1 The chemically novel acetohydroxamic acids, BW A4C, BW A137C and BW A797C, are potent inhibitors of the synthesis of leukotriene B4 (LTB4) from arachidonic acid by human leucocyte homogenates: the concentrations required for 50% inhibition (ICjo) were 0.1 ym, 0.8 pm and 0.5 JM respectively. Inhibition was less at higher concentrations of arachidonic acid.2 These compounds also inhibited the synthesis of ["4C]-5-HETE from ["4C]-arachidonic acid and the calcium-dependent synthesis of LTB4 from 5-HPETE. This, therefore, suggests that they inhibit 5-lipoxygenase and LTA4 synthase. 3 Concentrations of acetohydroxamic acids required to inhibit metabolism of arachidonic acid by cyclo-oxygenase, 12-lipoxygenase and 15-lipoxygenase were 10 to 100 times higher than those required to inhibit 5-lipoxygenase. 4 The compounds were potent inhibitors of LTB4 synthesis induced by the ionophore, A23187, in human intact leucocytes. This inhibition was reversed by washing the cells. They were also potent, selective inhibitors of LTB4 synthesis induced by A23187 in whole rat blood: binding to rat plasma proteins did not greatly reduce the effectiveness of the compounds. 5 The effects of the acetohydroxamic acids, administered either intravenously or orally to rats, on the synthesis of LTB4, and thromboxane B2 (TXB2) in A23187-stimulated blood ex vivo was studied. The three compounds caused dose-dependent inhibition of the synthesis of LTB4 but not

Myeloperoxidase (MPO) activity was measured in rabbit cornea and iris-ciliary body to quantitate the infiltration and accumulation of polymorphonuclear leucocytes (PMN's) following an inflammatory stimulus. Following injection of clove oil into the cornea, MPO activity could be detected in the cornea at 6 hr, reaching a maximum at 12 hr, and falling to non-detectable levels at 72 hr. MPO activity was only detected in the iris-ciliary body 24 hr after intracorneal clove oil injection. MPO activity in the iris-ciliary body increased in a dose-dependent manner following intravitreal injection of endotoxin. No MPO activity could be detected in cornea. Topical administration of dexamethasone inhibited MPO activity in cornea and iris-ciliary body 24 hr after intracorneal clove oil and intravitreal endotoxin injection, respectively. Measurement of MPO activity in ocular tissues could provide a useful tool to quantitatively evaluate the severity and time course of inflammation.

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We have compared the sensitivity of the prostaglandin synthetase systems derived from microsomal fractions of rabbit ocular tissues (anterior uvea, conjunctiva and retina) with other rabbit tissues such as the kidney medulla and spleen, to inhibition by indomethacin. Generation of prostaglandin‐like activity by the microsomal fractions from added arachidonic acid varied with the tissue used. Highest activity was found in the kidney medulla, then in descending order, the conjunctiva, anterior uvea, spleen, retina and cornea. Indomethacin was most potent in the spleen (ID50 0.045 μg/ml) then in decreasing order in the kidney medulla, conjunctiva, anterior uvea and weakest in the retina, where the ID50 for indomethacin was 50 μg/ml. The differential sensitivity to inhibition of the prostaglandin synthetase systems from different tissues is an important consideration in the development of new ocular anti‐inflammatory agents.