[Biopharmaceutical and clinico-pharmacological research on the intramammary preparation Cephamasten]. / Biofarmatsevtichni i klinikofarmakologichni prouchvaniia na intramamarniia preparat tsefamasten.

An animal drug formula, Cephamasten, for intramammary application in the treatment of mastitis-affected cows, ewes, and goats in the lactation period was worked out on the base of microbiologic, technologic, biopharmaceutic, and clinico-pharmacologic studies. Its active ingredient was the Pharmachim cephalexin-monohydrate. The consistence of Cephamasten has proved suitable for intracisternal introduction. It is tolerated well within the udder of cows, and it rapidly releases the antibiotic incorporated in it. The milk of the treated quarters has proved free from cephalexin after the 72nd hour of the last infusion. Cephamasten has shown high effectiveness in the treatment both of the preclinical and of the acute clinical mastitis. In the first case best results were obtained with the twofold treatment at a 24-hour interval, and in the second case--with the sixfold treatment at 12-hour intervals (intracisternal introduction of the preparation). In the case of generalized mastitis, in dependence on the severity of the process Cephamasten is to be applied at 4-6-12 intervals along with frequent milking and the parenteral application of other agents.

[Preclinical research on drug forms containing rifamycin SV intended for intramammary use]. / Predklinichni izsledvaniia vurkhu lekarstveni formi, sudurzhashti rifamitsin SV, prednaznacheni za intramamarna upotreba.

It was established, that LD50 of rifamycin SV--sodium salt, produced by the Research Institute on Microbiological Industry--Razgrad (People's Republic of Bulgaria)--RM, at p.o. applying on albino mice, albino rats and broilers is correspondingly greater than 4100.0 mg/kg m., greater than 5740.0 mg/kg m. and 1951.6 (1355.5 divided by 2810.1) mg/kg m. and at s. c. introducing into albino mice--815.9 (756.9 divided by 879.9) mg/kg m. From the prepared on the basis of RM-4 intramammary medicaments--RM-1, RM-2 and RM-3 for lactating cows and RM-4 for cows in the dry period, a good bearing have RM-1, RM-3 and RM-4. RM-1, RM-2 and RM-3, applied intracisternally a single time on lactating cows, and RM-4 on cows in the dry period, create antimicrobial levels with duration correspondingly 168, 72 and 48 h, and 35 days. RM almost does not penetrate in the neighbouring not treated quarters. Appropriate medicament for the lactating cows with average duration of emission is RM-3 (term of action 96 h) and for cows in the dry period RM-4 when applied 35 days before the calving.

[Postgraduate training in veterinary pharmacology]. / Sleddiplomno obuchenie po veterinarna farmakologiia.

The system of postgraduate training of veterinary pharmacology in the European countries is different--in some countries it is connected mainly with the intensive research work and with the obtaining of academic ranks (Ph. D., Dr. Sc.), in others--with attendance at special courses, with nonobligatory research work and with the obtaining of certificates (diplomas); in more countries are organized short-term courses for qualification and refreshment of the knowledge of the pharmacologists. There are no special forms of post-graduate work of pharmacologists for the pharmaceutical industry. Proposals are brought forward for postgraduate work of veterinary pharmacology in the range of European Association of Veterinary Pharmacology and Toxicology (E. A. V. Ph. T.)--unified system of special courses (long-term and middle-term) for specialization of the higher graduates and forms of education, connected with the obtaining of academic rank. There are recommended definite courses, including international, for raising the qualification and for refreshment of knowledge of the working veterinary pharmacologists, also courses, organized with the help of outstanding guest-scientists, invited in definite countries, and mutual visits of institutes and laboratories. For pharmacologists, in the pharmaceutical industry is recommended preliminarily 2-years education in universities or academies, and after that a special education in the research laboratories of the pharmaceutical firms. It is usefull for all courses to use not only the classic forms of education--lectures, but as well films, videos, computers etc.(ABSTRACT TRUNCATED AT 250 WORDS)

[Ergotrophic action of flavophospholipol during the fattening of geese]. / Ergotropnoto deistvie na flavofosfolipola pri ugoiavane na guski.

Experiments were carried out with a total of 144 geese of the Benkovska breed divided into 6 groups of 24 birds each. The average weight was 3.5 kg, the birds being compulsory fattened with steamed maize over an average period of 27 days. Flavophospholipol (flavofarm-NIHFI) was given at rates of 0, 4, 8, 12, and 16 ppm. The method of positive control check was employed--a group which was offered zinc-bacitracin--(bacifarmin) at 30 ppm. Under the effect of flavophospholipol the weight gain was 2.2 to 21.2 per cent higher, and the weight of the liver rose by 1.4-23.1 per cent. The intake of maize per kg of gain dropped by 2.5 to 15.7 per cent, and it was 1.8 to 16.9 per cent lower per kg of liver. When flavophospholipol was given at 16 ppm, a maximum effect was produced--21.0 percent higher gain, 23.1 per cent increase of the liver weight, 15.7 per cent drop of maize intake per kg of gain, and 16.9 per cent drop of maize intake per kg of liver. With geese that were offered bacifarmin these indices were 3.3, 11.9,, 4.8, and 10.7 per cent, respectively. The amount of flavophospholipol used correlated positively with its ergotropic effect. The liver quality with geese treated with flavophospholipol and bacifarmin was higher. No residual amounts of flavophospholipol were found in the meat, liver and viscera of the treated birds.

[Efficient drug forms and the means for using them in the intensive raising of animals]. / Ratsionalizirani lekarstveni formi i nachini na prilagane pri intenzivnoto otglezhdane na zhivotnite.

Stated is the use of promising therapeutic formulae that produce prophylactic, metaphylactic, and curative effects at lower input of labour and handling, inciting lower unrest with animals, belonging chiefly to the type of the so-called 'therapeutic systems'. Particular attention is paid to drugs for programmed, continuous, and checkable release of the active ingredients in compliance with what is needed at the time (sustained release forms)-type OROS (oral osmotic system), type 'liquid reservoir', type 'glass cylinders', tablets and boluses of higher relative weight, or multilayer and mosaic ones for ruminant animals (with extendable wings, inflatable and flowing ones of the float type), and some of them for monogastric animals. Beside the boluses for the forestomach of ruminants there are the hollow bridle for horses, the ear swabs (for resorptive application), the ocular (ocusert), nasal, and vaginal forms (for resorptive therapeutic use), the skin transmembrane therapeutic systems (TTS), the pourable (pour-on and spot-on) forms, 'autodas' osmotic mini-pumps, the depot-forms, the implants, the aerosol (inhalational) forms, the 'ear rings' (ear tags) as well as the dewlaps, the rings (for tails, limbs, and ears) and the medicated feeds and liquids, and the intramammary, intrauterine, and other therapeutic forms.

[Pharmacokinetics of amoxicillin trihydrate in sheep infected experimentally with Corynebacterium pyogenes and Escherichia coli]. / Farmakokinetika na amoksitsilin-trikhidrat pri ovtse, zarazeni eksperimentalno s Corynebacterium pyogenes i Escherichia coli.

A comparative experiment was carried out with sheep that were infected i/v and via the joints with Corynebacterium pyogenes and Escherichia coli, and with normal sheep left as controls. The pharmacokinetic parameters were determined of amoxicillin-trihydrate following its i/m application to all animals in a 20 percent oil suspension. It was found that there was delayed excretion of the antibiotic, and as a rule it was maintained in higher concentrations in the diseased animals. the differences were likely to be due to changes in the metabolic processes and to injury of the kidneys.

[Pharmacokinetics, biological availability and residues of sulfadoxine and trimethoprim when used jointly on calves]. / Farmakokinetika, biologichna nalichnost i ostatuchni veshtestva na sulfadoksin i trimetoprim pri suvmestno prilagane na teleta.

In calves (cross-breds--Bulgarian Brown Cattle breed and Black Spot Cattle bred) weighing about 189 kg pharmacokinetics of sulphadoxine (SD) and trimethoprim (TMP) was studied. The two substances were administered in combination (5 + 1) as a dosage form Tridoxin (Pharmachim, Bulgaria; 24% injectable solution) (TD) at a dose 15 mg/kg m. The results show that after intramuscular administration TD is absorbed relatively rapidly. SD and TMP have systemic availability 94.1 +/- 18.1% and 52.5 +/- 6.2% and produce blood levels, after a single dose of TD, higher than potentiated minimum inhibitory concentrations for 24-48 h and 5(4-8) h, respectively. Upon intravenous administration the two-compartmental model is applicable for the distribution and elimination of SD and TMP (for TMP in part of the animals one-compartmental model is applicable). The two substances are distributed relatively widely in organs and tissues. The biological half-life of TD--t1/2 beta for SD is 14.36 +/- 1.40 h and for TMP--2.40 +/- 0.31 (for one-compartmental model--1.92 +/- 0.26) h, Vd--429.9 +/- 16.9 ml/kg and for TMP in part of the animals one-compartmental model is applicable). The two substances are distributed relatively widely in organs and tissues. The biological half-life of TD--t1/2 beta for SD is 14.36 +/- 1.40 h and for TMP--2.40 +/- 0.31 (for one-compartmental model--1.92 +/- 0.26) h, Vd--429.9 +/- 16.9 ml/kg and for TMP in part of the animals one-compartmental model is applicable). The two substances are distributed relatively widely in organs and tissues. The biological half-life of TD--t1/2 beta for SD is 14.36 +/- 1.40 h and for TMP--2.40 +/- 0.31 (for one-compartmental model--1.92 +/- 0.26) h, Vd--429.9 +/- 16.9 ml/kg and 655.8 +/- 77.6 (for one-compartmental model--671.7 +/- 40.0) ml/kg, ClB--0.35 +/- 0.02 ml/kg/min and 2.87 +/- 0.35 (for one-compartmental model--4.15 +/- 0.80) ml/kg/min, respectively. After intramuscular injection at the dose used a suitable withdrawal time for meat and internal organs is 5 days and for milk--2 days.

[Pharmacological, toxicological, microbiological and pathohistological studies of gentamycin complex II]. / Farmakologichni, toksikologichni, mikrobiologichni i patokhistologichni prouchvaniia vurkhu gentamitsin kompleks II.

The acute toxicity was determined of the gentamycin complex II (GMC-II) for albino mice, containing gentamycin components in a varying ratio. The LD50 at intraperitoneal application was 347.7 mg/kg body mass, while at oral application it was 5,180 mg (4933 divided by 5439) mg/kg body mass. Histopathologically, (mice killed with high doses of GMC-II, given orally) there were diffuse hyperemia of the liver, parenchymal degeneration of the kidney tubuli epithelium, and edema and emphysema of the lungs. The local tolerance with regard to a 5 per cent solution of GMC-II applied to the conjunctiva of rabbits at twofold treatment proved to be good. Determined were the minimal inhibiting concentrations of 14 species of pathogenic organisms of great interest to veterinary medicine (Bacillus anthracis, Erysipelothrix insidiosa, Salmonella gallinarum, Escherichia coli, etc.). The antibacterial spectrum of GMC-II was similar to that of gentamycin sulphate, however, for some pathogenic organisms higher concentrations were required to produce and antimicrobial effect. Similarly to gentamycin sulphate GMC-II had limited absorbtion in the alimentary canal of clinically normal newborn pigs and of birds. At a high rate (0.05 g/kg body mass) GMC-II applied via the crop to birds it was found to maintain the lowest therapeutic concentration in the serum. At the rate of 0.012 (equal to 12000 IU) per kg of body mass for 24 hours GMC-II produced therapeutic effects in newborn pigs affected with colibacteriosis.

[Trial of trimedin action on chickens]. / Izpitvane deistvieto na trimedina pri pileta.

Investigations were carried out with a total of 421 broiler birds (four-line Cornish X Plymouth Rock hydbrids) within the age range of 2 days to 5 weeks. Determined was the acute toxicity of the combination sulfadimidine (SDM) + trimetoprim (TMP)--5 + 1 and the water-soluble formula of trimedin following the intraingluvial introduction with week-old birds. LD50 of the combinations SDM+TMP (5+1) was 3980 mg/kg (2780: 5690), and that of trimedin was 2038 mg/kg body mass. The biologic half-life of SDM ranged from 4.77 to 5.34 h, and that of TMP--from 4.81 to 5.71 h at the intraingluvial introduction of the combination SDM+TMP (5+1) at the rate of 0.06 g/kg. Demonstrated were the therapeutic levels of SDM and TMP during the whole period (10 days) of treatment with the combination SDM+TMP (5+1) given with the feed in conc. 500 ppm or at the application of trimedin alone via the drinking water in conc. 0.05%. It was found that trimedin used for 10 days with the drinking water in conc. 0.05 per cent with broilers at the experimental infection with Salmonella gallinarum-pullorum protected about 40 per cent of the birds, the latter remaining, however, carriers of the infection.

[Blood amoxicillin concentrations in agricultural animals and poultry treated intramuscularly with drug forms containing amoxicillin sodium and amoxicillin trihydrate]. / Kruvni kontsentratsii amoksitsilin pri selskostopanski zhivotni i ptitsi, tretirani muskulno s lekarstveni formi, sudurzhashti amoksitsilin-natrii i amoksitsilin-trikhidrat.

The sodium salts of ampicillin and amoxicillin at the single i/m application in 20 per cent water solutions at the rate of 10 mg per kg of body mass guaranteed close therapeutic concentrations of both antibiotics in the blood serum of birds and rabbits. Amoxicillin-trihydrate in a 20% water suspension applied i/m in a single dose of 10 mg/kg persisted in a therapeutic concentrations in the blood serum of birds for a longer time (10 hours) than ampicillin-trihydrate (8 hours). The oil suspension containing 20% amoxicillin-trihydrate guaranteed bacteriostatic serum concentrations in the course of 24 to 48 hours at single i/m application in doses of 20 and 30 mg/kg, depending on the amount and the species of animal. The optimal doses for calves and sheep were 20 mg/kg and 30 mg/kg injected at intervals of 24, resp., 48 hours, and for pigs and birds it were 30 mg/kg at 24-hour intervals. The choice of one or another dose depended on the sensitivity of the disease agents.

[Doxycycline hydrochloride administered in the drinking water to poultry]. / Doksitsiklinov khidrokhlorid, prilozhim s vodata za piene pri ptitsi.

Investigated were the acute toxicity, serum concentrations, and residual amounts of doxycycline in broiler chickens. It was found that the LD50 of doxycycline when applied via the crop to week-old broiler birds was 2500 mg/kg mass. The amount of 0.005 g/kg mass given orally to birds led to serum concentrations that on the eighteenth hour were found to drop up to subtherapeutic ones. When applied with the drinking water at the rate of 0.02 to 0.04 g l or kg feed it was well absorbed as early as the first hours. In such case the drug maintained therapeutic concentrations that were higher in the internal organs than those in the serum. The residual amounts of doxicycline hydrochloride when it was applied at 0.04 g/l of water or kg feed were found up to 48 h hour by the method of agar diffusion, using Bac. subtilis L2 as a test organism. The withdrawal time should amount to 72 hours.

[Tridoxin toxicity and tolerance in agricultural animals]. / Izsledvane vurkhu toksichnostta i ponosimostta ot selskostopanskite zhivotni na tridoksina.

It was found that LD50 of tridoxin (sulfadoxin-trimetoprim-5 + 1--State Economic Corporation Pharmachim) at i/m application to albino mica was 950 mg/kg, and of borgal (Hochst)--920 mg/kg. At oral application these values were 2650 and 2660 mg/kg, respectively. LD50 of tridoxin at i/m application to albino rats was 1075 mg/kg, and of borgal--1320 mg/kg; orally, these values were 3000 and 3260 mg/kg, respectively. When introduced into the crop of week-old broilers the LD50 values of fridoxin and borgal were 942 and 1670 mg/kg, respectively. The oral administration of tridoxin with the feed in 3 to 5 times higher amounts than was the therapeutic muscular dose to albino rats in the course of 30 days did not lead to clinical, clinical-and-biochemical, and histopathologic changes. The tolerance of tridoxin at a single i/m injection of a 5- times higher dose than the therapeutic one (0.075 g/kg) in the case of calves was good, with the exception of transient pain at the time of injection and shortly after that and the slight, transient slowing down of forestomach movements. The injection of amounts 3 and 5 times as high as the doses for pigs, sheep, and weaned lambs was tolerated well. The application to sheep was found to be more painful than in the case of calves and pigs.

[Intramammary drug forms of neotil in treating mastitis during lactation]. / Prouchvaniia vurkhu intramamarnata lekarstvena forma "neotil" za lekuvane na mastiti po vreme na laktatsiia.

Technological, biopharmaceutical, and clinico-pharmacological studies were carried out on the varying composition of drug formulas that included a tylosin base and neomycin sulfate, intended for the treatment of mastitis-affected cows during the lactation period. A base was developed of suitable viscosity and physico-chemical properties, that rapidly released the active ingredients included in it and made them penetrate in depth in the udder glandular tissue. Both the base and the drug formula Neotil were shown to be well tolerated. Following the single intracisternal infusion tylosin was excreted with the milk up to fifth milking (the 60th hour), and neomycin--up to the 4th milking (the 48th hour). When applied therapeutically in the case of clinical and subclinical mastitis Neotil led to the clinical and bacteriological recovery of 92.5 per cent of the affected quarters. Developed was a microbiological method for the analysis of the active ingredients contained in the drug formula and the milk secretion.

[Effect of salinomycin (K 364) on the fattening of pigs]. / Izsledvane vliianieto na salitsinomitsina (K 364) vurkhu praseta za ugoiavane.

Experiments with pigs of the White Bulgarian Improved breed of initial weight of 25 kg revealed that the oral administration of salinomycin at the rate of 50 ppm (from the beginning of treatment up to the 61st day) and 25 ppm (from the 62nd day up to the 117th day) with the feed led to the increase in weight gain by 10.9 per cent and in feed conversion by 7.4 per cent by the end of the experimental period. The effect of nutrition was manifested regularly in the course of both periods of fattening. The slaughter weight also rose under the effect of salinomycin. It should be noted that higher rates of treatment--100, resp. 50 ppm--for the respective periods led to the reduction of the stimulant action of salinomycin. Under the conditions to the investigation nitrovin did not show a clearly manifested nutrition effect.

[Current animal feeds with antimicrobial activity]. / Survremenni nutritivni sredstva s antimikrobno deistvie.

Among the growth-promoting substances and factors contributing to fodder utilization in growing farm animals, also called nutritive, ergotropic means, the antibiotics and some synthetic chemotherapeutics have acquired special importance. To avoid the hazardous effect in humans consuming products of animal origin there should be no residual amounts of these stimulating agents in such products. That is why it has been assumed in a number of countries to use for the same purpose only nutritive means that are not applied as therapeutic agents. Such means should neither induce resistence to antibiotics and chemotherapeutics in microorganism nor should they be resorbed by the alimentary tract (or resorption should be negligible) or they are rapidly eliminated from the animal body, leaving no residual amounts. They should likewise act chiefly against gram-positive organisms, inducing no allergic reactions in the animals. Described are the following nutritive antibiotics: flavophospholipol (bambermycin, menomycin--flavomycin, producing a nutritive effect also in ruminants with a developed forestomach, and rebuilds sensitivity in antibiotic-resistant organisms belonging to Enterobacteriaceae), avoparcin (avotan--also active in ruminants with a developed forestomach), virginiamycin (staphylomycin--escalin, stafac), zincbacitracin (bacipharmin, baciferm), grisin (kormogrisin, of a road spectrum, with an antimycotic effect, raising the fertilization rate and activating phagocitosis), vitamycin-A (vitamycin--active also at retinol deficiency, lambdamycin, nosiheptide (primofax), efrotomycin. Due consideration is given to such chemotherapeutics as nitrovin (payson, paison), carbadox (mecadox, fortigro, of a broad spectrum retained for a longer period in the body of pigs), olaquindox (bio-N-celbar--of a broad spectrum, particularly with regard to gram-negative organisms, applied at present as a therapeutic and prophylactic preparation), cyadox (with a broad sprectrum). The following polyether ionophoric antibiotics are mentioned: monensine (rumensine, elancoban), lassalocide (avatek, lasotek), slinomycin(eustin, ustin, coxistac), lonomycin (emercide), harasine. Dosage rates and other data are given characterising the respective preparations.

[Effect of salinomycin (K-364) on calves for fattening]. / Izsledvane vliianieto na salinomitsina (K-364) vurkhu teleta za ugoiavane.

Experiments with calves of initial weight of about 178 kg revealed that salimycin given with the feed at the rate of 0.5 mg/kg for 24 hours in the course of 269 days, and monensin used for comparison at 0.7 mg/kg for 24 hours led to the increase in the weight gain by 4.3 and 6 per cent, respectively. An increase in the conversion of forage was also established--6.3 and 9.5 per cent, respectively. Up to the sixth month of age the rise of the weight gain (as against the negative control group) with the calves treated with salimycin (11.7 per cent) was higher than that with calves that were given monensin (9.9 per cent). The combined application of salimycin (0.5 mg/kg for 24 h) and flavophospholipol (0.1 mg/kg for 24 h) led to the slight enhancement of the nutritive effect: with regard to the weight gain--by 1.7 per cent, and with regard to the conversion of forage--by 2.8 per cent.

[Effect of salinomycin on lambs for fattening]. / Vliianie na salinomitsina vurkhu agneta za ugoiavane.

When applied to male Trakiiska tunkorounna lambs of initial weight 18.6 kg in the course of 90 days at concentrations of 6 g, 12 g, and 24 g per ton of forage slinomycin brought about a rise of liveweight and average weight gain in the treated animals (for the weight gain 12.2, 16.7, and 19.4 per cent, respectively, as against the controls). The conversion rate (intake per kilogram of weight gain) was by 9.7, 16.6, and 22.2 per cent, respectively, higher. The intake of forage progressively dropped when offering higher concentration of the antibiotic, particularly during the second half of the experimental period. Highest was the effect of adding 24 g salinomycin to a ton of forage. Salinomycin induced no essential changes in the slaughter indices and in the content of cyanocobalamin in the meat. However, cyancobalamin was found to be at a higher level in the liver.

[Blood concentrations of sulfadimidine after the internal use of depot sulfadimezine granules in sheep]. / Kruvni kontsentratsii na sulfadimidin sled vutreshno prilagane na sulfadimezin-depo-granuli, pri ovtse.

A granular premixed form, called sulphadimesin-depot-granules, was produced, containing 40% of sulphadimine inserted into a hydrophobic matrix of hydrogeneric sunflower oil. After a single internal insertion into sheep by means of a stomach-tube or of a bottle on an empty stomach in a dose of 0.5 g/kg t, they caused bacteriostatic concentrations in blood plasma during 78 hours, and in a dose of 1.0 g/kg t--during 96 hours, whereas the sulphadimesin in tablets, applied in a dose of 0.2g/kg t, kept up a therapeutic concentration for 24 hours. The duration of the bacteriostatic level of sulphadimesin after the taking of the granules in a dose of 0.5 g/kg t and after the feeding, was 12 hours; after two treatment with a stomach-tube or of a bottle, on an empty stomach, in an initial dose of 1.0 g/kg t and a following one of 0.5 g/kg t, applied after a period of 96 hours--it was 174 hours. No side phenomena were observed, besides a temporary (for 12-24 h) slight slow-down of belly movements. For a prophylactic treatment of sheep it is recommended that the granules should be applied in the fodder and on an empty stomach, in an initial dose of 1.0 g/kg t, and 72 hours later in a dose of 0.5 g/kg t. For a curative treatment an internal insertion is recommended by means of a stomach-tube or of a bottle, on an empty stomach, in the same doses, at an interval of 96 hours.

[Toxicological studies of Bulgarian activated bentonite]. / Toksikologichni prouchvaniia vurkhu bulgarski aktiviran bentonit.

We studied the endurance of calves, lambs and pigs as well as the acute, subchronic and chronic toxicity for chickens with regard to bentonite of local origin, extra activated in a physico-chemical way. It was proved that the medicine was rather endurable with calves, lambs and pigs without causing intoxication or death after a single internal introduction in doses respectively 4138, 4130 and 1860 mg/kg t. LD0 of the activated bentonite for the chickens in the case of intra-crop application was over 18000 mg/kg t. During a 33-day extra addition to the fodder of chickens in quantities of 2 and 6% and during a 90-day introduction into concentrations 1, 3 and 5% the activated bentonite and not provoke any changes in the behaviour, overall state and in the clinical biochemical and electrolytic composition (Ca, P, K, Na) of the blood, but it caused suppression of growth ranging from 6 to 27% and brought about a higher expenditure of food for a single growth unit ranging from 4.7 to 12.1%. This was also observed when it was added to the morning ration of pigs in doses 1 and 5% (6 and 30 d/pig) without any influence over the health state of the pigs, but it slowed down growth ranging from 17.2 to 21.3% and a lower utilization of the fodder taken by 19 to 26%.

[Toxicity of hydroxyquinoline derivatives]. / Prouchvaniia vurkhu toksichnostta na niakoi khidroksikhinolinovi proizvodni.

We studied a 90 day toxicity in dogs of the compound broxyquinoline + broxaldine--5:1 (enteroquin), applied orally and daily in doses of 0.1 and 0.2/kg t/24 h. We established the toxic manifestations during the period after the 15th day of the treatment: leukopenia, neutropenia and lymphocytosis (by 0.2 kg t/24 h). After the second and fifth day we observed a decrease of appetite, depression of the CNS, paralyses, arrhythmia, progressing loss in weight, proteinorrhea (more pronounced with those receiving 0.2/kg t (24 h); lethal consequence with some part of the animals 25% (ba 0.1/kg t) and 50% (by 0.2 kg t). We found out pathohistologically necrobiotic changes in the medulla oblongata and the kidneys, toxic distrophy of the liver, blood-vessel injuries. The toxic changes observed can be interpreted in connection with the presence of a species specific reaction.