OBJECTIVE: To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. METHODS: The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. RESULTS: After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ² = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). CONCLUSIONS The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.
Adenosine Diphosphate/pharmacology* ; Adenosine Triphosphate ; Animals ; Molluscacides/pharmacology* ; Silica Gel/pharmacology* ; Snails ; Streptomyces ; Water

Adenosine receptors (AR) play an important role in the regulation processes for body temperature and vigilance states. During our previous studies, we noticed that aminophylline (a non-selective, blood-brain-barrier penetrably AR antagonist) could attenuate the effects of YZG-330 [(2R,3S,4R,5R)-2-(hydroxymethyl-5-(6-(((R)-1-phenylpropyl)amino)-9H-purin-9-yl)tetrahydrofuran-3, 4-diol] on lowering the body temperature. Hereby, we focused ourselves on the character of thermal regulation effect of YZG-330 in mice and tried to specify the receptor subtype via giving typical adenosine receptor antagonists. The results showed that both of the magnitude and lasting time of the effect that YZG-330 played on decreasing body temperature are in a dose-dependent manner: within the next 3 hour after intragastric administration (ig) of 0.25, 1 or 4 mg . kg-1 YZG-330, the extreme values on body temperature decreasing were (1.2 ± 0.3) °C, (3.6 ± 0.4) °C (P<0.001) and (7.4±0.5) °C (P<0.001), separately; whereas the duration that body temperature below 34 °C were 0, (10±5) and (153±4) min, separately. Adenosine A1 receptor (A1R) antagonist (DPCPX) could effectively reverse YZG-330's effect on decreasing body temperature, with intraperitoneal administration of DPCPX (5 mg . kg-1) 20 min prior than YZG-330 (4 mg.kg-1, ig), the extreme value on body temperature decreasing was (3.5 ± 0.7) °C (P<0.001), the duration that body temperature below 34 °C was (8±6) min (P<0.001). However, adenosine A2a receptor antagonist, SCH-58261, did not show any influence on the effects of YZG-330 at all. Combined with the fact that 8-SPT (a non-selective, blood-brain-barrier impenetrably AR antagonist) did not reverse the effect of YZG-330, we come to the conclusion that central-adenosine A, receptor plays a significant role on the thermal regulation effect of YZG-330.
Adenosine ; analogs & derivatives ; pharmacology ; Adenosine A1 Receptor Antagonists ; pharmacology ; Animals ; Body Temperature Regulation ; drug effects ; Mice ; Pyrimidines ; pharmacology ; Receptor, Adenosine A1 ; physiology ; Triazoles ; pharmacology ; Xanthines ; pharmacology

A2B adenosine receptor is involved in the control of mast cell degranulation, interleukin-8 synthesis and cell growth. A2B adenosine receptor antagonists may serve as novel drugs for asthma, Alzheimer' s disease, cystic fibrosis and type-II diabetes. Therefore, seeking for the highly selective A2B adenosine receptor antagonists has been one of great interest. The molecular basis, structure-activity relationship of selective A2B adenosine receptor antagonists and their interactions with A2B adenosine receptor were reviewed.
Adenosine ; pharmacology ; Adenosine A2 Receptor Antagonists ; Adenosine A3 Receptor Antagonists ; Adenosine-5'-(N-ethylcarboxamide) ; pharmacology ; therapeutic use ; Animals ; Anti-Asthmatic Agents ; therapeutic use ; Asthma ; drug therapy ; Humans ; Pulmonary Artery ; drug effects ; Structure-Activity Relationship ; Xanthines ; pharmacology

OBJECTIVETo test the different contrctile responses of extracellular nucleotides, such as ATP, UTP and nucleotide uridine adenosine tetraphosphate (Up4A) in gastric longitudinal muscle (LM) and circular muscle (CM). Examined the effect of P2X and P2Y receptor antagonists (in this study, we used IP5I and suramin) and cyclooxygenase inhibitor (indomethacin) on Up4A induced contractile responses in LM and CM.

METHODSThe rats were sacrificed and the stomachs were opened to gain LM and CM. Using organ bath system to assess contrctile responses of smooth muscle.

RESULTSUp4A could induce contractile responses in both CM and LM, which were similar with ATP and UTP. IP5 did not attenuate Up4A could induce contractions in both LM and CM, but suramin and indomethacin significantly inhibited Up4A contraction in CM, but not in LM.

CONCLUSIONOur results suggest that extracellular nucleosides and their inhibitors induce different responses between LM and CM.

Adenosine Triphosphate ; pharmacology ; Animals ; Dinucleoside Phosphates ; pharmacology ; Indomethacin ; Muscle Contraction ; Muscle, Smooth ; physiology ; Nucleotides ; pharmacology ; Rats ; Suramin ; Uridine Triphosphate ; pharmacology

The purpose of this study was to evaluate in vitro the effects of hydrocortisone and aminophylline on adenosine diphosphate (ADP)-induced platelet aggregation in horses. Blood samples from 30 healthy Thoroughbred horses were collected by via jugular venipuncture to assess platelet aggregation. Platelet-rich and platelet-poor plasma were prepared from all samples by centrifugation and divided into three different aliquots. In the first aliquot, platelet aggregation was measured after platelet activation with 1 microM and 0.5 microM ADP (Group A). In the other two aliquots, the effect of a 10 min preincubation with hydrocortisone (Group B) or aminophylline (Group C) on ADP-induced aggregation at final ADP concentrations of 1 microM and 0.5 microM was observed. Platelet aggregation, recorded by an aggregometer, was evaluated by measuring the maximum degree of platelet aggregation and the initial velocities of platelet aggregation were obtained. Our results demonstrated the inhibitory effect of hydrocortisone and the induction effect of aminophylline on equine platelet responses in vitro.
Adenosine Diphosphate/pharmacology ; Aminophylline/*pharmacology ; Animals ; Anti-Inflammatory Agents/*pharmacology ; Female ; Horses/*physiology ; Hydrocortisone/*pharmacology ; Male ; Platelet Aggregation/*drug effects

Poor stability existed in the anaphase of the high-cell-density fermentation of Saccharomyces crevisiae for S-adenosyl-L-methionine (SAM) production in 5 L fermentor. To improve the fermentation stability, we studied the addition of diammonium hydrogen phosphate, sodium glutamate and adenosine disodium triphosphate into glucose feeding solution. Study of four fed-batch cultures showed that, after 34 h fermentation, when dry cell weight reached 100 g/L, the addition of 50 g pre-L-methionine and glucose feeding with 10 g/L adenosine disodium triphosphate was optimal for SAM production. Under this condition, after 65.7 h fermentation, both the dry cell weight and the yield of SAM reached the maximum, 180 g/L and 17.1 g/L respectively.
Adenosine Triphosphate ; pharmacology ; Fermentation ; Phosphates ; pharmacology ; S-Adenosylmethionine ; biosynthesis ; genetics ; Saccharomyces cerevisiae ; enzymology ; genetics ; Sodium Glutamate ; pharmacology

OBJECTIVE: To investigate the anti-oxidative effect of ethyl pyruvate (EP) and taurine (TAU) on the quality of red blood cells stored at 4±2 ℃, hemolysis, energy metabolism and lipid peroxidation of the red blood cells in the preservation solution were studied at different intervals. METHODS: At 4±2 ℃, the deleukocyte red blood cells were stored in the citrate-phosphate-dextrosesaline-adenine-1 (CPDA-1) preservation (control group), preservation solution with EP (EP-AS), and TAU (TAU-AS) for long-term preservation. The enzyme-linked immunoassay and automatic blood cell analyzer were used to detect hemolysis and erythrocyte parameters. Adenine nucleoside triphosphate (ATP), glycerol 2,3-diphosphate (2,3-DPG) and malondialdehyde (MDA) kits were used to test the ATP, 2,3-DPG and MDA concentration. RESULTS: During the preservation, the rate of red blood cell hemolysis in EP-AS and TAU-AS groups were significantly lower than that in CPDA-1 group (P<0.01). The MCV of EP-AS group was increased with the preservation time (r=0.71), while the MCV of the TAU-AS group was significantly lower than that in the other two groups (P<0.05). The concentration of ATP and MDA in EP-AS and TAU-AS groups were significantly higher than that in CPDA-1 group at the 14th day (P<0.01). The concentrations of 2,3-DPG in the EP-AS and TAU-AS groups were significantly higher than that in the CPDA-1 group from the 7th day (P<0.01). CONCLUSION EP and TAU can significantly reduce the red blood cell hemolysis rate, inhibit the lipid peroxidation level of red blood cells, and improve the energy metabolism of red blood cells during storage. The mechanism of EP and TAU may be related to their antioxidation and membrane protection effect, so as to improve the red blood cell quality and extend the preservation time.
2,3-Diphosphoglycerate/metabolism* ; Adenine ; Adenosine Triphosphate/metabolism* ; Blood Preservation ; Citrates/pharmacology* ; Erythrocytes/metabolism* ; Glucose/pharmacology* ; Hemolysis ; Humans ; Pyruvates ; Taurine/pharmacology*

This study is to examine the sedative, hypnotic and anticonvulsive effects of an adenosine analogue, WS090501. The spontaneous locomotor activity was recorded by open field equipment, and the EEG of rats was recorded by polyphysiograph. Pentylenetetrazol (PTZ)-induced seizure model was used. The spontaneous locomotor activity was decreased by WS090501 at various doses (0.06, 0.13, and 0.25 mg x kg(-1)), and the decreasing rate was 28.4%, 47.1% and 61.2% respectively. Furthermore, the effect of WS090501 on spontaneous locomotor activity of mice can be antagonized by DPCPX, a selective adenosine A1R antagonist, but cannot be antagonized by SCH58261, a selective adenosine A2AR antagonist. The NREM sleep was significantly increased by WS090501 (0.05 and 0.2 mg x kg(-1)), and the increasing rate was 27.6% and 102.8%, respectively, at 6th hour after administration. The REM sleep decreased significantly at the higher dose. PTZ induced serious convulsion in mice. The latency of convulsion was prolonged, and the number of seizure and mortality decreased after administration of WS090501. These results show that WS090501 has potent sedative, hypnotic and anticonvulsive effects, which may be mediated through adenosine A1R.
Adenosine ; analogs & derivatives ; antagonists & inhibitors ; pharmacology ; Adenosine A1 Receptor Antagonists ; pharmacology ; Adenosine A2 Receptor Antagonists ; pharmacology ; Animals ; Anticonvulsants ; antagonists & inhibitors ; pharmacology ; Convulsants ; Electroencephalography ; Hypnotics and Sedatives ; antagonists & inhibitors ; pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Motor Activity ; drug effects ; Pentylenetetrazole ; Pyrimidines ; pharmacology ; Rats ; Rats, Wistar ; Seizures ; chemically induced ; prevention & control ; Sleep ; drug effects ; Triazoles ; pharmacology ; Xanthines ; pharmacology

In order to optimize the preservation of blood, 3 kinds of antioxidant were selected and each of them can be injected directly into vein, then the optimal dose of these antioxidants was chosen using statistical method; ISMC (injectio salvia miltiorrhizae composita), ginaton and the combination of ISMC and ginaton were added into blood as optimal dose, some references as ATP, EI and so on were observed during blood preservation. The results showed that all of the three kinds of antioxidants increased ATP, EI and decreased FHb during blood preservation. It is concluded that both of ISMC and ginaton can effectively optimize the preservation of blood and combination of ISMC and ginaton can produce additive effect.
Adenosine Triphosphate ; metabolism ; Antioxidants ; pharmacology ; Blood Preservation ; Erythrocytes ; drug effects ; physiology ; Humans ; Salvia miltiorrhiza

BACKGROUNDTime-intensity curves derived from microbubble destruction/refilling sequences and recorded using myocardial contrast echocardiography (MCE) can provide parameters that correlate with coronary blood flow. The response of these parameters to adenosine vasodilatation correlates with coronary flow reserve (CFR) measured by fluorescent microsphere techniques (FMT). Currently, no data exist regarding the effect of physiological variables, such as hypoxia, on the determination of CFR by MCE. The purpose of this study was to define the effects of decreases in blood partial pressure of oxygen (PO2) on CFR as measured by MCE.

METHODSStudies were performed in 9 closed chest swine. Low-energy, real-time MCE was performed with commercial instruments in short axis view at papillary muscle level while infusing BR1 at 30 ml/h. High-energy ultrasound bursts (referred to as FLASH frames) destroyed the bubbles every 15 cardiac cycles, and resultant time-intensity curves derived from these sequences were fitted to the exponential function y = A [1-e(-bt)] + c, from which the rate of signal rise (b) was obtained. CFR was calculated as the ratio of b values after adenosine infusion to baseline and was obtained during the control period and after decreasing blood PO2 by giving nitrogen via a respirator to create artificial hypoxic conditions. CFR was independently determined by FMT.

RESULTSNitrogen led to significant decreases in mean PO2, from (120.6 +/- 18.9) mmHg to (51.8 +/- 15.9) mmHg (P < 0.01). Adenosine produced a similar increase in CFR (2.5 fold vs 3.1 fold) as assessed by MCE and FMT during the control period. The decrease in PO2 post nitrogen resulted in a slight increase in values at rest: 0.46 +/- 0.15 to 0.53 +/- 0.18 for b and (1.39 +/- 0.66) ml x min(-1) x g(-1) to (1.72 +/- 0.30) ml x min(-1) x g(-1) for myocardial blood flow (MBF) (both P < 0.05). In addition, values decreased in response to adenosine using both techniques: 1.05 +/- 0.35 to 0.82 +/- 0.27 for b and (4.30 +/- 3.16) ml x min(-1) x g(-1) to (3.93 +/- 1.27) ml x min(-1) x g(-1) for MBF (both P < 0.05). Thus, CFR was markedly reduced under hypoxic conditions, to 1.4 by MCE (P < 0.05 compared with the baseline), and to 2.5 by FMT (P > 0.05 compared with the baseline).

CONCLUSIONSCFR values diminish under hypoxic conditions according to both MCE and FMT. The reductions in CFR involve both an increase in resting values and a decrease in post adenosine measurements, as determined by both techniques. The reduction in CFR under hypoxia is slightly greater using MCE than using FMT. Physiological variables, such as hypoxia, must be taken into consideration when assessing CFR by MCE.

Adenosine ; pharmacology ; Animals ; Coronary Circulation ; Echocardiography ; Hypoxia ; diagnostic imaging ; physiopathology ; Microspheres ; Swine