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Biomedical subjects

F Ferrari

Publications and source records attributed to F Ferrari.

At least 73 records · Page 4Linked to original sources

Role of IL-1 beta and corticosteroids in the regulation of the C/EBP-alpha, beta and delta genes in vivo.

We have examined the regulatory effects of interleukin 1 beta (IL-1 beta) on the activation of three different isoforms of the C/EBP family of transcription factors (alpha, beta and delta), in hepatocytes of normal and adrenalectomized (ADX) rats. C/EBP-beta and delta mRNA levels were enhanced by IL-1 beta, whereas that of C/EBP-alpha was not affected by treatment with this interleukin in both normal and adrenalectomized rats. The magnitude of the induction was strikingly higher for C/EBP delta in adrenalectomized animals, indicating a suppressive effect of corticosteroids in the IL-1 beta regulatory pathway. The pattern of C/EBP protein synthesis did not always reflect the mRNA findings. For C/EBP-alpha the protein synthesis was higher than expected in IL-1 beta treated ADX animals compared to normal rats. The pattern of C/EBP synthesis was the one that better reflected the pattern of the mRNA transcription. Differently, the induction of C/EBP-delta was not as pronounced as that of the corresponding mRNA in IL-1 beta treated ADX rats. Hormonal modulation of C/EBP transcription factors was studied in parallel with the hormonal induction of the Alpha-1-Acid Glycoprotein (AGP) gene, which is known to be highly induced in rat liver during the acute phase response. This short report also indicates an important role of corticosteroids in the regulation of transcription factors involved in IL-1 beta signalling during the acute phase response.

Adrenal Cortex Hormones↗

Sexual attraction and copulation in male rats: effects of the dopamine agonist SND 919.

Behavioral differences towards receptive females, involving latency to the first contact, amicable behavior, genital exploration, and copulatory pattern, were seen in sexually active (A), sluggish (S), and inactive (I) male rats classified on the basis of 11 consecutive mating tests. The D2 dopamine agonist SND 919 (1 mg/kg) was intraperitoneally administered to the three groups 25 min before a 12th test; the drug stimulated the copulatory behavior of A and S but not of I rats in which it diminished genital exploration and amicable behavior. In a 13th test, conducted 1 week later, 31% of I initiated mating, 16% of them reaching ejaculation. The stimulant effect of SND 919 on copulation in A rats was confirmed in further experiments where it was injected at 0.1 mg/kg, a dose selective for the D2 autoreceptors.

Animals↗

Influence of mucin type on polymer-mucin rheological interactions.

There are numerous in vitro methods with which to investigate the mucoadhesive properties of polymers. One recent method is based on the measurement of rheological interactions between polymer and mucin, which implies the use of mucins isolated from the mucous tissue. The extraction and purification of glycoprotein fraction, which is responsible for rheological interaction, can modify the native structure of mucin or spoil it with exogenous substances. Therefore the particulars of the mucin employed (origin, purification grade, the effect of further treatments such as freezing or freeze-drying) are likely to be critical for the interaction. The aim of this work was to compare some commercial mucins of differing origin and grade of purification for their rheological interaction with well-known mucoadhesive polymers (polyacrylic acid and sodium carboxymethylcellulose). For polyacrylic acid, which is sensitive to ions, we found rheological interaction to be strongly influenced by mucin type. The removal of ions, with dialysis, improved the interaction. For sodium carboxymethylcellulose, which is less sensitive to ions, rheological interaction proved to be less dependent on mucin type and improved upon glycoprotein solubilization.

Acrylic Resins↗

Behavioural assessment in rats of the antipsychotic potential of the potent dopamine D2 receptor antagonist, (-)eticlopride.

The effects of the selective D2 DA receptor antagonist, (-)eticlopride, a drug belonging to the benzamide class, were investigated on the D2 DA agonist SND 919- and CQP 201-403-induced stereotyped behaviour and on CQP 201-403-induced shaking, in rats, and on isolation-induced aggression, in mice. (-)Eticlopride was also tested over a wide dose range (5-1200 micrograms kg-1, s.c.) for sedative and cataleptic activity, in rats. For comparison, some experiments were performed with (-)sulpiride (10 and 40 mg kg-1, s.c.) The data obtained show that (-)eticlopride differs from (-)sulpiride and potentially modifies animal behaviour, whether spontaneous or induced; moreover, they suggest a potential clinical use for this neuroleptic in the management of psychotic states.

Aggression↗

Specificity of action of a herpes virus VP16/tetracycline-dependent trans-activator in mammalian cell cultures.

In this work, we have studied the activity of a tetracycline modulatable trans-activator (tTA) generated by fusing the DNA binding domain of the tetracycline repressor to the trans-activation domain of the Herpes simplex virus protein 16 (HSV VP16) (plasmid pUHD15-1Neo). In the three different cell lines studied (HTC, rat hepatoma; T47D, human breast cancer; SK-N-BE, human neuroblastoma), the expression of the luciferase gene under the control of a tetracycline operator sequence (plasmid pUHC13-3) was used as a control of the incorporation and the functionality of the trans-activator. Clones selected from these cells responded in a time and dose-dependent manner to the withdrawal of tetracycline. In all these clones, the tTA trans-activator not only modulates the activity of the luciferase gene, but also modulates the activity of a number of endogenous proteins, including C/EBP beta, the glucocorticoid receptor (GR), and SP1. In the transfected cells, the level of these transcription factors was strongly inhibited in the presence of tetracycline and was highly increased after tetracycline removal. Electrophoresis mobility shift assay (EMSA) and footprint experiments proved that the induced proteins are perfectly efficient in binding the DNA. Their transcriptional activity was also determined. In HTC/A9 cells, the level of the chloramphenicol acetyltransferase (CAT) expression driven by the promoter of the alpha 1-glycoprotein (AGP) gene was strongly enhanced at 72-84 hr following removal of tetracycline from the growth media. The accumulation of the endogenous AGP mRNA also increased at 84 hr. In the T47D/TA11 and SK-N-BE/C2.6 cells, a general activation of protein synthesis was also evidenced.

Animals↗

The Tübingen Glaucoma Study. Glaucoma filtering surgery--a retrospective long-term follow-up of 254 eyes with glaucoma.

A major focus of our study was the ability to predict the long-term success of filtering surgery. The results of glaucoma filtering surgery (trabeculectomy) as performed by the staff of the University Eye Hospital of Tübingen from 1988 through 1994 on 254 eyes of 214 patients are presented, with particular emphasis being placed not only on intraocular pressure (IOP) control but also the progression of glaucomatous damage (visual field loss or disc damage) and the etiology of visual acuity losses. There was an overall success rate of 64%. Rigid criteria for success included an IOP of less than 30 mmHg, no further visual field loss or disc damage, and no glaucomatous etiology for a decrease in visual acuity. A total of 35 eyes (13.8%) showed a loss of visual acuity after 6 months amounting to 2 or more Snellen lines, caused mainly by lens opacification, hypotony maculopathy, and "wipeout" (loss of the central visual field in the absence of another explanation). We found that there is a considerable risk for sudden loss of visual acuity after operation on older patients with small residual visual fields and severe hypotony on the 1st postoperative day. There was a 13% incidence of failure of blebs. A total of 34 eyes had an early IOP rise of more than 30 mmHg after surgery. A postoperative hypotony of less than 3 mmHg was more significantly seen in patients treated with 5-fluorouracil. Moreover, the results show that in some instances, a long-term use of topically applied glaucoma medication can adversely affect the results of fistulizing surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of synthetic and naturally occurring chalcones on ovarian cancer cell growth: structure-activity relationships.

This study was carried out to determine the effect of 15 different natural and synthetic chalcones on the proliferation of both established and primary ovarian cancer cells expressing type II oestrogen binding sites (type II EBS). The binding affinity of chalcones for type II EBS was also tested. At concentrations from 0.1 to 10 microM, chalcones inhibited ovarian cancer cell proliferation and [3H]oestradiol ([3H]E2) binding to type II EBS. Considering the structure-related variation in IC50 (concentration resulting in a 50% inhibition of cell growth) and Di50 (concentration resulting in a 50% displacement of [3H]E2 bound to type II EBS), it appeared that the presence of an alpha-beta double bond, the hydroxylation in 3 or 2 of ring B and the absence of a prenyl group were important to both the antiproliferative and binding activity. Structure-related variations in IC50 and Di50 were significantly concordant (Fisher's exact test: P = 0.0291), suggesting that there may be a type II EBS-mediated mechanism for chalcone antiproliferative activity. Our data indicate that chalcones could be considered as potential new anticancer drugs.

Binding Sites↗

[Identification of multivessel coronary disease using myocardial Thallium-201 and dipyridamole scintigraphy in acute myocardial infarction in the thrombolytic era].

Recently some Authors observed a low sensitivity of submaximal exercise thallium-201 myocardial scintigraphy for predicting multivessel coronary disease in patients with recent acute myocardial infarction (AMI) treated with thrombolytic therapy. The aim of our study was to evaluate the accuracy of dipyridamole thallium-201 single photon emission computerized tomography (DIP-SPECT) for predicting the location and the extent of coronary artery disease in patients with recent uncomplicated AMI and to compare the results obtained in patients treated with thrombolytic therapy (Group T) to those obtained in patients treated with non-thrombolytic therapy (Group NT). We examined 61 consecutive patients with recent uncomplicated AMI by predischarge DIP-SPECT as well as by coronary angiography. In the Group T the total number of reversible perfusion defects per patient was 2.6 +/- 1.9 of which 2.1 +/- 1.6 at infarct site and 0.5 +/- 0.7 in other coronary territories; similarly, in the Group NT the total number of reversible perfusion defects per patient was 2.5 +/- 1.6 (NS compared to Group T) of which 1.9 +/- 1.2 (NS compared to Group T) at infarct site and 0.5 +/- 0.8 (NS compared to Group T) in other coronary territories. In Group T, DIP-SPECT demonstrated a sensitivity of 84% with specificity of 60% for predicting critical (> or = 70%) stenoses at infarct site as well as a sensitivity of 54% with specificity of 54% in the other coronary territories (data are expressed in number of patients per cent). The sensitivity and specificity observed in Group NT did not differ significantly from those of Group T.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Angiography↗

The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat.

The selective D2 antagonist eticlopride, at a dose (0.01 mg/kg, s.c.) that fails to modify the normal behavior of rats, significantly reversed all the behavioral effects exerted by the selective D2 agonist SND 919 (0.1 mg/kg, i.p.), namely, the stimulation of stretching-yawning, penile erection and sedation and the inhibition of grooming. In the copulatory test, eticlopride at the same dose did not affect animal sexual behavior but potently counteracted the reduction in mount and intromission frequency and latency to ejaculation induced by SND 919 at 0.1 mg/kg, a behavioral pattern which might possibly be proposed as an animal model for human ejaculatio praecox.

Animals↗

Effect on rat feeding behavior of two selective D2 dopamine agonists.

B-HT 958 and SND 919, two selective agonists at D2 dopamine receptors, were examined for their influence on the feeding behavior of fasted rats. When food intake was determined in the rat's individual home cage, it was found to be reduced by both drugs at low sedative doses during the first hour after treatment and by SND 919 at the highest dose (which also elicits stereotypy) only 24 h later. However, SND 919 and B-HT 958 had no significant effect on feeding evaluated according to the X-maze and tube feeding tests. Analysis of the results, seen in the context of other behavioral signs produced by the drugs, suggests that data on feeding may vary depending on the experimental model used and can be modified by extraneous factors that interfere with a specific effect on food intake.

Adrenergic alpha-Agonists↗

A rare case of type I aortic dissection.

Aortic dissection is the most common acute disease of the aorta. It can occur in different clinical ways depending on the particular anatomical segments involved. The sudden appearance of claudicatio in the lower limbs may be indicative.

Adult↗

[Changes in the cell-mediated immune system in post-traumatic sepsis].

OBJECTIVE: We studied the alterations of cell-mediated immunity (CMI) in polytrauma patients and its relation with sepsis. DESIGN: a prospective study. SETTING: ICU, Ospedale Maggiore, Bologna (Italy). PATIENTS: We included in the study 42 patients with at least two of following criteria: 1) Trauma Score < or = 12; 2) Abbreviated Injury Score > or = 4; 3) Arterial Pressure on admission < or = 80 mmHg; 4) Injury Severity Score > or = 16. CMI examinations were carried out at three different post-traumatic times (T0-T2). Seventeen patients developed a sepsis within the first eight days from admission. RESULTS: Sepsis caused a temporary impairment in some lymphocyte subsets at T2. The patients who developed sepsis showed a significant subset percentage difference for CD3, CD3 activated (p < 0.05) and for interleukin-2 receptor (IL-2R) (p < 0.01) in comparison with the non septic group. At T2, the seven septic patients who died, showed a marked depression of IL-2 values (0.37 +/- 0.12 UI/ml) in comparison with the values of septic patients who survived (0.66 +/- 0.25 UI/ml; p < 0.01) and with the group of non septic patients (0.83 +/- 0.5 UI/ml; p < 0.001). Septic patients who had a IL-2 value of 0.45 or lower had a mortality of 75%. IL-2 values showed a specificity of 89% and a sensibility of 75% in predicting mortality in septic trauma patients. CONCLUSION: We believe that in polytrauma patients IL-2 values monitoring could be a reliable index of the disfunction of CMI and that IL-2R sieric levels could be a diagnostic marker of impending sepsis.

Adult↗

Predictive value of general movements in asphyxiated fullterm infants.

The developmental course of spontaneous motility was investigated in a group of 26 fullterm infants, affected by mild to severe hypoxic-ischaemic encephalopathy. Serial 1-h videorecordings were carried out from birth to 15-22 weeks and a quality assessment of general movements (GMs) was made from a replay of the videos. Neurological follow-up of the infants were continued until at least 18 months of age; neonatal EEG and neuro-imaging techniques (US-scan, CT or MRI) were also carried out in all cases. The results indicate that perinatal asphyxia has important effects on the spontaneous motility of fullterm infants. Hypokinesis occurred very frequently during the first days of life, followed by a transient or prolonged (lasting longer than 15-22 weeks) abnormal quality of GMs. In the first 2 weeks the results of GM assessment did not correlate with the simultaneous findings of neurological examination, neuro-imaging and EEG, whereas they did when the results at 15-22 weeks were considered. The changes in spontaneous motility and especially GM developmental trajectories were good predictors of the neurological outcome. The predictive value of GM assessment was found to be similar to that of EEG and neuro-imaging, and better than neurological examination.

Asphyxia Neonatorum↗

Influence of idazoxan on the dopamine D2 receptor agonist-induced behavioural effects in rats.

The behavioural effects in rats of the dopamine D2 receptor agonists, lisuride, B-HT 920 and SND 919, were variously influenced by pre-treatment with the selective alpha 2-adrenoceptor antagonist, idazoxan (2 mg/kg), depending on the nature of the effect in question and the doses of agonist employed. The influence of idazoxan on drug-induced stretching-yawning, penile erection, sedation, stereotyped behaviour, aggressiveness and mounting is described and tentatively interpreted in neurochemical terms, account being taken of the activity of respective alpha 2-adrenoceptor antagonist and dopamine receptor agonists used, at alpha 2-adrenoceptors and at different dopamine D2 receptor subtypes, pre- and postsynaptically located.

Adrenergic alpha-Antagonists↗

Progesterone induced expression of alkaline phosphatase is associated with a secretory phenotype in T47D breast cancer cells.

In our previous work we reported on stimulation of a tissue unspecific alkaline phosphatase (liver/bone/kidney, L/B/K) in the human breast cancer cell line T47D by progestins. Here we show that in these cells the synthetic progestin R5020 (Promegestone) induces transcription of a 2.7-kilobase ALP mRNA. In this cel line, maximal induction is reached after 24 hours, decreases to 50% after 72 hours and is sensitive to inhibitors of protein synthesis. The induction of ALP mRNA and enzyme activity is specific for R5020 and dexamethasone and is completely inhibited in the presence of 10(-7) M RU486. When treated with R5020 for 48 hours, T47D cells exhibit a substantially altered phenotype, lipid vacuoles accumulate all over the cytoplasm, conferring to the cells a secretory morphology. This phenotype is associated with increased ALP enzyme activity which is also maximal at 48 hours. This effect is progestin specific since other steroids do not lead to the same macroscopical changes.

Alkaline Phosphatase↗

In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCI.

Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and td of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and td between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t1/2 (7.12 h), while apparent t1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for Cmax and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p < 0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the 'Levy's plot' (per cent released versus per cent absorbed) approach and provided further support for the correlation found.

Adult↗

Biological monitoring of workers occupationally exposed to carbon disulphide in a rayon plant in Brazil: validity of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine samples taken in different times, during and after the real exposure period.

Fifteen workers from a rayon plant in Brazil were monitored. Air samples were taken during a mean period of 5.8 hours out of an 8 hour workshift, in three different adsorbing tubes. Five urine samples were taken at 4 hour interval from the beginning of the shift, and at the beginning of the next shift in which 2-thiothiazolidine-4-carboxylic acid (TTCA) concentration was analysed. Data from seventeen "individuals" were statistically studied, with the aim of establishing the best and the most practical sampling strategy of biological monitoring for workers occupationally exposed to CS2. For those chronically exposed to CS2, TWA air concentration lower than 30 and higher than 10 mg/m3, it was found that the higher the exposure levels, the lower was TTCA concentration in the end of shift urine samples. The results may be explained by dietary habits and/or by the small number of examined population or even eventual casualty. On the other hand they raise other hypothesis involving the chronicity of exposure which may lead to important changes in metabolism influencing the excretion rate of TTCA.

Air Pollutants, Occupational↗