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Biomedical subjects

M Pellegrini

Publications and source records attributed to M Pellegrini.

At least 19 recordsLinked to original sources
PubMed2006

Last Glacial mammals in South America: a new scenario from the Tarija Basin (Bolivia).

The chronology, sedimentary history, and paleoecology of the Tarija Basin (Bolivia), one of the richest Pleistocene mammalian sites in South America, are revised here based on a multidisciplinary study, including stratigraphy, sedimentology, geomorphology, paleontology, isotope geochemistry, and (14)C geochronology. Previous studies have indicated a Middle Pleistocene age for this classic locality. We have been able to obtain a series of (14)C dates encompassing all the fossil-bearing sequences previously studied in the Tarija Basin. The dated layers range in age from about 44,000 to 21,000 radiocarbon years before present (BP), indicating that the Tarija fauna is much younger than previously thought. Glacial advances correlated to marine isotopic stages (MIS) 4 and 2 (ca. 62 and 20 ka BP, respectively) are also documented at the base and at the very top of the Tarija-Padcaya succession, respectively, indicating that the Bolivian Altiplano was not dry but sustained an ice cap during the Last Glacial Maximum. The results of this multidisciplinary study enable us to redefine the chronological limits of the Tarija sequence and of its faunal assemblage and to shift this paleontological, paleoclimatological, and paleoecological framework to the time interval from MIS 4 to MIS 2.

Animals↗
PubMed2006

p66SHC promotes T cell apoptosis by inducing mitochondrial dysfunction and impaired Ca2+ homeostasis.

p66Shc, a redox enzyme that enhances reactive oxygen species (ROS) production by mitochondria, promotes T cell apoptosis. We have addressed the mechanisms regulating p66Shc-dependent apoptosis in T cells exposed to supraphysiological increases in [Ca2+]c. p66Shc expression resulted in profound mitochondrial dysfunction in response to the Ca2+ ionophore A23187, as revealed by dissipation of mitochondrial transmembrane potential, cytochrome c release and decreased ATP levels. p66Shc expression also caused a dramatic alteration in the cells' Ca2+-handling ability, which resulted in Ca2+ overload after A23187 treatment. The impairment in Ca2+ homeostasis was ROS dependent and caused by defective Ca2+ extrusion due at least in part to decreased plasma membrane ATPase (PMCA) expression. Both effects of p66Shc required Ca2+-dependent serine-36 phosphorylation. The mitochondrial effects of p66Shc were potentiated by but not strictly dependent on the rise in [Ca2+]c. Thus, Ca2+-dependent p66Shc phosphorylation causes both mitochondrial dysfunction and impaired Ca2+ homeostasis, which synergize in promoting T cell apoptosis.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Effects of intracellular pH and Ca2+ on the activity of stretch-sensitive cation channels in leech neurons.

The effects of intracellular pH and calcium on the activity of the leech mechanosensitive cation channels have been studied. These channels exhibited two activity modes denoted as spike-like (SL) and multiconductance (MC). In the absence of mechanical stimulation, acidification of the intracellular side of membrane patches from 7.2 to 6.2 reversibly increased the mean channel open time as well as the opening frequency in the SL mode. Channels in MC mode were activated by a pH(i) reduction from 7.2 to 6.2, but were inhibited at pH(i) 5.5. Unlike MC mode, SL mode was strongly activated by intracellular Ca(2+). Fura-2 imaging experiments showed that intracellular calcium was induced to increase by hypotonic cell swelling. The major component of this response did not require extracellular calcium. A component of the swelling-induced calcium response was sensitive to blockers of stretch-sensitive cation channels. The results indicate that the two activity modes of mechanosensitive channels of leech neurons respond differently to changes of intracellular pH and calcium. The sensitivity of the channel to micromolar concentrations of internal free calcium, along with its permeability to this ion, is consistent with a role in the amplification of mechanically induced Ca(2+) signals in leech neurons.

Action Potentials↗
PubMed2005

Is a long-term ranitidine-based triple therapy against Helicobacter pylori only a heritage of the past? A prospective, randomized clinicopharmacological study.

BACKGROUND: Acid suppression plus two antibiotics is currently considered the gold standard anti-Helicobacter pylori treatment, but the effective role of gastric antisecretory drugs is still poorly understood. AIMS: To compare a 14-day ranitidine-based triple regimen against Helicobacter pylori with one based on omeprazole, and to study the influence of antisecretory drugs on metronidazole pharmacokinetics in human plasma. METHODS: A total of 150 dyspeptic H. pylori-infected patients were randomized for ranitidine 300 mg b.d. (RCM group) or omeprazole 20 mg b.d. (OCM group) 14-day triple therapy, with clarithromycin 500 mg b.d. and metronidazole 500 mg b.d. On the eighth day of therapy, metronidazole pharmacokinetics was studied in plasma by high-performance liquid chromatography. The pharmacokinetic parameters (terminal half-life, area under the curve, peak-plasma level, peak time) of metronidazole were computed using standard non-compartmental methods. H. pylori status was monitored before and 4 weeks after the end of therapy by histology, serology and rapid urease test. RESULTS: On an intention-to-treat basis, eradication rates were 91 and 76% for the RCM and OCM groups respectively (P < 0.02). Significantly different pharmacokinetic parameters of metronidazole were found between the groups: peak-plasma level (P < 0.01) and area under the curve (P < 0.02). CONCLUSION: Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens.

Adolescent↗
PubMed2005

Application of a validated high-performance liquid chromatography-mass spectrometry assay to the analysis of m- and p-hydroxybenzoylecgonine in meconium.

A high-performance liquid chromatography (HPLC)-mass spectrometry (MS) assay, already validated for opiates and cocaine in meconium, has been re-applied for determination of m- and p-hydroxybenzoylecgonine, using nalorphine as the internal standard. Methodology included an initial extraction from the matrix by methanol and then a solid-phase extraction (SPE). A reversed-phase chromatography was used with a gradient of 1% acetic acid-acetonitrile coupled to atmospheric pressure ionization electrospray-mass spectrometry single ion monitoring mode. This method, validated in the range 0.005-1.00 microg analytes/g meconium, proved useful to identify and quantify these two metabolites in meconium samples, already tested for the presence of cocaine, benzoylecgonine and cocaethylene. A positivity of range of concentrations varied between 0.007 and 0.338 microg/g, confirming the importance of these two hydroxylated derivatives to monitor fetal exposure to cocaine.

Chromatography, High Pressure Liquid↗
PubMed2005

p66SHC: the apoptotic side of Shc proteins.

Initially identified as components of the signaling pathways triggered by receptor tyrosine kinases and leading to Ras activation, Shc proteins have been more recently implicated in the regulation of signals controlling not only cell proliferation, but also cell survival and apoptosis. Here we briefly review the current understanding of Shc proteins as promoters of apoptosis. Specifically, we focus on the 66 kDa isoform of ShcA, whose paramount importance in the regulation of oxidative stress responses leading to cell apoptosis and ageing has been by now firmly established.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Acute abdomen due to small bowel anisakiasis.

The popularity in Western countries of dishes based on raw fish has led to an increased incidence of anisakiasis, a human parasitic disease caused by the ingestion of live anisakid larvae. The entire digestive tract may be involved, but the stomach and the small intestine are the most frequently affected sites. We report a case of acute abdomen due to Anisakis simplex infection that caused small bowel obstruction.

Abdomen, Acute↗
PubMed2005

Prenatal exposure to arecoline (areca nut alkaloid) and birth outcomes.

The betel nut is commonly used as a drug by Asian populations. A high prevalence of adverse pregnancy outcomes has been reported in women who chewed betel quid during gestation. The hypothesis that chronic exposure of the fetus to arecoline (the principal alkaloid of the areca nut) is the cause was investigated in a clinical observational study on six newborns from Asian mothers who chewed betel nut during pregnancy.

Areca↗
PubMed2005

Respiratory insufficiency and limb muscle weakness in adults with Pompe's disease.

The objective of the present study was to prospectively evaluate relationships linking age, respiratory function and locomotor function in 29 outpatients with late-onset Pompe's disease and to retrospectively determine clinical outcomes. Using univariate regression analysis, vital capacity (VC) was weakly, but significantly, correlated to shoulder motility, Walton score and lower-limb Modified Medical Research Council score. Six patients were able to walk without a walking aid and with only the help of a handrail on the stairs (Walton score=3), although VC was <50%. No parameters were significantly correlated with age. As assessed retrospectively, VC and locomotion deteriorated over time in most patients. In contrast, among the 16 patients started on invasive or noninvasive ventilation with VC monitoring, eight had a VC increase at the first measurement time-point. The absence of correlation with age and the presence, in some patients, of severe respiratory insufficiency without severe limb girdle muscle weakness indicate that respiratory function should be monitored independently from the degree of peripheral muscle weakness. Mechanical ventilation and tracheostomy may improve vital capacity and should, therefore, be taken into account when evaluating treatments for the adult form of Pompe's disease.

Age Distribution↗
PubMed2004

HAIRVEQ: an external quality control scheme for drugs of abuse analysis in hair.

The Istituto Superiore di Sanità of Rome, Italy, in cooperation with Institut Municipal d'Investigaciò Mèdica of Barcelona, Spain, set up an external quality control program (HAIRVEQ) to evaluate reliability in hair testing for drug abuse by laboratories from the Italian National Health Service. Samples included in the program were real hair samples from drugs consumers. Prior to sending, hair samples were reduced to powdered form, mixed to ensure homogeneity and tested with GC/MS by four Reference Laboratories. Up to now, four different exercises have been concluded and 23 laboratories participated. Samples containing high and low concentrations of opiates, cocaine and metabolites, low concentrations of MDMA and two blank samples, were included in the intercomparison exercises performed in the first year of HAIRVEQ activities. Results show an insufficient performance of participating laboratories. About 82% of laboratories reported incorrect results on a qualitative basis (false positive and false negative results) for some of the submitted samples. More than one-half of laboratories reported quantitative results (60%). On the basis of the calculated z scores, only between 35 and 55% of results reported should be considered as satisfying. Guidelines have to be provided by Italian authorities for method validation as well as set of recommended cut-off concentrations to orientate laboratories in their quality objectives when developing analytical methodologies as tools to improve reliability and consequently performance of hair analysis.

Automobile Driving↗
PubMed2004

Preoperative pulmonary hemodynamics determines changes in airway and tissue mechanics following surgical repair of congenital heart diseases.

To characterize the effect of changes in pulmonary hemodynamics on airway and tissue mechanics, forced oscillatory input impedance of the respiratory system (Zrs) was measured between 0.4-12 Hz in two groups of children undergoing surgical repair of congenital heart disease (CHD) immediately before sternotomy and after chest closure during short apneic intervals. Children with lesions associated with high pulmonary blood flow and/or pressure (septal defects; HP group, n = 12) and children with hypoperfused lungs (tetralogy of Fallot; LP group, n = 12) were included in the study. Airway resistance (Raw), and coefficients of respiratory tissue damping (G) and elastance (H), were estimated from Zrs by model-fitting. A postoperative reduction in pulmonary blood flow and/or pressure in the HP group resulted in an immediate decrease in Raw of 29 +/- 9 (SE)% (P < 0.05), whereas children in the LP group had increases in Raw (24 +/- 17%, no significance) after surgery. No significant change was observed in G in either the HP (6.4 +/- 13%) or LP (27 +/- 23%) group, while H increased in children of both the HP (23 +/- 8%, P < 0.05) and LP (36 +/- 7%, P < 0.01) groups. These results suggest that the preoperative pulmonary hemodynamic condition determines changes in airway mechanics: surgical repair of CHD leads to an improvement in airway function only in children with congested lungs. The adverse effects of surgery, mechanical ventilation, and/or cardiopulmonary bypass may be responsible for the increased stiffness of the respiratory system observed in both groups of children.

Airway Resistance↗
PubMed2004

Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease.

The subthalamic nucleus (STN) has a key role in the pathophysiology of Parkinson's disease and is the primary target for high-frequency deep brain stimulation (DBS). The STN rest electrical activity in Parkinson's disease, however, is still unclear. Here we tested the hypothesis that pharmacological modulation of STN activity has rhythm-specific effects in the classical range of EEG frequencies, below 50 Hz. We recorded local field potentials (LFPs) through electrodes implanted in the STN of patients with Parkinson's disease (20 nuclei from 13 patients). After overnight withdrawal of antiparkinsonian therapy, LFPs were recorded at rest both before (off) and after (on) acute administration of different antiparkinsonian drugs: levodopa, apomorphine, or orphenadrine. In the off-state, STN LFPs showed clearly defined peaks of oscillatory activity below 50 Hz: at low frequencies (2-7 Hz), in the alpha (7-13 Hz), low-beta (13-20 Hz), and high-beta range (20-30 Hz). In the on-state after levodopa and apomorphine administration, low-beta activity significantly decreased and low-frequency activity increased. In contrast, orphenadrine increased beta activity. Power changes elicited by levodopa and apomorphine at low frequencies and in the beta range were not correlated, whereas changes in the alpha band, which were globally not significant, correlated with the beta rhythm (namely, low beta: 13-20 Hz). In conclusion, in the human STN, there are at least two rhythms below 50 Hz that are separately modulated by antiparkinsonian medication: one at low frequencies and one in the beta range. Multiple rhythms are consistent with the hypothesis of multiple oscillating systems, each possibly correlating with specific aspects of human STN function and dysfunction.

Action Potentials↗
PubMed2003

Development and validation of a liquid chromatography-mass spectrometry assay for the determination of opiates and cocaine in meconium.

A procedure based on liquid chromatography-mass spectrometry (LC-MS) is described for determination of 6-monoacetylmorphine, morphine, morphine-3-glucuronide, morphine-6-glucuronide, codeine, cocaine, benzoylecgonine and cocaethylene in meconium using nalorfine as the internal standard. The analytes are initially extracted from the matrix by methanol (6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or 0.01 M ammonium hydrogen carbonate buffer (morphine-3-glucuronide, morphine-6-glucuronide). Subsequently a solid-phase extraction with Bondelut Certify columns (6-monoacetylmorphine, morphine, codeine, cocaine, benzoylecgonine and cocaethylene) or ethyl solid-phase extraction columns (morphine-3-glucuronide, morphine-6-glucuronide) was applied. Chromatography was performed on a C(8) reversed-phase column using a gradient of acetic acid 1%-acetonitrile as a mobile phase. Analytes were determined in LC-MS single ion monitoring mode with atmospheric pressure ionisation-electrospray (ESI) interface. The method was validated in the range 0.005-1.00 microg/g using 1 g of meconium per assay and applied to analysis of meconium in newborns to assess fetal exposure to opiates and cocaine.

Calibration↗
PubMed2003

A novel biweekly pancreatic cancer treatment schedule with gemcitabine, 5-fluorouracil and folinic acid.

Pancreatic adenocarcinoma is a common disease considered to be poorly responsive to antiblastic treatment. Recent clinical and preclinical results suggest that a combined treatment of gemcitabine (GEM), 5-flurouracil (5-FU) and folinic acid (FA) offers a clinical benefit in patients with advanced pancreas adenocarcinoma. The aim of this phase II clinical trial was to evaluate the antitumour activity and toxicity of a novel biweekly schedule of this combination in patients with pancreatic adenocarcinoma. A total of 42 patients received a 30 min infusion of FA (100 mg m(-2)) and 5-FU (400 mg m(-2)) (FUFA) on days 1-3, and GEM 1000 mg m(-2) on day 1 every 15 days. We observed 13 objective responses (two complete, 11 partial) and 23 stable diseases. The median time to progression was 9.75 months (95% Confidence Interval (CI), 6.88-12.62) and the median overall survival was 13.10 months (95% CI 9.64-16.56). There were seven cases of each grade III gastroenteric and haematological toxicity. The GEM plus FUFA combination appears to be well tolerated and very active in patients with pancreatic carcinoma.

Adenocarcinoma↗
PubMed2003

In vivo study of the GC90/IRIV vaccine for immune response and autoimmunity into a novel humanised transgenic mouse.

Parathyroid hormone-related protein (PTH-rP), a secreted protein produced by prostate carcinoma and other epithelial cancers, is considered a key agent for the development of bone metastases. We investigated the construct GC90/IRIV, composed of immunopotentiating reconstituted influenza virosomes (IRIV) containing PTH-rP gene plasmids (GC90), as a potential tool for human anticancer immunotherapy into humanised mice transgenic for HLA-A(*)02.01, the human-beta2 microglobulin, and the human CD8alpha molecule. Intranasal administration of GC90/IRIV resulted in the induction of a PTH-rP-specific multiepitope cytotoxic T-cell (CTL) response. Cytotoxic T cells derived from vaccinated mice were capable of lysing in vitro syngenic murine PTH-rP transfectants and human HLA-A((*))02.01(+)/PTH-rP(+) prostate carcinoma LNCaP cells as well. The immune response capacity and the absence of any sign of toxicity and/or autoimmunity in vivo suggest the GC90/IRIV vaccine as a valid tool for active specific immunotherapy of human cancers and metastases overexpressing PTH-rP.

Animals↗