Effects of Fluorides,Cortico-Steroids and Tetracyclines on Extraction Wound Healing in Rats

The effects of locally applied fluorides, corticosteroids and tetracyclines upon the healing of extraction wounds were studied in 77 albino rats. It was found that the fluorides definitely inhibit bone resorption; the cortico-steroids markedly increase osteoclasis and bone resorp-tions; while the tetracyclines stimulate osteogenesis and bone deposition. These actions were limited from 3 to 10 days after these solutions were incorporated into the blood clot. These findings suggest further studies to explore the application of fluorides and tetracyclines to clinical problems such as tooth replants, tooth transplants and in extraction wound healing.     

抗菌新药Amadacycline的药理学研究进展

Amadacycline（PTK-0796）是具有广谱作用的第三代四环素类抗生素,其对多重耐药以及敏感的革兰阳性菌、革兰阴性菌、厌氧菌以及非典型病原体都有着很好的抗菌活性。与万古霉素、利奈唑胺等抗感染药物相比,A-madacycline有着很好的体内药效。对于皮肤及皮肤组织感染的患者,Amadacycline有着很好的疗效及安全性,未发生严重的不良反应事件,也未出现过不良反应导致停止用药的现象。总之,Amadacycline将会成为未来抗菌药物的＂明星＂。     

Assessment of in vivo efficacy of eravacycline against Enterobacteriaceae exhibiting various resistance mechanisms: a dose-ranging study and pharmacokinetic/pharmacodynamic analysis

After the pharmacokinetic (PK) profile of eravacycline, a novel fluorocycline, was defined, understanding its pharmacodynamic (PD) profile became essential. This study aimed to assess the correlation of the PK/PD index fAUC/MIC (ratio of area under the free drug concentration–time curve to MIC) and its magnitude with eravacycline's efficacy against Enterobacteriaceae using an immunocompetent murine thigh infection model to resemble the immunocompetent environment in eravacycline's clinical trials. Eight Enterobacteriaceae isolates with various resistance mechanisms were tested. Eravacycline doses ranged from 1–10?mg/kg/day and were given either once daily (q24h) or divided into doses every 12?h (q12h) over the 24-h treatment period. Antibacterial efficacy was measured as the change in log₁₀CFU at 24?h compared with 0?h controls. Composite data were modelled using a sigmoid E_max model. Eravacycline MICs ranged from 0.125–0.5?µg/mL. The mean fAUC/MIC magnitudes required for stasis and 1-log reduction for the eight isolates were 2.9?±?3.1 and 5.6?±?5.0, respectively. Whilst the humanised eravacycline regimen (2.5?mg/kg q12h) pharmacokinetically achieves an fAUC_0–24 that is higher than the fAUC_0–24 achieved with the 5?mg/kg q24h dose, the latter was associated with greater efficacy, raising a suggestive correlation of the peak free drug concentration to MIC (fC_max/MIC) ratio with eravacycline's efficacy. This study showed that the magnitudes associated with eravacycline's efficacy in an immunocompetent murine thigh model appear to be close to achievable targets in human. These data support further development of eravacycline for treatment of infections caused by drug-resistant Enterobacteriaceae.     

Characterization of tetracycline and methicillin resistant Staphylococcus aureus strains in a Spanish hospital: Is livestock-contact a risk factor in infections caused by MRSA CC398?

Tetracycline-resistance (Tet^R) has been postulated as a marker of the livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage CC398. Objectives of the study: to determine the spa-types and assigned MLST clonal complexes (CCs) among all 98 MRSA-Tet^R strains recovered during 2011–2012 (from different patients) in a Spanish Hospital, analyzing the possible correlation with livestock-contact of the patients. All 98 strains were assigned to 9 CCs: CC398 (60.2%), CC1 (19.4%), CC5 (12.2%), and other CCs (8.2%). The 98 patients were classified into three groups: (A) contact with livestock-animals (n = 25); (B) no-contact with livestock-animals (n = 42); (C) no information about animal contact (n = 31). A significant higher percentage of CC398 strains was obtained in group A (76%) than in group B (50%) (p < 0.05), being the percentage in group C of 61.3%. Most of MRSA-Tet^R-CC398 strains presented a multi-resistance phenotype, including erythromycin, clindamycin, and ciprofloxacin, and the most prevalent detected genes were tet(M) and erm(C). Three strains presented the phenotype macrolide-susceptibility/lincosamide-resistance and contained the vga(A) gene. MRSA-CC1 strains showed higher percentages of erythromycin/clindamycin resistance (95%/89%) than MRSA-CC398 strains (58%/63%), and this resistance was usually mediated by erm(C) gene. Most of MRSA-CC5 strains showed resistance to ciprofloxacin, tobramycin/kanamycin and erythromycin. None of the strains presented the genes lukF/lukS-PV, tsst-1, eta, etb or etd. All MRSA-CC398 strains lacked the genes of the immune-evasion-cluster, but MRSA-CC1 strains carried these genes (type E). In conclusion, although MRSA CC398 is detected in a significant higher proportion in patients with livestock-contact; its detection in people without this type of contact also indicates its capacity for human-to-human transmission.     

Wolbachia translation initiation factor-1 is copiously expressed by the adult,microfilariae and infective larvae of Brugia malayi and competitively inhibited by tetracycline

The intracellular alphaproteobacteria, Wolbachia, is considered to be a future antimacrofilarial drug target as it is obligatory for filarial endurance. Characterizing wolbachial proteins is necessary to understand wolbachial mechanisms and also for discovering new drug entities. Translation initiation factor-1 (Tl IF-1) is an indispensable prokaryotic factor concerned with bacterial viability. This factor is prioritized as one of the most potent antibacterial drug target. To investigate its role in filarial biology, recombinant Wol Tl IF-1 was purified on metal ion column. The factor was found folded in its monomeric native conformation, and contained a buried fluorophore. Molecular modeling revealed that the factor belonged to the Oligomer Binding family, and consisted of the highly conserved S1 domain with 81.6% of the amino acids occupying the allowed regions in Ramachandran plot. In addition, Wol Tl IF-1 exhibited selective binding to the 30S ribosomal subunit, which declined progressively with tetracycline addition. Tetracycline perturbs interaction of Thr18 and Asn32 of the factor with ribosomal protein S4. The factor was immune-localized in adult, microfilariae (Mf) and infective larvae (L3) of Brugia malayi by immunoblotting. High expression was also observed in Wolbachia within B. malayi Mf, L3 and female adult parasite along the gravid uteri by the confocal microscopy. Therefore, Wol Tl IF-1 appears to be an essential Wolbachia factor whose inhibition leads to extensive cell apoptosis and premature killing of adult worms, validating the antifilarial potential of the factor.     

Tetracycline: a cure all?

Tetracyclines are used to treat a range of oral conditions. Their efficacy in the treatment of periodontitis is well established, and they are authoritatively recommended in the management of avulsed teeth. There is a growing evidence base to support the use of tetracycline to treat recurrent aphthous stomatitis, but its use in white spongy naevus is limited to a handful of case reports. The mechanism of action in these conditions is either unknown or indicated to be through the inhibition of matrix metalloproteinases (MMP). The use of a single agent to treat diverse oral conditions has important implications for oral medicine.     

幽门螺杆菌对四环素耐药的机制研究进展

近年来,随着四环素被再次用于临床幽门螺杆菌(Helicobacter pylori, Hp)根除治疗,临床可能会出现Hp四环素耐药株,影响Hp的根除率。为了解Hp对四环素的耐药机制,促进建立快速筛查Hp四环素耐药株检测方法,指导临床医师为患者制定个性化Hp根治方案,本文对Hp感染及治疗现状及四环素耐药机制作一综述。     

Evaluation of plasmids in tetracycline resistant strains of Neisseria Gonorrhoeae and Ureaplasma Urealyticum in a case of severe urethritis

A young man who acquired gonococcal urethritis in the Far East was not cured by repeated i.v. treatment with a broad-spectrum penicillin. Cultures of pre- and post-treatment urethral specimens grew tetracycline-resistant penicillinase-producing Neisseria gonorrhoeae (PPNG) and tetracycline-resistant Ureaplasma urealyticum. The patient was successfully treated with erythromycin, to which both isolates were sensitive. The strain of N. gonorrhoeae carried a novel plasmid of 10.5 Md molecular mass in addition to plasmids previously observed in this organism. The strain of U. urealyticum carried two distinct plasmids, one with mass 4.9 Md and the other one with mass 8.1 Md. This report demonstrates that ureaplasmas can contain plasmids and raises the question if tetracycline resistance is controlled by plasmids or by the chromosome.Corresponding author.     

四环素局部注射治疗血管瘤的临床研究

1986年～1991年10月,应用四环素溶液注射治疗血管瘤305例,经随访3个月～48个月,肿瘤消失者278例,另27例仍在随访观察之中。介绍了四环素溶液的配制,注射方法,适应证,注射后的观察与护理;讨论了四环素的作用机理、并发症的诊断与治疗等。