Prevention of the mutagenic activation of an antischistosomal isothiocyanate in primates by an antibiotic

Administration of 4 nitro-4′ isothiocyano-diphenylamine (CGP 4540, amoscanate) to two nonhuman primates, Macaca mulatta and Cebus apella, resulted in the appearance of mutagenic material in the urines of these animals. Mutagenic metabolites of this drug could also be detected in the urines when the drug was administered to primates infected with Schistosoma mansoni and Schistosoma japonicum. As observed previously in mice, the mutagenic activation of amoscanate can be prevented in primates by coadministration of a single oral dose of erythromycin with no concomitant reduction in antischistosomal activity. The protective effect of erythromycin was confirmed in several crossover experiments. This dissociation of mutagenic from chemotherapeutic effects provides an opportunity to reduce serious potential long-term risks of this anti-schistosomal drug.     

Acute respiratory distress syndrome with transiently impaired left ventricular function and Torsades de Pointes arrhythmia unmasking congenital long QT syndrome in a 25-yr-old woman

We report a case of recurrent episodes of Torsades de Pointesarrhythmia in the setting of transiently impaired left ventricularejection fraction, acute respiratory distress syndrome, transienthypokalaemia and QT-prolonging drugs, in a previously healthy25-yr-old female patient. In the course of the clinical andgenetic work-up this patient was newly diagnosed with a mutationin KCNH2 encoding the     

Inhibition of the metabolism of brotizolam by erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism

AIMS: To obtain in vivo evidence for the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of brotizolam. METHODS: Fourteen healthy male volunteers received erythromycin 1200 mg day(-1) or placebo for 7 days in a double-blind randomized crossover manner. On the 6th day they received a single oral 0.5-mg dose of brotizolam, and blood samplings were performed for 24 h. RESULTS: Erythromycin treatment significantly increased the peak plasma concentration (P < 0.05), total area under the plasma concentration-time curve (P < 0.01), and elimination half-life (P < 0.01) of brotizolam. CONCLUSIONS: The present study provides in vivo evidence for the involvement of CYP3A4 in brotizolam metabolism.     

红霉素对弥漫性泛细支气管炎治疗作用的实验研究

目的探讨红霉素治疗弥漫性泛细支气管炎的作用机理。方法40只健康雄性SD大鼠随机分为三组：正常对照组、模型组和红霉素治疗组。红霉素治疗组于置管后7d按50mg／kg／a给予口服红霉素。实验60d后观察肺组织病理变化,应用ELISA方法测定血清与肺匀浆中TNF-α、IL-8的含量。结果血清中TNF-α、IL-8的含量三组 间无统计学差异（P〉0．05）;模型组肺匀浆中TNF—α及IL-8的含量较对照组明显增高（P〈0．05）,红霉素治疗组比模型组上述指标明显下降（P〈0．05）。结论细胞因子TNF-α、IL-8的释放可能与弥漫性泛细支气管炎的发病有关;红霉素治疗弥漫性泛细支气管炎可能是通过抑制细胞因子TNF-α、IL-8的释放而起作用的。     

Decreasing rates of resistance to penicillin, but not erythromycin, in Streptococcus pneumoniae after introduction of a policy to restrict antibiotic usage in Taiwan

A 16% decline in rates of penicillin resistance in Streptococcus pneumoniae isolates in Taiwan between 1998--1999 (25%) and 2001 (9%) was associated with a 46% decrease in total penicillin and other cephalosporin usage in 2001 compared with 1999. However, erythromycin resistance in S. pneumoniae remained high (94%), despite a 45% decrease in macrolide consumption between 1999 and 2001.     

New macrolide,lincosaminide and streptogramin B antibiotics

Importance of the field: New antibiotics are needed to overcome microbial resistance and to improve on the therapeutic index and clinical effectiveness of existing agents.

Area covered in this review: This review covers the journal and patent literature published from about the mid-2000s to 2010 to provide an overview of the large diversity of new chemical entities in the macrolide, lincosaminide and streptogramin B (MLS_B) class.

What the reader will gain: The review identifies areas of the greatest effort and recent results in pursuing structure–activity relationships among MLS_B antibiotics and highlights preclinical and clinical candidates that have arisen from these diverse discovery programs.

Take home message: Research on the MLS_B class appears promising for the eventual registration and commercialization of several new antibiotics that improve the clinical effectiveness of existing agents and combat antibiotic-resistant pathogens.     

Macrolide antibiotics in food-animal health

Several 14- and 16-membered-ring macrolide antibiotics have acquired important roles in the modern production of food animals. Macrolide antibiotics exhibit many similar antimicrobial properties whether used in veterinary or human medicine. In addition to their direct inhibitory action on micro-organisms, macrolides exert a variety of subinhibitory concentration (sub-MIC) effects that are being increasingly recognised as important factors in the explanation of therapeutic results. Macrolides achieve wide tissue distribution and high intracellular concentrations that contribute prominently to their efficacy. Another important factor governing efficacy is the complex interaction between macrolides, micro-organisms, and phagocytes that may enable the host defence system to enhance the antibiotic’s inhibitory action. A potential role for macrolides in modulating inflammatory processes has also been recognised. In both sub-MIC effects and interactions with the host immune system, different macrolides exert different responses that may reinforce or oppose each other. This complexity of responses requires additional studies in appropriate disease states and animal species in order to elucidate a more comprehensive understanding and explanation of in vivo outcomes.     

Recent pharmacological advances in the treatment of preterm membrane rupture,labour and delivery

Preterm delivery (before 37 completed weeks of gestation) is the major determinant of infant mortality. In women with a previous preterm birth associated with bacterial vaginosis, prophylactic antibiotics (e.g., metronidazole) reduce the risk of preterm birth and low birth weight. Trichomonas vaginalis increases the risk of preterm delivery, but metronidazole is not beneficial for this and may even be detrimental. Antibiotic use (e.g., erythromycin) prolongs pregnancy in late premature rupture and has health benefits for the neonate. However, antibiotics are probably not useful in preterm labour. Intramuscular 17α-progesterone and vaginal progesterone reduce the rate of preterm labour in high-risk pregnancies, including previous spontaneous preterm delivery. Magnesium sulfate, β₂-adrenoceptor agonists and the oxytocin-receptor antagonist, atosiban, are effective in reducing uterine contractions short-term, but there is little evidence that this leads to improved outcomes for the neonate. However, tocolysis with calcium-channel blockers does seem to lead to better outcomes for the neonate. Fetal side effects, such as ductus arteriosus constriction and impaired renal function, are associated with the inhibition of prostaglandin synthesis with indomethacin. New approaches and more effective drugs are required in the treatment of preterm delivery.     

Allergic contact dermatitis caused by topical antiacne drugs

Acne is a chronic inflammatory disease for which a long-lasting therapy, very often with topical drugs, is necessary. Despite the fact that several topical antiacne drugs (in particular, tretinoin, benzoyl peroxide, clindamycin and erythromycin) are used for many years, often on broad skin surfaces and for long periods of time, their potential for contact sensitization is low. Their potential for phototoxic and photoallergic reactions is also low. Much more frequent is irritant contact dermatitis caused by some of these drugs, in particular, retinoids and benzoyl peroxide, for which the short contact therapy has been recently suggested.     

EFFECT OF ERYTHROMYCIN ON GASTRIC DYSMOTILITY AND NEUROENDOCRINE PEPTIDES IN RATS WITH DIABETES MELLITUS

Objective To investigate the effect of erythromycin on the contractive activity of the isolated gastric antrum smooth muscle and somatostatin (SS), vasoactive intestinal peptide (VIP), motilin (MTL), and substance P (SP) in plasma and isolated gastric antrum tissue of diabetes mellitus (DM) rat models. Methods Thirty male Sprague-Dawley rats were divided into three groups: control group (n = 10), DM group (n =10), and erythromycin group (DM models with erythromycin treatment, n = 10). A single dose of streptozotocin (100 mg/kg,dissolved in 0.1 mol/L citric acid buffer, pH4.5) was injected intraperitoneally. After 48 to 72 hours, rats with blood glucose above 16.7 mmol/L and urine glucose level to be ( ) to ( ) over one week were considered successful DM models. The resting tension, mean contractile amplitude and frequency of spontaneous change in isolated longitudinal and circular gastric antrum smooth muscle strips were measured. SS, VIP, MTL, and SP levels in plasma and gastric antrum tissue were measured using radioimmunoassay. Results (1) In the isolated gastric antrum smooth muscle strips, the gastric motility parameters were lower in DM group than those in control group except circular smooth muscle contractile amplitude and longitudinal smooth muscle contractile frequency. The gastric motility parameters were significantly strengthened in erythromycin group, compared with DM group except longitudinal smooth muscle resting tension (P ＜ 0.01). (2) Plasma SS, VIP, and MTL concentrations in DM group were higher than those in control (P ＜ 0.05), while the SP level decreased (P ＜ 0.05). In the gastric antrum, SS of DM group was significantly higher than that of control group (P ＜ 0.01), while SP and MTL levels were lower than those of control group (P ＜ 0.05 and P ＜ 0.01, respectively). However, the level of VIP in gastric antrum tissue did not change among three groups. The plasma level of SS in erythromycin group was higher than that of DM group(P＜ 0.05). (3) The blood glucose was lower in erythromycin group than DM group (P ＜ 0.01).Conclusions Erythromycin has direct effects on contractive activity of gastric smooth muscle in diabetic rats, but there are few effects on neuroendocrine peptides. Gastric-motility disorders in diabetic rats have a correlation with the changes of neuroendocrine peptide levels in plasma and gastric antrum tissue.