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Biomedical subjects

D Monti

Publications and source records attributed to D Monti.

At least 163 records · Page 9Linked to original sources

DNA repair in lymphocytes from humans and rats with chronic iron overload.

A marked reduction of the proliferative capability after a mitogenic stimulus and a dramatic decrease of the capacity to repair DNA damages were found in lymphocytes from iron overloaded rats. These immunological parameters were not significantly different from controls in peripheral blood lymphocytes from patients with primary iron overload: hereditary hemochromatosis and porphyria cutanea tarda. This discrepancy could be due to the accelerated modality of iron overload in the rat model and to the fact that rat lymphocytes were obtained from an highly iron repleted microenvironment (i.e. spleen). Our data indicate that iron overload can affect the structure and/or the function of cellular DNA thus offering new insights on the close association of iron overload conditions and cancer.

Animals↗

Observations on the chemical structure and cytotoxic activity of marycin, a hematoporphyrin derivative.

This paper describes the preparation, chemical structure and cytotoxic activity of marycin, a hematoporphyrin derivative. Marycin has been prepared by condensing hematoporphyrin dimethyl ester in the presence of p-toluenesulfonic acid and reducing the product with lithium aluminum hydride. The product appeared to be pure by thin-layer chromatography (TLC) and high-performance liquid chormatography (HPLC). The product, analyzed by UV-visible absorbance and fluorescence spectra, appears to be related to the parent hematoporphyrin compound. The product was also analyzed by NMR and Mass spectra: a dimeric structure can be assigned to marycin: this appears to have an oxide bridge between C2-chains of two porphyrin units and hydroxyl groups instead of carboxyls. Marycin was screened for cytotoxic activity against ZR-75, MCF-7, HT-29, K-562, human tumor cell lines and the MRC-9 human embryonic cell line. Marycin decreases the growth index, measured in the radiometric assay, as 14CO2 production. The cytotoxic activity was dose-dependent and is attributable to the pure compound, marycin. Marycin is active at low doses but the activity varies with the cell line studied. The compound had low toxicity versus MRC-9 normal cell line. The compound is active without light activation. How marycin acts is a matter of speculation. Marycin is highly liposoluble and would be expected to have high toxicity for tumors.

Cell Survival↗

Preparation of spin-labelled sulfatides for EPR studies on model membranes.

Using the N-hydroxysuccinimide ester of the fatty acids, galactosylceramide I3-sulfate containing a 5-or 16-doxyl-stearoyl residue was prepared in good yield by acylation of the galactosylsphingosine I3-sulfate (lysosulfatide) obtained from the saponification of the bovine brain sulfatide. The EPR behavior of the two semisynthetic sulfatides was analyzed in natural sulfatide micelles and in multilamellar vesicles of egg phosphatidylcholine. The evaluated parameters demonstrate that these spin-labelled sulfatides can be used for the study of sulfatide behavior in lipid structures.

Animals↗

Short-term sleep laboratory evaluation of midazolam in chronic insomniacs. Preliminary results.

The effects of 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a] [1,4]benzodiazepine (midazolam, Ro 21-3981, Dormicum) in oral formulation of 15 and 30 mg on the sleep cycle of patients suffering from insomnia were assessed by means of polysomnographic recordings using a double-blind cross-over design. Both doses of midazolam were effective in improving sleep on short-term administration. In addition, significantly larger decrements of non-REM (NREM) sleep latency and of wake time through the 3rd third of night and nonsignificant trends toward smaller number of awakenings as well as shorter total wake time and longer NREM sleep time were induced by the 30 mg dose. Irrespective of the dosage sleep was almost exclusively increased at the expense of NREM sleep. Following 3 days treatment there was no rebound insomnia. These preliminary results suggest that the 15 mg dose could be appropriate in patients with difficulties in falling asleep, while the 30 mg dose would be more appropriate for patients who also experience difficulties in staying asleep.

Adolescent↗

Study of delta sleep-inducing peptide efficacy in improving sleep on short-term administration to chronic insomniacs.

The effects of delta sleep-inducing peptide (DSIP), on the sleep cycle of insomniac patients were assessed by means of polysomnographic recordings. DSIP in a dose of 25 nmol/kg or a placebo was administered i.v. during four nights using a double-blind crossover design. The number of nocturnal awakenings, non-rapid-eye-movement (NREM) sleep latency, total waking time and waking time after sleep onset were decreased under DSIP treatment, but no significant differences were found in comparison to baseline or to double-blind placebo nights. Total sleep time and NREM sleep time were increased by the peptide. Their increase was related to increases in stage 2, while stage 1, slow wave sleep (stages 3 and 4) and rapid-eye-movement sleep were not modified. For NREM sleep time and stage 2 sleep differences between DSIP and a placebo were significant, but the same differences existed already for the baseline values. It can be concluded that sleep improvement under DSIP treatment is of little clinical significance.

Adult↗

Are the vascular complications of diabetes mellitus preceded by an altered thromboxane/prostacyclin plasmatic ratio?

Although many data regarding the biosynthesis of thromboxane A2 and prostacyclin in diabetes mellitus have recently appeared in the literature, it is not clear whether an imbalance between the generation of the two prostaglandins might be connected to the vascular complications of diabetes. In the present review we have tried to emphasize the most significant aspects of these studies and we have focused on alterations of platelet prostacyclin receptors and on the effects of circulating immune complexes on platelets of diabetics. It is likely that studies on the release of platelet derived growth factor as well as more precise definitions of its action on vessel wall cells leading to a massive release of prostacyclin, will permit us to ascertain whether an alteration in prostaglandin ratio is linked to the genesis of the vascular complications in diabetics.

6-Ketoprostaglandin F1 alpha↗

Biliverdin as an electron transfer catalyst for superoxide ion in aqueous medium.

Stopped flow experiments gave evidence of the formation of a biliverdin-superoxide complex and/or a biliverdin radical anion by reaction of aqueous O2- with biliverdin. Such transient species are likely intermediates both in the bleaching of biliverdin, during exposure to the aerobic xanthine oxidase reaction, and in the reduction of ferricytochrome c under the same conditions.

Bilirubin↗

pH dependence of the water solubility of bilirubin photo-derivatives and its relevance to phototherapy.

Deoxygenated chloroform solutions of bilirubin were irradiated with visible light and continuously extracted with aqueous solutions at different pHs in the range of 7.20-8.20. The aqueous solutions became yellow rapidly and progressively: the higher their pH, the more intense their coloration. The water soluble E-isomers of bilirubin may not represent the only photoproducts transferred into water. It clearly appears from visible absorption measurements that the photopigment formed in our experiments can be partitioned from chloroform into water at pH as low as 7.2-7.4. Although the water solubility of the photopigment cannot be exactly calculated from experimental data, a direct relationship between water partitioning and water solubility can be reasonably assumed. The fact that the water solubility of the photopigment sharply increases in inverse proportion to the hydrogen ion concentration can be of great relevance to the treatment of jaundiced infants with phototherapy.

Bilirubin↗

The binding of bilirubin to albumin. A study using spin-labelled bilirubin.

Binding between human serum albumin and a spin-labelled derivative of bilirubin was investigated by circular dichroism, fluorescence quenching, electron spin resonance and visible spectroscopy. The orders of magnitude of the binding constants obtained by flurorescence quenching and electron spin resonance spectroscopies were 10(7) and 10(3) 1 . mol-1, respectively. These data suggest that most spin-labelled bilirubin interacts with human serum albumin at the side not holding the spin-labelled side-arm. CD measurements showed the presence of at least two sites, associated with opposite Cotton effects. It is worthy of note that the Cotton sign of the first site is inverted with respect to the corresponding one of bilirubin. CD measurements on mixed systems (spin-labelled bilirubin/human serum albumin/bilirubin) were also performed. The decomposition of the ternary curves shows that the rotatory power of bilirubin bound to human serum albumin is higher in the ternary system than in the binary (bilirubin/human serum albumin). The corresponding CD measurements for the binding between spin-labelled bilirubin and bovine serum albumin are also reported and discussed.

Animals↗

[Doppler ultrasonic method of blood velocity measurement in Raynaud's phenomenon].

Ten patients, 3 males and 7 females, aging less then 50 years (M: 37), suffering from at least one year for a Raynaud's phenomenon surely not due to a costo-clavicular syndrome, were studied. A Doppler ultrasound evaluation was first done recording the pressure and the speed at the omeral, radial, ulnar, and digital arteries. The patients were then submitted to an angiography in general anaesthesia through puncture of the omeral artery and to screening tests to detect possible associated immunopathological diseases. In the patients affected by Raynaud's phenomenon the vascular lesions are generally distal to the omeral artery; the only surgical indication is a thoracic gangliectomy. Our experience shows that the Doppler velocimetry gives all the data necessary to check the efficacy of a pharmacological treatment and to state a correct surgical indication.

Adult↗

Drugs affecting porphyrin and lipid metabolism in rats: effects exerted by allylisopropylacetamide and related molecules.

Allylisopropylacetamide (AIA), a drug known to cause lesions in porphyrin and lipid metabolism, and drugs with structure related to AIA [propylisopropylacetamide (PIA) and 2-isopropyl-4-hydroxyvaleric acid] were injected subcutaneously into rats. Measurements were taken of the effect of these compounds on the levels of 5-aminolevulinic acid synthetase (ALA synthetase) and hepatic porphyrins and on the values of hepatic and plasmatic triglycerides and plasma free fatty acids. To a different degree, both AIA and PIA increase the activity of ALA synthetase, and also increase the levels of hepatic porphyrins and hepatic and plasmatic triglycerides, while they both initially lower the levels of plasmatic free fatty acids (FFAs). The administration of 2-isopropyl-4-hydroxyvaleric acid has no effect on the parameters studied. The findings seem to suggest that the activity affecting porphyrin and lipid metabolism is connected in both cases with the presence of the amide function.

5-Aminolevulinate Synthetase↗