Polyphosphazene membranes and microspheres in periodontal diseases and implant surgery.

Membranes or microcapsules made from polyphosphazenes bearing amino acid side groups are proposed for the treatment of periodontal diseases. Polyphosphazene membranes, prepared with alanine ethyl ester and imidazole in the molar ratio of 80:20 as phosphorus substituents, gave a degradation rate that corresponded to the healing of the bone defect. These membranes were much more successful in promoting healing of rabbit tibia defects than polytetrafluoroethylene membranes. Antibacterial or anti-inflammatory drugs, useful in periodontal tissue regeneration, could be entrapped in the polyphosphazene membranes and released both in vitro and in vivo at a rate that ensured therapeutic concentrations in the surrounding tissue. Polyphosphazene microspheres, prepared with phenylalanine ethyl ester as a phosphorus substituent and loaded with succinylsulphathiazole or naproxen, were also obtained. The kinetics of release from these matrices were very convenient in yielding local concentrations of the two drugs that are useful per se or when mixed with hydroxyapatite for better bone formation.

Short-term versus continuous antimicrobial therapy for asymptomatic bacteriuria in pregnancy.

Asymptomatic bacteriuria was identified in 300 pregnant women prior to the 28th week of gestation. In one group of 200 women short-term treatment with either nitrofurantoin or sulfamethizole was given for 14 days, and in another group of 100 women continuous therapy with one of these drugs was given for the remainder of gestation. Weekly urine cultures were obtained from all the women. Of the women treated with short-term therapy, 65% were abacteriuric for the remainder of pregnancy following one course of therapy, 24% became abacteriuric but subsequently relapsed, 2% had reinfection after becoming abacteriuric, and 9% demonstrated no response. Following treatment with a second course of short-term therapy, another 19% of these women were cured for the remainder of their pregnancy, and 3.5% responded to a third course. In the continuous therapy group, 88% of the women became abacteriuric for the remainder of the gestation, 3% demonstrated relapse, 2% developed reinfection, and 7% had no response to the first drug given. These data demonstrate that short-term administration of antimicrobials, when combined with surveillance for recurrent bacteriuria, is effective for the management of the pregnant woman with asymptomatic bacteriuria.

Investigatiaons on drug-resistance of Shigella sonnei bacilli isolated in Poland in the years 1959-1972.

2538 strains of Shigella sonnei bacilli, isolated from patients in the years 1959-1972, have been tested for drug-resistance. The strains examined came from different regions of Poland. Drug-resistance has been determined by the method of "multi-arm" disks of filter-paper. In investigations 12 chemotherapeutics have been employed. The tests performed have shown that 63% of strains were resistant to one or more chemotherapeutics. The percentage of streptomycin-resistant strains, found in the investigations, was higher than that found by other authors. In the material examined 24% of strains were resistant to antibiotics, and sensitive to sulfathiazole. No strains resistant to eight or more chemotherapeutics applied have been found.

Disposition of sulfonamides in food-producing animals V: Disposition of sulfathiazole in tissue, urine, and plasma of sheep following intravenous administration.

The plasma, urine, and tissue sulfathiazole concentrations were determined at various times following intravenous administration to 12 sheep. The plasma and urine data were consistent with a one-compartment pharmacokinetic model, with an elimination half-life of 1.1 hr and a volume of distribution of 0.39 liter/kg. Sulfathiazole was eliminated by excretion of unchanged drug in urine (67%) and by formation of two metabolites. The data obtained from eight tissue sites were consistent with the one-compartment pharmacokinetic model presented and confirmed that tissue residues of sulfathiazole can be calculated from serum and urine drug concentration.

Water-soluble polycations as oral drug carriers (tablets).

New bioerodible materials that are noncross-linked and water-soluble copolymers of trimethylaminoethyl methacrylate chloride (TMAEMC) and methyl methacrylate (MMA) were synthesized and then bound to anionic drugs (diclofenac Na and Na sulfathiazote) to form water-insoluble complexes. These drug-polymer complexes release the bound drugs only in ionic media. Compressed tablets were prepared from these anion-exchange resins, and their release profiles follow zero-order kinetics (n > 0.89, where n is the release exponent). The effects of various excipients (dextrose, lactose, and microcrystalline cellulose) were studied, and the polymer composition was found to influence the duration of drug release. It was also found that the release of anionic drugs from drug-PTMAEM/MMA is linear and that it is possible to "tailor-make" their release kinetics by suitably altering the copolymer composition. When a high content of a water-insoluble excipient (i.e., microcrystalline cellulose) was used to fabricate the tablets, the release kinetics deviated from linearity (n = 0.73). In general, release kinetics were well described by a dissociation/erosion mechanism. Drug loading could be increased by increasing the exchange capacity of the polymer (i.e., by increasing the content of the quaternary amine monomer).

Determination of sulfathiazole in type C medicated swine feed by reversed-phase liquid chromatography with post-column derivatization.

A convenient method was developed for determination of sulfathiazole (STZ) in Type C medicated swine feed by reversed-phase liquid chromatography (LC) with post-column derivatization. Addition of extractant solution (0.2N HCl and 1.5% diethylamine in 25% methanol) and an internal standard (IS), sulfamethylthiazole (SMZ), to 5 g sample was followed by mechanical shaking for 1 h. The extract was clarified by chilling, centrifugation, and filtering before injection onto a C18 reversed-phase column. The mobile phase components were 2% acetic acid and 1:1 acetonitrile-methanol (83 + 17%, v/v). Run time was about 20 min. Determination and, largely, the method's selectivity were based on detection at 450 nm of the derivative formed by the post-column reaction of dimethylaminobenzaldehyde with the primary amine of the analyte and IS. The IS, SMZ, differs from STZ by a single substituent methyl group, is stable, and is readily resolved from STZ. Although SMZ is not commercially available, it can be synthesized with relative ease from purchased reagents and will be supplied by the authors to interested laboratories. In single-laboratory validation, linearity was demonstrated over the range of 0.055-550 microg/mL, well beyond the target concentration of 5.5 microg/mL. The estimated limit of detection was 0.04 microg/mL; the calculated limit of quantitation was 0.13 microg/mL (feed concentration of 2.4 g/T or 2.7 mg/kg). Wet-spiking trials with a variety of swine feed matrixes showed recovery to be 100-102% for the intended concentration range, 50-200 g/T, with coefficient of variation (CV) < 2%. The method ruggedness was verified with an overall CV of 2.9%.

Disposition of sulfonamides in food-producing animals: pharmacokinetics of sulfathiazole in sheep.

Plasma and urine data on sheep following administration of sulfathiazole as single intravenous and oral doses were examined. A one-compartment open model was developed to describe the pharmacokinetics of sulfathiazole in sheep. The drug was rapidly eliminated, primarily by renal excretion of unchanged sulfathiazole and metabolism to acetyl sulfathiazole, with a biological half-life of 1.3 hours. Sulfathiazole was absorbed slowly (half-life, 18 hours) and relatively completely (73%) after oral administration in solution.

Comparative efficacy of sulfamethazine and sulfathiazole in feed for control of Bordetella bronchiseptica infection in swine.

Seventy-two conventionally raised pigs were challenge exposed intranasally when approximately 3.5 weeks old with yolk-grown Bordetella bronchiseptica. Twenty-four pigs acted as noninfected, nonmedicated controls. Feed containing sulfamethazine or sulfathiazole (110 mg/kg of feed) was initiated in 2 groups of 24 infected pigs each 3 days after challenge exposure and was fed continuously for 56 days. Twenty-four infected pigs were given nonmedicated feed. Challenge exposure with the B bronchiseptica resulted in nasal bordetellosis characterized by isolations of the test organism from nasal cavities of infected control pigs at greater than 90% frequency through 28 days and from at least 50% of the pigs through 56 days. Moderate turbinate atrophy developed with a 48% increase in mean turbinate space in infected control pigs at necropsy. Performance was not affected by the infection which was confined to the nasal cavity. The B bronchiseptica isolation rate decreased faster (P less than 0.01) in the sulfamethazine group than in the sulfathiazole group. By day 42, sulfamethazine-medicated pigs were negative for B bronchiseptica in nasal swab samples; whereas 8% to 17% of sulfathiazole-medicated pigs were positive from days 42 to 56. Turbinate spacing measurements averaged 11% less in the sulfamethazine group than in the sulfathiazole group.

Effect of Haemonchus contortus infection on the clearance of antipyrine, sulfobromophthalein, chloramphenicol, and sulfathiazole in lambs.

A study was made to determine the effect of Haemonchus contortus parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of sulfobromophthalein or sulfathiazole from the plasma of lambs was unaffected by infection with H contortus. Clearance of antipyrine was enhanced by the infection, and thiabendazole treatment did not alter this effect. Clearance of chloramphenicol (CAP), administered as the succinate ester (CAPS), was not changed by the infection, but it was increased after treatment with thiabendazole. Changes in the mean body residence time and initial plasma concentration of CAPS and CAP after treatment with thiabendazole indicate that hydrolysis of CAPS to CAP was reduced. High concentrations of CAPS apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of CAP-glucuronide. Enhanced clearance of antipyrine following infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that the lambs did not have mature amounts of hepatic drug metabolizing enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second, infection of lambs by H contortus may have triggered an inductive response in hepatic cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic protein synthesis associated with the physiologic response to replace plasma proteins and other blood components lost through gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and glutathione-S-transferase apparently were not affected.

Oral bioavailability of sulphamethoxydiazine, sulphathiazole and sulphamoxole in dwarf goats.

To get a better insight into the oral bioavailability of sulphonamides in ruminants, sulphamethoxydiazine (pKa 7.0), sulphathiazole (pKa 7.2), and sulphamoxole (pKa 7.4) were administered to dwarf goats (n = 5). The drugs were given at 2-week intervals by the intravenous or intraruminal route at a dose of 100 mg per kg body weight. After IV injection, the mean half-life (t1/2 beta in h +/- SEM) was 0.80 +/- 0.10 h, 2.35 +/- 0.38 h, and 3.36 +/- 1.25 h, for sulphathiazole, sulphamoxole, and sulphamethoxydiazine, respectively and the mean distribution volume (Vd beta) was 0.23 +/- 0.05 l/kg, 0.23 +/- 0.04 l/kg, and 0.33 +/- 0.02 l/kg. After intraruminal administration, the mean bioavailability varied from 86.0 +/- 11.8% for sulphamethoxydiazine to 46.6 +/- 4.3% for sulphamoxole, and 52.6 +/- 7.2% for sulphathiazole. The elimination half-life was significantly prolonged, probably due to a low rate of drug absorption from the gastrointestinal tract. In contrast to chloramphenicol, the sulphonamides studied were stable when incubated in rumen fluid at 39 degrees C.

Serum activity/concentration profiles of a sustained-released formulation of sulphathiazole-trimethoprim (2.5:1) in calves.

Thirty-six two-week-old healthy Holstein-Friesian calves weighing between 52 and 58 kg were divided at random into three groups of 12; group A calves were given a single oral bolus containing 2.5 g sulphathiazole and 1 g trimethoprim in a sustained-release formulation; group B received the same doses of the drugs but the trimethoprim was not in a sustained-release formulation; group C received a bolus containing 2.5 g sulphathiazole and 0.5 g conventional trimethoprim. Blood samples were collected at intervals for two days, the serum was separated and the composite antibacterial activity profiles of the mixture were analysed by an agar-diffusion microbiological method. The mean maximum activities in the serum of the three groups were 23.4 microg/ml in group A, 9.25 microg/ml in group B and 8.01 microg/ml in group C. The mean areas under the curves of the serum activity time curves were 838 microg/ml/hour in group A, 216 microg/ml/hour in group B and 182 microg/ml/hour in group C.

Use of a uterine pessary to prevent infection of the uterus of the cow after parturition.

A uterine pessary containing penicillin, streptomycin, formosulphathiazole and ethinyloestradiol, was assessed for its efficacy in reducing the frequency and severity of uterine infections in cows after parturition. Fifteen pluriparous Holstein Friesian cows had pessaries inserted into the uterus within 24 hours after calving. Compared with 14 similar untreated cows there were significant reductions in the number infected by Actinomyces pyogenes and in the number exhibiting abnormal uterine discharges.

A clinical pathologic study of mercurialentis medicamentosus.

Thirty-one patients who used eye drops containing the preservative, phenylmercuric nitrate for from 3 to 15 years, developed a brownish pigmentation of the anterior capsule of the pupillary area. Light and electron microscopic studies on two lenses demonstrated deposits of dense particulate material resembling melanin pigment on and in the anterior capsule of the lens in the area of the pupil. Special studies, including electron microprobe analysis and neutron activation analysis established the presence of mercury in a lens with mercurialentis. No mercury was found in two lenses used as controls.

[The texture and properties of sulfaethidol tablets]. / Untersuchungen über die Textur und die Eigenschaften von Sulfaethidol-Tabletten.

Scanning-electron-microscopic and X-ray diffractometric studies on the effect of the pressing power on the physical parameters of compressed tablets and on the texture of tablets containing sulfaethidol as the active principle, have shown that the crystal structure remains unchanged. The alterations observed in the physical parameters can be explained on the basis of present knowledge of the texture.

Preparation of ethyl cellulose microcapsules using the complex emulsion method.

In the present work, an investigation was designed to encapsulate a drug with ethyl cellulose using the complex emulsion method. The technique involved the dispersion of the drug in chloroformic solution of ethyl cellulose, followed by emulsification of the polymer solution in water using sodium lauryl sulfate. After continuous stirring for 5 h at room temperature, the solvent evaporates and a rigid polymer film was formed. The optimum surfactant concentration was determined and the effect of different polymer concentrations and core/coat ratios on the quality of the microcapsules produced was investigated. Drug dissolution was retarded as a result of microencapsulation and was controlled by changing core/coat ratios. The dissolution pattern was indicative of the suitability of this technique for the preparation of prolonged action medication.

Bioavailability of sulfathiazole from flocculated and deflocculated suspensions and its implications.

Flocculation is commonly used to stabilize pharmaceutical suspensions. Flocculated and deflocculated suspensions of sulfathiazole were administered to healthy human volunteers. Bioavailability from these two types of suspensions was studied from urinary free drug excretion. Bioavailability was significantly lower from flocculated suspensions. The study indicates the necessity of studying all flocculated drug suspensions for bioavailability data.

[Studies on the antiviral activity of silver sulfathiazole]. / Badania przeciwwirusowej aktywnosci soli srebrowej sulfatiazolu.

Silver sulfathiazole shows strong antibacterial activity and good tolerance after topical application. The aim of the study was to determine the antiviral activity of silver sulfathiazole in tissue culture after incubation of drug and virus. The antiviral activity was measured after various periods of exposure and at different drug concentrations. The results obtained indicate the activity of silver sulfathiazole against Herpesvirus type 1 and type 2. This drug suppresses or completely inactivates the infectivity of virus. The antiviral effect is directly related to concentration of the drug and duration of exposure. At concentration of 10 micrograms/ml it has the highest activity after 30 minutes of exposure, however at a concentration of 20 micrograms/ml it induces a similar effect after 10 minutes. Silver sulfathiazole had antiviral activity similar to that of silver nitrate, while sulfathiazole alone was ineffective.

Travellers' diarrhoea: prevention by chemoprophylaxis.

The chemoprophylaxis of travellers' diarrhoea by iodochlorhydroxyquinoline combinations, neomycin and phthalsulphathiazole, furazolidone, bismuth salicylates and streptotriad is reviewed. Streptotriad is regarded as a highly effective prophylactic against travellers' diarrhoea. Some elementary food hygiene precautions are detailed.

[Results of treatment of dysentery patients with streptomycin-dependent vaccine in comparison with other methods of treatment]. / Rezul'taty lecheniia bol'nykh dizenteriei streptomitsinzavisimoi vaktsinoi v sopostavlenii a drugimi metodami terapii.

Comparative study of various methods of treatment was carried out on 777 patients suffering from acute dysentery with a bacteriologically confirmed diagnosis. To assess the therapeutic efficacy, along with consideration of clinical signs of the disease, immunoglobulin level was examined in the blood and coprofiltrates; also the state of reparative processes in the mucosa was appreciated by the histological examination of the biopsy material. Results of the work carried out indicated the inexpediency of the treatment of this disease with a combination of levomycetin and phthalazol. The use of live streptomycin-dependent dysentery vaccine was indicated in protracted torpid dysentery and was of no avail in acute form of the disease. A good therapeutic effect was observed with the application of pathogenetic therapy alone.

[The effect of ftalazol on the body allowance in rats of B-group vitamins]. / Vliianie ftalazola na obespechennost' organizma krys nekotorymi vitaminami gruppy B.

A certain decrease in the content of riboflavin in blood plasma and liver and its excretion in the urine were encountered 24-h after administration of phthalazol, according to the schedule of acute dysentery treatment, in rats with initial moderate deficiency in vitamins B1 and B2. The provision with vitamin B1 did not change in this case. The introduction of phthalazol was attended with a noticeable decrease in the excretion of pyridoxic acid but did not affect the B6 content in the liver and blood serum of the animals.