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G Saba

Publications and source records attributed to G Saba.

At least 19 recordsLinked to original sources
PubMed2001

Probing proteins in solution by (129)Xe NMR spectroscopy.

The interaction of xenon with different proteins in aqueous solution is investigated by (129)Xe NMR spectroscopy. Chemical shifts are measured in horse metmyoglobin, hen egg white lysozyme, and horse cytochrome c solutions as a function of xenon concentration. In these systems, xenon is in fast exchange between all possible environments. The results suggest that nonspecific interactions exist between xenon and the protein exteriors and the data are analyzed in term of parameters which characterize the protein surfaces. The experimental data for horse metmyoglobin are interpreted using a model in which xenon forms a 1:1 complex with the protein and the chemical shift of the complexed xenon is reported (Locci et al., Keystone Symposia "Frontiers of NMR in Molecular Biology VI", Jan. 9--15, 1999, Breckenridge, CO, Abstract E216, p. 53; Locci et al., XeMAT 2000 "Optical Polarization and Xenon NMR of Materials", June 28--30, 2000, Sestri Levante, Italy, p. 46).

Animals↗
PubMed1999

Cyclic pentapeptides of chiral sequence DLDDL as scaffold for antagonism of G-protein coupled receptors: synthesis, activity and conformational analysis by NMR and molecular dynamics of ITF 1565 a substance P inhibitor.

Under the hypotheses of a structurally related binding site for antagonists of G-protein coupled receptors and the ability of cyclic pentapeptides of chiral sequence D1L2D3D4L5 to form rigid structures with which probe the pharmacophoric specificity of these receptors, inhibitors of substance P were designed based on available structure-activity relationships. ITF 1565, cyclo[D-Trp1-Pro2-D-Lys3-D-Trp4-Phe5], antagonized substance P activity mediated by type 1 neurokinin receptor (NK1) whereas it acted weakly against NK2 and did not inhibit endothelin at all. The preferential conformation of the peptide was obtained from nmr spectroscopy and computer calculations, and shown to contain the same beta II-turn and gamma'-turn found in other cyclic pentapeptides with the same chiral sequence. The structure of the peptide was compared with that of the beta-D-glucose molecule that has been proposed as a semirigid scaffold for antagonists of G-protein coupled receptors. The gamma'-turn of the cyclic peptide superimposed well with beta-D-glucose in the chair conformation. Furthermore, when the side chains were considered, the aromatic groups of the two molecules were found to generally overlap. These results support the view of G-protein coupled receptors as possessing structurally similar binding sites for antagonists and suggest that cyclic pentapeptides of chiral sequence D1L2D3D4L5 may be useful as semirigid scaffolds for the design of antagonists of this family of receptors.

Animals↗
PubMed1999

Recognition and quantitation of cis-vaccenic and eicosenoic fatty acids in olive oils by 13C nuclear magnetic resonance spectroscopy.

The presence of 11-cis monoenoic fatty acids was detected in olive oil samples by means of 13C nuclear magnetic resonance spectroscopy, and the positional isomery on the glycerol backbone was derived. The 11-cis vaccenic and eicosenoic fatty acid resonances were recognized and the amounts of the fatty acids quantified. For comparison purposes, a quantitative analysis was also made by gas chromatography.

Carbon Isotopes↗
PubMed1998

23Na NMR studies of Na-DNA in the solid state.

23Na MAS, CP/MAS and quadrupole nutation NMR spectra and the 23Na spin-lattice relaxation times in Na-DNA with and without competing species (Mg2+, ethidium bromide and [Ru(phen)3]2+) reveal the presence of two sodium sites with different NMR parameters. While in the presence of Mg2+, sodium resides far from the surface of the DNA molecule, ethidium bromide and [Ru(phen)3]2+ displace sodium closer towards the surface.

Animals↗
PubMed1997

Long-term health effects of the occupational exposure to DDT. A preliminary report.

We conducted a proportional mortality study of 1043 deaths among men who took part in an antimalarial campaign in Sardinia, Italy from 1946 to 1950. DDT comprised 94% of the insecticide used during the campaign, and was sprayed over the soil of the entire region at an average concentration of 10 mg/m2, as well as in all dwellings and animal shelters. Expected deaths were derived from the proportional mortality rates of the general Italian male population, specific by cause, 5-year age groups, and 5-year calendar periods in the period from 1956 to 1992. The proportional mortality ratio (PMR) for cardiovascular diseases was significantly decreased, while nonmalignant respiratory diseases showed a 22% increase in risk of borderline statistical significance. Significant increases in risk among workers exposed to DDT in application or inspection jobs were observed for liver and biliary tract cancer (PMR = 228; 95% C.I. = 143-345) and multiple myeloma (PMR = 341; 95% C.I. = 110-795). The PMR for myeloid leukemia was also increased (PMR = 189; 95% C.I. = 38-552), although it was not statistically significant. PMRs for liver and biliary tract cancer and myeloid leukemia were also elevated among workers who did not have direct occupational contact with DDT (liver and biliary cancer: PMR = 210; 95% C.I. = 117-346; myeloid leukemia: PMR = 170; 95% C.I. = 19-614). No trends occurred according to length of employment in exposed jobs. These preliminary results are somewhat in agreement with experimental studies in rodents and previous epidemiologic findings. Expansion of the cohort to include all applications, and collection of information to improve exposure assessment is needed to clarify these findings.

DDT↗
PubMed1997

The interaction of DNA with intercalating agents probed by sodium-23 NMR relaxation rates.

We have investigated the changes of Na-23 NMR spin-lattice and spin-spin relaxation rates of Na-DNA in dilute aqueous solutions, induced by the intercalating drugs ethidium, propidium, 6,7-dihydro-pyrido[2',1':3,4]pyrazino[1,2-f]-phenanthridinediium dihydrate (dq2pyp) and by the electrostatic binder Mg2+. It has been found that the Na-23 spin-lattice relaxation is monoexponential, while the spin-spin relaxation follows a biexponential law. From the linear trends of the relaxation rates observed in the titration experiments of Na-DNA with the drugs we inferred the validity of a two-site model in the fast exchange limit. The relaxation rates of sodium in the bound state have been estimated by using the fraction of bound sodium ions per phosphate charge, predicted by the counterion condensation theory, and the number of sodium ions released per bound drug, calculated from salt dependent equilibrium binding studies. The results show that the addition of the competitors slow down the broad component of the spin-spin relaxation rate of bound sodium in the order dq2pyp approximately propidium < ethidium < Mg2+. This reduction is shown to be due mainly to the decrease of the quadrupolar coupling constant for the slow motions, thus indicating a decrease of the average electric field gradient at the sodium ions close to the DNA surface. We also show that the broad component of the spin-spin relaxation rate linearly correlates with the relative non-polyelectrolyte free energy. This result is discussed in terms of the non-polyelectrolyte interactions affecting R2bB, which can be partitioned into stacking interaction and interactions involving the molecular moieties of the intercalators exposed to the solvent in the minor groove.

Binding, Competitive↗
PubMed1996

Binding of Ru(II) polyazaaromatic complexes to DNA: A 23Na NMR spin-lattice relaxation study.

The possibility of using sodium-23 spin-lattice relaxation rate measurements to probe the interaction modes of Ru11 polyazaaaromatic complexes with DNA is investigated. The following complexes are considered: Ru(phen)3(2+) (phen = 1.10-phenanthroline), Ru(phen)2HAT2+ (HAT = 1,4,5,8,9,12-hexaazatriphenylene), and Ru(diMeTAP)3(2+) (diMeTAP = 2,7-dimethyl-1,4,5,8-tetraazaphenanthrene). The addition of Ru(diMeTAP)3(2+) to a solution of NaDNA leads to a decrease in the sodium-23 spin-lattice relaxation rate (R1) similar to the effect observed upon addition of Mg2+. This indicates that Ru(diMeTAP)3(2+) interacts like Mg2+ with DNA and consequently that the electrostatic interaction dominates the association with DNA, Ru(phen)3(2+) and Ru(phen)2HAT2+ diminish R1 more efficiently than Mg2+, in a manner similar to ethidium bromide, which is known for its intercalation properties. Thus interactions other than electrostatic occur between these two complexes and DNA. These results are in agreement with data obtained from other techniques, according to which Ru(phen)3(2+) and Ru(phen)2HAT2+ are located partially inside the DNA double helix, in contrast to Ru(diMeTAP)3(2+) which remains in the ionic atmosphere around the phosphate backbone.

Animals↗
PubMed1996

Perioperative changes in alpha 1-acid glycoprotein concentrations in infants undergoing major surgery.

alpha 1-Acid glycoprotein (AAG) is an acute phase protein that is responsible for binding basic drugs such as bupivacaine. In order to determine how AAG concentrations change in response to surgical stress, arterial blood samples were obtained from 50 infants undergoing major surgery, at induction of anaesthesia and daily for the next 7 days. AAG concentrations were measured using a rate nephelometric technique. The overall mean preoperative AAG concentration was 0.38 (SD 0.16) mg ml-1, although concentrations were significantly greater in infants undergoing urgent surgery compared with those undergoing elective surgery (P = 0.02). There were no significant correlations between gestational or postnatal age and preoperative AAG concentration. Mean AAG concentrations increased to 0.76 (0.18) mg ml-1 by day 4 after surgery and stayed at that concentration thereafter. Infants with preoperative AAG concentrations < 0.38 mg ml-1 showed a greater percentage increase in postoperative AAG concentrations than did infants with preoperative AAG concentrations > 0.38 mg ml-1 (P = 0.001). We conclude that preoperative measurement of AAG may identify those infants most at risk of drug toxicity in the early postoperative period.

Age Factors↗
PubMed1996

Trough:peak ratio of nifedipine gastrointestinal therapeutic system and nifedipine retard in essential hypertensive patients: an Italian multicentre study.

OBJECTIVE: To evaluate the antihypertensive effect of nifedipine gastrointestinal therapeutic system and retard in terms of trough:peak ratio efficacy. METHODS: According to a double-blind, randomized, crossover design, 58 patients with mild-to-moderate essential hypertension, after 1 month placebo washout, received 30 mg/day nifedipine gastrointestinal therapeutic system, 20 mg nifedipine retard twice a day and the corresponding placebos for 1 month. At the end of each treatment period, blood pressure was measured by using a mercury sphygmomanometer at trough and 1, 2, 3 and 4 h after the last dosing. The peak effect was identified as the maximum decrement induced by the three randomized treatments with respect to the value at the end of the placebo washout period during the 4 h interval. The trough:peak ratios of systolic and diastolic blood pressure were calculated as group ratios and individual ratios from decrements induced by nifedipine gastrointestinal therapeutic system and retard, corrected for those induced by randomized placebo. Patients were defined as responders to each randomized treatment if their diastolic blood pressure at trough time was reduced by at least 10 mmHg relative to that at the corresponding time at the end of placebo washout. RESULTS: Nifedipine gastrointestinal therapeutic system and retard significantly reduced blood pressure to a similar extent both at trough and at peak. Systolic and diastolic group trough:peak ratios in responders to nifedipine gastrointestinal therapeutic system (n = 41) were 0.80 and 0.88, respectively, and those in responders to nifedipine retard (n = 30) 0.84 and 0.93, respectively. The percentage of patients with trough:peak ratios > 0.50 was > 80% (systolic trough:peak ratios) and above 90% (diastolic trough: peak ratios) for both nifedipine formulations. CONCLUSIONS: Our data show that 30 mg/day nifedipine gastrointestinal therapeutic system and 20 mg nifedipine retard twice a day have a favourable trough:peak ratios efficacy when given as monotherapy to essential hypertensive patients.

Adult↗
PubMed1996

Mortality of lead smelter workers with the glucose-6-phosphate dehydrogenase-deficient phenotype.

The mortality experience of 1345 male workers in a lead and zinc smelting plant was followed from 1973 to 1991. Information on the erythrocyte glucose-6-phosphate dehydrogenase (G6PD) phenotype was available for 1,222 (90.9%) cohort members, which provided the opportunity to compare the mortality experience of G6PD-deficient subjects to wild-type-G6PD coworkers with similar exposure to lead. A significant decrease in mortality was observed among the total cohort as well as among the subcohort of production and maintenance workers. Most deaths (27 of 31) and all cancer deaths occurred among production and maintenance workers. Lung cancer mortality was lower than expected. Two deaths from stomach cancer were observed versus 0.6 expected. Mortality from all causes and cancer mortality were lower among production and maintenance workers with the G6PD-deficient phenotype compared to coworkers with the wild-type phenotype. Although the low statistical power of this study prevents conclusive inference, lead smelter workers with the G6PD-deficient phenotype did not suffer adverse health outcomes in terms of mortality from all causes and cancer mortality compared to coworkers with the wild-type G6PD.

Adult↗
PubMed1992

Analysis of sodium-23 nuclear magnetic resonance spin-lattice relaxation for the study of the intracellular sodium state.

Sodium-23 Nuclear Magnetic Resonance relaxation spectroscopy has been used to investigate the state of intracellular Na+ in control and CCl4-treated rat livers. The analysis of spin-lattice relaxation rates at 1.88 and 7.07 Tesla based on a two-site exchange model led to estimates of pertinent modulation times. Also it has been found that a relatively high quantity of Na+ (PB = 1.59 x 10(-2)) is bound to charged sites of intracellular macromolecules or membranes. The degree of binding strongly decreases in CCl4 treated rat livers.

Animals↗
PubMed1991

Proton and tritium NMR relaxation studies of peptide inhibitor binding to bacterial collagenase: conformation and dynamics.

The interaction of succinyl-Pro-Ala, a competitive inhibitor of Achromobacter iophagus collagenase, with the enzyme was studied by longitudinal proton and tritium relaxation. Specific deuterium and tritium labeling of the succinyl part at vicinal positions allowed the measurement of the cross-relaxation rates of individual proton or tritium spin pairs in the inhibitor-enzyme complex as well as in the free inhibitor. Overall correlation times, internuclear distances, and qualitative information on the internal mobility in Suc1 (as provided by the generalized order parameter S2) could be deduced by the comparison of proton and tritium cross-relaxation of spin pairs at complementary positions in the -CH2- CH2- moiety as analyzed in terms of the model-free approach by Lipari and Szabo. The conformational and motional parameters of the inhibitor in the free and enzyme-bound state were directly compared by this method. The measurement of proton cross-relaxation in the Ala residue provided additional information on the inhibitor binding. The determination of the order parameter in different parts of the inhibitor molecule in the bound state indicates that the succinyl and alanyl residues are primarily involved in the interaction with the enzyme activity site. The succinyl moiety, characterized in solution by the conformational equilibrium among the three staggered rotamers--i.e., trans: 50%; g+: 20%; g-: 30%--adopted in the bound state the unique trans conformation.

Alcaligenes↗
PubMed1988

The combination of a low-Na/high-K salt with metoprolol in the treatment of mild-moderate hypertension. A multicenter study.

To extend our previous findings that a low-Na/high-K salt (S) reduces BP in hospitalized patients, a multicenter study was performed. After a placebo period during which patients were informed by written instruction how to avoid only foods with a high Na content, 143 out-patients (84 males and 59 females, mean age 50.7 years, range 28-69) with DBP greater than or equal to 95 mm Hg randomly received for 4 weeks either metoprolol (M) 200 mg SR qd (67 patients), or S, 2 g bid to add to foods (76 patients). At the end of this period patients with DBP still greater than 90 mm Hg combined the two treatments for a further 4 weeks. Mean blood pressure (mm Hg), HR (bpm), 24-hrs urinary Na and K excretion were measured fortnightly. In comparison to pretreatment values MBP was significantly (P less than 0.01) reduced by both treatments, although to a greater extent in the M group already at the second week, without any further decrement thereafter. In the S group MBP decreased by 4.4 mm Hg and 27/76 patients were responders (DBP less than or equal to 90 mm Hg), while in the M group it was reduced by 9.0 mm Hg and 28/67 patients were responders. In the S group urinary Na excretion was significantly (P less than 0.01) lower than in the M group, and this difference was present until the end of period 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Plasma renin activity does not predict the antihypertensive efficacy of chlorthalidone.

It has been established that angiotensin II stimulation may limit the antihypertensive potential of diuretic therapy in some patients. It is less clear, however, whether renin-angiotensin II stimulation is the cause of the flat blood pressure dose-response relationship to diuretics. To investigate this, 75 out-patients with essential hypertension were treated with chlorthalidone 12.5, 25 or 50 mg o.d. for 3 weeks, in a double-blind, placebo controlled cross-over study. Chlorthalidone significantly reduced blood pressure in all the groups, a plateau being reached at 25 mg o.d. Similarly, plasma renin activity was increased by each dose level of chlorthalidone, but it showed a different trend, being increased to a comparable extent at 12.5 mg and 25 mg o.d., and still higher at 50 mg o.d. Thus, greater stimulation of renin was coincident with the levelling of the blood pressure response to chlorthalidone. However no significant correlation was found between interindividual plasma renin activity and change in blood pressure, either in the entire series, or in each treatment subset. The data suggest overall that renin stimulation may influence the characteristic dose-hypotensive response relationship to diuretic agents in antihypertensive therapy, but it is unlikely that measurement of individual plasma renin activity will provide an useful guide to the optimal dose of a diuretic agents.

Adult↗