Antagonism of the trypanocide,berenil, and the nematocide,morantel, by tubocurarine

Summary The tubocurarine antagonism, (pA₂ values) of acetylcholine, suxamethonium, morantel and berenil were calculated as 6.5, 6.3, 6.4 and 6.2 respectively with the toad rectus abdominis muscle. It is suggested that tubocurarine competitively inhibits the morantel and berenil induced contracture of the toad rectus abdominis muscle.     

CAR在乳鼠肠、肝、心、脑、肾、肺组织的表达

目的检测柯萨奇-腺病毒受体(CAR)在乳鼠肠、肝、心、脑、肾、肺组织中的表达变化,为研究CVB感染引发病毒性疾病与组织中CAR表达水平的关联性提供参考。方法采用荧光实时定量PCR和Western blot法测定正常BALB/c乳鼠肠、肝、心、脑、肾、肺组织中CAR受体在核酸水平和蛋白水平的相对表达量。结果定量PCR显示CAR在乳鼠脑、肺、肠组织中表达显著高于肝、肾、心组织,差异均有显著性(P<0.01)。Western blot检测发现与定量PCR结果基本一致。结论 CAR的表达存在组织特异分布的特点。     

Hypertension, the Kuna, and the epidemiology of flavanols

A low sodium diet has often been implicated in the protection of low blood pressure populations from hypertension, but several other dietary factors, including those as yet unidentified, may also be involved. The Kuna Indians of Panama are free of hypertension and cardiovascular disease, but this is changing with migration to urban areas. We compared the indigenous diet of Kuna Indians living on remote islands in Panama (Ailigandi), whose lifestyle is largely hunter-gatherer, with those who have moved to a suburb of Panama City (Vera Cruz). Between April and October 1999, members of a Kuna research team administered a 118-item food frequency questionnaire to133 adult Kuna from Ailigandi and 183 from Vera Cruz. Single 24-hour urine collections and nonfasting blood samples were obtained. The Kuna in Ailigandi reported consuming a 10-fold higher amount of cocoa-containing beverages, 4 times the amount of fish, and twice the amount of fruit as urban Kuna (P<0.05 by t test). Salt added was ample among those living in Ailigandi and Vera Cruz according to both self-report (7.1+/-1.1 and 4.6+/-0.3 tsp weekly) and urinary sodium levels (177+/-9 and 160+/-7 mEq Na/g creatinine), respectively. The low blood pressure of island-dwelling Kuna does not seem to be related to a low salt diet. Among dietary factors that varied among migrating Kuna, the notably higher intake of flavanol-rich cocoa is a potential candidate for further study.     

Effects of d-amphetamine,maprotiline, l-dopa,and haloperidol on the components of the predatory behavior of the ferret,Putorius furo l.

Ferret predation on rats was examined in an arena. One hour before the test one of the following drugs was administered: d-Amphetamine (0.8 and 1.4 mg/kg IM), maprotiline (10 and 40 mg/kg orally), l-dopa (30 and 60 mg/kg orally), or haloperidol (0.14 and 0.6 mg/kg IM). Provided that capture was successful, the sequence of the behavioral components was not changed by these drugs. With the exceptions of paw movements and rolling over, which were not affected by the drugs, the components of predatory behavior were influenced differently. This leads to the assumption that a drug affects different mechanisms which control behavior. It is assumed that dopamine is involved in the control of capture elicitation as well as in the control of pursuit and biting. Capture elicitation was inhibited by d-amphetamine and l-dopa, but not by maprotiline, and was even facilitated by haloperidol. The orientation of pursuit movements and biting was impaired by l-dopa and improved by haloperidol, whereas maprotiline did not influence these components.     

A comparison of the teratogenic activity of the antiepileptic drugs carbamazepine,clonazepam, ethosuximide,phenobarbital, phenytoin,and primidone in mice

The teratogenic activity of six commonly used antiepileptic drugs, carbamazepine, clonazepam, ethosuximide, phenobarbital, phenytoin, and primidone, was studied at three dose levels (3, 9, and 18 times the human therapeutic dose) in CD1 mice. The drugs, suspended in 1% carboxymethylcellulose, were administered by gastric intubationon Days 6–16 of pregnancy, which covers the period from implantation to the end of structural development. The dams were killed 1 day before term and the fetuses were examined. Full-length cleft palates were observed in all treated groups with the exception of the clonazepam-treated group. This defect was not observed in any of the control groups. Other defects such as exencephaly, enlarged cerebral ventricles, exomphalos, open eyes, undescended testes, abnormal palatal bones other than cleft palate, and fused ribs were seen less frequently. If these results are assessed by ranking the drugs in order of teratogenicity, assessed on either a pooled fetus or a pooled litter basis, the drugs fall into three categories: Phenytoin produced the highest incidence of teratogenic effects; carbamazepine, phenobarbital, and primidone produced a lower but still significant incidence of defects; and clonazepam and ethosuximide were the least teratogenic. Nevertheless, there was at least a two-fold increase in defects in these latter two treatment groups compared with the controls.     

Comparison of the disposition and of the metabolic pattern of Reboxetine, a new antidepressant, in the rat, dog, monkey and man.

The purpose of this study was to compare the disposition and the metabolic pattern of Reboxetine in several species, including man. [14C]-Reboxetine was given orally to the rat, the dog, the monkey (5 mg/kg) and man (2 and 4 mg/kg). Radioactivity was eliminated both by the renal and faecal route in the rat and the dog, mainly in urine in the monkey and man. Reboxetine was extensively metabolized. A number of urinary metabolites were quantified by radio-HPLC and tentatively identified by comparison with the retention times of reference compounds. Suggested routes of metabolic transformation are: 2-O-dealkylation; hydroxylation of the ethoxyphenoxy ring; oxidation of the morpholine ring; morpholine ring-opening; and combinations of these. Metabolites were partially or completely conjugated with glucuronic acid and/or sulphuric acid.     

Quantitative Characterization of the Interaction Space of the Mammalian Carbonic Anhydrase Isoforms I,II, VII,IX, XII,and XIV and their Inhibitors,Using the Proteochemometric Approach

The critical role of carbonic anhydrases in different physiological processes has put this protein family at the center of attention, challenging major diseases like glaucoma, neurological disorders such as epilepsy and Alzheimer's disease, obesity, and cancers. Many QSAR/QSPR (quantitative structure–activity/property relationship) researches have been carried out to design potent carbonic anhydrase inhibitors (CAIs); however, using inhibitors with no selectivity for different isoforms can lead to major side‐effects. Given that QSAR/QSPR methods are not capable of covering multiple targets in a unified model, we have applied the proteochemometric approach to model the interaction space that governs selective inhibition of different CA isoforms by some mono‐/dihydroxybenzoic acid esters. Internal and external validation methods showed that all models were reliable in terms of both validity and predictivity, whereas Y‐scrambling assessed the robustness of the models. To prove the applicability of our models, we showed how structural changes of a ligand can affect the selectivity. Our models provided interesting information that can be useful for designing inhibitors with selective behavior toward isoforms of carbonic anhydrases, aiding in their selective inhibition.     

Susceptibility to erythromycin of anaerobes of the genera Bacteroides, Fusobacterium, Sphaerophorus, Veillonella, Clostridium, Corynebacterium, Peptococcus, Peptostreptococcus

The minimal inhibitory concentrations (MIC) of erythromycin were determined by broth dilution tests for 313 anaerobic strains, most of which were clinical isolates. All the gram-positive anaerobes tested (84 Peptococcaceae, including 21 Peptostreptococcus anaerobius and 15 Peptococcus variabilis; 65 Corynebacterium acnes and 29 Clostridium strains, including 13 C. perfringens) were sensitive (MIC values 0.012 through 3.12 microgram erythromycin/ml); so were 111 cultures of gram-negative anaerobes (52 Bacteroides fragilis, 12 B. thetaiotaomicron, 7 B. vulgatus, 13 B. oralis, 4 B. melaninogenicus, 10 Sphaerophorus necrophorus, 2 Veillonella sp., 11 members of other species). Erythromycin at concentrations of 6.25 through 200.0 microgram/ml was active against 24 strains (1 B. fragilis, 4 Fusobacterium fusiforme, 9 Sph. freundi, 10 Sph. varius). The present results are compared to the limited number of reports existing with regard to the susceptibility of anaerobes to erythromycin.     

Electrophysiology of the mechanisms of action of the yew toxin, taxine, on the heart

The effects of the sulfate salt of taxine, the alkaloid mixture of the yew (Taxus baccata L.), on membrane currents of enzymatically isolated single ventricular cells of guinea pig were studied under current- or voltage clamp conditions. It was found that the drug inhibits both the sodium (INa) and the calcium current (ICa). The mean decrease of ICa and the maximum rate of rise of the action potential (dV/dtmax), an index of INa, and their standard errors under the influence of 10(-6), 10(-5), 10(-4) g/ml of taxine (control 100%) were 87.1 +/- 2.9, 67.8 +/- 2.8, 24.4 +/- 2.0 for the amplitude of ICa and 75.4 +/- 3.7, 53.3 +/- 7.5, 9.4 +/- 1.1 for dV/dtmax, respectively. Recovery from the effects of taxine is partially possible. Under the influence of taxine, inconsistent effects were observed on the potassium outward current. In conclusion the effect of taxine on the heart results from its ICa and INa inhibiting properties similar to those of other antiarrhythmic drugs.     

Bromocriptine,dihydroergotoxine, methysergide,d-LSD,CF 25-397, and 29-712: Effects on the metabolism of the biogenic amines in the brain of the rat

The effects of the ergolene derivatives bromocriptine, dihydroergotoxine, methysergide, d-LSD, CF 25-397, and 29-712 on the metabolism of the biogenic amines in the brain of the rat were investigated.All six ergolene derivatives were found to increase the concentration of 4-hydroxy-3-methoxyphenylethylene glycol sulphate in the brain stem, i.e., to increase the turnover of noradrenaline (NA). Since in brain homogenates the agents inhibited the binding of ³H-dihydroergocryptine to -adrenoceptors, but only weakly inhibited the binding of ³H-alprenolol to -adrenoceptors, it is suggested that the increased turnover of NA may be a consequence of a blockade of -adrenoceptors by ergolenes.All of the ergolenes increased the concentration of serotonin (5-HT) in the cortex, but only bromocriptine and 29-712 increased the concentration of 5-hydroxyindoleacetic acid (5-HIAA), the other compounds decreasing the concentration of this metabolite, i.e., inhibiting 5-HT turnover. Reserpine-induced PGO waves in the cat were inhibited by all six compounds, bromocriptine and 29-712 being the least active. Both of these findings suggest that the ergolenes possess serotonergic activity. The increase in the concentration of 5-HIAA after bromocriptine and 29-712 may be secondary to some action on other systems.The actions of the ergolenes on the metabolism of dopamine (DA) in the striatum are more complex. Bromocriptine, 29-712, and, to a much lesser extent, dihydroergotoxine reduced the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC), i.e., they inhibited DA turnover. These findings are compatible with the proposed dopaminergic activity of the drugs. CF 25-397 caused a slight increase in the DOPAC concentration at high doses, and d-LSD and methysergide caused pronounced increases. At doses below 1 mg/kg i.p., d-LSD decreased the DOPAC concentration. This biphasic effect of d-LSD may be due to interaction with different types of DA receptors or may reflect some secondary action of the compound.The profiles of activity of the various ergolenes are discussed. Bromocriptine and 29-712, wich have similar profiles of activity, can be clearly differentiated from the other ergolenes. CF 25-397 seems to be a potent and, at low doses, specific serotonergic drug.     

脑脉利颗粒中芍药苷，益母草碱，黄芪甲苷及盐酸水苏碱含量测定

目的：建立脑脉利颗粒中芍药苷,益母草碱,黄芪甲苷及盐酸水苏碱的含量测定方法。方法：采用甲醇、酸水等不同的溶剂提取,并采用高效液相色谱法,液质联用法等灵敏、专属的色谱方法进行含量测定。结果：每10g脑脉利颗粒中含有芍药苷 42.41 mg,益母草碱 1.73mg,黄芪甲苷 0.10 mg,盐酸水苏碱 37.98mg。结论：制剂中其他组分与所测定的各组分分离良好,不干扰测定,可用于脑脉利颗粒中芍药苷,益母草碱,黄芪甲苷及盐酸水苏碱的含量测定。     

Toxicity of the amphoteric surfactant, cocamidopropyl betaine, to the marine macroalga, Ulva lactuca

The degradation of the synthetic, amphoteric surfactant, cocamidopropyl betaine (CAPB) and its toxicity to the marine macroalga, Ulva lactuca, has been evaluated using several different physiological test end-points over different periods of exposure up to 120 h. Droplet surface angle measurements revealed that, following a period of acclimation of about 24 h, CAPB began to degrade and that primary degradation was complete within 120 h. Effective quantum yield (∆F/F_m′) and relative growth rates (RGRs) were the most sensitive measures of phytotoxicity, with CAPB concentrations at and above 10 mg l⁻¹ eliciting irreversible, time-dependent and/or dose-dependent responses. Cell membrane damage, estimated from measurements of ion leakage, was detected only at a concentration of 40 mg l⁻¹ after 48 h of exposure to CAPB but by 120 h damage was evident at all measured concentrations above 10 mg l⁻¹. These observations suggest that both CAPB and its metabolites are intrinsically toxic to U. lactuca. The findings of this study are discussed in terms of the environmental consequences of applying CAPB to control harmful algal blooms.