of CCl(4)-induced massive liver necrosis in the rat. This effect was probably mediated by activation of rapid and extensive hepatocyte regeneration. PVA might provide a novel, alternative approach to treat acute liver failure.

Alanine Transaminase↗

Portal vein oxygen supply through a liver extracorporeal device to treat acute liver failure in Swine induced by subtotal hepatectomy: preliminary data.

AIM: To determine whether the increase of oxygen supply in the portal system by a liver extracorporeal (L.E.O.NARDO) device is effective in treating swine with subtotal hepatectomy leading to acute liver failure (ALF). METHODS: Eight swine with ALF induced by 85% to 90% liver resection and 5 minutes of ischemia-reperfusion injury were randomly divided into two groups: four animals received L.E.O.NARDO treatment and four swine were not treated (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system. An extracorporeal device was interposed between the outflow and the inflow in order to monitor the hemodynamic parameters. Each treatment lasted 6 hours. Serum and liver samples were collected in both groups. The survival was assessed at 1 week. RESULTS: L.E.O.NARDO treatment yielded beneficial effects for subtotal hepatectomy-induced ALF in swine with decreased serum transaminases as compared with the untreated group. International normalized ratio recovered rapidly in the L.E.O.NARDO group, remaining significantly lower than in untreated animals. The 7-day survival of L.E.O.NARDO group swine was significantly higher than that of untreated animals, with a significant difference. Three swine in the L.E.O.NARDO group survived 1 week while none of the swine in the control group were alive at that time. CONCLUSIONS: Oxygen supply in the portal vein through the L.E.O.NARDO device is easily applicable, efficacious, and safe and may represent a novel approach for ALF in swine induced by subtotal liver resection.

Animals↗

Portal vein arterialization for the treatment of post resection acute liver failure in the rat.

INTRODUCTION: Hyperoxygenation of the liver has been suggested to improve its regenerative capacity. Thus, this study sought to determine whether an additional supply of oxygenated blood delivered by portal vein arterialization (PVA) was protective against acute liver failure induced by hepatectomy. METHODS: Sprague-Dawley rats (six per each group) were divided to either undergo PVA or be untreated after extended hepatectomy. Liver injury was evaluated by the serum alanine aminotransferase (ALT) levels. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. Serum ALT levels were significantly reduced in arterialized versus nonarterialized rats. PVA promotes liver regeneration. Finally, PVA significantly improved host survival compared to the controls: 90% versus 30%, respectively. CONCLUSION: These data suggested that an additional supply of arterial oxygenated blood through PVA promoted a rapid regeneration, leading to a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool to optimize hepatocyte regeneration.

Alanine Transaminase↗

Technical aspects of portal vein arterialization for acute liver failure: from rat lab to man.

Survival rates of patients with acute liver failure (ALF) without transplantation are poor. However, many of them die awaiting a transplant because of the donor organ shortage. Supporting these patients until an organ becomes available or until their own liver is able to regenerate itself thus avoiding transplantation is a major goal in their multidisciplinary treatment. Animal experimental studies have shown that portal vein arterialization (PVA) enhances the regenerative capacity of hepatocytes by increasing the oxygen supply to the liver after extended hepatectomy or in toxin-induced ALF models. Furthermore, we have reported the application of PVA in patients with ALF. We herein have described the technical aspects of the PVA procedure both in preclinical models and in man.

Acute Disease↗

Protective effect of portal vein arterialization in acute liver failure induced by hepatectomy in normal and fatty liver rat.

AIM: We sought to determine whether an additional supply of oxygenated blood achieved by partial portal vein arterialization (PPVA) was protective on normal or fatty liver (FL) in rats with acute liver failure (ALF) induced by hepatectomy. METHODS: Sprague-Dawley rats with normal or FL were segregated either to receive or not to undergo PPVA after hepatectomy. FL was induced by feeding a choline-deficient diet (5 days). PPVA was performed by anactamasing the left renal artery to the splenic vein with a stent following a left nephrectomy and splenectomy; the control rats underwent left nephrectomy and splenectomy only. Liver injury was evaluated by the serum alanine aminotransferase (ALT) level. The animals were sacrificed at 24 hours, 48 hours, and 7 days to collect blood and liver tissue samples for biochemical analysis. The 7-day survival was assessed in separate experimental groups. RESULTS: PPVA significantly increased Po2 and oxygen saturation in the portal blood compared to non PPVA rats. PPVA significantly improved the 7-day survival compared with controls in both groups: hepatectomy of normal liver (90% vs 30%) and hepatectomy of FL (75% vs 25%). Serum ALT levels were slightly lower in the PPVA groups compared with the non-PPVA groups without a significant difference. Prothrombin activity decreased soon after hepatectomy in the normal and the FL liver groups but recovered rapidly thereafter without differences between the PPVA and non-PPVA treated animals. CONCLUSION: An additional supply of arterial oxygenated blood through a PPVA promotes rapid resolution of ALF after partial hepatectomy in rats with normal or fatty livers, significantly improving 7-day survivals compared to hepatectomy controls.

Anastomosis, Surgical↗

Activity of trans-2-hexenal against Penicillium expansum in 'Conference' pears.

AIMS: To investigate the effects of trans-2-hexenal on blue mould disease, patulin content and fruit quality in 'Conference' pears. METHODS AND RESULTS: Fruits, wounded and inoculated with Penicillium expansum or non-inoculated, were exposed to trans-2-hexenal vapour treatment (12.5 microl l(-1)) at 20 degrees C. A greater reduction of decay was obtained by treatment application 24 or 48 h after inoculation, in contrast trans-2-hexenal application 2 h after inoculation was ineffective. Fruit storage temperature (-1 degrees C) after treatment did not affect the antifungal activity. Although 2-h exposure to trans-2-hexenal was effective in reducing blue mould, an exposure of at least 8 h was required to reduce fruit patulin content. Treatments did not affect fruit physical-chemical characteristics. After 6 days at 20 degrees C following exposure, trans-2-hexenal residue in treated fruits was less than the natural content of the compound in unripe fruits. CONCLUSIONS: trans-2-Hexenal treatment is effective in the reduction of blue mould infections and patulin content in Conference pears when applied 24-48 h after pathogen inoculation. SIGNIFICANCE AND IMPACT OF THE STUDY: trans-2-Hexenal could be a natural alternative to fungicides in the control of P. expansum infections. Further work is needed to study the methods and conditions avoiding the persistence of off-odours and off-flavours in pears after their exposure to trans-2-hexenal vapours.

Aldehydes↗

Double kidney transplantation: initial experience of the Bologna Transplant Center.

AIM: Double-kidney transplantation is performed using organs from marginal donors with a histological score not suitable for single kidney transplantation. The aim of the study is to verify the results obtained with double-kidney transplantation in terms of graft and patient survival and complications. METHODS: Between September 2001 and September 2004, 16 double-kidney transplantations were performed in our center. The kidneys were all perfused with Celsior solution and the mean cold ischemia time was 17.6+/-2.7 hours. In all cases a pre-transplant kidney biopsy was performed to evaluate the damage. Immunosuppression was tacrolimus based for all patients. RESULTS: Eight patients had good renal postoperative function while the other eight had acute tubular necrosis. Two of the patients who had severe acute tubular necrosis never recovered renal function. There was only one episode of acute rejection, while the incidence of urinary complications was 31.2%; there were two surgical revisions for intestinal perforation. The graft and recipient survival was 78.1% and 100% and 78.1% and 93.7% at 3 and 36 months. CONCLUSIONS: Double-kidney transplantation is a safe way to face the organ shortage. Moreover the score used in this study is useful to determine whether a kidney should be refused or suitable for single or dual-kidney transplantation. The results of our initial experience are encouraging, but this series is too small in number to consent a conclusive statement.

Aged↗

Pregnancy in patients with rheumatic diseases: psychological implication of a chronic disease and neuropsychological evaluation of the children.

As a consequence of the general improvement in the diagnosis and management of rheumatic diseases, patients achieve a better quality of life, with the possibility of a normal family life including one or more pregnancies. It is important, therefore, to consider the psychological aspects of these mothers' life and the influence of their chronic disease on their children is development. Several papers have reported the impact of systemic lupus erythematosus (SLE) on the quality of life. They found higher incidence of anxiety (from 15 to 45%) and depression (from 25 to 47%) compared to the general population. We have investigated the psychological influence of SLE on family planning, and we observed that it can interfere with physiological phenomena such as parenthood and the upbringing of children. The children of lupus mothers have a normal intelligence level for their age. What is emerging, however, is an increased incidence of learning disabilities compared to the general population. This observation suggests the importance of an early neuropsychological examination, in order to identify the children needing particular care. Therefore, psychological support seems to be an important help in the counseling of patients with rheumatic disease and in the future life of their children.

Adult↗

Neuropsychological development of children born to patients with systemic lupus erythematosus.

To verify the neuropsychological development in the offspring of patients with systemic lupus erythematosus (SLE), 47 children (23 male and 24 female) from affected women were studied. The tests applied were related to the children's ages: Griffiths scale up to four years, WPPSI and metaphonological tests (MP, evaluating the phonological consciousness) from four to six years of age, WISC-R test and Rey test (evaluating the visual-space abilities) from six years onwards; finally, specific tests for the diagnosis of learning disabilities (LD) between the ages of seven and 13. Intelligence levels were always normal (mean IQ score 106.32; median 104; SD 9.05). Three out of eight examined children failed MP, therefore may develop LD and will need further evaluation later. Fourteen children were specifically studied for LD and three reported scores lower than normal, but only two (who were brothers) were defined dyslexic. Antiphospholipid antibodies (aPL) were positive in the mothers of the three children with impaired LD tests. Other maternal autoantibodies or drugs administered during pregnancy did not seem to be related to LD. In conclusion, maternal SLE does not impair intelligence levels, but may increase the occurrence of LD particularly in male children (2/8 males examined, 25%). Both maternal aPL and genetic background may have pathogenetic implications.

Adolescent↗

Neonatal outcome in patients with rheumatic disease.

Rheumatic autoimmune diseases have a higher prevalence in women, particularly during their childbearing age. Due to improved management, an increasing number of patients plan and carry out one or more pregnancies. Therefore, a growing interest is being paid to the possible consequences of maternal disease and associated treatment on the fetus and newborn infant. If maternal disease is characterized by the presence of IgG isotype autoantibodies, these can cross the placenta with possible antibody-mediated damage to the fetus. This is typically the case of the so called neonatal lupus erythematosus (NLE); a similar mechanism has been shown in infants of patients with immune thrombocytopenic purpura (ITP) and, less frequently, in those from mothers with antiphospholipid syndrome (APS). Indeed, this last condition is often responsible for placental, rather than neonatal, pathology. In addition, immunosuppressive and other drugs administered to the mothers during pregnancy and lactation might affect the fetal and neonatal immune system development. Finally, mothers disease and/or treatment could be related to neuropsychological alteration reported in some of their children.

Antiphospholipid Syndrome↗

Effect of pH on axial ligand coordination of cytochrome c" from Methylophilus methylotrophus and horse heart cytochrome c.

The effect of protons on the axial ligand coordination and on structural aspects of the protein moiety of cytochrome c' ' from Methylophilus methylotrophus, an obligate methylotroph, has been investigated down to very low pH (i.e., 0.3). The unusual resistance of this cytochrome to very low pH values has been exploited to carry out this study in comparison with horse heart cytochrome c. The experiments were undertaken at a constant phosphate concentration to minimize the variation of ionic strength with pH. The pH-linked effects have been monitored at 23 degrees C in the oxidized forms of both cytochromes by following the variations in the electronic absorption, circular dichroism and resonance Raman spectra. This approach has enabled the conformational changes of the heme surroundings to be monitored and compared with the concomitant overall structural rearrangements of the molecule. The results indicate that horse heart cytochrome c undergoes a first conformational change at around pH 2.0. This event is possibly related to the cleavage of the Fe-Met80 bond and a likely coordination of a H(2)O molecule as a sixth axial ligand. Conversely, in cytochrome c" from M. methylotrophus, a variation of the axial ligand coordination occurs at a pH that is about 1 unit lower. Further, it appears that a concerted cleavage of both His ligands takes place, suggesting indeed that the different axial ligands present in horse heart cytochrome c (Met/His) and in cytochrome c" from M. methylotrophus (His/His) affect the heme conformational changes.

Animals↗

[Retinopathy of prematurity: incidence and risk factors].

The study analyses the incidence of the retinopathy of prematurity (ROP) and its correlation with the most important risk factors in neonates with gestational age (GE) < or = 32 weeks and/or with birth weight (BW) < or = 1500 g. The cohort of our study is composed by 305 preterms with Mean GE of 29.8 weeks and Mean BW of 1312 g, studied at the Neonatal Intensive Care Unit of the University of Parma during January 1993-December 1999. The incidence of ROP resulted 19.7% in our group and was inversely proportional to the GE and BW. No preterms with GE < or = 32 weeks presented retinopathy, while there has been an incidence of the 65% in the subjects with GE lower than 26 weeks. The most severe grade of ROP was mainly seen in the newborns with the lowest GE (31%), whilst only the 1.5% of the preterms with GE of 30-31 weeks developed ROP of stage 3 or 3+. Similar results were seen when the data were compared with the birth weight. However a direct relation was seen with the duration of the O2 therapy and with the typical pathologies of the prematurity, namely respiratory distress syndrome (RDS) and intraventricular haemorrhages (IVH). Among the other risk factors evaluated, the blood transfusion was the most relevant.

Humans↗

Role of the distal phenylalanine 54 on the structure, stability, and ligand binding of Coprinus cinereus peroxidase.

Resonance Raman and electronic absorption spectra obtained at various pH values for the Fe3+ form of distal F54 mutants of Coprinus cinereus peroxidase are reported, together with the Fe2+ form and fluoride and imidazole adducts at pH 6.0, 5.0, and 10.5, respectively. The distal phenylalanine residue has been replaced by the small aliphatic residues glycine and valine and the hydrogen-bonding aromatic residues tyrosine and tryptophan (F54G, -V, -Y, and -W, respectively). These mutations resulted in transitions between ferric high-spin five-coordinate and six-coordinate forms, and caused a decrease of the pKa of the alkaline transition together with a higher tendency for unfolding. The mutations also alter the ability of the proteins to bind fluoride in such a way that those that are six-coordinate at pH 5.0 bind more strongly than both wild-type CIP and F54Y which are five-coordinate at this pH value. The data provide evidence that the architecture of the distal pocket of CIP is altered by the mutations. Direct evidence is provided that the distal phenylalanine plays an important role in controlling the conjugation between the vinyl double bonds and the porphyrin macrocycle, as indicated by the reorientation of the vinyl groups upon mutation of phenylalanine with the small aliphatic side chains of glycine and valine residues. Furthermore, it appears that the presence of the hydrogen-bonding tyrosine or tryptophan in the cavity increases the pKa of the distal histidine for protonation compared with that of wild-type CIP.

Binding Sites↗

Spectroscopic characterization of recombinant pea cytosolic ascorbate peroxidase: similarities and differences with cytochrome c peroxidase.

Recombinant pea cytosolic ascorbate peroxidase (APX) has been characterized by resonance Raman (RR) and electronic absorption spectroscopies. The ferric and ferrous forms together with the complexes with fluoride and imidazole have been studied and compared with the corresponding spectra of cytochrome c peroxidase (CCP). Ferric APX at neutral pH is a mixture of 6- and 5-coordinate high-spin and 6-c low-spin hemes, the latter two species being dominant. The results suggest that the low-spin form derives from a water/hydroxo ligand bound to the heme iron and not from a strong internal ligand as observed in CCP at alkaline pH. Two Fe-Im stretching modes are identified, as in CCP, but the RR frequencies confirm a weaker His163-Asp208 hydrogen bond than in CCP, as suggested on the basis of the X-ray structure [Patterson, W. R., and Poulos, T. L. (1995) Biochemistry 34, 4331-4341]. The data show that CCP and APX have markedly different orientations of the vinyl substituents on the heme chromophore resulting from different steric constraints exerted by the protein matrix.

Ascorbate Peroxidases↗

Mutation of the distal arginine in Coprinus cinereus peroxidase--structural implications.

Heme peroxidases of prokaryotic, plant and fungal origin share the essential His and Arg catalytic residues of the distal cavity and a proximal His bound to heme iron. Spectroscopic techniques, in contrast to X-ray crystallography, are well suited to detect the precise structure, spin and coordination states of the heme as influenced by its near environment. Resonance Raman and electronic absorption spectra obtained at various pH values for Fe3+ and Fe2+ forms of distal Arg51 mutants of the fungal Coprinus cinereus peroxidase are reported, together with the fluoride adducts at pH 5.0. This basic catalytic residue has been replaced by the aliphatic residue Leu, the polar residues Asn and Gln and the basic residue Lys (Arg51-->Leu, Asn, Gln, and Lys, respectively). These mutations cause changes in the coordination and spin states of the heme iron, and in the v(Fe-Im) stretching frequency. The variations are explained in terms of pH-dependent changes, charge location, size and hydrogen-bonding acceptor/donor properties of the residue at position 51. The present work indicates that the hydrogen-bond capability of the residue in position 51 influences the occupancy of water molecules in the distal cavity and the ability to form stable complexes between anionic ligands and the heme Fe atom.

Amino Acid Sequence↗