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Biomedical subjects

S Morelli

Publications and source records attributed to S Morelli.

At least 19 recordsLinked to original sources

Chromosomal analysis of Astyanax fasciatus (Pisces, Characidae) from the Araguari river, Uberlândia, MG, Brazil.

The genus Astyanax is one of the most numerous of the family Characidae, comprising a large number of similar-shaped species, but displaying innumerable karyotypic variations in its chromosome number and/or structure. The literature describes A. fasciatus populations with diploid chromosome numbers varying from 2n = 45 to 2n = 48. In this study, A. fasciatus specimens captured in the Araguari River (Alto Paraná basin) were cytogenetically characterized, revealing a diploid chromosome number of 2n = 46. The nucleolar organizing regions (NORs), detected with silver nitrate staining, showed a multiple system with two pairs of marked chromosomes. These findings are congruent with those of other studies involving populations of the same species.

Animals↗

Quality assessment and cataloguing of telemedicine applications.

We created a Web catalogue of approved telemedicine systems that authoritative Italian research bodies had made available for more general use. The evaluation process was divided into two stages: (1) classification of the telemedicine systems and rough preliminary evaluation; (2) assessment of the telemedicine products and services. The scoring method was applied to four well-known telemedicine systems that had been tested in health-care settings: an echocardiology teleconsulting and analysis system; a ward nursing management system; a virtual cooperative system for the management of oncology patients and a telepathology system based on remotely controlled microscopy. After technical revision during the standardization/qualification process, the applications were transferred successfully to eight new health-care facilities. The methodology achieved the main goal of providing effective tools, such as a set of quality control procedures for telemedicine and telehealth projects and a Web catalogue of telemedicine applications with a standardized level of quality, available to all interested parties.

Cataloging↗

Diffusive and convective transport through hollow fiber membranes for liver cell culture.

For an efficient membrane bioreactor design, transport phenomena determining the overall mass flux of metabolites, catabolites, cell regulatory factors, and immune-related soluble factors, need to be clarified both experimentally and theoretically. In this work, experiments and calculations aimed at discerning the simultaneous influence of both diffusive and convective mechanisms to the transport of metabolites. In particular, the transmembrane mass flux of glucose, bovine serum albumin (BSA), APO-transferrin, immunoglobulin G, and ammonia was experimentally measured, under pressure and concentration gradients, through high-flux microporous hydrophilic poly-ether-sulphone (PES-HFMs) and poly-sulphone hollow fiber membranes (PS-HFMs). These data were analyzed by means of a model based on the mechanism of capillary pore diffusion, assuming that solute spherical molecules pass through an array of solvent-filled cylindrical pores with a diffusive permeation corrected for friction and steric hindrances. Additionally, resistances to the mass transfer were taken into account. Convective permeation data were discussed in terms of morphological properties of the polymeric membranes, molecular Stokes radius, and solute-membrane interactions according to information given by contact angle measurements. The observed steady-state hydraulic permeance of PS-HFMs was 0.972 L/m2hmbar, about 15.6-fold lower than that measured for PES-HFMs (15.2 L/m2h); in general, PS-HFMs provided a significant hindrance to the transport of target species. Diffusion coefficients of metabolites were found to be similar to the corresponding values in water through PES-HFMs, but significantly reduced through PS-HFMs (D(Glucose)(Membrane)=2.8x10(-6)+/-0.6x10(-6)cm2/s, D(BSA)(Membrane)=6.4 x 10(-7)+/-1 x 10(-7)cm(/s, D(Apotransferrin)(Membrane)=2.3 x 10(-7)+/-0.25 x 10(-7)cm2/s).

Ammonia↗

New modified polyetheretherketone membrane for liver cell culture in biohybrid systems: adhesion and specific functions of isolated hepatocytes.

There has been growing interest in innovative materials with physico-chemical properties that provide improved blood/cell compatibility. We propose new polymeric membranes made of modified polyetheretherketone (PEEK-WC) as materials with potential for use in biohybrid devices. PEEK-WC exhibits high chemical, thermal stability and mechanical resistance. Owing to its lack of crystallinity this polymer can be used for preparing membranes with cheap and flexible methods. We compared the properties of PEEK-WC membranes to polyurethane membranes prepared using the same phase inverse technique and commercial membranes. The physico-chemical properties of the membranes were characterised by contact angle measurements. The different parameters acid (gamma+), base (gamma-) and Lifshitz-van der Waals (gammaLW) of the surface free energy were calculated according to Good-van Oss's model. We evaluated the cytocompatibility of PEEK-WC membranes by culturing hepatocytes isolated from rat liver. Cell adhesion and metabolic behaviour in terms of ammonia elimination, urea synthesis and protein synthesis were evaluated during the first days of culture. Liver cells adhered and formed three-dimensional aggregates on the most tested membranes. PEEK-WC membranes promoted hepatocyte adhesion most effectively. Urea synthesis, ammonia elimination and protein synthesis improved significantly when cells adhered to PEEK-WC membrane. The considerable metabolic activities of cells cultured on this membrane confirmed the good structural and physico-chemical properties of the PEEK-WC membrane that could be a promising biomaterial for cell culture in biohybrid devices.

Animals↗

Novel PEEK-WC membranes with low plasma protein affinity related to surface free energy parameters.

There has been growing interest in innovative materials with specific physico-chemical properties that provide an improved blood/cell compatibility. In this paper we evaluated the performance of new membranes prepared from a modified polyetheretherketone (PEEK-WC) contacting human plasma proteins. These membranes were prepared by using the phase inversion technique. Membrane wettability and affinity to proteins were evaluated by means of contact angle experiments, roughness measurements, and quantitative UV analysis. The energy parameters of membrane surfaces were determined according to Good, van Oss and Chaudhury's theory. The extent of human albumin, fibrinogen and immunoglobulin G adsorption was related to quantitative expressions of the membrane surface hydrophilicity: the base parameter of surface free energy and the free energy of interfacial interaction. The performance of PEEK-WC membranes was compared to that of commercial membranes, which conventionally are used in biomedical applications. The experimental results showed a reduction of protein adsorption on PEEK-WC membranes with respect to other commercial membranes. The low protein affinity of PEEK-WC membranes is due to the intrinsic physico-chemical characteristics of the polymeric material which makes these membranes interesting for potential use in biomedical applications.

Adsorption↗

Epidemiological, clinical and therapeutic features of AIDS-related Mycobacterium kansasii infection during the HIV pandemic: an 11-year follow-up study.

OBJECTIVES: Optimal diagnosis and timely treatment of atypical mycobacteriosis, and especially Mycobacterium kansasii disease, remain a serious challenge for clinicians engaged in the management of the immunocompromised host. METHODS AND RESULTS: From more than 2700 hospitalizations (over 1800 patients) attributable to HIV-associated disorders over an 11-year period, 12 patients were found to have a confirmed M. kansasii infection. This reflects the recent reduction in the frequency of this HIV-related complication, which virtually disappeared after the introduction of potent antiretroviral combinations in 1996. In the early 1990s, the lack of effective antiretroviral regimens made frequent the association with AIDS, a mean CD4 lymphocyte count of nearly 20 cells/microL, and an extremely variable chest X-ray features. The recent detection of a further case was attributable to late recognition of very advanced HIV disease, complicated by multiple opportunistic disorders. CONCLUSIONS: Mycobacterium kansasii respiratory or disseminated infection continues to occur, and poses diagnostic problems in terms of late or missed identification as a result of slow culture and frequently concurrent opportunistic disease. Serious therapeutic difficulties also arise from the unpredictable in vitro antimicrobial susceptibility profile of these organisms, and from the need to start an effective combination therapy that does not interfere with other medications as soon as possible.

AIDS-Related Opportunistic Infections↗

Infective endocarditis from Enterococcus faecalis complicating colonoscopy in Heyde's syndrome.

A case of infective endocarditis from Enterococcus faecalis after colonoscopy in a patient with aortic stenoinsufficiency and bleeding intestinal angiodysplasia (Heyde's syndrome) is reported.A 77 year old man with aortic stenoinsufficiency presented with enterorrhagia and underwent a colonoscopy, which showed normal findings. Fifteen days later he developed a moderate degree of fever. Blood cultures were positive for E faecalis. An echocardiogram showed aortic valve vegetations, and infective endocarditis was diagnosed and successfully treated by antibiotics. Some months later, intestinal bleeding recurred and intestinal resection was performed. Histopathology showed angiodysplasia. In patients with Heyde's syndrome antibiotic prophylaxis should be considered before colonoscopy.

Aged↗

Two polyclonal antisera detect different AGE epitopes in human plasma samples.

Advanced glycation end products (AGEs), involved in the pathogenesis of diabetic complications, comprise a series of related chemical structures which might possess dissimilar immunogenic characteristics. In this study the levels of AGE in plasma samples from normal subjects (N=41) and diabetic patients (N=44) were measured by ELISA using two polyclonal antisera (named CF5 and CF199, respectively, and immunologically characterized) raised using two different immunogens and immunization techniques. Age levels were significantly higher in diabetic than in normal plasma samples (P<0.0001) with both antisera. However, CF199 detected higher AGE levels than CF5 both in normal (P<0.0001) and diabetic (P<0.005) samples. Pre-incubation with AGE-bovine serum albumin (BSA) caused the loss of most the reactivity of both antisera. Pre-incubation with carboxy-methyl-lysine-BSA (an oxidation-derived AGE) induced the loss of nearly all CF5 reactivity while CF199 retained a significant amount of activity against AGE antigens. Moreover, CF5 lost over 90% of its reactivity against BSA incubated with high glucose under non-oxidative conditions, suggesting its recognition of mainly oxidation-derived AGE epitopes. The different AGE levels measured by the two antisera suggests, therefore, that one single antiserum is unable to recognize all the various AGE epitopes which might be present, at any time, in tissues and body fluids in health and disease.

Diabetes Mellitus↗

Transgenic mice with dominant negative PKC-theta in skeletal muscle: a new model of insulin resistance and obesity.

Protein kinase C theta (PKC-theta) is the PKC isoform predominantly expressed in skeletal muscle, and it is supposed to mediate many signals necessary for muscle histogenesis and homeostasis, such as TGFbeta, nerve-dependent signals and insulin. To study the role of PKC-theta in these mechanisms we generated transgenic mice expressing a "kinase dead" mutant form of PKC-theta (PKC-thetaK/R), working as "dominant negative," specifically in skeletal muscle. These mice are viable and fertile, however, by the 6-7 months of age, they gain weight, mainly due to visceral fat deposition. Before the onset of obesity (4 months of age), they already show increased fasting and fed insulin levels and reduced insulin-sensitivity, as measured by ipITT, but normal glucose tolerance, as measured by ipGTT. After the 6-7 months of age, transgenic mice develop hyperinsulinemia in the fasting and fed state. The ipGTT revealed in the transgenic mice both hyperglycemia and hyperinsulinemia. At the molecular level, impaired activation of the IR/IRS/PI3K pathway and a significant decrease both in the levels and in insulin-stimulated activation of the serine/threonine kinase Akt were observed. Taken together these data demonstrate that over-expression of dominant negative PKC-theta in skeletal muscle causes obesity associated to insulin resistance, as demonstrated by defective receptor and post-receptorial activation of signaling cascade.

Animals↗

New instrumental set for the assessment of the hand functionality.

Hand motor deficits have been widely investigated, and several devices have been proposed for the selective and accurate study of specific hand motor tasks. Most studies have focused on the four, long fingers. The thumb function, although extremely important for the performance of most daily activities involving the hand, has scarcely been documented. A set of general-purpose, instrumental measuring devices has been designed and constructed at the authors' laboratory to measure and monitor the force each finger exerts separately, under isometric conditions, during pressing tasks. More generally, it is meant for the functional evaluation of the normal hand in different postures, but it also provides reliable measurements of the injured or deformed hand. The instrumental set is suitable for both biomechanical research and clinical applications. Effectively integrated with a visual feedback tool, it could be exploited in delivering and monitoring custom-designed rehabilitation programmes. The characteristics of the force transducers (range 0-100 N) were: inter-axis crosstalk < 4%; non-linearity < +/- 0.4% f.s.; hysteresis < 0.3% f.s.; overall accuracy +/- 1% f.s. The overall measurement system resolution was better than 0.1 N, and the keys response to the mechanical shock (acquired at 10 kHz) showed a resonance frequency of about 1 kHz. It was observed that the thumb contributed more than 30% of the overall pressing force.

Adult↗

Left-sided heart valve abnormalities and risk of ischemic cerebrovascular accidents in patients with systemic lupus erythematosus.

The aim of the study was to assess the relationship between ischemic cerebrovascular accidents (ICVAs), that is, transient ischemic attack (TIA) or stroke, and left-sided heart valve abnormalities (LHVAs) in patients with systemic lupus erythematosus (SLE). In total, 71 consecutive SLE patients were studied. At baseline, history, clinical and laboratory evaluations, as well as trans-thoracic echocardiography (TTE) were performed. From the original population, so patients were followed up for a mean time of 5.80 +/- 1.53 years. After a mean period of 5.39 +/- 1.42 years; 40 patients underwent a repeat TTE. Previous ICVA history was present at baseline in 16 patients (22.5%). Of these, 13 (81.2%) had evidence of LHVAs on TTE. Previous ICVAs were significantly associated to diagnosis of secondary anti-phospholipid syndrome (SAPS), positivity for anti-cardiolipin antibodies (aCl), and LHVAs. Multivariate analysis confirmed the correlation between previous ICVAs and LHVAs. LHVAs were not more commonly observed in patients with SAPS compared to patients without SAPS. At the end of follow-up, irrespective of any differences in antithrombotic treatment, ICVAs had occurred in 13 patients. During follow-up, ICVAs had recurred in seven patients, while a first event TIA occurred in one patient. Multivariate analysis confirmed the relationship between ICVAs and LHVAs, and a trend towards a positive correlation of the former with SAPS. This study demonstrates that LHVAs represent a compelling risk factor for the development of ICVAs in SLE patients. Conversely, SAPS and aCl positivity, although associated with ICVAs, did not clearly correlate with LHVAs in our study. These results provide insight on the pathogenesis of ICVAs and may give clues on the potential efficacy of preventive/therapeutic strategies in different SLE subpopulations.

Adolescent↗

Iron, hepatic stellate cells and fibrosis in chronic hepatitis C.

BACKGROUND/AIMS: In patients with chronic hepatitis C, hepatic iron concentration correlates with liver fibrosis. However, it is not clear whether this correlation merely reflects the presence of more active disease, or iron exacerbates chronic hepatitis C virus (HCV)-induced damage through activation of hepatic stellate cells and regeneration of hepatocytes. MATERIALS AND METHODS: We studied 72 HCV-positive patients, staged according to the Ishak's score system. We measured hepatic iron concentration with spectrophotometry and evaluated the number of hepatic stellate cells (using monoclonal antibody against alpha smooth muscle actin) and proliferating hepatocytes (using monoclonal antibody against Ki67). Iron and ferritin serum levels were also determined. RESULTS: Hepatic iron concentration correlated statistically with ferritin serum level (r = 0.59, P < 0.001), with grading (r = 0.47, P < 0.001) and staging (r = 0.51, P < 0.001) scores for chronic hepatitis in the whole group of patients. Hepatic iron concentration correlated positively with stellate cell number (r = 0.55, P = 0.004) and Ki67-positive hepatocyte number (r = 0.36, P = 0.08) in patients with chronic hepatitis C and low grading score (< 3). CONCLUSIONS: In patients with chronic hepatitis C and low grading score, hepatic iron could play a role in the activation of hepatic stellate cells and in the progression of fibrosis.

Actins↗

Advanced glycation end product levels in eye lenses, aorta, and tail tendon in transplanted diabetic inbred Lewis rats.

BACKGROUND: Pancreatic islet transplantation in diabetes, by restoring euglycemia, should in time correct the abnormal accumulation of advanced glycation end products (AGEs) over target tissues, thus delaying the development of late diabetic complications. METHODS: Homologous islet transplantation was performed in inbred Lewis rats 15 days (TA), 4 months (TB), and 8 months (TC) after streptozotocin diabetes. Group TA was studied for 12 months and groups TB and TC were studied for 4 months after transplantation. Normal (N) and diabetic (D) rats formed the control groups. Metabolic control in the transplant (T) groups was evaluated by oral glucose tolerance test. Blood glucose, glycated hemoglobin, and body weight were determined in all groups. AGE levels were determined by spectrofluorometry in eye lens proteins and by ELISA in aortic and tail tendon collagen. RESULTS: T groups showed normal oral glucose tolerance tests and metabolic parameters. The latter were altered in all D groups (P<0.005 to P<0.0001 versus N and T groups). AGEs were increased in the D groups (P<0.05 to P<0.001) versus the N groups. AGEs in the TA and TB groups were not different from those of the N groups but were significantly reduced (P<0.05 to P<0.001) when compared with those of the D groups. In the TC group, eye lens AGEs were significantly elevated (P<0.001) or significantly reduced (P<0.01) when compared with those of the N or D groups, respectively. Aortic collagen AGEs were elevated (P<0.01) by comparison with those of the N groups and not statistically different from those of the D groups. Tail tendon collagen AGE levels lay between those of the N and D groups, without reaching a statistical significance. CONCLUSIONS: These results indicate that primary and early secondary (groups TA and TB) but not late secondary (group TC) islet transplantations are capable of blocking or reducing an abnormal accumulation of AGEs, thus confirming the importance of preventive transplantation therapies.

Animals↗

Parathyroid hormone activation of map kinase in rat duodenal cells is mediated by 3',5'-cyclic AMP and Ca(2+).

In a previous study, we demonstrated that parathyroid hormone (PTH) stimulates in rat duodenal cells (enterocytes) the phosphorylation and activity of extracellular signal-regulated mitogen-activated protein kinase (MAPK) isoforms ERK1 and ERK2. As PTH activates adenylyl cyclase (AC) and phospholipase C and increases intracellular Ca(2+) in these cells, in the present study we evaluated the involvement of cAMP, Ca(2+) and protein kinase C (PKC) on PTH-induced MAPK activation. We found that MAPK phosphorylation by the hormone did not depend on PKC activation. PTH response could, however, be mimicked by addition of forskolin (5-15 microM), an AC activator, or Sp-cAMP (50-100 microM), a cAMP agonist, and suppressed to a great extent by the AC inhibitor, compound Sq-22536 (0.2-0.4 mM) and the cAMP antagonist Rp-cAMP (0.2 mM). Removal of external Ca(2+) (EGTA 0.5 mM), chelation of intracellular Ca(2+) with BAPTA (5 microM), or blockade of L-type Ca(2+)-channels with verapamil (10 microM) significantly decreased PTH-activation of MAPK. Furthermore, a similar degree of phosphorylation of MAPK was elicited by the Ca(2+) mobilizing agent thapsigargin, the Ca(2+) ionophore A23187, ionomycin and membrane depolarization with high K(+). Inclusion of the calmodulin inhibitor fluphenazine (50 microM) did not prevent hormone effects on MAPK. Taken together, these results indicate that cAMP and Ca(2+) play a role upstream in the signaling mechanism leading to MAPK activation by PTH in rat enterocytes. As Ca(2+) and cAMP antagonists did not block totally PTH-induced MAPK phosphorylation, it is possible that linking of the hormone signal to the MAPK pathway may additionally involve Src, which has been previously shown to be rapidly activated by PTH. Of physiological significance, in agreement with the mitogenic role of the MAPK cascade, PTH increased enterocyte DNA synthesis, and this effect was blocked by the specific inhibitor of MAPK kinase (MEK) PD098059, indicating that hormone modulation of MAPK through these messenger systems stimulates duodenal cell proliferation.

Animals↗

Spondylodiscitis and infective endocarditis: case studies and review of the literature.

STUDY DESIGN: This study evaluated the association between infective endocarditis and infective spondylodiscitis and its clinical features. OBJECTIVES: To report case studies of patients with spondylodiscitis complicating infective endocarditis. SUMMARY OF BACKGROUND DATA: Early diagnosis of infective endocarditis as the source of the spondylodiscitis is often difficult because clinical and radiologic patterns are similar to those present in spondylodiscitis alone. METHODS: The case records of the patients with infective endocarditis admitted to our Department from 1991-1998 were reviewed. The diagnosis of spondylodiscitis was made on the basis of clinical features and of typical radiologic signs. RESULTS: Among 30 patients affected by infective endocarditis, three also were affected by spondylodiscitis. All patients fully recovered after appropriate antibiotic therapy. CONCLUSIONS: In all patients with spondylodiscitis, infective endocarditis should be excluded, particularly in patients with a history of heart valve disease.

Adult↗

The stimulation of MAP kinase by 1,25(OH)(2)-vitamin D(3) in skeletal muscle cells is mediated by protein kinase C and calcium.

In previous work we have demonstrated that the steroid hormone 1,25(OH)(2)-vitamin D(3) [1,25(OH)(2)D(3)] stimulates in skeletal muscle cells the phosphorylation and activity of the extracellular signal-regulated mitogen-activated protein (MAP) kinase isoforms ERK1 and ERK2. In the present study we evaluated the involvement of Ca(2+) and protein kinase C (PKC) on 1,25(OH)(2)D(3)-induced activation of MAP kinase. The hormone response was found to depend on PKC stimulation since it was attenuated by the PKC inhibitors calphostin C (100 nM) and bisindolylmaleimide I (30 nM) and PKC downregulation by prolonged treatment with the phorbol ester TPA (1 microM). Removal of external Ca(2+), chelation of intracellular Ca(2+) with BAPTA (5 microM), inhibition of phosphoinositide-phospholipase C (PLC) by neomycin, the calmodulin antagonist fluphenazine (50 microM) and the specific inhibitor of calmodulin kinase II, KN-62 (10 microM), significantly decreased 1,25(OH)(2)D(3)-activation of MAP kinase. In addition, the Ca(2+)-channel blocker verapamil (5 microM) suppressed hormone-induced MAP kinase activity in these cells. Furthermore, the Ca(2+)-mobilizing agent thapsigargin and the Ca(2+)-inophore A23187 paralleled the phosphorylation of MAP kinase observed with 1,25(OH)(2)D(3). Taken together, these results indicate that PKC and Ca(2+) are two upstream activators mediating the effects of 1,25(OH)(2)D(3) on MAP kinase in skeletal muscle cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗