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.

[Carotenoids of the human eye in prenatal and early postnatal development].

The review deals with the role of carotenoids in the formation of the structural and functional differentiation of the macula--the area of the highest visual acuity of the human retina. The review also presents the data on detection of carotenoids (lutein) in the vitreous body of the human eye during its prenatal development and discusses their possible role in the development of the retina, particularly in relation to differentiation of the macular area. Macular dystrophy has been considered till recently as senile pathology. According to modern ophthalmologic observations, the number of cases of appearance of this pathology increases in young humans. Such a shift can be prevented by addition of carotenoids to the diet. This permits a conclusion that the permanent presence of carotenoids in the course of the whole human life is necessary for the formation and retention of structural and functional integrity of the macula.

[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.

[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).

[Regulation of the mitotic activity in the rat cornea in response to protective and therapeutic effects of para-aminobenzoic acid in experiments with roentgen radiation]. / Reguliatsiia mitoticheskoi aktivnosti v rogovitse krys pri zashchitnom i lechebnom deistvii paraaminobenzoinoi kisloty v opytakh s rentgenovskim oblucheniem.

The protective and therapeutic action of p-aminobenzoic acid (PABA), at doses effective in interferon induction (Akberova et al., 1999), was studied on the rat cornea in the experiments with X-irradiation (5 Gy). PABA at 10 mg/kg preserved the postradiation mitotic activity at the level of irradiated control, while at 1.4 and 100 mg/kg it increased the mitotic activity above the control level. In all experiments, PABA at all three doses decreased the rate of pathological mitoses in equal proportions to the total number of mitoses.

[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.

[Effect of para-aminobenzoic acid on the development of rat embryos when applied to pregnant females]. / Izuchenie vliianiia paraaminobenzoinoi kisloty na razvitie zarodyshei krys pri vozdeistvii na beremennykh samok.

In order to study the effects of para-aminobenzoic acid (PABA) on embryonic development, the pregnant rats were injected intraperitoneally daily with 0.3% PABA at 5 mg/kg (0.3 ml/200 g): in group 2 during the preimplantation period (days 1-6 of pregnancy), in group 3 during the period of organogenesis (days 6-16), and in group 4 during days 1-16. In group 5, PABA was injected intraperitoneally (at 15 mg/kg (0.3 ml/200 g, three times a day) during days 6-16 of pregnancy and in group 6, intragastrically as a suspension at 50 mg/kg during days 1-16. In the control (group 1), saline was injected intraperitoneally at 0.3 ml/200 g during days 1-16 of pregnancy. Autopsy of the females, counting of the number of yellow bodies and implantation sites and of the number of resorbed and died fetuses, and evaluation of development of the fetuses with an account of their mass, parieto-coccygeal size and placenta mass were performed on day 20 of pregnancy. Para-aminobenzoic acid at all tested doses does not exert a damaging effect and does not affect organogenesis. At doses 5 and 15 mg/kg, PABA does not affect growth but reduces the scattering of the extreme values of the parieto-coccygeal size and body mass, thus reflecting normalization of the growth of fetuses within the litter. At a dose of 50 mg/kg, the increase of body mass of the fetuses is insignificantly diminished (p < 0.05), which is usually normalized during postnatal development.

[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.