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Biomedical subjects

E Ferrari

Publications and source records attributed to E Ferrari.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effects of repeated exposures to xenon on rat adrenal cortex ultrastructure.

Xenon has many properties of the ideal anaesthetic and it has been proposed to replace classic volatile anaesthetics. Although some studies demonstrated that xenon does not induce gross morphological changes in major organs, little is known on its possible ultrastructural effects. The present study investigates the subcellular effects of repeated exposures to 70% xenon on rat adrenal cortex in comparison with N2O. Animals were divided into four groups: xenon-exposed, N2O-exposed, sham-exposed and controls. Exposed rats were placed into a sealed cage to breathe the respective gas mixture for 2.5 h/day for a week. Specimens of adrenal cortex for electron microscopy and blood samples for determination of corticosterone plasma levels were taken at the end of the last exposure or one week after the last exposure (recovery). Adrenal cortex from N2O- and sham-exposed rats mainly showed dilation of endoplasmic reticulum, whereas xenon-exposed rats also exhibited several cells with lipid droplets appearing subdivided into smaller droplets, irregular in shape and size. In all experimental groups, corticosterone plasma levels increased in comparison to controls. Both ultrastructural and hormonal changes were not detected anymore after one week from the last exposure. These findings indicate that xenon is able to induce subcellular changes in rat adrenal cortex, mainly at the level of lipid structures. The transient changes induced by xenon suggest that this gas can be regarded as a safer anaesthetic.

Adrenal Cortex↗
PubMed2001

The X-ray structure of a recombinant major urinary protein at 1.75 A resolution. A comparative study of X-ray and NMR-derived structures.

Major urinary proteins belong to the lipocalin family and are present in the urine of rodents as an ensemble of isoforms with pheromonal activity. The crystal structure of a recombinant mouse MUP (rMUP) was solved by the molecular-replacement technique and refined to an R factor and R(free) of 20 and 26.5%, respectively, at 1.75 A resolution. The structure was compared with an NMR model and with a crystallographic structure of the wild-type form of the protein. The crystal structures determined in different space groups present significantly smaller conformational differences amongst themselves than in comparison with NMR models. Some, but not all, of the conformational differences between the crystal and solution structures can be explained by the influence of crystallographic contacts. Most of the differences between the NMR and X-ray structures were found in the N-terminus and loop regions. A number of side chains lining the hydrophobic pocket of the molecule are more tightly packed in the NMR structure than in the crystallographic model. Surprisingly, clear and continuous electron density for a ligand was observed inside the hydrophobic pocket of this recombinant protein. Conformation of the ligand modelled inside the density is coherent with the results of recent NMR experiments.

Amino Acid Sequence↗
PubMed2001

Sugar complexes with metal(2+) ions: thermodynamic parameters of associations of Ca(2+), Mg(2+) and Zn(2+) with galactaric acid.

A solution study on the complex ability of galactaric acid (GalaH(2)) for complexation with Ca(2+), Mg(2+) and Zn(2+) ions is reported. The stability constants of the complex species are determined by means of potentiometric measurements. From the dependence of stability constants on temperature, the DeltaH degrees and DeltaS degrees values are also determined. The formation of the complex species is an endothermic process and DeltaH degrees and DeltaS degrees values suggest a chelate coordination mode of galactaric acid involving carboxylic oxygen and alpha-hydroxylic group. The prevailing species at acidic or neutral pH is [MGala] (M=Ca(2+), Mg(2+), Zn(2+)) which is also isolated in the solid state and characterised by means of IR spectroscopy. On increasing pH, the [MGalaH(-1)](-) species is also formed, where the coordinated OH group undergoes deprotonation.

Calcium↗
PubMed2001

Determining the binding capability of the mouse major urinary proteins using 2-naphthol as a fluorescent probe.

The mouse major urinary proteins (MUPs) are an ensemble of isoforms secreted by adult male mice and involved in sexual olfactory communication. MUPs belong to the lipocalin superfamily, whose conserved structure is a beta-barrel made of eight antiparallel beta-strands forming a hydrophobic pocket that accommodates small organic molecules. A detailed knowledge of the molecular mechanism associated to the binding of those molecules can guide protein engineering to devise mutated proteins where the ligand specificity, binding affinity, and release rate can be modulated. Proteins with such peculiar properties may have interesting biotechnological applications for pest control, as well as in food and cosmetic industries. In this work, we demonstrate that the fluorescent molecule 2-naphthol binds to the natural ligand's binding site of MUPs with high affinity. In addition, we show that 2-naphthol binds to MUPs in its protonated form, that its fluorescence is blue-shifted, and the quantum yield is increased, thus confirming the high hydrophobicity of the protein pocket and the absence of proton acceptors inside the binding site. At large the results presented, besides demonstrating that the use of 2-naphthol provides a convenient and quick method for testing MUPs binding activity and to ascertain the quality of the protein preparation, suggest that MUPs can represent an interesting system for studying the photophysical characteristics of fluorescent molecules in a highly hydrophobic environment.

Animals↗
PubMed2001

Age-related changes of the adrenal secretory pattern: possible role in pathological brain aging.

The biosynthetic dissociation of the adrenocortical secretion occurring with age may have a pathogenetic role in the pathophysiology of brain aging. We studied cortisol and DHEAS secretion in healthy old and young subjects, in senile dementia, in major depression of elderly subjects and in healthy centenarians. A clear age-related decline of DHEAS secretion was well evident in healthy centenarians, and a further decrease in DHEAS concentration was found in old depressed patients and moreover in the demented ones, by comparison with age-matched controls. The circadian profile of serum cortisol was clearly flattened in old subjects, due to the selective increase in the cortisol nocturnal levels, particularly evident in demented subjects; on the other hand, the morning serum cortisol levels were not significantly different among centenarians, young and old controls. The molar ratio between cortisol and DHEAS showed a significant age-related increase; the occurrence of senile dementia and of major depression played an additive role, by comparison to physiological aging. The qualitative and quantitative modifications of the adrenocortical secretion occurring with aging seem mainly dependent on age itself, but the occurrence of pathological conditions may amplify these changes. Since cortisol and DHEAS play opposite effects on the central nervous system, the evaluation of the ratio between cortisol and DHEAS seems to be a good marker of the neuroendocrine features in old subjects.

Adrenal Glands↗
PubMed2001

Light panretinal photocoagulation (LPRP) versus classic panretinal photocoagulation (CPRP) in proliferative diabetic retinopathy.

PURPOSE: We misled to verify whether a panretinal photocoagulation (PRP) performed using low levels of ARGON laser energy (light PRP) has the same efficacy as a PRP performed in a conventional fashion using argon green wavelengths (classic PRP) in eyes with high-risk proliferative diabetic retinopathy (HRPDR). Furthermore, we misled to compare the session number performed and the side effects produced by the two techniques. METHODS: Sixty-five eyes with HRPDR of 50 consecutive patients were enrolled in a prospective randomized controlled trial. In eyes selected for light PRP, a very light biomicroscopic effect on the retina was obtained for each spot. In eyes assigned to classic PRP, each spot produced a white-yellow biomicroscopic effect. Mean follow-up was 22.4 months +/- 9.7 in the light PRP and 21.6 months +/- 9.3 in the classic PRP group (p = 0.727). RESULTS: The initial mean logMAR visual acuity (VA) in the light PRP group was 0.12 +/- 0.13 and in the classic PRP group 0.14 +/- 0.15 (p = 0.493). The final mean VA in the former was 0.18 +/- 0.25, and in the latter 0.27 +/- 0.30 (p = 0.231). Median power was 235mW (100-540mW) for light and 420mW (200-950mW) for classic PRP (p < 0.001). Regression of HRPDR at the end of the follow-up was obtained in 30/31 eyes (97%) treated with classic PRP and in 31/34 eyes (91%) treated with light PRP (p = 0.615). The total mean session number was 7.4 +/- 2.4 for light and 9.9 +/- 2.2 for the classic PRP group (p < 0.001). Complications were more frequent in the classic PRP group. CONCLUSIONS: The efficacy of Light PRP is similar to that of classic Light PRP in eyes with HRPDR. Light PRP is associated with fewer complications and allows the reduction of the number of treatment sessions.

Adult↗
PubMed2001

Correlation between Bacillus subtilis scoC phenotype and gene expression determined using microarrays for transcriptome analysis.

The availability of the complete sequence of the Bacillus subtilis chromosome (F. Kunst et al., Nature 390:249-256, 1997) makes possible the construction of genome-wide DNA arrays and the study of this organism on a global scale. Because we have a long-standing interest in the effects of scoC on late-stage developmental phenomena as they relate to aprE expression, we studied the genome-wide effects of a scoC null mutant with the goal of furthering the understanding of the role of scoC in growth and developmental processes. In the present work we compared the expression patterns of isogenic B. subtilis strains, one of which carries a null mutation in the scoC locus (scoC4). The results obtained indicate that scoC regulates, either directly or indirectly, the expression of at least 560 genes in the B. subtilis genome. ScoC appeared to repress as well as activate gene expression. Changes in expression were observed in genes encoding transport and binding proteins, those involved in amino acid, carbohydrate, and nucleotide and/or nucleoside metabolism, and those associated with motility, sporulation, and adaptation to atypical conditions. Changes in gene expression were also observed for transcriptional regulators, along with sigma factors, regulatory phosphatases and kinases, and members of sensor regulator systems. In this report, we discuss some of the phenotypes associated with the scoC mutant in light of the transcriptome changes observed.

Bacillus subtilis↗
PubMed2001

Neurotransmitter and hormonal background of hostility in anorexia nervosa.

Marked hostility toward relatives, therapists and friends is very frequently observed in anorexia nervosa (AN) as expression of outward-directed aggressiveness which interferes with the therapeutic programs of the patients. With the purpose to investigate this aspect of the disorder and its biological background, we studied in anorexics some neurotransmitter-hormonal secretions which are known to modulate aggressivity-hostility by measuring plasma concentrations of total (TT) and free testosterone (FT), total estrogens (TE), the TT/E and FT/TE ratios, and the serotonergic function by measuring basal prolactin (PRL) levels and responses to stimulation with the specific serotonin (5-HT)-releasing agent D-fenfluramine (D-Fen). In 13 women with AN, 5 of the restricted (AN-R) and 8 of the bingeing/purging type (AN-BP) in an active phase of the disease, and in 13 healthy controls matched for sex and age, we measured hostility by the SCL-90 scale (subscale items 11, 24, 63, 67, 74, 81). Basal TT, FT, TE, TT/TE, FT/TE, PRL values and PRL responses to D-Fen and to saline administration were measured radioimmunologically in AN patients and controls. Hostility was significantly higher in AN patients than in controls, TT, FT and TE concentrations were significantly lower in AN patients than in controls, TT/TE ratio was significantly higher in AN patients than in controls, and FT/TE ratio was not different in the two groups. In AN patients and controls, hostility correlated positively with TT and FT values. Basal PRL values and responses to D-Fen administration were significantly lower in anorexics than in controls, but they did not correlate with the degree of hostility in either patients or controls. In conclusion, hostility is higher than normal in anorexics, and its severity seems to be linked to the secretion of FT and not to the alterations in the 5-HT function.

Adolescent↗
PubMed2001

Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates.

The aim of this review was to examine the evidence for age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in both physiological and pathological aging, on the basis of the many data in the literature, as well as of our personal findings. A statistically significant circadian rhythmicity of serum cortisol was maintained in elderly subjects, even if with a reduced amplitude of the 24 h fluctuations and a trend to an increase of the serum levels in the evening and at night-time, in comparison with young controls. Furthermore, an age-related impairment of HPA sensitivity to steroid feedback was present in elderly people. The occurrence of senile dementia amplified the changes already present in physiological aging. While the cortisol secretion was generally well maintained in aging, the adrenal production of dehydroepiandrosterone and of its sulfate (DHEAS) exhibited an age-related decline. Therefore, the cortisol/DHEAS molar ratio was significantly higher in elderly subjects and even more in demented ones, than in young controls. Due to the opposite effects of cortisol and DHEAS on the brain and particularly on the hippocampal region, the imbalance between glucocorticoids and androgens occurring in physiological and even more in pathological aging, may have adverse effects on the function of this region, whose key role in learning and memory is well known.

Aging↗
PubMed2001

Botulinum toxin type a neuromuscular blockade in the treatment of equinus foot deformity in cerebral palsy: a multicenter, open-label clinical trial.

BACKGROUND: Focal spasticity of the gastrocnemius-soleus muscles causes equinus gait in children with cerebral palsy (CP). Botulinum toxin type A (BTX-A), a neuromuscular blocking agent, reduces muscle tone/overactivity in dystonia, stroke, and CP. OBJECTIVE: A prospective, open-label, multicenter clinical trial evaluated the long-term safety and efficacy of repeated intramuscular injections of BTX-A on equinus gait in CP children. METHODS: Nine centers enrolled 207 children. BTX-A injections (4 U/Kg) were given approximately every 3 months (maximum dose 200 U per treatment). Outcome measures included a Physician Rating Scale of gait, ankle range of motion measurements, and the incidence and profile of adverse events. RESULTS: One hundred fifty-five (75%) of 207 children completed at least 1 year with a total of 302 patient years of BTX-A treatment. The mean duration of BTX-A exposure was 1.46 years per patient. Dynamic gait pattern on the Physician Rating Scale improved in 46% of patients (86/185) at first follow-up. The response was maintained in 41% to 58% of patients for 2 years. Both gait pattern and ankle position improved at every visit. The most common treatment-related adverse events included increased stumbling, leg cramps, leg weakness, and calf atrophy in 1% to 11% of patients. No treatment-related serious adverse events were reported. Only 6% (7/117) of patients with pre- and postantibody samples had both detectable antibodies and a subsequent treatment failure. CONCLUSION: BTX-A proved both safe and effective in the chronic management of focal muscle spasticity in children with equinus gait.

Adolescent↗
PubMed2001

[The best in 2000 on thrombosis].

It is nearly impossible to follow and integrate all the new information in each subspeciality of cardiology. In the last months, important data has been published which may change clinical practice. In this domain, over half the cases of suspected coronary chest pain would only require a very short stay in a chest pain unit. The history, an accurate evaluation of symptoms, the application of Bayesian analysis, ECG interpretation and serum troponine measurement, associated with a degree of clinical experience, will allow orientation of the patient to a coronary care unit or hospital discharge (with possible out-patient referral). Patients with true unstable angina will no longer be treated by continuous intravenous injection of non-fractionated heparin because, in theory and in practice, this has been replaced with subcutaneous LMW heparin.... On the other hand, the electric syringe will continue to be required for the integration of the anti-GPIIB-IIIA for the treatment of unstable angina after the recommendations published concomitantly in the United States and Europe. This type of patient, especially with a "positive" troponine, will probably not be kept waiting long before referral to the catheter laboratory for coronary angiography and revascularisation. The long-term results of the FRISC II trial are confirmed by an even earlier invasive approach (Tactics-Timi 18) using anti-GPIIb-IIIa. In the first hours, and independently of other older prognostic factors, it will be possible to "predict or compare" the risk of coronary recurrence based on the results of certain biological "markers". In many centres, cases with ST elevation on the ECG could well be included in a phase III "medical protocol", associating a half-dose thrombolytic and an anti-GPIIb-IIIa. Finally, patients who will have been admitted to the chest pain unit with a suspected pulmonary embolism, for example because they had not been treated prophylactically with aspirin before hip surgery, will probably have the choice, after d-dimer measurement, between pulmonary scintigraphy and helicoidal CT scan. If the diagnosis of pulmonary embolism is confirmed, a single subcutaneous injection of LMW heparin could replace the conventional continuous intravenous injection of heparin. The earliest possible oral anticancer ... pardon me I anticoagulant treatment should be prescribed and explained.

Fibrinolytic Agents↗
PubMed2001

In vivo and in vitro percutaneous absorption of [(14)C]di-N-butylphthalate in rat.

This study evaluated the toxicokinetics of [(14)C]di-n-butylphthalate ([(14)C]DBP) after an intravenous administration (1 and 10 mg/kg, in Cremophor) or a topical application (10 microl/cm(2); 10 cm(2), neat) in haired male Sprague-Dawley rats. Additional in vivo and in vitro percutaneous penetration studies of [(14)C]DBP were conducted on male and female haired rats and male hairless rats. After intravenous administration, unchanged DBP disappeared rapidly from the plasma, following a two-exponential function (T1/2beta = 5-7 min). The peak levels of monobutylphthalate (MBP) and its glucuronide conjugate (MBP-Gluc) occurred 1 to 2 and 20 to 30 min after administration, respectively. These metabolites were intensively and rapidly excreted in urine (57% of the dose). However, about 35% of the dose recovered in urine was primarily excreted in bile (mainly as MBP-Gluc) and underwent hepatobiliary recycling. Unchanged DBP was barely detectable in excreta. DBP rapidly penetrated the skin, which constituted a reservoir. The absorption flux determined for 0.5 to 8 and 8 to 48 h of exposure were 43 and 156 microg/cm(2)/h, respectively. The higher flux may be due to radial diffusion of DBP in the stratum and/or epidermis. The in vivo and in vitro experiments revealed that DBP was intensively metabolized into the skin. In vivo percutaneous absorption flux was very similar in male and female haired rats. In contrast, the percutaneous absorption determined in vivo and in vitro was higher in hairless than in haired male rats. Absorption flux was accurately estimated from urinary excretion rate of MBP or MBP-Gluc.

Animals↗
PubMed2001

Toxicokinetics and metabolism of 1,2-diethylbenzene in male Sprague Dawley rats--part 2: evidence for in vitro and in vivo stereoselectivity of 1,2-diethylbenzene metabolism.

In a previous study, it was shown that the neurotoxic compound 1,2-diethylbenzene (1,2-DEB) is mainly hydroxylated in the alkyl chain to give 1-(2'-ethylphenyl)ethanol (1,2-EPE) and excreted in urine of rats as two glucuronide compounds (GA1 and GA2). Some findings have suggested that the two enantiomers of 1,2-EPE are formed in vivo. In the present study, a chiral high-performance liquid chromatography method was developed to separate the two enantiomers of 1,2-EPE from a synthesized racemic mixture. Absolute configuration of both enantiomers was determined after esterification with (R)-(+)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetic acid and analysis of their (1)H NMR spectra in CCl(4) added with Eu (fod)(3). The two main urinary metabolites, GA1 and GA2, from [(14)C]1,2-DEB-treated Sprague-Dawley rats (80 mg/kg, i.p.) were identified, after hydrolysis with beta-glucuronidase from Escherichia coli, as (R) and (S) glucuronide conjugates of 1,2-EPE, respectively. In vitro hydroxylation of 1,2-DEB and glucuroconjugation of 1,2-EPE were under stereoselective control in S9 fraction or microsomes from male Sprague-Dawley rat liver. The V(max) and K(m) constants for (R)1,2-EPE enantiomer formation determined in S9 fraction were greater than those for the (S) enantiomer. In the plasma of bile duct-cannulated rats, the ratio was 1.2 +/- 0.02 over the 1- to 4-h period after oral administration of [(14)C]1,2-DEB (100 mg/kg). In contrast, the glucuroconjugation rate of (S)1,2-DEB enantiomer was 4 times that of (R)1,2-EPE glucuroconjugation. A similar ratio of (R) to (S)1,2-EPE glucuronide conjugates was obtained in the plasma of bile duct-cannulated rats.

Animals↗
PubMed2001

[When is antivitamin K therapy indicated in the stable coronary patient?].

In the cardiac patient, there are clinical situations where antivitamin K is indicated more by the co-existing pathological associations or by a particular thrombogenic situation than by the cardiac disease itself. The presence of an embologenic abnormal rhythm, an apical thrombus or a large anterior akinesis are recognised as situations where antivitamin K must be discussed and, except for absolute contraindication, initiated. The studies undertaken for several decades are highly instructive and their contributions are considerable in the different questions which could be asked regarding the efficacy of antivitamin K. In particular they have the merit of signalling the correct directions to take and the errors to avoid. Concerning the evolution of cardiac disease, it must be admitted that the very good results of antivitamin K treatment alone at high dose are to be balanced against their haemorrhagic risk. The studies testing the association of low-dose aspirin with moderate-dose antivitamin K (INR 2 to 2.5) are to date very promising. The evaluation of the understanding of the treatment by patient education remains a major stage when initiating antivitamin K treatment in the cardiac patient.

4-Hydroxycoumarins↗
PubMed2001

[Duration of antivitamin K therapy in venous thromboembolic disease. Certainties and uncertainties].

The necessity of anticoagulant treatment after a pulmonary embolus or a deep venous thrombosis has been demonstrated. The modalities of this treatment have been well established, especially the usefulness of initial heparin therapy followed by a period of antivitamin K treatment with an "ideal target INR" between 2 and 3. One of the last questions in this therapeutic protocol is the duration of antivitamin K treatment. The choice of duration of treatment must be made on numerous criteria. It is necessary to distinguish the circumstances of the occurrence of the DVT or the PE and the context. It is thus possible for less than 3 months treatment in secondary venous thrombo-embolic disease, which occurs in precise, recognised circumstances for which the cause will have been controlled. Otherwise, in so-called idiopathic venous thrombo-embolic disease, which is distinguished by a higher prevalence of recurrences, it is known that long-term antivitamin K treatment is effective for the thrombo-embolic recurrences but at the price of a risk of haemorrhage. Finally thrombo-embolic recurrences also benefit from a long treatment. These circumstances of occurrence are thus important in order to decide the choice of treatment duration. But, in our opinion, the compliance to antivitamin K treatment remains the primary criterion to consider. The dilemma facing the prescriber is to evaluate the risk-benefit ratio of each patient, asking especially if the antivitamin K treatment surveillance of a particular patient will be done as well as in the randomised studies. For the future, long-term antivitamin K does not perhaps represent the only therapeutic option. The results of studies evaluating the durations of long-term treatment with less intense levels of anticoagulation (INR < 2) as well as therapeutic alternatives to antivitamin K (antiaggregants or other antithrombins) are awaited.

4-Hydroxycoumarins↗