Antagonistic action of corynebacteria and bacilli of a skin ecotype on staphylococci

582 strain of corynebacteria and 235 cultures of bacilli isolated from the skin surface of mammary glands of 120 nursing women were studied for their antagonistic action on staphylococci. It is established that bacilli, especially Bacillus subtilis, B. firmus and B. alvei exert more pronounced inhibitory effect on staphylococci. Representatives of the family Corynebacteriaceae possess a weak antagonistic action both on coagulase-positive and on coagulase-negative species. The ability of coryneform bacteria to retain the colonization resistance is supposed to be due to other factors. Antagonistic properties of B. subtilis are shown expedient to be used for elimination of hospital strains of Staphylococcus aureus from the skin of mammary glands.     

（－）SPD和（－）THP对蓝斑核去甲肾上腺素能神经元自发放电的影响

利用在体记录大鼠蓝斑核神经元单位放电,研究了（－）ＳＰＤ和（－）ＴＨＰ对其放电活动的影响。结果表明：（－）ＳＰＤ通过去甲肾上腺素α２受体,以剂量依赖方式增强蓝斑核神经元放电,但较大剂量却对神经元放电有一定抑制。然而（－）ＴＨＰ可使蓝斑核去甲肾上腺素能神经元出现可逆性放电抑制。     

左旋千金藤啶碱D1激动—D2阻滞作用引起伏核双相放电活动的电生理研究

为确定左旋千金藤啶碱（ＳＰＤ）对中脑边缘ＤＡ神经系统的作用特性,本研究采用细胞外记录的电生理学方法,观察微电泳和尾静脉给药对６－ＯＨＤＡ损毁及未损毁大鼠的伏核（ＮＡｃ）单位放电的影响。结果显示：ＳＰＤ累积给药（０．０２－２ｍｇ／ｋｇ,ｉｖ）可诱发ＮＡｃ神经元双相放电特征,即小剂量抑制、大剂量兴奋。预先给予Ｄ２受体拮抗剂ｓｐｅｐｅｒｏｎｅ,ＳＰＤ则仅产生兴奋效应,并被Ｄ１拮抗剂ＳＣＨ－２３３９０所翻     

Neuromechanisms of reciprocal interrelation between jaw-opening and jaw-closing muscles in the cat (author's transl)]

Neural controlling mechanisms between the digastric (jaw-opening) and masseter (jaw-closing) muscles were studied in the cat. High threshold afferent impulses from the anterior belly of the digastric muscle to masseteric montoneurons in the trigeminal motor nucleus induced an EPSP-IPSP sequence of potentials with long latency, and high threshold afferent impulses from the masseter muscle also exerted a similar effect on digastric motoneurons in the same nucleus innervating the anterior belly of the digastric muscle. These results suggest that reciprocal inhibition via Ia interneurons as observed between the flexor and extensor muscles in the spinal cord does not exist between the digastric and masseter muscles in the cat. However, the respective motoneurons innervating the masseter and digastric muscles receive inputs of early excitation-late inhibition via high threshold afferent nerve fibers from each antagonistic muscle. As such, since EPSPs preceding IPSPs are recognized, these high threshold afferent impulses may exert not only a reciprocal inhibitory effect, but also a synchronous excitatory or inhibitory effect on the antagonistic motoneurons.     

四种鬼臼毒素类似物对美洲大蠊腹神经索动作电位的作用

为了解鬼臼毒素对昆虫神经系统的影响,采用胞外记录电生理方法观察了4种鬼臼毒素类似物对美洲大蠊Periplaneta americana 中枢神经自发放动作电位的影响。结果显示: 在0.1 mmol/L的浓度下,4种物质对美洲大蠊中枢神经自发放动作电位的作用不同。脱氧鬼臼毒素可完全抑制美洲大蠊中枢神经自发放动作电位的产生,其抑制作用可逆;β-阿朴苦鬼臼毒素对美洲大蠊中枢神经自发放动作电位的作用是先兴奋后抑制;鬼臼毒素对美洲大蠊中枢神经自发放动作电位有抑制作用,其抑制作用不完全;4′-去甲鬼臼毒素对大蠊中枢神经自发放动作电位无影响。结果提示,4种鬼臼毒素类似物对昆虫中枢神经自发放动作电位的影响方式与其结构官能团密切相关。     

Adrenomedullin impairs the profibrotic effects of transforming growth factor-beta1 through recruiting Smad6 protein in human renal tubular cells.

Adrenomedullin (AM) was originally identified as a vasodilator peptide, and has recently been shown to be an antiproliferative factor in renal mesangial cells, suggesting that adrenomedullin may impair the progression of glomerulosclerosis. This study was to investigate the effect of adrenomedullin on transforming growth factor-beta1 (TGF-beta1)-stimulated cell growth, synthesis of extracellular matrix (ECM) components and the related molecular mechanism in a human tubular epithelial cell line HK-2. TGF-beta1 inhibited cell proliferation induced by fetal bovine serum, but neither AM itself affectted cell proliferation, nor did AM influence TGF-beta1-caused cell growth arrest. However, AM beginning at 10(-8) M alleviated the action of TGF-beta1-stimulated cellular collagen synthesis and secretion of fibronectin into cell culture supernatant. Activation of Smad proteins is known to be the key signaling pathway of the profibrotic effect of TGF-beta1, AM at 10(-8) M exerted no effect on TGF-beta1-induced Smad2 phosphorylation, but prevented the suppression of the inhibitory Smad6 protein by TGF-beta1 and restored Smad2-Samd6 complex formation. Our results suggest that AM can attenuate TGF-beta1-mediated renal tubulointerstitial ECM turnover via an antagonistic mechanism of inhibitory Smad in TGF-beta1-elicited signaling.     

An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells

We have previously demonstrated that adenosine controls the release of catecholamines (CA) from carotid body (CB) acting on A2B receptors. Here, we have tested the hypothesis that the control is exerted via an interaction between adenosine A2B and dopamine D2 receptors present in chemoreceptor cells. Experiments were performed in vitro in CB from 3 months rats. The effect of A2B adenosine and D2 dopamine agonists and antagonists applied alone or in combination were studied on basal (20%O2) and hypoxia (10%O2)-evoked release of CA and cAMP content of CB. We have found that adenosine A2 agonists and D2 antagonists dose-dependently increased basal and evoked release CA from the CB while A2 antagonists and D2 agonists had an inhibitory action. The existence of A2B-D2 receptor interaction was established because the inhibitory action of A2 antagonists was abolished by D2 antagonists, and the stimulatory action of A2 agonists was abolished by D2 agonists. Further, A2 agonists increased and D2 agonist decreased cAMP content in the CB; their co-application eliminated the response. The present results provide direct pharmacological evidence that an antagonistic interaction between A2B adenosine and D2 dopamine receptors exist in rat CB and would explain the dopamine-adenosine interactions on ventilation previously observed.     

On the effects of tranexamic acid and its isobenzedrine ester on plasminogen activation and streptokinase induced fibrinolysis

A comparison between the inhibitory capability of Tranexamic acid (AMCA) and its isobenzedrine ester (IB-AMCA) on the streptokinase and urokinase induced plasminogen activation, indicated in vitro a higher potency of the ester derivative. A peculiar activatory rather than inhibitory effect on the plasminogen activation was exerted by AMCA and aminocaproic acid at relatively low concentrations. Attempts to show in vivo the in vitro observed differences between AMCA and IB-AMCA action are reported.     

Relationship between group JK corynebacteria and the biotypes of Corynebacterium genitalium and Corynebacterium pseudogenitalium

Twenty-six strains of group JK corynebacteria had the same colonial morphology and biological reactions as the biotypes of the biovars of Corynebacterium genitalium and C. pseudogenitalium. Therefore, group JK corynebacteria can be assigned to the biovars of C. genitalium or C. pseudogenitalium. Although the strains differed in sensitivity to 16 antibiotics tested by Sensi-Discs or by the Micro-Media technique, they are uniformly sensitive to 4-5 micrograms/mL of vancomycin. Medium containing 10 micrograms vancomycin/mL was bactericidal and the killing time was dependent on the concentration. The rate of mutation to resistance to 10 micrograms vancomycin was greater than 1 in 10(10) corynebacteria. Therefore, vancomycin sensitivity is a stable characteristic of these corynebacteria which also indicates that group JK corynebacteria are strains of either C. genitalium or C. pseudogenitalium. Since group JK corynebacteria are considered pathogens, this finding supports the belief that C. genitalium is a pathogen and suggests that some biotypes of the commensal C. pseudogenitalium may infect compromised hosts.     

Antagonistic activity of a natural fungal population towards pathogenic bacteria. An in vitro study.

In the present work, we performed in vitro testing of 33 species of fungi of the subdivision Deuteromycotina isolated from water and sediment of the Kolubara River for antagonistic action towards 11 species of pathogenic bacteria. Of gram-negative bacteria, the species most sensitive to metabolic fluid of the fungi were Proteus mirabilis, Salmonella enteritidis, and Shigella sonnei, while the most resistant were Klebsiella pneumoniae and Salmonella typhimurium. Of gram-positive bacteria, the most sensitive species was Staphylococcus aureus, while the most resistant was Enterococcus faecalis. Of the tested fungi, Penicillium canescens, P. simplicissimum, P. thomii, Aspergillus fumigatus, A. ochraceus, and Fusarium culmorum exerted inhibitory action on the greatest number of species of pathogenic bacteria, while Verticillium lateritium, V. tenerum, Phoma humicola, and Botrytis cinerea had an inhibiting effect on the least number of species.     

The effect of cyclic GMP on phosphofructokinase from rat tissues.

In view of the recently proposed hypothesis of biologic regulation through opposing influences of cyclic AMP and cyclic GMP, and since cyclic AMP is a well-known allosteric activator of phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11), the effect of cyclic GMP on the activity of this enzyme from several rat tissues was investigated. It was found that cyclic GMP exerted an inhibitory effect on the activity of rat heart and skeletal muscle phosphofructokinase. This effect was most pronounced under conditions in which the enzyme was partially inhibited by ATP or by citrate. Cyclic GMP also antagonized the deinhibitory action of cyclic AMP and other allosteric activators, such as glucose 1,6-bisphosphate or AMP, on the ATP or citrate-inhibited heart or muscle phosphofructokinase. In contrast to the heart and skeletal muscle phosphofructokinase, the adipose-tissue enzyme was not affected by cyclic GMP to any significant degree. The antagonistic action of cyclic GMP to the activation of heart-phosphofructokinase, may suggest a mechanism by which the activity of phosphofructokinase is synchronized with the activity of glycogen phosphorylase, as a result of acetylcholine action in heart, to achieve a decrease in total glycogenolysis and glycolysis.     

Spatial summation of inhibitory influences in the eye of Limulus,and the mutual interaction of receptor units

The inhibitory influences exerted mutually among the receptor units (ommatidia) of the lateral eye of Limulus are additive. If two groups of receptors are illuminated together the total inhibition they exert on a "test receptor" near them (decrease in the frequency of its nerve impulse discharge in response to light) depends on the combined inhibitory influences exerted by the two groups. If the two groups are widely separated in the eye, their total inhibitory effect on the test receptor equals the sum of the inhibitory effects they each produce separately. If they are close enough together to interact, their effect when acting together is usually less than the sum of their separate effects, since each group inhibits the activity of the other and hence reduces its inhibitory influence. However, the test receptor, or a small group illuminated with it, may interact with the two groups and affect the net inhibitory action. A variety of quantitative effects have been observed for different configurations of three such groups of receptors. The activity of a population of n interacting elements is described by a set of n simultaneous equations, linear in the frequencies of the receptor elements involved. Applied to three interacting receptors or receptor groups equations are derived that account quantitatively for the variety of effects observed in the various experimental configurations of retinal illumination used.     

Antagonistic effect of cAMP and cGMP on the kinetic behaviour of phosphofructokinase from rat erythrocytes and reticulocytes

Fructose-6-phosphate (F6P)-saturation curves (up to 5 mM F6P) for phosphofructokinase (PFK) have been studied at physiological pH (7.1) and inhibitory (1.5 mM) or non-inhibitory (0.25 mM) ATP levels, in rat erythrocytes and reticulocytes. The addition of 300 microM cAMP to control samples activates the enzyme and displaces F6P-saturation curve towards the left, while the addition of cGMP inhibits the enzyme and shifts the curve to the right. The cAMP positive allosteric effect is more evident at inhibitory ATP levels, while the inhibitory effect of cGMP is very similar at both ATP levels. This antagonistic effect is exerted at the same regulatory site, since cAMP also activates the enzyme when cGMP is previously present in the reaction mixture. The physiological significance of this antagonism is not yet clear.     

Effect of substances that alter the level of intracellular cAMP on the reaction of human lymphocytes blast transformation]

Effects of cholera toxin, cholera anatoxin, theophylline and dibutyryl cyclic AMP (db-cAMP) on the PHA-induced DNA synthesis have been studied. It was shown that toxin, db-cAMP and theophylline suppressed mitogen-induced 3H-TdR incorporation and blast-transformation in a dose-related manner. When both toxin and theophylline were given together to PHA-stimulated lymphocytes, the inhibitory effects of these two agents were additive. The inhibitory effects of db-cAMP and theophylline were additive too. This inhibitory effects could be due to the elevation of intracellular cAMP. Cholera anatoxin exerted an inhibitory action on the PHA-stimulated lymphocytes. The inhibitory effects on lymphocyte DNA synthesis by anatoxin and theophylline were not additive. These results suggest that the effects of cholera toxin are mediated by cyclic AMP, but effects of cholera anatoxin may be associated with some other mechanism.     

Suppressive effects of the anti-oxidant N-acetylcysteine on the anti-malarial activity of artesunate

The anti-oxidant drug N-acetylcysteine (NAC) has been proposed as adjunctive treatment in severe falciparum malaria. However, this might inhibit the anti-malarial drug action of the artemisinins, which are thought to exert their parasitocidal action through oxidative damage. We studied the interaction between NAC and artesunate as well as quinine in an in vitro drug sensitivity assay. Combination with NAC reduced the parasitocidal effect of artesunate only within the first 6 h of incubation, whereas no interaction was observed with quinine. Pre-incubation of P. falciparum with NAC resulted in a similar inhibitory effect on the anti-malarial activity of artesunate, whereas no inhibition was observed when NAC was added 2 h after parasite exposure to artesunate. Assessment of parasite maturation inhibition by the standard Giemsa's staining was in accordance with the use of a vital staining. The results herein caution the use of adjunctive treatment for malaria infection. Combination of antagonistic drugs may lead to adverse effects.     

Effects of daunomycin on the microtubular network: a cytochemical study on a human melanoma cell line

The interaction of daunomycin (DAU), an anthracyclinic antibiotic employed as antitumoral agent, with microtubules, has been investigated by cytochemical and morphological methods on a human melanoma cell line (H14). Results obtained indicated that DAU was able to modulate the microtubule reassembly in cells treated with colcemid; such an effect proved to be dose-dependent. In particular, it has been observed that a low dose of DAU (0.05 microM) seemed to favor the microtubule reassembly whereas a higher dose (0.10 microM) impaired this process. In addition, when the anthracyclinic antibiotic was employed together with colcemid, both the cell detachment and the depolymerization of microtubules induced by the mitotic poison were hampered. These effects were dose-dependent and were better accomplished when DAU was used at an equimolar or at higher dose than that employed for the antimicrotubular agent. Moreover, the treatment of cells with DAU alone induced the stabilization of the microtubules, making them more resistant to the action of antimicrotubular agents. This effect could in part explain the antagonistic action exerted by DAU against colcemid. These observations seem to confirm that the microtubular network is an important target involved in the mechanism of action of the anthracyclinic antibiotics.     

A cAMP-dependent protein kinase inhibitor modulates the blocking action of ATP and 5-hydroxydecanoate on the ATP-sensitive K+ channel.

We studied the blocking mechanism of 5-hydroxydecanoate, a novel antiarrhythmic agent, on the ATP-sensitive K+ channel in the single ventricular myocytes using the inside-out patch clamp technique. The channel activity in response to 5-hydroxydecanoate varied with each membrane patch corresponding to the sensitivity to ATP. In this condition the exogenous application of cAMP or cAMP-dependent protein kinase (PKA) obviously recovered the ATP-sensitive K+ channel activity after channel deactivation. By contrast, in membrane patches exhibited low sensitivity to ATP, endogenous cAMP-dependent protein kinase inhibitor (PKI) depressed the channel activity and restored the inhibitory action of 5-hydroxydecanoate and ATP on the channel. These results suggest that PKA-PKI system is involved in the regulatory mechanism of gating activity of the ATP-sensitive K+ channel and the blocking action of 5-hydroxydecanoate and ATP appears to be exerted by potentiating the inhibitory action of PKI on the channel.     

A correlative study of RU38486 biopotency and competition with [3H]dexamethasone for receptors in the rat central nervous system

Dexamethasone inhibitory action on the release of adrenocorticotrophin has been studied using in vitro anterior pituitary preparations. This inhibition is reversed when the animal is given the antiglucocorticoid compound RU38486 simultaneously with dexamethasone. RU38486 acts at the receptor level and in the cytosolic binding study, it competes with [3H]dexamethasone for the binding sites in pituitary. Such competition is even more pronounced in hypothalamus and hippocampus, indicating that RU38486 also exert its antagonistic action at these sites.     

The effect of histamine on the rosette-forming ability of T-lymphocytes upon immunization with DPT vaccine and its components

The influence exerted by histamine on the capacity of T-lymphocytes for spontaneous rosette formation in intact animals and in animals immunized with adsorbed DPT vaccine and its components has been studied. Histamine at a concentration of 10(-3) M has been found to produce an inhibitory effect on the capacity of lymphocytes in the blood and spleen of guinea pigs immunized with adsorbed DPT vaccine and its components for spontaneous rosette formation. This effect of histamine has proved to be even more pronounced after the immunization of the animals with adsorbed DPT vaccine and Bordetella pertussis suspension, which is probably due to their sensitizing action.     

亚麻立枯病拮抗菌的筛选、生防效果及发酵条件优化

【目的】从健康亚麻植株的根际土壤中筛选对亚麻立枯病菌具有较强抑菌作用的拮抗菌,优化其产生抑菌活性物质的发酵条件,为其生防利用奠定基础。【方法】采用稀释平板涂布法和对峙培养法进行拮抗菌的筛选;根据菌株形态学特征、生理生化特性以及16S r RNA基因序列分析对其进行鉴定;利用温室抗病实验确定其生防效果;通过单因素实验和均匀设计实验优化其发酵条件。【结果】分离筛选到一株对亚麻立枯病菌具有显著拮抗作用的细菌HXP-5,且其对另外7种植物病菌真菌均有拮抗作用;鉴定菌株HXP-5为枯草芽孢杆菌;温室抗病实验结果表明其生防效果可达71.22%;其产生抑菌活性物质的最佳发酵条件为:葡萄糖为2.3%,胰蛋白胨+酵母粉(3:1)为0.25%,Na Cl为0.18%,发酵时间为72 h,发酵温度为27°C,转速为210 r/min,250 m L摇瓶装液100 m L,接种量为1.7%。【结论】经鉴定,对亚麻立枯病病菌具拮抗作用的菌株HXP-5为枯草芽孢杆菌,且对亚麻立枯病具有较强的防治效果,发酵条件进行优化后其对亚麻立枯病病原菌显示出更强的拮抗作用。