Tong Jing Yi Hao Formula Alleviates Ornidazole-Induced Oligoasthenospermia in Rats by Suppressing ROS/MAPK/HIF-1 Pathway.

BACKGROUND: Tong Jing Yi Hao Formula (TJYHF) is a Traditional Chinese medicine used for oligoasthenospermia (OAS) treatment. However, the role of TJYHF against OAS is unclear. This study was an initial attempt to solve this problem. METHODS: Rats were randomly allocated to normal, ornidazole (Orn), levocarnitine (450 mg/kg), low-dose TJYHF (6.5 g/kg) and high-dose TJYHF (26 g/kg) groups, each consisting of six rats. Oral administration of Orn (400 mg/kg) for 4 weeks was used to induce OAS, followed by oral doses of the respective drugs for an additional 4 weeks. Parameters, including the testicular index, epididymis index, testicular volume, sperm parameters, sex hormone levels, histological changes and markers of oxidative stress, were evaluated to assess the effects of treatment. The potential mechanism involved in the therapeutic effects of TJYHF was studied by evaluating the activity and expression levels of key molecules within the reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK)/hypoxia-inducible factor 1 (HIF-1) pathway. RESULTS: Compared with healthy rats, the Orn-induced rats demonstrated decreases in testicular index, epididymis index, testicular volume, sperm concentration, total sperm count, percentage of forwarding sperm motility, total sperm motility, testosterone, spermatogenic epithelium, reproductive cell, glutathione peroxidase, superoxide dismutase and glutathione and increases in sperm deoxyribonucleic acid fragmentation index, follicle-stimulating hormone, luteinizing hormone and malondialdehyde. In the testicles, an enhancement in the ROS level and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) was observed after Orn challenge. Moreover, the protein expression levels and immunostaining intensity of p38 and HIF-1α increased, indicating the activation of the ROS/MAPK/HIF-1 pathway. All of the aforementioned changes exhibited statistical significance (p < 0.01). Compared with Orn-induced rats, TJYHF effectively rescued the Orn-induced aforementioned disorders. Mechanistically, TJYHF suppressed the ROS level and ERK1/2, JNK and p38 phosphorylation levels. Besides, it reduced the protein expression levels and immunostaining intensity of p38 and HIF-1α, demonstrating the inactivation of the ROS/MAPK/HIF-1 pathway. Notably, the aforementioned enhancements demonstrated statistical significance (p < 0.01). CONCLUSIONS: TJYHF exerted a beneficial effect on reproductive function in OAS rats through the inhibition of the ROS/MAPK/HIF-1 pathway.

Injectable chitosan/ß-glycerophosphate hydrogels with sustained release of BMP-7 and ornidazole in periodontal wound healing of class III furcation defects.

The aim of this study was to determine the effect of bone morphogenetic protein-7 (BMP-7) and ornidazole (ORN) loaded Chitosan/ß-glycerophosphate (CS/ß-GP) thermosensitive hydrogels on periodontal regeneration. CS/ß-GP hydrogels with and without BMP-7 and ORN were compared with respect to physicochemical properties, release kinetics, and antimicrobial activity in vitro, and periodontal regeneration properties in class III furcation defects in beagles via radiography, histology including immunohistochemical staining of osteoblasts and osteoclasts, and histometric analysis. CS/ß-GP hydrogels with and without BMP-7 and ORN had comparable physicochemical properties and gelation kinetics. Release kinetics showed that the hydrogels were capable of stable and sustained release of BMP-7 and ORN. The hydrogels loaded with ORN exhibited obvious antimicrobial activity against P. gingivalis. Histometric analysis quantitatively showed significantly more new bone and cementum, and less connective tissue in defects implanted with BMP-7 loaded hydrogels compared with hydrogels without BMP-7. The number of osteoclasts reduced significantly in the CS/BMP-7/ORN and CS/BMP-7 groups, while the number of osteoblasts increased significantly in these groups. Our findings showed that BMP-7 and ORN conferred additional advantages to the CS/ß-GP hydrogel in periodontal regeneration and suggest potential consideration of this approach for periodontal therapy.

Resistance profile survey of 50 periodontal strains of Actinobacillus actinomyectomcomitans.

BACKGROUND: Antibiotic resistance has been increasingly described among bacterial species colonizing periodontal pockets, particularly in Prevotella and Porphyromonas spp. strains producing beta-lactamases, and frequently associated with resistance to tetracycline and erythromycin. These resistance genes may be carried on motile genetic elements, or transposons, capable of interspecies and intergeneric transmission among bacterial strains colonizing a same ecological niche. The aim of this prospective study was to determine the resistance profile of Actinobacillus actinomycetemcomitans and the prevalence of A. actinomycetemcomitans strains producing beta-lactamases in periodontal pockets. METHODS: Fifty strains of A. actinomycetemcomitans were isolated from 42 patients with adult periodontitis. No patient had periodontal or antibiotic therapy in the previous 6 months. Bacterial samples were collected from periodontal pockets > or =5 mm, appropriately diluted, inoculated onto selective medium (chocolate blood agar with bacitracin 75 microg/ml and vancomycin 5 microm/ml) and incubated for 5 days at 37 degrees C in air with 5% CO2. After conventional identification, susceptibility testing to 11 antibiotics was performed by the broth dilution method, in trypticase soy broth supplemented with yeast extract, hemin, and 0.1% NaHCO3 to maintain microaerophilic conditions in the microtitration plate wells by CO2 formation. RESULTS: No strain demonstrated resistance to amoxicillin, amoxicillin-clavulanic acid combination, pristinamycin, or ciprofloxacin at the breakpoint, but 40% of the strains were slightly resistant to penicillin G, and 4% were resistant to erythromycin, 90% to spiramycin, 18% to clarythromycin, 4% to tetracycline, 72% to metronidazole, and 12% to ornidazole. Amoxicillin, followed by tetracycline and erythromycin, was the most effective antibiotic on A. actinomycetemcomitans. The phenotypic research of a beta-lactamase was negative for all the strains tested. CONCLUSIONS: In this work, most A. actinomycetemcomitans strains were resistant to metronidazole, but the amoxicillin-metronidazole association may be of interest against subgingival anaerobic and capnophilic mixed flora. Pristinamycin and ciprofloxacin appeared as effective alternative monotherapies against A. actinomycetemcomitans. The threat of beta-lactam antibiotic resistance related to beta-lactamase production is currently not a problem with A. actinomycetemcomitans as it has been reported in oral anaerobes.

Investigation of the potential role of Enterococcus faecalis in the pathophysiology of experimental peritonitis.

Two nonfatal models of peritonitis differing by the duration and the severity of the disease were studied in rats by implantation of Escherichia coli and Bacteroides fragilis with or without increasing concentrations of Enterococcus faecalis. Results were evaluated at 3 or 6 days after inoculation. The highest enterococcal concentrations (10(9) cfu/mL) enhanced the severity of the infection, evident by increased emaciation, increased peritoneal counts of E. coli and B. fragilis, and increased frequency of E. coli and B. fragilis bacteremia compared with enterococcus-free animals. Six therapeutic regimens (low-dose amoxicillin + low-dose gentamicin, high-dose amoxicillin + high-dose gentamicin, pefloxacin, ornidazole, pefloxacin + ornidazole, imipenem + gentamicin) were tested. All treatments failed to eradicate E. faecalis except the combination pefloxacin + ornidazole, which achieved a significant reduction of local bacterial counts and suppressed bacteremia. Enterococcus played an important role in the mechanisms of bacterial synergy in experimental peritonitis. However, eradication of enterococcus did not seem possible by conventional antienterococcal therapy.