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Biomedical subjects

P Magni

Publications and source records attributed to P Magni.

At least 19 recordsLinked to original sources
PubMed2002

Cobalamin (vitamin B(12)) positively regulates interleukin-6 levels in rat cerebrospinal fluid.

We have previously demonstrated that the repeated intracerebroventricular (i.c.v.) microinjection of interleukin-6 (IL-6) prevented the myelinolytic lesions of cobalamin-deficient (Cbl-D) central neuropathy [or subacute combined degeneration (SCD)] in totally gastrectomized (TGX) rats. We therefore hypothesized that cobalamin (Cbl) may actually regulate IL-6 levels in rat cerebrospinal fluid (CSF). We measured IL-6 levels in the CSF of rats made Cbl-D by means of total gastrectomy (TG) or chronic feeding with a Cbl-D diet and killed at different times from the beginning of the experiment, and found that IL-6 levels significantly and progressively decreased over time. Chronic 2-month Cbl administration started 1 week after surgery prevented the decrease in IL-6 levels and, when it was started 2 months after surgery, it significantly increased IL-6 levels, but not to presurgical values. We also investigated whether IL-6 decrease might be ultimately due to the Cbl-deficiency-linked decrease in epidermal growth factor (EGF) synthesis. Repeated i.c.v. administrations of EGF to TGX rats did not modify CSF IL-6 levels. These results, together with those of a previous study showing the preventive effect of IL-6 treatment on SCD lesions, demonstrate that: (i) Cbl selectively regulates CSF IL-6 levels; and (ii) decreased IL-6 availability plays a role in the pathogenesis of the experimental SCD, in which no evidence of inflammatory and/or immunological reaction has been observed.

Animals↗
PubMed2002

Nonparametric AUC estimation in population studies with incomplete sampling: a Bayesian approach.

The estimation of the AUC in a population without frequent and/or fixed individual samplings is of interest because the number of plasma samples can often be limited due to technical, ethical and cost reasons. Non-linear mixed effect models can provide both population and individual estimates of AUC based on sparse sampling protocols; however, appropriate structural models for the description of the pharmacokinetics are required. Nonparametric solutions have also been proposed to estimate the population AUC and the associated error when particular sampling protocols are adopted. However, they do not estimate the individual AUCs and lack flexibility. Also a semiparametric method has been proposed for addressing the problem of sparse sampling in reasonably well designed studies. In this work, we propose and evaluate a nonparametric Bayesian scheme for AUC estimation in population studies with arbitrary sampling protocols. In the stochastic model representing the whole population, the individual plasma concentration curves and the "mean" population curve are described by random walk processes, allowing the application of the method to the reconstruction of any kind of "regular" curves. Population and individual AUC estimation are performed by numerically computing the posterior expectation through a Markov chain Monte Carlo algorithm.

Algorithms↗
PubMed2001

Compartmental model identification based on an empirical Bayesian approach: the case of thiamine kinetics in rats.

Compartmental models are a very popular tool for the analysis of experiments in living systems. There are three main aspects that have to be taken into account: the degree of detail of the model, its a priori identifiability and the a posteriori (numerical) identifiability. In some cases, where standard approaches are adopted, the models can be either a priori or a posteriori unidentifiable. The paper proposes model identification within a Bayesian framework, to solve a posteriori unidentifiability problems. In particular, a stochastic simulation algorithm is proposed to perform a Bayesian identification of compartmental models, and an empirical Bayesian technique is proposed to propagate information among multiple experiments. The power of this methodology was demonstrated by evaluating the kinetics of thiamine under several experimental conditions. The complexity of the existing model (nine parameters) and limited experimental data (8/12 for each model) caused a posteriori identifiability problems when standard approaches were adopted. The application of the methodology identifies all 28 models (four tissues under seven different conditions).

Animals↗
PubMed2001

Control of the expression of human neuropeptide Y by leptin: in vitro studies.

Neuropeptide Y (NPY) participates in the regulation of reproduction and food intake. The adipose-secreted hormone, leptin, has also been involved in these processes, and has been shown to exert its effects in part by controlling NPY synthesis and release at the hypothalamic level. In the present study, we utilized the SH-SY5Y human neuroblastoma cell line, to study the leptin-NPY interrelationships. SH-SY5Y cells were found to express leptin receptors (RT-PCR and Western blot analyses). A 24-h treatment with leptin at different concentrations did not affect NPY gene expression, but resulted in a stimulation of NPY release. This stimulated secretion was blocked by the combined treatment with leptin and the muscarinic agonist carbachol or the phorbol ester TPA. Leptin and carbachol also caused an increased intracellular content of NPY. In conclusion, the SH-SY5Y human neuroblastoma cell line appears to be a suitable in vitro model for studying the pharmacological effects of leptin on the biosynthesis and secretion of NPY.

Blotting, Northern↗
PubMed2001

Expression of neuropeptide Y receptors in human prostate cancer cells.

BACKGROUND: Neuroendocrine molecules are now believed to play a significant role in the progression of human prostate cancer (CaP), especially in the androgen-independent stage. MATERIALS AND METHODS: In the present study, we evaluated the presence and the function of the receptors for neuropeptide Y (NPY) in human CaP cell lines (the androgen-dependent LNCaP, and the androgen-independent DU 145 and PC-3). RESULTS: The presence of high-affinity binding sites for NPY was shown on PC-3 cells (radioreceptor assay). Reverse transcription-polymerase chain reaction analysis indicated that these sites correspond to the Y1 and Y2 receptor isoforms. A Y1 receptor protein (70 kDa) was also detected in PC-3 cell extracts by Western blot analysis. The activation of these receptors by NPY resulted in a reduction of forskolin-induced cAMP accumulation and an increase of [Ca2+]i. Moreover, a prolonged treatment with NPY induced a dose-related proliferation of PC-3 cells. CONCLUSIONS: By showing that NPY receptors are expressed in the androgen-independent cell line PC-3 and that their activation results in cell proliferation, the present date suggest that NPY-related mechanisms might be relevant in certain stages of CaP, such as the progression of the disease during the androgen-independent stage.

Androgens↗
PubMed2001

Improving dialysis services through information technology: from telemedicine to data mining.

This paper discusses the issues related to use of Information Technology (IT) solutions in dialysis, and describes the implementation of some of them in a medium size dialysis center. First, starting from the analysis of the organization of public-health nephrology services, the potential role of IT is highlighted. Second, the main directions for IT exploitation in dialysis, namely telemedicine and automated monitoring of dialysis sessions are discussed. Third, the on-field implementation of these services is described, together with some preliminary results. The work here presented shows how IT may improve dialysis services by ameliorating quality and reducing costs.

Ambulatory Care Facilities↗
PubMed2000

Leptin: a possible link between food intake, energy expenditure, and reproductive function.

Several regulatory substances participate in the regulation of both food intake/energy metabolism and reproduction in mammals. Most of these neuropeptides originate and act in the central nervous system, mainly at specific hypothalamic areas. Leptin represents a signal integrating all these functions, but originating from the periphery (adipose tissue) and carrying information mainly to central structures. Observations in rodent models of leptin deficiency have suggested that leptin participates in the control of reproduction, in conjunction with that of food intake and energy expenditure. Indeed, leptin administration resulted in the restoration of normal body weight, food intake, and fertility in the ob mouse, lacking circulating leptin. Specific targets of leptin in the hypothalamus are neurons expressing neuropeptide Y, proopiomelanocortin and gonadotropin-releasing hormone, but the presence of leptin receptors in peripheral reproductive structures suggests that leptin might also act at these sites. Human obesity is often associated with reproductive disturbances. The situation in humans is more complex than in the animal models of leptin deficit and the presence of leptin resistance in these subjects is suggested. In conclusion, leptin fits many requirements for a molecule linking the regulation of energy balance and the control of reproduction.

Animals↗
PubMed2000

Retinoic acid negatively regulates neuropeptide Y expression in human neuroblastoma cells.

Retinoids are involved in the regulation of development and differentiation in many tissues, including the nervous system, where they have been associated with some neurotransmitter systems. In the present study, we evaluated the effects of all-trans retinoic acid (RA) on the biosynthesis and secretion of neuropeptide Y (NPY), a widely expressed neuroregulatory peptide. The SH-SY5Y human neuroblastoma cell line has been used as the in vitro model system. Treatment with 10 microM RA induced a marked decrease in NPY gene expression after as little as 3-6 h of incubation and resulted in its almost complete suppression at 12-24 h and after a 6-day differentiating treatment. The NPY content in cell extracts and the NPY secreted and accumulated in the culture medium were also reduced by exposure to 10 microM RA at 12 and 24 h and at 6 days. Moreover, RA treatment for 6 days, but not for 24 h, resulted in a marked stimulation of proNPY processing to mature NPY. The presence of negative retinoic acid-response elements in the human NPY promoter (up to -1078 bp) was excluded by a computer search. When SH-SY5Y cells were treated simultaneously with 20 nM TPA and 10 microM RA for 24 h, the marked stimulatory effect of TPA alone was completely suppressed. These observations suggest that the expression of NPY in SH-SY5Y human neuroblastoma cells is negatively regulated by RA at the level of gene expression, probably by mechanisms involving the interaction of activated RARs with transcription factors (such as AP-1).

Blotting, Northern↗
PubMed2000

Intelligent analysis of clinical time series: an application in the diabetes mellitus domain.

This paper describes the application of a method for the intelligent analysis of clinical time series in the diabetes mellitus domain. Such a method is based on temporal abstractions and relies on the following steps: (i) 'pre-processing' of raw data through the application of suitable filtering techniques: (ii) 'extraction' from the pre-processed data of a set of abstract episodes (temporal abstractions); and (iii) 'post-processing' of temporal abstractions; the post-processing phase results in a new set of features that embeds high level information on the patient dynamics. The derived features set is used to obtain new knowledge through the application of machine learning algorithms. The paper describes in detail the application of this methodology and presents some results obtained on simulated data and on a data-set of four diabetic patients monitored for > 1 year.

Artificial Intelligence↗
PubMed2000

Deciding when to intervene: a Markov decision process approach.

The aim of this paper is to point out the difference between static and dynamic approaches to choosing the optimal time for intervention. The paper demonstrates that classical approaches, such as decision trees and influence diagrams, hardly cope with dynamic problems: they cannot simulate all the real-world strategies and consequently can only calculate suboptimal solutions. A dynamic formalism based on Markov decision processes (MPPs) is then proposed and applied to a medical problem: the prophylactic surgery in mild hereditary spherocytosis. The paper compares the proposed approach with a static approach on the same medical problem. The policy provided by the dynamic approach achieved significant gain over the static policy by delaying the intervention time in some categories of patients. The calculations are carried out with DT-Planner, a graphical decision aid specifically built for dealing with dynamic decision processes.

Cholecystectomy↗
PubMed2000

Bayesian analysis of blood glucose time series from diabetes home monitoring.

This paper describes the application of a novel Bayesian estimation technique to extract the structural components, i.e., trend and daily patterns, from blood glucose level time series coming from home monitoring of insulin dependent diabetes mellitus patients. The problem is formulated through a set of stochastic equations, and is solved in a Bayesian framework by using a Markov chain Monte Carlo technique. The potential of the method is illustrated by analyzing data coming from the home monitoring of a 14-year old male patient.

Adolescent↗
PubMed2000

Bayesian identification of a population compartmental model of C-peptide kinetics.

When models are used to measure or predict physiological variables and parameters in a given individual, the experiments needed are often complex and costly. A valuable solution for improving their cost effectiveness is represented by population models. A widely used population model in insulin secretion studies is the one proposed by Van Cauter et al. (Diabetes 41:368-377, 1992), which determines the parameters of the two compartment model of C-peptide kinetics in a given individual from the knowledge of his/her age, sex, body surface area, and health condition (i.e., normal, obese, diabetic). This population model was identified from the data of a large training set (more than 200 subjects) via a deterministic approach. This approach, while sound in terms of providing a point estimate of C-peptide kinetic parameters in a given individual, does not provide a measure of their precision. In this paper, by employing the same training set of Van Cauter et al., we show that the identification of the population model into a Bayesian framework (by using Markov chain Monte Carlo) allows, at the individual level, the estimation of point values of the C-peptide kinetic parameters together with their precision. A successful application of the methodology is illustrated in the estimation of C-peptide kinetic parameters of seven subjects (not belonging to the training set used for the identification of the population model) for which reference values were available thanks to an independent identification experiment.

Adult↗
PubMed1999

Expression of a leptin receptor in immortalized gonadotropin-releasing hormone-secreting neurons.

Leptin is secreted by adipocytes and regulates food intake and energy balance through the activation of specific receptors (OB-R). Recent evidence suggests that it is also involved in the control of reproductive processes, by possibly acting on central and peripheral targets. In particular, it has been shown that leptin may indirectly stimulate GnRH release from hypothalamic fragments by acting on interneurons impinging on GnRH-secreting neurons. The possibility that leptin might additionally modulate the activity of GnRH-secreting neurons in a direct way has been addressed in the present study, by using the immortalized GnRH-secreting cell line GT1-7. The presence of OB-R messenger RNA (mRNA) (long form) was detected by RT-PCR analysis of total RNA from GT1-7 cells. An OB-R protein is also expressed in these cells, as shown by immunocytochemistry and by Western blot analysis. The latter has revealed the presence of a single immunoreactive OB-R with an approximate size of 130 kDa. To study the functionality of these receptors, the effect of leptin treatment on GnRH secretion and gene expression in GT1-7 cells were evaluated. Under static conditions, GnRH release was stimulated by exposure to low concentrations of leptin (10(-12) M after 30 min; 10(-10) M after 60 min). The 10(-12) M dose was selected for studying the effect of leptin on GnRH secretion under dynamic conditions. To this purpose, GT1-7 cells were placed in a perifusion system; treatment with leptin (10(-12) M) for 60 min stimulated GnRH release with no changes of pulse frequency. On the contrary, exposure to leptin (10(-12)-10(-10) M) for 1, 3, 6, and 24 h did not affect GnRH gene expression in GT1-7 cells. The present results indicate that GT1-7 cells possess OB-Rs and that leptin may directly affect their function. Taken together with the available reports, these findings suggest that leptin might participate in the regulation of reproductive processes by acting at multiple levels, both centrally and peripherally.

Animals↗
PubMed1998

Cholinergic muscarinic mechanisms regulate neuropeptide Y gene expression via protein kinase C in human neuroblastoma cells.

Neuropeptide Y (NPY) participates in the control of several functions in the nervous system. NPYergic neurons present in brain areas involved in cognitive processes are linked to ascending projections of the cholinergic system, a finding that suggests a role for acetylcholine in the control of these cells. In the present study, the effect of the activation of cholinergic muscarinic receptors on the expression of the human NPY gene was assessed. The SH-SY5Y neuroblastoma cell line was used as an in vitro model of human neurons; NPY mRNA levels were evaluated by Northern blot analysis. The results indicate that: (a) the expression of the human NPY gene in SH-SY5Y cells is stimulated by the cholinergic muscarinic agonist, carbachol; (b) this effect is mediated by the M3 muscarinic receptor subtype, as indicated by the inhibitory effect of the M3 antagonist 4-DAMP; (c) protein kinase C (PKC) activation plays an important role in the induction of NPY gene expression in this system, as suggested by experiments with the PKC activator, TPA, and the PKC inhibitor, GF 109203X; (d) the stimulation of NPY mRNA levels by TPA and by carbachol in SH-SY5Y cells requires de novo synthesis of RNA and protein. In conclusion, the present study shows that the activation of PKC-coupled muscarinic receptors as the M3 subtype positively modulates the expression of the human NPY gene in SH-SY5Y neuroblastoma cells, via PKC-related mechanisms.

Carbachol↗
PubMed1998

Presence of 5alpha-reductase isozymes and aromatase in human prostate cancer cells and in benign prostate hyperplastic tissue.

BACKGROUND: Prostate trophism depends on DHT formed from T by the enzyme 5alpha-R. Two 5alpha-R isoforms with different biochemical characteristics have been cloned. Also estrogens might contribute to the prostate growth; however, their intraglandular formation by the enzyme aromatase is still debated. The aim of the present study was to verify whether (a) only one or both isoforms of the 5alpha-Rs are expressed in the prostate cancer cell line LNCaP and in BPH, or (b) the aromatase is present in these samples. METHODS: The profile of the pH optimum of the 5alpha-Rs was evaluated "in vitro" in LNCaP cells by the production of labeled 5alpha-reduced metabolites either from [14C]-T or [14C]-D4 at pH 3.5-8. The gene expression of the two 5alpha-Rs and of the aromatase in LNCaP cells and in BPH specimens was analyzed by RT-PCR combined to Southern blot analysis, using specific sets of oligonucleotides. The tissue localization of 5alpha-R1 was analyzed by immunohistochemistry using an anti-5alpha-R1 polyclonal antibody. RESULTS: (a) In LNCaP cells, the formation of 5alpha-reduced metabolites from the respective precursors increases progressively as a function of pH, being the highest at neutral pH values; (b) the 5alpha-R1 isoform is expressed in both LNCaP cells and in BPH, while the 5alpha-R2 mRNA is present only in BPH, but not in LNCaP cells; and (c) no aromatase transcripts were observed either in BPH or in LNCaP cells. CONCLUSIONS: A careful examination of the possible differential expression of T-activating enzymes, particularly in prostate cancer, would be of help to choose the appropriate treatment.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1998

Mining biomedical time series by combining structural analysis and temporal abstractions.

This paper describes the combination of Structural Time Series analysis and Temporal Abstractions for the interpretation of data coming from home monitoring of diabetic patients. Blood Glucose data are analyzed by a novel Bayesian technique for time series analysis. The results obtained are post-processed using Temporal Abstractions in order to extract knowledge that can be exploited "at the point of use" from physicians. The proposed data analysis procedure can be viewed as a Knowledge Discovery in Data Base process that is applied to time-varying data. The work here described is part of a Web-based telemedicine system for the management of Insulin Dependent Diabetes Mellitus patients, called T-IDDM.

Algorithms↗
PubMed1998

A new approach to optimal dynamic therapy planning.

Therapy planning is a very complex task. One of its crucial aspect is the derivation of therapeutic plans taking into account the dynamic aspect of the decision problem. This paper deals with dynamic decision problems using Influence Views, a novel graphical formalism based on Markov Decision Processes (MDPs) framework, in order to solve decision problems in which the optimal choice has to be revised periodically in accordance to the evolution of the patient's conditions. The proposed methodology has been applied to the plan of the prophylaxis in patients affected by a mild Hereditary Spherocytosis.

Child↗