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M Grassi

Publications and source records attributed to M Grassi.

At least 55 records · Page 3Linked to original sources

Novel hydrogel system from scleroglucan: synthesis and characterization.

New hydrogels 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 appreciably different properties. Water uptake by the hydrogel with a low degree of crosslinking was remarkably affected by ionic strength. The diffusion of a model molecule (theophylline) through the swelled crosslinked polymers was studied and the theoretical analysis leading to the calculation of permeability coefficients in different environmental conditions is reported. Tablets prepared with one of the new hydrogels behaved as swellable monolithic systems suitable for sustained drug release.

Bromides↗

Metastatic rat carcinoma cells express a new retrotransposon.

Genes differentially expressed by a rat bladder carcinoma NBT-II cells and their in-vivo-selected metastatic M-NBT-II variant were analysed. Amplification and cloning of a 277-bp B sequence, exclusively expressed by the M-NBT-II cells, were performed, and this sequence was detected as a 6.7-kb RNA. This fragment shares 46-50% identities with the gag-related protein of mouse and hamster Intracisternal A Particles (IAPs). Screening of a M-NBT-II cDNA library with the B probe selected a 1671-bp sequence corresponding to the 5' end of a novel retrotransposon member of the rat IAP family. This sequence has a strong identity with the Ecker Rat IAP (ERA-IAP) except for the B portion and has an open reading frame potentially encoding a 114-amino-acid gag retrovirus-related protein. Rearrangement of this new retrotransposon could be relevant with the tumor progression in our model system since it is only expressed in the M-NBT-II in-vivo-selected carcinoma metastasis.

Amino Acid Sequence↗

Mathematical modelling of drug permeation through a swollen membrane.

This work proposes two different mathematical models (linear and numerical) able to simulate the drug permeation through a swollen membrane sandwiched by two external layers (trilaminate system). Moreover, a solid drug dissolution phenomenon in the donor compartment may be accounted for. Indeed, this is a situation that may often occur in permeation experiments. An insufficient stirring of the donor and of the receiver volume may give rise to two sandwiching layers and the target of a constant drug concentration in the donor compartment may be accomplished by putting a solid drug amount in the saturated donor solution. The linear model shows the advantage of having an analytical expression which extremely simplifies the calculation of the drug diffusion coefficient D inside the membrane. Its main drawback lies in the fact that it works only for thin trilaminate systems. The numerical model is more general than the linear one, as it works for all kind of trilaminate thickness and it may account for a solid powder dissolution in the donor compartment. Of course, it does not have an analytical solution and, thus, the D determination is less easy to perform as the numerical model is more time consuming than the linear one. These two models are then compared with the classical approach developed by Flynn and Barrie in order to better define its validity limits.

Diffusion↗

The SFL activity secreted by metastatic carcinoma cells is related to laminin 5 and mediates cell scattering in an integrin-independent manner.

We have previously reported that an in vivo-selected metastatic variant of NBT-II rat carcinoma cells, M-NBT-II, produces and secretes a factor with cell-scattering activity, SFL, that is potentially involved in tumor progression. This biological activity was purified and characterized as a laminin 5 (LN5) -related protein. This SFL/LN5 protein consists of the (alpha)3, (beta)3 and (gamma)2 chains of expected sizes. Laminin 5 is a multifunctional secreted glycoprotein thought to be involved in cell adhesion and migration, mainly via its interaction with (alpha)3(beta)1 and (alpha)6(beta)4 integrins. SFL/LN5, and purified human laminin 5, induced the scattering and motility of MDCK cells and the formation of actin stress fibers and focal contacts in A549 cells. These events were dependent on activation of the small GTP-binding protein Rho. (Alpha)v colocalized with vinculin in the focal contacts of activated cells whereas (alpha)3 and (alpha)6 integrins did not. Blocking antibodies directed against (alpha)3 and (alpha)6 integrins or the laminin 5 integrin-binding site did not abolish SFL/LN5 biological activity, which, in contrast, was completely inhibited by heparin. Thus, SFL/LN5 activity in epithelial cell scattering and cytoskeletal reorganization is probably independent of integrin receptors.

Animals↗

Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families.

We assessed the expression of the epidermal growth factor (EGF)-related peptides, cripto-I (CR-I) and amphiregulin (AR), in a small panel of human colon adenomas and carcinomas. CR-I immunoreactivity was found in 17/31 (55%) of colon adenomas, and in 33/39 (84%) colon carcinomas. AR immunostaining was observed in 16/26 adenomas (61%) and in 20/26 carcinomas (77%). CR-I and AR staining were also assessed in 29 specimens from 24 individuals that belong to families with high incidence of colorectal carcinoma, and in 5 non-high risk individuals. Expression of CR-I was detected in 18/29 (62%) of high risk colon mucosa specimens, but only in 1/5 (20%) specimens from non-high risk individuals, while AR staining was found in 20/29 (69%) and in 4/5 (80%) of colon mucosa samples from high and low risk individuals, respectively. A majority (21/29; 72%) of the specimens from the high risk individuals had a high proliferative rate, as measured by Ki-67 staining. A statistically significant correlation was found between high proliferative rate, increased expression of CR-I and reduced expression of AR in the mucosa specimens from high risk individuals, suggesting that these might represent early events in colon tumorigenesis.

Adenoma↗

[Impact on tumor angiogenesis and tumor progression of expression of the 18 kd and 24 kd isoforms of FGF-2].

The role of FGF-2 in tumor progression and tumor cell invasiveness was investigated using the rat bladder carcinoma cells NBT-II, which do not constitutively express FGF-2 or its membrane-spanning receptor. The NBT-II cells were transfected using expression vectors encoding either the 18 kD or the 24 kD isoform of FGF-2. The 24 kD isoform contains a nuclear localization signal. The transfected NBT-II cells that expressed 18 kD FGF-2 produced and secreted this factor as the biologically active form and retained an epithelial morphology. When injected to nude mice, the tumorigenic potential of these cells was not increased over that of non-transfected NBT-II cells; however, although the time to tumor development was long, the tumors were highly vascularized, indicating secretion of the angiogenic factor FGF-2. The transfected NBT-II cells that expressed 24 kD FGF-2 varied in their morphological appearance and did not secrete FGF-2; immunofluorescence and Western-blot studies showed that the FGF-2 was mainly intranuclear. When injected to nude mice, these cells produced tumors and migrated not only to the lymph nodes but also to the lungs where they produced metastases. In aggregate, these data indicate that stimulation of angiogenesis is not sufficient to increase tumor growth and that nuclear FGF-2 acts as a tumorigenic and metastasis-promoting factor in the NBT-II carcinoma model.

Animals↗

Plaque formation and gingivitis after supervised mouthrinsing with 0.2% delmopinol hydrochloride, 0.2% chlorhexidine digluconate and placebo for 6 months.

OBJECTIVES AND METHODS: A double-blind, randomized, 6-month clinical trial with parallel group design in 162 patients with gingivitis divided into three rinsing groups was conducted in order to study the efficacy and safety of a flavoured solution of delmopinol hydrochloride 2 mg ml-1 (0.2% w/v, Decapinol Mouthwash) used for supervised mouthrinsing in one rinsing group, in comparison with chlorhexidine digluconate 2 mg ml-1 (0.2% w/v, Hibitane Dental) in a second rinsing group, and placebo in the third group. The criteria of the Plaque Index (PI) were used to assess plaque formation. Bleeding on probing (BOP) to the bottom of the pocket with a standard pressure was used as the primary gingivitis assessment. The occurrence of supragingival dental calculus and extrinsic tooth staining were also assessed. In addition, patients were asked to report adverse events at each visit. RESULTS: Delmopinol and chlorhexidine exhibited lower scores of the mean PI and the BOP percentage than placebo, both at the 3-month and 6-month examinations. Furthermore, both active solutions showed a higher extent of staining of the teeth than placebo during these two observation periods. Rinsing with chlorhexidine resulted in more dental calculus than placebo after 6 months. Chlorhexidine showed lower scores for plaque formation and gingivitis development but higher scores of supragingival dental calculus (after 6 months) and tooth staining than did delmopinol. Both active solutions were reported by the patients--approximately to the same extent but more frequently than placebo--to induce taste alterations and a transient anaesthetic sensation of the oral mucosa. However, subjective staining of the teeth and tongue was reported by 16% of the delmopinol patients, but by 86% of the patients rinsing with chlorhexidine for 6 months. Furthermore, 24% of the patients in the chlorhexidine group, 9% in the delmopinol group and 4% in the placebo group wished to withdraw from treatment. CONCLUSIONS: The results from this clinical trial indicate that supervised rinsing with 0.2% delmopinol hydrochloride or with 0.2% chlorhexidine digluconate twice daily for 60 s as a supplement to normal mechanical oral hygiene procedures resulted in less plaque formation and gingivitis than rinsing with placebo. Although chlorhexidine was more effective than delmopinol regarding plaque formation and gingivitis, it was considered by the patients as less tolerable.

Adult↗

Heart transplantation 1985-1998: 13-years experience at Angelo De Gasperis Cardio-Thoracic Department-Milan.

BACKGROUND: After 13 years of transplant experience in our center, we analyzed the results in the overall population and in particular subgroups of heart transplant recipients. We tried to identify risk factors for both early (3 months) and late (over 3 months) mortality after heart transplantation. METHODS: The data on 461 patients transplanted from November 1985-June 1998 were reviewed. To study risk factors for mortality, the results for 313 patients operated on from June 1985-June 1995 were studied and analyzed with a multivariate logistic regression and Cox's proportional hazard model. Seventy pre-, intra- and postoperative variables were considered including patient demographics, clinical status, hemodynamic parameters, donor characteristics, donor-recipient HLA mismatches, complications, and immunosuppressive protocols. We also compared results for patients transplanted from 1985-1991 (Group 1) and from 1992-1998 (Group II) to assess improvements due to changes in indications and in perioperative treatments. RESULTS: Overall mortality in the entire population was 20.2% (93/461). The 30-day, 3-month and late mortality rates were 8.0%, 10.2%, 11.1%, respectively. Group II mortality rates were 6.5%, 8.5% and 6.8%, respectively, despite a significant increase in Status I patients (20.6% in Group I vs 49.0% in Group II, p = 0.0001). The main causes of death were graft failure (24.7%), cardiac allograft vasculopathy (18.3%), and infection (16.1%). The mean follow-up of the 414 recipients who survived more than 3 months was 54.0 +/- 37.3 months. Actuarial survival was 87.4%, 79.2% and 68.9% at one, 5 and 10 years, respectively. The difference in the 5-year actuarial survival rates between Group I and Group II patients was statistically significant (73.5% vs 83.9%, p = 0.0135). The transpulmonary gradient, right atrial pressure and mid-high doses of donor inotropic support were identified as independent risk factors for early mortality. The number of moderate rejections at biopsy and early posttransplant infections were identified as independent risk factors for late mortality. The results of patients transplanted while on ventricular assist devices, urgent and elective patients and combined heart and kidney transplants were also reported. CONCLUSIONS: The overall results of our 13-year experience are very satisfying in relation to early and late mortality, with a significant favorable trend between patients transplanted in the early era (1985-1991) and those transplanted in the recent era (1992-1998). Pulmonary hypertension and elevated preoperative right filling pressure appear to indicate a significantly increased risk of early death and only marginally influence late survival, which is principally influenced by severe postoperative complications. Good results were achieved in combined heart and kidney transplantation and among patients who deteriorated during the waiting period and were supported with ventricular assist devices. The early and late outcomes for urgent (status I) and elective (status II) heart transplant patients were comparable.

Adolescent↗

Combined heart and kidney transplantation: an effective therapeutic option--report of six cases.

Six cases of combined heart and kidney transplantation with organs from the same donor are reported. All six patients suffered from primary end-stage kidney disease, two chronic glomerulonephritis, two glomerulosclerosis, one chronic pyelonephritis and one with unknown etiology. Four patients were undergoing hemodialysis. Three patients had the diagnosis of ischemic heart disease, one dilated cardiomyopathy secondary to congenital heart disease, two idiopathic dilated cardiomyopathy. Five were males and one female. Ages ranged from 38 to 54 years. On-site or short-distance young donors with normal renal function and good cardiac function necessitating low inotropic support were selected. ABO compatibility was used exclusively. Orthotopic heart transplantation was performed first. During cardiopulmonary bypass, hemofiltration was used in four cases. Kidney transplantation was performed immediately after the closure of the chest. Diuresis was immediate in all cases. No cardiac rejection was documented at EMB. Renal function normalized within few days with no signs of kidney rejection. All six patients are alive and well with normal cardiac and renal function at a mean follow-up of 43 months. Patients and donors selection associated with a proper surgical strategy and prompt immunosuppressive therapy administration make the combined heart and kidney transplantation an effective therapeutic option.

ABO Blood-Group System↗

Synergistic gelation of xanthan gum with locust bean gum: a rheological investigation.

Many industrial products often include in their formulation more than one polysaccharide to achieve the desired properties during and after processing. Many such mixed systems behave as would be expected from the known properties of the individual polymers. In others, however, their properties are superior to those of either component alone, or may be qualitatively different. In many polysaccharide systems, the combination of a gelling polymer with a nongelling one gives rise to strong synergistic effects, as a consequence of interaction among different chain polymers and formation of mixed junction zones. Probably, the most exploited mixed gels, especially by the food industry, are those involving the microbial polysaccharide xanthan gum (XG) and the plant galactomannans, like locust bean gum (LBG). Concentrated aqueous systems of LBG and XG display quite different rheological properties: the former show the behaviour typical of hyperentangled macromolecular solutions, whereas the flow and viscoelastic properties of XG systems correspond to those of tenuous, weak-gel networks. Interestingly, when mixed together these macromolecules interact to form a firm, thermoreversible gel with synergistic effects. In the present paper we report the results of a thorough investigation of both polymer concentration and temperature effects on the rheological properties of mixed LBG-XG systems in 20 mM KCl under continuous and oscillatory flow conditions. Under continuous shear at 25 degrees C, pure LBG shows the flow properties of a macromolecular solution, with a shear-thinning behaviour and a Newtonian region at low shear rates, whereas the rheological behaviour of XG and all LX mixed systems is that typical of weak-gels. Furthermore, in the mixed systems the viscosity values do not increase monotonically with increasing xanthan concentration, but the synergistic effect has a maximum in accordance with the XG:LBG ratio 1:1. As the temperature is increased from 25 degrees C to 85 degrees C, whilst the LBG system do not show any qualitative change but there is only a parallel, downward shift of viscosity values, in the case of xanthan there is a dramatic change in the corresponding curve profiles, due to the thermally induced helix-coil conformational transition. The differences in the rheological behaviour of the systems examined can be better shown through dynamic tests at 25 degrees C. The strain sweeps performed at constant frequency of oscillation reveal that the mixed systems show higher sensitivity to strain amplitude, and lower strain values must be attained to ensure linear viscoelastic properties. The mechanical spectra clearly show the influence of composition on the viscoelastic properties of these biopolymer systems. All LX systems show the mechanical spectra typical of polysaccharide gels: G' is always much greater than G" and is nearly independent of the applied frequency over a wide frequency range. In addition, the marked gap between the elastic responses of the pure LBG and the LX 1:3 systems demonstrates the strong effect of the initial addition of xanthan to the pure LBG, especially in the low frequency range, whereas the highest synergistic effect is attained for the LX 1:1 system. A comprehensive description of the frequency dependence of both moduli can be suitably obtained through the four-parameter Friedrich model, which belongs to the class of fractional derivative approaches viscoelasticity. The same thermal effect is observed for the XG and all LX mixed systems considered, indicating a progressive change from the behaviour of a typical gel to that of a quasi-solution state, when temperature is increased from 25 degrees C to 85 degrees C. Among all mixed systems, the LX 1:1 has the highest values of the moduli at any temperature considered, and is characterized by the highest gel-sol transition temperature. (ABSTRACT TRUNCATED)

Carbohydrate Sequence↗

[Alcoholism and HCV-antibody association. Effects on the course and severity of chronic liver disease].

BACKGROUND: The authors evaluated the role of the association alcohol-hepatitis C virus on the course and severity of chronic liver disease; they also regard the researches of many authors on this subject. MATERIALS AND METHODS: 280 consecutive patients, suffering from chronic liver disease and admitted to the Department of Medical Hydrology of Rome University ''La Sapienza'' are studied. Fifty-nine of them were affected by chronic alcoholic liver disease without evidence of hepatitis virus infection (AC-), 58 were alcoholic and positive for HCV antibody (AC+), 163 positive for HCV antibody and non alcoholic (NAC+). They are divided according to the diagnosis into chronic hepatitics, cirrhotics and those affected with hepatocarcinoma; among them 193 patients, age and sex matched, are evaluated as regards the course and severity or the chronic liver disease. RESULTS: In the total of 280 patients the hepatic damage arises significantly faster in the alcoholic and anti-HCV positive than in other patients. In the age and sex matched, in alcoholic and HCV positive patients the hepatocarcinoma significantly prevailed (AC-: 8.2%, NAC+: 9.4%, AC+: 19%; p=0.04). The three groups of cirrhotics did not show a significant difference with respect to the severity of the disease evaluated according to Child-Pugh criteria. CONCLUSIONS: Our research confirms the role of the association of HCV virus infection and alcoholism on the severity and impairment of chronic liver disease.

English Abstract↗

[Heart transplantation 1985-1995: 10 years experience at the "Angelo De Gasperis" center. Improvement of results by progress in operative criteria].

BACKGROUND: At 10-years from beginning of transplant experience in our Center we analyzed the overall results in an attempt to identify risk factors for early (3 months) and late (over 3 months) mortality after heart transplantation (HTx). METHODS: The data of 313 patients transplanted from November 1985 to June 1995 were studied and analyzed with a multivariate logistic regression and Cox's proportional hazard model. Seventy pre, intra and postoperative variables were considered: demographics, clinical status, hemodynamic parameters, donor characteristics, donor-recipient mismatch, complications, immunosuppressive protocols. In this paper we compared results in patients operated on from 1985 to 1990 (Group I) and from 1991 to 1995 (Group II) in order to assess improvements due to changes in HTx indication and in perioperative treatments. RESULTS: Overall mortality in the entire group was 19.8% (62/313): 30-days, 3 months and late mortality rates were 8.0%, 10.2%, 10.7% respectively. In Group II mortality rates were 7.1%, 8.6% and 2.8% respectively despite significant increase in Status I patients (21.5% in Group I vs 40.1% in Group II, p = 0.0008). Main causes of early death were: graft failure (46.9%), infection (28.1%), acute- rejection (12.5%). Main causes of late death were: cardiac allograft vasculopathy (40.0%) and neoplasm (23.3%). The mean follow-up of the 281 survivors more than 3 months is 45.6 +/- 30.0 months (range 3 to 120 months). Actuarial survival is 86.9 +/- 1.9%, 78.4 +/- 2.7% and 70.7 +/- 3.9% at 1, 5 and 10 years respectively. The difference in the 5-years actuarial survival between Group I and Group II patients is statistically significant (70.7 +/- 4.2% vs 84.5 +/- 4.5%, p = 0.005). TPG (OR 1.19), RAP (OR 1.13) and MD-HD inotropic support of donor (OR 3.81) were identified as independent risk factors for early mortality. Number of moderate rejection at biopsy (OR 1.56) and early postTx infection (OR 3.37) were identified as independent risk factors for late mortality. CONCLUSIONS: The overall results of our ten-year experience are very satisfying in relation to early and late mortality, with a significant favourable trend between patients transplanted in the early era (1985-1990) and those transplanted in the recent era (1991-1995). The study confirm that morbidity and mortality have the highest incidence during the early post-transplantation phase. Pulmonary hypertension and elevated preoperative right filling pressure appear to indicate a significantly increased risk of early death and only marginally influence late survival that is principally related to the severe postoperative complications. Differently from other observations, among the donor-related and recipient-donor matching variables, this analysis evidenced as significant only the need for MD-HD catecolamines during donor-management.

Actuarial Analysis↗

[Current aspects of therapy of primary biliary cirrhosis].

The authors expose the epidemiological features of PBC and outline the role of the immunologic disorders in the disease's pathogenesis. The main clinic and laboratory features of the PBC, its course and pathology are also synthesized. The authors describe the drugs employed in the therapy of the PBC: cortisone, azathioprine, metotrexate, chlorambucil, colchicine, D-penicillamine and hydrophilic bile salts; the favourable risk-benefice rate of colchicine, azathioprine and hydrophilic bile salts is outlined, even if they are poorly active on the disease's course. The use of lyposoluble vitamins is stressed, to improve malabsorption's syndromes. At the end the role of orthotopic liver transplant is regarded.

Adult↗

[The treatment of chronic viral hepatitis with recombinant alpha-2 interferon: meta analysis and clinical contribution].

The Authors have developed a work of meta-analysis on the employment of IFN in the virus-correlated chronic hepatitis. They have examined World literature on: virus causing chronic hepatitis, type and duration of the treatment, criteria in the choice of the observed patients, clinical effects, effects on the virus, effects on the isto-pathologic situation. Have been considered the useful actions at the end of the treatment and in the follow-ups, so to evaluate the permanence of favourable effects. Have been also reminded the main collateral effects, even about frequency and intensity, as the various Authors relate. There are quite clear data indicating: efficacy in B-correlated chronic hepatitis greater than in C-correlated ones, greater efficacy in the treatments with Interferon with duration of more then 6 months in chronic hepatitis C. Doses greater than those generally employed appear not to give better results. The Authors moreover show the results of a clinical survey they made on patients with chronic hepatitis HBsAg+/HBeAg+ (treated with IFN-alpha 2r 5 MU t.i.w. for six months) and chronic hepatitis anti-HCV+ (treated with IFN-alpha 2r 3 MU t.i.w. for six months). The results confirm the efficacy of IFN in B-correlated chronic hepatitis (50% of sustained response) and its scarce efficacy in C-correlated chronic hepatitis for treatment shorter than 12 months (9.1% of sustained response).

Adult↗