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Biomedical subjects

F Ferrari

Publications and source records attributed to F Ferrari.

At least 55 records · Page 3Linked to original sources

Genetic alterations of the retinoblastoma-related gene RB2/p130 identify different pathogenetic mechanisms in and among Burkitt's lymphoma subtypes.

Alterations of cell cycle-associated genes probably contribute to the pathogenesis of Burkitt's Lymphoma (BL), in addition to c-myc translocation. Mutations disrupting the nuclear localization signal of the retinoblastoma-related gene RB2/p130 have been documented recently in BL cell lines and primary tumors. Given the importance of the RB2/p130 gene in controlling cell growth, mutations of this gene may result in uncontrolled cell proliferation. We tested the expression and genomic organization of the RB2/p130 gene in relation to the proliferative features of a series of BL samples collected from the endemic and sporadic regions, regardless of whether the samples were acquired immune deficiency syndrome (AIDS)-related. The expression of the Rb2/p130, p107, and cell proliferation-related proteins (cyclin A and B) was determined by immunohistochemistry. The structures of exons 19 through 22 of the RB2/p130 gene, encoding for the B domain and C terminus, were analyzed by polymerase chain reaction (PCR) analysis and single-strand conformation polymorphism (SSCP) technique. The direct PCR products were sequenced to identify the actual mutations. Our results suggest that BL is composed of a mixture of molecular types with distinct genetic and phenotypic patterns, probably resulting from different pathogenetic mechanisms. In endemic BL, the RB2/p130 gene is mutated in most of the cases, and the protein is restricted to the cytoplasm. In AIDS-related BL, high levels of nuclear expression of the wild-type pRb2/p130, p107, and cell proliferation-related proteins were detected. This finding is in line with the molecular mechanisms observed in virus-linked oncogenesis. Sporadic BLs were mainly characterized by the low nuclear values of the wild-type pRb2/p130 and, conversely, the high values of p107. The increased cell proliferation due to different alterations of cell growth control by Rb-related proteins may be the first step in lymphomagenesis, during which additional genetic changes, including missense mutations of c-myc, may subsequently occur.

Adolescent↗

Characterization of chitosan hydrochloride-mucin interaction by means of viscosimetric and turbidimetric measurements.

In the present work the interaction between chitosan hydrochloride (HCS) and two different types of mucin - one obtained from bovine submaxillary glands and the other from porcine stomach - was investigated. Two hydration media were tested: distilled water and 0. 1 M HCl. Intrinsic viscosity, which provides information about polymeric chain conformation, was assessed in both media for HCS and bovine submaxillary mucin. Changes in the specific viscosity of HCS-mucin mixtures were observed as a function of the polymer:mucin weight ratio. The formation of interaction products was indicated by a minimum in the specific viscosity. Such a minimum occurred at different polymer:mucin weight ratios depending on the hydration medium and mucin type. This suggested a different stoichiometry of interaction. Turbidimetric measurements were also effected in order to evidentiate the eventual precipitation of the polymer-mucin interaction products. While in distilled water the precipitation of the interaction product did occur, in acidic medium, although a minimum in specific viscosity was observed, no precipitate was formed. The two techniques employed, viscosimetric and turbidimetric, allowed us to investigate for both mucins the influence of hydration medium on the formation of the HCS-mucin interaction products and to conclude that a slightly acid-neutral pH favours the interaction between HCS and mucins.

Animals↗

Early neurological signs in preterm infants with unilateral intraparenchymal echodensity.

UNLABELLED: The aim of the study was to document the early developmental course of neurological signs in a group of preterm infants at risk for hemiplegia due to unilateral intraparenchymal echodensity (UIPE). Sixteen preterm infants with UIPE and sixteen controls were given serial neurological examinations, according to the protocols currently adopted in the different NICUs of the project. Moreover, the quality assessment of their general movements (GMs) was assessed subsequently from videotapes, from birth until around four months postterm. At two years, 12 of the UIPE infants showed hemiplegia and one suffered from asymmetrical diplegia. The findings of the traditional neurological examination were abnormal for the large majority of the UIPE infants, although normal findings were also recorded in some cases, especially during the preterm period. Asymmetries were found after term age in nine UIPE and in two control infants. From the first observation onwards, all infants with UIPE showed bilaterally abnormal GMs and in those with unfavourable outcome fidgety movements (FMs) were absent. At the FMs period (9-16 weeks postterm), all infants with subsequent hemiplegia showed asymmetry of distal segmental movements which were reduced or absent on the side contralateral to the lesion. CONCLUSIONS: Unilateral brain lesions induce clear neurological signs and abnormal GMs in particular, although these abnormalities are not initially asymmetrical. A reduction of segmental movements on one side of the body during the third month postterm is highly predictive of hemiplegia.

Age Factors↗

EEG in assessing hydroxycobalamin therapy in neonatal methylmalonic aciduria with homocystinuria.

We performed serial electroencephalograms (EEG) in a newborn with methylmalonic aciduria and homocystinuria to assess the effects of hydroxycobalamin (OHcbl) therapy on the CNS. Diagnosis was made at 22 days of age: she had torpor, failure to thrive and hypotonia of the limbs, and intermittent opisthotonus. The first EEG, performed on the first day of therapy, showed abnormal and immature transients, low voltage and very long flat periods in the discontinuous part of the tracing. These features quickly improved during therapy. After 13 days of OHcbl therapy, the EEG tracing became normal for conceptional age and showed normal sleep phases with only minor anomalies; only mild hypotonia still remained and biochemical parameters normalized. The decrease in blood homocysteine (index of blood detoxification) was statistically correlated to the reduction of the length of flat periods in EEG (p < 0.01). In conclusion, changes in neonatal EEG, particularly the length of interburst periods in the intermittent part of the tracing, appeared to be a reliable index for evaluating drug effectiveness in methylmalonic aciduria and homocystinuria.

Electroencephalography↗

[Psychosocial intervention model of neonatal intensive care in Modena].

Many authors agree that psychosocial factors influence the psychophysical development of the infant. These factors must be taken into account in the neonatal care. At the neonatal intensive care unit (NICU) of the University Hospital of Modena, physicians, psychologist and nurses cooperate to take care of each newborn with a difficult psychosocial background. Together they individuate and select newborns with psychosocial difficulties, plan an integrated action and, eventually, address the family to the community services. We describe our experience with 106 cases from 1996 to 1999. The integrated action included observation of parental behavior within the NICU and psychological support for parents by means of psychological counselling. Many meetings among physicians, nurses, psychologist and the social worker were needed to achieve good results. The aim of the project was to define a method to provide individualized actions in order to favour psychophysical health of newborns and their families.

Humans↗

[Model of integrated hospital project for the management of patients at risk of sudden death syndrome].

Home cardiorespiratory monitoring (HM) is an accepted practice in infants at high risk for Sudden Infant Death Syndrome (SIDS) as those with the following conditions: 1) Siblings of SIDS; 2) Apparent Life Threatening Events (ALTE); 3) Apneas of prematurity. From 1998 the Division of Neanotology of the Policlinico of Modena has followed prospectively infants at high risk for SIDS, in collaboration with the General Health Service. To support the clinical trial 10 apnea monitors were provided by the General Health Service and managed from the Department of Neonatology. During 18 months 24 infants have been followed by HM, and among then 20 were at risk of SIDS (11 female and 9 male): 7 were siblings of SIDS (35%); 10 had previous episodes of ALTE (50%); 3 were born prematurely and had persistent apneas before discharge (15%). The mean period of HM was 5.85 months. None of the infants died for SIDS or had episodes of ALTE that required resuscitation measures. In only one case parents stopped earlier than recommended, but personal interview to parents showed that all the others families gained benefits and reassurance from HM.

Humans↗

[A case of female pseudohermaphroditism caused by maternal androluteoma].

Female pseudohermaphroditism is a condition characterized by various degree of external genitalia virilization in a patient with female internal genitalia and karyotype (XX). External genitalia is masculinized congenitally when female fetus is exposed to excess androgenic environment. Fetal metabolic abnormalities, like congenital adrenal hyperplasia, are the most common causes of female pseudohermaphroditism, however there is a low incidence of gestational hyperandrogenism caused by maternal pathology. We report a case of female pseudohermaphroditism secondary to a maternal ovarian luteoma of pregnancy producing androgenic hormones. The newborn presented a severe degree of external genitalia virilization with high urogenital sinus (stage Prader V). Moreover we describe the main steps of diagnostic iter that are necessary both to exclude other causes of virilization and to study all anatomical aspects in view of the surgical correction. The operation consists in two phases of action: an early clitorisvulvoplasty according to Passerini-Glazel and a late vaginal pull-through with anterior saggital transanorectal approach (ASTRA).

Disorders of Sex Development↗

[Sepsis caused by Corynebacterium xerosis in neonatology: report of a clinical case].

The pathogenicity of the nondiphtheria corynebacteria, most commonly known as coryneform bacteria in humans has been recognized in the last two decades. Corynebacterium xerosis is part of the normal flora of the skin, nasopharynx, conjunctives and it has recently been isolated from vaginal swabs. During the last few years, there has been an increased number of case reports claiming an association of C. xerosis with diseases, like septicemia, endocarditis, pleuropneumonia, peritonitis, osteomyelitis, septic arthritis, mediastinitis, meningitis, ventriculitis specially in immunocompromised patients or surgical patients. Infections due to C. xerosis have been reported rarely in newborn. We report a case of sepsis due to C. xerosis in a newborn without evident immunodeficiency. Our case further support the recognition of C. xerosis as a human pathogen and reinforces the fact that it should not be routinely considered as a contaminant.

Corynebacterium Infections↗

[Neonatal cystic fibrosis: report of 2 cases].

Cystic fibrosis is the most common life-limiting recessive genetic disorder in Caucasian. It is caused by mutations of CFTR gene (cystic fibrosis transmembrane conductance regulator); at present over 500 mutations are known. Cystic fibrosis as a cause of respiratory distress in the neonate is quite rare. In neonatal period the most important clinical manifestations are meconium ileum and much rarely cholestatic jaundice. We present two cases of cystic fibrosis in newborns. In the first one, we point out the strict association between meconium ileum and cystic fibrosis. The patient underwent a surgical treatment for meconium ileum and the diagnosis was rapidly confirmed by genetic analysis and sweat test. The second one had intestinal obstruction from birth caused by meconium ileum associated with ileal atresia; besides, he developed cholestatic jaundice, severe and rapidly progressive respiratory disease. He died at 102 degrees day of age for cardiac failure. The diagnosis of cystic fibrosis, supported by typical clinical features and high level of serum trypsin, unfortunately wasn't confirmed by genetic analysis (lambda F508/neg), in addition, the sweat test wasn't reliable because an inadequate quantity of sweat was collected.

Cystic Fibrosis↗

Inside-out vs. standard vein graft to repair a sensory nerve in rats.

Nerve regeneration in a sensory nerve was obtained by the application of different techniques: inside-out vein graft (IOVG group) and standard vein graft (SVG group). These techniques provide a good microenvironment for axon regeneration in motor nerves, but their efficiency for regeneration of sensory nerves is controversial. The saphenous nervtce was sectioned and repaired by the inside-out and standard vein graft techniques in rats. After 4, 12, and 20 weeks the graft and the distal stump were observed under electron microscopy. In each studied period, the pattern, diameters, and thickness of the myelin sheaths of the regenerated axons were measured in the graft and distal stump. A comparative study about the regenerated nerve fibers by these two different techniques was performed. Regenerated nerve fibers were prominent in both vein grafts 4 weeks after the surgical procedures. On the other hand, in the distal stump, regenerated nerve fibers were observed only from 12 weeks. In both inside-out vein graft and standard vein graft statistical difference was not observed about the diameters and thickness of the myelinated fibers after 20 weeks. On the other hand, the inside-out group had greater regenerated axon number when compared to the standard group. There is a capillary invasion in both graft and distal stump, especially in the IOVG group. The regenerated axons follow these capillaries all the time like satellite microfascicles. After 20 weeks, the diameters of regenerated fibers repaired by the standard vein graft technique were closer to the normal fibers compared to the inside-out vein graft. On the other hand, the pattern of these regenerated axons was better in the IOVG group.

Animals↗

Influence of the cannabinoid agonist HU 210 on cocaine- and CQP 201-403-induced behavioural effects in rat.

Acute injection of the cannabinoid agonist HU 210 (6.25-100 microg/kg, i.p.) dose-dependently inhibited rat locomotor activity and rearing, while subchronic treatment with the drug (once daily for 7 days) at the same doses only diminished locomotion. Acute but not subchronic administration of HU 210 (12.5-50 microg/kg, i.p.) potently counteracted acute and subchronic cocaine (15 mg/kg, i.p.)-induced hyperlocomotion and enhanced rearing. The acute cannabinoid (6.25-100 microg/kg, i.p.) also inhibited locomotor activity, stereotyped behaviour and shaking elicited by the D1/D2 agonist CQP 201-403 (500 microg/kg, i.p.). On the contrary, subchronic treatments with HU 210 enhanced CQP 201-403-induced locomotor activity and potently stimulated escape attempts. Discussion centers on the influence of cannabinoids on experimental models of psychosis.

Animals↗

Cannabimimetic activity in rats and pigeons of HU 210, a potent antiemetic drug.

Preliminary behavioral experiments in rats with the cannabinoid agonist HU 210 (12.5-100 microg/kg i.p.) showed that it has a potent cannabimimetic profile similar to that of delta9THC; the drug dose dependently depressed locomotor activity, rearing, and grooming and elicited vocalization and circling at the highest doses. In subsequent studies on pigeons, HU 210 (12.5-50 microg/kg s.c.) confirmed its sedative effects; it also afforded protection against vomiting induced by cisplatin (7.5 mg/kg i.v.) and emetine (20 mg/kg s.c.) and emetine-induced head shake.

Animals↗

Learning impairment produced in rats by the cannabinoid agonist HU 210 in a water-maze task.

To ascertain whether the cannabinoid agonist HU 210 (25, 50, or 100 microg/kg, IP) influences rat spatial learning, water-maze performance was examined in the place (hidden platform)--and cue (visible platform)--versions of the Morris water maze. In addition, other unlearned behaviors were examined, namely, vocalization and wall hugging during the place task, and motor abilities during a motor test battery. The results obtained show that HU 210 at 50 or 100 microg/kg (once daily for 4 days, 60 min before a daily session) impaired learning in the place version but not in the cue one; wall hugging and enhanced vocalization were also displayed by the animals in the fourth session. Motor activity was compromised by the same treatment schedule. When the drug was discontinued, the effects produced by HU 210 at 50 microg/kg reversed in 3 days, while disruption of acquisition and vocalization caused by HU 210 at 100 microg/kg remained after 7 days' abstinence. Discussion centers on the possible specific cognitive mechanisms affected by the drug and on aspecific factors (i.e., anxiety-like state), which may contribute to the impairment of spatial learning.

Animals↗

Titration of AAV-2 particles via a novel capsid ELISA: packaging of genomes can limit production of recombinant AAV-2.

We demonstrate the rapid and reliable quantification of physical AAV-2 (adeno-associated virus type 2) particles via a novel ELISA based on a monoclonal antibody which selectively recognizes assembled AAV-2 capsids. Titration of a variety of recombinant AAV-2 (rAAV) preparations revealed that at least 80+percent of all particles were empty, compared with a maximum of 50percent in wild-type AAV-2 stocks, indicating that the recombinant genomes were less efficiently encapsidated. This finding was confirmed upon titration of CsCl gradient fractions from recombinant and wild-type AAV-2 stocks. ELISA-based measurement of capsid numbers revealed a large number of physical particles with low densities corresponding to empty capsids in the recombinant, but not in the wild-type AAV-2 preparations. Moreover, additional expression of VP proteins during rAAV production was found to result in an excessive capsid formation, whilst yielding only minor increases in DNA-containing or transducing rAAV particles. We conclude that encapsidation of viral genomes rather than capsid assembly can be limiting for rAAV production, provided that a critical level of VP expression is maintained. The feasibility of quantifying AAV-2 capsid numbers via the ELISA allows determination of physical to DNA-containing or infectious particle ratios. These are important parameters which should help to optimize and standardize the production and application of recombinant AAV-2.

Antibodies, Monoclonal↗

Study of the antinociceptive action of the ethanolic extract and the triterpene 24-hydroxytormentic acid isolated from the stem bark of Ocotea suaveolens.

We describe here the antinociceptive action of the crude extract (CE), the chemical isolation and characterisation and preliminary pharmacological analysis of 24-hydroxytormentic acid, isolated from the stem bark of Ocotea suaveolens (Lauraceae). The CE given by i.p. or p.o. routes, 30 min and 1 h prior, produced significant inhibition of abdominal constrictions caused by acetic acid and also inhibited both phases of formalin-induced licking in mice. The antinociception caused by the CE, given by i.p. and p.o. routes, lasted up to 4 and 2h, respectively. When assessed in the hot-plate test, the CE was inactive. Its antinociceptive action was not associated with non-specific effects such as muscle relaxation or sedation. The antinociception of CE was not influenced by naloxone, L-arginine or DL-p-chlorophenylalanine methyl ester, when assessed against the formalin assay. The triterpene 24-hydroxytormentic acid, given i.p. 30 min before testing, produced significant, dose-related and equipotent antinociceptive action against both phases of formalin-induced licking in mice. These results demonstrate, for the first time, the occurrence of the triterpene 24-hydroxytormentic acid in the stem bark of Ocotea suaveolens, and show that the CE and 24-hydroxytormentic acid exhibit marked antinociception against the neurogenic and the inflamamtory algesic responses induced by formalin in mice. The mechanism by which this compound and CE produces antinociception still remains unclear, but is unlikely to involve the activation of opioid, nitric oxide or serotonin systems or non-specific peripheral or central depressant actions.

Analgesics↗