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M Grassi

Publications and source records attributed to M Grassi.

At least 37 records · Page 2Linked to original sources
PubMed2003

Scleroglucan/borax: characterization of a novel hydrogel system suitable for drug delivery.

A new hydrogel, with scleroglucan using borax as a crosslinker, has been prepared. The physical gel has been loaded with a model molecule (theophylline) and the release of the drug from the gel was evaluated. The same system was used to prepare tablets and the delivery of theophylline in different environmental conditions (HCl and SIF) was determined. A recent theoretical approach has been applied to the dissolution profiles obtained from the tablets and a satisfactory agreement has been found with the experimental data. Furthermore, the diffusion coefficient of the model molecule was evaluated according to a suitable strategy that was tested on two set of data obtained with different set-ups (permeation and diffusion experiments). A simplified mathematical approach allows to reduce the two-dimensional problem of the Fick's second law in a one-dimensional system leading to a much easier handling of the data without loosing the accuracy of the original problem in two dimensions. The characterization of the gel has been also carried out following the kinetics of swelling in terms of water uptake.

Borates↗
PubMed2002

Premature arterial and venous events in three families. Effect of folate levels and MTHFR mutation mediated by family/generation and homocysteine levels.

Plasma homocysteine levels result from the effect of genetic and environmental factors. We investigated the hypothesis of familial association between folates, methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia with acute events, studying three families through pedigree analysis and log-linear graphical models. In 43 subjects, 13 had homocysteine levels of >15 micromol/l. In Family A, premature venous and arterial events occurred in father and son, respectively. In Family B, several arterial premature events occurred and very high homocysteine level was found in a healthy 18-year-old nephew. In Family C, stroke occurred at the age of 16 in a boy. In all three families, all subjects with premature cardiovascular events had high homocysteine level as well as MTHFR mutation, either homozygous or heterozygous. The present results underline that hyperhomocysteinemia has a direct conditional association with cardiovascular events. Moreover, homocysteine level is a variable that links the indirect association of folates, MTHFR mutation and cardiovascular event.

Adolescent↗
PubMed2001

113Cd-NMR and fluorescence studies of the interactions between Cd(II) and extracellular organic matter released by Selenastrum capricornutum.

113Cd NMR spectra were measured in solution for a series of adducts between the extracellular organic matter (EOM) of the green alga Selenastrum capricornutum and cadmium(II). From the results it appears that EOM forms complexes with Cd(II), which are in a fast exchange in NMR time scale. Thus the observed shift is the molar average of limit values for the exchanging free and bound cadmium species. Definite support for this dynamic stems from an extensive 113Cd NMR equilibrium analysis. Although in principle a multiple binding mode cannot be excluded, our 113Cd NMR findings and the consideration that carbohydrates are the prevailing constituents of algal releasing in stationary growth phase led us to suggest a carbohydrate type coordination. This hypothesis is also supported by NMR studies on model compounds. However, this is probably an oversimplified view of the binding which does not properly account for the fluorescence results. Fluorescence spectroscopy provided further evidence of the EOM binding process also allowing a discrimination between the fluorophoric groups involved. The addition of Cd(II) affected both fluorescence intensity and peak position in the "humic-like" band (between 340 and 400 nm Ex). Finally, the 113Cd NMR and synchronous fluorescence measurements showed a linear correlation between 113Cd chemical shifts and EOM concentration (as fluorescence intensity at 340 and 360 nm). NMR and fluorescence data suggest the existence of structurally different binding sites (carbohydrate-like and humic-like) which appear somehow related. Further, they definitely put in evidence the EOM-Cd interaction together with the specific organic components mostly involved.

Cadmium↗
PubMed2001

Theoretical considerations on the in vivo intestinal permeability determination by means of the single pass and recirculating techniques.

This paper deals with the development of proper mathematical models for the calculation of the in vivo rat intestinal drug permeability resorting to two different kinds of experimental methods: the single pass and the recirculating perfusion techniques. In particular, in the single pass case, attention is focused on the effect of water exchange between the flowing solution and the intestinal wall, as this can sensibly affect the permeability determination. In both the single pass and the recirculating perfusion method, a complete radial mixing of the flowing solution is supposed to hold, so that drug concentration and solution velocity are radius independent. Nevertheless, they depend on the intestinal axial position. Accordingly, two distinct models are built up by resorting to microscopic mass balances. The reasonably good data fitting performed by the recirculating perfusion model ensures that the most important factors affecting the passive drug (Antipyrine) diffusion through a rat intestinal wall are properly accounted for. Moreover, the reliability of the developed models and the experimental tests is proved by the fact that the drug (Antipyrine) permeability determined by means of the two methods is statistically equal.

Algorithms↗
PubMed2001

Experimental determination of the theophylline diffusion coefficient in swollen sodium-alginate membranes.

In this paper attention is focused on the determination of the drug diffusion coefficient in a swollen polymeric membrane referring to a recent mathematical model (linear model). The main advantage deriving from its use is that, despite its analytical nature and its ability to account for the most important aspects characterising a permeation experiment, it can also be applied in the case of thick membranes. To check the model reliability, a comparison is made with a more complex numerical model and with a largely employed model in terms of data fitting quality. To this purpose, particular care is devoted to the experimental and theoretical tools employed to calculate the auxiliary parameters required by the three models, and with the aim of getting a drug diffusion coefficient value as accurate as possible. Theophylline was chosen as model drug owing to its wide employment in the pharmaceutical field. Membranes were prepared with sodium alginates hydrogels at three different polymer concentrations. The present analysis demonstrates the reliability of the linear model and reveals that the theophylline diffusion coefficient is not significantly affected by the polymer concentration. Indeed, such a parameter is reflected in different membrane thicknesses rather than in different mesh sizes of the polymeric network.

Alginates↗
PubMed2001

Adult human heart microvascular endothelial cells are permissive for non-lytic infection by human cytomegalovirus.

OBJECTIVE: Human cytomegalovirus (CMV) infection has been linked to chronic heart disease. The mechanism of CMV dissemination to the heart remains unknown. CMV antigens and nucleic acid sequences have been detected in endothelial cells (ECs) in vivo, and ECs are fully permissive hosts to CMV replication in vitro. This report examines the characteristics of CMV replication in primary cultures of human heart microvascular ECs (HHMECs). METHODS: Capillary ECs were isolated from heart tissue biopsies of six patients at the time of heart surgery. HHMECs were infected with CMV and viral antigens were detected by immunofluorescence assay using monoclonal antibodies as specific reagents. Cytokine and chemokine release in the supernatant of sham- and CMV-infected cells was quantitated by ELISA. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyse expression of mRNA for adhesion molecules. RESULTS: CMV was found to productively infect HHMECs without cytolytic effects. Infected cultures released high levels of pro-inflammatory chemokines and enhanced their adhesion molecule expression. CONCLUSIONS: Our data provide new insights into the mechanism of CMV dissemination to the heart, signalling the need for further investigation of the pathogenetic role of this virus in cardiac disorders.

Adult↗
PubMed2001

CD11b expression identifies CD8+CD28+ T lymphocytes with phenotype and function of both naive/memory and effector cells.

A previously unreported CD8(+)CD28(+)CD11b(+) T cell subset occurs in healthy individuals and expands in patients suffering from primary viral infections. In functional terms, these cells share the features of naive/memory CD8(+)CD28(+)CD11b(-) and terminally differentiated effector CD8(+)CD28(-)CD11b(+) subpopulations. Like CD28(-) cells, CD28(+)CD11b(+) lymphocytes have the ability to produce IFN-gamma, to express perforin granules in vivo, and to exert a potent cytolytic activity. Moreover, these cells can respond to chemotactic stimuli and can efficiently cross the endothelial barrier. In contrast, like their CD11b(-) counterpart, they still produce IL-2 and retain the ability to proliferate following mitogenic stimuli. The same CD28(+)CD11b(+) subpopulation detected in vivo could be generated by culturing naive CD28(+)CD11b(-) cells in the presence of mitogenic stimuli following the acquisition of a CD45RO(+) memory phenotype. Considering both phenotypic and functional properties, we argue that this subset may therefore constitute an intermediate phenotype in the process of CD8(+) T cell differentiation and that the CD11b marker expression can distinguish between memory- and effector-type T cells in the human CD8(+)CD28(+) T cell subset.

CD28 Antigens↗
PubMed2001

Effects of mud-pack treatment on plasma cytokine and soluble adhesion molecule levels in healthy volunteers.

BACKGROUND: The suggested hypothesis of a direct anti-inflammatory property of mud-pack treatment has led us to speculate that its action on the cytokine network might counteract the heat-stress-related effects on platelet and endothelial cell function often reported following hot-spring baths. Therefore, the present study was designed to investigate the effects of a cycle of 12 daily mud-pack treatments on bio-humoral markers of inflammation, as well as on markers of in vivo platelet and/or endothelial cell activation, in plasma samples obtained from healthy volunteers. METHODS: Blood samples were obtained before (T(0)), at the end of the first treatment (T(1)) and after a cycle of 12 daily mud-pack treatments (T(2)). Plasma cytokines (TNF-alpha IL-1beta, and IL-6) and adhesion molecules (sP-selectin, sE-selectin and sVCAM) levels, as well as hematocrit and complete and differential blood cell counts were determined at every time point. RESULTS: Plasma sP-selectin levels were not modified during treatment, as were not sE-selectin or sVCAM. Similarly, IL-1beta and TNF-alpha levels were unchanged through a 12 daily mud-pack treatment. Conversely, plasma IL-6 levels were significantly lowered at the end of a 20-min 47 degrees C mud-pack treatment (p<0.01). CONCLUSIONS: The lack of effects on in vivo platelet and/or endothelial cell activation suggests that hot mud-pack treatment might be used as a relatively safe procedure in patients with atherothrombotic disorders.

Adult↗
PubMed2001

A crosslinked system from scleroglucan derivative: preparation and characterization.

Matrices obtained by a crosslinking reaction between the polycarboxylated derivative of scleroglucan (sclerox) and 1,6-hexanedibromide have been prepared and characterized. Different ratios between the alkane dihalide and sclerox yielded products with different properties. Water uptake by the hydrogel with a low degree of crosslinking was remarkably affected by ionic strength. The determination of the crosslink density is led by simultaneously solving two Flory equilibrium equations referring to two different conditions characterized by the presence or the absence of a salt in the swelling agent. Moreover, the swelling kinetics was studied by means of a recently proposed model. Finally, the permeation of two model molecules (theophylline and polystyrene sulphonate-sodium salt) through the hydrogels was evaluated.

Cross-Linking Reagents↗
PubMed2001

Classification methods for the identification of 'case' in epidemiological diagnosis of asthma.

The identification of the asthmatic 'case' in epidemiological research is a controversial issue. This study was aimed at classifying asthmatic subjects using a statistical decision rule that minimised the misclassification rate with respect to the clinicians' diagnosis. The rule was defined by a combination of predictors that are easily observed in epidemiological studies (asthma-like questions, physiological tests) without necessarily including the clinical opinion of expert physicians. From pooled data on 1103 subjects at the three Italian centres of the European Community Respiratory Health Survey (ECRHS) a post-consensus clinicians' diagnosis of asthma was obtained, and seven predictors were selected from among 18 potential candidates (specificity ranged from 64 to 99%, but sensitivity ranged from 22 to 62%). This data set was processed with tree-structured classifier techniques (the Classification And Regression Trees, CART), classical discriminant analysis (Fisher's Linear Discriminant Function, LDF), and the neural network method (Multi-Layer Perceptron, MLP model). The results suggest that modifications of the 'classification tree' provide a more useful decision rule, sensitive (93%) and specific (85%), than either LDF or MLP. The decision tree is readily interpretable from a clinical perspective and uses five out of the seven predictors (in descending hierarchical order: ever had asthma, current asthma, shortness of breath, atopy and wheezing and breathless). The findings seem to indicate a considerable success with respect to previous epidemiological studies and await repetition in other ECHRS populations.

Adult↗
PubMed2001

Selection and characterization of active hammerhead ribozymes targeted against cyclin E and E2F1 full-length mRNA.

Proliferation of vascular smooth muscle cells is generally accepted as a key event in the development of restenosis following percutaneous transluminal angioplasty. To prevent human restenosis, we have designed a molecular strategy based on hammerhead ribozymes targeted against the mRNA of cyclin E and E2F1, two proteins relevant in cell cycle progression whose regulation is interconnected by a positive feedback loop. Following the identification of accessible ribozyme target sites by RNase H mapping, several hammerhead ribozymes were generated that cleave with comparable efficiency two different splice forms of cyclin E mRNA and the full-length and a truncated form of E2F1 RNA, respectively. The most active ribozymes were tested in vitro under single-turnover conditions yielding k(react)/K(m) ratios between 36 and 73 x 10(4) M(-1) min(-1), which places them in the top range ribozymes targeted against long and structured substrates. In addition, we show that the most active ribozyme selected in vitro reduces specifically and significantly (p < 0.0028) proliferation of cultured human vascular smooth muscle cells (VSMC).

Base Sequence↗
PubMed2001

Persistent hepatitis G virus (HGV) infection in chronic hemodialysis patients and non-B, non-C chronic hepatitis.

Three groups of patients have been studied longitudinally for 24 months to analyze the role of hepatitis G virus (HGV) in hepatic disease. Group 1 consisted of 50 patients with non-B, non-C chronic hepatitis, group 2 consisted of 44 hemodialyzed patients, and group 3 consisted of 50 healthy blood donors. The presence of HGV RNA was detected by both reverse transcription-polymerase chain reaction (RT-PCR) and capillary zone electrophoresis (CZE). At the baseline visit the HGV RNA was detected in seven out of 50 patients with non-B, non-C chronic hepatitis, in two out of 44 hemodialyzed patients, and in three out of 50 healthy blood donors. HGV-infected hemodialyzed patients and HGV viremic blood donors had serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels within normal limits. During the follow-up period the two HGV-positive hemodialyzed patients and the three infected healthy blood donors did not show any sign of hepatic disease. There were no significant differences between HGV-positive patients in the three groups at the beginning and at the end of the follow-up. No considerable deterioration of general health conditions was observed on the basis of clinical and laboratory data in HGV-positive chronic hepatitis patients. Finally, HGV does not seem to be responsible for hepatic disease.

Alanine Transaminase↗
PubMed2001

[Prevalence of dyspepsia in liver cirrhosis: a clinical and epidemiological investigation].

BACKGROUND: To evaluate the prevalence and severity of dyspepsia in patients with liver cirrhosis. METHODS: A questionnaire was distributed to 33 consecutive patients suffering from liver cirrhosis (22 males and 11 females, mean age 65.5 years; 24 with post-hepatitis liver cirrhosis and 9 with alcohol- based cirrhosis) to evaluate dyspeptic symptoms. Patients receiving prolonged treatment at home with anti-acid drugs immediately prior to hospitalisation were excluded from the study. RESULTS: Twenty-eight patients complained of dyspeptic disorders. An organic cause of symptoms could not be identified in 8 patients (24.2%), whereas the following were identified as the causes of organic dyspepsia in the remaining 20 patients, in order of frequency: gastroesophageal reflux disease (55%), congestive gastropathy (40%), gastric or duodenal ulcer (30%) and gallbladder stones (35%). Lastly, a combination of at least two of these morbid conditions was found in 10 patients (50%). The severity of dyspeptic symptoms was similar in both organic and functional forms; symptoms tend to occur with moderate intensity, worsening in parallel with the aggravation of liver disease. CONCLUSIONS: Dyspepsia is a very frequent phenomenon in cirrhotic patients; it is normally sustained by an organic cause. The predominance of functional forms in liver cirrhosis is practically the same as that reported in the general population.

Aged↗
PubMed2000

Mathematical Modeling of Drug Release from Microemulsions: Theory in Comparison with Experiments.

The topic of this paper is the study of the drug release from a drug-loaded microemulsion by reverting to a new mathematical model overcoming some drawbacks of previously proposed models. In particular, attention is focused on the mathematical expression of the drug fluxes existing between the oil and water phases during drug release. Indeed, not only the drug release kinetics, but also the drug oil-water partition coefficient strongly depend on these fluxes. Two microemulsion are considered: the first is composed by water, Tween80 as surfactant, and Triacetin as oil phase, while the second is composed by water, Tween80 as surfactant, and a Triacetin-benzylic alcohol mixture (1 : 1) as oil phase. Both of them are loaded by Nimesulide, an oil-soluble drug of considerable industrial relevance. The drug release is performed by resorting to a permeation experiment (Franz cells apparatus) as it demonstrated to be the most reliable methodology. The good agreement between the experimental permeation data and the model best-fitting ensures that the most important phenomena ruling this kind of drug release were properly accounted for by the new proposed model. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Drug release from an ensemble of swellable crosslinked polymer particles.

This paper presents a new model suitable to describe the drug release from drug delivery systems constituted by an ensemble of drug loaded crosslinked polymer particles. The model accounts for the main factors affecting the drug release such as the particle size distribution, the physical state and the concentration profile of the drug inside the polymeric particles, the viscoelastic properties of the polymer-penetrant system and the dissolution-diffusion properties of the loaded drug. In order to check the validity of the model, release experiments were performed by using crosslinked polyvinyl-pyrrolidone (PVP) particles and two different model drugs, MAP (medroxyprogesterone acetate) and TEM (Temazepam). MAP and TEM were chosen because of their completely different dissolution behaviours in water. In particular, TEM undergoes a phase transition to the crystalline state upon dissolution when it is loaded in the polymeric network in the amorphous state. The comparison with the experimental results confirms that the most important factors determining the drug release kinetics can be properly accounted for.

Antineoplastic Agents, Hormonal↗
PubMed2000

Congenital intrapericardial aneurysm of the left atrial appendage.

Congenital aneurysmal dilatation of the left atrial appendage is a rare but correctable lesion. It represents a diagnostic dilemma in patients with cardiomegaly and is commonly associated with supraventricular arrhythmias and life-threatening systemic embolization. We describe the diagnostic evaluation and surgical treatment during 1997 of a patient with congenital aneurysmal dilatation of the left atrial appendage. The patient was discharged previously from our hospital in 1967 with the diagnosis of congenital dilatation of the pulmonary artery.

Child↗