dinoprost and Erythema

Hypotensive and other ocular effects were studied for 24 hr after topical application of prostaglandin F2 alpha as the tromethamine salt (PGF2 alpha) in 45 normotensive human subjects. After baseline intraocular pressure (IOP) measurements, 62.5 micrograms, 125 micrograms and 250 micrograms of PGF2 alpha dissolved in 50 microliter of saline was applied to one eye of 15 subjects for each dose tested. Contralateral control eyes received 50 microliter of saline. As compared with the IOP of the contralateral control eyes, topical application of 62.5 micrograms PGF2 alpha caused a significant IOP reduction at 1-12 hr, with a maximal IOP reduction of 2.2 mm Hg at 2 hr. Treatment with 125 micrograms of PGF2 alpha lowered IOP significantly at 1-21 hr, with a maximal reduction of 3.1 mm Hg at 9 hr. Administration of 250 micrograms PGF2 alpha produced a significant reduction of IOP, which lasted for at least 24 hr. A maximal IOP reduction of 2.9 mm Hg occurred at 7 hr. Pupillary diameter was not altered. Aqueous flare and anterior chamber cellular response were not seen in any of the eyes of the subjects at any time after topical application of 62.5-250 micrograms PGF2 alpha. The drug caused side effects consisting of reddened skin of lower lid, ocular irritation, conjunctival hyperemia and headache.

Topics: Administration, Topical; Adult; Dinoprost; Erythema; Eye; Female; Headache; Humans; Hyperemia; Intraocular Pressure; Male; Middle Aged; Reference Values; Time Factors

Sunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids, and their subsequent metabolism by cyclooxygenases (COXs) and lipoxygenases (LOXs) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and, for 72 h, examined expression of proinflammatory and anti-inflammatory eicosanoids using LC/ESI-MS/MS, and examined immunohistochemical expression of COX-2, 12-LOX, 15-LOX, and leukocyte markers, while quantifying clinical erythema. We show that vasodilatory prostaglandins (PGs) PGE(2), PGF(2alpha), and PGE(3) accompany the erythema in the first 24-48 h, associated with increased COX-2 expression at 24 h. Novel, potent leukocyte chemoattractants 11-, 12-, and 8-monohydroxy-eicosatetraenoic acid (HETE) are elevated from 4 to 72 h, in association with peak dermal neutrophil influx at 24 h, and increased dermal CD3(+) lymphocytes and 12- and 15-LOX expression from 24 to 72 h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72 h. Sunburn is characterized by overlapping sequential profiles of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.

Topics: Adult; Alprostadil; CD3 Complex; Cyclooxygenase 2; Dinoprost; Dinoprostone; Eicosanoids; Erythema; Female; Humans; Hydroxyeicosatetraenoic Acids; Lipoxygenase; Male; Middle Aged; Neutrophil Infiltration; Skin; Spectrometry, Mass, Electrospray Ionization; Sunburn; Tandem Mass Spectrometry; Ultraviolet Rays

Oral administration of niacin (nicotinic acid) at pharmacologic doses that reduce serum cholesterol levels induces intense flushing in humans. We have recently shown that the vasodilation following ingestion of niacin is due to the release of prostaglandin (PG) D2. However, the site from which PGD2 is released is not known. It has previously been shown that topical application of methylnicotinate causes local cutaneous erythema. Thus, we investigated whether topical methylnicotinate causes a release of PGD2 locally from skin and the possibility that skin may be a major contributor to the release of PGD2 when niacin is administered by mouth. Topical administration of methylnicotinate (10(-1) M) to the forearms of human volunteers resulted in 58- to 122-times increases in levels of PGD2 and 25- to 33-times increases in levels of the metabolite of PGD2, 9 alpha,11 beta-PGF2, in blood drawn from the antecubital vein draining the treated sites. Increased levels of PGD2 and 9 alpha,11 beta-PGF2 were not found in blood drawn simultaneously from veins in the contralateral arm, indicating that the PGD2 was released from the site of methylnicotinate application. The release of PGD2 in response to topically applied methylnicotinate occurred in a dose-dependent manner over the concentration range of 10(-3) to 10(-1) M. The release of PGD2 was not accompanied by a release of histamine, suggesting that the release of PGD2 was not from the mast cell. Following oral ingestion of niacin, levels of PGD2 in superficial venous blood draining the skin were 14 to 1200 times higher than the level in arterial blood supplying the skin of the same arm. This finding indicates that the skin is a major site from which PGD2 is released following oral ingestion of niacin. These studies thus indicate that the cutaneous vasodilation that occurs following oral administration of niacin is primarily due to a release of PGD2 from a niacin responsive cell that resides in the skin.

Topics: Administration, Oral; Administration, Topical; Adult; Dinoprost; Erythema; Histamine Release; Humans; Mast Cells; Middle Aged; Niacin; Nicotinic Acids; Prostaglandin D2; Skin; Vasodilation

Prostaglandin (PG) production by guinea pig epidermal cells was evaluated at various incubation intervals in normal and UV-exposed cultures. Prostaglandins have been implicated as mediators of the early phase of erythema in skin exposed to sunlight or UV-radiation. Using a density gradient centrifugation procedure, the epidermal cells were fractionated according to the various maturation stages of epidermal keratinocytes: high-density epidermal cells (HDEC) consisting of round, less mature cells; low-density epidermal cells (LDEC) consisting of polygonal keratinized cells; and intermediate-density epidermal cells (IDEC) consisting of both HDEC and LDEC. When cultures of 1 X 10(6) cells were incubated at 37 degrees C in 5% CO2 the highest concentrations of five PG moieties measured were present in supernatants from the LDEC cultures as compared to those of IDEC or HDEC. Levels of PGF 2 alpha were much higher than the rest, which were found in the order PGF2 alpha greater than PGE2 greater than PGE1 greater than 6-keto-PGF1 alpha greater than thromboxane (TX)B2. UV-irradiation induced increases in all but TXA2 production. These results identify and quantitate five compounds produced as a result of exaggerated activity of the cyclooxygenase induced by UV-irradiation.

Topics: Animals; Cell Differentiation; Dinoprost; Erythema; Female; Guinea Pigs; In Vitro Techniques; Prostaglandins; Prostaglandins F; Skin; Ultraviolet Rays

The inside skin of the forearm of healthy volunteers was irradiated with an infrared (IR) lamp for 1 hr, resulting in the rapid appearance of an erythema and an elevation of skin surface temperature from 30 +/- 1 degree C to 38 +/- 2 degrees C within 5 min. The erythema and elevated skin surface temperature decayed within 10-30 min when the IR irradiation was stopped. Suction blisters were raised on nonirradiated skin and on irradiated skin both during irradiation and at various times after irradiation stopped. Elevated levels of free arachidonic acid, PGE2, PGD2, PGF2 alpha and 6-oxo-PGF1 alpha were found up to 24 h after irradiation. By 48 h the prostaglandin levels had returned to control values whereas the free arachidonic acid levels were still elevated at 72 h. The peak level of 6-oxo-PGF1 alpha appears between 0-6 h whereas for PGE2, D2, and F2 alpha it is between 6-16 h, suggesting a different cellular source for this prostaglandin.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Arachidonic Acids; Dinoprost; Dinoprostone; Erythema; Female; Forearm; Humans; Male; Middle Aged; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Skin; Skin Temperature; Ultraviolet Rays

1 In order to test the proposal that the anti-inflammatory effect of corticosteroids is attributable to inhibition of release of the prostaglandin precursor, arachidonic acid, the effect of systemic prednisolone on arachidonic acid and prostaglandin levels in abdominal skin of six patients receiving this treatment for alopecia totalis, was studied. 2 Inflammation was produced in an area of abdominal skin by topical application of 5% w/w tetrahydrofurfuryl nicotinate (THFN) cream. 3 The erythema produced was assessed visually, and exudate recovered from normal and inflamed skin, by a suction bulla technique. 4 Arachidonic acid and PGE2 and PGF2 alpha levels, as measured by gas chromatograph-mass spectrometry (GC-MS) were significantly elevated in the reddened (THFN) treated skin, compared with control areas. 5 After prednisolone treatment both arachidonic acid and prostaglandin levels in THFN-treated areas were suppressed near to values obtained from untreated skin, before prednisolone therapy. There was partial reduction of THFN induced erythema in three out of six subjects. Levels of arachidonic acid on control skin were not affected by the steroid. 6 These results provide direct evidence that steroids inhibit prostaglandin formation by blocking evoked rise in the concentration of free arachidonic acid. The relationship of this effect, in human skin, to the anti-inflammatory action of systemic steroids is uncertain.

Topics: Adolescent; Adult; Arachidonic Acids; Dermatitis; Dinoprost; Dinoprostone; Erythema; Furans; Humans; Male; Middle Aged; Nicotinic Acids; Prednisolone; Prostaglandins; Prostaglandins E; Prostaglandins F; Skin