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P Soldani

Publications and source records attributed to P Soldani.

At least 37 records · Page 2Linked to original sources

Gender difference in noise stress-induced ultrastructural changes in rat myocardium.

Male and female rats were exposed to noise 6 h daily for 7 days running and the effect of stress was evaluated both on myocardium ultrastructure and plasma corticosterone level. Both sexes showed subcellular alterations of cardiomyocytes; mitochondria, in particular, which resulted the most affected organelles, exhibited diluted matrix and cristolysis; in some areas, the sarcoplasmic reticulum appeared vesiculated. Quantitative analysis of altered mitochondria revealed that atrial myocardium was more affected in males than in females. Moreover, corticosterone plasma assay showed, in exposed animals, a growing increase without significant gender differences. The present findings suggest a more marked involvement of male sex when challenged with noise stressor.

Animals↗

Suramin-induced ultrastructural changes in the testis of albino rats.

The effect of chronic suramin administration on rat testis was evaluated. The animals were given the drug twice a week for two months, following a treatment schedule comparable to that used in cancer therapy. Light microscopic sections revealed vacuolizations near the basal lamina, germ cells very little differentiated, together with immature cells located in the lumen of seminiferous tubules. Ultrastructural changes were revealed in the form of a decrease in nuclear density with evaginations of the nuclear envelope and sometimes ruptures of the plasmatic membrane. Changes in the Sertoli cells consisted of cytoplasm vacuolizations, in which some lysosomes, containing degraded material such as myelin-like figures, were present.

Animals↗

Recombinant anti-human melanoma antibodies are versatile molecules.

The low cost, high versatility, and reliable production of bacterially produced recombinant antibody fragments speeds up the development of tumor-targeting agents. High-quality recombinant anti-melanoma antibodies are much sought after in the scientific community. We cloned the murine antibody 225.28S, currently used in radioimmunoimaging of human melanoma lesions, in single-chain Fv configuration (scFv) for soluble expression in bacteria. The recombinant antibody fragment conserved the binding specificity of the parental antibody. In order to arm the scFv(225.28S) with biologically useful effector functions, we developed vectors for soluble expression of scFv(225.28S) in bacteria that allow both covalent and noncovalent chemical antibody modification at positions that do not interfere with antigen binding. An expression vector was developed that appends a cysteine residue at the C-terminal extremity of the recombinant antibody, thus allowing reaction with thiol-specific reagents, including 99mTc labeling, at a position that does not interfere with antigen binding. The scFv(225.28S) was also successfully expressed with a casein kinase II substrate tag that enables efficient and stable 32P labeling. For noncovalent antibody modification, we developed an expression vector that appends the human calmodulin gene at the C-terminal extremity of scFv(225.28S). The calmodulin domain is poorly immunogenic and can be targeted with chemically modified high-affinity calmodulin ligands. The recombinant anti-human melanoma antibodies described in this article should prove useful "building blocks" for the development of anti-melanoma diagnostic and therapeutic strategies.

Amino Acid Sequence↗

Clinical and experimental evidence of inhibition of testosterone production by suramin.

The effect of suramin on testosterone production was evaluated in cancer patients, adult male rats, rat Leydig cells, and NCI-H295 human adrenal cancer cells. Testosterone plasma levels markedly decreased in 14 patients receiving suramin as a therapy for refractory cancer, and in 8 of them, the plasma LH and/or FSH levels increased beyond the normal range. The hCG stimulation test (5000 IU, im) was performed in 8 patients and induced an average 2.1-fold increase in testosterone levels over baseline values. Testicular histology after suramin treatment was available in 1 patient who died of progressive disease; this revealed atrophy of seminiferous tubules and reduced Leydig cells in the interstitium. A significant reduction in plasma testosterone was also observed in rats given 18 mg/kg suramin, ip, twice weekly for 8 weeks, whereas plasma LH and FSH levels did not change significantly. Cytohistochemistry of testes from suramin-treated rats showed a reduced number of 3 beta-hydroxysteroid dehydrogenase-positive cells within the interstitium compared to controls, and light microscopy revealed severe impairment of spermatogenesis. Suramin inhibited the production of testosterone by isolated rat Leydig cells as well as the conversion of pregnenolone to progesterone by the 3 beta-hydroxysteroid dehydrogenase enzyme extracted from rat testes, with 50% inhibitory concentrations (IC50 values) of 108.2 and 87.5 micrograms/mL, respectively. Furthermore, suramin reduced the release of testosterone into the culture medium of NCI-H295 adrenal cancer cells with IC50 values of 91.2 and 83.9 micrograms/mL after 6 and 12 days, respectively. These data provide the first evidence in patients that suramin treatment produces a marked reduction in the circulating levels of testosterone, a result that was also obtained in experimental models.

3-Hydroxysteroid Dehydrogenases↗

The action of diazepam on noise-induced alterations in rat atrial tissue: an ultrastructural study.

The effects of pretreatment with a benzodiazepine, diazepam, on the atrial tissue of rats exposed to noise were studied by means of electron microscopy. Examination of ultrathin sections showed that acute stress caused swelling of mitochondria with cristolysis and matrix dissolution. In diazepam-pretreated and noise-exposed animals atrial cardiomyocytes did not reveal noteworthy changes in comparison with controls and the majority of mitochondria were well preserved. Present findings indicate that diazepam is able to exert a protective action on cardiac alterations due to noise exposure, especially at the mitochondrial level.

Animals↗

Morphohistochemical relationships between adrenal cortex and major salivary glands in response to chronic suramin treatment.

Adult male albino rats received 18 mg/kg i.p. of suramin twice a week, comparable to the human therapeutic situation. Sacrifices took place after 30 and 60 days of treatment. Adrenal cortex and major salivary glands were examined, using morphological and histochemical methods, in order to obtain a) confirmation of adrenocortical damage reported previously and b) original data for the major salivary glands. In rats the submaxillary gland in particular has already been found to be closely related to the functional conditions of the adrenal cortex. In all organs examined, alterations already evident in 30 day-treated rats, were constantly more marked and widespread in 60 day-treated animals. At the end of the treatment the adrenal cortex showed morphological (poor differentiation of the zona glomerulosa, hypertrophic cell clusters in the zona fasciculata) and histochemical (different distribution of neutral lipids, cholesterol and delta 5-3 beta-hydroxysteroid dehydrogenase) changes. Damage (vacuolizations, lymphocytic infiltrates) observed in major salivary glands was shown to be more marked and widespread in the submaxillary gland, confirming its functional dependence on adrenocortical activity.

3-Hydroxysteroid Dehydrogenases↗

Age-related changes in the noradrenergic pattern and receptor responses of the rat cardiovascular system after repeated microwave exposure.

In the present research the effect of repeated microwave exposure on the noradrenergic pattern by histofluorescence method and on receptor-mediated responses using alpha and beta agonists in myocardium and aorta of young-adult and aged rats was studied. Young-adult irradiated rats showed an increase in noradrenergic innervation more marked in myocardial tissue, while an increase in maximal response to the agonist was found only at aortic level. Aged stressed rats exhibited an increase in fluorescent fibres at atrial and aortic level, but in the atrial section this increase was found to be less evident than in young-adult animals. Functional data in aged rats revealed a more marked decrease in maximal response ratio (M.R.R.) of myocardial tissue than in young-adult rats, together with a noticeable decrease in maximal response at aortic level. These results indicate no direct correlation between morphological and functional data. Participation of both central and peripheral mechanisms is suggested.

Aging↗

Ultrastructural changes in atrial tissue of young and aged rats submitted to acute noise stress.

Young and senescent rats were exposed to audiogenic stress for 6 h running and the effects of the treatment on the atrial myocardium were evaluated. In both young and senescent animals subcellular alterations of atrial cardiomyocytes were seen, consisting mainly of changes at the mitochondrial level. In particular, sections from young treated rats exhibited swollen mitochondria with lysis of their cristae and dissolution of the matrix. An enlargement was observed of the space between the outer and inner membranes of the mitochondria, which also showed an increase in size. In addition, aged treated specimens revealed decreased density of the sarcoplasm and marked heterogeneity in the myofibril pattern with ruptures and loss of continuity of the myofilaments.

Age Factors↗

Noradrenergic innervation and receptor responses of cardiovascular tissues from young and aged rats after acute microwave exposure.

Young and senescent rats were exposed to 2,450 GHz microwaves for 45' and the effects of this treatment on the noradrenergic pattern and beta-cardiac and alpha-aortic receptorial functions were evaluated. In young animals, an increase in noradrenergic innervation was observed, while no functional modification was shown. In aged rats the increase in fluorescent fibers was almost the same as that observed in young rats, but significant variations in functional responses were found. Both at atrial and ventricular levels responses to the beta-agonist isoprenaline were unmodified in their affinity indices, but showed a marked decrease in the maximal responses; by contrast the activity of noradrenaline on the aortic alpha-adrenoceptors showed a great increase in maximal response without changes in the pD2 values. These results suggest that the predominant effect of microwave exposure consists in an increase in the noradrenergic pattern, and this effect is not related to the functional modifications.

Aging↗

Morphofunctional changes in the noradrenergic innervation of the rat cardiovascular system after varying duration of noise stress.

One, six and twelve hs of exposure to acoustic stress showed different influences on the noradrenergic pattern and receptor function of the rat atria and aorta. Moreover, the lipid content of the adrenal cortex and hepatic glycogen were histochemically evaluated in the same animals to correlate these observations with the previous results. The increase in exposure time induced a corresponding increase in sympathetic innervation, which was more evident at cardiac level. The functional results showed that the potency of the agonists on the alpha- and beta-adrenoceptors does not vary, with the exception of 6-h treatment, which affected beta-receptors. By contrast, the M.R.R. of beta-receptors proved to be modified in all treatments, suggesting that noise stress affected mainly postreceptorial mechanisms linked to beta-adrenoceptors rather than their density or affinity; no significant functional modifications were observed when alpha-receptors were considered.

Adrenal Cortex↗

A model of the rabies virus glycoprotein active site.

The glycoprotein from the neurotropic rabies virus shows a significant homology with the alpha neurotoxin that binds to the nicotinic acetylcholine receptor. The crystal structure of the alpha neurotoxins suggests that the Arg 37 guanidinium group and the Asp 31 side-chain carboxylate of the erabutoxin have stereochemical features resembling those of acetylcholine. Conformational studies on the Asn194-Ser195-Arg196-Gly197 tetrapeptide, an essential part of the binding site of the rabies virus glycoprotein, indicate that the side chains of Asn and Arg could also mimic the acetylcholine structure. This observation is consistent with the recently proposed mechanism of the viral infection.

Amino Acid Sequence↗

Suramin inhibits bFGF-induced endothelial cell proliferation and angiogenesis in the chick chorioallantoic membrane.

The effects of suramin, an inhibitor of growth factor mitogenic activity, were evaluated on basic fibroblast growth factor (bFGF)-induced proliferation of bovine aortic endothelial cells and on angiogenesis in the chorioallantoic membrane (CAM) of chick embryos. The role of bFGF gene expression in endothelial cell growth was also investigated by using an antisense oligodeoxynucleotide to bFGF. The 4-fold increase in [3H]-thymidine uptake in endothelial cells in vitro upon stimulation with 10 ng ml-1 of bFGF was inhibited by suramin 300 micrograms ml-1. bFGF antisense oligomer (10 microM) reduced [3H]-thymidine incorporation in exponentially growing cells by 76%; this effect was reversed by bFGF 10 ng ml-1. In the CAM of chick embryos suramin 50 micrograms was a more potent inhibitor of angiogenesis than the combination of heparin 60 micrograms/hydrocortisone 50 micrograms; the mean value of the area with reduced vascularity was significantly larger in suramin-treated CAMs (2.4 cm2) than in heparin/hydrocortisone (0.6 cm2), while the reduction of vascular density was similar (- 35 and - 29% compared to controls, respectively), In conclusion, the effects of treatments with bFGF and bFGF antisense oligomer demonstrate that bFGF plays a relevant role in endothelial cell proliferation and may be the target of suramin since the drug is able to suppress basal and bFGF-induced endothelial cell growth; in addition to this, suramin is a more potent angiogenesis inhibitor in the CAM than the combination of heparin/hydrocortisone.

Allantois↗

Effects of subacute exposure to noise on the noradrenergic innervation of the cardiovascular system in young and aged rats: a morphofunctional study.

The effects of subacute noise stress on the noradrenergic pattern and receptor-mediated responses were examined in aorta and atria of young and aged rats. Noise exposure increased the density of noradrenergic fibres and responses to the beta-adrenergic agonist isoprenaline in the cardiac tissue of young animals. In aged rats, the stressing stimulus markedly increased the maximal response to the alpha-agonist on the aortic musculature; on the contrary, a reduced responsiveness to the beta-agonist was observed at the cardiac level, without any noteworthy changes in the noradrenergic pattern in comparison to aged controls. The present results indicate that subacute noise stress induces both morphological and functional modifications of the noradrenergic nervous system and also that after subacute noise stress, morphological changes do not necessarily correspond exactly to functional data; the latter show responses that are more widely differentiated than the morphological ones.

Aging↗

[Morpho-histochemical observations on the liver parenchyma of adult albino rats subjected to acute acoustic stress].

The hepatic noradrenergic innervation and the glycogen cellular content, after acoustic stress, were studied by the fluorescence and P.A.S. methods, respectively, in 7-month-old male albino rats exposed to continuous intense noise for 60' and 8 hours. While the 60'-treatment did not cause noteworthy changes in adrenergic fibers and a decrease in PAS-positive material, the 8 h.-treatment induced a significant increase of catecholamines content, in addition to a non homogeneous response to PAS reaction by hepatocytes surrounding the portal spaces or the lobular central veins. The authors ascribe the effect of the 8 h.-treatment to a partial adaptation of hepatocytes to acoustic stress.

Adaptation, Physiological↗

Binding properties of monoclonal antibodies to rabies virus.

The monoclonal antibodies (mAbs) obtained by immunizing mice with a tetradecapeptide corresponding to the 190-203 region of rabies virus glycoprotein, involved in binding to the acetylcholine receptor (AchR), displayed different specificities to different rabies virus strains. These mAbs, when used in immunofluorescence tests, allowed differentiation of wild rabies viruses from the attenuated ones.

Amino Acid Sequence↗

HPLC immunoaffinity purification of rabies virus glycoprotein using immobilized antipeptide antibodies.

It has been reported that the acetylcholine receptor may be used by the rabies virus to concentrate at sites in proximal to peripheral nerves. It has also been reported that the binding site for the receptor is located within the 190-203 region of the virus glycoprotein on the basis of its structural homology with the toxic center of snake neurotoxins, which are well known cholinergic ligands. We prepared monoclonal antibodies against the synthetic tetradecapeptide having the same sequence as the putative binding site of the rabies virus. One of three antibodies (clone 2PV 36-74) was able to recognize both the whole virus and its peplomeric glycoprotein and could bind acetylcholine. It was also able to inhibit the binding both of alpha-bungarotoxin and rabies virus glycoprotein to the acetylcholine receptor. We have covalently bound 2PV 36-74 to an HPLC affinity column and utilized it for specific purification of rabies virus glycoprotein. The immunoaffinity chromatographic method we describe is very sensitive and highly specific. Moreover this procedure does not denature the sample and is vary rapid and efficient.

Animals↗