[Effect of paraaminobenzoic acid on interleukine-6 production in patients with herpetic keratitis].

The purpose of the study was to compare the effect of para-aminobenzoic acid (PABA) (actipol) on tear interleukin-6 (IL-6) levels in patients with herpetic keratitis and in peripheral blood cells of volunteers in vitro. Enzyme immunoassay was used to measure lacrimal fluid IL-6 levels in the actipol and acyclovir groups before and 1, 2, 3, 4, and 7-8 days after therapy and after clinical recovery in 30 patients with herpetic keratitis. A control group comprised apparently healthy volunteers (n=13, 26 eyes) who used actipol instillations into the conjunctival sac 4-5 times a day. The spontaneous production of cytokines and their production in response to the induction with different PABA concentrations (0.001, 0.01, 0.1, and 10 microkg/ml) were studied on peripheral blood cells taken from 9 volunteers. In the patients with herpetic, actipol was found to reduce and normalize tear IL-6 levels while acyclovir failed to produce this effect. In the healthy individuals, actipol did not affect IL-6 production in the anterior segment of the eye. All study PABA concentrations exerted a modulating effect on the production of IL-6 in the peripheral blood cells in vitro.

[Comparative evaluation of the antioxidant activity of para-aminobenzoic acid and emoxipin in the cornea and crystalline lens (an experimental study)]. / Sravnitel'naia otsenka antioksidantnoi aktivnosti paraaminobenzoinoi kisloty i émoksipina v rogovitse i khrustalike (éksperimental'nye issledovaniia).

Antioxidant effect of paraaminobenzoic acid (PABA) in the retina upon different routes of its administration has been revealed previously. In this study we investigated the antioxidant effect of PABA in the cornea and lens of rats after its parabulbar injection. Antioxidant activity of PABA was compared to that of emoxipin. One hour after hypoxic hypoxia the animals were parabulbarly injected with PABA solutions (0.007-0.08%) and 1% emoxipin. The eyes of intact animals and rats exposed to hypoxia alone served as the control. The levels of lipid peroxidation products (hydroperoxide, malonic dialdehyde) and catalase activity in the cornea and lens were measured 1, 3, 6, and 11 h after injections. PABA in all studied concentrations essentially decreased the elevated levels of hydroperoxides and malonic dialdehyde and normalized catalase activity. The level of lipid peroxidation products and catalase activity normalized 24-28 h after hypoxia, while after PABA it normalized within 2-11 h. Antioxidant activity of emoxipin in the lens and cornea was the same as that of optimal antioxidant concentrations of PABA (0.02% for the cornea and 0.06% for the lens). Hence, PABA in a wide range of concentrations (0.007-0.06%) is characterized by sufficiently high antioxidant activity in tissues of the anterior segment of the eye (cornea and lens) upon local administration.

[Time course of interferon status of patients with herpetic keratitis during treatment with actipol, a new inteferon inducer]. / Dinamika interferonogo statusa u bol'nykh s gerpeticheskimi keratitami pri lechenii novym induktorom interferona aktipolom.

Interferon (IFN) status was evaluated in 20 patients with various forms of herpetic keratitis over the course of treatment with actipol (0.07% para-aminobenzoic acid). Actipol was injected subconjunctivally parabulbarly in combination with instillations into the conjunctival sac or only instilled, depending on the disease severity. The following parameters were evaluated: 1) total content of various IFN types in circulating blood and 2) leukocyte capacity to produce IFN in vitro in patient's whole blood cells. IFN-alpha was induced with Newcastle disease virus and IFN-beta with staphylococcal enterotoxin. Before treatment IFN-producing capacity of blood cells in vitro was decreased in 60% patients and was normal or increased in 40%. Plasma concentrations of IFN were moderately increased in 45% patients. All IFN parameters in patients with initially disordered IFN status normalized during actipol therapy and after clinical cure and did not change in the patients with initially normal IFN values. Hence, local actipol therapy in patients with various forms of ophthalmic herpes modifies IFN status.

[Effect of actipol on interferon level in tears (clinico-laboratory study)]. / Vliianie aktipola na uroven' interferona v sleznoi zhidkosti (kliniko-laboratornye issledovaniia).

High interferon-inducing activity of a new antiviral drug actipol (0.007% para-aminobenzoic acid) instilled into the eye was demonstrated in animal experiments. In the present study the effect of actipol on interferon production in ocular tissues was investigated clinically. Interferon (IFN) content was measured in washings from the conjunctiva in 20 patients with herpetic keratitis, treated by actipol. Actipol was instilled frequently or injected subconjunctivally parabulbarly. The reference group consisted of 7 patients with herpetic keratitis treated with acyclovir locally. IFN titer was the last dilution of the sample ensuring 50% cell protection in comparison with complete cell destruction in the virus control. The samples were collected before, on days 1, 2, 3, 7 of treatment, and after clinical cure. Time course of IFN concentrations was wave-like in all the patients. The peak of IFN content surpassed the initial level 2-4-fold in all patients (26.13 +/- 5.9 vs. 58.9 +/- 4.4 U/ml, p < 0.01), which seems to be due to actipol induction of IFN production in the surface structures of the eyeball. In the reference group IFN content did not increase in comparison with the control during treatment. Hence, actipol induces the production of IFN in the surface eyeball structures in patients with various forms of herpetic keratitis.

[The new interferon inducer Aktipol in the treatment of herpetic keratitis]. / Novyi induktor interferona aktipol v lechenii gerpeticheskogo keratita.

Previous experiments demonstrated the efficiency of 0.007% para-aminobenzoic acid (PABA) in the treatment of dendriform herpetic keratitis in rabbits and showed the interferonogenic activity of local administration of PABA in this concentration in ocular tissues. A new drug Aktipol based on 0.007% PABA was developed for the treatment of viral diseases of the eyes. The drug was used in the treatment of patients with surface herpetic keratitis. It was instilled into the conjunctival sac (2 drops 8-10 times a day) or instillations were combined with subconjunctival, parabulbar injections 1-3 times a week, depending on the disease severity and course. Clinical studies demonstrated that Aktipol is effective in the treatment of surface forms of herpetic keratitis (118 patients). Cure was attained in 89.8% patients in 11.3 +/- 0.6 days. Aktipol is superior to IDU (cure in 70.6% patients) and is comparable to that of acyclovir (87.7%). Aktipol accelerates ulcer healing, resorption of infiltration, and cure by 4-5 days in comparison with IDU and is comparable to acyclovir. Aktipol is better tolerated than antiviral IDU agents and acyclovir ointment.

[Para-aminobenzoic acid--an interferon inducer]. / Paraaminobenzoinaia kislota--induktor interferona.

Para-aminobenzoic acid (PABA) was shown to be an early type interferon inductor. PABA (10 micrograms/ml) induced interferon production in vitro in the cells of human peripheral blood and in vivo in albino mice (10 mg/kg). The results of the study suggested that PABA was able to induce production of interferon-alpha/beta in various immunocyte populations. By its interferonogenic activity PABA was comparable with the known interferon inductors. One of the mechanisms of the previously described in vivo antiherpes action of PABA can be attributed to its interferon inducing activity.

[The effect of Hirudo therapy on a change in the activity of retinal transport adenosinetriphosphatases in the rabbit with photic eye damage]. / Vliianie girudoterapii na izmenenie aktivnosti transportnykh adenozintrifosfataz setchatki krolika pri svetovom povrezhdenii glaz.

Effect of Hirudo therapy on the activities of transport adenosine triphosphatases (ATPases) of the retina and pigmented epithelium (PE) is studied in normal and albino rabbits whose eyes were exposed to potent illumination (100,000 Lux at the level of the cornea for 90 min). The exposure decreased the activities of ATPase, which did not recover in any of animal groups. Hirudo therapy immediately after illumination increased the enzymes activity in pigmented animals in comparison with intact control: by 20% in the retina and by 23% in PE; Mg-ATPase activity increased by 23% in the retina and decreased by 10% in PE. In subsequent 24 h, ATPase activities decreased, but in comparison with exposed retina the activity of Na,K-ATPase in the retina was 70% increased and in PE 78% increased; the activities of Mg-ATPase were increased by 33 and 8%, respectively. Complete recovery of ATPase activities was attained in 8 days. In albino animals, ATPase activities did not recover completely, but they were notably higher than in intact controls. Hirudo therapy before illumination had a marked protective effect.

[Study of interferon-inducing activity of para-aminobenzoic acid injected subconjunctivally in rabbits]. / Izuchenie interferonindutsiruiushchei aktivnosti paraaminobenzoinoi kisloty v glazakh krolikov pri subkon''iunktival'nom vvedenii.

Para-aminobenzoic acid (PABA) is an early interferon inductor. The present study assesses the interferon-inducing activity of PABA (0.007 and 0.06% solutions) and poludan (Poly A:U) injected subconjunctivally to rabbits. Interferon (If) titer in the conjunctival washings and anterior chamber humor was assessed 4-48 h after injection of If inductors. After the first injection of 0.007% PABA, If titer in the conjunctival washings was constantly increasing and reached the maximum after 48 h (64-128 U/ml). Repeated injection of PABA after 5 days still more stimulated the production of If, with the peak after 24 h (128 U/ml); after 48 h the titer of If was still high. If titers induced by 0.007% PABA and poludan were compatible after both injections in the conjunctiva but not in the anterior chamber humor. With poludan, the maximum If titer (16 U/ml) was observed 6 h postinjection, after which it was no longer detected, while after PABA the maximum If titer (64 U/ml) was observed during the 4th and 12th hours postinjection and then decreased, remaining rather high after 24 h. After 0.06% PABA, If titers were 2-4 times lower in all experiments than after 0.007% PABA. The detected interferon-inducing activity of PABA suggests its therapeutic efficacy in ocular diseases involving disorders in If production.

[Effects of Hirudo therapy on lipid peroxidation and catalase activity of the rabbit retina after light-induced eye injuries]. / Vliianie girudoterapii na perekisnoe okislenie lipidov i aktivnost' katalazy setchatki krolika pri svetovom povrezhdenii glaz.

Effect of Hirudo therapy on the level of lipid peroxidation (LPO) products and catalase activity in the retina and pigmented epithelium (PE) after exposure to intensive illumination is assessed. Light injury to the eye (100,000 lux in 90 min) leads to accumulation of LPO products and suppression of catalase activity. Hirudo therapy after potent light exposure of the eye decreased the level of hydroperoxide and malonic dialdehyde and normalized retinal and PE catalase activity, thus exerting a therapeutic antioxidant effect. Hirudo therapy before illumination did not notably protect the eye as regards the content of LPO products and catalase activity.

[Comparative assessment of antioxidant activity of para-aminobenzoic acid and emoxipin in retina]. / Sravnitel'naia otsenka antioksidantnoi aktivnosti paraaminobenzoinoi kisloty i émoksipina v setchatke.

Effect of para-aminobenzoic acid (PABA) on lipid peroxidation (LPO) in rat and guinea pig retina exposed to hypoxic hypoxia is studied. PABA was injected intraperitoneally and parabulbarly before and after hypoxic exposure. Antioxidant activities of PABA and emoxipin were compared. An intraperitoneal injection of PABA in a dose of 10 mg/kg 24 h before hypoxia virtually completely prevented accumulation of lipid peroxides and preserved catalase activity in the retina. Parabulbar injection of 0.01% PABA solution 1 h before hypoxia prevented LPO intensification, stabilized catalase activity in hypoxia, and protected the retina starting from the moment immediately after hypoxic exposure. The efficacy of 0.01% PABA is comparable with that of 1% emoxipin, and a 0.01% solution of emoxipin is less effective than PABA in the same concentration. PABA exerts an antioxidant effect after hypoxia by decreasing the abnormally high level of lipid peroxides and reducing catalase activity in the retina after parabulbar injection of the drug. All the studied concentrations of the drug (from 0.007 to 0.08%) are active, but the optimal dose for the retina is 0.04%. By its efficacy this concentration is equivalent to 1% emoxipin.