Synthesis of certain mercapto-and aminopyrimidine derivatives as potential antimicrobial agents

Reaction of ethyl 4-chloro-2-phenylpyrimidine-4-carboxylate (4) with 5-chloro-2-methylthiophenol or 3-aryl-4-phenyl-1,2,4-triazole-5-thiol yielded the corresponding thioethers (5) and (8a, b), respectively. Careful alkaline hydrolysis of (5) yielded the corresponding carboxylic acid (6). Reaction of (4) withp-aminoacetophenone yielded compound (10) which was reacted with certain aromatic aldehydes to afford the α, β-unsaturated ketones (11a–d). Condensation of (11a–d) with malononitrile or phenylhydrazine yielded the 2-amino-3-cyanopyridines (12a–f) or the 2-pyrazolines (13a, b), respectively. Seven representative compounds were tested for theirin vitro antimicrobial activity against some pathogenic micro-organisms, some of them were proved to be active.     

伤寒杆菌的耐药性与伤寒的爆发流行

本文报道55株散发和38株爆发伤寒菌株的药物敏感试验、质粒检测及R质粒传递试验的结果。所有受检菌均出现不同程度的耐药现象,严重者耐药达8种之多;爆发株对常用抗菌素的耐药性明显高于散发株。R质粒的接合传递试验结果初步表明,散发株可传递性R质粒检测结果阴性,但发现一起爆发中,流行株携带有可传递性R质粒,由于检测菌株数尚少,其意义有待进一步探讨。     

Effects of sanguinarium, chlorhexidine and tetracycline on neutrophil viability and functions in vitro

The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells. Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time. Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections. However, their effects on host immune cells during different treatment regimens are not known. Due to their ability to serve as the first line of host defense against microbial infections, we have compared the effects of these antimicrobial agents on human neutrophil functions and viability. The results show that SANG is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested. However, exposures of neutrophils to very low concentrations of SANG (0.001%) inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min. Increasing the exposure time results in a similar inhibition of neutrophil functions, albeit at 50–100 fold lower concentrations of SANG. CHX rapidly disrupts the cell membrane of both crevicular and peripheral blood neutrophils at concentrations above 0.005% within 5 min, and inhibition of all neutrophil functions is due to its lytic properties. While TET is least toxic to neutrophils, a dose dependent inhibition of neutrophil functions is dependent on the calcium concentrations of the cellular environment, and is observed only above 0.04% or higher concentrations in the absence of calcium. The data suggest that a critical cumulative concentration of these drugs is essential for their toxicity and inhibition of neutrophil functions. Therefore, both the length of exposure and the dose of the drug both are critical while considering the effectiveness of SANG, CHX or TET in the treatment of infections. Furthermore, due to differences in their mechanisms of action, the consequences of their effects on neutrophils may have significant bearing on tissue pathology as well as on their therapeutic efficacy.     

Antibiotic proteins of polymorphonuclear leukocytes

Abstract: The polymorphonuclear leukocyte (PMN) plays an essential role in the innate defense of the mammalian host against bacterial invaders. Responding chemotactically, the PMN delivers a complex antibiotic arsenal to sites of infection. Among these cytotoxic systems is an array of antimicrobial proteins and peptides that the PMN directs at microorganisms both before (i.e. extracellularly) and after sequestration into a phagocytic vacuole. In addition to their microbicidal capacity, several of these proteins bind to and neutralize the endotoxic activity of Gram-negative bacterial lipopolysaccharides (LPS). In this review the principle features of these antibiotic proteins are briefly summarized with emphasis on their possible actions in biological settings. In many instances, additional functions independent of cytotoxicity have been described raising the possibility that some of these proteins subserve multiple roles in inflammation.     

感染性眼内炎致病原因及病原菌分布

目的 了解感染性眼内炎的致病原因、病原菌分布及耐药情况。方法 回顾性分析2016年1月-2018年12月某院病历系统中感染性眼内炎患者的临床资料。结果 90例感染性眼内炎主要由眼外伤所致（56.7%）,20例（22.2%）由眼部手术后引起,其中19例（95.0%）为白内障手术合并人工晶状体植入术引起。52株感染性眼内炎致病菌中,革兰阳性菌占50.0%（26株）,主要为表皮葡萄球菌（13株）,革兰阴性菌占30.8%（16株）,主要为铜绿假单胞菌（6株）、肺炎克雷伯菌（4株）。表皮葡萄球菌对万古霉素、利奈唑胺、利福平、替加环素敏感率为100.0%,对青霉素及苯唑西林敏感率较低（<50%）。结论 感染性眼内炎多由眼外伤和眼部手术尤其是白内障手术引起,致病菌以表皮葡萄球菌、铜绿假单胞菌和肺炎克雷伯菌为主。     

男性非淋病性尿道炎患者支原体的检测和对10种抗菌药物的敏感性试验

为了解解脲支原体和人型支原体在男性非淋病性尿道炎(NGU)中的致病作用和它们的体外药物敏感状况,运用微量肉汤稀释法对支原体进行10种抗菌药物的敏感性测定。在268例疑为NGU的男性患者中,85例（31.7%）支原体培养阳性,其中UU感染71例（26.5%）,MH感染4例（1.5%）,MH+UU感染10例（3.7%）,85例阳性患者的支原体株对10种抗菌药物的高度敏感性依次为交沙霉素（81.2%）、克拉霉素（73.0％）、司巴沙星（70.6%）、罗红霉素（67.1%）、阿奇霉素（55.3%）、强力霉素（28.2%）、美满霉素（16.5%）、氧氟沙星（15.3%）、环丙沙星（14.2%）、培氟沙星,发现11株对四环素类和喹诺酮类（除司巴沙星外）交叉耐药。认为支原体的定期耐药性监测,对临床用药有重要意义。     

Role of Burkholderia pseudomallei–Specific IgG2 in Adults with Acute Melioidosis,Thailand

Melioidosis is a life-threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei. An effective vaccine is needed, but data on protective immune responses in human melioidosis are lacking. We used ELISA and an antibody-dependent cellular phagocytosis assay to identify the major features of protective antibodies in patients with acute melioidosis in Thailand. We found that high levels of B. pseudomallei–specific IgG2 are associated with protection against death in a multivariable logistic regression analysis adjusting for age, diabetes, renal disease, and neutrophil count. Serum from melioidosis survivors enhanced bacteria uptake into human monocytes expressing FcγRIIa-H/R131, an intermediate-affinity IgG2-receptor, compared with serum from nonsurvivors. We did not find this enhancement when using monocytes carrying the low IgG2–affinity FcγRIIa-R131 allele. The findings indicate the importance of IgG2 in protection against death in human melioidosis, a crucial finding for antibody-based therapeutics and vaccine development.