Nano drug delivery systems and gamma radiation sterilization.

In recent years, drug delivery systems such as liposomes and microparticles have been used in clinic for the treatment of different diseases and from a regulatory point of view, a parenterally applied drug and drug delivery systems must be sterile and pyrogen free. Radiation sterilization is a method recognized by pharmacopoeias to achieve sterility criteria of parenterals. It has the ability to kill microorganisms in therapeutic products. The ability of, however, irradiation might also affect the performance of drug delivery systems. One of the most critical points is irradiation dose, because certain undesirable chemical and physical changes may accompany with the irradiation, especially with the traditionally applied dose of 25 kGy. Its ionizing property may cause fragmentation of covalent bond. The care must be paid to the applied dose. In this research, the effects of gamma irradiation on different drug delivery systems such as chitosan microparticles, liposomes, niosomes and sphingosomes were investigated. According to the experimental data, it can be concluded that gamma irradiation can be a suitable sterilization technique for liposome, niosome and sphingosome dispersions. When all irradiated drug carrier systems were taken into consideration, chitosan glutamate microparticles were found as the most radioresistant drug delivery system among the others.

In vitro/in vivo evaluation of the efficiency of teicoplanin-loaded biodegradable microparticles formulated for implantation to infected bone defects.

Chronic osteomyelitis is still the cause of many problems in orthopaedics in terms of therapy and infection persistence. Four-to-six week systemic antibiotic therapy is required along with bone and soft tissue debridement in the therapy of chronic osteomyelitis. Prolonged-release local antibiotic therapy has been taken into consideration due to the side effects encountered in long-term high dose antibiotic use and the duration of hospitalization of the patients. Although local antibiotic therapy has been achieved by bone cement, a second surgical operation is needed for the removal of the system. On the other hand, heat generation during cement curing limits the use of heat-sensitive active ingredients. The most frequent osteomyelitis inducing micro-organism is gram (+) Staphylococcus aureus. In this study, teicoplanin, a glycopeptide antibiotic, active on gram (+) bacteria, was incorporated in a synthetic polymer in order to prepare a microsphere formulation for implantation to bone defects. Particle size, surface characteristics, loading capacity and in vitro release characteristics of the microspheres were determined as well as stability assessment of teicoplanin under accelerated conditions. In vivo studies were performed on rabbits and the microparticles were implanted intra-articularly to the lateral condylus of the femur. Antibiotic presence was detected by a microbiological assay from synovial fluid sample aspirated throughout 5 weeks. In the light of these evaluations, microspheres prepared from PLGA (75:25) (Mw 136,000) polymer were determined to be effective, and promising for obtaining prolonged local antibiotic release.

Biodegradable implantable teicoplanin beads for the treatment of bone infections.

Parenteral antibiotic therapy for acute bone infections, soft tissue infections and osteomyelitis may result in high serum concentrations, associated with nephrotoxic, ototoxic and allergic complications. After taking these above mentioned disadvantages into consideration, recent investigations have explored the use of antibiotic-loaded biodegradable implants, incorporating antibiotics for potential use in the treatment of bone infections. In this study, biodegradable implants containing teicoplanin for the prevention or the treatment of bone infections were designed by using sodium alginate as the polymer material. Therefore, teicoplanin, a glycopeptide antibiotic, active against gram-positive bacteria was incorporated in a natural polymer in order to prepare bead formulation for implantation purpose in bone for the localized treatment of osteomyelitis. In vitro characterization was realized by determining particle size, surface characteristics, loading capacity and in vitro release characteristics of the beads.

Synthesis and antimicrobial evaluation of some new thiazolo[4,5-d] pyrimidines.

In this study, by starting from ethyl 4-amino-2,3-dihydro-3-methyl-2-thioxothiazole-5-carboxylate (1), the compounds having 2,3-dihydro-3-methyl-5-mercapto-6-methyl/ethyl-2- thioxothiazolo[4,5-d]pyrimidin-7(6H)-one (2a, 2b) structure and their 5-(4'-nonsubstituted/-substituted benzoylmethyl)thio derivatives (3a-h) were synthesized. The chemical structures of the compounds were proved by IR, 1H-NMR and elemental analysis data. In vitro antimicrobial activities of the synthesized compounds were investigated against some bacteria and yeasts using the microdilution method. In view of the antimicrobial activity results, a significant inhibitory effect was observed only for compound 2a against Gram-positive bacteria and yeasts, whereas the other compounds had no remarkable activity against the tested microorganisms.

Synthesis of some 1-(2-naphthyl)-2-(imidazole-1-yl)ethanone oxime and oxime ether derivatives and their anticonvulsant and antimicrobial activities.

In this study, oxime and oxime ether derivatives of anticonvulsant nafimidone [1-(2-naphthyl)-2-(imidozole-1-yl)ethanone] were prepared as potential anticonvulsant compounds. Nafimidone oxime was synthesized by the reaction of nafimidone and hydroxylamine hydrochloride. O-Alkylation of the oxime by various alkyl halides gave the oxime ether derivatives. Anticonvulsant activity of the compounds was determined by maximal electroshock (MES) and subcutaneous metrazole (scMet) tests in mice and rats according to procedures of the Antiepileptic Drug Development (ADD) program of the National Institutes of Health (NIH). In addition to anticonvulsant evaluation, compounds were also screened for possible antibacterial and antifungal activities because of the structural resemblance to the azole antifungals, especially to oxiconazole. All compounds were evaluated against three human pathogenic fungi and four bacteria using the microdilution method. Most of the compounds exhibited both anticonvulsant and antimicrobial activities; the O-alkyl substituted compounds (2, 3, 4 and 5) were found to be more active than the O-arylalkyl substituted compounds in both screening paradigms.

New thiazolo[4,5-d]pyrimidine derivatives as potential antimicrobial agents.

In this study, by starting from ethyl 4-amino-2,3-dihydro-3-phenyl-2-thioxothiazole-5-carboxylate (1), three compounds having 2,3-dihydro-3-phenyl-5-mercapto-6-alkyl/phenyl-2-thioxothiazolo[4,5- d]pyrimidin-7(6H)-one (2a-c) structure and their 5-(4'-nonsubstituted/-substituted benzoylmethyl)thio derivatives (3a-l) were synthesized. The antimicrobial activities of the synthesized compounds were investigated against some bacteria and fungi using the microdilution method. 2,3-Dihydro-3,6-diphenyl-5-(4'-bromobenzoylmethyl)thio-2-thioxothiazolo [4,5-d]pyrimidin-7(6H) one (3k) possessing remarkable activity against Gram-positive bacteria and yeast like fungi was found to be the most active compound in this series.

Effects of tenoxicam on neutrophil chemotaxis in rheumatoid arthritis and healthy controls.

Using a modified Boyden chambers method, polymorphonuclear leucocyte (pmnl) random migration and chemotactic responsiveness were compared in 20 rheumatoid arthritis patients with that of 10 healthy controls receiving tenoxicam. Random migration and chemotaxis of neutrophils were examined before drug administration, following 2 hours and 7 days of drug administration and one week after the end of the 7-day-administration of this compound. There was no statistically significant difference between the chemotactic migration of neutrophils in healthy volunteers and patients with RA. The mean chemotactic value in patients with RA and healthy controls was significantly low at 2 hours after drug administration when compared with that before drug administration (p < 0.01). The comparison of the decreases in mean chemotactic values in patients with RA and healthy controls showed no statistical difference. At the end of 7-day-administration, neutrophil chemotaxis was significantly decreased in patients with RA (p < 0.01); however, in healthy controls it was decreased as well, but statistical difference could not be obtained. One week after drug withdrawal, neutrophil chemotaxis turned to baseline values in both groups. We suggest that tenoxicam is a potent inhibitor of neutrophil chemotaxis.

[Staphylococcal biotyping and the use of computers]. / Stafilokoklarin biyokimyasal tiplendirilmesi ve bilgisayar kullanimi.

Ninety coagulase negative staphylococci isolated from various clinical specimens in Clinical Microbiology laboratory of Hacettepe University Faculty of Medicine, were biotyped using a special computer program. Types of 30 strains isolated from pus were found to be S. epidermidis (36.7%), S. haemolyticus (20%), S. simulans (13.3%) and S. hominis (10%) respectively. Among the strains isolated from blood S. epidermidis was again the predominant microorganism (40%), followed by S. haemolyticus (20%) and S. simulans (10%).

[Comparison of two different media-atmosphere combinations on the isolation of group A beta-hemolytic streptococci from throat cultures]. / Farkli iki besiyeri-atmosfer kombinasyonunun bogaz kültürlerinden A grubu beta hemolitik streptokok izolasyonuna etkilerinin karsilastirilmasi.

In this study effects of incubation of sheep blood agar medium in aerobic conditions and incubation of sulfamethoxazole-trimethoprim containing sheep blood agar medium in 5 to 10% CO2, of the isolation of group A beta hemolytic streptococci from throat cultures were compared. 608 throat swab specimens were studied. Each agar medium was evaluated after 24 and 48 hours of incubation period. The aerobic incubation of sheep blood agar plates for 24 hours yielded 108 (17.7%) strains of beta hemolytic streptococci, of these 96 (15.8%) strains being group A. 113 (18.5%) strains of beta hemolytic streptococci were isolated after 48 hours of incubation and 100 (16.4%) of these were group A. The number of beta hemolytic streptococci isolated in 5 to 10% CO2 atmosphere for 24 hours was 62 (10.2%), and 57 (9.3%) of these were group A. When the incubation period was prolonged to 48 hours, the total number of beta hemolytic streptococci isolated increased to 82 (13.5%) and 76 (12.5%) of these were determined as group A. The difference between these two combinations was significant for 24 hours of incubation, but not significant for 48 hours of incubation. The highest isolation rate for group A streptococci was achieved in aerobic incubation of sheep blood agar plates for 48 hours.

[Identification of Pseudomonas species isolated from various clinical specimens and their susceptibility to ofloxacin]. / Klinik örneklerden izole edilen pseudomonas türlerinin saptanmasi ve ofloksasin'e karsi duyarlilik durumlarinin arastirilmasi.

In this study Pseudomonas species isolated from various clinical specimens were identified and susceptibility of these species to ofloxacin was investigated. The identification of 88 Pseudomonas isolates was performed according to their pigment production, type of haemolysis, growth on cetrimide medium and growth at 42 degrees C. Oxidase test was also employed to all of these strains. Macrodilution method was used in order to investigate in vitro activity of ofloxacin against these strains. All of 88 isolates were identified as P. aeruginosa. Ofloxacin was found to have an MIC 50 value of 2 micrograms/ml and an MIC 90 value of 16 micrograms/ml for these isolates. Susceptibility to ofloxacin was observed in 86.4% of 88 P. aeruginosa.