[Impressionable cytology method in diagnostics of dry eye syndrome.]

Analysis of the cellular composition of the eyeball conjunctival prints and evaluation of the informative of the cytomorphological method of research in the diagnosis of dry eye syndrome (DES). Cytological examination using impression cytology was performed in 72 patients: 60 patients with DES and 12 without eye disease (control group). The main component of cytological sample in patients with DES are (a) squamous epithelium (hyperkeratocytes); (b) groups and clusters of flattened epithelial cells; (c) a small amount (up to five in the preparation) of goblet cells. Impression cytology method improves the accuracy of diagnosis of DES.

Hypoxia as pathogenic factor affecting the eye tissues: The selective apoptotic damage of the conjunctiva and anterior epithelium of the cornea.

The effect of acute hypoxia on the occurrence of apoptosis in eye cells in rats placed in a pressure chamber was studied. Selective primary lesion of cells of the conjunctiva and the anterior corneal epithelium was found. A possible role of the simulated hypoxic conditions in the dry eye syndrome pathogenesis, which is accompanied by primary lesion of cells in the anterior eye surface tissues is discussed.

[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.

[New biological properties of p-aminobenzoic acid]. / Novye biologicheskie svoistva paraaminobenzoinoi kisloty.

p-Aminobenzoic acid (PABA) is a cyclic amino acid, belongs to the vitamin B group, and is used as a protective drug against solar insolation and in diagnostic tests for the state of the gastrointestinal tract in medicine. We were the first to establish that PABA is an inducer of endogenous interferon and immunomodulator and displays a virucidal, synergistic antiviral effect when combined with chemical drugs and the properties of a direct anticoagulant. Based on these properties, we elaborated a new medicinal drug "Actipol" which was introduced in clinical practice.

[Actipol in treating stromal herpetic keratitis]. / Aktipol v lechenii stromal'nogo gerpeticheskogo keratita.

Actipol (0.007% paraaminobenzoic acid--PABA) is a new interferon (IFN) inductor. It was recently introduced into ophthalmological practice. Its efficiency in surface herpetic keratitis is proven. We studied the therapeutic efficiency of actipol in the treatment of stromal herpetic keratitis and compared the results with combined therapy with acyclovir (ACV) and leukocytic IFN. The main group (141 patients) were treated with actipol and the reference group (40 patients) with ACV ointment and leukocytic IFN. Local injections of actipol in combination with its instillations into the conjunctival sac led to cure of 67.3% patients with stromal herpetic keratitis; this treatment was more effective than combined local ACV + leukocytic IFN therapy (clinical cure in 45% cases). Epithelialization in the actipol group was observed 2 days sooner, infiltration resorption and clinical cure 4 days sooner than in the reference group. Relatively high visual acuity in the actipol group was presumably due to the reparogenic effect on the corneal stroma and antithrombotic, fibrinolytic, and antioxidant activity of PABA. Hence, actipol is an effective drug for the treatment of stromal herpetic keratitis, exerting virtually no side effects.

[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.

[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.

[Antithrombotic activity of para-aminobenzoic acid]. / Antitromboticheskaia aktivnost' paraaminobenzoinoi kisloty.

Mechanisms of the anticoagulant activity of p-aminobenzoic acid (PABA) were studied. The specific antithrombin activity of PABA is aIIa = 7.00 +/- 0.32 IU/mg and the specific antiactivated factor Xa activity is aXa = 6.70 +/- 0.12 IU/mg. Study of the antithrombotic activity of PABA in rats with a model of venous stasis showed that intravenous injection of PABA at a dose of 1.5 mg/kg prevented the experimental thrombosis development 1.5 h after injection. The activity exhibited a peak 3 h after drug injection and ceased by the 5th hour. Equal antithrombotic activity in the rat blood plasma was observed for fraxiparin at a dose of 40 aXa IU/kg and PABA at 25 aXa IE/kg (1.5 mg/kg). At the same time, PABA affected neither the number of thrombocytes nor their response to the thrombocyte aggregation factors (ADP or adrenaline).

[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 antithrombotic activity of para-aminobenzoic acid in experimental thrombosis]. / Antitromboticheskaia aktivnost' paraaminobenzoinoi kisloty pri éksperimental'nom tromboze.

It was shown for the first time that p-aminobenzoic acid (PABA), in addition to the previously described fibrinolytic activity, exerts the properties of a direct anticoagulant both in vitro and in vivo. PABA not only displays antithrombin activity, but also inhibits activated factor X and, upon intravenous injection to rats and rabbits, shows the antithrombotic effect. The most pronounced antithrombotic affect was observed at a dose of 1.5 mg/kg. PABA at 0.5 mg/kg has insignificant efficacy and at 3 mg/kg, a high efficacy, but induces hemolysis of erythrocytes in about a half of cases. Equally efficient antithrombotic activity of blood plasma of rats was noted after intravenous injection of low molecular weight heparin "Fraxiparin" at 40 anti-Xa U/kg and PABA at 25 anti-Xa U/kg (1.5 mg/kg). Unlike "Fraxiparin", which exerts an immediate effect, the effect of PABA was expressed within 1.5 to 5 h after injection with a peak of antithrombotic activity at 3 h (which correlates with anti-IIa and anti-Xa activities of plasma) and terminated by 5 h after injection. For PABA, the ratio of anti-Xa to anti-IIa activities (an important parameter, which determines the antithrombotic potential of drugs) equals 2.4. PABA at 0.5 or 1.5 mg/kg did not affect the number of thrombocytes, while at 3 mg/kg, it decreased the number of thrombocytes by 20%. Thus PABA at 1.5 mg/kg, which has a high anticoagulant activity and does not cause side effects, is most interesting for further studies.

[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.

[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.

[Para-aminobenzoic acid in therapy of experimental keratitis caused by herpes simplex virus in rabbits: the therapeutic effect and decrease of infectious titer]. / Para-aminobenzoinaia kislota v lechenii eksperimental'nogo keratita, vyzvannogo virusom prostogo gerpesa u krolikov: terapevticheskii effekt i snizhenie infektsionnogo titra.

Para-aminobenzoic acid (PABA) in low concentrations exerted an antiherpetic effect with a good therapeutic result in rabbits with experimental keratoconjunctivitis caused by herpes simplex virus (HSV) (experimental group). In group 2 (control) 0.9% NaCl solution was used as placebo. The animals were infected by instillation of HSV-1 on the cornea predissected with a bifurcation needle. The severity of keratitis was assessed in scores after A. A. Kasparov et al. PABA and placebo were administered starting from day 3 postinfection as subconjunctival injections and then instillations. In experimental group (5 rabbits, 10 eyes) the degree of keratitis reduced from 3.0 +/- 0.2 to 1.7 +/- 0.1 points within the first 4 days. Complete epithelialization was over by day 4.4 +/- 0.4, clinical cure was attained by days 12-13. In control group (6 rabbits, 12 eyes) erosion of the cornea and severity of keratitis increased from 2.9 +/- 0.07 to 3.8 +/- 0.2 points by day 4 postinoculation after placebo was started, after which it reduced; epithelialization was over by day 8.2 +/- 0.3, clinical cure by days 13-14. Infective titer in the cornea was determined in VERO cell culture from the degree of virus-induced cytopathogenic effect and expressed in lgTCE50. On day 13 this parameter was reliably higher in the control group in comparison with the experimental (3.2 vs. 1.8), this confirming the virucidal effect of PABA.