BackgroundOsteoarthritis (OA) is a common joint disease that causes disabilities in elderly adults. However, few long-lasting pharmacotherapeutic agents with low side effects have been developed to treat OA. We evaluated the therapeutic effects of intra-articular injections of hydrogels containing hyaluronic acid (HA) and doxycycline (DOX) in a rabbit OA model.ResultsThirteen week old New Zealand White rabbits undergone a partial meniscectomy and unilateral fibular ligament transection were administered with either normal saline (NT), HA, DOX or HA-DOX hydrogels on day 0, 3, 6, 9 and 12; animals were also examined the pain assessment in every three days. The joint samples were taken at day 14 post-surgery for further histopathological evaluation. The degree of pain was significantly attenuated after day 7 post-treatment with both HA and HA-DOX hydrogels. In macroscopic appearance, HA-DOX hydrogel group showed a smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation in compare to HA or DOX treatment alone. In the areas with slight OA changes, HA-DOX hydrogel group exhibited normal distribution of chondrocytes, indicating the existence of cartilage regeneration. In addition, HA-DOX hydrogels also ameliorated the progression of OA by protecting the injury of articular cartilage layer and restoring the elastoviscosity.ConclusionOverall, from both macroscopic and microscopic data of this study indicate the injectable HA-DOX hydrogels presented as a long-lasting pharmacotherapeutic agent to apply for OA therapy.
Extended-spectrum beta-lactamases (ESBLs) are plasmid-mediated class A enzymes commonly found in the family Enterobacteriaceae, mainly in Klebsiella pneumoniae. Flavonoids have also been reported to possess antimicrobial activity. In this study, the in vitro activities of 18 antibiotics and 12 flavonoids against 20 ESBL-producing K. pneumoniae isolates were evaluated. All of these isolates were susceptible to imipenem and cefmetazole, but were resistant to ampicillin, ampicillin/sulbactam, aztreonam, cefazolin, cefoperazone, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, piperacillin and ticarcillin. Susceptibilities to amikacin, amoxicillin/clavulanate, cefoxitin, ciprofloxacin and gentamicin were variable. Myricetin, a flavonol, inhibited ESBL-producing K. pneumoniae isolates at a high minimum inhibitory concentration (MIC) (MIC(90) value 256 mg/mL), but exhibited significant synergic activity against ESBL-producing K. pneumoniae in separate combination with amoxicillin/clavulanate, ampicillin/sulbactam and cefoxitin. Because of the low-toxic nature of flavonoids, the combination of antibiotics and flavonoids is a potential new strategy for developing therapies for infections caused by ESBL-producing bacteria in the future.
Novel therapies are needed to address the public health problem posed by methicillin-resistant STAPHYLOCOCCUS AUREUS (MRSA). In this study, we determined the effects of combinations of antibiotics and plant polyphenols against 20 clinical isolates of MRSA. The IN VITRO activities of 10 antibiotics and 15 natural polyphenols against the isolates were evaluated by determining minimum inhibitory concentrations (MICs). All isolates were susceptible to vancomycin and resistant to rifampicin, while susceptibilities to ciprofloxacin varied. Among the 15 natural polyphenols, kaempferol (3,4',5,7-tetrahydroxyflavone) and quercetin (3,3',4',5,7-pentahydroxyflavone) showed the lowest MICs. In checkerboard assays, combinations of rifampicin and either kaempferol or quercetin acted synergistically or partially synergistically against the clinical MRSA isolates. Rifampicin combined with kaempferol or quercetin exhibited good beta-lactamase inhibitory effects (57.8 % and 75.8 %, respectively) against a representative isolate according to nitrocefin analysis. The study results and ready availability and low toxicity of plant polyphenols warrant further investigations on the therapeutic potential of combination therapies for MRSA infections.
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