Biomedical subjects

S Flock

Publications and source records attributed to S Flock.

24 records · Page 2Linked to original sources

PubMed1994

Interaction of two peptide-acridine conjugates containing the SPKK peptide motif with DNA and chromatin.

The interaction between DNA and two peptide-acridine conjugates containing one (1) or two (2) moieties of the Ser-Pro-Lys-Lys (SPKK) minor groove-binding peptide motif has been studied by a combination of hydrodynamic, biochemical and spectroscopic methods including diffusion-enhanced luminescence energy transfer (DELET) measurements with a Tb(III) lanthanide chelate as donor. Viscometric titrations do not reveal any significant difference between the two hybrid molecules which both unwind (by about 15 degrees) and extend the DNA similarly. DELET measurements show that the acridinyl chromophore of compounds 1 and 2 is much more accessible than that of a simple monointercalating drug such as acridine orange or ethidium. The accessibility factor increases proportionally with the peptide length, reflecting the extent of perturbation imposed upon the intercalating chromophore by the binding to DNA of the peptide moiety of the hybrids. Experiments with the osmium tetroxide-bispyridine reagent indicate that the two hybrid compounds both affect the local conformation of DNA rendering certain thymine residues conspicuously accessible to the probe. The drug-induced sites of hyperreactivity towards OsO4 in DNA are very similar with the exception of a short run of three T residues which is attacked more strongly in the presence of tetrapeptide-acridine conjugate 1 than with the octapeptide-acridine conjugate 2. These results are fully in agreement with previous footprinting studies and support the view that a minimum of two SPKK motifs is required to mimic the AT-specific minor groove binding antibiotic netropsin. On the basis of the DNA-binding properties of these two peptide-acridine hybrids, we present DNA-binding models in which the acridinyl moiety of compound 1 protrudes slightly outside the double helix but remains more or less parallel to the plane of the base-pairs. In contrast, with compound 2, where the octapeptide SPKKSPKK is bound to the minor groove, we postulate that the chromophore lies only partially overlapped with the base pairs in the intercalation site and, in addition, the heterocyclic chromophore is significantly tilted with respect to the double helix axis. Electric linear dichroism and DELET measurements with chromatin reveal that the presence of histone proteins affects the intercalative binding of compound 2 while it has practically no effect on the binding of compound 1.

Acridines↗

PubMed1993

Tumor specific response to photodynamic therapy.

The exact mechanism by which photodynamic therapy (PDT) causes tumor destruction has not been elucidated. Early reports indicated that PDT causes direct cellular effects probably mediated by unstable oxygen species, resulting in cellular oxidation and death. More recently, PDT effects on tumor blood flow have been implicated, and there are questions as to whether the PDT response is specific to tumor tissue. Rats were implanted with a window chamber containing either a mammary adenocarcinoma or a piece of inert surgical sponge. After growth of the tumor was ascertained, all rats were given 5 mg/kg Photofrin intraperitoneally, and then were irradiated with 630 nm light 24 hours post-injection. Caliper thickness and reflectance measurements were performed before and after irradiation; all animals were sacrificed 72 hours post-PDT and the chambers submitted for histologic analysis. Animals implanted with tumors demonstrated marked edema of the chamber with an associated decrease in reflectance. No edema response was noted in the chambers containing inert sponge, or in any controls. Nonselective PDT effects (characterized by a marked foreign body response) in chambers containing sponge was not seen. Histologic analysis of treated specimens corroborate the above data.

Animals↗

PubMed1993

The copper vapor laser for treatment of cutaneous vascular and pigmented lesions.

BACKGROUND: Clinical experience has shown that a variety of skin lesions are treatable with rapidly pulsed yellow and green light of the copper vapor laser. OBJECTIVE: To review the development, use, complications, and efficacy of the copper vapor laser when utilized for cutaneous lesions. METHODS: Articles were identified through a MEDLINE search, review of these articles' bibliographies, and advice from expert physicians who have used the copper vapor laser. RESULTS: A variety of vascular and pigmented cutaneous lesions are effectively treated with the copper vapor laser. A distinct advantage for hypertrophic or cobblestoned port-wine stains and most types of facial telangiectasia is seen when this laser's results are compared with the results of other available laser systems. Complications, including scarring, are rarely observed. CONCLUSION: The copper vapor laser is a useful addition to the family of lasers that are used for cutaneous conditions.

Facial Neoplasms↗

PubMed1992

Effect of aspirin on photodynamic therapy utilizing chloroaluminum sulfonated phthalocyanine (CASP).

The efficacy of photodynamic therapy (PDT) is mediated through a direct vascular effect. Interference with platelet function and resulting vascular stasis have been recently demonstrated utilizing the photosensitizer dihematoporphyrin ether (DHE). We examined the effect of aspirin, a known inhibitor of both cyclooxygenase and platelet activity, on PDT using chloroaluminum sulfonated phthalocyanine (CASP). Thirty-six rats implanted with a window chamber were given either 0.1 mg/kg (low dose) or 10 mg/kg (high dose) aspirin immediately before, immediately after, or 6 hours after the completion of CASP-PDT. Aspirin in either dosage did not appear to have any effect on the window vasculature when given immediately after light exposure. A moderate inhibition of vascular response was seen in animals treated with aspirin pre-PDT, whereas high-dose aspirin completely abrogated the CASP-PDT vascular response when given 6 hours post-PDT. These data indicate that aspirin can effect CASP-PDT in both time-dependent and dose-dependent fashions.

Animals↗

PubMed1991

An implantable tumor-window chamber model for the study of photodynamic therapy.

In order to study both the anti-tumor effects and early vascular events in photodynamic therapy, a useful animal model has been developed. A window chamber is surgically placed on the dorsum of the Fischer-344 rat, and 500-microns fragments of the rat mammary adenocarcinoma 13672 are placed under direct vision into the subcutaneous tissue. Implantation of the chamber has been successfully completed in more than 50 rats. The operative procedure is straightforward and is accomplished in less than 1 hour. Using tumor fragments, tumor viability has been 60%. We have demonstrated obvious and reproducible neovascularization occurring as soon as 1 day after implantation. The application of this system to an experimental protocol comparing the photosensitizers dihematoporphyrin ether (DHE) and chloraluminum sulfonated phthalocyanine (CASP) has yielded important information on early vascular events resulting from photodynamic therapy.

Adenocarcinoma↗

PubMed1991

Chloroaluminum sulfonated phthalocyanine versus dihematoporphyrin ether: early vascular events in the rat window chamber.

The development of a simple and well-tolerated rat window chamber has allowed direct comparison of the vascular effects of two photosensitizers, chloroaluminum sulfonated phthalocyanine (CASP) and dihematoporphyrin ether (DHE). CASP and DHE were given 4 days after the implantation of the window chamber. Photodynamic therapy (PDT) with CASP was performed 24 hours after intravenous injection (10 mg/kg) with light at 675 nm (power density 200 mW/cm2, incident energy 100 J). DHE was given in a similar fashion (5 mg/kg intraperitoneally; light at 630 nm with matching power density and energy settings 24 hours after injection). Using videomicroscopic and integrating sphere measurements, marked differences were noted in the vascular effects of these photosensitizers. DHE caused immediate hemorrhage and disruption of the postcapillary venules, while CASP induced vascular spasm starting 4 hours after the completion of PDT. Forty-eight hours after PDT, both systems demonstrated a loss of chamber-induced neovascularization.

Animals↗