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Biomedical subjects

P Rossi

Publications and source records attributed to P Rossi.

At least 109 records · Page 6Linked to original sources

The effect of revascularisation of an ischaemic lower limb on leukotriene E4 production.

It has previously been shown that leukotriene E4 production is increased both in acute and chronic lower limb ischaemia. The aim of this study was to measure the effect of revascularisation on leuktriene E4 excretion in chronic lower limb ischaemia. Revascularisation did not affect significantly on leukotriene E4 excretion (preop. 34.9+/-7.1 pg/mg creatinine, postop. 24.5+/-4.7 pg/mg creatinine, n=10, P<0.238). We suggest that the enhanced leukotriene E4 production continues after revascularisation which may have a therapeutical implication.

Aged↗

Effects of levosimendan, a novel inotropic calcium-sensitizing drug, in experimental septic shock.

OBJECTIVE: Levosimendan is a novel inodilator that improves cardiac contractility by sensitizing troponin C to calcium. This drug has proved to be effective in treating advanced congestive heart failure but has not been evaluated in septic settings. The purpose of the present study was to study the effects of this drug in a porcine model of endotoxemia. DESIGN: Prospective experimental study. SUBJECTS: Fourteen landrace pigs. INTERVENTIONS: All animals were anesthetized and catheterized for measurement of central and pulmonary hemodynamics. Ultrasonic flow probes were placed around the renal artery and portal vein to measure blood flow. A tonometer was placed in the ileum to measure mucosal pH. Levosimendan was given to six animals as a bolus (200 microg x kg(-1)) followed by a continuous infusion (200 microg x kg(-1) x hr(-1)). Thirty minutes after onset of levosimendan treatment, all animals received endotoxin (20 microg x kg(-1) x hr(-1) for 3 hrs). MEASUREMENTS AND MAIN RESULTS: At baseline, levosimendan induced a systemic vasodilation with a reduction in blood pressure and an increase in heart rate. A tendency to an increase in cardiac index did not reach statistical significance (p =.055). Cardiac index and systemic oxygen delivery were markedly improved in the levosimendan group during endotoxemia. Systemic vascular resistance and blood pressure were reduced in the levosimendan group. The latter parameter, however, was only different from the control group during the initial phase of endotoxin shock but not at the late, most pronounced phase of shock. Levosimendan also efficiently attenuated endotoxin-induced pulmonary hypertension. Portal venous blood flow and gut oxygen delivery were improved, but no concomitant reduction in endotoxin-induced intestinal mucosal acidosis was observed. Renal blood flow was unaffected, as was the endotoxin-induced increase in plasma endothelin-1-like immunoreactivity. These findings support previous reports of calcium desensitization as a potential component in septic myocardial depression. Furthermore, the vasodilatory properties of this drug were well tolerated in the current model of hypodynamic endotoxin shock, and they may have contributed to improved regional blood flow as seen in the gut as well as improved systemic perfusion by means of reduced biventricular afterload. CONCLUSION: Pretreatment with levosimendan in pigs subjected to endotoxin shock improved cardiac output and systemic and gut oxygen delivery. In addition, pulmonary hypertension largely was attenuated without any adverse effects on gas exchange. These results are promising in several aspects, but the role of levosimendan in the treating circulatory failure in sepsis remains to be established.

Animals↗

Body composition analysis and changes in airways function in obese adults after hypocaloric diet.

STUDY OBJECTIVES: To determine the relationship between weight-loss and pulmonary function indexes, focusing on forced expiratory flows (ie, FEV(1), forced expiratory flow at 50% of vital capacity [FEF(50)], forced expiratory flow at 75% of vital capacity, and forced expiratory flow at 25 to 75% of vital capacity [FEF(25--75)]). Specifically, to determine the effect of losses in total and segmental fat mass (FM) and of modifications in lean body mass, after restricted hypocaloric diet, on pulmonary function among obese adults. DESIGN: Cross-sectional, observational. SETTINGS: Human Physiology Division, Faculty of Medicine and Surgery, "Tor Vergata" University, Rome, Italy. PATIENTS: Thirty obese adults (mean [+/- SD] baseline body mass index [BMI], 32.25 +/- 3.99 kg/m(2)), without significant obstructive airway disease, were selected from among participants in a weight-loss program. MEASUREMENTS AND RESULTS: Anthropometric, body composition (BC), and respiratory parameters of all participants were measured before and after weight loss. Total and segmental lean body and FM were obtained by dual-energy x-ray absorptiometry. Dynamic spirometric tests and maximum voluntary ventilation (MVV) were performed. The BC parameters (ie, body weight [BW], BMI, the sum skinfold thicknesses, thoracic inhalation circumference, thoracic expiration circumference, total FM, and trunk FM [FMtrunk]) were significantly decreased (p < or = .0001) after a hypocaloric diet. The mean vital capacity, FEV(1), FEF(50), FEF(25-75), expiratory reserve volume, and MVV significantly increased (p < or = 0.05) with weight loss. The correlation coefficient for Delta FEF(25--75) (r = 0.20) was numerically higher than Delta FEF(50) and Delta FEV(1) (r = 0.14 and r = 0.08, respectively) for the BW loss. Moreover, the correlation coefficient for Delta FEF(25--75) (r = 0.45) was significantly higher (p < or = 0.02) than those for Delta FEF(50) and Delta FEV(1) (r = 0.38 and r = 0.15, respectively) for FMtrunk loss. CONCLUSIONS: This study shows that a decrease in total and upper body fat obtained by restricted diet was not accompanied by a decrease in ventilatory muscle mass. FMtrunk loss was found to have improved airflow limitation, which can be correlated to peripheral airways function.

Adult↗

[Tolerance of orbital implants. Retrospective study on 14 years].

UNLABELLED: The authors report the results of enucleations performed from 1985 to 1998 and the different orbital implants used. MATERIAL AND METHODS: All patients undergoing enucleation from 1985 to 1998 were studied. RESULTS: 68 men and 32 women had an enucleation. The main indication was tumoral diseases, principally choroidal melanomas and ciliary melanomas (respectively, 26 and 8). More rarely the indication was orbital metastasis or eyelid carcinoma. The follow indications were traumatisms and neovascular glaucomas. The orbital implants used were mainly Allen implants, silicone implants and hydroxyapatite implants. The main complication was the expulsion of the implant, which occurred in about 20% of the cases, for the most part in the group of silicone and tunnel implants patient. These expulsions were found less with hydroyxapatite implants. For the hydroxyapatite implants we also noticed the some conjunctival erosion. The expulsion of the implant occurred most often before 2 years. CONCLUSION: The authors report on the survey of orbital implants used for 14 years. They noticed the high frequency of expulsions when they used tunnel or silicone implants and better results with hydroxyapatite implant.

Adolescent↗

The first water-soluble 3(10)-helical peptides.

Two water-soluble 3(10)-helical peptides are synthesized and fully characterized for the first time. The sequence of these terminally blocked heptamers comprises two residues of the Calpha-trisubstituted alpha-amino acid 2-amino-3-[1-(1,4,7-triazacyclononyl)]propanoic acid and five residues of a Calpha-tetrasubstituted alpha-amino acid (either alpha-aminoisobutyric acid or isovaline). Using CD and NMR techniques we were able to show that both heptapeptides are well structured in water, and that the type of conformation adopted is indeed the ternary 3(10)-helix.

Journal Article↗

Photoproduction of straight phi(1020) mesons on the proton at large momentum transfer

The cross section for straight phi meson photoproduction on the proton has been measured for the first time up to a four-momentum transfer -t = 4 GeV2, using the CLAS detector at the Thomas Jefferson National Accelerator Facility. At low four-momentum transfer, the differential cross section is well described by Pomeron exchange. At large four-momentum transfer, above -t = 1.8 GeV2, the data support a model where the Pomeron is resolved into its simplest component, two gluons, which may couple to any quark in the proton and in the straight phi.

Journal Article↗

Influence of donor age on bovine pancreatic islet isolation.

BACKGROUND: Pancreatic islets from pigs are largely used for experimental studies. However, pancreas harvesting requires modification of conventional slaughtering to reduce ischemia time. It has been shown that bovine pancreatic islets can be more easily obtained and they show satisfactory in vitro and in vivo function. To improve the isolation procedure we compared the effect of bovine donor age on islet isolation. METHODS: Islets were isolated by collagenase digestion and sequential sieving from calves (6 months of age) and from adult bovine (> 16 months of age). After isolation the number of islet equivalents was calculated and histological and immunohistochemical studies performed. The purity and viability of islet for each preparation was also estimated. In vitro function of islets was evaluated by static insulin secretion assay, and alginate encapsulated islets were transplanted in streptozotocin-induced diabetic rats for in vivo functional evaluation. RESULTS: A significantly higher number of islets were obtained from calf pancreas, compared with adult bovine pancreas. Hystological examination showed intact morphologic features of islets. The purity of islet preparations was higher from calf pancreas than from adult pancreas. Cell viability, and insulin production in presence of high glucose concentration, were not affected by donor age. All animals receiving microencapsulated islets from calves showed normoglycemia for prolonged periods (17-40 days). CONCLUSIONS: These results indicate that pancreatic islet isolation is more efficient from juvenile bovine than from adult. Calf pancreas is a good and convenient source of tissue for massive islet isolation for experimental studies.

Aging↗

Long-term potentiation of intrinsic excitability at the mossy fiber-granule cell synapse of rat cerebellum.

Synaptic activity can induce persistent modifications in the way a neuron reacts to subsequent inputs by changing either synaptic efficacy or intrinsic excitability. After high-frequency synaptic stimulation, long-term potentiation (LTP) of synaptic efficacy is commonly observed at hippocampal synapses (Bliss and Collingridge, 1993), and potentiation of intrinsic excitability has recently been reported in cerebellar deep nuclear neurons (Aizenmann and Linden, 2000). However, the potential coexistence of these two aspects of plasticity remained unclear. In this paper we have investigated the effect of high-frequency stimulation on synaptic transmission and intrinsic excitability at the mossy fiber-granule cell relay of the cerebellum. High-frequency stimulation, in addition to increasing synaptic conductance (D'Angelo et al., 1999), increased granule cell input resistance and decreased spike threshold. These changes depended on postsynaptic depolarization and NMDA receptor activation and were prevented by inhibitory synaptic activity. Potentiation of intrinsic excitability was induced by relatively weaker inputs than potentiation of synaptic efficacy, whereas with stronger inputs the two aspect of potentiation combined to enhance EPSPs and spike generation. Potentiation of intrinsic excitability may extend the computational capability of the cerebellar mossy fiber-granule cell relay.

Action Potentials↗

Polyamine macrocycles incorporating a phenolic function: their synthesis, basicity, and coordination behavior toward metal cations. Crystal structure of a binuclear nickel complex.

The synthesis and characterization of two new polyazamacrocycles, 1,4,7,10-tetraaza[12](2,6)phenolphane (L1) and 1,4,7,10,13-pentaaza[15](2,6)phenolphane (L2), are reported. Both ligands incorporate the 2,6-phenolic unit within the cyclic framework. The basicity behavior and the ligational properties of L1 and L2 toward Ni(II), Zn(II), and Cu(II) were determined by means of potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol dm-3). UV spectra were used to understand the role of the phenolic function in the stabilization of the cations. L1 and L2 behave as pentaprotic bases under the experimental conditions used. The UV spectra showed that the deprotonation of the phenolic function occurs at low pH values for both ligands, giving rise to the simultaneous presence of positive and (one) negative charges on the macrocycle. While L1 forms only mononuclear complexes, L2 can also form binuclear species with all the metal ions investigated. In the mononuclear species of both ligands, one nitrogen atom close to the phenol remains unbound. The UV spectra revealed that the phenol, bridging the two metal ions in phenolate form, plays an important role in the stabilization of the binuclear complexes of L2. The coordination sphere of the two metals is completed by adding a secondary ligand such as water molecules or OH-, in any case preferring substrates able to bridge the two close metal ions. These results are confirmed by the crystal structure of [Ni2(C16H28ON5)(H2O)2Cl2]Cl.H2O.CH3OH (space group P21/a, a = 14.821(5) A, b = 10.270(4) A, c = 17.663(6) A, beta = 108.87(3) degrees, V = 2544(2) A3, Z = 4, R1 = 0.0973, wR2 = 0.2136). This structure displays a Ni(II) binuclear complex of L2 in which the phenolic oxygen and a chlorine ion bridge the two close Ni(II) ions.

Journal Article↗

Identification of nine novel mutations in the Bruton's tyrosine kinase gene in X-linked agammaglobulinaemia patients.

Mutations in the Bruton's tyrosine kinase (BTK ) gene are responsible for X-linked Agammaglobulinemia (XLA), an immunodeficiency caused by a block in B cell differentiation. Non Isotopic RNAse Cleavage Assay (NIRCA), followed by sequencing was used to screen for BTK mutations in 11 Italian XLA patients. Nine novel mutations were identified: 6 missense (Y39S, L512P, L512Q, R544G, S578Y, E589K), one non-sense (Q260X), one frameshift (1599-1602del GCGC) and one in-frame insertion (2037-2038insTTTTAG), that represents the first case of premature stop codon introduction in the BTK coding frame. These data support the high molecular heterogeneity of BTK gene in XLA disease and provide new insight to the diagnosis and to the role of BTK domain in XLA and in B cell signal transduction and development. Hum Mutat 15:117, 2000.

Agammaglobulinaemia Tyrosine Kinase↗

An azacrown-functionalized peptide as a metal ion based catalyst for the cleavage of a RNA-model substrate.

The previously synthesized, terminally blocked heptapeptide Ac-Aib-ATANP-Aib-Aib-ATANP-Aib-Aib-OMe (1a), where ATANP is (S)-2-amino-3-[1-(1,4,7-triazacyclononane)]propanoic acid and Aib is alpha-aminoisobutyric acid, which is soluble in neutral water where it largely adopts a 3(10)-helical conformation, has been studied, as bimetallic complex [metal ions: Cu(II), Ni(II), Zn(II)], for the transphosphorylation catalysis of the RNA-model substrate 2-(hydroxypropyl)-p-nitrophenyl phosphate (HPNP). A detailed analysis was carried out with the Zn(II) dinuclear complex. Comparison with the mononuclear Zn(II) complex with 1,4,7-triazacyclononane (3) points to cooperativity between the two Zn(II) ions in the process catalyzed by 1a-2Zn(II). On the contrary, the dinuclear Zn(II) complex of dipeptide Ac-(ATANP)(2)-OMe (2), lacking any ordered conformation, is less active than 3-Zn(II). The kinetic analysis suggests the following: (a) the peptide is conformationally very robust and does not loose activity up to 50 degrees C; (b) the substrate binds to the peptide-Zn(II) complex, although not all modes of complexation allow us to take advantage of the cooperativity between the two metal centers. The maximum rate acceleration estimated at pH 7 for the fully bound substrate is ca. 200-fold compared with the uncatalyzed process.

Alanine↗

Role of c-kit in mammalian spermatogenesis.

The tyrosine-kinase receptor c-kit and its ligand, stem cell factor (SCF), are essential for the maintenance of primordial germ cells (PGCs) in both sexes. However, c-kit and a post-meiotic-specific alternative c-kit gene product play important roles also during post-natal stages of spermatogenesis. In the adult testis, the c-kit receptor is re-expressed in differentiating spermatogonia, but not in spermatogonial stem cells, whereas SCF is expressed by Sertoli cells under FSH stimulation. SCF stimulates DNA synthesis in type A spermatogonia cultured in vitro, and injection of anti-c-kit antibodies blocks their proliferation in vivo. A point mutation in the c-kit gene, which impairs SCF-mediated activation of phosphatidylinositol 3-kinase, does not cause any significant reduction in PGCs number during embryonic development, nor in spermatogonial stem cell populations. However males are completely sterile due to a block in the initial stages of spermatogenesis, associated to abolishment of DNA-synthesis in differentiating A1-A4 spermatogonia. With the onset of meiosis c-kit expression ceases, but a truncated c-kit product, tr-kit, is specifically expressed in post-meiotic stages of spermatogenesis, and is accumulated in mature spermatozoa. Microinjection of tr-kit into mouse eggs causes their parthenogenetic activation, suggesting that it might play a role in the final function of the gametes, fertilization.

Animals↗

MRI and motor evoked potential findings in nondisabled multiple sclerosis patients with and without symptoms of fatigue.

Fatigue is a common symptom of multiple sclerosis (MS) even in the early phases of the disease, when neurological disability is usually still not present. To investigate the pathophysiology of fatigue we compared neurophysiological (motor evoked potentials of the four limbs, MEPs) and brain magnetic resonance imaging (MRI) findings in two groups of nondisabled MS patients, those with (n=15) and those without (n=15) fatigue. Fatigue was assessed by an interview and scored by the Fatigue Severity Scale. The two groups were matched for sex, age, disease duration, Expanded Disability Status Scale score, pyramidal Functional System (FS) score, and depression score. MEPs were abnormal in five patients with fatigue and in one patient without fatigue. A significant association was found between the patient scores on the Fatigue Severity Scale, and the burden of MRI lesions (r=0.5; P< 0.005). Significantly higher parietal lobe (P< 0.05), internal capsule (P< 0.05), and periventricular trigone (P< 0.05) lesion loads were found in patients with fatigue than in those without. Our results agree with a central nervous system origin of fatigue in MS patients. This symptom might be a consequence either of a functional deafferentation of the cortex due to cortico-subcortical interconnection damage or of a demyelination in critical sites of the CNS, such as the cortico-spinal tract.

Adolescent↗

Variable use of therapeutic interventions for children with human immunodeficiency virus type 1 infection in Europe.

UNLABELLED: Although a range of antiretroviral drugs are available for use in children, the appropriate paediatric regimen remains unclear. In a survey to investigate policies and practices relating to the therapeutic management of children infected by the human immunodeficiency virus (HIV), a postal questionnaire was sent to a named paediatrician in 70 major HIV centres in 13 European countries in early 1998. A total of 64 paediatricians (91%) responded. Pneumocystis carinii pneumonia prophylaxis was found to be routine in all centres, although considerable variation existed regarding the time of starting and stopping therapy. Prophylaxis for fungal infections and recurrent bacterial infections was common, with cytomegalovirus prophylaxis being less frequent. Although most centres (89%) used all five currently available nucleoside analogues (ziduvodine, lamivudine, stavudine, didanosine, zalcitabine), there was considerable variability regarding the availability of protease inhibitors. Most respondents delayed initiation of antiretroviral therapy until evidence of disease progression was apparent. The initial prescription of 38% of clinicians was triple therapy and that of 57% prescribed double therapy. Policies varied regarding the modification to regimens in response to disease progression and emergence of side effects and drug resistance. Clinical practice was informed by a number of sources, including centre-specific and national guidelines. Most respondents affirmed the need for European guidelines. CONCLUSION: Approaches to the therapeutic management of paediatric human immunodeficiency virus infection differ across Europe.

Antiviral Agents↗

[IGM hyperimmunoglobulinemia anti-phosphatidylethanolamine antibodies of the IgM isotype: clinical and biological study of 72 patients with immune disorders].

PURPOSE: Antiphosphatidylethanolamine antibodies (aPE) are zwitterionic antiphospholipid antibodies that have been recently described in antiphospholipid syndrome. IgM is the most frequently observed isotype. We assessed the potential relationship between serum IgM levels and their presence. METHODS: Seventy-two patients (66 females, 6 males) positive for aPE of the IgM isotype were followed up for 2 years. They suffered from either an autoimmune disease or had clinical signs suggesting the existence of antiphospholipid syndrome or other immune disorders. Seventy-two control patients (58 females, 14 males) of similar age, with other immune disorders were also included in the study. For each of them, the IgM level was obtained and hyper-immunoglobulinemia M (hyper-IgM) was defined as a value upper than 2.5 g/L. Search for aPE of the IgM isotype was made using an in-house Elisa test. RESULTS: Half of the aPE-positive patients had serum hyper-IgM, whereas none of the aPE-negative patients had hyper-IgM. All IgMs were polyclonal. There was a positive correlation (r = 0.57, P = 0.001) between the level of IgM and the optical densities obtained by Elisa. The presence of a hyper-IgM did not modify the clinical manifestations (arterial and venous thromboses, recurrent fetal losses), nor the positivity of lupus anticoagulant, anticardiolipin and anti-beta-2-glycoprotein 1 antibodies. CONCLUSION: The positive correlation between the IgM level and aPE level is of value, as it suggests a possible relationship between lymphocytic activation and auto-antibodies production, which does not concern only aPE. Further studies regarding the antigenic specificity of IgM will probably provide further insights on IgM and phospholipid interactions.

Adult↗

A simple method for estimating conduction velocity of the spinothalamic tract in healthy humans.

OBJECTIVES: The object of this study was to establish a method for estimating the conduction velocity (CV) of the spinothalamic tract (STT) in relation to clinical application. METHODS: The CV of the STT was estimated by an indirect method based on that reported by Kakigi and Shibasaki in 1991 (Kakigi R, Shibasaki H. Electroenceph clin Neurophysiol 80 (1991) 39). Laser-evoked potentials (LEP) were measured in 8 subjects following hand (LEPH) and foot (LEPF) laser stimulation. The conduction times recorded at the scalp (P340, P400 and N150 potentials) were considered as the summation of peripheral and central components. The peripheral conduction times were calculated by measuring the latency of the electrical cutaneous silent period (from the same stimulus site of LEPs), corrected for F- and M-wave latency values. RESULTS: The CV of the STT ranged between 8.3 and 11.01 m/s and its mean value was found to be approximately 9.87+/-1.24 m/s. The CV of the STT obtained by the N150 latencies overlapped that obtained by the P340/P400 latencies. CONCLUSIONS: Our data suggest that our method appears appropriate and useful for practical clinical purposes, furnishing an additional tool for investigating the physiological function of small-fiber pathways.

Brain↗