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Biomedical subjects

L Rossi

Publications and source records attributed to L Rossi.

At least 145 records · Page 8Linked to original sources

Lack of R117H mutation in the cationic trypsinogen gene in patients with tropical pancreatitis from Bangladesh.

The etiology of nonalcoholic chronic pancreatitis, occurring in tropical regions, is unknown. Although environmental factors may play a role in its pathogenesis, a specific genetic predisposition may be necessary. The genetic mutation responsible for hereditary pancreatitis was described recently. Unlike in patients with hereditary pancreatitis, we found a lack of the R117H mutation in the cationic trypsinogen gene in all patients with tropical pancreatitis from Bangladesh.

Adolescent↗

Chronic mania. Family history, prior course, clinical picture and social consequences.

BACKGROUND: Mania with chronic course has been overlooked in the recent literature. Our aim was clinically to characterise and validate this form of mania. METHOD: We evaluated 155 people with DSM-III-R mania and assessed their family history, temperament, symptomatology and course. We used a semi-structured interview for mood disorders, as well as the Comprehensive Psychopathological Rating Scale and the Scale for the Assessment of Positive Symptoms. RESULTS: Twenty (13%) had a chronic course arising from a background of hyperthymic temperament and recurrent mania, with a deteriorative pattern. Clinically, they were characterised by a significantly high rate of almost constant euphoria, grandiose delusions and related delusions, but had relatively low rates of sleep disturbance, psychomotor agitation and hypersexuality. CONCLUSION: Even with current therapies a significant number of people with bipolar disorders have a deteriorative outcome associated with the gradual disappearance of acute mania with an increase in megalomanic delusions, alienation from loved ones and decreased likelihood of medical and psychiatric care.

Adolescent↗

Intrauterine growth retardation: evidence for the activation of the insulin-like growth factor (IGF)-related growth-promoting machinery and the presence of a cation-independent IGF binding protein-3 proteolytic activity by two months of life.

Thirty-seven children with intrauterine growth retardation (IUGR) were enrolled in a 3-mo longitudinal study. Weight, length, and knee-heel length (by knemometry) were measured at birth and at 7, 14, 30, 60, and 90 d. GH, IGF-I, IGF binding protein (BP)-3, IGFBP-1, and C-peptide were measured at birth and at 2 mo. IGFBP-3 Western immunoblotting and proteolytic activity assay were also performed. Twenty-five newborns with birth weight appropriate for gestational age were chosen as controls. At birth IUGR newborns showed levels of GH and IGFBP-1 significantly higher, and IGF-I, IGFBP-3, and C-peptide significantly lower than control subjects. At 2 mo GH and IGFBP-1 levels decreased, whereas IGF-I, IGFBP-3, and C-peptide rose, attaining the concentrations found in control subjects at birth. Baseline peptide levels as well as their 2-mo variations did not correlate with the gain in weight, supine length, and knee-heel length recorded at 3 mo. Fourteen of nineteen IUGR cord blood samples showed the presence of the intact approximately 42-39-kD IGFBP-3 doublet and the major approximately 29-kD fragment. At 2 mo the IGFBP-3 band pattern was characterized by the predominance of a approximately 18-kD fragment in 6 of 19 tested IUGR infants. The incubation of 2-mo IUGR samples with normal adult serum induced the appearance of the approximately 18-kD band, which was not modified by the addition of EDTA. These results suggest that: 1) the IGF-related growth-promoting mechanism is impaired in IUGR children at birth but is fully restored at 2 mo; 2) the cord blood levels of GH, IGF-I, IGFBP-3, IGFBP-1, and C-peptide are not predictive of the weight and length gain during the first 3 mo of life; 3) IUGR children have at least two different IGFBP-3 proteases, one cation-dependent protease that is present at birth and able to yield the major approximately 29-kD IGFBP-3 fragment and a second one, with a different activation timing, which exhibits cation independence and induces the formation of a approximately 18-kD IGFBP-3 form.

Adult↗

IGF-I and IGF-binding protein-1 are related to cortisol in human cord blood.

OBJECTIVE: To assess cortisol concentrations in cord blood and investigate their relationships with the IGF system. STUDY DESIGN: Fifteen newborns with birth weight appropriate for gestational age (AGA) and 30 children with intrauterine growth retardation (IUGR) were studied. Serum samples were collected from umbilical cord blood and cortisol, IGF-I and IGF-binding proteins (IGFBPs)-1 and -3 were measured. IUGR infants were followed up for 3 months with repeated measurements of weight, supine length and knee-heel length (by knemometry). RESULTS: IUGR newborns showed significantly greater concentrations of IGFBP-1 (P<0.0001) and lower concentrations of IGF-I (P< 0.0001) and IGFBP-3 (P< 0.0001) than did controls. In AGA children, cortisol correlated inversely with IGF-I (r=-0.75, P< 0.002) and directly with IGFBP-1 (r=0.52, P <0.05), whereas no correlation between cortisol and IGF system-related variables was observed in IUGR. Finally, in IUGR children an inverse correlation was found between length gain in the first trimester of life and cortisol concentrations at birth (r=-0.54, P < 0.005). CONCLUSIONS: Cortisol might be a physiological regulator of fetal growth, at least in the last part of pregnancy, by modulating IGF-I and IGFBP-1 release under conditions of fetal stress. In IUGR children, a rearrangement of this growth control mechanism seems to occur. The close inverse relationship of cortisol with linear growth, if confirmed by large-scale studies, suggests cord blood cortisol to be potentially predictive of early postnatal catch-up growth in IUGR infants.

Fetal Blood↗

Discrete T-lymphocytic leptomeningitis of the ventral medullary surface in a case of Sudden Unexpected Infant Death.

The Authors report the case of a 4 month old female infant dying suddenly and unexpectedly. At post-mortem examination, nothing significant was found, except a focal T-lymphocytic brainstem leptomeningitis, involving the ventral medullary surface (VMS) particularly coincidental with the pyramids, with involvement of the outer layer of the nucleus arcuatus (NARC). Moreover, the NARC itself presented, on serial sections, interdigitated subdivisions. To the present authors' best knowledge, no case has been recordered in the literature, as yet, exhibiting VMS inflammation, evidently acquired (likely viral) in nature, associated to a NARC developmental defect, altogether bespeaking for the etio-pathogenic importance of such a combined pathology of the central chemosensitive field among the long debated mechanisms of SIDS.

Journal Article↗

[Research on Culicidae attracted to dog bait in Piedmont].

Dog attracted mosquitoes were collected in Piedmont (NW Italy) in 1992 and 1993. Sampling sites where chosen on ecological and epidemiological basis, according to the results of a previous study on the distribution and prevalence of canine filariosis in this region. Dog baited traps were operated monthly (two nights/site from June to September) in six plain sites differing in the prevalence of heartworm infected dogs (including two sites where no positivity was recorded). A single capture was carried out in July-August in three more plain and four hill localities, as well as in a prealpine and a suburban zone inside the heartworm endemic area. The following species were collected (number of specimens in brackets): Aedes caspius (2255), Ae, cantans (1), Ae. cinereus (1), Ae, geniculatus (7), Ae. vexans (58), Aedes spp. (221), Anopheles claviger (1), An. maculipennis s.l. (405), Coquillettidia richiardii (16), Culex modestus (6361), Cx. pipiens (2032), Cx. territans (2), Culex spp. (94), Culiseta annulata (1). Cx. pipiens was captured in 15 sites, Cx. modestus and Ae. caspius in 13, and 12, respectively, An. maculipennis s.l. in 7, Ae. vexans in 6, Cq. richiardii in 4, Ae. geniculatus in 3, Cx. territans in 2, Ae. cantans, Ae. cinereus, An. claviger and Cs. annulata in one. Species abundance and relative composition differed between habitats and between similar habitats with a different prevalence of microfillaraemic dogs. Regression analysis of heartworm prevalence vs. mosquitoes abundance demonstrated a positive linear relationship. Data suggest that four species (Ae. caspius, An. maculipennis s.l., Cx. modestus and Cx. pipiens) are playing a major role in the transmission of canine filariosis in Piedmont.

Animals↗

The prevention of Dirofilaria repens infection with ivermectin/pyrantel chewables.

This trial was conducted to test the efficacy of ivermectin/pyrantel chewables in preventing the development of Dirofilaria repens in dogs. The trial included 155 dogs from an endemic area in North-Western Italy. Prior to enrollment in the study, none of the dogs had microfilariae of D. immitis or D. repens in a concentration test, and all dogs were also seronegative for adult heartworm antigen. Animals remained with their owners and were dosed six times, at monthly intervals according to body weight. Efficacy against D. repens was evaluated approximately 6 and 12 months after the first dosing. None of the treated dogs was found to harbour microfilariae of D. repens or D. immitis on either occasion, whereas 6 of 24 untreated controls had circulating D. repens microfilariae at the final testing. The treatment was well accepted by all dogs.

Administration, Oral↗

Ascites free-water dynamics in decompensated cirrhosis: effects of an acute Hemaccel infusion.

BACKGROUND: Plasma-expanders (PE) are commonly employed to reduce the hemodynamic effects of large-volume paracentesis in patients with decompensated cirrhosis. The aim of this paper is to investigate the effects of PE acute administration on ascites dynamics in cirrhotic patients. METHODS: Wash-out intraabdominal pressure (IAP), ascites volume and free-water peritoneal clearance (FWPC) were evaluated in six decompensated cirrhosis by means of a methylene-blue (MB) dilution method. The method is based on the compartmental analysis of MB peritoneal clearance and has been validated by previous deuterium oxide studies. Immediately after the MB dilution test, a rapid Hemaccel i.v. infusion (500 ml 3.5% in 15 min) was perform-ed in all subjects, thereafter carrying out a second MB test. The obtained results were analyzed by two-way variance analysis. RESULTS: IAP and ascites volume values were not appreciably modified by the PE treatment. Following the Hemaccel infusion, only a fair reduction of FWPC values (from 88.33+/-7.78 to 76.98+/-8.09 ml/min) was observed. CONCLUSIONS: The results obtained indicate that, at least at the employed doses, Hemaccel acute administration has a low impact on the ascites dynamics in decompensated cirrhotics. These data cannot therefore support the hypothesis of a therapeutic use of PE in ascitic patients, but to avoid excessive plasma volume reductions in association with a large volume paracentesis.

Journal Article↗

In vivo evidence of apoptosis in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disease characterized by progressive atrophy of the right ventricular myocardium with fibro-fatty replacement and the risk of electrical instability and sudden death. The disease is often familial and the aetiopathogenesis is still unknown. Recently apoptosis (genetically determined cell death) was postulated to account for progressive loss of myocardium. To establish whether apoptosis is present in ARVC, right ventricular endomyocardial biopsies from 20 patients with clinical and histological diagnosis of ARVC were examined by electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling method (TUNEL). Apoptotic index was calculated as the percentage of positive nuclei in sections stained by TUNEL. Cell proliferation activity was also assessed by argyrophilic staining of the nucleolar organizer region (AgNOR) and MIB-1 antibody analysis. Twenty biopsies taken from patients during monitoring of cardiac transplantation (grade 0 rejection) served as control. Occurrence of apoptosis was correlated with clinical history duration and the presence of acute symptoms and signs like angina, pyrexia, erythrocyte sedimentation rate and creatine phosphokinase elevation, as well as ST segment elevation on basal electrocardiogram. Electron microscopy and TUNEL revealed presence of apoptotic myocytes in seven cases (35%) with a mean apoptotic index of 24.4+/-9.8. The remaining 13 patients and all of the 20 controls were negative both at the electron microscopy and TUNEL. Presence of apoptosis appeared to be significantly related to clinical history duration of less than 6 months (P < 0.001) and presence of acute symptoms and signs (P = 0.007). AgNOR staining and MIB-1 antibody analysis ruled out cell proliferation activity. In conclusion, apoptosis is present in endomyocardial biopsies of patients with ARVC, especially in the early symptomatic phase of disease. Myocardial destruction with replacement by fat may be episodic rather than gradual and continuous.

Adult↗

Erythrocyte engineering for drug delivery and targeting.

A new procedure for the encapsulation of non-diffusible drugs into human erythrocytes was developed. With as little as 50 ml of blood and by using a new apparatus, it was possible to encapsulate a variety of biologically active compounds into erythrocytes in 2 h at room temperature and under blood-banking conditions. The process, which is based on two sequential hypotonic dilutions of washed red cells followed by concentration with a haemofilter and resealing of red cells, allows a 35-50% cell recovery and approx. 30% encapsulation of added drugs. The resulting processed erythrocytes have a normal survival in vivo and can be modified further, with the same apparatus, to increase their recognition by tissue macrophages to perform as a drug-targeting system. The new equipment designed and built for this procedure was named 'Red Cell Loader'.

Cell Membrane Permeability↗

Hyperplasia of the aorticopulmonary paraganglia: a new insight into the pathogenesis of sudden infant death syndrome?

In this study, the Authors search for morphologic alterations in the aorticopulmonary paraganglia (APP) of sudden infant death syndrome (SIDS) victims when compared with age-matched controls. Morphometric studies on serial sections of the APP were performed with an image analyzer in combination with a standard microscope attached to a video camera. APP hyperplasia, characterized by an increase in some parameters such as number, mean lobule diameter and total glomic tissue volume when compared with age-matched controls, was observed in 23.8% of SIDS victims. Similar alterations have been reported in peripheral chemoreceptors of animals and human beings who are chronically hypoxemic. In SIDS, it could reflect an abnormal chemoreceptor function, contributing to an altered respiration control.

Age Factors↗

Use of nonvolatile buffers in liquid chromatography/mass spectrometry: advantages of capillary-scale particle beam interfacing.

The use of nonvolatile buffers like phosphate and citrate is usually incompatible with mass spectrometric detection or may heavily interfere with ion generation. In the case of conventional HPLC flow rates, the continuous buffer deposition produces fouling of the mass spectrometer ion source and may worsen the performance of any LC/MS interface as well. Our research group demonstrated that reducing the mobile phase flow rate in a particle beam interface improves the nebulization and enhances the overall performance. We have also assumed that such a modification may better handle potentially instrument harmful solvents or nonvolatile HPLC buffers. Since the presence of salts does not interfere with the electron ionization process, the particle beam interface can be considered, in principle, particularly suitable for those chromatographic separations that benefit from nonvolatile buffers. The microscale flow rate interface, developed in our laboratory, generates an aerosol from 1 microL/min of mobile phase flow rate. Under these conditions, the absolute amount of a nonvolatile buffer actually introduced into the system is approximately 1/1000 of that carried by a conventional HPLC column, slowing its deposition. This assumption was verified with a real-world application requiring the use of a phosphate buffer at a maximum concentration of 10 mM. It involved the determination of dexamethasone, an anti-inflammatory drug, in human blood after its administration to a patient. Several crucial mass spectral and chromatographic parameters were monitored during a 35-day period of intense use. Neither appreciable signal modification nor evident buffer deposition was observed during the test period, with only a normal and limited run-by-run and day-by-day variation of the instrument response.

Anti-Inflammatory Agents↗

Nuclear association of cyclin D1 in human fibroblasts: tight binding to nuclear structures and modulation by protein kinase inhibitors.

The association of cyclin D1 with nuclear structures was investigated in normal human fibroblasts by using hypotonic detergent extraction procedures, immunofluorescence quantitation with flow cytometry, and Western blot analysis. About 20% of the total cellular levels of cyclin D1 was found to be tightly bound to nuclear structures, being the complex formation resistant to DNase I treatment and to high salt extraction. Maximal levels of the insoluble form of the protein were found in the middle to late G1 phase of the cell cycle. Cell fractionation and immunoprecipitation techniques after in vivo 32P-labeling showed that both soluble and nuclear-bound forms of cyclin D1 were phosphorylated. Both fractions were reactive to an anti-phosphotyrosine antibody, while only the latter was detectable with an anti-phosphoserine antibody. Treatment with the protein kinase inhibitor staurosporine, which induces a cell cycle arrest in early G1 phase, strongly reduced cyclin D1 phosphorylation. Concomitantly, the ratio of nuclear-bound/total cyclin D1 levels was reduced by about 60%, compared with the control value. The protein kinase A specific inhibitor isoquinoline-sulfonamide (H-89) induced a similar reduction in the ratio, with no significant modification in the total amount of protein. In contrast, both calphostin C and bisindolylmaleimide, specific inhibitors of protein kinase C, consistently increased by 30-50% the ratio of nuclear-bound/total amount of the cyclin protein. These results suggest that, during the G1 phase, formation of an insoluble complex of cyclin D1 occurs at nuclear matrix structures and that this association is mediated by a protein kinase A-dependent pathway.

Cell Division↗

Multiparametric staining to identify apoptotic human cells.

To analyze relevant features of HeLa and HL60 cells driven into apoptosis by etoposide, we have developed a new "tricolor" assay, based on the simultaneous analysis in the single cell of chromatin condensation, DNA degradation, and cellular poly(ADP-ribose) synthesis. The latter reaction is catalyzed by poly(ADP-ribose)-polymerase (E.C. 2.4.2.30), an enzyme which is activated by the presence of DNA free ends. The protocol consists in the visualization of apoptotic cells by Hoechst staining, TUNEL assay, and immunoreaction with anti-poly(ADP-ribose) antibody. We thus provide the first evidence that endogenous poly(ADP-ribose) production is indeed stimulated in cells undergoing apoptosis after treatment with antitumoral drugs, and that the monitoring of this endogenous enzymatic reaction, combined with morphological and other biochemical parameters, should facilitate the detection of apoptotic cells.

Adenosine Diphosphate Ribose↗

Accuracy of two newly described D-dimer tests in patients with suspected deep venous thrombosis.

Accumulating evidence suggests that the ELISA determination of D-Dimer might be a useful tool for the exclusion of deep vein thrombosis (DVT) of lower extremities, because of its high sensitivity and negative predictive value. However, conventional ELISA assay is time-consuming and, therefore, is not suitable for emergency use. To evaluate the accuracy of two rapid assays recently described, 126 consecutive outpatients with the clinical suspicion of DVT underwent the NycoCard D-Dimer and the Instant I.A. D-Dimer determination, using venography as the reference test. In all patients, the conventional ELISA assay was also performed. Venography confirmed the presence of DVT in 30 patients (23.8%), and ruled out the diagnosis in the remaining 96. Instant I.A D-Dimer was positive in 28 patients with DVT (sensitivity, 93.3%), and negative in 90 subjects free from thrombosis (specificity, 93.8%). Nycocard D-Dimer correctly identified 27 patients with DVT (sensitivity 90.0%), and was negative in 77 subjects free from thrombosis (specificity, 80.2%). Sensitivity, specificity, negative and positive predictive values of both tests did not differ from those found with the classic ELISA method. In conclusion, both Instant I.A. D-Dimer and Nycocard D-Dimer assays show a great potential for clinical use.

Adult↗

Substituted indole-2-carboxylates as in vivo potent antagonists acting as the strychnine-insensitive glycine binding site.

A series of indole-2-carboxylates bearing suitable chains at the C-3 position of the indole nucleus was synthesized and evaluated in terms of in vitro affinity using [3H]glycine binding assay and in vivo potency by inhibition of convulsions induced by N-methyl-D-aspartate (NMDA) in mice. 3-[2-[(Phenylamino)carbonyl]ethenyl]-4,6-dichloroindole-2-carboxyl ic acid (8) was an antagonist at the strychnine-insensitive glycine binding site (noncompetitive inhibition of the binding of [3H]TCP, pA2 = 8.1) displaying nanomolar affinity for the glycine binding site (pKi = 8.5), coupled with high glutamate receptor selectivity (> 1000-fold relative to the affinity at the NMDA, AMPA, and kainate binding sites). This indole derivative inhibited convulsions induced by NMDA in mice, when administered by both iv and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The effect of the substituents on the terminal phenyl ring of the C-3 side chain was investigated. QSAR analysis suggested that the pKi value decreases with lipophilicity and steric bulk of substituents and increases with the electron donor resonance effect of the groups present in the para position of the terminal phenyl ring. According to these results the terminal phenyl ring of the C-3 side chain should lie in a nonhydrophobic pocket of limited size, refining the proposed pharmacophore model of the glycine binding site associated with the NMDA receptor.

Animals↗