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Biomedical subjects

G Saba

Publications and source records attributed to G Saba.

At least 19 recordsLinked to original sources

Therapeutic and neurophysiologic aspects of transcranial magnetic stimulation in schizophrenia.

The use of repetitive transcranial magnetic stimulation (rTMS) in psychiatry provides the therapeutic field with a new tool. Since its introduction in the mid 1980s, the vast majority of studies have focussed on depression. A growing body of evidence suggests that rTMS is effective in the treatment of depression if dorsolateral prefrontal cortex is stimulated. Less is known about its efficacy in schizophrenia. Neuroimaging investigations in schizophrenia suggest abnormalities in the prefrontal and temporoparietal cortex (TPC), which are correlated with psychopathological dimensions. Based on its modulatory effect, rTMS seems to be a promising tool in exploring cortical excitability and reducing auditory hallucinations (AH) and negative symptoms. Neurophysiologic studies of patients suffering from schizophrenia using rTMS indicate high cortical excitability and a lack of transcallosal inhibition. In the therapeutic field, researches provide encouraging results, even though some studies indicate limited benefits. The most promising therapeutic effect seems to be the capability of rTMS to reduce AH if TPC is targeted using slow-frequency. The current paper aims to provide a review of the literature of the use of rTMS in schizophrenia.

Antipsychotic Agents↗

Transcranial magnetic stimulation in the treatment of schizophrenic symptoms: a double blind sham controlled study.

BACKGROUND: Schizophrenia is a disabling disease with a significant proportion of patients experiencing persistent symptoms. Repetitive transcranial magnetic stimulation (rTMS) is a promising new therapeutic tool that could benefit to schizophrenic patients. In this study we sought to assess the efficacy of active rTMS compared to sham stimulation in the treatment of patients with schizophrenia. METHOD: Eighteen schizophrenic patients according to DSM-IV criteria were randomly allocated to receive active or sham rTMS for 10 days over the left temporoparietal cortex (80% of the motor threshold, 1Hz, five trains of 1 min). Psychopathological dimensions were measured with the positive and negative syndrome scale and clinical global impression at baseline and after 10 session of rTMS. RESULTS: All patients were improved at the end of the trial but no significant group differences were found. Patients receiving sham stimulation showed the same pattern of improvement compared to active condition on all the subscales of the positive and negative syndrome scale and clinical global impression scores (p>0.05). CONCLUSION: In our study, active rTMS failed to show superiority over sham stimulation in the treatment of schizophrenic symptoms. Although previous results have shown that rTMS reduces auditory hallucination, its efficacy on other positive schizophrenic symptoms is not yet established. Nevertheless, the results of our study, even though negative, provide further insights in the pathophysiology of schizophrenia.

Adult↗

A 23Na NMR study of the effect of D(+) and L(-) arabitol on NaDNA in aqueous solution.

The 23Na NMR quadrupolar relaxation in NaDNA aqueous solutions has been investigated in the presence of D(+) and L(-) arabitol. Quite different results were produced by the enantiomers, i.e. the addition of D(+) arabitol produced a small increase of the 23Na NMR relaxation rates, while in the presence of L(-) arabitol a significant decrease was observed. These findings were analysed and discussed in terms of an effective interaction of L(-) arabitol with DNA.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗