Antioxidant properties of dihydropyridines in isolated rat hearts

Isolated Sprague-Dawley rat hearts were perfused under constant flow conditions. Hearts were treated with vehicle or treatment buffers, including nisoldipine, nifedipine, or the optical isomers (+)- or (-)-nisoldipine. H2O2 (500-600 microM) was then added to the treatment buffer for 12 min. H2O2 was removed and perfusion continued with treatment buffers (10 min) followed by control buffer (20 min). Contractile function decreased following perfusion with H2O2. Contractile function was protected was protected in a concentration-dependent manner (nisoldipine=19,26,50,63 and 78%; nifedipine = 23, 37, 55,61, and 63% of pre-peroxide function, 0, 0.1, 0.5 1.0, and 5 microliter, respectively). There were no significant differences between equal concentrations of nisoldipine and nifedipine. Contractile function was equally protected by both (+)- and (-)-nisoldipine compared with vehicle-treated hearts (56, 67, and 16%, of pre-peroxide function, respectively). Biochemical analyses indicated that H2O2 damaged plasma membranes (increased lactate dehydrogenase leak) and caused lipid peroxidation (elevated tissue thiobarbituric acid reactive substances). Biochemical changes were equally reduced by nisoldipine and nifedipine treatments and by (+)- and (-)-nisoldipine. The treatment groups have widely differing IC50 values as calcium channel antagonists, yet they had equal effects in reducing oxidative injury, suggesting that this beneficial effect is not mediated by calcium antagonism.     

Biological properties of strain of Yersinia enterocolitica isolated from humans

A total of 1300 patients were examined; this number included patients suffering from food poisoning and with suspected dysentery hsopitalized at the isolation hospital; patients with diarrheal diseases under observation of the intestinal unit of the sanitary-epidemiological station, and patients with acute or exacerbation of chronic affection of the bile tracts. A total of 28 Yersinia enterocolitical strains were isolated from these patients, this constituting 2.1% of the total number os examinations. The strains isolated were typical by ciological properties and were referred to the 3rd and 9th serological and the 3rd and 4th biochemical types.     

Antioxidant properties of the triaminopyridine, flupirtine

Flupirtine is a triaminopyridine-derived centrally acting analgesic, which interacts with mechanisms of noradrenergic pain modulation. Recently, it has been found to display neuroprotective effects in various models of excitotoxic cell damage, global and focal ischemia. Although this profile suggests that flupirtine acts as an antagonist of the N-methyl-D-aspartate (NMDA) and glutamate-triggered Ca2+ channel, there is no direct interaction with the receptor. In this paper, we examined whether flupirtine can act as an antioxidant and prevent free radical-mediated structural damage. Flupirtine at 5-30 microM inhibited ascorbate/ Fe2+ (1-10 microM)-stimulated formation of thiobarbituric reactive substances, an indicator of lipid peroxidation, in rat brain mitochondria. Interestingly, we found an increasing effectiveness of the drug at higher iron concentrations. Additionally, higher concentrations of flupirtine also provided protection against protein oxidation, as demonstrated by a decrease in protein carbonyls formed after treatment of rat brain homogenates with ascorbate/Fe2+. In PC12 cell culture, flupirtine at 10-100 microM was able to attenuate H2O2-stimulated cell death and improve the survival by 33%.     

Virulence and colonization-associated properties of Helicobacter pylori isolated from children and adolescents

OBJECTIVE: We describe the sonographic appearance and vascularization of hemangiomas and determine if vessel density and peak systolic Doppler shifts distinguish hemangiomas from other superficial soft-tissue masses. SUBJECTS AND METHODS: Our pilot study included 20 infants and children with hemangiomas who were to undergo biopsy before treatment with interferon alpha-2b. We used Doppler sonography to determine the number of vessels per square centimeter, peak arterial Doppler shift, resistive index, and signs of arteriovenous shunting. All hemangiomas showed high vessel density (more than five per square centimeter) and high Doppler shifts (more than 2 kHz), and these two factors became our diagnostic criteria. A prospective study of 116 patients was then carried out. One hundred sixteen consecutive pediatric patients with superficial soft-tissue masses were examined using Doppler sonography; sonographic findings were compared with the final diagnoses that were established by biopsy, CT, or clinical follow-up. RESULTS: The final diagnoses included 70 hemangiomas, 20 venous malformations, three arteriovenous malformations, three arteriolocapillary malformations, and 20 other masses. Fifty-nine lesions showing high vessel density (more than five per square centimeter) and a peak arterial Doppler shift exceeding 2 kHz were correctly diagnosed as hemangiomas (sensitivity, 84%; specificity, 98%). One arteriovenous malformation showed high vessel density and high Doppler shifts, but none of the other masses that were not hemangiomas did. Eleven patients with hemangiomas who were being treated with interferon at the time of the study fulfilled only one of the two diagnostic criteria. CONCLUSION: High vessel density and high peak arterial Doppler shift can be used to distinguish hemangiomas from other soft-tissue masses.     

Biological properties of Streptococcus bovis bacteriophages isolated from lysogenic cultures and sheep rumen

Biological characteristics of eleven phages for Streptococcus bovis were investigated; seven phage were isolated from ovine rumen and four were virulent mutants of temperate phages of lysogenic cultures. The phages had many properties in common: similar morphology of negative colonies, the identical spectrum of lytic action, related antigens, absolute or high requirement of calcium ions, thermolability, and inactivation by the content of the rumen. Their susceptibility to the inactivating action of acetic acid, urea and temperature was however different. Chloroform and phenol may be used during purification and conservation of the phages.     

Nucleotide and actin binding properties of the isolated motor domain from Dictyostelium discoideum myosin

Nucleotide and actin binding properties of the truncated myosin head (S1dC) from Dictyostelium myosin II were studied in solution using rabbit skeletal myosin subfragment 1 as a reference material. S1dC and subfragment 1 had similar affinities for ADP analogues, epsilon ADP and TNP-ADP. The complexes of epsilon ADP and BeFx or AIF4- were less stable with S1dC than with subfragment 1. Stern-Volmer constants for acrylamide quenching of S1dC complexes with epsilon ADP, epsilon ADP.AIF4- and epsilon ADP.BeFx were 2.6, 2.9 and 2.2 M-1, respectively. The corresponding values for subfragment 1 were 2.6, 1.5 and 1.1 M-1. The environment of the nucleotide binding site was probed by using a hydrophobic fluorescent probe, PPBA. PPBA was a competitive inhibitor of S1dC Ca(2+)-ATPase (Ki = 1.6 microM). The binding of nucleotides to subfragment 1 enhanced PPBA fluorescence and caused blue shifts in the wavelength of its maximum emission in the order: ATP approximately ADP.AIF4- approximately ADP.BeFx > ATP gamma S > ADP > PPi. In the case of S1dC, the effects of different nucleotides were smaller and indistinguishable from each other. S1dC bound actin tighter than S1 (Kd = 7 nM and 60 nM, respectively). The actin activated MgATPase activity of S1dC varied between preparations, and the Vmax and K(m) values ranged between 3 and 7 s-1 and 60 and 190 microM, respectively. S1dC showed lower structural stability than S1 as revealed by their thermal inactivations at 35 degrees C. These results show that the nucleotide and actin binding of S1dC and subfragment 1 are similar but there are some differences in nucleotide and phosphate analogue-induced changes and the communication between the nucleotide and actin binding sites in these proteins.     

The biological properties of Haemophilus influenza isolated from healthy children and from patients with acute and chronic respiratory diseases

The comparative study of the biological properties of H. influenzae strains isolated from healthy children and from patients with acute and chronic respiratory diseases has been made, taking into account the biochemical features (biotypes) and adhesive activity of these strains. Differences in various biotypes of H. influenzae strains isolated from patients with bronchopulmonary diseases and from healthy carriers have been established. H. influenzae strains isolated from various sources differ by their adhesive properties: strains isolated from patients with acute bronchopulmonary diseases have the highest adhesive activity, while strains isolated from healthy controls have the lowest adhesive activity. The data thus obtained indicate the possible dependence of the degree and duration of the colonization of the respiratory tract by H. influenzae on the biological properties of these microorganisms. The monitoring of the sensitivity of H. influenzae strains to antibiotics has demonstrated that these strains retain high sensitivity to ampicillin, chloramphenicol, gentamicin and exhibit a tendency towards an increase in resistance to penicillin and erythromycin.     

A study of animal pathogenicity of staphylococci isolated from pathological material and its correlation with biochemical properties

A simple and rapid procedure to make yeast cells permeable by agitating with toluene-ethanol, (TE) 1:4, v/v was developed. The permeated cells retained their ability to catalyze certain enzyme reactions. Temperature and duration of agitation during TE treatment played an important role in retention of the catalytic potential of permeated cells. The in situ assay using permeated cell preparations was more sensitive even in the absence of added cofactors than in the vitro assay in detecting assimilatory nitrate reductase (NAD(P)H:nitrate oxidoreductase, EC 1.6.6.2) (NAR) activity in Candida utilis. Using in situ assay technique, different mechanisms regulating the biosynthesis of NAR in C. utilis were investigated. Nitrogen starvation did not lead to derepression of NAR. NO3-ions were absolutely essential for induction and maintenance of high levels of NAR activity. Cells grown on ammonium nitrate possessed relatively lower levels of NAR. Kinetics of NAR induction were followed as a function of time and inducer concentration. The influence of various cations on the induction of NAR by nitrate was investigated. A wide range of D-amino acids induced NAR synthesis. Of 22 L-amino acids tested only phenylalanine induced significant levels of NAR. Various intermediates of the pathway of nitrate reduction influenced the rate of NAR induction. There was a rapid disappearance of in vivo activity of the enzyme of induced yeast cells on nitrogen starvation, and the rate of loss was accelerated by the presence of NH4+.     

白花丹素的提取及其抗氧化活性研究

[目的]从白花丹中提取活性成分白花丹素,研究抗氧化活性并探讨作用机理.[方法]利用柱层析法从白花丹的乙醇提取液中分离得到其活性成分白花丹素,通过核磁共振、红外光谱,质谱等谱学方法鉴定化合物结构;运用磷钼酸盐法测定不同浓度白花丹素的总抗氧化能力;运用碘量法测定不同浓度白花丹素抑制花生油脂过氧化的能力.[结果]白花丹素表现出较强的总抗氧化能力,能明显抑制油脂过氧化,且呈正相的剂量效应和时间效应,各处理浓度的抗氧化能力也基本表现出优于BHT(1.0 mg∥ml)的抗氧化能力.[结论]白花丹素萘醌环的酚羟基是抗氧化作用的主要活性基团,白花丹素的抗氧化能力是抗肿瘤作用的重要机制之一.     

云南松低聚原花青素抗氧化活性研究

[目的]为云南松低聚原花青素的进一步研究和应用提供依据.[方法]从还原能力、DPPH自由基和羟基自由基清除作用3个方面对云南松低聚原花青素抗氧化活性进行测定.[结果]云南松低聚原花青素的还原能力稍好于合成抗氧化剂BHT;DPPH自由基和羟基自由基的丰抑制浓度(IC50)分别为1.89和1.31 mg/ml,而BHT对二者的半抑制浓度分别为3.00和1.81 mg/ml,云南松低聚原花青素对DPPH自由基和羟基自由基的清除作用强于BHT,且该清除作用与样品浓度存在一定的量效关系.[结论]云南松低聚原花青素具有较强的抗氧化活性.     

Release of renin from glomeruli isolated from rat kidney

Cardiovascular and behavioural responses elicited by novel, noxious or aversive stimuli have been studied in dogs and cats. Hindlimb blood flow, heart rate and arterial blood pressure increased in dogs when an orienting response was elicited by a novel stimulus (a sound). Similar cardiovascular responses occurred in dogs to mild noxious stimulus and in cats displaying a threatening posture when confronted by a dog. The cardiovascular components of the orienting response to a sound habituated with repetition of the sound. In two dogs however sensitization (increase) of the response occurred with reped by repetition of the confrontations: the vasodilation in the muscles waned and eventually was replaced by vasoconstriction while the cardiac acceleration and pressor response persisted. The threatening response was the most persistent. The modification of the behavioural and cardiovascular aspect of the response was not developing in parallel. The cardiovascular pattern was altered before any apparent changes of the behavioural pattern occurred. The cardiovascular responses of the noxious stimulus in dogs and cardiovascular components of the defence reaction in cats were readily conditioned to a sound. The possible role of the modification of the cardiovascular pattern in defence reactions in pathogenesis of hypertension is discussed.     

Effect of cardiolipin on functional properties of isolated rat liver mitochondria

Receptor-type serine/threonine kinases (RSKs) have been organized into two distinct classes known as types I and II on the basis of sequence similarity. However, experiments have shown ligand specificities in the two classes and as a result type I and type II receptors can often bind to a common ligand. The transforming growth factor-beta- (TGF-beta) specific receptors represent such a case, where both type I and II receptors (T beta RI and T beta RII) are observed. Of additional interest is the observation that heteromeric associations of type I and II receptors can also enable signaling. To further elucidate the function of various RSKs, the extracellular domains of both alpha and beta chains from human granulocyte-macrophage colony-stimulating factor receptors were linked to transmembrane cytoplasmic domains of RSKs. Chimeric receptors of human granulocyte-macrophage receptor (hGMR) alpha with T beta RI and hGMR beta with T beta RII were expressed in murine pre-B cell-derived Ba/F3 cells. These chimeras formed heteromeric complexes, transmitted TGF-beta signals, and were down-modulated in response to human granulocyte-macrophage colony-stimulating factor. However, experiments utilizing these chimeric receptors in different combinations revealed that only heteromeric associations of transmembrane cytoplasmic domains mediated signaling and down-modulation. Chimeric receptors with transmembrane cytoplasmic domains of activin receptor type II and bone morphogenetic protein receptor type II also provided signals in conjunction with chimeric T beta RI. As a result, these type II receptors may share a common potential to signal via T beta RI. hGMR-RSK chimeric receptors may be useful tools for the identification and characterization of the divergent signals mediated by individual RSKs.     

The biological properties of Rahnella aquatilis strains isolated in different regions

This study examines stress in the parents of adolescents and young adults with an intellectual disability and compares it with stress reported by parents with offspring without an intellectual disability. An initial qualitative pilot study lead the authors to Baine et al's Stress Scale. The Baine et al scale is relatively new and addresses aspects of stress not previously investigated among the parents of people with an intellectual disability, namely, stress from the difficult relationship with health professionals and service providers and negative community attitudes to people with an intellectual disability. Because of the relevance to nurses, particular interest is paid to stress from the relationship parents have with health professionals and service providers. The study found significantly greater stress in the parents of young people with an intellectual disability in all aspects of stress examined, including stress from the individual with the disability, internal family stress, stress from the financial strain of having a family member with a disability, stress from community attitudes and stress perceived from the relationship with health professionals and service providers. These findings are distressing in the light of government and service agency policies of community care and independent living. This paper makes recommendations relevant to nurses and identifies difficulties for parents of young people with an intellectual disability in the implementation of current government policy.     

Identification and properties of a major plasma metabolite of irinotecan (CPT-11) isolated from the plasma of patients

Irinotecan [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11)] is a promising water-soluble analogue of camptothecin [S. Sawada et al., Chem. & Pharm. Bull. (Tokyo), 39: 1446-1454, 1991]. We have reported previously the presence of an important polar metabolite, in addition to 7-ethyl-10-hydroxycamptothecin (SN-38) beta-glucuronide, in samples of plasma taken from patients undergoing treatment with CPT-11 (L.P. Rivory and J. Robert, Cancer Chemother. Pharmacol. 36: 176-179, 1995; L. P. Rivory and J. Robert, J. Cromatogr., 661: 133-141, 1994). Plasma samples (0.5 ml) containing comparatively large amounts of this metabolite were extracted by solid-phase columns and subjected to high-performance liquid chromatography and mass spectrometry in parallel to fluorometric detection. The metabolite yielded [M + 1] ions with a m/z of 619, representing the addition of 32 atomic mass units to CPT-11. Purified fractions were subjected to proton nuclear magnetic resonance, and the structure determined, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycampothecin (APC), was further validated following synthesis. Like CPT-11, APC was found to be only a weak inhibitor of the cell growth of KB cells in culture (IC50, 2.1 versus 5.5 micrograms/ml for CPT-11 and 0.01 microgram/ml for SN-38, the active metabolite of CPT-11) and was a poor inducer of topoisomerase I DNA-cleavable complexes (100-fold less potent than SN-38). In contrast to CPT-11, APC was not hydrolyzed to SN-38 by human liver microsomes or purified human liver carboxylesterase. Furthermore, APC did not inhibit the hydrolysis of CPT-11 in these preparations. Interestingly, APC was only a weak inhibitor of acetylcholinesterase in comparison to CPT-11 and neostigmine. It appears likely, therefore, that APC does not contribute directly to the activity and toxicity profile of CPT-11 in vivo.