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PubMed1989

[Production of volatile fatty acids in the rumen of calves during dietary-microbial stimulation and early weaning].

The contents of volatile fatty acids in the rumen fluid were studied in calves at an early (seven weeks of age) and traditional weaning term (nine weeks of age). Weaning at the age of seven weeks enabled to save 16.2 kg of milk replacer per calf; there was also a lower content of concentrates in the starter feed with a supplement of Amylastim. The health condition of the calves was good in both groups. The average daily weight gains for the period from the second to the ninth week of age were 0.550 kg in the early weaned calves and 0.690 kg in the calves weaned at a normal time. Early weaning had a positive influence on the development of rumen metabolism. Calves weaned at the age of seven weeks, compared with those weaned at the age of nine weeks, had much higher concentrations of VFA (p less than 0.05) in rumen fluid (at the age of seven weeks: 130.49 mmol per litre vs. 111.53 mmol per litre; at the age of eight weeks: 119.74 mmol per litre vs. 96.98 mmol per litre). Early weaned calves had the statistically significantly (p less than 0.05) higher proportions of propionic acid, butyric acid, i-butyric acid, and valeric acid. Later-weaned calves had the significantly higher (p less than 0.05) contents of acetic acid and i-valeric acid.

Animal Feed↗
PubMed1988

Polycystic ovarian disease: animal models.

The reproductive systems of human beings and other vertebrates are grossly similar. In the ovary particularly, the biochemical and physiologic processes are identical not only in the formation of germ cells, the development of primordial follicles and their subsequent growth to Graafian follicles, and eventual ovulation but also in anatomic structure. In a noncarcinogenic human ovary, hypersecretion of androgen causes PCOD. Such hypersecretion may result from a nonpulsatile, constant elevated level of circulating LH or a disturbance in the action of neurotransmitters in the hypothalamus. In studying the pathophysiology of PCOD in humans, one must be aware of the limitations for manipulating the hypothalamic-pituitary axis. Although the rat is a polytocous rodent, the female has a regular ovarian cyclicity of 4 or 5 days, with distinct proestrus, estrus, and diestrus phases. Inasmuch as PCOD can be experimentally produced in the rat, that species is a good model for studying the pathophysiology of human PCOD. These PCOD models and their validity have been described: (1) estradiol-valerate, (2) DHA, (3) constant-light (LL), and (4) neonatally androgenized. Among these, the LL model is noninvasive and seems superior to the others for study of the pathophysiology of PCOD. The production of the polycystic ovarian condition in the rat by the injection of estrogens or androgens in neonate animals, or estradiol or DHA in adult rats, or the administration of antigonadotropins to these animals all cause a sudden appearance of the persistent estrus state by disturbing the metabolic and physiologic processes, whereas exposure of the adult rat to LL causes polycystic ovaries gradually, similar to what is seen in human idiopathic PCOD. After about 50 days of LL, the rat becomes anovulatory and the ovaries contain thickened tunica albuginea and many atretic follicles, and the tertiary follicles are considerably distended and cystic. The granulosa and theca cells appear normal histologically, although some of the stromal cells appear hypertrophic. The anatomic features consequent to polycystic ovaries resulting from LL are similar to those in human PCOD, and both rat and human PCOD ovarian cells still retain the ability to respond to FSH/LH, LHRH, and unilateral ovariectomy. In the estradiol valerate rat model, although the anatomy and physiology of the ovary resemble those of PCOD patients, the progressive degeneration of the hypothalamus and the altered response of the pituitary to LHRH make this model inappropriate for studying the hypothalamic-pituitary-ovarian axis in the polycystic ovary condition.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Comparative toxicity study of hydrocortisone 17-butyrate 21-propionate (HBP) ointment and other topical corticosteroids in rats.

Comparative systemic and topical toxicity in male rats treated on the dorsal skin for 14 consecutive days with a volume of 0.15 g/100 g (body weight) of 0.1% hydrocortisone 17-butyrate 21-propionate (HBP) ointment, 0.05% clobetasol propionate (CP) ointment, 0.1% predonisolone 17-valerate 21-acetate (PVA) ointment and 0.1% diflucortolone valerate (DV) ointment was studied. In all the treated groups body weight gain was suppressed, serum concentration of total cholesterol and triglycerides increased and the lymphatic tissues and skin were atrophic. The DV and CP groups had adrenal atrophy and renal lesions, and the DV group also had gastric and hepatic lesions. The systemic effect of HBP ointment was weaker than that of the other drugs (DV greater than CP much greater than PVA greater than HBP). All the drugs significantly reduced the skin fold thickness in treated areas throughout the application period. The dermal atrophic effect of HBP ointment was also relatively weaker than that of the other drugs. From the above evidence, it was concluded that HBP ointment was less toxic than the other topical corticosteroids.

Administration, Topical↗
PubMed1985

The 65-kDa phorbol-diester hydrolase in mouse plasma is esterase 1 and is immunologically distinct from the 56-kDa phorbol-diester hydrolase in mouse liver.

Esterase 1, a well-characterized mouse plasma protein of unknown function, has activity against a wide range of ester substrates including beta-alanine nitrophenyl esters and 17 beta-esters of estradiol. In this article, we report that esterase 1 is also responsible for a majority of the phorbol-12-ester hydrolase activity in mouse plasma. Incubation of homogeneous esterase 1 with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) at either 4 or 37 degrees C for up to 18 h yielded phorbol 13 alpha-acetate as the only hydrolysis product. Specific polyclonal antibodies to esterase 1 inhibited 95% of PMA hydrolysis by a purified esterase 1 preparation and 65% of PMA hydrolysis by mouse plasma. Perfused mouse liver homogenates contain two distinct phorbol diester hydrolases with apparent molecular masses of 65 kDa and 56 kDa, respectively. The 65-kDa protein appears to be immunologically identical to the plasma enzyme, while the 56-kDa protein, found in liver but not in plasma, is immunologically distinct. Phorbol 12-myristate, phorbol 12,13-dibutyrate, and PMA were found to be competitive inhibitors of the beta-alanine-nitrophenyl esterase activity of esterase 1 with Ki values of approximately 7 microM. Phorbol 13-acetate and phorbol itself were less effective with Ki values of 37 and 140 microM, respectively. Sodium salts of valeric and myristic acids did not inhibit at 10 microM. The above results indicate that efficient substrate binding requires a phorbol 12-ester. Similar results were obtained with estradiol 17 beta-valerate which is a better substrate for esterase 1 than is PMA. Our results strongly suggest that esterase 1 and a recently described phorbol ester hydrolase isolated from mouse serum (Saito, M., and Egawa, K. (1984) J. Biol. Chem. 259, 5821-5826) are the same and are immunologically and kinetically distinct from the 56-kDa phorbol 12-ester hydrolase in mouse liver.

Animals↗
PubMed1985

Molecular level studies with anthracyclines.

There is steadily growing interest in the characterization of chemotherapeutic agents at the molecular level. Such characterization ideally involves the elucidation of structural properties such as configuration, conformation and tautomeric or mesomeric form, establishes the effect of chemical substitution on structural properties and provides insight into probable intermolecular interactions that are environmentally dependent. The interpretation of these data can be important for the design of new chemotherapeutic agents. The authors are presently investigating the anthracyclines, particularly members of the daunomycin and nogalamycin families, in an effort to better understand their behaviour at the molecular level. These studies have drawn upon analysis of single crystal structures determined with X-ray diffraction data and solution studies employing ultraviolet and circular dichroism spectroscopies. Crystal structures have been determined for 7-con-O-methylnogarol, 7-deoxynogarol, 9-deacetyldaunomycin, adriamycin-14-valerate (AD-48), and N-trifluoroacetyladriamycin-14-valerate (AD-32). Solution studies have concentrated on the study of the interaction of selected anthracyclines with oligonucleotides of known sequence. The oligonucleotides used were: d-(5GTCATGAC), d-(5GTCGCGAC) and the non-self complementary pair d-(5GTCGTCA) and d-(5TGACGAC).

Antibiotics, Antineoplastic↗
PubMed1975

Inhaled corticosteroids compared with oral prednisone in patients starting long-term corticosteroid therapy for asthma. A controlled trial by the British Thoracic and Tuberculosis Association.

Inhaled beclomethasone dipropionate and inhaled betamethasone valerate have been compared with oral prednisone in the treatment of 75 patients with asthma who were starting long-term corticosteroids for the first time. Both of the inhaled corticosteroids controlled asthma as well as did oral prednisone in those who had responded to therapy in the initial period of the trial. A daily dose of 400 mug of inhaled drug was approximately equivalent to 7-5 mg daily of prednisone. Prednisone suppressed the adrenal response to tetracosactrin, whereas the mean responses in the groups receiving inhaled corticosteroids did not change significantly from pre-trial values. The 30% incidence of other systemic unwanted effects of prednisone contrasted sharply with the low incidence (5%) of symptomatic oropharyngeal candidiasis in the patients receiving inhaled corticosteroids. In a sample of 19 patients no change in exfoliative cytology was detected over the period of the trial nor was there any evidence of fungal colonisation of the bronchial tree. There was no difference between the three treatment groups in the number of antibiotic courses prescribed. The persistent production of sputum made no difference to the response to inhaled corticosteroids. Patients not on sodium cromoglycate did as well in the trial as those receiving sodium cromoglycate. Both inhaled beclomethasone dipropionate and inhaled betamethasone valerate have advantages over oral prednisone in the maintenance treatment of patients with asthma, but in the management of exacerbations systemic corticosteroids will usually be needed as a supplement to inhaled therapy.

Administration, Intranasal↗
PubMed1984

Short-chain fatty acids in the normal human feces.

The short-chain fatty acids ( SCFAs ) have been studied in the feces of 20 healthy subjects--10 methane excretors and 10 non-methane excretors. The analytical procedure included homogenization of fecal samples followed by vacuum distillation and subsequent gas chromatography. This method for analysis of fecal SCFAs showed recoveries of the individual acids from 90% to 109% and coefficients of variation for the inter-assay reproducibility from 6.0% to 19.7%, highest for those acids present in the smallest concentrations. There was no difference in the concentrations or relative compositions of SCFAs between methane-excreting subjects and non-methane-excreting subjects. The concentrations of SCFAs , given as mmol/kg feces (wet weight), were (median and range): total, 76.8 (27.9-187.7); acetic acid, 37.4 (12.8-103.4); propionic acid, 12.5 (4.5-27.8); i-butyric acid, 2.2 (0.7-3.8); n-butyric acid, 12.4 (4.0-53.0); i-valeric acid, 3.2 (0.8-5.9); n-valeric acid, 2.4 (0.6-3.8) and n-caproic acid, 0.5 (0.0-3.6). The study shows that the SCFAs are quantitatively the most important anions in the feces of healthy subjects. The pronounced individual variations in the concentrations of SCFAs are real biological variations and cannot be explained by methodological variations.

Adult↗
PubMed1984

IgG-induced experimental immune synovitis: hormonal modulation of in vitro splenic immune responses to homologous antigens.

The effect of oestrogen or anti-oestrogen administration on gross pathology and in vitro cell-mediated immune responses to homologous IgG, native and denatured interstitial collagens and PPD was studied in an IgG-induced rabbit model of immune synovitis. During induction of synovitis, rabbits were administered oestradiol valerate (0.075 mg/kg/day) or tamoxifen, an anti-oestrogen (2.0 mg/kg/day, high dose or 0.5 mg/kg/day, low dose) or placebo injections. Low dose tamoxifen administration was associated with significant improvement P less than 0.05 in immune synovitis with regard to gross pathology, when compared to placebo and the oestradiol treatment group. High dose tamoxifen treatment was not associated with significant improvement in observed synovitis. With regard to cell-mediated immune responses, spleen cells derived from immune synovitis rabbits were observed to increase 3H-thymidine uptake on incubation with native or denatured homologous collagens. Modulation of these immune responses to antigens was observed in anti-oestrogen treated rabbits with immune synovitis. In vitro cell-mediated immune responses to denatured type I, II and III collagens, PPD, as well as native type II and III collagens were not observed in the low dose tamoxifen treatment group. However, in vitro immune responses to these antigens were observed in spleen cell cultures from immune synovitis rabbits treated with either high dose tamoxifen or oestradiol valerate. The data suggest that in vivo anti-oestrogen administration can modulate the in vitro cell-mediated immune response to connective tissue constituents observed in immune synovitis. Concomitant with reduced immune responses is a significant reduction in the observed lesions of the inflammatory response.

Animals↗
PubMed1983

Topical therapy for perioral dermatitis.

Six patients with perioral dermatitis were successfully treated with a combination of 1.5 percent erythromycin topical solution twice a day and topically applied hydrocortisone valerate cream. Application of erythromycin solution seems to be an effective topical therapy. Hydrocortisone valerate cream, when used in a controlled, tapered regimen seems to prevent acute rebound flare of perioral dermatitis from previous high-potency steroid use or abuse.

Administration, Topical↗
PubMed1978

Effect of adriamycin and analogs on the nuclear fluorescence of propidium iodide-stained cells.

Adriamycin (ADR) and N-trifluoroacetyladriamycin-14-valerate, respectively, inhibit and enhance the nuclear fluorescence of cells stained with propidium iodide for DNA per cell estimation by flow cytometry. In cells incubated with ADR, the reduction in fluorescence is gradually manifested due to the slow intracellular drug transport. In contrast the effect of N-trifluoroacetyladriamycin-14-valerate on propidium iodide nuclear fluorescence is seen within 5 min of incubation. The effect of ADR on propidium iodide nuclear fluorescence could be detected in vivo even after 24 hr of ADR administration.

Animals↗
PubMed1982

In vitro and ex vivo binding to uterine progestin receptors of the rat as a tool to assay progestational activity of glucocorticoids.

The competition of some widely employed glucocorticoids with the binding of [3H]-promegestone, a highly potent synthetic progestagen, to uterine cytosol progestin receptors of the immature rat has been studied both in in vitro and ex vivo experiments. The relative binding affinities (RBA's) to progesterone were determined in vitro: fluocinolone acetonide greater than triamcinolone acetonide greater than betamethasone 17-valerate greater than prednisolone, betamethasone, triamcinolone and cortisol. After pretreating rats in vivo with progesterone or chlormadinone acetate (subcutaneously), a dose-dependent decrease in in vitro binding of [3H]-promegestone to uterine cytosol was evident. Similar decreases were obtained after pretreatment with some of the other glucocorticoids tested. Potency ratios to progesterone, arbitrarily set at 1.0, were: fluocinolone acetonide 86.7, triamcinolone acetonide 5.6, betamethasone valerate 4.1, chlormadinone acetate 2.6. Prednisolone, betamethasone, triamcinolone and cortisol were inactive. Both the in vitro and the ex vivo results clearly indicate that glucocorticoids interact with the uterine cytosol progestin receptor system, depending on their chemical structures; this interaction may account for some of their unwanted side-effects in the endocrine system. Moreover, this experimental system may prove to be a useful tool for evaluation of the progestational activities of glucocorticoids and other steroids, using the rat as an animal model.

Animals↗
PubMed1981

Required presence of both estrogen and pituitary factors for the growth of human breast cancer cells in athymic nude mice.

Estrogen, prolactin, and other pituitary factors are implicated in the etiology of human breast cancer. In the present study, the effects of estrogen and factors from GH3 rat pituitary tumor cells on the growth of T-47D human breast cancer cells were tested in athymic nude mice. Four groups of nude mice were used: Group 1 (T) received s.c. injection of T-47D cells only; Group 2 (TE) mice were given injections of estradiol valerate and T-47D cells; Group 3 mice were given injections of T-47D and GH3 cells (TG), one cell type on each flank; and Group 4 received estradiol valerate and T-47D and GH3 cells (TEG). We found that the human breast cancer cells, T-47D, did not proliferate in Groups 1 and 3 despite the presence of high circulating levels of prolactin and growth hormone produced by the growing GH3 pituitary tumors in Group 3. This suggested that prolactin and growth hormone were not sufficient to stimulate the growth of human breast cancer cells. T-47D cells exhibited only moderate growth in Group 2 but proliferated rapidly in Group 4. The T-47D tumors of Group 4 were 8 times larger than those in Group 2 after 42 days of growth. These results demonstrate that the simultaneous presence of estrogen and pituitary growth factors are required for maximal growth of T-47D human breast cancer cells in nude mice. The identity of the pituitary-dependent growth factor(S) that stimulates the growth in vivo of human breast cancer cells remains to be elucidated.

Animals↗
PubMed1980

Fermentation of 1,2-O-iso-propylidene-D-glucofuranose ("monoacetone glucose") by anaerobic bacteria.

Various species of Clostridium, Bacteroides, Propionibacterium and Eubacterium were incubated in a 1% solution of 1,2-O-iso-propylidene-D-glucofuranose in a peptone-yeast-extract (PY) medium according to the VPI-technique. The volatile and non volatile acids were investigated by gas-liquid chromatography. All microorganisms showed a pattern of VFA different from that one produced by the glucose containing medium. In most microorganisms the formation of acetic acid was suppressed while the production of propionic, butyric, valeric and iso-valeric acids was stimulated. The production of succinic acid was not affected. Simultaneous determination of monoacetone glucose and glucose in the culture medium showed that the glucose analogue is used to a lesser extent than glucose.

Anaerobiosis↗
PubMed1995

Effects of nephrotoxic beta-lactam antibiotics on the mitochondrial metabolism of monocarboxylic substrates.

UNLABELLED: The nephrotoxic beta-lactam antibiotics (beta-lactams) cephaloridine, cephaloglycin and imipenem are toxic to the mitochondrial transport and (secondarily) oxidation of succinate and other dicarboxylic substrates. However, compared to cephaloglycin, cephaloridine is minimally toxic to the mitochondrial uptake and uncoupled oxidation of the short-chain fatty anion butyrate. Further studies were therefore done to compare the early effects of nephrotoxic doses (300 mg/kg body weight) of imipenem, cephaloridine and cephaloglycin on the mitochondrial metabolism of three important monocarboxylic substrates, butyrate, valerate and pyruvate, in rabbit renal cortex. The following was found: 1) imipenen reduces the oxidation of all three monocarboxylates, within 0.5 to 1 hr after administration. 2) The respiratory toxicity of cephaloglycin is essentially the same as that of imipenem with all three substrates. 3) cephaloridine causes little or no toxicity to pyruvate or butyrate oxidation and is significantly less toxic than imipenem or cephaloglycin to valerate oxidation. 4) The effects of the three beta-lactams on butyrate and pyruvate uptake parallel their effects on butyrate and pyruvate oxidation. CONCLUSIONS: Imipenem and cephaloglycin have essentially the same patterns of toxicity to the mitochondrial metabolism of all metabolic substrates that have been tested. Although cephaloridine has similar effects on dicarboxylic substrates, it is significantly less toxic to the mitochondrial metabolism of pyruvate and the short-chain fatty anions. It is proposed that cephaloridine's zwitterionic charge may restrict its ability to acylate monocarboxylic and other anionic carriers, resulting in less nephrotoxicity than might otherwise result from its uniquely high intracellular concentrations and singular ability among the toxic beta-lactams to produce oxidative injury.

Animals↗
PubMed1994

Augmentation of gamma-globin gene promoter activity by carboxylic acids and components of the human beta-globin locus control region.

Butyric acid increases fetal hemoglobin synthesis in adult animals and in erythroid cells in culture and induces the gamma-globin gene promoter in transient expression experiments in K562 cells (McDonagh KT, Nienhuis AW, Blood 78:255a, 1992 [abstr, suppl 1]). We compared the effect of butyrate and other short-chain carboxylic acids in transient expression studies with K562 cells using an expression plasmid bearing a luciferase reporter gene driven by the normal human A gamma-globin gene promoter. Butyrate (4 carbons) increased the activity of the human A gamma-globin gene promoter up to 123 times. Marked augmentation of the normal gamma-promoter activity was also noted with 5-carbon valeric acid (up to 394 times) and 3-carbon propionic acid (up to 129 times). The branched isobutyric acid as well as phenylacetate showed less ability to increase promoter activity. Addition of the tandemly repeated AP-1/NF-E2 (AP) enhancer sequences from hypersensitive site 2 (HS2) of the locus control region (LCR) increased gamma-promoter activity up to 24 times. Addition of a nearby 16-bp conserved motif (CM) in HS2 (Safaya S, Rieder RF, Blood 78:146a, 1992 [abstr, suppl 1]) to the AP-containing plasmid construct further increased gamma-promoter activity. In the presence of butyrate, the plasmid bearing both the AP and CM sequences showed gene expression up to 477 times greater than that of the basal gamma-promoter-driven luciferase plasmid in the absence of inducer. A plasmid bearing the herpes simplex thymidine kinase promoter was also tested and gene expression was markedly increased by the same organic acids. MEL cells responded to butyrate, valerate, and propionate with induction of hemoglobin synthesis. Responses to isobutyrate and 6-carbon caproate required higher concentrations of the compounds. Thus, other short-chain organic acids as well as butyrate increase gamma-promoter activity in the transient expression system, and this activity can be further augmented by incorporating LCR elements into the expression vector. Nonglobin promoters also respond to the same carboxylic acids.

Animals↗
PubMed1994

[The effect of cadmium on the protozoan population and rumen fermentation of feed in an artificial rumen].

In our experiment, the effects of 5, 10 and 20 mg cadmium per kg dry matter (DM) on protozoan population and rumen fermentation of feed ration consisting of 11.7 g DM of hay and 2.8 g DM of barley (80: 20%) were followed in artificial rumen (Rusitec). The results of the experiment showed that the addition of 5 and 10 mg cadmium per kg DM less significantly (P < 0.05) decreased the digestibility of DM, organic matter and neutral detergent fibre and significantly (P < 0.01) decreased the digestibility of cellulose of feed ration. It is interesting that the addition of 20 mg cadmium per kg DM did not influence these parameters. Although the total gas production showed a tendency of decrease due to the influence of the addition of 5, 10 and 20 mg cadmium/kg DM, methane and CO2 production was not altered. However, cadmium significantly influenced the production of individual volatile fatty acids-VFA's (mmol/day). The addition of 5, 10 and 20 mg cadmium per kg DM significantly increased acetic acid production (by 10-20%) and decreased propionic acid production (by 18-30%). Therefore, the acetate: propionate ratio was significantly increased (from 1.57 to 2.45-2.60) by the addition of cadmium. The production of n-valeric and iso-valeric acids was also significantly decreased in comparison with the control. The decrease of individual VFA's was more significant at the higher amount of cadmium added into the fermentation system. The proportions of individual VFA's in total VFA production expressed in molar % showed a similar character. The changes in the production of individual VFA's due to the influence of the addition of 5, 10 and 20 mg cadmium per kg DM caused a decrease in energetic efficiency of VFA's (P < 0.001) in comparison with the control. The other parameters of rumen fermentation - utilization of glucose, adenosine triphosphate (ATP) production, fermented hexose, fermented amino acids and fermented organic matter (OMF) were not influenced by the cadmium addition. Although the total microbial matter production in effluent and undigested feed (residues) was significantly (P < 0.001) decreased by the addition of 5, 10 and 20 mg cadmium per kg DM, the efficiency of microbial synthesis expressed as YATP and g microbial N/kg OMF was not changed and achieved the values 11.78-12.68 (YATP), 25.56-28.35 (g microbial N/kg OMF), respectively. The total protozoan population was significantly decreased by the cadmium addition mainly as a result of the decrease of infusoria of Entodinium spp.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗
PubMed1994

[Study on odor control using wood vinegars (II). Application of wood vinegars to piggery wastes].

The effectiveness of wood vinegars was studied for controlling offensive odors from piggery wastes. Odorant chemicals and the sense of odors from piggery farm, covered with polyvinylchloride film to prevent the volatilization to ambient air, were measured in both laboratory and in situ in order to evaluate the degree of deodorization. The results obtained were as follows: 1. The odorant chemicals from piggery wastes were identified as ammonia, methyl sulfide, hydrogen sulfide, butyric acid and valeric acid. Among them, the major chemicals being responsible for the sense of odor were butyric acid and valeric acid. 2. In a laboratory experiment using an air tight vessel, the amount of wood vinegars needed for deodorization of piggery wastes was 6.6%; The removal efficiency of the odorant chemicals volatilized from the wastes was from 70 to 90% of control levels. 3. In situ test at a piggery farm showed that removal efficiency of odorant chemicals was similar to that of the laboratory experiment. In sensory tests, authorized by the Environmental Protection Agency of Japan, minimal offensive odors were observed with the addition of 6.6% wood vinegars. Furthermore, flies were rarely observed, indicating that wood vinegars may play an important role as a repellent.

Acetates↗
PubMed1978

Inhibition of ultraviolet and phototoxic dermatitis in the mouse.

The effect of inhibitors on the inflammatory oedema elicited by medium-wave ultraviolet radiation (UVB) and long-wave ultraviolet radiation (UVA) in combination with chlorpromazine has been studied in the mouse, by means of a quantitative technique. Inhibition of the UVB reaction was observed with indomethacin, acetylsalicylic acid and betamethasone valerate, whereas the latter compound only was effective in the phototoxic state. No inhibition was obtained with hydrocortisone, phenylbutazone, epsilon-aminocaproic acid, polyphloretin phosphate, clemastin, alpha-tocopherol or ascorbic acid. With indomethacin and betamethasone valerate there was no inhibition at high doses when the compound was administered before UVB irradiation. These results are in accordance with a proposed central role for the prostaglandins in UVB inflammation. It is suggested that the phototoxic reaction to chlorpromazine may not be due to mediator action but rather to the effect of toxic photoproducts.

Animals↗