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Biomedical subjects

G Giorgi

Publications and source records attributed to G Giorgi.

At least 19 recordsLinked to original sources

NMDA receptor inhibition prevents tolerance to cocaine.

Male rats were treated with cocaine by utilizing two different experimental paradigms. One group of animals received a low dose (10 mg/kg, IP) of cocaine for 7 days. A second group received 40 mg/kg IP of cocaine for 3 days. In both experimental groups, half the animals were concomitantly treated with 0.25 mg/kg IP (+)-5methyl-10,11-dihydro-5H-dibenzo-[a,d]-cyclohepten-5,10- imine maleate (MK-801), a noncompetitive NMDA receptor antagonist. Rats treated with the low dose of cocaine after 7 days developed tolerance to the stimulation of locomotor activity induced by cocaine and by the dopamine D2 agonist quinpirole. Rats treated with 40 mg/kg of cocaine showed a marked behavioral sensitization. Both these effects, tolerance and sensitization, were prevented by coadministration of MK-801, thus suggesting these two phenomena are different aspects of a common neuronal response in which NMDA transmission plays a crucial role.

Animals

Effect of non-steroidal anti-inflammatory drugs on glutathione levels in various organs of rat.

Since glutathione (GSH) depletion (about 20% of total GSH content) can impair the cell's defence against the toxic actions of drugs and may lead to cell injury and death, we examined the effect of piroxicam, naproxen and ketoprofen on GSH levels in various organs of the rat (brain, eye, liver, stomach, heart, leg adductor muscle). Ketoprofen in brain and leg adductor muscle dramatically decreases the GSH levels, giving rise to potential cellular toxicity.

Animals

Molecular cloning and expression of a human heat shock factor, HSF1.

Human cells respond to heat stress by inducing the binding of a preexisting transcriptional activator (heat shock factor, HSF) to DNA. We have isolated recombinant DNA clones for a human HSF (HSF1) by screening cDNA libraries with a human cDNA fragment. The human HSF1 probe was produced by the PCR with primers deduced from conserved amino acids in the Drosophila and yeast HSF sequences. The human HSF1 mRNA is constitutively expressed in HeLa cells under nonshock conditions and encodes a protein with four conserved leucine zipper motifs. Like its counterpart in Drosophila, human HSF1 produced in Escherichia coli in the absence of heat shock is active as a DNA binding transcription factor, suggesting that the intrinsic activity of HSF is under negative control in human cells. Surprisingly, an independently isolated human HSF clone, HSF2, is related to but significantly different from HSF1 [Schuetz, T. J., Gallo, G. J., Sheldon, L., Tempst, P. & Kingston, R. E. (1991) Proc. Natl. Acad. Sci. USA 88, 6911-6915].

Amino Acid Sequence

Influence of probenecid on P-amino hippurate kinetics.

The influence of probenecid on p-amino hippurate (PAH) kinetics was investigated in rat. Probenecid was administered i.p. (25, 50, 100, 150 and 200 mg/kg) two hours before PAH administration (25 mg/kg i.v.). The distribution and the rate of elimination of PAH was influenced by probenecid co-administration: the distribution decreased after probenecid doses higher than 150 mg/kg and the rate of elimination decreased after doses higher than 50 mg/kg.

Animals

Interaction of purine nucleotides with inert paramagnetic Cr(III) probes evaluated by NMR relaxation effects. Molecular mechanics calculations on Cr(III) and Co(III) polyphosphate complexes.

The 1H NMR relaxation effects produced by paramagnetic Cr(III) complexes on nucleoside 5'-mono- and -triphosphates in D2O solution at pH' = 3 were measured. The paramagnetic probes were [Cr(III)(H2O)6]3+, [Cr(III)(H2O)3(HATP)], [Cr(III)(H2O)3(HCTP)] and [Cr(III)(H2O)3(UTP)-, while the matrix nucleotides (0.1 M) were H2AMP, HIMP-, and H2ATP2-. For the aromatic base protons, the ratios of the transverse to longitudinal paramagnetic relaxation rates (R2p/R1p) for the [Cr(III)(H2O)6]3+/H2ATP2-, [Cr(III)(H2O)3(HATP)]/H2ATP2-, [Cr(III)(H2O)3(HCTP)]/H2ATP2 and [Cr(III)(H2O)3(UTP)]-/H2ATP2 systems were below 2.33 so the dipolar term predominates. For a given nucleotide, R1p for the purine H(8) signal was larger than for the H(2) signal with the [Cr(III)(H2O)6]3+ probe, while R1p for the H(2) signal was larger with all the other Cr(III) probes. Molecular mechanics computations on the [Cr(III)(H2O)4(HPP)(alpha,beta)], [Cr(III)(NH3)4(HPP)(alpha,beta)], [Co(III)(NH3)3(H2PPP)(alpha,beta,gamma)] and [Co(III)(NH3)4(HPP)(alpha,beta)] complexes gave calculated energy-minimized geometries in good agreement with those reported in crystal structures. The molecular mechanics force constants found were then used to calculate the geometry of the inner sphere [Cr(III)(H2O)6]3+ and [Cr(III)(H2O)3(HATP)(alpha,beta,gamma)] complexes as well as the structures of the outer sphere [Cr(III)(H2O)6]3(+)-(H2AMP) and [Cr(III)(H2O)6]-(HIMP)- species. The gas-phase structure of the [Cr(III)(H2O)3(HATP)(alpha,beta,gamma)] complex shows the existence of a hydrogen bond interaction between a water ligand and the adenine N(7)(O...N = 2.82 A). The structure is also stabilized by intramolecular hydrogen bonds involving the -O(2')H group and the adenine N(3) (O...N = 2.80 A) as well as phosphate oxygen atoms and a water molecule (O...O = 2.47 A). The metal center has an almost regular octahedral coordination geometry. The structures of the two outer-sphere species reveal that the phosphate group interacts strongly with the hexa-aquochromium probe. In both complexes, the nucleotides have a similar "anti" conformation around the N(9)-C(1') glycosidic bond. However, a very important difference characterizes the two structures. For the (HIMP)- complex, strong hydrogen bond interactions exist between one and two water ligands and the inosine N(7) and O(6) atoms, respectively (O...O = 2.63 A; O...N = 2.72, 2.70 A). For the H2AMP complex, the [Cr(III)(H2O)6]3+ cation does not interact with N(7) since it is far from the purine system. Hydrogen bonds occur between water ligands and phosphate oxygens. The Cr-H(8) and Cr-H(2) distances revealed by the energy-minimized geometries for the two outer sphere species were used to calculate the R1p values for the H(8) and H(2) signals for comparison with the observed R1p values: 0.92(c), 1.04(ob) (H(8)) and 0.06(c), 0.35(ob) (H(2)) for H2AMP; and 3.76(c), 4.53(ob) (H(8)) and 0.16(c), 0.77(ob) s-1 (H(2)) for HIMP-.(ABSTRACT TRUNCATED AT 400 WORDS)

Chromium

Developmental effects of modifiers of the vg mutant in Drosophila melanogaster.

An analysis of the modifiers affecting the expression of the vg gene was performed. We selected for weak and strong expression of the vg mutant in F2 segregating populations obtained by crossing a vestigial stock with an Oregon laboratory stock (O) and with a wild strain (B) captured near Bologna, Italy. The selection for enlarged wings was more effective in the vg B population where wild wings appeared from the 10th generation. The assay of the three major chromosomes showed that the modifiers are located on chromosomes 2 and 3. The mutant imaginal disc cell death phenotype is evident in vg/vg strains that have a wild-type wing phenotype. It is suggested that the selected modifiers do not prevent cell death but induce regenerative growth.

Animals

Kinetics of amiloride in rat following oral and intravenous administration.

The disposition profile of amiloride, a potassium sparing agent, was studied in rats by using an HPLC method coupled to spectrofluorometric detection. Amiloride was administered orally and intravenously at the dose of 10 mg/Kg. The most relevant pharmacokinetic parameters are described for both administration routes.

Administration, Oral

Effect of buspirone on glutathione hepatic levels in rat.

The effect of oral administration of buspirone (0.5-1.0 and 2.0 mg/Kg) on GSH levels was studied in rat liver. The modulating activity of buspirone on hepatic content of this tripeptide is clearly opposite to that of DAZ, put into evidence by us in previous works. Thus our observations let us hypothesize a different mechanism of action for buspirone than that for benzodiazepines.

Administration, Oral

Glutathione (GSH) in human stomach mucosa.

The role of glutathione and its function in patients affected by carcinoma and ulcer was studied. The dramatical decrease of this tripeptide evidenced by the authors, demonstrates its fundamental role in the above mentioned pathologies and permits to formulate a hypothesis of therapeutic presidium for some substances (e.g. cysteine), that showed to be able in recovering normal glutathione levels.

Adult

A comparative study of doxazosin versus atenolol in mild-to-moderate hypertension.

Doxazosin, a quinazoline derivative, is a selective alpha 1-inhibitor that reduces calculated coronary heart disease risk by lowering blood pressure while favorably affecting blood lipid levels. The aim of this study was to compare the efficacy and toleration of doxazosin with atenolol, one of the most frequently used cardioselective beta-blockers in Italy. Forty patients with mild-to-moderate hypertension were treated with either atenolol (100 mg) or doxazosin (mean dose, 3.3 mg) once daily for 8 weeks. Both drugs significantly reduced supine and standing systolic and diastolic blood pressures. Atenolol induced marked bradycardia, whereas doxazosin had very little effect on heart rate. Doxazosin produced a favorable effect on blood lipid levels by decreasing triglyceride and total cholesterol levels and increasing high-density lipoprotein cholesterol and high-density lipoprotein total cholesterol ratio. Atenolol had exactly the opposite effect on blood lipid levels. Both drugs had equivalent toleration profiles. It was concluded that doxazosin was as effective as atenolol in reducing elevated supine and standing blood pressures. In addition, doxazosin had a beneficial effect on lipid profiles and minimal effect on heart rate. Therefore doxazosin may reduce calculated coronary heart disease risk in hypertensive patients.

Adolescent

Genetic and environmental influences on serum levels of immunoglobulins and complement components in monozygotic and dizygotic twins.

The influence of hereditary and environmental factors in the regulation of the serum levels of IgM, IgG and IgA and of the Complement components C3, C4 and factor B has been studied. For this purpose, sera from 9 monozygotic twin pairs, from 10 dizygotic twin pairs and from two control groups were analyzed. The first control group consisted of three healthy donors analyzed once a week for three weeks, as a genetic identity experimental control, while the second one was constituted by nine subjects randomly selected as a genetic heterogeneity control. The results indicate that the serum proteins with immunological functions can be subdivided into three groups. The first, represented by IgM and IgG, appears to be under strict genetic control; the second, represented by IgA and C3, appears to be influenced either by genetic or environmental factors; the third one, including C4 and factor B, is strongly influenced by environmental factors.

Adolescent

Thiazolidine-4-carboxylic acid toxicity and glutathione levels in various organs of the rat.

Thiazolidine-4-carboxylic acid (TC) (a precursor of intracellular cysteine) was administered to rats at 50 mg/kg and at 400 mg/kg by an i.p. route and at 800 mg/kg per os, and the levels of glutathione (GSH) in gastric mucosa, gastric wall and liver were determined. GSH levels in the eyes were measured after oral administration of TC. No changes in GSH levels were observed at 50 mg/kg from 1 to 48 h. An initial increase of liver GSH levels was followed by a decrease (up to 12 h) at 400 mg/kg i.p. After oral administration of 800 mg/kg an initial increase of GSH levels in the liver and gastric mucosa was followed by a decrease (up to 24 h); the GSH levels in the gastric wall showed a persistent decrease. No significant changes were seen in the GSH levels of the eyes.

Animals