Biomedical subjects

S Grasso

Publications and source records attributed to S Grasso.

At least 19 recordsLinked to original sources

PubMed2006

The inflammatory abdominal aortic aneurysm and coronary artery disease. Case report and review.

Inflammatory abdominal aortic aneurysm (IAAA) is defined as an unusually thickened aneurysmatic wall, encircled by a wide dense perianeurysmal and/or retroperitoneal fibrosis with adjacent tissues adhesion, and is now considered as an extreme shape of the common phlogistic process involved in atherosclerotic plaque formation. Latest studies demonstrated that inflammation plays an important role in coronary disease and in other atherosclerosis manifestations. We introduce the clinical case of a patient with IAAA who developed an acute myocardial infarction 6 months after the surgical procedure on the aorta. Through a literature review about IAAA we stress the clinical usefulness of the inflammatory markers as independent predictors in management of patients with coronary disease and we present the hypothesis, related to the introduced case, of an advanced coronary disease, aggravated or clinically revealed after the cytokine storm related to important localized inflammatory engagements or great vascular surgery treatments.

Aortic Aneurysm, Abdominal↗

PubMed2003

Adaptive responses to the stress induced by hyperthermia or hydrogen peroxide in human fibroblasts.

Perturbation of oxidant/antioxidant cellular balance, induced by cellular metabolism and by exogenous sources, causes deleterious effects to proteins, lipids, and nucleic acids, leading to a condition named "oxidative stress" that is involved in several diseases, such as cancer, ischemia-reperfusion injury, and neurodegenerative disorders. Among the exogenous agents, both H(2)O(2) and hyperthermia have been implicated in oxidative stress promotion linked with the activation of apoptotic or necrotic mechanisms of cell death. The goal of this work was to better understand the involvement of some stress-related proteins in adaptive responses mounted by human fibroblasts versus the oxidative stress differently induced by 42 degrees C hyperthermia or H(2)O(2.) The research was developed, switching off inducible nitric oxide synthase (iNOS) expression through antisense oligonucleotide transfection by studying the possible coregulation in the expression of HSP32 (also named HO-1), HSP70, and iNOS and their involvement in the induction of DNA damage. Several biochemical parameters, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), reactive oxygen species formation, glutathione levels, immunocytochemistry analysis of iNOS, HSP70, and HO-1 levels, genomic DNA fragmentation (HALO/COMET assay), and transmembrane mitochondrial potential (deltaPsi) were examined. Cells were collected immediately at the end of the stress-inducing treatment. The results, confirming the pleiotropic function of i-NOS, indicate that: (i). HO-1/HSP32, HSP70, and iNOS are finely tuned in their expression to contribute all together, in human fibroblasts, in ameliorating the resistance to oxidative stress damage; (ii). ROS exposure, at least in hyperthermia, in human fibroblasts contributes to growth arrest more than to apoptosis activation; and (iii). mitochondrial dysfunction, in presence of iNOS inhibition seems to be clearly involved in apoptotic cell death of human fibroblasts after H(2)O(2) treatment, but not after hyperthermia.

Antioxidants↗

PubMed2002

Chromatographic determination of 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-ones in rat plasma: relationship to their anticonvulsant activity.

The present investigation was designed to develop an assay suitable for pharmacokinetic studies of new compounds, i.e. the novel 7,8-methylenedioxy-4H-2,3-benzodiazepin-4-one derivatives (2a and 2b), acting as non-competitive AMPA-receptor antagonists. A reversed-phase high-performance liquid chromatographic method has been developed to determine the time-course of plasma concentrations of derivatives 2a and 2b administered intraperitoneally to Sprague-Dawley rats. The separation of compounds studied and a N-methyl-2,3-benzodiazepin-4-one derivative as internal standard (I.S.) from plasma, were carried out by liquid-liquid extraction using diethyl ether. The samples were injected onto the analytical column (Partisil 10 ODS) eluted with acetonitrile/0.01 M acetate buffer (pH 5.3) at a flow-rate of 2 ml/min and detected at 240 nm. Compounds 2a, 2b and I.S. gave retention times of 8.5, 5.25 and 11.1 min, respectively. The selectivity of the method was satisfactory. The mean recovery from spiked rat plasma ranged from 86.7 to 91.6% for 2a, and from 85.1 to 87.0% for 2b. The procedures were validated with a good reproducibility and linear response from 0.0625 to 2 microg/ml, with a regression coefficient of 0.9932 for 2a and 0.9854 for 2b. The lower limit of quantification (LOQ) was taken as 15 ng/ml for the two compounds. 2a and 2b showed no signs of significant degradation in rat plasma during storage at -20 degrees C and following freeze/thaw cycles. Moreover, plasma levels of the tested compounds have been correlated with their anticonvulsant activity, determined in vivo in genetically epilepsy-prone rats. Due to its sensitivity, the method was suitable for application to pharmacokinetic study.

Animals↗

PubMed2002

[Uterus in a male: persistent Mullerian duct syndrome. Report of a case with embryological considerations].

We describe a case of persistent mullerian duct syndrome incidentally found in a 79-year-old man. It was characterized by the presence of a uterus-like retroperitoneal mass composed of an ovoidal corpus and rudimental portio with a central lumen. Histologically the mass was leiomyomatous in nature, closely resembling myometrium, while the central lumen was lined by a monolayer of ciliated cuboidal to columnar epithelium similar to embryo-fetal celomatic epithelium. Although this is a dysembryogenetic syndrome due to the lack of regression of the mullerian duct, it may be incidentally discovered in elderly patients, as in the present case during hernioplastic surgery. We also briefly discuss the regression of mullerian duct, focusing on morphological features observed in a large collection of human embryos and fetuses, in order to better understand the pathogenesis of a "uterus' in a male without evidence of sexual abnormalities.

Aged↗

PubMed2001

7-Chloro-1-(2,6-difluorophenyl)-1H,3H-thiazolo.

The title molecules, C(15)H(9)ClF(2)N(2)S and C(16)H(12)F(2)N(2)S, respectively, display the well known butterfly-like conformation with a flat thiazolobenzimidazole system. In both compounds, the mean plane through the tricyclic system is almost perpendicular to the 2,6-difluorophenyl ring. This arrangement of the aryl group is determined by two intramolecular hydrogen bonds and by an attractive F.S interaction.

Anti-HIV Agents↗

PubMed2001

Synthesis and anticonvulsant activity of novel and potent 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-ones.

The synthesis and anticonvulsant activity of 1-aryl-7,8-methylenedioxy-1,2,3,5-tetrahydro-4H-2,3-benzodiazepin-4-(thi)ones (4a-d) and their 3-N-alkylcarbamoyl derivatives (4e-h) are reported. The new compounds possess marked anticonvulsant properties, comparable to those of the dehydro analogues 3 and higher than that of GYKI 52466 (1). Noteworthy, compound 4c shows a longer-lasting anticonvulsant activity. Electrophysiological experiments show that derivative 4c is less effective than 1 and 3c to reduce the KA-evoked currents in cerebellar granule neurons.

Animals↗

PubMed2001

Proportional assist ventilation.

Partial ventilatory support techniques are intended for patients who are unable to maintain a normal alveolar ventilation, despite normal central control for respiration. Proportional assist ventilation (PAV) is a novel mode of partial ventilatory support in which the ventilator generates an instantaneous inspiratory pressure in proportion to the instantaneous effort of the patient. In theory, PAV should normalize the neuro-ventilatory coupling by making the ventilator an extension of patient's respiratory muscles, while leaving to the patient the entire control of all aspects of breathing. PAV, however, shares a common problem with the conventional partial ventilatory support modes. In mechanically ventilated patients, the respiratory system impedance may change over time. These changes may impair the good matching between ventilator output and patient's ventilatory demand and lead to patient-ventilator asynchrony. To take full advantage of PAV, the authors believe that PAV should continuously and automatically adapt to the respiratory system passive mechanics, assessed by continuous noninvasive measurement of total elastance and resistance.

Algorithms↗

PubMed2001

Comparative immunohistochemical analysis of the expression of cytokeratins, vimentin and alpha-smooth muscle actin in human foetal mesonephros and metanephros.

The human mesonephros is currently regarded as a simplified version of the foetal metanephros, primarily due to the close morphological resemblance between these two structures. The aim of the present study was to define whether human mesonephric and foetal metanephric nephrons share immunophenotypical traits in their corresponding structures (glomeruli, proximal and distal tubules). For this purpose we first investigated immunohistochemically the overall expression and topographical distribution of cytokeratins 7, 8, 18, 19, and 20, vimentin and alpha-smooth muscle actin in mature mesonephric nephrons and compared the results with those obtained in maturing-stage foetal metanephric nephrons. No expression of cytokeratins 7 and 20 was found. Cytokeratins 8, 18, and 19 and vimentin showed a restricted and basically coincident expression along the different components of both mesonephric and metanephric nephrons. These findings indicate that the intermediate filament protein profile of human mature mesonephric nephrons closely recapitulates that observed in developing metanephros and thereby strengthens the concept that human mesonephros, a transient ontogenic structure, is largely similar to the foetal metanephros. The sole difference between human mesonephros and foetal metanephros was the divergent expression of alpha-smooth muscle actin. This protein exhibited an increasingly accentuated mesangial expression paralleling the morphological maturation of metanephric glomerulus, whereas it was absent from the mesonephric one. This would suggest that the mesangial cells in these two renal structures have a different function during the foetal life.

Actins↗

PubMed2001

Synthesis and structure-activity relationships of 2,3-benzodiazepines as AMPA receptor antagonists.

There is increasing evidence of the potential therapeutic utility of glutamate receptor antagonists in the treatment of several neurodegenerative disorders, including stroke and epilepsy. In the last few years noncompetitive AMPA receptor antagonists have received considerable attention due to their therapeutic potentiality. The discovery of GYKI 52466, the prototype of noncompetitive AMPA receptor antagonists endowed with anticonvulsant and neuroprotective properties, induced growing interest on 2,3-benzodiazepine derivatives. This review covers the chemistry and pharmacology of this important class of AMPA receptor antagonists.

Anti-Anxiety Agents↗

PubMed2001

[The glial cell in the ontogenesis of the human peripheral sympathetic nervous system and in neuroblastoma].

The developmental role of glial cells in the human peripheral sympathetic nervous system is still unclear. Immunohistochemical studies on human embryos and fetuses reveal that the migrating clusters of undifferentiated neuroblasts contain sustentacular cells and are completely separated from adjacent tissues by a peripheral layer of Schwann-like cells and continuous basement membrane. This topographic distribution seems to be strategic and suggests a role of glial cells and extracellular matrix in migration and differentiation processes of undifferentiated neuroblasts. A similar distribution pattern between glial cells/extracellular matrix and neuroblasts can be observed in neuroblastomas exhibiting a microscopic nodular growth pattern, providing additional evidence that neuroblastoma represents an arrest in the differentiation/maturation of cells during the ontogenesis of the human peripheral sympathetic nervous system. Although it is commonly believed that Schwann cells in neuroblastoma arise from cells "infiltrating neoplasia", arising from peripheral nerves adjacent tumor, our ontogenetic findings suggest that the glial cell component of neuroblastoma derives from that normally associated with developing neuroblasts. We discuss the normal development of the three lineages of the human peripheral sympathetic nervous system (ganglial, neuroendocrine or chromaffin, and glial), with special emphasis on glial cells and extracellular matrix components and on the comparison between ontogenesis and neuroblastoma.

Basement Membrane↗

PubMed2000

Synthesis and anticonvulsant activity of novel and potent 6,7-methylenedioxyphthalazin-1(2H)-ones.

In this paper, we describe the synthesis of a series of novel substituted 4-aryl-6,7-methylenedioxyphthalazin-1(2H)-ones. The anticonvulsant activity of these compounds against audiogenic seizures was evaluated in DBA/2 mice after intraperitoneal (ip) injection. Most of these derivatives are more active than 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (1, GYKI 52466), a well-known noncompetitive AMPA receptor antagonist. As deduced by the rotarod test, all the compounds exhibit a toxicity lower than that of 1. Within the series of derivatives submitted to investigation, 4-(4-aminophenyl)-2-butylcarbamoyl-6,7-methylenedioxyphthalazin -1(2H)-one (21) proved to be the most active compound and is 11-fold more potent than 1 (i.e., ED50 3.25 micromol/kg for 21 versus ED50 35.8 micromol/kg for 1). When compared to 1, compound 21 as well as its analogue 4-(4-aminophenyl)-6,7-methylenedioxyphthalazin-1(2H)-one (16) show a longer lasting anticonvulsant activity. Compound 21 also effectively suppresses seizures induced in Swiss mice by maximal electroshock (MES) and pentylenetetrazole (PTZ). Furthermore, it antagonizes in vivo seizures induced by 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), 2-amino-3-(3-hydroxy-5-tert-butyl-isoxazol-4-yl)propionic acid (ATPA), and kainate (KA), and its anticonvulsant activity is reversed by pretreatment with aniracetam. Using the patch-clamp technique, the capability of derivatives 16 and 21 to antagonize KA-evoked currents in primary cultures of granule neurons was tested. They behaved as antagonists, but they proved to be less effective than 1 and 1-(4-aminophenyl)-3,4-dihydro-4-methyl-3-N-methylcarbamoyl-7,8-met hylenedioxy-5H-2,3-benzodiazepine (2, GYKI 53655) to reduce the KA-evoked currents.

Acoustic Stimulation↗

PubMed2000

Dichotomic effects of IFN-gamma on the development of systemic lupus erythematosus-like syndrome in MRL-lpr / lpr mice.

Systemic lupus erythematosus (SLE)-prone female MRL-lpr / lpr (MRL-lpr) mice were treated with mouse or rat IFN-gamma under different experimental conditions, both prophylactically in 6- to 8 week-old animals and therapeutically in 12- to 18-week-old SLE-affected mice. It was found that IFN-gamma heterogeneously modulated the course of the disease in MRL-lpr mice. When administered prophylactically, IFN-gamma favorably modulated the histological, serological and clinical signs of the disease. Relative to untreated or PBS-treated control animals, the MRL-lpr mice which received IFN gamma were virtually free of inflammatory infiltration of the kidneys and the lungs, had lower levels of azotemia with reduction of both circulating IgG1, IgG2a and IgG3 and anti-double strand (ds) and single strand (ss) DNA antibodies, milder skin vasculitis, significantly reduced enlargement of their lymph nodes and lower weight of the spleens. IFN-gamma also lowered the rate of mortality of MRL-lpr mice. In contrast to these findings, therapeutically administered IFN-gamma worsened the course of the disease in MRL-lpr mice, which exhibited increased proteinuria, higher levels of IgG2a and IgG3 and anti-ds and -ss DNA antibodies, more aggressive nephritis and died at an earlier age than PBS-treated control mice. The dichotomic effect of IFN-gamma on disease manifestation in MRL-lpr mice offers new insights into the complex role of this cytokine in the regulation of systemic autoimmunity such as SLE.

Animals↗

PubMed2000

Cathepsin D is a marker of ganglion cell differentiation in the developing and neoplastic human peripheral sympathetic nervous tissues.

Cathepsin D (CD) is an aspartic proteinase which has been immunolocalised in intestinal ganglion cells of human neonates and adults. The aim of the present study was to define whether CD is a reliable ganglion cell differentiation marker in routinely fixed, paraffin-embedded tissues. For this purpose, we investigated immunohistochemically the expression and distribution of CD in the developing human peripheral sympathetic nervous system (PSNS) and gastroenteric nervous system (GENS), and in childhood neuroblastic tumours (NTs; neuroblastomas, ganglioneuroblastomas and ganglioneuromas), where ganglion cells differentiate from immature neuroblastic cells. During ontogenesis, CD expression is restricted to ganglion cell lineage with a progressively more intense cytoplasmic staining, mirroring the morphological differentiation of ganglion cells with increasing gestational ages. In neoplastic tissues, CD immunoreactivity was restricted to neuroblastic cells showing morphological features of gangliocytic differentiation (differentiating neuroblastomas, ganglioneuroblastomas) as well as to neoplastic ganglion cells (ganglioneuroblastomas, ganglioneuromas). We conclude that CD is a reliable ganglion cell differentiation marker, which can be used routinely to stain developing and mature ganglion cells in formalin-fixed, paraffin-embedded tissues. Furthermore, our results indicate that CD immunoreactivity in childhood NTs recapitulates the changes during normal PSNS development, as previously reported for Bcl-2 oncoprotein, c-ErbB2, insulin-like growth factor 2 and beta2-microglobulin. This is consistent with the current view that childhood NTs exhibit gene expression profiles mirroring those occurring during PSNS ontogenesis.

Adult↗

PubMed2000

Synthesis and in vitro antitumour activity evaluation of 1-aryl-1H,3H-thiazolo[4,3-b]quinazolines.

A series of 1H,3H-thiazolo[4,3-b]quinazolines (2a-i) were synthesized and evaluated for their in vitro antitumour activity against ca. 60 human tumour cell lines. They exhibited moderate (2c, 2d, 2f and 2g) to strong (2a, 2b, 2e, 2h and 2i) cell-growth inhibition at a concentration of 10(-4) M, but weak activity at lower concentrations. Only 1-(2,6-dichlorophenyl)-1H,3H-thiazolo[4,3-b]quinazoline (2h) possesses a significant growth inhibitory activity on 22 cell lines at a concentration of 10(-5) M.

Antineoplastic Agents↗

PubMed2000

Sustentacular cells in sporadic paraganglioma-like medullary thyroid carcinoma: report of a case with diagnostic and histogenetic considerations.

Sustentacular cells (SCs) are glial supporting cells of the fetal, adult normal, and neoplastic extra and adrenal human chromaffin cell lineage. SCs have also been identified in some cases of medullary thyroid carcinoma (MTC), raising both diagnostic and histogenetic problems. We report a rare case of a sporadic paraganglioma-like variant of MTC showing numerous S-100 protein and glial fibrillar acid protein (GFAP) positive SCs encircling neoplastic cells in a nesting (Zellballen) pattern similar to that observed in paragangliomas or pheochromocytomas. Although stromal amyloid deposits were only focally detected, diagnosis was immunohistochemically confirmed by immunoreactivity of the neoplastic cells for cytokeratin, CEA, calcitonin, chromogranin A, neuron-specific-enolase, and synapthopysin. As for the histogenesis of SCs, if we assume that MTC is a neural crest-derived tumor, it is likely that these cells reflect the ability of the common precursor cell to differentiate towards a sustentacular-type glial cell lineage in addition to the typical neuroendocrine one. This viewpoint is supported by the evidence that rare cases of MTC may contain neoplastic or supporting cells showing a multidirectional differentiation (usually neuroendocrine and melanocytic) that recapitulates the different cell lineages arising from the developing neural crests.

Carcinoma, Medullary↗

PubMed2000

Proportional assist ventilation.

Acute respiratory failure due to derangement of mechanical properties of respiratory system and/or to neuromuscular weakness has been defined as "poor neuroventilatory coupling.'' Proportional assist ventilation (PAV) is an innovative mode of partial ventilatory support designed to "amplify'' patient inspiratory effort and thus to restore a normal "neuroventilatory coupling.'' Potential advantages of PAV in terms of more physiologic patient-ventilator interactions have been evaluated by several studies. We review the literature to elucidate the state of the art of the clinical implementation of PAV.

Journal Article↗

PubMed2000

Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

Adult↗

PubMed2000

Pressure-time curve predicts minimally injurious ventilatory strategy in an isolated rat lung model.

BACKGROUND: We tested the hypothesis that the pressure-time (P-t) curve during constant flow ventilation can be used to set a noninjurious ventilatory strategy. METHODS: In an isolated, nonperfused, lavaged model of acute lung injury, tidal volume and positive end-expiratory pressure were set to obtain: (1) a straight P-t curve (constant compliance, minimal stress); (2) a downward concavity in the P-t curve (increasing compliance, low volume stress); and (3) an upward concavity in the P-t curve (decreasing compliance, high volume stress). The P-t curve was fitted to: P = a. tb +c, where b describes the shape of the curve, b = 1 describes a straight P-t curve, b < 1 describes a downward concavity, and b > 1 describes an upward concavity. After 3 h, lungs were analyzed for histologic evidence of pulmonary damage and lavage concentration of inflammatory mediators. Ventilator-induced lung injury occurred when injury score and cytokine concentrations in the ventilated lungs were higher than those in 10 isolated lavaged rats kept statically inflated for 3 h with an airway pressure of 4 cm H2O. RESULTS: The threshold value for coefficient b that discriminated best between lungs with and without histologic and inflammatory evidence of ventilator-induced lung injury (receiver-operating characteristic curve) ranged between 0.90-1.10. For such threshold values, the sensitivity of coefficient b to identify noninjurious ventilatory strategy was 1.00. A significant relation (P < 0.001) between values of coefficient b and injury score, interleukin-6, and macrophage inflammatory protein-2 was found. CONCLUSIONS: The predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.

Animals↗