[Autochthonous human dirofilariasis].
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Aged↗
Biomedical subjects
F Ferrari
Publications and source records attributed to F Ferrari.
1H NMR spectra of normal urines: reference ranges of the major metabolites.
Serial urine samples from 50 normal subjects were studied by 1H NMR spectroscopy operating at 300 MHz. Analyses of the spectra have shown the presence of the following metabolites in 100% of the normal subjects: Creatinine, lactate, alanine, citrate, dimethylamine, trimethylamine-N-oxide, glycine and hippurate. Other analytes, such as creatine, valine, betaine, leucine and isoleucine, were sometimes found. All metabolites were quantified on the basis of peak heights and were expressed as mmol/mol of creatinine. The study of metabolic profiles in serial samples allowed us to evaluate intra-individual variability and physiological changes due to feeding. The aim of our report is to define standard conditions for this analytical technique and to calculate confidence intervals for the major metabolites in normal urine samples, such as preliminary and mandatory stages for clinical diagnostic 1H NMR utilization.
Adult↗
An early marker for neurological deficits after perinatal brain lesions.
BACKGROUND: In normal awake infants, fidgety movements are seen from the age of 6 weeks to 20 weeks. The aim of the study was to test the predictive value of absent or abnormal spontaneous movements in young infants for the later development of neurological deficits. METHODS: In a collaborative study involving five hospitals we collected data on the normal and abnormal quality of fidgety movements of 130 infants and compared it with assessments of neurological development done longitudinally until the age of 2 years. On the basis of ultrasound scans infants were classified as at low-risk or at high-risk of neurological deficits. Infants were videoed for 1 h every week from birth to discharge and then for 15 min every 3 to 4 weeks; quality of general movements was assessed. Repeated neurological assessments were also done until 24 months of corrected age. FINDINGS: 67 (96%) of 70 infants with normal fidgety movements had a normal neurological outcome. Abnormal quality or total absence of fidgety movements was followed by neurological abnormalities in 57 (95%) of the 60 infants (49 had cerebral palsy and eight had developmental retardation or minor neurological signs). Specificity and sensitivity of fidgety movement assessment were higher (96% and 95%, respectively) than of ultrasound imaging of the infants' brain (83% and 80%, respectively). INTERPRETATION: Our technique of assessing spontaneous motor activity can identify and distinguish between those infants who require early intervention for neurological abnormalities and those who do not. Our technique is simple, non-intrusive, reliable, quick, and can be done on very young infants.
Biomarkers↗
Comparison between observation of spontaneous movements and neurologic examination in preterm infants.
OBJECTIVE: The Prechtl method of qualitative assessment of general movements (GMs) has been shown to be a good predictor of neurologic outcome in fetuses, preterm infants, and term infants. The aim of this study was to compare the results of this new technique with those of traditional neurologic examination and of cranial ultrasonography in preterm infants. METHODS: Serial videotape recordings (with off-line assessment of GMs), ultrasound examination of the brain, and neurologic examinations were performed from birth until about 6 months of corrected age, on a group of 66 preterm infants whose gestational age ranged from 26 to 36 weeks (mean 30.7 weeks). The agreement between the two techniques and their predictive power, with respect to the neurologic outcome at 2 years of corrected age, were evaluated for five different age groups from preterm age to 65 weeks of postmenstrual age. RESULTS: Overall agreement of the neurologic and GM findings was 80.3% and strongly age related (lower during the preterm and term periods and higher thereafter). At all ages the results of GM observation correlated highly with neurologic outcome; they showed higher sensitivity and specificity than the neurologic examination. This held true in particular before term age, when poor neurologic responses might be related to transient complications, and at term age, mainly because of infants with normal neurologic examination results but unfavorable outcome. During the preterm period the ultrasound results showed a better specificity and a lower sensitivity to outcome than GM findings. CONCLUSIONS: The results of this study indicate that quality assessment of GMs should be added to traditional neurologic assessment, neuroimaging, and other tests of preterm infants for diagnostic and prognostic purposes.
Child Development↗
Involvement of dopamine D2 receptors in the effect of cocaine on sexual behaviour and stretching-yawning of male rats.
The effect of cocaine (7.5, 15 and 30 mg/kg) administered in acute or subchronic mode, on the mating behaviour of sexually active male rats varied in a dose- and mode-dependent manner. Regardless of mode of treatment, 30 mg/kg markedly impaired the rats copulatory ability and impairment continued for a week after suspension of subchronic treatment. An acute dose of 15 mg/kg reduced intromission frequency, while in subchronic mode it also reduced ejaculation latency. Mount frequency was increased by 7.5 and 15 mg/kg, but only on first injection. In the case of sexually-naive male rats, acute administration of cocaine (3-30 mg/kg) stimulated penile erections at 7.5 mg/kg and motor hyperactivity at all doses. (-) Eticlopride (0.025 and 0.05 mg/kg), a DA D2 antagonist, counteracted cocaine-induced motor hyperactivity but not penile erection, which it enhanced. (-) Eticlopride at the same doses also antagonized cocaine potentiation of lisuride (0.2 mg/kg)-induced behavioural effects. When male rats treated with subchronic cocaine (15 mg/kg) were injected with the DA D2 agonist SND 919 (0.1 mg/kg), they displayed a more marked stretching-yawning behaviour than control animals receiving SND 919 at the same dose. The involvement of DA D2 receptors in cocaine-induced effects is suggested.
Animals↗
Involvement of dopamine receptors in the antipsychotic profile of (-) eticlopride.
The present study was performed to assess the effects exerted by the dopamine (DA) D2/D3 antagonist (-) eticlopride on rodent behavioral models considered to be predictive of antipsychotic activity, namely, antagonism toward DA agonist-induced stereotyped behavior (SB), and ketamine-and cocaine-induced hypermotility. (-) Eticlopride (10-50 micrograms/kg) dose-dependently inhibited SB elicited by SND 919 (10 mg/kg), CQP 201-403 (0.5 mg/kg), and 7-OH-DPAT (5 mg/kg); moreover, it significantly counteracted the hypermotility induced in rats and mice by ketamine (5 and 10 mg/kg). When (-) eticlopride was injected before cocaine (15 mg/kg) either acutely or subchronically administered in male rats, it also potently antagonized the hypermotility typically induced by the drug. These results are discussed in the light of putative D2/D3 receptor involvement, and are considered as predictive of antipsychotic potential.
Animals↗
The glucocorticoid receptor regulates the binding of C/EPBbeta on the alpha-1-acid glycoprotein promoter in vivo.
A complex interaction between the Glucocorticoid Receptor (GR), C/EBPbeta, and other transcription factors activate the Alpha-1 Acid Glycoprotein (AGP) promoter in HTC(JZ-1) rat hepatoma culture cells. This effect is mediated by the so-called Steroid Responsive Unit (SRU) of the AGP promoter that contains several binding sites for C/EBP transcription factors, some of which overlap with the Glucocorticoid Responsive Element (GRE). Our in vivo footprinting experiments revealed that the GRE- and the C/EBP-binding sites were already occupied glucocorticoid dependently in HTC(JZ-1) cells 10 min after dexamethasone administration (10(-6) M). Furthermore, local changes in the chromatine structure shown by the appearance of DNAse I hypersensitive sites (HS sites) also took place. These changes were probably dependent on a tissue-specific organization of the chromatine at the SRU because they were not detectable in a different glucocorticoid-responsive cell line (PC12) that did not express AGP. Here, we have also shown that withdrawal of dexamethasone or addition of the anti-glucocorticoid RU486 were able to revert the pattern induced by dexamethasone in vivo. The disappearance of the protected region and the hypersensitive sites, typical of the hormone activated promoter, confirmed the necessity of the GR to be bound by the agonist and the inability of the GR-antagonist complex to bind the DNA. By functional assays, we showed that the occupancy of the SRU by these transcriptional proteins in vivo correlated with the activation of the AGP gene transcription. With these results, we have shown that one of the functions of the GR to activate transcription of the AGP gene is to recruit C/EBPbeta and to maintain it bound at its target DNA sequences (SRU). This process was not accomplished by RU486.
Adrenal Gland Neoplasms↗
Effects of (-)eticlopride and 7-OH-DPAT on the tail-suspension test in mice.
The dopamine (DA) D2/D3 antagonist (-)eticlopride (0.02, 0.05 and 0.1 mg/kg), dose-dependently increased immobility in the mouse tail-suspension test. Chronic treatment with the same compound (0.05, 0.1 mg/kg, x 14 days) produced a different effect, decreasing immobility when animals were tested 24 h after the last injection. The DA D3 agonist, 7-OH-DPAT, acutely administered before the same test, behaved biphasically, increasing and decreasing mice immobility at low (0.05 and 0.1 mg/kg) and high (1 and 2 mg/kg) doses, respectively. Chronically administered 7-OH-DPAT reduced the immobility time at 2 mg/kg but not at 0.1 mg/kg. These effects, coupled with measurements of locomotor activity and evaluation of mice behaviour in different conditions, are discussed in the light of putative DA involvement in depressive states and are considered as predicting antidepressant potential.
Animals↗
[Anesthesiologic management of susceptible children at risk for malignant hyperthermia].
In order to prevent malignant hyperthermia (MH) in children, the authors are currently using a perioperative anaesthetic protocol. In vitro contracture tests with halothane and caffein are performed in selected patients: those with previous signs suggestive of MH, but not severe enough for a definite diagnosis; those with susceptibility to MH in their relatives; those affected by myopathies or other disorders very frequently associated with MH. Even though CK should be considered an unreliable predictor of MH susceptibility, trigger agents are avoided in children with high and constant CK levels. However, prophylactic dantrolene is never employed. In this way, over the last decade no episodes of classic malignant hyperthermia in a large number of children submitted to anaesthesia (more than 50,000) have been observed.
Anesthesia, General↗
Synthesis, resolution, and preliminary evaluation of trans-2-amino-6(5)-hydroxy-1-phenyl-2,3-dihydro-1H-indenes and related derivatives as dopamine receptors ligands.
The present work reports the synthesis of enantiomeric pairs of the trans-2-amino-6-hydroxy-1-phenyl-2,3-dihydro-1H-indene [(+)-14a, (-)-14a] and trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1 H-indene [(+)-14b, (-)-14b] and their N,N-di-n-propyl [(+)-and (-)-15a,b], N-methyl-N-allyl [(+)-and (-)-16a,b], and N-methyl-N-n-propyl [(+) and (-)-17a,b] derivatives obtained by a combination of stereospecific reactions and optical resolution. The new compounds were evaluated for their affinity at the dopamine D1 and D2 receptors. The amines (+)- and (-)-14a, incorporating the D1 pharmacophore 2-phenyl-2-(3-hydroxyphenyl)ethylamine in a trans extended conformation, and their derivatives displayed D1 and D2 affinity in the nanomolar range. On the other hand, the enantiomers (+)- and (-)-14b, (+)- and (-)-15b displayed high affinity and selectivity for the D1 receptor. In a preliminary behavioral study on rats (+)-14b, and to a greater extent (+)-15b, promoted episodes of intense grooming, thus indicating that they act as central D1 agonists. The trans-2-amino-5-hydroxy-1-phenyl-2,3-dihydro-1H-indenes (+)-14b and (+)-15b represent selective D1 agonists lacking a catechol group, which should meet the prerequisites for a central nervous system penetration.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Manganese effects on the human neuroblastoma cell line SK-ER3.
SK-ER3 cells were recently demonstrated to represent a valuable model for the study of estrogen-inducible differentiation of neural cells in culture. This system may constitute an important tool also for the analysis of the effects of neurotoxic drugs. The present study demonstrates that short term exposure to Mn causes increased proliferation rate of SK-ER3 cells regardless of their differentiation. Long term treatment causes cell death in undifferentiated cells at concentrations of the metal as low as 100 nM. When the cells are differentiated with estrogens, death is observed only with a Mn concentration two orders of magnitude higher. Measurement of neurite extension and quantitation of tyrosine hydroxylase content after long-term exposure to the metal allow the conclusion that Mn does not alter the state of differentiation of SK-ER3 cells induced by the treatment with the hormone. The study underlines the importance of studying the effect of Mn in proliferating neural cells and demonstrates the toxic role of micromolar concentrations of the metal in fully differentiated neural cells. Since other authors produced evidence of effects of the metal on cell death and proliferation only at millimolar concentrations, and none described its proliferative activity, the model utilized in the present study seems to be of particular interest.
Cell Differentiation↗
Activation of the neuroendocrine response in heart failure: adaptive or maladaptive process?
Congestive heart failure is a clinical syndrome in which the capacity of the heart to maintain cardiac output is impaired. As a consequence, blood pressure is threatened and endocrine and paracrine mechanisms are activated to preserve circulatory homeostasis and to maintain blood pressure. At terminal stages, a complex multiorgan syndrome develops with severe pump failure, intense systemic vasoconstriction, and avid water and sodium retention. Increasing evidence points to humoral circulating or locally synthesized substances as one of the causes of the terminal consequences of heart failure. Therefore, the hypothesis that the syndrome of heart failure is, at least in part, a humoral disease has developed and is obtaining scientific credibility. Consequently, the neuroendocrine response to heart failure is no longer viewed as a compensatory beneficial mechanism. Instead, we have learned through the years that pharmacological treatment aimed at reducing the effect of the neuroendocrine response is indeed clinically and prognostically advantageous for the patient.
Adaptation, Physiological↗
Multicystic encephalomalacia in term infants.
The terms "multicystic encephalomalacia" and "subcortical leucomalacia" (SCL) are used to describe the presence of areas of necrosis that develop into cystic lesions inside the brain. These lesions are generally due to severe asphyxia and/or hypotension. The designation SCL can also be used to describe the extent and the seat of the lesion in the brain or to distinguish subcortical lesions from periventricular and/or combined ones. In this study we give an account of our experience with eight newborns admitted to our neonatal intensive care unit, who presented clinical-neurological alterations and encephalomalacic lesions whose presence was documented by ultrasonography.
Asphyxia Neonatorum↗
Behavioral effects induced by the dopamine D3 agonist 7-OH-DPAT in sexually-active and -inactive male rats.
The present study investigates the effects induced by the putative DA D3 agonist 7-OH-DPAT (0.1 and 1 mg/kg, s.c.) on: (1) the sexual behavior of male rats, categorized on the basis of seven consecutive mating pre-tests as sexually-active (SA) and sexually-inactive (SI); and (2) stretching-yawning, penile erection, sedation and stereotyped behavior of the same animals. The data obtained show that 7-OH-DPAT at both doses modifies the copulatory pattern of SA rats, facilitating ejaculation mechanisms, but fails to increase the sexual drive of the animals as is evident from the ineffectiveness in SI rats. The second major finding is that the two groups of rats, which are markedly different as regards sexual typology, exhibit different behavioral responses to 7-OH-DPAT.
Animals↗
Influence of eticlopride on cocaine- and DA D2 agonist-induced behavioral effects in rats.
The influence of the DA D2 antagonist (-) eticlopride on cocaine- and DA D2 agonist-induced behavioral effects was investigated by means of two series of experiments, in rats. In the first 10-day series, coadministration of (-) eticlopride (10 and 50 micrograms/kg, SC) always potently inhibited cocaine (15 mg/kg, IP)-induced hypermotility but did not modify the penile erection (PE)-enhancement produced by the drug at the first injection; it actually counteracted the inhibitory effect of subchronic cocaine on PE. In the second series, (-) eticlopride, at the same doses, antagonized PE elicited by various DA D2 agonists at nonstereotyping doses; when, along with PE, stereotyped behavior was induced, only the latter was inhibited by (-) eticlopride, which even increased PE.
Animals↗
Differential behavioral response to dopamine D2 agonists by sexually naive, sexually active, and sexually inactive male rats.
This study was performed with male rats categorized as sexually naive (SN), sexually active (SA), or sexually inactive (SI). In a first experiment the effects of dopamine (DA) D2 agonist SND 919 (0.05, 1, and 10 mg/kg) on the copulatory behavior of SN, SA and SI rats were assessed. In a second experiment the DA D2 agonist B-HT 920 (0.2 mg/kg) was used, and examination was limited to SN and SA rats. The effects exerted on stretching-yawning, penile erection, and sedation by the same compounds at the same doses in these three rat categories were also investigated. The main findings were that SND 919 and B-HT 920 facilitated ejaculation in SA rats, and that the rats that were different as regards level of sexual activity exhibited different behavioral responses to the two DA agonists.
Animals↗
Chemical and preliminary analgesic evaluation of geraniin and furosin isolated from Phyllanthus sellowianus.
The present study describes the occurrence of two ellagitannins in the ethanolic extract of the leaves and stems of Phyllanthus sellowianus (Euphorbiaceae). Their preliminary antinociceptive properties were also evaluated. The two ellagitannins were identified on the basis of 1H- and 13C-NMR spectra data and by mixed co-TLC and co-HPLC injection with an authentic sample of furosin and geraniin. Preliminary pharmacological analysis revealed that both furosin and geraniin (3 to 30 mg/kg, i.p.), given 30 min before testing, exhibited significant and dose-related antinociceptive properties against acetic acid-induced abdominal constrictions in mice. Geraniin and furosin were about six- to seven-fold more potent at the ID50 level (micromol/kg) as analgesics than aspirin and acetaminophen, respectively, although they were less efficacious when compared with the standard drugs. These data extend our previous studies and indicate that the two ellagitannins isolated from P.sellowianus, identified as furosin and geraniin are, at least in part, responsible for the antinociceptive actions reported previously for the hydroalcoholic extract of P.sellowianus and other plants belonging to the genus Phyllanthus.
Abdominal Pain↗
Chemical and pharmacological studies of Phyllanthus caroliniensis in mice.
The aim of this study was to isolate and characterize the constituents of the hydroalcoholic extract (HE) of the leaves, stems and roots from P. caroliniensis, and also to evaluate the preliminary antinociceptive action of the HE and purified compounds in mice. Phytosterols, quercetin, gallic acid ethyl ester and geraniin were identified in P. caroliniensis on the basis of 1H and 13C NMR spectral data and by mixed co-TLC and co-HPLC injection with authentic samples. The HE of P. caroliniensis (10-100 mg kg-1, i.p.) inhibited, in a dose-related manner, acetic acid-induced abdominal constrictions in mice, with a mean ID50 value of 23.7 mg kg-1. In the formalin test, the HE given intraperitoneally (1-30 mg kg-1) or orally (25-600 mg kg-1) caused graded inhibitions of both the neurogenic (first phase) and the inflammatory response (late phase) of formalin-induced licking. The HE was 54-fold more effective in inhibiting the late phase than it was in inhibiting the first phase of the formalin test, with mean ID50 values of 3.6 and 196.4 mg kg-1, respectively. The HE failed, however, to affect the oedematogenic response associated with the late phase of formalin-induced pain. In addition, the reference drug, aspirin, given intraperitoneally (1-100 mg kg-1) or orally (100-600 mg kg-1), caused significant inhibition of the late but not the first phase of the formalin test. Pharmacological analysis also revealed that quercetin, gallic acid ethyl ester and a semi-purified fraction of flavonoids (1-100 mg kg-1, i.p.) exhibited graded and significant antinociception against acetic acid-induced abdominal constriction. The mean ID50 values (mg kg-1) for these effects were: 18.8, 34.7 and 5.3, respectively. It is concluded that quercetin, gallic acid ethyl ester and some as yet unidentified flavonoids might account for the antinociceptive action reported for the HE of P. caroliniensis.
Analgesics↗