Post-interventional arterial remodelling: from the clinic to the molecular bases. Proceedings of the 1st International Workshop, Naples, October 2002.
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Animals↗
Biomedical subjects
F Rossi
Publications and source records attributed to F Rossi.
Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors.
The mesostriatal dopaminergic system influences locomotor activity and the reinforcing properties of many drugs of abuse including nicotine. Here we investigate the role of the alpha4 nicotinic acetylcholine receptor (nAChR) subunit in mediating the effects of nicotine in the mesolimbic dopamine system in mice lacking the alpha4 subunit. We show that there are two distinct populations of receptors in the substantia nigra and striatum by using autoradiographic labelling with 125I alpha-conotoxin MII. These receptors are comprised of the alpha4, beta2 and alpha6 nAChR subunits and non-alpha4, beta2, and alpha6 nAChR subunits. Non-alpha4 subunit-containing nAChRs are located on dopaminergic neurons, are functional and respond to nicotine as demonstrated by patch clamp recordings. In vivo microdialysis performed in awake, freely moving mice reveal that mutant mice have basal striatal dopamine levels which are twice as high as those observed in wild-type mice. Despite the fact that both wild-type and alpha4 null mutant mice show a similar increase in dopamine release in response to intrastriatal KCl perfusion, a nicotine-elicited increase in dopamine levels is not observed in mutant mice. Locomotor activity experiments show that there is no difference between wild-type and mutant mice in basal activity in both habituated and non-habituated environments. Interestingly, mutant mice sustain an increase in cocaine-elicited locomotor activity longer than wild-type mice. In addition, mutant mice recover from depressant locomotor activity in response to nicotine at a faster rate. Our results indicate that alpha4-containing nAChRs exert a tonic control on striatal basal dopamine release, which is mediated by a heterogeneous population of nAChRs.
Animals↗
Unusual radiographic appearance of lung carcinoma in a cat.
A 15-year-old, female Siamese cat presented with multiple cavitary lung lesions on thoracic radiographs. This was confirmed histologically to be a well-differentiated bronchioloalveolar carcinoma. To the authors' knowledge, this radiographic pattern has not previously been reported in association with bronchioloalveolar carcinoma in cats.
Adenocarcinoma, Bronchiolo-Alveolar↗
Modification of patients' endogenous bacterial flora during hospitalization in a large teaching hospital in Naples.
The increasing attention addressed to methicillin-resistant staphylococci, vancomycin-resistant enterococci (VRE) and Extended Spectrum beta-Lactamases (ESbetaL)-producing enterobacteria is due to their etiologic role especially in nosocomial infections. In March 2001 we started an 8-month microbiological prospective surveillance of patients in the General Surgery, Orthopedic and Obstetric & Gynecology wards of the Azienda Universitaria Policlinico, 2nd University of Naples, Italy, to monitor the possible changes in endogenous flora during patients' hospital stay and the possible emergence of bacterial resistance. Data concerning antibiotic surgical prophylaxis (antimicrobial agent and duration) and length of hospitalization (pre- and post-surgery) were also collected. All patients underwent a microbiological screening by culturing nasal, pharyngeal and rectal swabs performed at admission and during hospitalization. Overall, 526 nasal swabs, 506 pharyngeal swabs and 482 rectal swabs were performed. Methicillin-resistant staphylococci were isolated from nasal swabs at admission in 2.1% of patients and in 7.5% of patients during hospitalization (day-14). VRE and ESbetaL-producing strains were isolated from rectal swabs in 1.9 and 4.7% of patients, respectively, with no change during hospital stay. Nasal and pharyngeal flora significantly changed after 7-14 days of hospitalization, Gram-negative microorganisms being isolated more frequently following hospitalization. The authors conclude that excessive hospital stay duration, along with the inappropriate duration of surgical antibiotic prophylaxis could be important causes of bacterial flora modification.
Adult↗
Antibacterial resistance of community-acquired respiratory tract pathogens recovered from patients in Latin America: results from the PROTEKT surveillance study (1999-2000).
PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms. Thirteen centers from Argentina, Brazil and Mexico participated during 1999-2000; they collected 1806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277). Overall, 218 (42.1%) of the S. pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3%) were penicillin-resistant and 79 (15.3%) were erythromycin-resistant. Mexico had the highest prevalence of penicillin (76.5%) and erythromycin (31.2%) resistance. Of 77 erythromycin-resistant S. pneumoniae tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1 possessed both erm(B) and mef(A) mechanism. All S. pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H. influenzae isolates, 88 (16.9%) produced beta-lactamase, ranging from 11% (Brazil) to 24.5% (Mexico). Among M. catarrhalis isolates, 138 (98.6%) produced beta-lactamase. Twenty-four (8.7%) of the S. pyogenes isolates were erythromycin-resistant; resistance being attributable to mefA (n=18), ermTR (n=5) and ermB (n=1). All H. influenzae, M. catarrhalis and S. pyogenes were fully susceptible to telithromycin. Methicillin resistance was found in 26.5% of the S. aureus isolates (Argentina 15%; Mexico 20%; Brazil 31.3%). Telithromycin was effective against 97.7% of methicillin-susceptible isolates. PROTEKT confirms that antibacterial resistance is an emerging problem in Latin America. The previously reported high levels of pneumococcal resistance to the beta-lactam and macrolides were exceeded. New agents that do not induce resistance or that exert low selective pressure, e.g. telithromycin, are essential to safeguard future antibacterial efficacy.
Anti-Bacterial Agents↗
S-adenosyl-L-methionine for treatment of depression, osteoarthritis, and liver disease.
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Cholestasis, Intrahepatic↗
Effects of docosahexaenoic acid on [Ca(2+)](i) increase induced by doxorubicin in ventricular rat cardiomyocytes.
The clinical use of doxorubicin (DXR) is limited by cardiotoxicity partially due to interference with intracellular Ca(2+) homeostasis and involving the activation of the sarcoplasmic reticulum (SR) Ca(2+) release channels. It is known that docosahexaenoic acid (DHA) is able to potentiate the sensitivity of cancer cells to DXR. The aim of our study was to further evaluate the effects of DHA on [Ca(2+)](i) overload induced by DXR in adult rat ventricular cardiomyocytes in order to verify if DHA interferes with DXR-induced cardiotoxicity too. [Ca(2+)](i) was measured by microfluorimetry. Our data demonstrated that 100 microM DXR induced a statistically significant [Ca(2+)](i)-increase in cardiomyocytes perfused with CaCl(2) Krebs solution (from 135.7 +/- 15 nM to 560.2 +/- 49 nM, n = 9, p < 0.01) and with Ca(2+)-free Krebs solution (from 89.3 +/- 15 nM to 551.1 +/- 35 nM, n = 9, p < 0.01). Treatment with 10 microM DHA for 20 min significantly suppressed DXR [Ca(2+)](i)- increase in cells perfused with CaCl(2) Krebs solution (142.3 +/- 12 nM, n = 9, p < 0.01) and in Ca(2+)-free procedures (100.4 +/- 12 nM, n = 9, p < 0.01). Caffeine 10 mM significantly increased [Ca(2+)](i) in cardiomyocytes perfused with CaCl(2) Krebs solution (from 135.7 +/- 15 nM to 979.2 +/- 17.8 nM, n = 9, p < 0.01) and with Ca(2+)-free Krebs solution (from 89.3 +/- 15 nM to 891.1 +/- 30 nM, n = 9, p < 0.01). Treatment with 10 microM DHA for 20 min suppressed caffeine [Ca(2+)](i)-increase in cardiomyocytes perfused with CaCl(2) Krebs solution (174.2 +/- 28 nM, n = 9, p < 0.01) and in Ca(2+)-free procedures (161.9 +/- 34 nM, n = 9, p < 0.01). In conclusion, our results suggest that DHA is able to prevent acute modifications of calcium homeostasis induced by DXR probably interfering with SR Ca(2+) release channels.
Animals↗
Effects of docosahexaenoic acid on calcium pathway in adult rat cardiomyocytes.
In this study we examined the effect of polyunsaturated fatty acids (PUFAs), in particular of docosahexaenoic acid (DHA), on calcium homeostasis in isolated adult rat cardiomyocytes exposed to KCl, ET-1 and anoxia. Free [Ca(2+)](i) in rat cardiomyocytes was 135.7 +/- 0.5 nM. Exposure to 50 mM KCl or 100 nM ET-1 resulted in a rise in free [Ca(2+)](i) in freshly isolated cells (465.4 +/- 15.6 nM and 311.3 +/- 12.6 nM, respectively) and in cultured cells (450.8 +/- 14.8 nM and 323.5 +/- 14.8 nM respectively). An acute treatment (20 minutes) with 10 microM DHA significantly reduced the KCl- and ET-1-induced [Ca(2+)](i) increase (300.9 +/- 18.1 nM and 232.08 +/- 11.8 nM, respectively). This reduction was greater after chronic treatment with DHA (72 h; 257.7 +/- 13.08 nM and 192.18 +/- 9.8 nM, respectively). Rat cardiomyocytes exposed to a 20 minute superfusion with anoxic solution, obtained by replacing O(2) with N(2) in gas mixture, showed a massive increase in cytosolic calcium (1200.2 +/- 50.2 nM). Longer exposure to anoxia induced hypercontraction and later death of rat cardiomyocytes. Preincubation with DHA reduced the anoxic effect on [Ca(2+)](i) (498.4 +/- 7.3 nM in acute and 200.2 +/- 12.2 nM in chronic treatment). In anoxic conditions 50 mM KCl and 100 nM ET-1 produced extreme and unmeasurable increases of [Ca(2+)](i.) Preincubation for 20 minutes with DHA reduced this phenomenon (856.1 +/- 20.3 nM and 782.3 +/- 7.6 nM, respectively). This reduction is more evident after a chronic treatment with DHA (257.7 +/- 10.6 nM and 232.2 +/- 12.5 nM, respectively). We conclude that in rat cardiomyocytes KCl, ET-1 and anoxia interfered with intracellular calcium concentrations by either modifying calcium levels or impairing calcium homeostasis. Acute, and especially chronic, DHA administration markedly reduced the damage induced by calcium overload in those cells.
Animals↗
Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1.
AIMS/HYPOTHESIS: This study aimed to evaluate the effects of hyperglycaemia on the evolution of myocardial infarction and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor 1alpha (HIF-1alpha) in the rat. METHODS: We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1 alpha gene expression. These parameters were also evaluated in isolated hearts of non-diabetic rat, in condition of high glucose concentration. RESULTS: In streptozotocin (STZ)-diabetic rats (in vivo study), myocardial infarct size was greater (p<0.01) in hyperglycaemic rats (22 mmol/l) than in normoglycaemic (7 mmol/l) or non-diabetic rats. In euglycaemic conditions, basal expression of HIF-1alpha mRNA was not appreciable, but increased steadily after ischaemia (762+/-86%, p<0.001); this response was blunted in hyperglycaemic STZ-rats (6.8+/-6% of the control, p<0.001) and improved in euglycaemic STZ-rats (58+/-10%). The changes in myocardial Rac1 mRNA expression paralleled those of HIF-1alpha. In isolated hearts from non-diabetic rats (in vitro study), perfusion with high glucose (33 mmol/l) produced an infarct size (58+/-2% of the area at risk) not different from that obtained in hyperglycaemic STZ-rats (57+/-2%). Similar changes in the expression of HIF-1alpha and Rac1, which were prevented by glutathione infusion (0.3 mmol/l) were also observed. CONCLUSION/INTERPRETATION: Both hyperglycaemia and high glucose concentrations increased basal HIF-1alpha and Rac1 expression, suggesting a state of pseudohypoxia. These findings show that myocardial infarct size in the rat is increased in hyperglycaemic conditions and is associated with a reduced expression of the HIF-1alpha gene. These changes are reversed, totally or partially, by normoglycaemia or glutathione suggesting a role for reactive oxygen species generation brought about by hyperglycaemia.
Animals↗
The aging heart and exercise training.
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Journal Article↗
Prevalence of beta-lactamase production in H. influenzae isolated in Latin America in 1998-1999: results of the LASER study.
The objective of this study was to assess the prevalence of beta-lactamase production in Haemophilus influenzae clinical isolates obtained throughout Latin America and the West Indies in 1998-1999. Isolates were collected from 15 centres (seven countries), identified by standard methods and grouped by patient age. The overall prevalence of beta-lactamase production was 17.8% (270/1513 isolates). The prevalence of beta-lactamase positive strains varied between countries, with the highest prevalence detected in Panama (23.4%, 29/124) and the lowest in the West Indies (10.5%, 4/38). beta-Lactamase-positive strains were more frequently isolated from children aged < or =3 years (22.0%) and from adults aged > or =65 years (26.5%). The high prevalence of beta-lactamase production found should be considered when choosing empirical antibiotic therapy where H. influenzae is suspected.
Adult↗
Surgical injury of rat arteries: genetic control of the remodelling process.
OBJECTIVES: Remodelling and restenosis are complex biological processes responsible for bypass and percutaneous transluminal coronary angioplasty failures which are likely to affect many hundreds of genes. We evaluated the effectiveness of topically applied antisense oligonucleotides in reducing the translation of the messenger RNA for the transcription factor c-myc and in reducing stenosis. METHODS: Surgery was performed under sterile conditions; 60 Wistar-Kyoto male rats were anaesthetized by ketamine. The carotid arteries were isolated through a median incision in the anterior neck region. At the same point, 0.5 mm longitudinal incisions were performed. Haemostasis was obtained by an adventitial 8.0 stitch. Thirty animals were given 150 microg of c-myc antisense oligonucleotide (Group A) while the other 30 animals received 150 microg of c-myc control sense oligonucleotide (Group B). Oligo molecules were locally applied through 100 microl of 20% pluronic gel. Rats were sacrificed at 30 days; carotid arteries were explanted and stained. Qualitative histological analysis was performed in all cases; serial sections were made every 25 micro in seven consecutive rats for each group. Morphometric analysis was also performed, luminal and medial area values recorded and the ratio between the two areas calculated. Data from each animal were compared with the corresponding contralateral carotid artery and expressed as mean+/-standard deviation. Statistical comparison between the two groups was carried out by one-way ANOVA text. RESULTS: Qualitative histological analysis showed marked remodelling with complete disarray of vessel wall, neointima accumulation and evidence of elastic fibres in the adventitia of all animals of Group B versus Group A. Morphometric analysis showed a significant reduction in the lumen area in Group A animals together with increased values of the medial area versus Group B animals. In addition, the ratio between the lumen and medial area was significantly higher in Group A than in Group B (2.61+/-0.18 versus 1.14+/-0.33, P<0.0001). CONCLUSIONS: c-myc antisense oligonucleotides applied intraoperatively can reduce post-operative stenosis.
Analysis of Variance↗
The involvement of sensory neuropeptides in airway hyper-responsiveness in rabbits sensitized and challenged to Parietaria judaica.
BACKGROUND: C-fibres have received considerable attention in the context of airway hyper-responsiveness (AHR), in fact several lines of evidence suggest that tachykinins might be involved in the pathogenesis of AHR. OBJECTIVE: The aim of this study was to investigate the role of capsaicin-sensitive sensory C-fibres and tachykinins in rabbits sensitized to the major allergen of Parietaria judaica pollen (Par j1). METHODS: Airway responsiveness was determined by exposing sensitized rabbits to cumulative concentrations of aerosolized histamine before and after an allergic challenge and after a pre-treatment with either vehicle or capsaicin or tachykinin receptor antagonists. Bronchoalveolar lavage was performed following histamine challenge and total and differential cell counts were performed. RESULTS: In sensitized rabbits, an AHR to inhaled histamine was observed 24 h after a Par j1 challenge. Capsaicin pre-treatment inhibited the AHR achieved 24 h following antigen exposure (P < 0.01). Pre-treatment with the tachykinin NK2 receptor antagonist, SR 48968, significantly reduced the antigen-induced AHR (P < 0.05), while pre-treatment with tachykinin NK1 (SR 140333) and NK3 (SR 142801) receptor antagonists did not significantly modify it. Bronchoalveolar lavage fluid obtained from vehicle and capsaicin-treated rabbits challenged with Par j1 exhibited no significant differences in total and differential cell counts. CONCLUSIONS: Parietaria judaica-induced AHR in immunized rabbits was shown to be inhibited by pre-treatment with capsaicin, an effect that is not related to an action on the associated pulmonary infiltration of eosinophils. The involvement of NK2 receptor stimulation in this phenomenon also suggests that NK2 receptor antagonists may be useful for investigating mechanisms of bronchopulmonary alterations in asthmatic patients.
Aerosols↗
Use of TLD in evaluating diagnostic reference levels for some radiological examinations.
The European Council Directive 97/43 introduces diagnostic reference levels (DRL) for all medical examinations involving ionising radiation. Each department has to evaluate patient dose and to compare that value with the DRL adopted by its member state. Italian law, applying the Directive, states that reference levels must be measured every 2 years. Quantities that must be measured are entrance surface dose or air kerma, or other dosimetric quantities. In our work, clinical measurements on patients were made by positioning a thermoluminescence dosemeter (TLD) over the skin of a statistically significant number of patients for each projection of each examination. As there is no national guideline for these measurements in Italy, the aim of this work was to establish a method based both on European publications and on clinical experience. Three different modalities were considered: conventional radiography, computed radiography and mammography. Accordingly, differently shaped types of TLD were required, especially for mammography where the beam energy is lower.
Automation↗
Transient post-traumatic hemidiaphragmatic paralysis in two cats.
A diagnosis of post-traumatic hemidiaphragmatic paralysis was made in two cats. Both cats had a history of trauma and paradoxical inward movement of the abdominal wall at inspiration. Thoracic radiographs were taken at inspiration and expiration. Although the images were suggestive of hemidiaphragmatic paralysis, definitive diagnosis was reached by fluoroscopy in one cat and by ultrasonography in the second. Both cases resolved spontaneously and diaphragmatic function was normal at follow-up.
Animals↗
Positive blood alcohol concentration and road accidents. A prospective study in an Italian emergency department.
STUDY OBJECTIVE: To examine if a positive blood alcohol concentration (BAC) at the time of crash (>or=0.50 g/l), independently of any clinical evidence and laboratory results indicating acute alcohol intoxication, is associated with specific features of patients involved, specific types of injury, and characteristics of the accident. METHODS: In this prospective cohort study, the BAC was measured in adult patients who had been injured and who were admitted to an Italian emergency department within four hours after a road accident. Altogether 2354 trauma patients were included between January to December 1998 out of 2856 eligible subjects. RESULTS: BAC exceeded 0.50 g/l in 425 subjects (18.1%), but was in a toxic range (>1.00 g/l) in only 179 subjects (7.6%). BAC positivity was significantly more common in men, in young subjects, in subjects driving cars or trucks, and in persons involved in a crash during night time and at weekends. It was associated with higher trauma severity, but no differences were found in injury body distribution according to vehicle type. In multivariate logistic regression analysis, the risk of a positive BAC in injured patients at the time of crash was independently associated with night time (odds ratio: 3.48; 95% confidence intervals: 2.46 to 4.91), male sex (3.08 (2.36 to 4.01)), weekend nights (1.21 (1.05 to 1.41)), and age (0.92 (0.86 to 0.99) per decades). CONCLUSION: In injured patients after a road accident, a BAC at the time of crash in a non-toxic range (>or=0.50 g/l) is associated with specific characteristics of crash, as well as increased risk of higher trauma severity. More careful monitoring is needed in young men during weekend nights for highest risk of BAC positivity after a road accident.
Accidents, Traffic↗
Oral contraceptives and venous thromboembolism: which are the safest preparations available?
Oral contraceptive therapy is associated with a fourfold increased risk of venous thromboembolism as compared with age-matched non-users. The composition of oral contraceptives has varied considerably during the past two to three decades. The estrogen content (ethinylestradiol) has decreased and is now less than 0.03 mg/pill. This was done on the assumption that estrogen was the main culprit for thrombotic complications. Subsequently it was found that the progestins contained in the pill could also play a thrombogenic role. This was particularly maintained to be so for the third-generations progestins, namely gestodene or desogestrel. These gonane progestins have been widely used since the early 1990s, because they appeared to have a lesser androgenic effect. A careful and impartial evaluation of the literature seems to indicate that third-generation progestins are associated with a slight increase in thrombotic risk. However, the significance of this difference remains to be proven. In fact, a relative risk of only two in retrospective studies may have limited effect and disappear in prospectives studies. The role of associated risk factors, both congenital and acquired, has been often overlooked in most of the papers dealing with the subject. This may be important. Preparations containing third-generation progestins are probably associated with a slight increase in thrombosis risk. It is the responsibility of the physician to select the preparation most suited for a given patient. As a general rule it may be safe to start with a preparation containing second-generation progestins. However there is no need for "a pill scare" and it does not seem justified to have women already taking pills containing third-generation progestins to switch to other preparations. If a woman taking preparations containing third-generation progestins experience symptoms, it is probably safe to advise that patient not to take any oral contraceptive pill in the future, regardless of the type. The same is true for women who experience symptoms while taking second-generation progestins preparations.
Contraceptives, Oral↗
Development of a website for clinical microbiology in Brazil.
The quality of Brazilian health services, including clinical microbiology laboratories, varies enormously. We established a Website to provide different professionals with up-to-date information and to create a virtual Brazilian microbiology community. The Website became operational in February 2000 and had 198,976 hits in the subsequent 20 months. There were 1031 user registrations in its virtual community. Different microbiology topics were discussed and three virtual training courses (representing about 300 printed pages of information) were given. The e-learning centre and the Brazilian virtual community created by this Website have facilitated distance learning, and have encouraged professional integration within Brazilian clinical microbiology.
Brazil↗