Biomedical subjects
Publications and source records attributed to R Rosa.
We report a 3-year-old boy with isolated 3-methylcrotonyl-coenzyme A deficiency with unexpectedly severe presentation, seizures and history of cerebral ischae-mic episode.
We studied the amino acid and lipid dynamics during embryogenesis of Homarus gammarus. Major essential amino acids (EAA) in the last stage of embryonic development were arginine, lysine and leucine; major nonessential amino acids (NEAA) were glutamic acid, aspartic acid, valine and glycine. The highest percent of utilization occurred in respect to EAA (27.8%), mainly due to a significant decrease (p<0.05) of methionine (38.3%) and threonine (36.0%). NEAA also decreased significantly (p<0.05, 11.4%), namely serine (38.1%), tyrosine (26.4%) and glutamic acid (25.7%). In contrast, the free amino acid content increased significantly (p<0.05) during embryonic development, especially the free nonessential amino acids (FNEAA). In the last stage, the most abundant FNEAA were glycine, proline, alanine and taurine, and the major free essential amino acids (FEAA) were arginine, lysine and leucine. Lipid content decreased significantly (p<0.05) during embryonic development. A substantial decrease in all neutral lipid classes was observed (>80% of utilization). Major fatty acids were 16:0, 18:0, 18:1n-9, 18:2n-6, 18:3n-3, 20:5n-3 and 22:6n-3. Unsaturated (UFA) and saturated fatty acids (SFA) were used up at similar rates (76.5% and 76.3%, respectively). Within UFA, monounsaturates (MUFA) were consumed more than polyunsaturates (PUFA) (82.9% and 67.5%, respectively).
The objective of this study was to analyse the modulatory effect of proteins released by cultured Leishmania infantum promastigotes on the cellular immune response of infected susceptible (BALB/c) and more resistant (C57BL/6) mice strains after 30 and 45 days of infection. One month after parasite inoculation, L. infantum released protein fractions (High, Inter, and Low according to molecular weight) stimulated C57BL/6 mice spleen cells to proliferate and to express cytokines. Following the decrease of parasite load only the Low protein fraction induced a considerable release of IL-4. In BALB/c mice, specific immune response to protein fractions was only observed at the higher parasitic level, with the fraction Inter promoting the production of IL-4 and fractions High and Low inducing high levels of IL-12. These results point out to a role of these proteins fractions in the modulation of host immunity, that depending on the host genetic background and parasite magnitude, seem to be critical in the control of parasite replication levels, thus avoiding premature host death.
The aim of this study was to investigate the biochemical changes that occur during sexual maturation of the squids Illex coindetii and Todaropsis eblanae. In both species, amino acids and protein content increased in the gonad throughout maturation, but the allocation of these nitrogen compounds from the digestive gland and muscle was not evident. A significant (P < 0.05) increase in the content of lipids and fatty acids was observed in the gonad and digestive gland. It seems that both species take energy for egg production directly from food, rather than from stored products. Analyses for cholesterol revealed a significant (P < 0.05) increase in the gonad, and the lipid content differences between species are potentially related to different feeding ecologies. The glycogen reserves in the gonad increased significantly (P < 0.05), suggesting that glycogen has an important role in the maturation process. It was evident that sexual maturation had a significant effect upon the gonad energy content, but because the energy variation in the digestive gland and muscle was nonsignificant (P > 0.05), there was no evidence that storage reserves are transferred from tissue to tissue.
The TRIGA RC-1 1MW reactor operating at ENEA Casaccia Center is currently being developed as a second neutron imaging facility that shall be devoted to computed tomography as well as neutron tomography. In order to reduce the gamma-ray content in the neutron beam, the reactor tangential piercing channel was selected. A set of Monte Carlo simulation was used to design the neutron collimator, to determine the preliminary choice of the materials to be employed in the collimator design.
The effect of spermatogenesis and oogenesis on protein, lipid, glycogen, cholesterol and energy contents, total amino acid and fatty acid profiles of Eledone cirrhosa and Eledone moschata tissues (gonad, digestive gland and muscle) was investigated. A significant (p<0.05) increase in the amino acids and protein content of the gonad throughout sexual maturation (namely in oogenesis) was observed, but the allocation of these nitrogen compounds from the digestive gland and muscle was not evident. The major essential amino acids (EAA) in the three tissues were leucine, lysine and arginine. The major nonessential amino acids (NEAA) were glutamic acid, aspartic acid and alanine. A significant increase in lipid and fatty acid contents of gonad and digestive gland was observed. There was also little evidence of accumulated lipid storage reserves being used for egg production. It seems that for egg production Eledone species use energy directly from food, rather than from stored products. Most of saturated fatty acid (SFA) content of the three tissues was presented as 16:0 and 18:0, monounsaturated fatty acid (MUFA) content as 18:1 and 20:1 and polyunsaturated fatty acid (PUFA) content as 20:4n-6, 20:5n-3 and 22:6n-3. Cholesterol and glycogen contents significantly increased in gonad and digestive gland throughout maturation while the muscle revealed no obvious pattern. If Eledone's component sterols are of a dietary origin, a considerable variation in the cholesterol content between species might be expected on the basis of the sterol composition of their prey. Although spermatogenesis and oogenesis had a significant effect (p<0.05) in gonad and digestive gland energy content, the biochemical composition of digestive gland and muscle may not be primarily influenced by sexual maturation, but rather by other biotic factors such as feeding activity, food availability, spawning and brooding.
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The complete assignment of the 1H and 13C NMR spectra of bendaline (BNDL) was performed by mono-dimensional and homo- and hetero-correlated two-dimensional NMR experiments. The interaction between bendaline and albumin was also studied by the analysis of the motional parameters spin-lattice relaxation times, allowing the motional state of the BNDL free and bound with albumin to be defined. In absence of albumin the indazolacetic and benzylic moieties are characterized by roughly the same mobility and by positive sigma (cross-relaxation rates) values. In the presence of the macromolecule, the indazolacetic and benzylic moieties and the lysine change their motional behaviour to different extents, as indicated by correlation times. Data obtained in absence and in presence of the protein show that the molecular moiety of the bendaline most involved in the binding with albumin is the fragment H-4 H-5. The binding constant was evaluated at 2.4x10(3)M(-1).
BACKGROUND: The advantages of treating morbidly obese patients via the laparoscopic approach have been demonstrated, in particular, for adjustable silicone gastric banding, but this operation is associated with a high rate of late complications. Gastric bypass and malabsorbitive procedures are feasible via the laparoscopic approach, but they entail a prolonged operating time and a consistently high morbidity rate. Laparoscopic vertical banded gastroplasty represents an effective alternative. METHODS: We performed 250 consecutive LVBG between November 1995 and February 2000. The procedure consisted of a personal technique designed to reproduce, by laparoscopy, MacLean's modification of the standard open Mason vertical-banded gastroplasty, with a calibrated transgastric window, a complete division between the staple lines, and a 5-cm-circumference polypropylene collar. RESULTS: The operative time was 95 min and the conversion rate was 0.8%. Operative mortality was nil; early and late complications, respectively, were 4.4% and 4%; the reoperation rate was 2%. Global results at 4 years were as follows: excess weight loss (EWL) 61%, success rate (excess weight <50%) 76.9%, body mass index (BMI) 29.4 kg/m2. In morbidly obese patients, the EWL at 4 years was 62.2%, with a 77.4% success rate and a 28.4 kg/m2 BMI; in superobese patients, the EWL at 4 years was 54.9% with a 50% success rate and a 35.5 kg/m2 BMI. The overall follow-up rate was 92%. CONCLUSIONS: LVBG is an effective and safe operation in morbidly obese patients, providing good weight loss with a low morbidity rate, no mortality, and minimum discomfort. However, in superobese patients, the weight loss results are disappointing; in these patients, LVBG is questionable and more complex procedures should be considered.
The effects of the environmental contaminants methylmercury (MeHg) and inorganic mercury (HgCl(2)) on cell viability, intracellular calcium concentration ([Ca(2+)](i)), and reactive oxygen species (ROS) generation were studied in rat cerebellar granule neuron cultures using fluorescent methods. MeHg exhibited an LC(50) (2.47 microM) tenfold lower than that of HgCl(2) (26.40 microM). To study the involvement of oxidative stress and Ca(2+) homeostasis disruption in mercury-induced cytotoxicity, we tested the neuroprotective effects of several agents that selectively interfere with these mechanisms. After a 24 hr exposure, the cytotoxic effect of both mercury compounds was reduced by thapsigargin, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase; the Ca(2+) channel blocker flunarizine; and the Na(+)/Ca(2+) exchanger blocker benzamil. All these compounds decreased the mercury-mediated [Ca(2+)](i) rise. These results indicate that Ca(2+) influx through Ca(2+) channels and the Na(+)/Ca(2+) exchanger and Ca(2+) mobilization from the endoplasmic reticulum are involved in mercury-mediated cytotoxicity. The antioxidants probucol and propyl gallate reduced the HgCl(2) toxicity. Probucol and vitamin E partially inhibited the MeHg toxicity after a 24 hr period, whereas propyl gallate completely prevented this effect. Probucol slightly reduced ROS generation in methylmercury-exposed cultures and decreased mercury-mediated rise of [Ca(2+)](i). Propyl gallate abolished ROS generation and partially inhibited the increase of [Ca(2+)](i) induced by both mercury compounds. Propyl gallate also protected human cerebral cortical neuron cultures from the MeHg effect even after 72 hr of MeHg exposure, thus showing a long-lasting effect. Our data suggest that disruption of redox equilibrium and Ca(2+) homeostasis contribute equally to HgCl(2)-mediated toxicity, whereas oxidative stress is the main cause of MeHg neurotoxicity.
We describe a patient with a pure motor chronic demyelinating polyneuropathy with an IgM monoclonal component showing anti-GM2, GalNAc-GD1a and GalNAc-GM1b reactivity whose common epitope appears to be -[GalNAcbeta1-4Gal(3-2alphaNeuAc)beta1]. We used intracellular recording to study how IgM from this patient affected neurotransmitter release in the mouse diaphragm in vitro. Adding serum (and specifically, the purified monoclonal IgM component) blocked the nerve-evoked response in both quantal content and evoked endplate potential (EPP) amplitude in a complement-independent and reversible manner. The IgM increased the frequency of spontaneous miniature endplate potentials (MEPPs) in a complement-dependent and reversible manner but had no effect on MEPP amplitude.
The effect of vaccinating patients with sustained undetectable HIV-1 viremia (VL) achieved with highly active antiretroviral therapy was prospectively investigated. During the 1998 influenza immunization period, 39 HIV-1-infected patients who showed a VL<20 copies/ml for at least 6 months before the study entry date were vaccinated for influenza. Twenty-two vaccinees were immunized at entry. Seventeen controls were followed for 4 weeks after entry, crossing over then to the vaccination group. The proportion of patients with undetectable VL was not significantly different between the vaccination and control groups 2 and 4 weeks after entry. Therefore, influenza immunization of patients with undetectable viremia achieved with highly active antiretroviral therapy does not seem to affect VL.
Numerical simulations of energy filtering effects on backscattered electron images of semiconductor multilayers are reported. The theoretical investigation has been performed for a wide range of energies, 1-40 keV, and for beam incidence angles between 90 degrees (normal incidence) and 20 degrees. Quite a general purpose of this research concerns the investigation of the optimum energy conditions and of their implications. It will be shown that the optimum energy defines an operating context suitable to ensure a compositional contrast enhancement; i.e. a minimum threshold current and a maximum resolution, without energy filtering, independent of the beam incidence angle. This optimum energy, depending on the specimen and its details, is, however, of the order of a few keV or less for specimen details having a size of the order of few nm. When the performance of the electron gun does not allow to work at low energy it is necessary to operate at an energy higher than the optimum one, the energy filtering can produce positive effects. Yet in those circumstances there is an optimum energy loss window suitable to minimise the threshold current. It spreads from 10-30%, depending on the primary energy and size of the compositional detail, for normal incidence, to a few per cent for high incidence angles and high energy. The simulation results for these last conditions are in agreement with the well-known experimental results obtained with the low-loss methods.
BACKGROUND/AIMS: The rate of progression to cirrhosis of chronic hepatitis C might be related to an upregulation of TNF-alpha/Fas pathways. METHODS: The serum levels of soluble TNF-alpha type II receptor (sTNFr-II) and soluble Fas antigen (sFas) were analyzed in patients with different histological outcomes of chronic parenterally acquired HCV infection of similar duration. RESULTS: One hundred and forty-five HCV-infected patients had a known duration of infection. Twelve (8.3%) patients had minimal changes and were assigned to the case group. The control group was selected from the 24 (17%) patients with cirrhosis and the 54 (37%) with chronic active hepatitis (CAH). Two controls, one with CAH and one with cirrhosis, were paired with the cases following these criteria: duration of infection, transmission route and sex. The proportions of genotype 1b and HCV RNA serum levels were similar among the groups. The median serum levels of sTNFr-II and sFas were significantly lower in the case group than in the control groups. The cases were significantly younger when they became infected than the control groups. Indeed, most cases were infected within the first 10 years of life. sTNFr-II and age at infection were independently associated with the minimal injury case group. When sTNFr-II was excluded from the logistic regression model, sFas and age at infection were independently associated with the case group. CONCLUSION: The rate of progression of parenterally acquired chronic hepatitis C to end-stage liver disease might be related to an upregulation of the TNF-alpha/Fas pathways and an age-dependent host response.
Inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, such as simvastatin, lower circulating cholesterol levels and prevent myocardial infarction. Several studies have shown an unexpected effect of HMG-CoA reductase inhibitors on inflammation. Here, we confirm that simvastatin is anti-inflammatory by using a classic model of inflammation: carrageenan-induced foot pad edema. Simvastatin administered orally to mice 1 hour before carrageenan injection significantly reduced the extent of edema. Simvastatin was comparable to indomethacin in this model. To determine whether the anti-inflammatory activity of simvastatin might affect atherogenesis, simvastatin was tested in mice deficient in apoE. Mice were dosed daily for 6 weeks with simvastatin (100 mg/kg body wt). Simvastatin did not alter plasma lipids. Atherosclerosis was quantified through the measurement of aortic cholesterol content. Aortas from control mice (n=20) contained 56+/-4 nmol total cholesterol/mg wet wt tissue, 38+/-2 nmol free cholesterol/mg, and 17+/-2 nmol cholesteryl ester/mg. Simvastatin (n=22) significantly (P<0.02) decreased these 3 parameters by 23%, 19%, and 34%, respectively. Histology of the atherosclerotic lesions showed that simvastatin did not dramatically alter lesion morphology. These data support the hypothesis that simvastatin has antiatherosclerotic activity beyond its plasma cholesterol-lowering activity.
The treatment of severe autoimmune diseases has been recently revitalized by the introduction of intense immune suppression with immune ablative intent followed by three different procedures. These are allogeneic hematopoietic stem cell transplantation (HSCT), autologous HSCT (using either marrow or peripheral blood), and intense immune suppression without stem cell support. Current trials suggest that high dose immune suppressive therapy with or without autologous hematopoietic stem cell support can induce remission of previously refractory disease. Follow-up is too brief to determine if intense immune suppression, and more specifically autologous HSCT, will ultimately cure SLE. It is conceivable that an allogeneic source of stem cells from a normal donor (e.g. HLA matched sibling) will be required to achieve a cure. It is also possible that autologous HSCT, even if not curative, may prolong the life of patients with otherwise high-risk features. In carefully selected patients, the potential benefits of this procedure may outweigh the risks.
Laboratory recovery and confirmation of the etiologic agent in necrotizing retinochoroiditis are problematic. Tissue culture and intraocular antibody titers were compared as adjuncts to clinical diagnosis for toxoplasmic retinochoroiditis: the correlations were 91 and 67%, respectively. Isolation of Toxoplasma gondii may establish a definitive diagnosis in patients with toxoplasmic retinochoroiditis.
The presence in plasma of an electronegative LDL subfraction [LDL(-)] cytotoxic for endothelial cells (ECs) has been reported. We studied the effect of LDL(-) on the release by ECs of molecules implicated in leukocyte recruitment [interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1)] and in the plasminogen activator inhibitor-1 (PAI-1). LDL(-), isolated by anion-exchange chromatography, differed from nonelectronegative LDL [LDL(+)] in its higher triglyceride, nonesterified fatty acid, apoprotein E and apoprotein C-III, and sialic acid contents. No evidence of extensive oxidation was found in LDL(-); its antioxidant and thiobarbituric acid-reactive substances contents were similar to those of LDL(+). However, conjugated dienes were increased in LDL(-), which suggests that mild oxidation might affect these particles. LDL(-) increased, in a concentration-dependent manner, the release of IL-8 and MCP-1 by ECs and was a stronger inductor of both chemokines than oxidized LDL (oxLDL) or LDL(+). PAI-1 release increased slightly in ECs incubated with both LDL(-) and oxLDL but not with LDL(+). However, no cytotoxic effects of LDL(-) were observed on ECs. Actinomycin D inhibited the release of IL-8 and MCP-1 induced by LDL(-) and oxLDL by up to 80%, indicating that their production is mediated by protein synthesis. Incubation of ECs with N:-acetyl cysteine inhibited production of IL-8 and MCP-1 induced by LDL(-) and oxLDL by >50%. The free radical scavenger butylated hydroxytoluene slightly inhibited the effect of oxLDL but did not modify the effect of LDL(-). An antagonist (BN-50730) of the platelet-activating factor receptor inhibited production of both chemokines by LDL(-) and oxLDL in a concentration-dependent manner. Our results indicate that LDL(-) shows proinflammatory activity on ECs and may contribute to early atherosclerotic events.