Biomedical subjects

A Kubin

Publications and source records attributed to A Kubin.

10 recordsLinked to original sources

PubMed2005

Hypericin--the facts about a controversial agent.

Hypericin is a naturally occurring substance found in the common St. John's Wort (Hypericum species) and can also be synthesized from the anthraquinone derivative emodin. As the main component of Hypericum perforatum, it has traditionally been used throughout the history of folk medicine. In the last three decades, hypericin has also become the subject of intensive biochemical research and is proving to be a multifunctional agent in drug and medicinal applications. Recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin; intriguing information even if confirmation of data is incomplete and mechanisms of these activities still remain largely unexplained. In other contemporary studies, screening hypericin for inhibitory effects on various pharmaceutically important enzymes such as MAO (monoaminoxidase), PKC (protein kinase C), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450), has yielded results supporting therapeutic potential. Research of hypericin and its effect on GABA-activated (gamma amino butyric acid) currents and NMDA (N-methyl-D-aspartat) receptors also indicate the therapeutic potential of this substance whereby new insights in stroke research (apoplexy) are expected. Also in the relatively newly established fields of medical photochemistry and photobiology, intensive research reveals hypericin to be a promising novel therapeutic and diagnostic agent in treatment and detection of cancer (photodynamic activation of free radical production). Hypericin is not new to the research community, but it is achieving a new and promising status as an effective agent in medical diagnostic and therapeutic applications. New, although controversial data, over the recent years dictate further research, re-evaluation and discussion of this substance. Our up-to-date summary of hypericin, its activities and potentials, is aimed to contribute to this process.

Animals↗

PubMed1999

5-aminolevulinic acid-mediated photodynamic therapy of intraepithelial neoplasia and human papillomavirus of the uterine cervix--a new experimental approach.

The aim of this study was to treat patients for ectocervical dysplasia [cervical intraepithelial neoplasia (CIN) grades 1 and 2] and associated human papilloma virus (HPV) infections with photodynamic therapy (PDT). In 20 patients, 5-aminolevulinic acid (5-ALA, 12% w/v) was applied topically with a cervical cap 8 h prior to illumination. A thermal light source (150 W halogen lamp) emitting a broadband red light (total energy: 100 J/cm2, fluence rate: 90 mW/cm2) was used for superficial illumination of the portio. In addition, an Nd:YAG pumped dye laser (652 nm) was used to illuminate the cervical canal (total energy: 50 J/cm2, fluence rate: 300 mW/cm2). Preliminary results of follow-ups at 1, 3, 6, and 9 months posttherapy showed a cytological improvement in the grading of the PAP smears in 19 patients and the eradication of cervical HPV in 80%. These results demonstrate that ectocervical dysplasia and associated HPV infections can be treated by PDT.

Administration, Intravaginal↗

PubMed1999

Antagonistic effects of combination photosensitization by hypericin, meso-tetrahydroxyphenylchlorin (mTHPC) and photofrin II on Staphylococcus aureus.

Photodynamic therapy involves the application of a photosensitizer activated by visible light to generate cytotoxic reactive oxygen. In addition to clinical investigations, in vitro studies concerning photodynamic potency of sensitizers as well as quantification of illumination procedures are necessary. In our investigation, the objective was to evaluate not only the effects of photosensitizer and light on Gram-positive Staphylococcus aureus, but also to investigate possible synergistic or antagonistic effects of these sensitizers. Therefore, we used hypericin, Photofrin II, porfimer sodium and meso-tetrahydroxyphenylchlorin (mTHPC) alone, as well as in combination. Log-phase cells of S. aureus exhibited a marked sensitivity to white thermal light irradiation in the presence of Photofrin II and mTHPC. However, hypericin caused a rather stimulated growth expressed in increased optical density (OD) and increase of total cell count (TCC) of the culture. Combination sensitization of S. aureus by Photofrin II and mTHPC with hypericin likewise caused a stimulation of bacterial growth. No synergistic effects were obtained by combination of Photofrin II and mTHPC; photoresponse of S. aureus was rather decreased by using combined porphyrins. In comparison, TCC and colony-forming units (CFU) were suppressed in the presence of mTHPC after an illumination procedure as well as in dark reactions. These effects were also obtained in the combination photosensitization by mTHPC and Photofrin II. In the presence the of hypericin, photodynamic effects of mTHPC and Photofrin II were inhibited. It was finally concluded that hypericin in our model is not a proper sensitizer for combination photo-sensitization due to antagonistic effects on photodynamic activity of mTHPC and Photofrin II.

Cell Culture Techniques↗

PubMed1999

Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

Administration, Topical↗

PubMed1997

Measurement of inotropic effects by a newly developed guinea pig papillary muscle bioassay.

In order to measure inotropic influences of physiologically occurring substances and drugs we used a newly developed guinea pig papillary muscle (GPPM) bioassay. GPPM were suspended in air and surface coated with buffer (Krebs-Henseleit solution). The muscles were stimulated (pulsating direct current, 1.5 V; 0.5 Hz, 20 ms duration) which led to contraction. This method enables measurements of inotropic effects up to 5 days, contrary to previous studies (1 day), in which immersions of GPPM in buffer were performed. In order to investigate the comparability of the new method we measured the effect of metabolites (citric acid cycle), lactic acid, lactate, and extracellular pH on muscle contractility. The H(+)-dependent decrease of the contractile force of the GPPM can be compensated by an increased Ca(2+)-concentration. Further, the influence of catecholamines (isoproterenol) on the contractility was investigated. As a result, isoproterenol caused arrhythmias and extrasystoles as it was observed in clinical studies. Several pharmaceutical substances were tested to show the reproducibility and repeatability of the bioassay.

Acid-Base Equilibrium↗

PubMed1996

Natural products derived from plants as potential drugs for the photodynamic destruction of tumor cells.

Chlorophyll and some of its synthetically produced derivatives are important sensitizers in photodynamic cancer therapy. Other natural products from plants with light dependent activity include quinones like hypericin and fagopyrin. These compounds have extended pi-electron systems which upon photoexcitation with visible light are responsible for singlet oxygen production. Other plant constituents which show UV light induced photosensitizing activity are furanocumarins like psoralen and angelicin, aflatoxins and alkaloids, as well as thiophene derivatives, terthienyl and several polyacetylenes. The photodynamic properties of a chelidonium alkaloid derivative and data for its potential clinical applicability are given.

Antineoplastic Agents↗

PubMed1996

Wavelength-dependent photoresponse of biological and aqueous model systems using the photodynamic plant pigment hypericin.

Photodynamic eradication of tumour cells in vivo depends on the presence of a photosensitizer, light delivery to the cells, and an oxygen supply. Hypericin, a polycyclic quinone with absorption maxima in the ultraviolet and visible ranges, was prepared for clinical use as a photosensitizer. Due to antitumoral and antineoplastic activities as well as the generation of singlet oxygen after photoexcitation, hypericin was applied in clinical oncology and photodynamic therapy. Hypericin was administered subcutaneously (20 micrograms hypericin in 200 microliters Nacl/pyridine solution) into the ante brachium (forearm) of two volunteers. After the diffusion and equilibration of 120 min phototesting was carried out using outdoor light exposure, halogen lamp, laser 514 nm (argon), laser 632 nm (argon dye) and laser 670 nm (diode laser), from 60 to 120 J cm-2. Positive phototests to outdoor light exposure, halogen lamp and laser 514 nm were characterized by rubescence, oozing, vesiculation and darting pain. Phototests with laser 632 nm and 670 nm showed no effects after irradiation. When hypericin was administered topically on skin, erythema and flaring could not be induced by any irradiation. These results suggest that hypericin is a potent photosensitizer only within the UV and green light ranges. This characteristic photoresponse could also be obtained in guinea pig papillary muscle (GPPM) bioassay, which may be established as a model for photosensitizer testing. Irradiation of hypericin-incubated GPPM with 514 nm (20 J cm-2) led to a decrease of the contractile force of about 31%. However, excitation with 632 nm and 670 nm did not cause inotropic effects on GPPM. In addition, hypericin and Photosan 3 were shown to be capable of sensitizing the photo-oxidation of sodium linoleate. This assay should be established for testing interactions between photosensitizers and light sources in vitro.

Animals↗

PubMed1996

Hypericin in phototherapy.

We describe the first local use of hypericin as photosensitizer for photodynamic therapy in a patient with recurrent malignant mesothelioma. Hypericin is a polycyclic quinone, which has been shown to possess in vivo and in vitro antiretroviral and photosensitizing activity; moreover, it is used in depressive disorders. The semiquinone radical, singlet oxygen, and superoxide anion radical are reported to be the toxic agents in hypericin phototherapy. Our first experience with locally applied hypericin in a superficial tumor-plate was performed 8 weeks after the systemic administration of hematoporphyrin derivatives. For tumor light illumination we used an argon pumped dye laser tuned to 632 nm. Owing to satisfactory results, we repeated the same therapy 4 weeks later- and no therapeutic effect was noted. Following this, we proved the interstitial application of HPD and the combination of interstitial HDP and superficially applied hypericin. The subsequent light illumination 6 hours later had no efficacy in the HDP-photosensitized area but there was tumor destruction in the field with both administered photosensitizers. Our first experience suggests a potentiation of two photosensitizers: hematoporphyrin derivatives and hypericin.

Aged↗

PubMed1983

[Use of the proteinase inhibitor alpha 2-macroglobulin in synovial fluids of arthritis of different origins and its relation to serologic parameters].

Collagen and proteoglycan are major constituents of the articular cartilage. In rheumatic disorders joint damage is attributed to the excessive action of proteoglycan degrading proteinases (P) and specific collagenases, which are released by connective tissue- and inflammatory cells in the synovial compartment. Collagenase is secreted in a latent form, which requires activation by a variety of serine-proteinases. Thus, several different proteinases are involved in pathogenesis of joint disease. alpha 2-macroglobulin was shown to be the major inhibitor of proteinases in complex biological fluids. To assess the utilization of alpha 2M by proteinases in synovial fluids (SF) from different arthritides we have employed a newly introduced solid phase immuno-sorbent assay, which allows concentration of alpha 2M and its proteinase-complexes from biological fluids. Most pronounced utilization of alpha 2M (up to 50% of total SF alpha 2M) was found in marked joint inflammation as judged from RF, immunocomplexes, C3 complement activation and acute phase reactants. Supported by animal experiments, which revealed that alpha 2M.P complexes but not native alpha 2M induce synovitis in rabbits after repeated intra-articular administration, it is suggested that pathophysiological rise of alpha 2M.P may impair cellular functions in inflammatory connective tissue, e.g. synovial tissue.

Antigen-Antibody Complex↗

PubMedDate not supplied

Photodynamic action of meta-tetrahydroxyphenylchlorin (mTHPC) on an ovarian cancer cell line.

Meta-tetrahydroxyphenylchlorin (mTHPC) exhibits significant cytotoxicity against a variety of human cells in culture in combination with light, but also in dark reaction. The ovarian cancer cell line SK-OV3 was incubated with various concentrations of mTHPC and in comparison with Taxol and Cisplatin: then the effect on cell growth was determined. mTHPC exhibited an IC50 of 0.9 muM after 24 hours incubation (IC50 of 1.25 after 2 hours), whereas Cisplatin and Taxol, which, have been used as first line agents for the treatment of ovarian carcinomas, inhibited cell proliferation with an IC50 concentration of 4.6 muM and 78 nM after 24 hours incubation, respectively. Incubation of SK-OV3 cells with mTHPC for 5 days resulted in cytostatic cytotoxicity at a concentration of 0.5 muM. The photodynamic effect of mTHPC depends/among other parameters/on the concentration of the dye present. In combination with light (approximately 15 J/cm2) a linear relationship between the dose of mTHPC and the amount of necrotic cells was observable. Higher concentrations of mTHPC caused necrosis of the ovarian tumor cells. The intracellular concentration of mTHPC showed a linear increase up to 28.6 nM (incubation concentration). In summary, these studies demonstrated that mTHPC exhibits potent antiproliferative activity by inducing necrosis after application of light. MTHPC might be a promising agent with cytostatic and photodynamic properties for the treatment of metastasing ovarian carcinomas. A sensitive PCR method was not able to show the induction of apoptosis in the SK-OV3 ovarian cell line. Using propidium staining, it could be proved that the cell death was caused by necrosis and not through apoptosis after irradiation with light.

Antineoplastic Agents↗