Effect of chloroquine wash-out period of photosensitizers in the skin and selected organs in rats.

In the last decade, photodynamic therapy has become an alternative method for the diagnosis and therapy of tumors. In human medicine hematoporphyrin derivatives, sulfonated hydrophilic meso-tetraphenylporphyrin (TPPS4) and an oligomer of hematoporphyrin (Photosan 3), are widely used. Chloroquine is used for the treatment of porphyria cutanea tarda for its power to release porphyrins from the liver tissue. The kinetics of two porphyrin photosensitizers TPPS4 and Photosan 3 in the skin and some organs as well as the effect of chloroquine on the porphyrin excretion and their accumulation in skin and organs of Wistar rats were studied. TPPS4 exhibited maximum fluorescence in skin 48 h after application with decreasing to basal level from the 8th to the 14th day. Maximum fluorescence was reached at 72 hours after Photosan 3 application and it decreased to basal level during 96 hours after application. TPPS4 caused significantly higher fluorescence compared to Photosan 3. Chloroquine after oral administration did not change the fluorescence of skin, but it significantly decreased the TPPS4 concentration in rat organs if chloroquine treatment started 3 days or 2 weeks after TPPS4 application. Chloroquine significantly decreased the serum TPPS4 concentration during the period of 28 days. Fluorescence of skin was significantly higher and lasted longer after application of TPPS4 compared to Photosan 3. Chloroquine after oral administration did not influence the fluorescence of the skin, but it significantly decreased the TPPS4 concentration in rat organs. This effect could be useful in photodynamic therapy for mobilizing exogenous porphyrins from tissues after parenteral photodynamic therapy.

[Photodynamic diagnosis and therapy in dermatology. Experience with use of TPPS4 in skin diseases]. / Fotodynamická diagnostika a terapie v dermatologii. Zkusenosti s aplikací TPPS4 u nekterých kozních afekcí.

BACKGROUND: Some skin lesions e.g. basal cell carcinomas are sometimes difficult to remove completely and frequent relapses can develop after their imperfect removal. In case the patient refuses to undergo a radical surgical intervention, more painful alternative like cryotherapy comes into consideration as a method of tumour destruction. Not even such a procedure does guarantee complete destruction of all tumour cells. During the last years new diagnostics and therapeutic methods like photodynamic diagnostic and photodynamic therapy have been developed and they became subjects of our interest. METHODS AND RESULTS: Lesions were treated with photosensitizer (meso-tetra-para-sulphonato-phenyl-porfine-TPPS4) administered in an injection or in the ointment under occlusion. Six to 24 hours later we checked presence of photosensitizer in the lesions and in positive cases we irradiated the lesions with light of suitable wave length (630 nm). CONCLUSIONS: PDD and PDT were used for diagnostics and treatment of different dermatoses (basal cell carcinomas, malignant melanoma metastases, verrucae vulgares, keratoacanthomas, solitary lesions of T lymphoma--mycosis fungoides, m. Bowen, psoriasis vulgaris, pustulosis palmoplantaris, solar keratoma) with very good medical and cosmetic effect. Results are presented in the table. Authors do not consider the PDT to be the only and miraculous method relevant to treatment of all skin tumours or other skin diseases. They are of the opinion that this technique, when properly used, can extend the scale of therapeutic methods. The advantage of PDT is its selectivity, good tolerance and generally good cosmetic effect.

[Therapy of pruritus using ultraviolet irradiation in patients on hemodialysis]. / Terapie pruritu UV zárením u hemodialyzovanych pacientu.

BACKGROUND: Patients with chronic renal insufficiency (CHRI) frequently suffer from generalized pruritus, which is difficult to palliate. One of the treatments with favourable effect on pruritus is UV radiation. METHODS AND RESULTS: Fifteen patients were exposed to UVB radiation in doses from 20 to 45 s or from 1 min and 20 s to 18 min (i.e. 0.09-0.18 J/cm2 to 1.9-4.32 J/cm2). Ten of the treated patients reported a marked regression of pruritus, three a slight relief and two of them did not notice any change in the intensity of itching. Another four patients were exposed to the UVA radiation from 0.5 J/cm2 to 10.0 J/cm2 With exception of one female patient non-of them revealed any improvement in the intensity of pruritus the irradiation. CONCLUSIONS: UVB is probably highly effective on inhibition of pruritus and thus can be used as an efficient method, which extends contemporary antipruriginous treatment of patients with CHRI. However, so far it is difficult to explain its favorable effect.

[The effect of ibuprofen on the composition of tissue lipids in an experiment]. / Vliv ibuprofenu na slození tkánových lipidu v experimentu.

BACKGROUND: Number of drugs is used in human medicine for a long time therapy. Their side effects on lipid metabolism are mostly unknown. Clinical testing of drugs concerns usually biochemical parameters involved in the liver and kidney function. The aim of our study was to search the effect of ibuprofen on the lipid composition in the important organs. Ibuprofen was chosen as a representative of currently used nonsteroidal antiinflammatory drugs. METHODS AND RESULTS: Group of 14 Crl-NMRI-BR male mice, approximately 8 weeks old, 30.5 +/- 1.2 g initial body mass, was used in the experiment. Animals were divided into 2 identical groups. One of them received 0.6 mg of ibuprofen per day (animal model for human dose 1200 mg/day) in the diet for a period of 6 weeks. After this time, animals were killed by decapitation, individual organs were excised, washed with physiological saline and lyophilized. Total lipid content was determined gravimetrically. Individual lipid classes were separated by thin-layer chromatography. Fatty acid profiles (in the form of methyl esters) in these lipid classes were analyzed by capillary gas chromatography using fused silica column 25 m x 0.25 mm I.D. with the chemically bonded stationary phase CP-WAX 52 CB (Chrompack, The Netherlands). The treatment resulted in the increased body mass of 7.9 +/- 1.7 g, which, in comparison with that of control group (4.9 +/- 3.4 g) was not statistically significant. Liver mass increased from 1.62 +/- 0.21 g to 1.86 +/- 0.19 g (p < 0.05). Total lipid content in the liver increased from 52.8 +/- 15.4 to 91.7 +/- 10.9 mg/g (p < 0.01). Changes in the fatty acid composition were most important in the kidney tissue. Relative levels of polyunsaturated fatty acids increased in phosphatidylethanolamine from 27.6 +/- 6.1 mol% to 33.9 < 0.6 mol% (p < 0.05) for n6 fatty acids and from 8.7 +/- 2.1 to 14.7 +/- 1.1 mol% (p < 0.001) for n3 fatty acids. These changes were compensated by the opposite ones in the relative content of saturated fatty acids from 49.7 +/- 7.0 mol% to 41.1 +/- 0.7 mol% (p < 0.05) and monoenoic fatty acids from 14.0 +/- 2.0 mol% to 10.4 +/- 0.9 mol% (p < 0.01). Changes in the fatty acid composition of the liver and heart lipids were mostly not statistically significant. CONCLUSIONS: An unusual component was observed in the triacylglycerol fraction of heart tissue, which was identified by the gas chromatography-mass spectrometry as a mixture of approximately 80% of isopropyl myristate and 20% of isopropyl palmitate. Absolute content of this component was not determined.

Changes in the liver, kidney and heart fatty acid composition following administration of ibuprofen to mice.

Crl:NMRI-BR male mice received 0.6 mg/day of ibuprofen (animal model for human dose 1200 mg/day) in the diet for a period of 6 weeks. This treatment resulted in increased body mass, liver mass, and total lipid content in the liver tissue. Changes in the fatty acid composition in the individual lipid classes were most important in kidney tissue; levels of polyunsaturated fatty acids were increased in phospholipids and decreased in neutral lipids. These changes were compensated for by opposite changes in the levels of saturated and monoenoic acids. Similar changes were also observed in liver and heart lipids. An increased level of an unusual component was observed in heart tissue, which was identified as isopropyl myristate by GC-MS and verified by comparing the mass spectra and retention times with those of synthetic standards.