STRUCTURE AND BIOLOGICAL ACTIVITY OF LIPIARMYCIN
Actinoplanes deccanensis ATCC21983, the producer of antibiotics lipiarmycin A3 and A4, furnished also a related antibiotic designated lipiarmycin B, active against Gram-positive bacteria, including anaerobes, and against Neisseria. The structures of the two major components, B3 and B4, were elucidated from their physico-chemical properties, XHand 13C NMRspectra and fast atom bombardmentmass spectra data in comparison with lipiarmycins A3andA4.
Fidaxomicin (OPT-80) for the treatment of Clostridium difficile infection
Importance of the field: Clostridium difficile infection (CDI) has become an increasingly important healthcare-associated complication in many countries. CDI outbreaks, a new ‘hypervirulent’ form and increased worldwide rates have underscored four urgent unmet needs for this disease: i) effective prevention of CDI; ii) therapies to produce faster resolution of CDI symptoms; iii) therapies to treat severe CDI more effectively and reduce its mortality; and iv) therapies to reduce the CDI recurrence rate following treatment. Areas covered in this review: Fidaxomicin, a new macrocyclic antibiotic, has demonstrated potent in vitro activity against C. difficile with limited or no activity against normal fecal flora. It is minimally absorbed from the intestinal tract, even in the presence of intestinal inflammation. When tested against oral vancomycin in clinical studies of CDI therapy, it has equivalent efficacy for curing CDI at end of treatment and a comparable safety profile to that agent. However, fidaxomicin therapy of CDI is associated with significantly fewer CDI recurrences in the 28 days following treatment. Symptom resolution is also slightly quicker in some CDI patients. Additional fecal flora analysis in the CDI trials showed that fewer individuals developed intestinal colonization with vancomycin-resistant enterococci (VRE) among the fidaxomicin-treated group. This new molecule, which has just completed two large Phase III multicenter studies, successfully addresses two of the four urgent and unmet needs for dealing with CDI. What the reader will gain: Fidaxomicin is as effective and as safe as vancomycin therapy for treating CDI but is associated with far fewer recurrences post-treatment and a decreased risk of VRE acquisition. Take home message: Fidaxomicin is a potential new therapy for CDI which has the capacity to substantially decrease post-treatment recurrences and is as safe and well-tolerated as standard vancomycin treatment.
Improvement of scopolamine-induced memory impairment by Z-ajoene in the water maze in mice
Z-ajoene, a major compound containing sulfur in oil-macerated garlic products, exhibited inhibitory effects against scopolamine-induced memory impairment in mice using the Morris water maze test. The effects of Z-ajoene were observed dose-dependently (0.25-25 mg/kg). At the highest dosage, the memory performance of mice was improved compared to normal mice. The acetylcholinesterase (AChE) activity in the brain was reduced by administration of Z-ajoene dose-dependently. However, alliin and diallyl disulfide, organosulfur compounds from garlic, did not improve memory performance nor AChE inhibitory effect. These results suggest that Z-ajoene may act on the cholinergic system and on memory impairment caused by excess activity of AChE.