OBJECTIVETo study the relaxant effect of ethanol on the isolated rabbit corpus cavernosum and its possible mechanism.

METHODSThe tension of isolated smooth muscle strips was recorded by the platform physiological graphed, and the concentrations of cAMP and cGMP in the rabbit corpus cavernosum were measured by 125I radioimmunoassay.

RESULTSThe 1.25% (V/V) ethanol significantly augmented the corporal relaxation induced by isoprenaline (10(-9) - 10(-5) mol/L). Ethanol-induced relaxation was inhibited by 100 micromol/L and 300 micromol/L SQ22536 (an adenylate cyclase inhibitor). Emax was depressed from (105.12 +/- 3.39) % to (97.00 +/- 2.57) % in the presence of 100 micromol/L SQ22536 or (91.09 +/- 2.42) % in the presence of 300 micromol/L SQ22536. EC50 was increased from (1.18 +/- 0.09)% (V/V) to (1.36 +/- 0.10) % in the presence of 100 micromol/L SQ22536 (P < 0.05) or (1.68 +/- 0.13) % (in the presence of 300 micromol/L SQ22536) (P < 0.05) respectively. Ethanol significantly elevated the level of cAMP but not that of cGMP in the isolated rabbit corpus cavernosum, and it also significantly enhanced the activity of the adenylate cyclase (AC) extracted from the rabbit corpus cavernosum in a dose-dependent manner.

CONCLUSIONEthanol has a relaxant effect on the isolated rabbit corpus cavernosum, which may be associated with the cAMP signaling pathway.

Animals ; Central Nervous System Depressants ; pharmacology ; Cyclic AMP ; metabolism ; Ethanol ; pharmacology ; In Vitro Techniques ; Male ; Muscle Relaxation ; drug effects ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; physiology ; Rabbits ; Signal Transduction ; drug effects

OBJECTIVETo further investigate the action mechanisms of berberine (Ber), and assess the effects of Ber on the in vitro formation of cGMP and cAMP in the isolated rabbit corpus cavernosum.

METHODSIsolated segments of the rabbit corpus cavernosum were exposed to different concentrations of Ber, and, the dosage-dependent accumulations of cGMP and cAMP were determined in the tissue samples by means of 125I radioimmunoassay. Responses of the isolated tissue preparations to Ber were compared with those obtained with the reference compound sildenafil (Sil).

RESULTSBer increased cGMP concentrations directly (P < 0.05). In the presence of sodium nitroprusside (SNP), a stimulatory agent of cGMP, both Ber and Sil increased cGMP with increasing dosage (P < 0.01), the EC, values being 1.32 and 0.67 micromol/L respectively. With the same concentration, neither Ber nor Sil influenced the cAMP level significantly (P > 0.05). In the presence of PGE1, a stimulator of cAMP, Ber and Sil also raised the cAMP level concentration (P < 0.01 ), the EC, values being 4.90 (Ber) and 6.53 (Sil) micromol/L respectively.

CONCLUSIONBer can increase cGMP and cAMP concentrations in the corpus cavernosum smooth muscles, which may contribute to its action of relaxing corpus cavernosum smooth muscles.

Animals ; Berberine ; pharmacology ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Dose-Response Relationship, Drug ; In Vitro Techniques ; Male ; Muscle, Smooth ; drug effects ; metabolism ; Penis ; drug effects ; metabolism ; Rabbits ; Radioimmunoassay

The present study utilized LC-MS and HPLC approaches to characterize the metabolites of neferine in rat liver after an oral administration of 20 mg x kg(-1), and investigated the involvement of CYP450 isoforms in the metabolism of neferine by their selective inhibitors in vitro, separately. In positive ionization mode, besides neferine, four metabolites (M1-M4) were detected. M2 (the major metabolite) and M4 were identified as liensinine and isoliensinine by comparison with reference substances. Moreover, according to the analysis of metabolic rule of parent drug (neferine), M1 and M3 may be desmethylliensinine and desmethyl-isoliensinine, respectively. Furthermore, the metabolism of neferine in rat liver microsomes showed that the percentage inhibition of the major metabolism (liensinine) formation was 80.5% by quinidine (10 micromol x L(-1), selective CYP2D1 inhibitor) and 25.7% by ketoconazole (1 micromol x L(-1), selective CYP3A1 inhibitor). Neferine was mainly metabolized by CYP2D1 or CYP3A1 to liensinine, isoliensinine, desmethyl-liensinine and desmethyl-isoliensinine.
Administration, Oral ; Alcohol Oxidoreductases ; antagonists & inhibitors ; Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; Benzylisoquinolines ; administration & dosage ; isolation & purification ; metabolism ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP3A ; Cytochrome P450 Family 2 ; Isoquinolines ; metabolism ; Ketoconazole ; pharmacology ; Male ; Microsomes, Liver ; metabolism ; Nelumbo ; chemistry ; Phenols ; metabolism ; Plants, Medicinal ; chemistry ; Quinidine ; pharmacology ; Rats ; Seeds ; chemistry ; Spectrometry, Mass, Electrospray Ionization

AIMTo explore the effects of lipoteichoic acid (LTA) induced delayed preconditioning (PC) on hypoxia-reoxygenation (H/R) injury of cultured human coronary artery endothelial cells (HCAECs), and to investigate the potential role of endogenous nitric oxide (NO) participated in the protective mechanism.

METHODSHCAECs were incubated for 2 h in a hypoxic atmosphere and reoxygenated for 4 h in a normoxic atmosphere. The delayed PC was induced by pretreatment with LTA (30 or 300 microg x L(-1)) for 4 h before 24 h recovery. The extent of cellular injury after reoxygenation was assessed by the percentage of cellular injury with Trypan blue exclusion and by the amount of lactate dehydrogenase (LDH) in culture media. The NO level of the culture media was measured spectrophotometrically. Furthermore, HCAECs were exposed to 300 microg x L(-1) of LTA for 4 h, and to detect the expression of eNOS mRNA by RT-PCR method after cells were recovered from different points.

RESULTSLTA pretreatment significantly decreased the percentage of the killed cell and the concentration of LDH in media. Also, LTA pretreatment obviously raised the concentrations of NO in culture media. The protective effects of LTA were abrogated by pretreatment with N-monomethyl-L-arginine (L-NMMA). Moreover, the expression of eNOS mRNA was significantly upregulated after HCAECs exposure to LTA for 4 h following 2 h or 4 h recovery.

CONCLUSIONLTA could induce the delayed protection against H/R induced endothelial injury and dysfunction of cultured HCAECs. NO produced by eNOS acts initially as a trigger and subsequently as a mediator of delayed PC.

Adult ; Cell Death ; Cell Hypoxia ; Cells, Cultured ; Coronary Vessels ; cytology ; metabolism ; Endothelial Cells ; cytology ; metabolism ; Female ; Humans ; Ischemic Preconditioning, Myocardial ; L-Lactate Dehydrogenase ; metabolism ; Lipopolysaccharides ; isolation & purification ; pharmacology ; Myocardial Reperfusion Injury ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Staphylococcus aureus ; chemistry ; Teichoic Acids ; isolation & purification ; pharmacology

China ; epidemiology ; Diabetes Mellitus ; diagnosis ; epidemiology ; metabolism ; Glycated Hemoglobin A ; metabolism ; Humans ; Prevalence

Objective To evaluate the molluscicidal effects of different formulations of niclosamide ethanolamine salt in marshlands. Methods The molluscicidal effects of spraying with 25% suspension concentrate of niclosamide ethanolamine salt (25% SCN) and 50% wettable powder formulation of niclosamide ethanolamine salt (50% WPN), and dusting with 4% niclosamide ethanolamine salt dustable powder (4% DP) for controlling Oncomelania hupensis snails were investigated and compared in the fields, and the cost-effectiveness was analyzed. Results The corrected mortalities and the reduced rates of density of snails were 54.37%, 91.70%, 92.76%, 79.50%, and 59.55%, 95.93%, 97.63%, 94.15%, respectively, on 3, 7, 15, 30 d after spaying with 25% SCN, those on 3, 7, 15, 30 d after dusting with 4% DP were 59.10%, 91.83%, 95.56%, 93.34% and 65.03%, 94.93%, 97.61%, 97.28%, respectively; and those on 3, 7, 15, 30 d after spraying with 50% WPN were 76.29%, 91.68%, 93.12%, 81.59% and 81.24%, 97.02%, 97.84%, 95.27%, respectively. The cost of spraying with 25% SCN was 0.21 Yuan/m², that of dusting with 4% DP was 0.39 Yuan/m², and that of spraying with 50% WPN was 0.23 Yuan/m² for snail control in the marshland. The cost of reduced one percentage of the corrected mortalities and the density of snails in controlling snails by 25% SCN, 4% DP and 50% WPN on 15 d were 22.68, 40.63, 25.17 Yuan and 21.54, 39.78, 23.95 Yuan, respectively. Conclusions The three different formulations of niclosamide are reliable and effective for snail control in marshlands. There are some differences among the different molluscicides in start time, pharmacodynamic characteristics, spraying methods in the field, cost of snail control, and influencing factors. Therefore, we need reasonably select the suitable molluscicides according to the environmental characteristics and working condition.