Search PubMed⌕ Search

Biomedical subjects

G Sartor

Publications and source records attributed to G Sartor.

13 recordsLinked to original sources
PubMed1992

Hyperthermia in clinical practice: preliminary results and current problems in the treatment of 21 patients.

From February 1988 through February 1991, 21 patients were managed by superficial hyperthermia and radiotherapy. Nineteen patients had received previous treatment; the most common histology was breast carcinoma. Twenty-six cycles of combined hyperthermia and radiotherapy were delivered: 4 complete responses (15.4%), 17 partial responses (65.4%), 1 minimal partial response (3.8%), 3 stable diseases (11.6%) and 1 disease progression (3.8%) were obtained. The median duration of response was 7 months (range 1-16) for responding and 4 months (range 2.5-4) for non-responding patients. The toxicity encountered (confined mostly to epithelitis--7/21 patients) was completely reversible. In our experience, hyperthermia combined with radiotherapy proved to be an effective treatment. However, some problem that emerged during treatment planning and delivery showed the need for further development and research into hyperthermic devices and thermometry systems.

Adult↗
PubMed1992

The binding of 4',6-diamidino-2-phenylindole to bovine serum albumin.

The binding of 4',6-diamidino-2-phenylindole (DAPI) to bovine serum albumin (BSA) has been investigated between pH 6 and 8, in 0.05 M phosphate buffer at 20 degrees C, by fluorescence titrations and the results analyzed according to a procedure previously reported (R. Favilla and A. Mazzini, Biochim. Biophys. Acta 788 (1984) 48). The dye binds to the protein with a blue shift of about 4 nm in its fluorescence emission maximum, but with an enhancement factor of 10 of its fluorescence quantum yield. The dissociation constant decreases from 100 microM to 54 microM as the pH is increased from 6 to 8, with a constant number of nearly three equivalent binding sites. The complete displacement of DAPI bound to BSA by Ca2+ suggests a possible specificity of this substantially electrostatic interaction. The fluorescence decay of DAPI bound to the protein shows a double exponential kinetics, with a tau 1 = 0.97 ns and tau 2 = 2.78 ns. These results, compared with those obtained for DAPI alone, tau 1 = 0.16 ns and tau 2 = 2.8 ns, are rationalized in terms of two different rotamers of DAPI. Both rotamers are able to bind to the protein, but only one of them undergoes an intramolecular proton transfer, from the 6-amidinium group to the indole aromatic ring, in the excited singlet state of DAPI alone. When DAPI interacts with BSA this transfer does not occur and consequently a large increase of fluorescence is observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Fluorescence and CD studies on the conformation of the gastrin releasing peptide in solution and in the presence of model membranes.

The conformation of the heptacosapeptide hormone, gastrin releasing peptide, has been studied in buffer and in the presence of lipids, using static and dynamic fluorescence and CD. The results obtained show that, in buffer, the hormone exists in a collection of flexible, random coil type conformers, characterized by a beta-turn between residues 14-19. On the other hand, organic solvents can induce some degree of ordered secondary structure in the peptide chain. The marked changes, observed in CD and fluorescence spectra upon addition of lysolecitin micelles and dimyristoylphosphatidylserine vesicles, clearly show that the peptide interacts with lipids, assuming a lipid specific configuration. Interestingly, no significative spectroscopic changes are produced by exposure to dimyristoylphosphatidylcholine vesicles both in the gel and liquid-chrystalline phases, suggesting a requirement for negatively charged lipids during the process of hormone-membrane interaction.

Amino Acid Sequence↗
PubMed1991

Postnatal maturation of rat intestinal membrane: lipid composition and fluidity.

1. We studied the lipid composition and the fluidity of small intestine brush border membrane (BBM) of rats of different age: 'very young' (5-7 weeks old), 'young' (9 weeks old), 'adult' (30 weeks old) and 'old' (85 weeks old). 2. Fluorescence anisotropy, as assessed by 1,6-diphenyl-1,3,5-hexatriene probe (DPH), was increased from very young to adult rats. 3. In agreement with these results the lipid composition in adult animals showed a lower lipid/protein ratio (derived mainly from a lower content of total polar lipids) and an increase of cholesterol esters and sphingomyelin (SM) saturation index. 4. A marked decrease of the order parameter was observed in the 'old' group, accompanied by a decreased cholesterol/phospholipid ratio. 5. The percentage distribution of membrane phospholipids significantly changed during development, but the modifications were not correlated with the anisotropy of DPH.

Aging↗
PubMed1991

The Swedish Childhood Diabetes Study: a seven-fold decrease in short-term mortality?

Since 1 July 1977 all Swedish children aged 0-14 years with newly diagnosed Type 1 diabetes have been recorded on a central register. Out of 3228 patients registered up to 31 December 1985, 10 children (seven boys) had died during this time period. The overall mortality was 0.75 per 1000 patient-years. When compared with the general population the standardized mortality ratio (SMR) for both sexes was 2.09 (95% confidence limits 1.14-3.83). When analysed separately for sex, the higher mortality remained significant for males only (SMR = 2.61, 1.28-5.32). Five deaths were most probably due to diabetes and the remaining five were due to accidents, other diseases and, in one case, not identifiable with certainty. In comparison with previous studies there was a very low mortality in young-onset diabetic patients. However, short-term mortality is still significantly raised even in a country with a good economic and educational patient status and easy access to free hospital care.

Accidents↗
PubMed1991

The role of the side chain in the antioxidant activity of ubiquinones.

The question has been addressed whether the side chain contributes to the antioxidant activity of Ubiquinones. The length, the chemical composition and structure of the chain have been considered. The effect of the actual concentration of the quinone in egg lecithin vesicles has been investigated by means of both UV spectroscopy and time resolved fluorescence quenching experiments of 12-AS. The results indicate that the antioxidant properties of the quinone do not seem to depend on the side chain.

Antioxidants↗
PubMed1990

Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM?

The chronic hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) evolves gradually and is usually preceded by more transient hyperglycemia, classified as impaired glucose tolerance (IGT). Already in this phase, there is an increased risk of cardiovascular complications, and many IGT subjects, like NIDDM patients, often display several of the metabolic and circulatory disturbances that are associated with hyperglycemia, e.g., insulin resistance, hyperinsulinemia and/or hyperproinsulinemia, delayed insulin release, dyslipidemia, and hypertension. Therefore, and because untreated hyperglycemia is a self-perpetuating condition, early detection and early intervention may be necessary to prevent the progression and complications of NIDDM. This in turn would necessitate screening procedures, and the therapeutic goal should include both euglycemia and normalization of plasma insulin, plasma lipids, and blood pressure. A study in the German Democratic Republic indicated that the mortality in screening-detected NIDDM patients did not differ from that in patients detected in routine care. In a Swedish study on screening-detected NIDDM subjects, only those who had IGT rather than manifest NIDDM could maintain fasting blood glucose less than or equal to 6 mM for 5 yr by hypocaloric dietary regulation alone. In those with screening-detected NIDDM, the delayed acute insulin release and net postprandial hyperglycemia were improved by addition of glipizide, and most managed to attain and maintain fasting blood glucose less than or equal to 6 mM for approximately 2 yr after such addition. However, after 4 yr, there was an increase in blood glucose, suggesting that preventive intervention either may not be possible or may have to start in the IGT phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 2↗
PubMed1989

Lipid peroxidation and physical properties of smooth and rough hepatoma microsomes.

Smooth and rough endoplasmic reticulum of two Morris hepatomas, the slow growing 9618A and the fast growing 3924A, have been isolated, and their biochemical composition, supramolecular organization, and response to the action of peroxidative agents have been studied. Cytochrome P450 content and lipid availability are the limiting factors of their peroxidizability. The hemoprotein content is reduced about 80% in hepatoma 9618A and is virtually absent in hepatoma 3924A. The peroxidizability decreases with increasing growth rate of the tumor. The protein, phospholipid, and cholesterol content, the fatty acid composition as well as the double bond index, and the saturated and unsaturated fatty acid content are reported. Differences have been found between normal liver and tumors and between the fractions within a given tumoral tissue. The molecular order, as determined by fluorescence anisotrophy decay of DPH, increases in total microsomes and in the smooth fraction going from liver 9618A to 3924A, whereas for the rough fraction it is the same in liver and hepatoma 9618A; in 3924A it increases of about 30%. Fluidity decreases in total microsomes going from liver to 3924A, to 9618A. In both the purified fractions it decreases with increasing deviation of the tumor.

Animals↗
PubMed1986

Tryptophan interactions of gramicidin A' channels in lipids: a time-resolved fluorescence study.

The evolution of the incorporation of cation transport channels into lysolecithin micelles by gramicidin A was followed by measuring the ns time-resolved fluorescence of the tryptophan residues. In all samples, the tryptophan fluorescence could be resolved into three exponentially decaying components. The three decay times ranged from 6 to 8 ns, 1.8 to 3 ns, and 0.3 to 0.8 ns, depending on the emission wavelength. The fractional fluorescence of each component changed with incubation time. The long lifetime component had a reduced contribution to the total fluorescence while the short decay time component increased. The fluorescence spectra could be resolved into three distinct fluorescent components having maxima at 340 nm, 330 nm and 323 nm after 90 min of incubation, and 335 nm, 325 nm and 320 nm after 24 h of incubation. These maxima were, respectively, associated with the long, medium and short decay components. The fluorescence decay behaviour was interpreted as representing three families of tryptophans, the short lifetime component being due to a stacking interaction between tryptophan residues. The variation with incubation time suggests a two-step process in the channel-lipid organization. The first is associated with the conformational change of the polypeptide as it takes up a left-handed helical head-to-head dimer structure in the lipid. The second step is proposed to involve changes originating from membrane assembly and intermolecular interactions between channels as they form hexameric clusters.

Gramicidin↗
PubMed1979

Long-term treatment of subjects with borderline glucose tolerance.

Subjects with borderline glucose tolerance are at a higher risk of suffering and dying from cardiovascular disease than subjects with normal glucose tolerance. Our data on the progression to overt diabetes and our data on cardiovascular morbidity and mortality suggests that tolbutamide treatment reduces these risks. In any case, we have no data supporting the theory that tolbutamide promotes cardiovascular damage.

Blood Pressure↗
PubMed1978

Serum tolbutamide and chlorpropamide concentrations in patients with diabetes mellitus.

A selective and sensitive gas chromatographic technique was used to measure the steady-state serum concentrations of tolbutamide and chlorpropamide in 97 patients with maturity-onset diabetes mellitus who had been taking these drugs (37 tolbutamide, 60 chlorpropamide) for at least a year. No other antidiabetic agents had been given. The serum tolbutamide concentrations varied widely between the patients (from close to zero to 370 mumol/l (100 mug/ml)), yet the variation in dosage was only sixfold (0.5-3.9 g daily). The serum chlorpropamide concentrations varied even more widely (from close to zero to 882 mumol/l (244 mug/ml)), though the dosage variation was fourfold (125-500 mg daily). There was no systematic relation between dosage and serum concentrations of the drugs.Only 2 (5.4%) of the tolbutamide-treated patients and 10 (16.7%) of the chlorpropamide-treated patients had normal fasting blood glucose concentrations (below 5.5 mmol/l (99 mg/100 ml)), and fewer than half had values below 8.0 mmol/l (144 mg/100 ml). In most cases, therefore, the treatment was insufficient.There was no significant difference in mean fasting blood glucose concentrations between the two treatment groups. The mean steady-state concentration of chlorpropamide, however, was significantly higher than that of tolbutamide. Thus, contrary to common belief, the intrinsic activity of chlorpropamide is apparently not greater than that of tolbutamide. The alleged greater potency of chlorpropamide seems to be related wholly to kinetic differences, such as the less extensive metabolic degradation and slower elimination of the drug.We conclude that treatment with sulphonylureas in conventional dosage is far from optimal and that monitoring the concentrations of these drugs in the blood may help to improve their efficacy.

Adult↗
PubMedDate not supplied

Coenzyme Q-3 as an antioxidant. Its effect on the composition and structural properties of phospholipid vesicles.

Coenzyme Q-3 incorporated into the lipid bilayer at physiological concentration provided an 80% inhibition of the lipid peroxidation induced by ferrous ions. In coenzyme Q-containing vesicles, the fluorescence lifetime and the fluorescence anisotropy decay of the probe, 1,6-diphenyl-1,3,5-hexatriene, were measured in order to find out if the presence of the quinone can cause variations in the membrane organization. Our data show that two distinct populations of the probe were present and that both populations were available to quenching by coenzyme Q. The overall effects of coenzyme Q on the static and dynamic properties of the model membranes were: a very small effect in the ordering of the fatty acid chain, and a more noticeable decrease of the probe correlation time and, therefore, an increase in membrane fluidity at increasing quinone concentration. When vesicles were peroxidized in the absence of the coenzyme Q, the fluidity markedly decreased; in its presence, the fluidity was nearly unchanged. The results suggest that the antioxidant properties of coenzyme Q can be ascribed to its ability to react with free radicals. The effect on the fluidity of the lipid bilayer might imply that a requisite for a molecule to act as an efficient antioxidant could be its ability to readily diffuse within the membrane.

Antioxidants↗