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The aim of this study was to evaluate the potential use of albumin microspheres as a drug delivery system to provide sustained release of dexamethasone in vivo. Pharmacokinetic studies were carried out in sheep and tissue distribution in rats given dexamethasone in two injectable forms--water suspension of dexamethasone associated with albumin microspheres and water-ethanol solution of dexamethasone. When dexamethasone was associated with albumin microspheres the amount of free dexamethasone, available for absorption did not reach the high values typical of the pattern of release of dexamethasone from water-ethanol solution. The time of withdrawal in lactating cows after i.m. administration of DXM-AM was found to be 5 days. The release of dexamethasone from the albumin microspheres was accomplished gradually thus allowing sustained levels of the corticosteroid to be maintained for several days in blood plasma, milk, liver, kidney and muscles.

Comparative investigations were carried out on the absorption, antianemic action, and growth effect with newborn pigs with FB-82 and dextrofer-100 (an iron dextran complex with 100 mg Fe3+ per cm3) injected i/m. The FB-82 is a combined preparation of 3500000 IU Tylosine tartrate, 0.008 g cyanocobalamin, 0.5 g pyridoxine hydrochloride, 0.1 g tartaric acid, and iron dextran up to 100 cm3 (= 100 mg Fe3+/cm3). Dextrofer-100 enriched with 50 mg Zn, 0.5 mg Co, 200 micrograms cyanocobalamin, and 100 mg pyridoxine hydrochloride for 100 cm3 under the compound name of fericin was also used to compare the anti-anemic effect of FB-82 and dextrofer-100. It was found that FB-82 applied to newborn pigs in a single dose of 2 cm3, i/m, was well absorbed; it developed high concentrations of tylosine in the plasma, and its sideremia and antianemic action were similar to those induced by an equivalent (with regard to iron) amount of dextrofer-100, whereas the result concerning the hematocrit value was better. Compared to dextrofer-100 the FB-82 preparation have better protection to pigs (lowered the mortality rate) and induced better development of the animals. Fericin did not differ essentially from FB-82 in terms of its effect on the red blood picture, however, the percent of protected pigs was lower.

Studied were the acute toxicity (albino mice and rats, chicken broilers), species specific tolerance (lambs, sheep, goats, pigs, calves, chicks, chickens), and subchronic toxicity (albino rats, pigs, pulets) of tiabendazole Pharmachim (TP). It was found that LD50 of TP at the oral application to albino mice, weighing 18-20 g was 2.7 g (2.14 divided by 3.40) per kg for albino rats weighing 120-200 g it proved technically undeterminable. For broilers at one month it was 4.0 g (2.54 divided by 6.28) per kg. LD50 of TP of the firm Merck Sharp and Dome for albino mice was 2.9 g (2.28 divided by 3.68), and for broilers -- 5.0 g (4.31 divided by 5.8) per kg. The lethal dose for lambs was 400 mg/kg, for sheep -- 800 mg/kg, for goats -- 500 mg/kg, and for calves -- 500 mg/kg. When treated with amounts of 450 and 850 mg/kg pigs vomited. The same was true of drugs when offered the preparation at the rate of 300 mg/Kg chicks and chickens tolerated amounts of 500 mg/kg. TP was well tolerated by pigs, rats, and pullets when given with the feed for 30 days in 0.1 per cent conc.; in 0.4% conc. (pigs), 0.5% (albino rats), 0.3% (pullets), and 1% (albino rats and pullets) led to the arrest of growth and rise of transaminases and urea in the blood serum (rats and pigs) and the adverse effect of the red blood picture (rats, pigs, and pullets). Histologically, there were vascular troubles and granular degeneration that predominated in the kidneys, and were more slightly expressed in the remaining parenchymal organs.

An 'in vitro' microbiologic method was employed to follow up the activity of gentamycin diluted in bovine and swine sera and bound to proteins isolated from them, in the course of continuous storing. It was found that the protein solutions of gentamycin retain their activity for one year under refrigerator conditions (4 degrees C), whereas with the freeze-drying of these solutions storage could be effected at room temperature. It was established through the method of balanced dialysis that gentamycin binds with the proteins of swine sera, and to a largest extent with native serum (30 per cent) and to a lower one--with globulins (15--16.2 per cent). The protein complexes of gentamycin proved entirely reversible and the process of binding was shown to have no influence on the minimal bacteriostatic concentration of the antibiotic with regard to Bacillus mycoides HB2.

Tested was the monensin-Na Pharmakhim preparation (commercial formula Monensin-100, a 10 per cent premix of monensin-sodium) with weaned lambs with regard to toxicity, tolerance, nutritive action, distribution, and residual amounts in the body as well as with special reference to its effect on meat quality. It was found that doses of 15 mg/kg body mass were well tolerated, with no changes in both behaviour and appetite. The minimum lethal dose was 30 mg/kg b. m. Medicated feed, containing Monensin-100 at rates 10, 20, and 30 ppm, offered to the animals in the course of 90 days produced a positive effect after the 30th day, acting best in conc. of 30 ppm. In the amounts referred to Monensin-100 negligibly stimulated the process of hemopoiesis; more substantial was the improvement of the carbohydrate metabolism, raising the amount of blood sugar (better at the rate of 30 ppm). Histologic investigations of parenchymal organs of the animals treated with nutrient amounts of the preparation revealed no degenerative changes. Neither was there any negative effect on the tested organoleptic, physico-chemical, and microbiological indices of the meat obtained following the use of Monensin-100 in the concentrations referred to. The withdrawal time at slaughtering weaned lambs that had been offered Monensin-100 with the feed in the course of 90 days with regard to the concentrations cited above was shown to be at least 48 hours.

Studied was the species-specific tolerance and the subchronic toxicity of the arprinocid coccidiostatic (9-/2-chloro-6-fluorophenylmethyl/9H-pirineamine) in the form of a 12% premix with trade mark Arpocox, Merk Sharp and Dohme Research Laboratories. It was found that at single oral application arprinocid led to the intoxication of broiler birds at 50 mg/kg, turkey poults-at up to 18 mg/kg, ducklings--up to 18 mg/kg, goslings--up to 6 mg/kg, calves--up to 10 mg/kg, lambs--up to 60 mg/kg, pigs--up to 30 mg/kg. The lethal dose for chickens was over 100 mg/kg, turkeys and duckling--30 mg/kg, and goslings--18 mg/kg. Arprinocid given with the feed to chicken broilers in conc. 60 ppm for 30 days did not lead to side effects. In conc. of 120 and especially 180 ppm there was retardation of growth with birds and inhibition of hemopoiesis. With pigs the preparation in conc. 60 to 180 ppm given with the feed had no effect on the growth and consumption of feeds; in 120 ppm and especially in 180 ppm it inhibited the hemo- and erythropoiesis. With chickens and pigs arprinocid in 180 ppm did not cause degenerative and inflammatory changes in the liver, kidneys, heart, spleen, testes, ovaria, adrenals, thyroid, and skeletal muscles.

Studied were the acute and subchronic toxicity of monensin-Na in pigs. The investigations were carried out with elancoban-100, containing 10 per cent monensin-Na. A total of 46 pigs were used, weighing 15 to 60 kg. The preparation was applied individually via the nose or with the feed. It was found that nasally at 5 mg/kg the preparation did not lead to intoxication; rates of 10 and 20 mg/kg proved toxic, and a dose of 30 mg/kg was lethal. Feed containing 300 ppm of monensin-Na given but once led to intoxication and death with part of the animals. Pig tolerated well continuous (33 days) intake of feed that contained the sodium salt of monensin in concentrations of 120 and 240 ppm - no changes in the general status and behaviour were observed, nor were there any deviations in the morphologic and biochemical composition of the blood. It was demonstrated that the low amounts of monensin stimulated the weight gain of pigs. On the other hand, the clinical picture of the intoxication consisted in going off feed, higher pulse and respiration rates, involvement of the nervous system (depression of the nociceptive, eye closure, and ear reflexes, paresis of the hind limbs, and in severe cases - of the forelimbs too), hematuria in most of the animals, higher SGPT activity, and delayed ESR. Morphologically, there were vascular and slightly manifested degenerative changes in the parenchymal organs, red to brown urine in the bladder, strongly enlarged gallbladder, and catarrhal and hemorrhagic gastroenteritis. Histologically, there was granular and fatty degeneration of the kidneys, liver, and heart, hyperemia, perivascular and pericellular edema and degenerative changes in the glial cells of the berebrum, cerebellum, and medulla oblongata.

Studies were carried out to establish the severity of anemia in newborn pigs of sows under various raising technologies and some aspects of its drug prophylaxis. It was found that in the swine-breeding complexes that were investigated more than 50 per cent of the day-old piglets had the subclinical form of anemia (6 to 8 g% of hemoglobin content). With some raising technologies (tying the sows up to the feeders) about 17 per cent of the pigs were born with pathologic anemia (the hemoglobin content was below 6 g%). With the introduction of the new technologies the pigs were born with lower erythrocyte count of the blood. The decrease in the indices of the red blood picture (with some technologies there was also a drop of the serum iron) was seen in the sows too (better manifested when these were tied up to the feeders). The intamuscular injection of the fericin preparation of ferridextran, zinc, and vitamin B12 and B6 (doses of 4.0 g Fe3+) to the sows 21 days prior to farrowing neither hypochlorosis nor erythropenia of the newborns could be overcome. On the other hand, the i/m introduction in the thigh region of the preparation dextrofer-100 at the rate of 200 mg Fe3+ in a single injection to the newborns prevented anemia for 30 days. A second injection 7 days later of one more dose of the preparation did not bring about an essential improvement in the development of pigs. The single dose of 100 mg Fe per pig in the form of dextrofer-100 was not sufficient to produce an optimal antianemic effect.

Rabbits and pigs were used to study the resorption and retention of gentamycin dissolved in swine gamma globulin, swine polyglobulin, in water (gentamycin ampoules) and as a combined preparation with gamma-globulin and vitamins (gentaglobin). It was found that the protein solutions of gentamycin as compared to the water solutions at i/m application to rabbits and pigs give higher and persistent concentrations in the blood serum. At muscular application to pigs at the rate of 0.002/kg gentaglobin was retained in bacteriostatic concentrations in the blood serum for 12 hours. In pigs the gentamycin preparation, no matter what solvent was used, was eliminated comparatively very quickly through the bile and urine. It is stated that the quarantine for gentaglobin-treated pigs intended for slaughter should be 72 hours, the kidneys of such animals being excluded from human consumption. Gentamycin in the gentaglobin preparation has been found to retain its activity in the course of one year at +4 degrees C.

Studied was the preparation diazepam-pulvis for suspension (DPS) with regard to its tranquillizing and myorelaxing doses, inhibiting the aggression, and preventing the stress conditions in domestic animals and birds. It was established that at oral application to pigs at rates of 1 to 2 mg/kg body mass DPS produced a pronounced tranquillizing effect, while at 3 mg/kg it led to myorelaxation as well. In sheep tranquillizing effect was seen when amounts of 3 to 5 mg/kg body mass were used, and myorelaxation was achieved with 6.6 to 13.2 mg/kg. In male calves tranquillization was manifested after doses of 3 mg/kg body mass were applied. In hens the tranquillizing dose was found to be 3 mg/kg body mass, and the myorelaxing one--4 mg/kg; in cocks the respective doses were 5 and 7 mg/kg body mass. At the rate of 3 mg/kg body mass DPS was found to enhance the thiopental-sodium narcosis. When offered to pigs at 2 mg/kg body mass in admixture with the feed DPS led to tranquillization and suppression of the active and passive defense response. No full prevention of cannibalism could be achieved. The daily administration in the course of 30 days with the ration of bull-calves at the rate of 3 mg/kg body mass was shown to calm the animals under loose housing in boxes and affect favourably their weight gain. Admixed with the feed of cocks at 5 mg/kg DPS suppressed aggressiveness.

Studied were the new Bulgarian hydrosol preparations Hydro-AD3EC, Hydro-AD3EK, and Hydro-EC. Their tolerance was investigated with the use of albino Wistar rats, the resorption and retention (by their liver content) of retinol and d, 1-alfa-tocopherol was investigated in young broiler chickens, the resorption of ascorbic acid was followed up in White English layers, the antihemorrhagic effect of Hydro-AD3EK was studied in rats with experimentally induced hemorrhagic diathesis offering 30 mg ethyl biscoumacetate (pellentan tablets) with the feed. It was found that the oral application of the first three hydrosol preparations to albino rats at the rate of 12.5 cm3/body weight (equal to 10-15 effective doses for birds) did not produce toxic effects. The retinol and d, 1-alfa-tocopherol constituents of AD3EC and AD3EK, given with the drinking water to birds, were well resorbed and were deposited in the liver. Fuller resorption was observed with the use of AD3EC. The ascorbic acid of AD3EC and AD3EK when these were offered per os to adult chickens was resorbed quickly, which was better expressed with AD3EC. AD3EK in oral application to rats produced antihemorrhagic effects. The use of these preparations in a prophylactic scheme with young broilers shortened the fattening period and improved the feed conversion.

Tested was the teratogenic and embryotoxic action of linkomycin hydrochloride with both placental and nonplacental animals. It was found that when applied twice, orally, to albino rats on the 4th day of pregnancy at the rate of 250 mg/kg body mass (=5 ED50), and once to chick embryos at 50 mg per egg the antibiotic raised the percent of pre- and postimplantation loss of embryos. In a series of applications (oral) from the 3rd up to the 19th day at 50 mg/kg body mass to rats as well as in a single application to chick embryos at 10, 20, and 50 mg per egg linkomycin showed no teratogenic effects.

Ronidazol-Pharmachim (RPh) in the form of 10 per cent water-soluble powder was studied in terms of resistance to various values of pH of the surrounding medium, acute toxicity, the species-specific tolerance of various mammals of it, its subchronic toxicity and residual amounts with pigs. The preparation was found to be stable in water solutions (pH 5.0 to 9.0) in the course of at least 96 hours, and in n HCl--for more than a month. At oral administration LD50 of RPh was 34000 mg (2982 divided by 3876) per kg for albino rats weighing 150-200 g. At intraperitoneal injection in the form of pure substance LD50 was 1500 mg (1320 divided by 1690) per kg. With pigs at single oral application at the rates of 20, 60, and 180 mg/kg (= 20-30 times the ED50) RPh was tolerated with no changes in the behaviour and appetite. When used with the drinking water at rates of 60, 180, and 300 ppm in the course of 30 days there was no unfavourable effect on the gain and the blood picture and no injury of the structure of viscera of pigs. In concentrations of 180 ppm it was shown to stimulate the growth of pigs. The withdrawal time with pigs given RPh with the drinking water was at least 72 hours after the preparation was offered last.

Studied was the preparation thiabendazole-Pharmachim (TBZ-Ph), produced by the Economic Corporation "Pharmachim". In some of the experiments TBZ-Ph was comparatively studied with the Merck & Sharp and Dom preparation (TBZ-MShD), Switzerland. It was found that the light absorption maximum of TBZ-Ph was at 302 nm. Thermostability studies revealed that the preparation was comparatively stable in the course of 6 months at room temperature and at 4 degrees and 40 degrees C. When stored in the form of 1 per cent medicated feed at room t degrees, 4 degrees, and 40 degrees C it showed no deviations as against the check samples over a period of 70 days. TBZ-Ph was shown to possess slight photosensitivity; it was not hygroscopic. In oral administration to sheep and pigs at the rate of 100 mg per kg body mass, in the form of a 10 per cent water suspension TBZ-Ph was absorbed through the gastro-intestinal membrane. It was retained in the blood serum of sheep up to the 24th hour. The preparation was shown to gain access to almost all viscera and striated muscles, persisting in them for some twenty days. Following the oral application in a dose of 100 mg/kg it reached the mammary gland of lactating ewes and was detected in the milk in maximum concentrations as early as the 3rd hour (5.8 to 12.3 ppm); in the course of the following hours concentrations dropped, and in individual animals the preparation was traced up to the 96th hour.

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%.

Studied was the preparation Teravit Pharmachim in terms of its physical and chemical properties, antimicrobial activity, resorption, retention, and distribution, within the body of chickens and albino rats. It was found that Teravit Pharmachim was strongly sensitive to light, slightly hygroscopic, and relatively heat resistant. It showed good antimicrobial activity with regard to both Gram-positive and Gram-negative organisms. At 60-day feed application to albino rats at the rates of 30 and 300 mg/kg it stimulate the growth of test animals, and at the rate of 1500 mg/kg it delayed their development but did not produce negative effects on the red and white blood picture. Teravit Pharmachim was shown to bind the proteins of the body liquids and tissues, which depended on the biologic substrate and the antibiotic concentration. At the single oral application (chickens) or the administration with feed in the course of 60 days (albino rats) Teravit Pharmachim was resorbed depending on the dose, was retained in the blood, and was further followed up in the internal organs. It was eliminated from the body for about 3 to 5 days, did not cumulate in the ovarian follicles, and was not excreted with the eggs.

Investigations were carried out on the medicines mastiriphin--intramammary syringes, (Mf) in two variants "A" and "B", meant for the treatment of acute mastitis with cows and also mastiriphin depot--intramammary syringes (Mf-depot), as well as two variants with indications for subclinical mastitis cows, containing both medicines in 10 g with 80,000 VI rifampicin, SEC "Pharmachem". Experiments were carried out for determining the stability of the medicines at different pH. The investigations were carried out with 23 lactating and 22 non-lactating cows. Both the degree of retention and the velocity of elimination of rifampicin from the milk and the lactic secretion. It was proved in vitro that rifampicin is stable in a neutral milk milieu (pH 7) in the course of 24 hours, and while in acid or alkaline milieu it was quickly eliminated Mf "A" in the case of intramammary introduction created high bacteriostatic (therapeutic) concentrations in the milk of the lactating animals till the sixth (eighth hour, whereas Mf "B" and the imported analogue rifamasten, provided twice as high levels of antibiotic. Mf-depot "B" introduced in a intramammary way with non-lactating cows was retained in the lactic secretion between 15 and 20 days. The quarantine time limits for using the milk taken from cows, treated in an intramammary way, proved to be 72 hours.

The acute and subchronic toxicity of monenzine (preparation Elancoban -- 100 of Elanco Co., USA) to male lambs for fattening aged 3-4 months and weighing 16-28.5 kg was studied. It was established that the single per oral dose of 5 mg/kg weight of the natrium monoenzine salt causes a temporary lack of appetitie but no changes in the behavior and the general state of the animals. The use of a 10 and 30 mg/kg weight dose of the preparation led to death of the lambs on the 72nd-120th hour. The toxicity was clinically manifested by anurexia, arumination, ataxia, paresis, and paralysis of the limbs, tachicardia, taxipnea, hypothermia and showed down and weakened rumen movements. Erosive rumitis and abomasis, catharrhalhemorrhagis duodenitis, hemorrhages on the epicardis, hyperremia and parenchymal organ oedema, 3-4 times increased gall-bladder with numerous nodes having a sunken center on its walls were observed pathologo-anatomically, while microscopically blood vessel disturbances (hyperremia, hemorrhages and oedema) of the lungs, heart, spleen, endocrinal glands (thyroid, adrenal and hypophysis), the brain, and the leptomeninges, liver distrophy, distrophic nephrosis and necrotic holecystitis were obvious. Following a long term (30 days) application to the fodder in 10 and 50 g/t doses, monenzine-natrium does not have a negative effect on the behaviour, general condition, clinical and biochemical blood composition and the structural build up of the inner organs, but in the first 5-10 days of the treatment it causes loss of appetite. Additional specific investigations are needed to elucidate the effect of the preparation on body gain.

Studies are the following preparations, produced by "PHARMACHIM": tylosine-base (Tylosine-50), tylosine tartarate (Tylosine pulvis) and tylosine phosphate (substance and granules) and their analogues: tylosine-base (Tylan-50), tylosine tartarate (Tylan soluble) and tylosine phosphate (Tylan AF 99), produced by the "Elanco" Company. The biological activity of the preparation was determined by means of the microbiological method of diffusion in agar. In the case of all experimental treatments, the preparations were compared in conformity with their biological activity expressed in IU/mg of the preparations. The minimum inhibition concentrations of the preparations were determined by the method of serial dilutions in liquid nutritive media on 19 different pathogenic strains. The antispirochetal activity of the preparations compared was tested on 130 cockerels and pullets, experimentally infected with Borrelia anserina of the Surnevo and Pamoukchii serotypes. The application of the preparations started simultaneously with the infection or 24 and 48 hrs after it and continued for days. No significant differences are found in the antibacterial and antispirochetal activities of the Bulgarian tylosine preparations and those manufactured by the "Elanko" Company. The tylosine base does not differ significantly in its antimicrobial and antispirochetal activities from the tylosine phosphate and the tylosine tartarate when equal in IU concentrations and doses are applied.

Investigated were the Bulgarian preparation dextrofer-100 (Pharmachim) and miofer-100 (Farbwerke, Hoechst, West Germany)--iron-dextran preparations with 100 mg Fe3+/cm3 each. Use was made of 62 domestic cats, 8 guinea pigs, and 18 albino rats. tI was found that the venous introduction of iron-dextran complexes into uretane-treated cats at rates of 100 to 500 mg Fe3+/kg body mass lowered the blood pressure by 10 to 65 per cent; the depressive effect was more strongly manifested with the use of miofer-100. At 100 mg Fe3+/kg and higher doses led to alfa-adrenolytic manifestations (an inverse effect of noradrenaline), and did not change the action of acetyl-choline, histamine, and serotonin. At venous injection the iron-dextran complexes diminished the amplitudes of the heart contractions (with cats in situ). With regard to the nervous-and-muscle condition these preparations were found to manifest an action that resembled that of curare (the effect produced by miofer was stronger). Dextrofer-100 in a five-fold application to guinea pigs at the rate of 0.2 cm3+ (= 20 mg Fe3+) blocked the sensibilizing action of horse serum--it gave protection from an aphylactic shock in about 70 per cent of the animals. In muscular application to albino rats with experimentally induced dextran edema this preparation manifested an antiedema action. The iron-dextran complexes lowered the contraction capacity of ileum sections (taken from guinea pigs) that was manifested under the action of serotonin and histamine.

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.

A pharmacologic evaluation was made of a technologic model of a liquid drug form (code name phi B-82), having the following composition: tylosine tartrate 3500000 UI, cyanocobalamine 0.008 g, pyridoxin hydrochloride 0.500 g, tartaric acid 0.100 g, and feridextran (dextrofer-100) up to 100 cm3; pH from 5.5 to 6.5, and Fe3+ 100 mg/cm3. It was found that phi B-82 at i/m application to rabbits, subcutaneous injection to albino mice, and intra-abdominal introduction to albino rats and mice at rates that were equal to ED100 and 3 to 5 times higher than those used with pigs did not lead to local and total lack of tolerance. The acute toxicity (LD50) of phi B-82 at intra-abdominal application to 18-20 g albino mice was 29.2 cm3/kg. The single muscular application to guinea pigs at 2 cm3 per kg of body mass showed good absorption of the preparation - it did not differ essentially from those of dextrofer-100 and aquaous solution of tylosine tartrate used in equivalent amounts. The bacteriostatic concentrations of tylosine were maintained for 24 hours. It was shown that the optimal effect would be produced by a combined preparation having the qualities of the feridextrane complexes with a rapid absorption and those of the erythropoietic vitamins of the B12 group and B6 along with the participation of tylosine as an antibiotic.

A combined preparation, biofer, was studied, defining its clinical and pharmacological capacity. Featuring in its composition are: normal bovine gammaglobulin, 8.0 g; ferridextran (dextrofer-100), 32 cm2 (= 3.2 g Fe); cuprum sulfuricum, 0.32 g (= 0.08 Cu); Co chloride, 0.18 g (= 0.08 Co); cyancobalamin, 0.0032 g; and protein hydrolysate up to 100 cm3, at pH = 7.0-7.2. The local and total tolerance of animals for biofer was studied along with the acute toxicity, absorption, and retention in the body of test animals and calves as well as the antianemic action in albino mice and calves. It was found that at 4 degrees C to 8 degrees C the shelf life of biofer was 2 years. Its LD50 at subcutaneous injection to albino rats was 11.7 cm3/kg body mass. At the rate of 0.6 cm3/kg (i/m) rabbits did not manifest local and total intolerance; at 1.8 cm3/kg there was no local inflammation, however, a transient drop of appetite was seen; at 3 cm3/kg rabbits manifested intoxication with exitus. At i/m introduction to rabbits and calves biofer was more slowly absorbed than dextrofer-100. The liver and spleen of animals injected with biofer showed higher values for copper. In i/m application to anemic albino rats biofer showed a better antianemic effect than dextrofer-100. In calves it activated to a better extent both erythropoiesis and leukopoiesis.

The indices of the red and white blood picture were studied in a total of 788 calves, aged up to 30 days, 541 out of which were born in the winter-spring months, and 253 of which were born on the same farms in the summer-autumn months, originating from 17 dairy farms of 6 regions of the country. It was found that the calves born on industrial cattle-breeding farms were comparatively often affected with anemia, showing lower hemoglobin level, hematocrit values, and erythrocyte count along with hypoferremia. More widely occurring was the anemia in calves during the winter-spring period as well as in twin calves and calves of cows that gave birth for the first time. Simmenthals and Simmenthal crosses were shown to suffer more often from anemia than the calves of the Bulgarian Brown and Black-and-white breeds and their crosses. There were no sexual differences with regard to the hematologic indices. The percent of day-old diseased calves was comparatively high.

Studied was a broth received from the T. Dokov leather factory in Etropole, prepared of swine skin subepidermal layer (BSSS). As many as 28 samples of BSSS were studied with regard to crude protein, crude fats, and aldehyde and peroxide numbers. The tolerability of BSSS was tested on a total of 150 Wistar albino rats after storing at various temperatures. Studied were also 10 batches of BSSS in fresh state (up to the 24th hour after receiving from the factory) as well as at intervals of up to 10 days in air-tight condition, at temperatures of 4 to 8 degrees C; 18 to 20 degrees C; and 37 degrees C. BSSS was administered orally, undiluted, at the rate of 3 ml/100 g body mass. The subchronic toxicity of BSSS was examined with two species of animals--pigs and broiler birds. BSSS was found to contain 12.2 to 14 g% proteins and 12.57 to 42.0 g% fats. When stored at 37 degrees C in nonsterile conditions its shelf life is but 24 hours, and at 4 degrees C it can be kept up to 10 days. It was tolerated well by rats, birds, and pigs when offered in fresh state. When mixed with other feed it did not lower the appetite of animals and could replace about 25-30 per cent of the daily protein ration. This, in turn, did not lead to changes in the white and red blood cell counts and in the biochemical composition of blood nor to changes in the internal organs and the striated muscles.

Studied was a drug formula of tetraolean for i/m application, containing tetracycline hydrochloride and oleandomycin phosphate in a 2:1 ratio, produced by the Antibiotic Works, Razgrad, and released in flasks of 500 mg and 1.0 g. It was followed up with regard to its tolerable serum concentrations for rabbits, calves, pigs, and horses. It was found that in therapeutic amounts tetraolean was well tolerated and did not lead to local and general disturbances. In higher doses it was found to form transient oedema in the site of injection. Intramuscularly, tetraolean was well absorbed in the site of application, and, according to the animal species, it developed proper plasmal therapeutic concentrations at the following rates: calves--20 mg/kg body mass at 12-hour intervals; pigs--10 mg/kg at 6-hr intervals, or 20 mg/kg at 12-hr intervals; horses--10 mg/kg at 12-hr intervals or 20 mg/kg at 24-hr intervals.

Comparative studies were carried out with dextrofer-100 with B12 and dextrofer-100 in terms of acute toxicity (albino mice), absorption (rabbits, pigs, and lambs), deposition of iron in the liver and spleen (rabbits, pigs, and lambs) and antianemic action (pigs and lambs). It was found that LD50 of dextrofer-100 with B12 at i/v introduction into 18-20-gram albino mice was 1750 mg Fe3+/kg body mass; with regard to toxicity it was shown to correspond to the British Veterinary Code. The toxicity of dextrofer-100, studied by the same test, was practically undeterminable. By the level of sideremia dextrofer-100 with B12 did not differ essentially from dextrofer-100 and was said to belong to preparations with rapid absorption. It was most rapidly absorbed in pigs, rabbits and lambs following next. It supplied enough iron to the reticuloendothelial organs--in pigs it was (on a percent basis) highest in the liver, and in lambs--in the spleen. In pigs on the 10th day following treatment with dextrofer-100 with B12 the liver was shown to have vitamin B12 5 times as much. By its antianemic effect at i/m application to newborn pigs and lambs dextrofer-100 with B12 did not differ essentially from dextrofer-100 (its action was negligibly broader), however, it was beneficial to the growth of pigs.