Comparison of the determination of β-lactam antibiotic drugs in plasma of rabbits by means of HPLC and of a microbiological assay

The present study compares the determination of the plasma concentrations of ampicillin, amoxycillin and cefuroxime in rabbits, by means of high performance liquid chromatography and the microbiological assay. The correlation coefficient between the data obtained by these methods are for ampicillin 0.991, amoxycillin 0.994 and cefuroxime 0.991. Plasma constituents interfering with amoxycillin in theHplc determinations, were not encountered in the plasma of man.     

Modulation of release of ATP in the major pelvic ganglion of rats

用荧光素－荧光素酶方法测定大鼠盆总神经节腺苷三磷酸（ＡＴＰ）释放．钠通道阻断剂河豚毒素（１μｍｏｌ·Ｌ－１）抑制电刺激诱发的盆总神经节ＡＴＰ的释放．灌流液中去除Ｃａ２＋并加入ＥＧＴＡ（１ｍｍｏｌ·Ｌ－１）后消除ＡＴＰ的释放．腺苷（１００μｍｏｌ·Ｌ－１），Ａ１腺苷受体激动剂环戊腺苷（０．１μｍｏｌ·Ｌ－１），毒蕈碱性受体激动剂氧化震颤素（１μｍｏｌ·Ｌ－１）和５－羟色胺（１００μｍｏｌ·Ｌ－１）减少ＡＴＰ的释放．Ａ１腺苷受体拮抗剂８－环戊基－１，３－二丙基黄嘌呤（１０ｎｍｏｌ·Ｌ－１），α２肾上腺素受体拮抗剂育亨宾（３μｍｏｌ·Ｌ－１），Ｄ２多巴胺受体拮抗剂舒必利（２０μｍｏｌ·Ｌ－１）和组胺（１００μｍｏｌ·Ｌ－１）增加ＡＴＰ的释放．结果提示，在大鼠盆总神经节存在着作为神经递质参与突触传递的ＡＴＰ释放．Ａ１腺苷受体，毒蕈碱性受体，α２肾上腺素受体，Ｄ２多巴胺受体，５－羟色胺受体及Ｈ１组胺受体激动剂或拮抗剂可以通过节前机制影响ＡＴＰ的释放     

Analysis of electronic structures of physostigmine analogs

ＡｎａｌｙｓｉｓｏｆｅｌｅｃｔｒｏｎｉｃｓｔｒｕｃｔｕｒｅｓｏｆｐｈｙｓｏｓｔｉｇｍｉｎｅａｎａｌｏｇｓＨＵＺｅｎｇＪｉａｎ，ＪＩＡＮＧＨｕａＬｉａｎｇ，ＣＨＥＮＪｉａｎＺｈｏｎｇ，ＣＨＥＮＫａｉＸｉａｎ１，ＪＩＲｕＹｕｎ（Ｓｈａｎｇｈａｉ...     

Effects of schisanhenol on antitumoractivity of adriamycin

<正> It was suggested that adriamycin (ADM) may have at least two mechanisms of tissue damage. One, which involves lipid peroxidation, is blocked by the free radical scavenger, appears to play a major role in the development of cardiomyopathy. The other, which may involve binding of ADM to DNA, appears to be the major determinant of ADM toxicity for tumor cells. So the antitumor efficiency of ADM may be dissociated from its side effect of     

The effect of pimozide on variable-interval performance: A test of the ‘anhedonia’ hypothesis of the mode of action of neuroleptics

A quantitative behavioural test system based on Herrnstein's (1970) equation was used to test a prediction derived from the anhedonia hypothesis of neuroleptic action, that pimozide should increase the value of the behavioural parameter K _H (the reinforcement frequency needed to maintain the half-maximal response rate in variable-interval schedules). On the basis of theoretical considerations, it was shown that the equation implies that a drug which exerts such an effect on K _H must have a more profound suppressant effect on performance maintained by low reinforcement frequencies than on performance maintained by high reinforcement frequencies. Fifteen rats were trained under variable-interval 10-s and variable-interval 100-s schedules, and the effect of pimozide (0.125, 0.25, 0.33, and 0.5 mg/kg) was tested on performance maintained under each schedule. The drug suppressed performance maintained under both schedules in a dose-dependent manner, and there was no tendency for the drug to exert a greater effect on performance maintained under the lower reinforcement frequency. These results do not provide any evidence that the effect of pimozide on variable-interval performance is due to an anti-hedonic effect; rather, they are compatible with the hypothesis that pimozide impairs the capacity to respond.     

(Journal of China University of Geoscien

转化及土壤重金属污染的治理等方面起重要作用,关于有机酸是否影响矿物风化的问题,自1826年Sprengel和Julien为土壤中的有机酸是否在矿物溶解中扮演重要角色展开争论以来,已经持续     

Study of anti-inflammatory activities of α-d-glucosylated eugenol

Inflammation is an immune response against a variety of noxious stimuli, such as infection, chemicals, and physical injury. Eugenol, a natural phenolic extract, has drawn much attention for its various desirable pharmacological functions and is, therefore, broadly used in our daily life and medical practice. However, further usage of eugenol is greatly limited due to its unwanted properties, such as physicochemical instability, poor solubility, and high-dose cytotoxicity. In hopes of extending its applicability through glycosylation, we previously reported a novel, efficient, and high throughput way to biosynthesize α-d-glucosylated eugenol (α-EG). In this study, we further explored the potential superior properties of α-EG to its parent eugenol in terms of anti-inflammatory activities. We demonstrated that α-EG was an effective anti-inflammatory mediator in both non-cellular and cellular environments. In addition, the non-cellular inhibitory effect of α-EG could be amplified by α-glucosidase, which ubiquitously exists in cytoplasm. Furthermore, α-EG exhibited a superior anti-inflammatory effect to its parent eugenol in a cellular environment. In words, our findings collectively suggest that α-EG is a stronger anti-inflammatory mediator and may thereby serve as a desirable substitute for eugenol and a potential therapeutic prodrug in treating inflammatory diseases in the future.     

Cases analysis of rational use of medicine（45） Hypertension of Pregnancy

1.患者简介患者,女性,19岁,妊娠25周时,出现头痛,恶心,上腹部不适,血压162/108 mmHg,间隔6小时后再测血压,仍是162/108 mmHg。患者无高血压患病史。尿蛋白检查:+诊断:子痫前期(原名先兆子痫)2.用药     

Inhibitiory Effect of Scoparone on Inflammatory Mediator of Asthmatic Models of Guinea Pigs

Aim Bronchial asthma is a chronic inflammatory disease of the airways, is characterized by massive infiltration of eosinophils and airway hyperreactivity （ AHR）, which are caused by overproduction of inflammatory factors. It was reported that Scoparone possessed anti-inflammation and calcium antagonistic effects. We found that the dilatory effect of scoparone on the tracheal smooth muscle of guinea-pig, hence we presumed that scoporone might cure bronchial asthma. There has not been any report about anti-inflammation activity of scoparone on asthma, so we investigated the anti -inflammation activity of scoparone via using asthmatic models of guinea pig.     

Mode of Action: Reduction of Testosterone Availability—Molinate-Induced Inhibition of Spermatogenesis

Molinate is a preemergent herbicide that has been demonstrated to affect reproduction in the rat via alterations in sperm production. A wealth of standard toxicological studies and targeted research efforts relating to this adverse effect is available, and these were used to evaluate the utility of the Human Relevance Framework (HRF) for noncancer health effects. The hypothesized mode of action involved inhibition of the hydrolysis of cholesterol from high-density lipoprotein in the rat testes, followed by an androgen withdrawal syndrome on spermatogenesis. Some evidence is available that a similar mode of action would not be operable in humans. Despite the wealth of studies conducted in the rat, the weight of evidence is insufficient to define the mode of action for reproductive toxicity in the male rat. A principal deficiency in the database was discordance between the exposure levels observed to cause biochemical disturbances in the testes related to the hypothesized mode of action and the dose levels observed to induce the adverse outcome on spermatogenesis. For this reason, a complete MOA/human relevance analysis is not possible and, based on traditional risk assessment principles, any toxic effects are assumed to be relevant for human risk assessment.     

A series of outbreaks of food poisoning?

A series of independently occurring episodes which were notified individually as 'food poisoning' were, after investigation, linked to a common source water supply.     

The changes of expressions of gene and protein of APP cleaveing enzyme in the hippocampus of ordinary old rats

Object： To approach the biological basis of AD in eld. Methods： 15 young and 15 old healthy female rats supplied by experimental animal centre of Central South University were decapitated and the hippocampus tissues were extracted for the test of expressions of mRNA of APP cleaveing enzyme and test of protein of BACE1 and ADAM10 through RT-PCR and western blotting. Results： （1） Compaied with young rats,     

Influence of molecular properties on oral bioavailability of lipophilic drugs – Mapping of bulkiness and different measures of polarity

The biopharmaceutical assessment of new drug candidates based on their chemical structure is important in drug discovery and development. The scope of this study is to focus on lipophilic drugs and to clarify the role of their chemical predictors on oral bioavailability in humans. First their chemical properties were calculated from molecular modeling and the bioavailability data was obtained from the literature. The data was then analyzed by a partial least square method including non-linear terms. Significant coefficients were identified from a group of polarity- and solubility-related properties. Contour plots were constructed mapping molecular weight together with different polarity factors. Depending on the molecular weight a maximal bioavailability was found at solubility parameters of about 31–35 (J/cm³)^1/2 and HLB values of roughly 4–12. The mapping of lipophilic drugs also revealed that a solubility parameter of less than 20 (J/cm³)^1/2 or a HLB of smaller than unity is critical for the drug-likeness of new compounds.     

Exercise responses of healthy subjects in the evaluation of cardioselectivity ofβ-blockers

Summary The effects of intravenous propranolol, metoprolol, acebutolol and placebo on exercise-induced changes in heart rate and peak flow rate (PFR) have been studied in a group of healthy subjects. The three -blockers produced significant and comparable reductions in exercise-induced tachycardia and the magnitude of the reduction was related to the log plasma concentration of each drug. Significant cardiac -blockade was detectable for three hours after giving propranolol and for four hours after metoprolol and acebutolol. The exercise-induced changes in PFR were small and variable and were not significantly affected by any of the drugs. We conclude that, contrary to published reports, exercise-induced changes in heart rate and PFR in healthy subjects do not provide a satisfactory test system for assessing the selectivity of -blockers.     

An investigation of the mutagenic activity of salamide – a major impurity of hydrochlorothiazide

Hydrochlorothiazide is a widely used antihypertensive agent and one of its major impurities, salamide (4-amino-6-chlorobenzene-1,3-disulphonamide), has a chemical structure containing a primary amino group, a functional group that has previously been reported to be associated with carcinogenic activity. It is known that hydrochlorothiazide purity is a challenging problem for the pharmaceutical industry. As there were no prior mutagenicity data for the impurity salamide, the aim was to investigate its mutagenicity in this study. Salamide was tested for mutagenic potential in Salmonella typhimurium TA98, TA100, TA 1535, TA 1537, and E. coli WP2 uvrA?+?E. coli WP2 [pKM101] strains at six different concentrations, the highest concentration being the 5000?μg/plate. In both the presence and absence of the metabolic activation system, no mutagenic activity was observed. Results indicated that salamide should be classified as an ordinary impurity and controlled according to Q3A(R2) and Q3B(R2) guidelines.     

Micelles of Different Morphologies—Advantages of Worm-like Filomicelles of PEO-PCL in Paclitaxel Delivery

Purpose

Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly (ε-caprolactone) (PEO [5 kDa]–PCL [6.5 kDa]) in order to compare loading and delivery of hydrophobic drugs.

Materials and Methods

Worm-like micelles of this degradable copolymer are nanometers in cross-section and spontaneously assemble to stable lengths of microns, resembling filoviruses in some respects and thus suggesting the moniker ‘filomicelles’. The highly flexible worm-like micelles can also be sonicated to generate kinetically stable spherical micelles composed of the same copolymer.

Results

The fission process exploits the finding that the PCL cores are fluid, rather than glassy or crystalline, and core-loading of the hydrophobic anticancer drug delivery, paclitaxel (TAX) shows that the worm-like micelles load and solubilize twice as much drug as spherical micelles. In cytotoxicity tests that compare to the clinically prevalent solubilizer, Cremophor^® EL, both micellar carriers are far less toxic, and both types of TAX-loaded micelles also show fivefold greater anticancer activity on A549 human lung cancer cells.

Conclusion

PEO–PCL based worm-like filomicelles appear to be promising pharmaceutical nanocarriers with improved solubilization efficiency and comparable stability to spherical micelles, as well as better safety and efficacy in vitro compared to the prevalent Cremophor^® EL TAX formulation.

     

Lack of involvement ofδ-opioid receptors in mediating the rewarding effects of cocaine

The non-selective opioid antagonist naltrexone and the partial agonist buprenorphine have been reported to reduce cocaine self-administration (SA) and relapse in both humans and rhesus monkeys. Data suggesting an involvement of-opioid receptors in modulating the conditioned rewarding effects of cocaine were also recently presented. In view of such findings, the present SA and place conditioning studies were conducted to examine the influence of the selective-opioid receptor antagonist naltrindole upon the rewarding effects of cocaine. Sprague-Dawley rats were trained to self-administer cocaine (1.0 mg/kg per infusion) on an FR2 schedule of reinforcement. Dose-response and antagonist testing commenced once stable rates of cocaine SA were achieved. For antagonist testing, rats received naltrindole (0.03–10.0 mg/kg, IP) 30 min prior to the start of 2-h SA sessions. SA behavior in response to cocaine delivery (0.25 and 1.0 mg/kg per infusion) was then determined. Naltrindole in doses of 0.03–3.0 mg/kg did not alter the number of cocaine infusions taken by the rats. A higher dose of naltrindole (10.0 mg/kg), which markedly depressed locomotor activity, resulted in a 16% reduction of cocaine (0.25 mg/kg per infusion) SA behavior. When SA sessions were terminated and naltrindole (1.0 mg/kg) was administered repeatedly for 3 days, no alterations in the re-acquisition of cocaine SA were seen. Place conditioning studies also failed to find an effect of naltrindole (0.1–3.0 mg/kg) on cocaine (10 mg/kg) — induced conditioned place preferences. Naltrindole, by itself, did not induce significant place conditioning. These data fail to indicate a role of-opioid receptors in modulating either the positive reinforcing or conditioned rewarding effects of cocaine. Furthermore, they suggest that the therapeutic actions of naloxone, naltrexone and buprenorphine on cocaine SA behavior may not result from the specific blockade of-opioid receptors.     

A review of the fate of inhaled α-quartz in the lungs of rats

The distribution of dust particles within the lungs and their excretion are highly associated with their pulmonary toxicity. Literature was reviewed to discern pulmonary translocation pathways for inhaled α-quartz compared to those for inhaled TiO₂. Accordingly, it was hypothesized α-quartz particles in the alveoli were phagocytized by alveolar macrophages but silica-containing macrophages remained in the alveoli for longer time in contrast to the rapid elimination from the alveoli seen for TiO₂-containing macrophages. In addition, it was presumed that free silica particles are translocated in the interstitium, possibly through the cytoplasm of Type I epithelial cells, as observed with TiO₂. Free silica particles are presumed to be phagocytized by interstitial macrophages soon after the particles penetrate the interstitium; these dust cells are then translocated to the ciliated airway regions in the lumen through bronchus-associated lymphoid tissue (BALT). The pulmonary retention half-time of dust particles in rats exposed to α-quartz is several times longer than that of rats exposed to TiO₂, as long as the lung dust burden is ≈ 3?mg. The reduced pulmonary particle clearance ability in rats exposed to α-quartz aerosol is presumably attributed to the long-term retention of dust cells both in the alveoli and in the interstitium; this retention may be caused by the reduced chemotactic abilities of α-quartz-containing dust cells. However, the accumulation of α-quartz-containing dust cells in the lungs is not associated with the occurrence of pulmonary inflammation.     

Blockade of γ-aminobutyric acid-receptors of the B-subtype inhibits the dopamine-induced enhancement of the release of cholecystokinin-like immunoreactivity from slices of rat dorsal caudatoputamen

Summary When slices of rat dorsal caudatoputamen (= neostriatum) are incubated in vitro, Choecystokinin-like immunoreactivity (CCK-LI) is released upon addition of veratridine (3.75 mol/l). This release is affected by dopamine and by -aminobutyric acid (GABA)-receptor agonists. Dopamine enhances the release by stimulating dopamine D₂-receptors and decreases it via D₁-receptors. GABA_A-receptor agonists enhance the veratridine-induced release of CCK-LI, while GABA_B-receptor agonists decrease it. In the present investigation, it was examined whether GABA-receptors are involved in the effect which dopamine exerts via D₂-receptors. The GABA_A-receptor antagonist bicuculline (10 mol/l)and the blocker of the GABA_A-receptor ionophore picrotoxin (1 mol/l) did not affect the dopamine (0.1 mol/1)-induced increase in the release of CCK-LI. However, the GABA_A-receptor agonist muscimol (1 mol/l) not only enhanced the release of CCK-LI, but also prevented a further enhancement by dopamine (0.1 mol/l). This effect of muscimol was blocked by bicuculline (10 mol/l). In the presence of -amino-n-valeric acid (0.1 mmol/l), which has been described to block GABA_B-receptors, dopamine no longer enhanced the veratridine-induced release of CCK-LI. -Amino-n-valeric acid also inhibited the pronounced enhancement of the release of CCK-LI caused by dopamine (0.1 mol/l) and 1 mol/l in the presence of the preferential D₁-receptor antagonist SCH 23390. The effect of -amino-n-valeric acid persisted in the presence of bicuculline (10 mol/l and 100 mol/l). (+)-Baclofen, a partial agonist at GABA_B-receptors, and the stereoisomer (–)-baclofen, a full agonist, also prevented the effect of dopamine on the veratridine-induced release of CCK-LI. The effects of both drugs may be due to desensitization of GABA_B-receptors, which has been described to develop quite rapidly. It is concluded that -amino-n-valeric acid blocks GABA_B-receptors and in this way prevents the enhancement of the veratridine-induced release of CCK-LI caused by dopamine via D₂-receptors. These data are interpreted as evidence that dopamine and GABA-neurons can directly or indirectly interact in the rat neostriatum. Send offprint requests to D. K. Meyer at the above address