[Control of the rabbit's IOP after topic instillation of antiglaucomatic latanoprost and amino acid arginine with lysine mixture]. / Regulácia VOT králikov topickou insti- láciou zmesi antiglaukomatika latono- prostu s aminokyselinami arginínom a lyzínom.

PURPOSE: To evaluate the effect of locally instilled 10% L-arginine.HCI and 10% L-lysine.2HC1.2H20 in 0.005% Latanoprost (Xalatane) mixture on the physiological IOP in rabbits. METHODS: After instillation of the arginine and lysine in 0.005% latanoprost mixture into the left conjunctival sac of 5 female rabbits of the New Zealand White species the, IOP was measured at the time of instillation, and 5, 15, 30, 60, 120, 180, 240 min. and 24 hours after the instillation. The right eye was used as the control. RESULTS: The mixture of arginine with lysine in 0.005% latanoprost decreased significantly the IOP value. The decrease had two peaks. The major decrease of the IOP was observed after 30 min. (3.1 mmHg) and after 24 h (5.0 mmHg) after instillation of this mixture. Between 120 min. and to 240 min., the mild decrease of the mean value of the IOP was found at the control eye as well. CONCLUSIONS: The mixture of arginine with lysine in 10 % concentration in 0.005 % latanoprost (Xalatane) decreased significantly the physiological IOP values in rabbits during the whole experiment. The decrease was significant in comparison both to the IOP of the control eye and to the effect of the amino acids arginine and lysine alone.

[Changes of the physiological intraocular pressure (IOP) values after the application of latanoprost and amino acid glycine mixture in rabbits]. / Odpoved' fyziologického vnútroocného tlaku králikov na latanoprost s amino kyselinou glycín.

PURPOSE: The influence of the mixture of amino acid 10% L-glycine.HCl and antiglaucomatic 0.005% Latanoprost (XALATAN) on the physiological IOP values in rabbits is evaluated in this paper. METHODS: Experiments were performed on 5 female rabbits of the New Zealand White species. The 0.005% Latanoprost alone, the 10% L-glycine.HCl alone and the mixture of 10% L-glycine.HCl in 0.005% Latanoprost were instilled into the left conjunctival sac. The IOP and pupillary diameter were measured before, and 5, 15, 30, 60, 120, 180, 240 minutes and 24 hours after the instillation. The right eye was used as control. RESULTS: a/ after the instillation of the 0.005% Latanoprost, the significant decrease of the physiological IOP in rabbits was found 5, 15, and 30 min after the application. Maximal decrease (by 33.6%) was measured after 30 min. In the period from 60 to 240 min., the IOP decrease occurred also in the control eye; b/ decrease of the IOP after the instillation of the amino acid L-glycine.HCl (10% concentration) has no significant value; after 15, 30 and 60 min, the IOP decreased also in the control eye; c/ after the instillation of the 10% L-glycine.HCl and 0.005% Latanoprost mixture the physiological IOP showed no significant decrease during 24 hours. The physiological IOP values of the control eyes during this experiment remained unchanged. CONCLUSIONS: The effect of the mixture of 10% amino acid L-glycine.HCl in 0.005% Latanoprost on the decrease of the physiological IOP values in rabbits was not significant. The average decrease of the IOP value was the same as the non-significant decrease of the individual components.

[The effect of glycine with timoptol on the rabbit IOP physiological values]. / Ucinok glycínu s Timoptolom na fyziologické hladiny VOT králikov.

PURPOSE: the mixture of 10% L-glycine.HCl in 0.5% Timoptol, intensity and duration of effect on the physiological IOP is evaluated in this work. METHODS: Experiments were performed on 5 rabbits of the New Zealand White species. The mixture and its components were individually instilled into the left conjunctival sac. The right eye was used as control. RESULTS: after instillation of the 10% L-glycine.HCl and 0.5% Timoptol mixture the IOP showed significant decrease compared with the control eye during 24 hour evaluation. Maximal decrease for 33% (8.5 torr) was measured in 60th min., compared with the decrease for 30.5% (7.6 torr) in 120th and for 28% in 30th min. On the contrary, both substances alone--the 10% L-glycine.HC1 and 0.5% Timoptol decrease the physiological IOP values only no significantly compared with their mixture and the control eyes. The mean value of the pupilar diameter was 7.8 mm on both eyes. CONCLUSIONS: We assume that the decrease of the physiological IOP value is caused by a new metabolite--the "bioantiglaucomatic" created by interaction of glycine and Timoptol in vitro. The effect of this mixture on the decrease of the physiological IOP values is 8-times stronger compared with Timoptol and 4.3-times stronger compared with glycine. Application of such already prepared bioantiglaucomatic in the clinical practice can contribute to the more effective, safe and reliable therapeutic effect on the IOP in glaucomatic disease.

[Reduction of the physiologic IOP value after instilation of the mixture of the 2 amino acid's (L-lysine and L-arginine) in timoptol--experiment on rabbit's]. / Redukcia fyziologickej hodnoty VOT zmesou 2 aminokyselín (lyzínu a arginínu) v Timoptole v experimente u králika.

UNLABELLED: To evaluate influence of mixture of the 2 amino acids (L-arginine-HCL and L-lysi-ne.2HCL.H2O) in the antiglaucomatic--beta-blocker Timoptol--on the physiologic intraocular pressure (IOP) in rabbits (experiment). METHODS: The mixture of 10% L-lysine.2HCL.H2O + 10% L-arginine.HCL in 0.5% Timoptol was instilled into the left conjunctival sac of the 5 adult rabbit's (female of the New Zealand White species) and the right eye was used as control. The IOP and pupilar diameter were measured before and in 5th, 15y th, 30th, 60th, 120th, 180th and 240th min. and 24 hours after the instillation. RESULTS: The experimental results proved that the non-selective beta-blocker Timoptol interacts at the same time with two amino acids. The mixture of 10% L-lysine.2HCL.H2O + 10% L-arginine.HCL in 0.5% Timoptol decreased the physiologic IOP in two phases. The first phase started from application up to 15th min. In this period parallel IOP decrease occurred also in control eye (with no significant difference). The second phase started in 30th min. after the instillation and lasted until the end of experiment. In this phase the control eye IOP remained linear after the initial over the baseline increase. The eye with instilled mixture showed significant IOP decrease (p < 0.01). Maximum difference between the two IOP's was measured in the 180th (7.3 mmHg; 35.4%). From this moment IOP slightly increased up to the 24th hour showing still significantly lower level--5.0 mmHg (24.3%) compared with the control (p < 0.01). CONCLUSIONS: Results proved that in the mixture of 10% L-lysine.2HCL.H2O + 10% L-argi-nine.HCL in 0,5% Timoptol a new substance, the "specific bioantiglaucomatic" is created by interaction. Compared with the substances alone, mixture of the 2 amino acids in the antiglaucomatic decreased the physiologic intraocular pressure (IOP) in rabbits (experiment) with high significance for 24 hours.

[Changes of physiological intraocular pressure (IOP) in rabbits after administration of the amino acid lysine and the antiglaucoma drug latanoprost (Xalatan)]. / Zmeny fyziologického VOT u králikov po aplikácii aminokyseliny lyzínu s antiglaukomatikom latanoprostom (Xalatanom).

PURPOSE: To show and underline specific character of influence of the mixture of 10% L-lysine.2HCl.2H2O in 0.005% latanoprost on physiological levels of IOP. METHODS: The mixture of 10% L-lysine.2HCl.2H2O in 0.005 % latanoprost (Xalatan), or separately 0.005 % latanoprost and 10% L-lysine.2HCl.2H2O respectively were in weekly intervals instilled into the conjunctival sac of the left eye of five rabbits (females of "New Zealand white" bred). The IOP levels and the size of the pupil were measured in minute 5, 15, 30, 60, 120, 180, and 240 after the instillation. The right eye was considered as a control. RESULTS: The amino acid L-lysine.2HCl.2H2O by itself did not influence the IOP or the size of the pupil; latanoprost until minute 30 lowered the IOP, in minute 55 exceeds the IOP the level of the control eye. Since minute 60 until 240, the IOP changed irregularly and insignificantly. The mixture of 10% solution of L-lysine.2HCl.2H2O in latanoprost 0.005% insignificantly lowered the IOP until min. 30, after rapid elevation in min. 50 exceeds the IOP of the control eye, and since min. 60, the IOP remains above the control eye's IOP with the same course of levels. SUMMARY: The amino acid L-lysine.2HCl.2H2O alone did not change the physiological IOP. Latanoprost 0.005% significantly lowered the IOP until min. 30. High level of interactive specificity as well as duration of influence of the mixture of respective amino acid with respective antiglaucomatic drug was established.

[The rabbit IOP and pupil values after application of aminoacid L-lysine and antiglaucomatic Timoptol mixture]. / Ucinok zmesi aminokyseliny L-lyzínu v antiglaukomatiku Timoptole na vnútroocný tlak a pupilu králikov.

OBJECTIVE: In this article authors focused to influence the physiologic IOP values after application of the aminoacid 10% L-lysine.2HCl.2H2O in 0.5% Timoptol eye drops mixture in experiments. METHODS: 0.5% Timoptol, followed by 10% L-lysine.2HCl.2H2O and mixture of 10% L-lysine.2HCl.2H2O with 0.5% Timoptol was instilled weekly into the left conjunctival sac of 5 adult rabbits (females of the New Zealand White species). The IOP and pupilar diameter were measured in 5, 15, 30, 60, 120, 180 and 240 min. after instillation. The right eye was used as control. RESULTS: In experiments authors observed that: a) the aminoacid 10% L-lysine.2HCl.2H2O is without influence on the physiologic value of the IOP; b) 0.5% Timoptol compared with control eye nonsignificantly decreased the rabbit IOP; c) after instillation of 10% L-lysine.2HCl.2H2O and 0.5% Timoptol mixture the IOP showed decrease of the physiologic IOP in two periods. The initial non-significant period of the IOP decrease was measured after application up to the 60th min. The identical values were also in the control eye. However, the major decrease of the IOP compared with control eye was observed during the second period starting from 60th min. up to the end of experiments (to the 4th hour) after instillation of this mixture. The mean value of this significant decrease was 3.3 torrs of the physiologic IOP value showing regular and linear effectivity in the experimental eye. In the control eye the second period was without decrease of the IOP. CONCLUSIONS: The results demonstrate that the Timolol alone decreased the physiologic IOP no significantly, the aminoacid L-lysine.2HCl.2H2O is without influence on the physiologic value of the IOP. In experiments we confirmed that in a mixture of aminoacid L-lysine.2HCl.2H2O with antiglaucomatic 0.5% Timoptol a new substance was created, a new "bio-antiglaucomatic", responsible for more significant decrease of the physiologic IOP.

[IOP in rabbits after instillation of a mixture of the antiglaucomatic Cosopt and the aminoacid L-argininin HCL into the conjunctival sac]. / Vnúitroocný tlak králikov po instilácii zmesi antiglaukomatika COSOPTu s aminokyselinou L-arginínom.HCL do spojovkového vaku.

OBJECTIVE: The article documents results of experiments focused to influence the physiological IOP values after application of the COSOPT eye drops (double combination of bbb-blocker and carbonic anhydrase inhibitor), aminoacid 10% L-arginin.HCl and their mixture in rabbits. METHODS: COSOPT followed by 10% L-arginin.HCl and mixture of 10% L-arginin.HCl with COSOPT was instilled weekly into the left conjunctival sac of 5 adult rabbits (females of the New Zealand White species). The IOP and pupilar diameter were measured in 5, 15, 30, 60, 120, 180, 240 min. and 24 hours after instillation. The right eye was used as control. RESULTS: The antiglaucomatic COSOPT no significantly decreased the rabbit IOP during 24 hours (mean value 1.85 %) in vivo. The aminoacid 10% L-arginin.HCl achieved significant decrease of the IOP: the mean value was 16.03% reaching maximum in 60th and 180th min. After instillation of the 10% L-arginin.HCl and COSOPT mixture in the IOP showed significant decrease with mean value of 9,64% (except values in 5th min. and 24th hour). Compared with control eye, the major decrease of the IOP was measured in 240th min. (mean value 17.98%). However even in 24 hours after instillation the IOP was not reaching the values of the control eye, shoving also the IOP decrease. CONCLUSION: We assume that in a double combination of antiglaucomatics in COSOPT a new substance was created. This substance interacted in vitro with the aminoacid 10% L-arginin.HCl resulting in a new "bio-antiglaucomatis" better penetrating into the target area. This new substance was responsible for more significant decrease after the mixture application compared with COSOPT alone. The presence of aminoacid can slow down the undesirable effect of the antiglaucomatics together with the possible neuroprotection.

[Reaction of the physiological IOP in rabbits after application of the latanoprost (Xalatan) and amino acid L-arginine HCl mixture]. / Reakcia fyziologického vnútroocného tlaku králika na Latanoprost (Xalatan) a jeho zmesi s aminokyselinou L-arginínom x HCL.

Authors present results of series of experiments focused to influence the IOP by antiglaucomatics in rabbits (New Zealand White) with physiological IOP. Adding of the 10% amino acid L-arginine x HCl to the 0.005% Xalatan eye drops intensifies activity of antiglaucomatics resulting in 9.5% average reduction of the IOP in a four-hour experiments (with maximum in 15th min.--19.3%), compared with application of both substances alone. Size of the pupil was not affected. Based on our experimental results we assume that the increased activity of the 0.005% Xalatan mixture with 10% amino acid L-arginine x HCl created a new complete metabolite--"bio-antiglaucomaticum". According to our observations this metabolite caused increase of the uveo-scleral outflow leading to the striking reduction of the physiological IOP in rabbits.

[Comparison of the effectiveness of a mixture of 10% L-arginine and HCl combined with 0.5% Timoptol and with 2% Trusopt: and the individual components on intraocular pressure in an experiment on rabbits]. / Porovnanie efektivity zmesi aminokyseliny 10% L-arginínu x HCl v 0.5% timoptole a v 2% trusopte a jednotlivých zloziek na VOT v experimente u králikov.

The presented experimental work is focused to examine effectivity of the amino acid 10% L-arginine x HCl mixture with antiglaucomatic--2% Trusopt (carbonic anhydrase inhibitor) and with 0.5% Timoptol (non-selective beta-blocker) and of the each single compound on intraocular pressure (IOP). In the group of 5 rabbits (New Zealander White) with physiological levels of IOP already the single amino acid L-arginine x HCl decreased the IOP (for 18.4% compared with 0.5% Timoptol and for 9.7% with 2% Trusopt). In case of mixture with the mentioned antiglaucomatics the L-arginine x HCl significantly increases their activity. The showed results indicate the presence of the free amino acids and their interaction with the adequate antiglaucomatic is required for correct action. Based on this interaction a new bio-active metabolite is created (possibly called as "bio-antiglaucomatic").

[Intraocular pressure in rabbits after administration of 10% L-arginine HCl in 2% Trusopt]. / Vnútroocný tlak králikov po aplikácii 10% L-arginínu.HCl v 2% Trusopte.

In this contribution publish the observation that addition of 10% L-arginin.HCl to the 2% Trusopt eye drops intensifies activity of antiglaucomatics with an important reduction of the normal intraocular pressure (IOP) in rabbits New Zealand white namely from 15 up to 240 minutes, compared with application of both substance alone. Size of the pupil was not affected. Based on our experimental results we assume that this increasing activity of Trusopt mixture with amino acid L-arginin.HCl created a new metabolite. According to our observations this metabolite caused reduction of the humor aqueous production and together with the increased of the uveo-scleral outflow leads to the striking reduction of the IOP.

[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits]. / Zmes timoptolu s L-arginínom.HCl: regulátor vnútroocného tlaku u králikov.

In our experimental study were determined changes IOP an pupil after application mixture of aminoacid 10% L-arginine.HCl in 0.5% Timoptol into the conjunctival sac of left eye of 5 healthy albinotic rabbits (the New-Zeland White species). The right eye was control. Our results proved that the mixture of 0.5% Timoptol with 10% L-arginine.HCl has significantly decreases IOP against the control eye during the whole experiment. The maximum of decrease IOP was reached in 60th min. (20.1%; 4 torr) and in 240th min. (10.7%; 2.1 torr). In comparison with effect of mixture of both compartments, the 10% L-arginine.HCl and 0.5% Timoptol applicated alone caused only non-significant IOP decrease. Papilar diameter in both eyes were identical (7-7.5 mm) during the whole experiment. We suggest that the interaction of L-arginine.HCl with Timoptol causes formation of the new metabolite which is, in fact already effective component; this new substance decreases production of aqueous humor of corpus ciliare and the IOP is decreased in this way in physiological conditions. Utilization of this knowledge in clinical conditions could contribute to better utilization and more harmless use of antiglaucomatics in glaucoma disease therapy. For that reason, more longtime studies should be performed to evaluate the effect of this new metabolite in local application.

The free amino acids and the aqueous humor pH after antiglaucomatics in vitro.

Authors present comparison of the previous results on the influence of free amino acids of the aqueous humor in rabbits and human on the pH of the aqueous humor in vitro. Four clinically used antiglaucomatics were added (2% Trusopt--pH 5.33; 0,005% Xalatan--pH 6.4; 0.5% Timoptol--pH 6.80 and 1% Pilocarpine--pH 5.87) into the aquired aqueous humor of rabbits (pH 7.59) and human (pH 7.11 +/- 0.11). After their instillation pH of the aqueous humor immediately decreased towards acid levels. The pH changes after Timoptol, Xalatan and Pilocarpine showed a similar time pattern and after return to the baseline values the pH shifted to alkaline levels. In case of Trusopt instillation the pH value reached the baseline of the aqueous humor after 240 min. Almost no pH changes were recorded from 240 min up to 24 hours after all tested antiglaucomatics. From the wiev on the speed of activity and effectivity depending on time required to reach the initial pH value of the aqueous humor we to make this order: Pilocarpine>Timoptol>Xalatan>Trusopt. Comparing our results the effect of antiglaucomatics is connected with different composition and also with shift of the aqueous humor pH towards slightly alkaline level (similar effect in rabbits and human). Results presented in this work are theoretical but also practical contribution to the treatment of glaucoma. (Fig. 1, Ref. 38.).

[Physiologic significance of the interaction between timolol and free amino acids in eye structures]. / Fyziologický význam interakcie timololu s volnými amínokyselinami v struktúrach oka.

The authors analyze the interaction of timolol maleate (Timoptol, Léciva Prague) with free amino acids with regard to the effect on intraocular pressure. The different colour reaction of an amino acid mixture with Timoptol, the decline of radioactivity of Na[I125] tyrosine with Timoptol and the formation of 8 radioactive fractions after addition of Timoptol to Na[I125] indicate: a) the specificity of interaction of each amino acid with Timoptol; b) suggest that between Timoptol and free amino acids a firm covalent bond develops with the concurrent development of a new biologically active metabolite. Evidence of the presence of a new metabolite is important from the aspect of understanding and more accurate definition of the action of Timoptol in tissue structures of the eye and thus also for possible effective treatment of glaucoma.

[Change in the pH of aqueous humor after administration of anti-glaucoma agents in rabbits in vivo]. / Odpoved' pH komorového moku králikov na antiglaukomatiká za in vivo podmienok.

In this contribution the activity of antiglaucomatics--2% pilocarpine (pH 5.98), 0.5% timoptol (pH 6.58) and 0.005% xalatan (pH 6.83) is emphasized from the view of pH values and changes of the pH values of the rabbit aqueous humor in vitro after their application. The rabbit's aqueous humor pH is 7.59--similar to the human healthy eye (7.5-7.6). We observed that these antiglaucomatics decrease the aqueous humor pH to the acid levels in the following order: 2% pilocarpine > 0.5% timoptol > 0.005% xalatan. The most significant decrease was measured immediately after the application. From the view of speed of response and effectivity in time achieving the pH of the normal aqueous humor we constate the following order: 0.005% xalatan > 0.5% timoptol > 2% pilocarpine. The changes in pH of the aqueous humor after application of these antiglaucomatics are directly connect with their physiologic function in the eye. Moreover, they also point out the importance of the pH dependence of the antiglaucomatics applicated into the conjunctival sac in the treatment of the glaucoma disease.

[The pH reaction in aqueous humor to antiglaucoma agents of various concentrations and pH levels]. / Odpoved' pH komorového moku l'udí na antiglaukomatiká s rôznou koncentráciou a pH.

The authors investigated the effect on pH of the aqueous humour in man (collected before surgery of senile cataract, where the pH of the aqueous humour was within the range of 6.80-7.46 (7.11 +/- 0.11), after administration of antiglaucomatic drugs with a different concentration and pH (0.005% Xalatan--pH 6.43, 0.5% Timoptol--pH 6.80, 1% Pilocarpine--pH 5.87, 2% Trusopt--pH 5.33) under conditions in vitro. All mentioned antiglaucomatic drugs immediately reduced the pH of the aqueous humour towards acid values in the following order: Trusopt-Xalatan-Pilocarpine-Timoptol. pH changes of aqueous humour after addition of Timoptol, Xalatan, Pilocarpine have the same course in time, and shift to alkaline pH values. The pH of aqueous humour after addition of Trusopt reached only during the 240th minute levels of the control aqueous humour. The pH values after all antiglaucomatic drugs did not change between 240 minutes and 24 hours. As regards the rate of activity and extent of effect in conjunction with the time when the pH of the control aqueous humour was attained the authors recorded the following order: Pilocarpine-Timoptol-Xalatan-Trusopt.