BACKGROUNDOur previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen.

METHODSThirty-two adult male rats were divided into four groups randomly: group GH, rats were fed orally with gossypol acetic acid (GA, 12.5 mg×kg(-1)×d(-1)) and desogestrel (DSG, 0.125 mg×kg(-1)×d(-1))/ethinylestradiol (EE, 0.025 mg×kg(-1)×d(-1))/testosterone undecanoate (TU, 100 mg×kg(-1)×d(-1)); group G, a single dose of GA (12.5 mg×kg(-1)×d(-1)) was given; group H, the same dosage of DSG/EE/TU as in group GH were administered; group C, rats were treated with vehicle (1% methyl cellulose) as control. Testes and epididymis were removed at 8 weeks post-treatment for evaluating their weight, volumes, volume fraction, and total volume of testicular tissue structures and the seminiferous tubule diameter using stereological assay. Sperm cell numbers and the motility of epididymal sperm were quantitated by flow cytometry and morphological methods.

RESULTSCompared with group C, spermatogenesis was normal in group G and suppressed in groups H and GH. Similar changes of testicular tissue structures and sperm number were found in groups H and GH. The decreases of epididymal sperm number and motility in group GH were greater than that of the low-dose gossypol or steroid hormones alone group.

CONCLUSIONSThe suppression of spermatogenesis was induced by steroid hormones in the combined regimen, and the epididymis was the target organ of low-dose gossypol. Combined use of low-dose gossypol and steroid hormones played a comprehensive antifertility role in their synergistic effect on reducing the number and motility of epididymal sperm.

Animals ; Desogestrel ; pharmacology ; Epididymis ; drug effects ; Ethinyl Estradiol ; pharmacology ; Flow Cytometry ; Gossypol ; analogs & derivatives ; pharmacology ; Male ; Random Allocation ; Rats ; Sperm Motility ; drug effects ; Spermatogenesis ; drug effects ; Spermatozoa ; drug effects ; Testis ; drug effects ; Testosterone ; analogs & derivatives ; pharmacology

BACKGROUND: The aim of this study was to evaluate antibiotic consumption by adult patients at a single university hospital in Korea between 2001 and 2012. METHODS: We used the 2004 World Health Organization Anatomical Therapeutic Chemical Classification System definition of defined daily doses (DDD) per 1,000 patient-days to calculate the annual antibiotic consumption for 18 antibiotic groups. Chi-square linear-by-linear analysis was performed to evaluate antibiotic consumption trends for each group. RESULTS: Average annual antibiotic consumption during 2001-2012 was 644.6 DDD/1,000 patient-days (standard deviation, 33.3 DDD/1,000 patient-days). Although no statistically significant change was observed during the study period, consumption of first- and second-generation cephalosporins, and aminoglycosides was significantly decreased, while that of beta-lactam/beta-lactamase inhibitors, fourth-generation cephalosporins, carbapenem, glycopeptide, linezolid, colistin, and quinolone increased significantly. CONCLUSION: The total amount of prescribed antibiotics did not change, but the use of broad-spectrum antibiotics increased during the study period.
Adult ; Aminoglycosides ; Anti-Bacterial Agents ; Cephalosporins ; Classification ; Colistin ; Hospitals, University ; Humans ; Korea ; World Health Organization ; Linezolid

Aim To investigate the protective effect of tetramethylpyrazine ( TMP ) on cerebral ischemia/reper¬fusion ( I/R) injury in diabetes mellitus ( DM ) rats based on full-length transcriptome sequencing tech¬nique and the underlying mechanism. Methods The rat model of DM was induced by intraperitoneal injec- tion of streptozotocin (STZ,50 mg • kg" ) . The global cerebral I/R model of rats was established by double vessel occlusion (2-VO) for 10 min and reperfusion for 16 h. TMP (40 mg • kg ) was injected intraperitone-ally every day. Brain water content detection, HE stai¬ning, Nissl staining and TUNEL staining were used to evaluate the neuroprotective effect of TMP on cerebral I/R injury in DM rats. The differentially expressed genes were screened by full-length transcriptome se¬quencing. The possible candidate genes and metabolic pathways of TMP for cerebral ischemia protection in DM rats were screened by functional annotation and metabolic pathway enrichment analysis, and verified by RT-qPCR and Western blot. Results TMP treatment could reduce the degree of brain edema, increase the number of Nissl bodies and neurons, and significantly reduce cell necrosis and apoptosis after cerebral I/R in DM rats. GO enrichment analysis showed that the dif¬ferentially expressed genes after TMP treatment were mainly enriched in biological functions such as inflam¬matory response, transcription factor complex, growth factor activity and so on. KEGG pathway analysis showed that it was mainly concentrated in apoptosis, Toll-like receptor and other signaling pathways. Among them TMP down-regulated genes included TLR2, MyD88, IL-lp, Caspase-3, etc. The results of RT-qPCR and Western blot confirmed that TMP could down-regulate TLR2, MyD88, NF-KB, IL-10, IL-6 and Caspase-3 , and up-regulate the mRNA and protein expression of Bcl-2. Conclusions TMP may amelio¬rate neuronal apoptosis by inhibiting inflammatory re¬sponse, which improves cerebral I/R injury in DM rats, and the pathway may be TLR2/MyD88/NF-KB signaling pathway.

Objective To explore how dihydrotestosterone (DHT) affects the expression of anti-Müllerian hormone (AMH) in primary rat follicular granulosa cells, and then provides a new experimental basis for the role of DHT and AMH in follicular development. Methods Granulosa cells was extracted from the ovaries of 95 21 days SD female rats for primary culture. Firstly, cell morphology were detected by HE staining and follicke stimulating hormone receptor (FSHR) immunofluorescence detected cell purity after 48 hours of cell culture. Then, cells were randomly divided into control group (without drug intervention), 10