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Biomedical subjects

Claudio Rossi

Publications and source records attributed to Claudio Rossi.

At least 19 recordsLinked to original sources

Solution behavior of a sugar-based carborane for boron neutron capture therapy: a nuclear magnetic resonance investigation.

The physico-chemical properties of beta-lactosyl-closo-orthocarborane in water solution were investigated by multinuclear NMR, (13)C NMR relaxation, and ab-initio calculations. This molecule represents a potentially selective boron carrier in Boron Neutron Cancer Therapy (BNCT) and exhibits amphiphilic characteristics. Its structural and dynamic features were studied comparing NMR data acquired in both aggregating and non-aggregating conditions. Aggregates are characterized by rapid exchange with the bulk and by high sensitivity to temperature conditions. An unusually stable intra-molecular CH...O hydrogen bond was found to persist in water solution both for the free molecules and after aggregate formation. At the same time, inter-molecular specific CH()O interactions do not seem effective in the aggregate formation process, which appears to take place only on non-specific hydrophobic basis.

Boranes↗

The bio-optical properties of CDOM as descriptor of lake stratification.

Multivariate statistical techniques are used to demonstrate the fundamental role of CDOM optical properties in the description of water masses during the summer stratification of a deep lake. PC1 was linked with dissolved species and PC2 with suspended particles. In the first principal component that the role of CDOM bio-optical properties give a better description of the stratification of the Salto Lake with respect to temperature. The proposed multivariate approach can be used for the analysis of different stratified aquatic ecosystems in relation to interaction between bio-optical properties and stratification of the water body.

Ecosystem↗

Comparative analysis of the effects of locally used herbicides and their active ingredients on a wild-type wine Saccharomyces cerevisiae strain.

Herbicides are released to the environment with potential ecotoxicological risks for mammals. Yeast is a good model to elucidate toxicity mechanisms. We investigated how three commercial herbicides (Proper Energy, Pointer, and Silglif) and their active ingredients (respectively, fenoxaprop-P-ethyl, tribenuron methyl, and glyphosate) can affect biological activities of an oenological Saccharomyces cerevisiae strain, which may be resident on grape vineyards of the same geographical areas where herbicides are used. The use of commercial grade herbicides employed in Italy allowed us to reproduce the same conditions applied in crops; at the same time, assaying pure single active compounds made it possible to compare the effects obtained with commercial formulations. Interestingly, we found that while pure active compounds affect cell growth and metabolism at a lower extent, commercial preparations have a significant major negative influence on yeast biology.

Fermentation↗

Drug-protein recognition processes investigated by NMR relaxation data. A study on corticosteroid-albumin interactions.

In this paper we investigated the interaction processes occurring at the protein-solvent interface for prednisolone-albumin and prednisone-albumin systems, using an approach based on the analysis of proton selective relaxation rate enhancements of the ligand in the presence of the macromolecule. The contribution from the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index[A]L(T) and the normalized affinity index [AI(N)]L(T) which removes the effects of motional anisotropies and different proton densities, and isolates the contribution due to a decrease in the ligand dynamics caused by the binding with the protein. This approach allowed the comparison of the binding ability of prednisolone and prednisone towards albumin.

Animals↗

Metabolic response to exogenous ethanol in yeast: an in vivo NMR and mathematical modelling approach.

The understanding of the metabolic behaviour of complex systems such as eukaryotic cells needs the development of new approaches that are able to deal with the complexity due to a large number of interactions within the system. In this paper, we applied an approach based on the combined use of in vivo NMR experiments and mathematical modelling in order to analyze the metabolic response to ethanol stress in a wild-strain of Saccharomyces cerevisiae. Considering the cellular metabolic processes resulting from activation, inhibition, and feed-back activities, we developed a model able to describe the modulation of the whole system induced by an external stress due to increasing concentrations of exogenous ethanol. This approach was able to interpret the experimental results in terms of metabolic response to exogenous ethanol in the yeast. The robustness and flexibility of the model enables it to work correctly at different initial exogenous ethanol concentrations.

Carbon Isotopes↗

The role of wetlands in the chromophoric dissolved organic matter release and its relation to aquatic ecosystems optical properties. A case of study: Katonga and Bunjako Bays (Victoria Lake; Uganda).

Chromophoric Dissolved Organic Matter (CDOM) is an important component in freshwater and marine ecosystems and plays direct and indirect role in biogeochemical cycles. CDOM originates from the degradation process of organic materials, usually macrophytes and planktons. The present work examines the importance of wetland derived CDOM on the optical and bio-optical properties of two bays of Lake Victoria (Uganda, Africa). This was achieved by determining the attenuation and extinction coefficients of filtered and unfiltered water samples from two equatorial bays on the Ugandan coastline of Lake Victoria. Katonga Bay is a wetland lined bay that receives water from the Katonga river, while Bunjako Bay is an outer bay between Katonga Bay and Lake Victoria. The results showed that attenuation was highest in Katonga Bay and the role of CDOM is most dominant near the river inlet. The quantity and quality of CDOM is extremely different in the two bays: in Katonga Bay it is possible to hypothesize a terrestrial origin of CDOM (transported by the wetland river). On the contrary, in Bunjako Bay, spectral measurements of absorption indicate a modified CDOM and/or alternative CDOM source. The terrestrial CDOM in Katonga Bay is more capable of absorbing harmful UV radiation than the CDOM present in the Bunjako Bay. The resulting optical environment in the former bay presented a water column with a very limited penetration of harmful UV radiation, while a higher penetration was observed in the Bunjako Bay.

Ecosystem↗

Spatial and temporal variations of the inherent and apparent optical properties in a shallow coastal lake.

Apparent and inherent optical properties in the coastal lagoon of Fogliano were measured in three seasonal surveys in 2002. Irradiance data from in situ measurements of ultraviolet and visible wavebands permitted to estimate the related attenuation coefficients. Laboratory extinction measurements on filtered (0.22 microm) and unfiltered water samples were also performed. The integrated approach between in situ and laboratory measurements allowed the determination of the role of the suspended and dissolved matter in the attenuation and extinction of ultraviolet and visible radiation within the water column. As noted, the impact of the suspended and dissolved matter on the lake optical quality was influenced by wind resuspension of particulate matter: the relative role of dissolved matter in the absorption of UV and visible radiation was prevailing at low wind velocity conditions (less than 2.2 m s(-1)), while at high wind velocities (3.9 m s(-1)), particulate matter resuspension strongly influenced the attenuation and the extinction measurements. The extinction in the analyzed wavelengths of filtered and unfiltered water samples and the in situ irradiance measurements allowed us to define new optical parameters and important correlations with limnological and classical optical measurements. By sampling at high spatial resolution (18 stations in 4 km2), it was possible to evidence a spatial gradient of the optical and limnological properties, these distributions showed a consistent pattern in all three surveys, and were important for the characterization of the chromophoric dissolved organic matter that was estimated with the spectral slope of the extinction curve spectra. A relatively higher spectral slope was found in the southern basin with respect to the northern, where the maximum values of the attenuation coefficients and limnological parameters were found. These results suggest different sources of dissolved organic matter and/or a different level of photobleaching.

Fresh Water↗

Synthetic polymers as biomacromolecular models for studying ligand-protein interactions: a nuclear spin relaxation approach.

In this paper, we applied an NMR methodology based on the analysis of selective spin-lattice relaxation rate enhancements of ligand protons induced by interaction processes between prednisolone and a synthetic copolymer, namely poly(N-isopropylacrylamide-co-N-acryloil-L-phenylalanine), in order to investigate this system as a model for studying drug-biomacromolecules interactions. The contribution from the bound ligand fraction to the observed relaxation rate in relation to macromolecule concentration allowed the calculation of the normalized affinity index [A(N)(I)](T)(L), in which the effects of motional anisotropies and different proton densities have been removed. This parameter, which represents the global affinity of the ligand towards the macromolecule, isolates the contribution due to a decrease in the ligand dynamics caused by the binding with the copolymer. The affinity index calculated for prednisolone-copolymer complex compared to that obtained for prednisolone-albumin system, suggested that synthetic polymers as models of biomacromolecules can play an important role in drug-protein interaction studies.

Animals↗

Estimate of the effects of ultraviolet radiation on the mortality of Artemia franciscana in naupliar and adult stages.

The impact of different doses of artificial ultraviolet (UV) radiation on the growth stages of a marine zooplankton was investigated using laboratory microcosms. Mortality percentages of naupliar and adult samples of Artemia franciscana were recorded in relation to different UV doses (single exposure: 75, 150, 300, 600, 1,200, 2,400, 3,900, 7,800 J m(-2)) at specific observation times after exposure (24, 48, 72, 96 and 120 h). The relationship between mortality percentage and UV dose showed significant differences in relation to the zooplankton growth stage. The elevated susceptibility of the naupliar samples to UV radiation is described through a mortality model based on a logistic equation. The data analysis shows that the slope of mortality versus dose remains the same for the two growth stages while the lethal dose in the naupliar stage was 3.3 smaller than that determined for the adult stage. The slope of the UV mortality rate versus post-incubation time was found to be significantly different (P<0.05) at low UV doses for the two life stages examined, i.e. naupliar and adult. The lower value of LD(50) in naupliar stages compared to that for adults confirms that in the early growth stage this marine zooplankton is more susceptible to UV radiation.

Animals↗

Morphological anomalies in pollen tubes of Actinidia deliciosa (kiwi) exposed to 50 Hz magnetic field.

The role of the pollen grain, with respect to the reproductive process of higher plants, is to deliver the spermatic cells to the embryo sac for egg fertilisation. Delivery occurs through the pollen tube, a self produced organ that is generated when the pollen grain reaches the stigma surface. The effect of magnetic fields on pollen tube growth was reported in a recent publication by Germanà et al. Pollen tube growth is an interesting candidate for the detailed study of the effects of electromagnetic fields on cytoplasmic structures and organelles. In this research Actinidia deliciosa (kiwifruit) pollen grains were germinated in the presence of an alternating magnetic field (50 Hz). Our results, although of preliminary nature, show that pollen tube growth is affected by magnetic fields. The analysis of the observed anomalies in the pollen tube appear to be the result of changes in the ionic charges within the pollen tube cytoplasm.

Actinidia↗

Does carvedilol impair insulin sensitivity in heart failure patients without diabetes?

BACKGROUND: An increased risk for impaired glucose tolerance or diabetes was shown in patients on beta-blockers, whereas alpha1 blockers seem to have favorable effects on glycemic profile. In this study, the metabolic effect of carvedilol in nondiabetic patients with chronic heart failure (CHF) was evaluated. METHODS AND RESULTS: Twenty-eight nondiabetic CHF patients were enrolled. Before being started on carvedilol and on the highest tolerated dose, each patient underwent an oral glucose tolerance test and fasting insulin, glycohemoglobin, lipid concentrations were measured and insulin sensitivity indices (HOMA, ISI-gly, and ISI-composite) were calculated. An impaired glucose tolerance was found (2-hour glycemia 144 +/- 42 mg/dL), with a fasting glycemia at upper limits of normal (108 +/- 13 mg/dL) and no significant differences between basal and carvedilol treatment measurements. Fasting insulinemia significantly decreased during carvedilol treatment (13.6 +/- 7.3 versus 9.8 +/- 5.1 muU/mL; P = .022), with a reduction of the HOMA index (3.75 +/- 1.95 versus 2.73 +/- 1.47; P = 034) and an increase of the ISI-gly index (0.85 +/- 0.22 versus 1.03 +/- 0.31; P = .025). The lipoprotein profile did not significantly change. CONCLUSION: Carvedilol might have some positive metabolic effects on increasing insulin sensitivity that would make it suitable for diabetic patients that have a worse prognosis than non diabetic patients with CHF.

Adrenergic beta-Antagonists↗

Chemical waves and pattern formation in the 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/water lamellar system.

The present work deals with the spatially extended oscillatory Belousov Zhabotinsky reaction-diffusion system carried out in an anisotropic environment of phosphatidylcholines/water binary system, which presents layered aqueous domains separated by lipid bilayers. We report the occurrence of stable Turing patterns, spiral waves, and other exotic structures in phospholipids bilayers that are generally used as a models for cell plasma membranes.

1,2-Dipalmitoylphosphatidylcholine↗

Boronphenylalanine insertion in cationic liposomes for Boron Neutron Capture Therapy.

Cationic liposomes are widely used as carriers of biomolecules specifically targeted to the cell nucleus. p-Boronphenylalanine (BPA) is a powerful anti-tumor agent for Boron Neutron Capture Therapy (BNCT). In this paper, (1)H and (13)C NMR was used to study the insertion of BPA in mixed liposomes, made up by the positively charged 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The boronated drug was distributed between the water phase and the liposomes. The location site of BPA into the lipid bilayer was investigated and the boron-substituted aromatic ring was found inserted in the hydrophobic region, whereas the amino acidic group was oriented towards the aqueous environment. Further information was given by proton spin-lattice relaxation rates.

Boron Compounds↗

Characterization of persistent intramolecular C-H...X(N,O) bonds in solid state and solution.

The formation of intramolecular CH...X(N,O) bonds and their persistence in solution were studied by X-ray crystallography and NMR techniques in two different rotamers of a molecule containing the ortho-carborane cage, an amide group and a quinoline ring. Experimental data were confirmed by theoretical ab initio calculations. From the resolved structure of the two forms of this potentially active drug for boron neutron capture therapy, accurate bonding and geometric parameters were extracted for this non-classic hydrogen interaction, and their strength was calculated. These findings provided new insight in the theory of CH...X bonds, which appear stronger and less rare than it was previously thought.

Journal Article↗

Solution structure of rifaximin and its synthetic derivative rifaximin OR determined by experimental NMR and theoretical simulation methods.

The solution structure of rifaximin and its derivative rifaximin OR (open ring) was determined by combining NMR experimental results, theoretical simulation of two-dimensional NMR spectra by complete relaxation matrix analysis (corma), and molecular dynamics calculations. In this study the structural rearrangements due to the opening of the aliphatic chain of rifaximin after the reduction process to form rifaximin OR were investigated. Close spatial proximity of CH(3)(14) and H28b protons detected by 2D-ROESY spectrum of rifaximin OR, which was not present in rifaximin and the down-field shift of CH(3)(34) protons in rifaximin OR (1)H spectrum were crucial to understand the structural modifications, which occurred within the system. The aliphatic chain of rifaximin OR was found to be no longer symmetrical with respect to the aromatic moiety. Although no dramatic structural rearrangements were detected, the aliphatic chain moved toward CH(3)(14), causing a reduction of the aromatic shielding contribution in particular on CH(3)(34).

Anti-Infective Agents↗

In vivo 13C-NMR and modelling study of metabolic yield response to ethanol stress in a wild-type strain of Saccharomyces cerevisiae.

In this paper the combined use of in vivo (13)C-nuclear magnetic resonance spectroscopy and mathematical modelling allowed the analysis of the response to ethanol stress in a wild-type strain of Saccharomyces cerevisiae, in terms of a reduced metabolic activity. The model developed succeeded in describing and interpreting the effects of increasing concentrations of exogenous ethanol. In particular, the ratio between the kinetic constants associated with ethanol production and glucose consumption gave the estimation of the metabolic yield of the processes in perfect agreement with experimental results.

Carbon Isotopes↗

The effect of strong static magnetic field on lymphocytes.

We investigated whether static electromagnetic fields (EMFs) at a flux density of 4.75 T, generated by an NMR apparatus (NMRF), could promote movements of Ca2+, cell proliferation, and the eventual production of proinflammatory cytokines in human peripheral blood mononuclear cells (PBMC) as well as in Jurkat cells, after exposure to the field for 1 h. The same study was also performed after activation of cells with 5 mg/ml phytohaemagglutinin (PHA). Our results clearly demonstrate that static NMRF exposure has neither proliferative, nor activating, nor proinflammatory effects on both normal and PHA activated PBMC. Moreover, the concentration of interleukin-1beta, interleukin-2, interleukin-6, interferon, and tumour necrosis factor alpha (TNFalpha) remained unvaried in exposed cells. Exposure of Jurkat cells statistically decreased the proliferation and the proliferation indexes, which 24 and 48 h after exposure were 0.7 +/- 0.29 and 0.87 +/- 0.12, respectively. Moreover, in Jurkat cells the [Ca2+]i was higher than in PBMC and was reduced significantly to about one half after exposure. This is consistent with the decrease of proliferation and with the low levels of IL-2 measured. On the whole, our data suggest that NMRF exposure failed to affect the physiologic behaviour of normal lymphomonocytes. Instead in Jurkat cells, by changing the properties of cell membranes, NMRF can influence Ca2+ transport processes, and hence Ca2+ homeostasis with improvement of proliferation.

Caffeine↗

The effect of exposure to high flux density static and pulsed magnetic fields on lymphocyte function.

We investigated whether a combination of static electromagnetic field (EMF) at a flux density of 4.75 T together with pulsed EMF at a flux density of 0.7 mT generated by an NMR apparatus (NMRF), could promote movements of Ca(2+), cell proliferation, and the eventual production of proinflammatory cytokines in human lymphocytes as well as in Jurkat cells, after exposure to the field for 1 h. The same study was also performed after activation of cells with 5 micro g/ml phytohaemagglutinin (PHA) immediately before the exposure period. Our results clearly demonstrate that NMRF exposure increases the [Ca(2+)](i), without any proliferative, or activating, or proinflammatory effect on both normal and PHA stimulated lymphocytes. Accordingly, the levels of interferon gamma, tumor necrosis factor alpha, interleukin-1beta, interleukin-2, and interleukin-6 remained unvaried after exposure. Exposure of Jurkat cells statistically decreased the [Ca(2+)](i) and the proliferation. This is consistent with the low levels of IL-2 measured in supernatants of these cells after exposure. On the whole our data suggest that static and pulsed NMRF exposure contribute synergistically in the increase of the [Ca(2+)](i) without any activating or proinflammatory effect either in normal or in PHA challenged lymphocytes. In Jurkat cells, by changing the properties of cell membranes, NMRF exposure can influence Ca(2+) transport processes and hence Ca(2+) homeostasis, causing a marked decrease of proliferation.

Calcium↗