1,721,222 research outputs found
Benzo- and tetrahydrobenzo-furocoumarins: new potential photochemotherapeutic drugs.
No full textThe synthesis and photobiological activity of new benzo- and tetrahydrobenzo-furocoumarins are described. In order to evaluate the biological activity of these compounds, inhibition of growth assay was performed on human neoplastic cell lines (HL-60 and HeLa), in the dark and after UV irradiation. Some of the new structures revealed strong photobiological activity, so that their affinity for the macromolecule in vitro was studied. DNA binding was evaluated using various techniques, such as flow linear dichroism, fluorimetric titration and thermal transition experiments. The capacity of the various benzo- and tetrahydrobenzo-furocoumarins to photoreact with DNA was studied following photoadduct formation by means of spectrophotometric measurement
Endogenous adrenomedullin system regulates the growth of rat adrenocortical cells cultured in vitro
No full textThe expression of adrenomedullin (AM) system (AM and its receptors), as mRNA and protein, has been detected in the mammalian adrenal zona glomerulosa (ZG) cells. Evidence has been also provided that exogenous AM is able to enhance in vivo and in vitro the proliferative activity of ZG cells. However, the possibility that endogenous AM system may act as a physiological ZG growth regulator has not yet been demonstrated. Hence, we investigated whether the prolonged (48-72 h) suppression of AM gene transcription by a specific antisense oligonucleotide or the long-lasting (24-96 h) blockade of AM receptors by the selective antagonist AM(22-52) are able to affect the growth of rat ZG cells cultured in vitro. Freshly dispersed cells were incubated for 3 h with an AM antisense or a scrambled oligonucleotide, then they were cultured for 48 or 72 h, and proAM mRNA expression and AM content was checked by reverse transcription-polymerase chain reaction and radioimmune assay, respectively. Other ZG cells were cultured in the presence of AM and/or AM(22-52). Growth assay showed that AM (10(-8) M) decreased and AM(22-52) (10(-6) M) increased the duplication time of cultured cells. AM (10(-8) M) raised proliferation index and decreased apoptotic index of cultured cells, and AM(22-52) reversed these effects. AM(22-52) (from 10(-7) to 10(-6) M) and pAM gene suppression by the antisense oligonucleotide significantly lowered proliferation index and increased apoptotic index of cultured cells, both these effects being abrogated by AM (10(-8) M). It is concluded that endogenous AM system plays a relevant role in the autocrine-paracrine regulation of cultured rat ZG-cell growth
Antiproliferative effect of indigoid pigments isolated from human urine.
No full textTwo indigoid pigments, red indirubin and blue indigotin, were isolated from the urine of healthy male subjects. The two pigments were assayed on HL60 (human promyelocytic cell line) cells. Preliminary results revealed the antiproliferative effect of the pigments. Indigotin seemed more effective than indirubin
Experimental defect in rabbit urethra repaired with acellular aortic matrix
No full textUrethral reconstruction following failed hypospadias repair or post-traumatic chronic stricture requires adequate amounts of tissue. Many surgical techniques utilizing different types of biological tissues have been attempted: (a) vascularized skin flaps from the prepuce, scrotum or penile shaft; (b) full-thickness free skin grafts; (c) vesical or buccal mucosa grafts; (d) ureter; artery; vein and appendix tissue. More recently, biodegradable polymers have also been used as delivery vehicles of urothelial cells in animals. It has been demonstrated that the implant of an acellular tissue matrix in the bladder can guide the regeneration of urothelium, blood vessels, smooth muscle and nerves. The aim of this study was to create an experimental model of urethral defect, and then repair it by implanting homologous acellular aortic grafts as urethral substitutes. An acellular matrix was obtained by detergent enzymatic treatment of rabbit thoracic aorta. The growth of urethral epithelium was verified in vitro, and homologous acellular vessels were then implanted in rabbits, bridging a previous surgical urethral defect. The outcome of reconstructive surgery was evaluated histologically at 10 days, 3 weeks, 3 and 12 months. As the time after surgery increased, the neourothelium became less thick, signs of inflammatory response disappeared, and the orientation of collagen fibrils and smooth muscle fascicles resembled that of a normal urethra. The implants displayed abundant vascularization, and the luminal surface started to become irregular. Acellular blood vessels may represent a promising approach to urethral defect therapy for different reasons: (a) unlimited availability, (b) readily obtainable in different lengths and gauges, (c) the potential for being organized as tissue bank, and (d) that just one simple surgical procedure is needed. Nevertheless, before this technique can be applied in humans, it must be tested in more species and animals
Inhibition of growth, morphological and morphometrical changes induced by amido-anthraquinone derivatives in NCTC 2544 an HeLa cells.
No full textIn this work, we have studied cytotoxicity induced in NCTC 2544 and HeLa cell lines by two newly-synthesised potential anticancer drugs, the amido-anthraquinone derivatives 8-diethylaminopropionamido-1,4,5-trihydroxy-9,10-anthracenedione bromide (A888) and 5,8-bisdiethylaminopropionamido-1,4-dihydroxy-9,10-anthracenedione dibromide (A890). The results have been compared to the results obtained with mitoxantrone, a well-known anticancer agent. Using the neutral red uptake assay, A888 showed less cytotoxic action compared to mitoxantrone and A890. According to the results of morphological analysis after exposure for five hours, anthraquinone derivatives induced the formation of cytoplasmic vacuoles and changes in the arrangement of nucleus in both cell lines. On the basis of morphometrical analysis, we have observed an increase in total cellular area with a decrease in the nuclear/cytoplasmic ratio. We have found that the increase in total cellular area was higher in NCTC 2544 cells than in HeLa cells. From these data, we can conclude that NCTC cells are more sensitive to the compounds tested than HeLa cells. However, the growth inhibition assay and morphological analysis did not confirm these results
Role of endogenous adrenomedullin system in the regulation of secretion and growth of rat adrenal cortex.
No full textThe expression of components of the adrenomedullin (AM) system (AM and its receptors) has been detected in mammalian adrenal zona glomerulosa (ZG) cells, and evidence has been provided that AM is able to inhibit agonist-stimulated aldosterone secretion from and to enhance the proliferative activity of ZG cells. However, there has been no evidence that the endogenous AM system acts as a physiological regulator of ZG function. Hence, we investigated whether the suppression of AM gene transcription by a specific antisense oligodeoxynucleotide (ODN) is able to alter the secretion and growth of rat ZG cells cultured in vitro. ZG cell cultures were examined 0, 2, 4, 6 and 8 days after treatment with scrambled sense (S)-ODN (control cultures) and AM antisense (A)-ODN. Control cultures, as well as freshly dispersed ZG cells and ODN-untreated cultures, expressed AM as mRNA and protein. A-ODN treatment suppressed AM expression within 4 days and the suppression lasted until day 6. Confluent control cultures displayed basal and angiotensin-II (Ang-II), K(+)- and adrenocorticotropic hormone (ACTH)-stimulated aldosterone secretions similar to those of ODN-untreated cultures. A-ODN treatment magnified the aldosterone response to Ang-II and K+ at days 4 and 6 (but not at day 8), without affecting the basal or ACTH-stimulated secretion. As compared to ODN-untreated and control cultures, non-confluent A-ODN-treated ones showed a 40% elongation in the duplication time, a significant decrease in the proliferation index, and a marked rise in apoptotic index from day 4 to day 8. In conclusion, our study validates the use of A-ODN to block the endogenous AM system, showing that suppression of AM-synthesis requires at least 2 days to become appreciable and persists for at least 6 days. Moreover, it provides the first evidence that endogenous AM plays a physiological role in cultured rat ZG cells, by exerting a buffering action on their acute secretory response to Ang-II and K+ and by maintaining normal basal proliferative and apoptotic activities
Antiproliferative activity and phototoxicity of some methyl derivatives of 5-methoxypsoralen and 5-methoxyangelicin
No full textThe in vitro antiproliferative activity and in vivo phototoxicity of some methyl derivatives of 5-methoxypsoralen and 5-methoxyangelicin, i.e. 4,4'-dimethyl-5-methoxyangelicin (compound I), 3,4'-dimethyl-5-methoxyangelicin (compound II), 4,4'-dimethyl-5-methoxypsoralen (compound III); and 3,4'-dimethyl-5-methoxypsoralen (compound IV), have been investigated. The effects of the compounds were evaluated in vitro on HL60 and A431 cells, using 5-methoxypsoralen as the reference compound. In both cell lines compound I, II and III showed better antiproliferative activity than compound IV and 5-methoxypsoralen. Scanning electron microscopy revealed that all the compounds induced the formation of blebs and blisters on a A431 cell surface. Significant variations in the nuclear area strictly related to the toxicity of the compounds have been shown in both cell lines. Skin irritancy in vivo was evaluated by mean of histopathological responses on guinea-pig skin. For each compound a damage index was determined by morphometrical analysis of empty spaces in the epidermis. Histopathology revealed skin phototoxicity of compounds which lacked erythemogenic activity by visual scoring. By coupling cytotoxicity data in vitro to skin sensitization ones in vivo, compound I proved a promising candidate for use in clinical trials since due to a high inhibitory effect on the growth of human cell lines coupled to low skin phototoxicity
VEGF Embedded Sol-Gel Derived Silica Polymers as Supports for the Neovascularization of Bioengineered Implants
No full textBovine corneal stroma and epithelium reconstruted in vitro: characterization and response to surfactans
No full textIn order to define safety profiles and proper handling procedures for new industrial products, it is essential to determine their potential for ocular irritation. The Draize test is normally employed but it involves using rabbits. There is today a great need for all researchers to limit the use of animals for laboratory experiments and to encourage the development and adoption of alternative in vitro methods to evaluate the potential toxicity of new products. This study proposes a three-dimensional model of bovine corneal stroma and epithelium that is not only easy to reproduce but may also be used in the toxicological field as an alternative to animal experimentation. The data presented here show that this model allows the growth of epithelium similar in features to in vivo epithelium. Basal cells are cube-shaped, whereas superficial areas are horizontally longer; desmosomes and 64 kDa keratin, as a marker for differentiation of corneal epithelial cells, are both expressed; the basal lamina is synthesised also. The 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay was carried out on the model to evaluate the toxicity of some surfactants: benzalkonium chloride, Triton X-100, sodium dodecylsulphate and Tween 20. Since the in vitro data fit very well the results of the Draize test in vivo as reported in the literature, the three-dimensional culture may be used to predict the potential cytotoxicity of surfactant
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