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Biomedical subjects

G Jori

Publications and source records attributed to G Jori.

At least 109 records · Page 6Linked to original sources

Haematoporphyrin and atherosclerosis in the broad-breasted white turkey: distribution and quantitation in thoracic and abdominal aorta.

Rapidly replicating tissues such as malignant neoplasms accumulate porphyrins and often display a typical fluorescence. Previous authors observed a selective fluorescence due to injected porphyrins also in atheromatous plaques, while no fluorescence was observed in the plaque-free arterial wall. We have performed quantitative studies on the distribution of haematoporphyrin in the broad-breasted white turkey, in which hypertension and atherosclerosis occur spontaneously. In this experimental model the aortic atherosclerotic lesions are confined to the abdominal tract, and the thoracic tract exhibits a hypertrophic media. After haematoporphyrin injection, larger porphyrin concentrations were observed in the inner than in the outer portion of the abdominal aorta. An opposite behaviour was observed in the thoracic tract. Notably, haematoporphyrin was progressively cleared from the thoracic media, while its concentration remained relatively stable in the inner portion of the abdominal aorta up to four days after the injection. This indicates a selective and prolonged retention of haematoporphyrin within the atherosclerotic lesions.

Animals↗

Hematoporphyrin binding to cultured aortic smooth muscle cells from spontaneously atherosclerotic turkey.

Porphyrins are known to be accumulated in vivo by tumors and atherosclerotic plaques. We studied the interaction of cultured aortic smooth muscle cells (SMC) from spontaneously atherosclerotic Broad Breasted White Turkeys (BBWT) with free hematoporphyrin (Hp) and low density lipoprotein (LDL)-Hp complexes. A significantly higher binding of LDL-Hp to SMC as compared to free Hp was observed. These data indicate that porphyrin binding to vascular SMC represents a possible mechanism for porphyrin accumulation by atherosclerotic plaques. This process is mediated, at least in part, by LDL.

Animals↗

Lipoprotein binding to cultured aortic smooth muscle cells from normotensive and hypertensive rats.

Little is known about the pathophysiological mechanisms responsible for the higher incidence of atherosclerosis in hypertensive subjects. In view of the known atherogenic role of low-density lipoproteins (LDL), the aim of the present study was to evaluate possible differences in LDL binding to cultured aortic smooth muscle cells from normotensive and hypertensive rats. We studied the time-dependence and dose-dependence of LDL binding to both cell types. Low density lipoprotein binding to smooth muscle cells from the hypertensive rat was significantly higher than that to smooth muscle cells from the normotensive rat. This mechanism might explain the higher incidence of atherosclerotic lesions observed in hypertension.

Animals↗

Retention of haematoporphyrin in the aorta of hypertensive rats: in-vivo and in-vitro studies.

Porphyrins are known to be accumulated and retained by tumours and atherosclerotic plaques. This property has been used for a new therapeutic approach called photodynamic therapy. In this study we assessed whether the presence of arterial hypertension could modify porphyrin turnover in the vascular wall. At various times after intravenous injection, haematoporphyrin concentration was assessed by a spectrophotofluorimetric method in the aortas of normotensive and hypertensive rats. Moreover, we studied the binding of haematoporphyrin to cultured smooth muscle cells obtained from normotensive and hypertensive rats. Larger amounts of haematoporphyrin were accumulated by the aorta of hypertensive rats and cleared at a slower rate, compared with normotensive rats. As for in-vitro experiments, cultured smooth muscle cells from hypertensive rats bound larger amounts of haematoporphyrin than cells from normotensive rats.

Animals↗

Structural and functional differences between fetal and adult serum albumin.

The binding of bilirubin with adult of fetal human serum albumin has been studied by steady-state fluorescence emission spectroscopy. The 1:1 complex between bilirubin and the two albumin samples shows very similar fluorescence properties, as well as essentially identical accessibility of the protein-bound bilirubin to fluorescence quenchers added to the aqueous medium. The intramolecular distance between bilirubin and the single tryptophyl residue can be estimated to be 2.4 +/- 0.2 nm for both proteins by singlet-singlet energy transfer. These findings suggest that fetal and adult human serum albumin have a very similar three-dimensional structure; the different binding capacity for bilirubin displayed by the two proteins is likely to be the consequence of small differences in the physico-chemical properties of some amino acid residues close to the bilirubin binding site, as indicated by pH-titration experiments of the intrinsic albumin fluorescence.

Bilirubin↗

Photodynamic therapy of malignant brain tumors: clinical results of, difficulties with, questions about, and future prospects for the neurosurgical applications.

Photodynamic therapy (PDT) has been applied in a variety of oncological fields with good results. In neurosurgery, the clinical series are limited and the number of treated patients is not statistically significant. This work examines the results of PDT performed in our clinic and discusses some difficulties and causes of failure of this method in neurosurgical patients. Eight patients with malignant brain tumors underwent PDT. All had been treated previously by operation and radiation therapy and one patient had also received chemotherapy. At 24 hours after the i.v. injection of hematoporphyrin (5 mg/kg body weight), the tumor was removed as radically as possible and the residual tumor bed was exposed to either 630-nm light from an argon-dye laser or 600- to 680-nm light isolated from the emission of a quartz-halogen lamp. The type of sensitizer, the irradiation methods, and the peculiarities of glial tumors are examined as possible causes of failure. The longer survivals of some patients with glial tumors treated by PDT may make this treatment suitable when traditional therapies fail.

Adult↗

Steady-state and time-resolved spectroscopic studies on the hematoporphyrin-lipoprotein complex.

The interaction of hematoporphyrin (Hp) with the isolated rabbit lipoprotein fractions very low density lipoproteins, low-density lipoproteins, and high-density lipoproteins has been studied by steady-state and time-resolved spectroscopy. The porphyrin appears to be bound to both the apoprotein and the lipid phase. The two populations of lipoprotein-bound Hp molecules can be distinguished on the basis of the fluorescence excitation spectrum, decay constants of the lowest excited singlet and triplet states, and accessibility to oxygen. Upon Hp binding, the intrinsic fluorescence emission of apolipoproteins is quenched at least in part via singlet-singlet energy transfer from tryptophyl residues to the porphyrin moiety. The binding of Hp with the protein matrix can be adequately described on the basis of Scatchard analysis, whereas the interaction of Hp with the lipid core can be described as the partitioning of the dye between a hydrophobic and an aqueous phase. The Hp binding capacity of lipoproteins is maximal for very low density lipoproteins.

Animals↗

Spectroscopic studies on Zn(II)-phthalocyanine in homogeneous and microheterogeneous systems.

The absorption and fluorescence properties of Zn2+-phthalocyanine (Zn-Pc) have been characterized in homogeneous and microheterogeneous media. By our preparation procedure, the phthalocyanine can be associated in a monomeric state with cationic micelles, unilamellar liposomes, and low-density lipoproteins; the distribution of Zn-Pc in the hydrophobic phases appears to be controlled by the nature of the lipid environment. The potential use of liposome-bound Zn-Pc for photosensitization studies in aqueous media and for phototherapeutic applications in vivo is briefly discussed.

1,2-Dipalmitoylphosphatidylcholine↗

Pharmacokinetic studies with zinc(II)-phthalocyanine in tumour-bearing mice.

Zn(II)-phthalocyanine (Zn-Pc) incorporated into unilamellar liposomes of dipalmitoylphosphatidylcholine has been injected intraperitoneally (0.5 mg kg-1) to BALB/c mice bearing a transplanted MS-2 fibrosarcoma. The drug is specifically transported by serum lipoproteins and cleared from the serum via the bile-gut pathway in a biphasic process: approximately 60% of Zn-Pc is eliminated with a serum half-life of approximately 9 hours, while the remaining aliquot is eliminated at a very slow rate. Several normal tissues take up the drug within 3 hours after administration but release it almost completely after 24-48 hours. On the other hand, the tumour shows a maximum concentration of Zn-Pc (approximately 0.6 microgram g-1 of tissue) after 18-24 hours; at this time, the ratio between the Zn-Pc levels in the tumour and the muscle (which represents the surrounding normal tissue) is approximately 7.5. The results are discussed in terms of a possible use of Zn-Pc as a photosensitizer in the photodynamic therapy of tumours.

Animals↗