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At least 1,207 records · Page 67Linked to original sources

PubMed2000

Olfactory foraging by Antarctic procellariiform seabirds: life at high Reynolds numbers.

Antarctic procellariiform seabirds forage over vast stretches of open ocean in search of patchily distributed prey resources. These seabirds are unique in that most species have anatomically well-developed olfactory systems and are thought to have an excellent sense of smell. Results from controlled experiments performed at sea near South Georgia Island in the South Atlantic indicate that different species of procellariiforms are sensitive to a variety of scented compounds associated with their primary prey. These include krill-related odors (pyrazines and trimethylamine) as well as odors more closely associated with phytoplankton (dimethyl sulfide, DMS). Data collected in the context of global climatic regulation suggest that at least one of these odors (DMS) tends to be associated with predictable bathymetry, including upwelling zones and seamounts. Such odor features are not ephemeral but can be present for days or weeks. I suggest that procellariiforms foraging over vast distances may be able to recognize these features reflected in the olfactory landscape over the ocean. On the large scale, such features may aid seabirds in navigation or in locating profitable foraging grounds. Once in a profitable foraging area, procellariiforms may use olfactory cues on a small scale to assist them in locating prey patches.

Animals↗

PubMed1989

Interactions of heterocyclic Maillard products with the hepatic microsomal monooxygenase system.

1. Interactions of methyl-substituted pyrazines, and other constituents of Maillard products generated during heat treatment of food, with hepatic microsomal mixed-function oxygenases were studied in vitro. 2. Spectral interactions of N-containing heteroaromatic compounds with the cytochrome P-450 system are type I or type II depending on the state of induction, and are relatively weak. Inhibition of 7-ethoxycoumarin O-deethylation by these compounds is ten times lower than that of metyrapone, agreeing with the weak spectral interaction. Inhibition is competitive for 2,3-dimethylquinoxaline, and complex for 2,5-dimethylpyrazine and 2,3,5,6-tetramethylpyrazine. 3. Spectral and inhibitory interactions indicate biotransformation. This was studied with 2,3,5,6-tetramethylpyrazine; the metabolite formed was identified as 2-hydroxymethyl-3,5,6-trimethylpyrazine. Metabolism to the N-oxide did not occur.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1980

Acute oral toxicity of selected flavor chemicals.

The acute oral lethal doses are reported in rats or mice for 63 substances which are used in flavorings. For specific groups of compounds which contain several representatives of one structural class, some effects of structure on acute oral toxicity were observed. For pyrazines, the addition and position of methyl groups affected the toxicity while the substitution of ethyl for methyl had little effect. Toxicity increased with the proximity of the methyl group. The thiazoles and thiazolines tested had similar toxicities regardless of the side groups. The furan thioesters tested were about equally toxic, a fact which would be consistent with hydrolysis to the acid plus thiol.

Animals↗

PubMed2001

Effects of milk fat, cocoa butter, or selected fat replacers on flavor volatiles of chocolate ice cream.

Selected volatile compounds of chocolate ice creams containing 0.6, 4.0, 6.0, or 9.0% milk fat or containing 2.5% milk fat, cocoa butter, or one of three fat replacers (Simplesse, Dairy Lo, or Oatrim) were analyzed by gas chromatography and gas chromatography-mass spectrometry using headspace solid-phase microextraction. The headspace concentration of most of the selected volatile compounds increased with decreasing milk fat concentration. Fat replacers generally increased the concentration of volatiles found in the headspace compared with milk fat or cocoa butter. Few differences in flavor volatiles were found between the ice cream containing milk fat and the ice cream containing cocoa butter. Among the selected volatiles, the concentration of 2,5-dimethyl-3(2-methyl propyl) pyrazine was the most highly correlated (negatively) with the concentration of milk fat, and it best discriminated among ice creams containing milk fat, cocoa butter, or one of the fat replacers.

Animals↗

PubMed2004

Volatile free fatty acids as ripening indicators for Serra da Estrela cheese.

Serra da Estrela cheese is an artisanal cheese manufactured from raw ewe's milk coagulated with Cynara cardunculus; it is highly appreciated for its unique flavor and bouquet. This research effort focused on a search for the molecules responsible for those organoleptic characteristics. Eighty cheeses manufactured in 4 dairies located in the Appelation d'Origine Protegee region of Serra da Estrela, Portugal, were thus assayed for volatiles, in an attempt to characterize their odorous profile. Cheeses were analyzed from the time of manufacture up to 180 d of ripening. The volatile fraction was assayed by solid phase microextraction-gas chromatography/mass spectroscopy, and several compounds belonging to different chemical groups (e.g., fatty acids, esters, carbonyl compounds, pyrazines, and sulfur compounds) were detected in that traditional cheese. Among these, free fatty acids (FFA) were quantitatively the dominant family present. Furthermore, sensory descriptors for the typical aroma of this cheese included acidic, sweaty, and sheepy-like. Acetic, isobutyric, and isovaleric acids increased in concentration during the ripening process up to 90 d, and remained constant thereafter. Preliminary sensory analysis was performed by addition of the major FFA to an unripened cheese matrix; results showed that they could successfully be used as ripening indicators for this cheese. Such key molecules may thus be used to monitor ripening, and hence find the optimal consumption time for this gourmet dairy product.

Animals↗

PubMed2000

An amiloride-sensitive and voltage-dependent Na+ channel in an HLA-DR-restricted human T cell clone.

We investigated changes in voltage-gated Na+ currents and effects of extracellular Na+ on proliferation in HLA-DR-restricted human CD4+ alphabeta T cells after stimulation with a non-self antigenic peptide, M12p54-68. In the absence of antigenic peptide, neither single (n = 80) nor APC-contacted (n = 71) T cells showed voltage-gated inward currents recording with whole-cell patch-clamp techniques, even with Ca2+ and Na+ ions present in the perfusion solution. However, with the same recording conditions, 31% (26 of 84) of APC-contacted T cells stimulated with the antigenic peptide showed voltage-dependent inward currents that were elicited from -60 mV. The inward currents were not inhibited in extracellular Ca2+-free conditions or in the presence of 1 mM NiCl2. However, they were completely inhibited in extracellular Na+-free conditions, which were made by replacing Na+ with iso-osmotic N-methyl-d -glucamine or choline. The Na+ currents were insensitive to tetrodotoxin, a classical blocker of Na+ channels, but were dose-dependently inhibited by amiloride, a potassium-sparing pyrazine diuretic. Furthermore, the Ag-specific proliferative response of T cells was completely inhibited in Na+-free Tyrode's solution and was suppressed by amiloride in a dose-dependent manner. Our findings suggest that activation of amiloride-sensitive and voltage-gated Na+ channels would be an important step to allow an adequate influx of Na+ and maintain a sustained high Ca2+ level during T cell activation.

Amiloride↗

PubMed1977

Cephalosporins. I. Cephaloglycin analogs with six-membered heterocycles in the C-3 side chain.

Cephaloglycin analogs with six-membered heterocycles in the C-3 side chain have been prepared by nucleophilic substitution of 7-aminocephalosporanic acid with appropriate azine thiols followed by 7-N-acylation with phenylglycine by the mixed anhydride method. Seventeen thiols of non-substituted or substituted pyridines, pyridazines, pyrimidines, pyrazines and triazines were used as the S-nucleophiles. In general, pyridazine thiols gave cephalosporins processing good antimicrobial activity against both gram-positive and gram-negative bacteria. Among them 6-hydroxypyridazine-3-thiol gave the most active compound of this series, BB-S 118 (1f), which was significantly more active than cephalexin and cephaloglycin in vitro against gram-positive and gram negative bacteria.

Animals↗

PubMed1976

[Experiments in the diagnosis and therapy of stylesiasis in sheep].

Tested were several methods for the diagnosis of sheep stylesiasis - the study of washings, successive decantation, flotation after Füleborn and with the use of zinc sulfide - obtaining no favourable results. Immunobiologic methods, such as the skin allergic test and the complement-fixation test had no practical diagnostic value either. Sheep infected with S. globipunctata reacted positively to antigens of M. expansa, M. benedeni, and A. centripunctata. A total of 15 anticestode agents were tested to treat stylesias-isaffected animals. Bithionol and lead arsenate caused the shedding of Stylesia strobilae up to 100 per cent, however, about 50 per cent of the scolexes with the necks, attached to the intestinal wall, remained intact and produced strobilae. Cyclosamide, dichlorophen, trichlorophen, sulphen, dibromsulphen, and sulfoxide removed the strobilae, but did not almost act on the scolexes and necks, which later on developed strobilae. Praciquantel (isochinoline-pyrazine, EMBAU, droncit-Bayer) at the rate of 15 mg/kg is 100 per cent effective against S. globipunctata, M. expansa, M. benedeni, M. automnalia, and A. centripunctata, and has been tested for the first time as an anticestode means against the Anoplocephalite parasites in sheep. It has no unpleasant odor and taste, is practically untoxic (therapeutic index over 20), and could be used in group treatment of sheep.

Animals↗

PubMed1998

Synthesis and antimycobacterial activity of some heteroarylcarboxamidrazone derivatives.

A series of pyridine-2-, pyrazine-2- and quinoline-2-carboxamidrazone derivatives was prepared in an automated fashion and tested against Mycobacterium fortuitum in a rapid screen. Seven pyridine-2-carboxamidrazone derivatives were investigated further and four were found to have inhibitory activity with compound 4af being the most active. The structure activity implications are discussed.

Anti-Bacterial Agents↗

PubMed1999

[Detection of pyrazinamidase activity for differentiation of Campylobacter, Arcobacter, and Helicobacter spp. by using a high-performance liquid chromatography method].

A high-performance liquid chromatography method was investigated for the detection pyrazinamidase activity by Campylobacter, Arcobacter, and Helicobacter spp. Pyrazine carboxilic acid, one of the end products of pyrazinamide hydrolysis by microorganisms, was detected by using a high-performance liquid chromatography (HPLC). A loopful of organism colonies was emulsified in 0.5 ml of a 0.5% pyrazinamide solution. The suspens on was incubated in a 37 degrees C water bath for 18-20 hr. After centrifugation, the supernatant was analyzed by HPLC. This HPLC method does not require microaerobic incubation and was easy to interpret for strains with weak enzymatic activity. By this method, we tested 111 clinical isolates, type and reference strains of Campylobacter spp., Arcobacter spp., and Helicobacter spp. , C. jejuni, C. jejuni subsp. doylei, C. coli, C. upsaliensis, C. lari, C. lari (urease+), C. helveticus, C. hyolei, C. sputorum subsp. fecalis, C. gracilis, C. concisus, C. curvus were positive for pyrazinamidase. C. fetus subsp. fetus, C. hyointestinalis, C. sputorum subsp. sputorum, C. sputorum subsp. bubulus, C. mucosalis, A. butzleri, A. skirrowii, A. cryaerophilus, H. pylori, H. cinaedi, H. fennelliae, H. mustelae, H. felis, H. muridarum, H. canis, H. nemestrinae, H. pamentensis, H. pullourum were negative.

Amidohydrolases↗

PubMedDate not supplied

Qualitative and quantitative analysis of new amino acid derivatives of anticonvulsant activity.

Qualitative and quantitative methods for analysis of three new amino-acidic anticonvulsants of low neurotoxicity: pyrazole-3,5-dicarboxylic acid benzylamine (1), pyrazine-2-carboxylic acid benzylamine (2) and (R, S) N-acetyl-2-pyrrolidone-5-carboxylic acid benzylamide (3) have been developed. Qualitative analysis included characteristic reactions, chromatographic (TLC) investigations, IR and UV spectra interpretation and quantitative analysis involved spectrophotometric, chromatographic (HPLC) and acidimetric methods.

Amino Acids↗

PubMed2002

[Ononis arvensis in vitro--abiotic elicitation].

The effect of two abiotic elicitors--two newly synthesized compounds (substituted anilides of pyrazine-2-carboxylic acids)--on the formation of flavonoids in the callus culture of Ononis arvensis L. was tested. The compounds markedly influenced the production of flavonoids in an in vitro culture. Particularly after elicitation with a solution of compound No. 1 (4-hydroxyanilide 6-chloro-5-terc.butylpyrazine-2-carboxylic acid) in a concentration of 3.32.10(-7) mol.l-1 and within 48 hours of elicitation an increase in flavonoid formation by 976% versus the control took place.

Anilides↗

PubMed2002

Activation of presynaptic 5-hydroxytryptamine 2A receptors facilitates excitatory synaptic transmission via protein kinase C in the dorsolateral septal nucleus.

Effects of 5-hydroxytryptamine (5-HT) on EPSPs and EPSCs in the rat dorsolateral septal nucleus (DLSN) were examined in the presence of GABA(A) and GABA(B) receptor antagonists. Bath application of 5-HT (10 microm) for 5-10 min increased the amplitude of the EPSP and EPSC. (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (10 microm), an agonist for 5-HT1A and 5-HT7 receptors, did not facilitate the EPSP. alpha-Methyl-5-HT (10 microm), a 5-HT2 receptor agonist, increased the amplitude of the EPSC. Alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (10 microm) and 6-chloro-2-(1-piperazinyl)pyrazine (10 microm), selective 5-HT2B and 5-HT2C receptor agonists, respectively, had no effect on the EPSP. The 5-HT-induced facilitation of the EPSP was blocked by ketanserin (10 microm), a 5-HT2A/2C receptor antagonist. However, N-desmethylclozapine (10 microm), a selective 5-HT2C receptor antagonist, did not block the facilitation of the EPSP induced by alpha-methyl-5-HT. The inward current evoked by exogenous glutamate was unaffected by 5-HT. 5-HT (10 microm) and alpha-methyl-5-HT (10 microm) increased the frequency of miniature EPSPs (mEPSPs) without changing the mEPSP amplitude. The ratio of the paired pulse facilitation was significantly decreased by 5-HT and alpha-methyl-5-HT. The 5-HT-induced facilitation of the EPSP was blocked by calphostin C (100 nm), a specific protein kinase C (PKC) inhibitor, but not by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (10 microm), a protein kinase A inhibitor. Phorbol 12,13-dibutyrate (3 microm) mimicked the facilitatory effects of 5-HT. These results suggest that 5-HT enhances the EPSP by increasing the release of glutamate via presynaptic 5-HT2A receptors that link with PKC in rat DLSN neurons.

Animals↗

PubMedDate not supplied

Synthesis of a new antischistosomally active and toxicologically tolerant C-12 monothione surrogate of the universal antihelmintic praziquantel.

A new C-12 monothione mimic (III) of the universal antihelmintic Praziquantel (I) namely, 2-cyclohexylthiocarbonyl( 1,2.3,6,7,11b)-hexahydro-4H-pyrazino[2-1a] isoquinoline-4-one was chemically synthesized and structurally elucidated (Elemental analysis. El-Mass, 13C-NMR and IR spectroscopy). Antischistosomal potency in the order of -76% comparable to that for our newly reported C-12 and C-4 dithion mimic II (-70%) and Praziquantel. Praziquantel (100%, mice infected with S. mansoni cercariae), was realized. Toxicological evaluation (mice liver and kidney functions) and biochemical parameters (cholesterol, triglycerides, albumin, total serum proteins and amino acid profile of liver protein homogenate) were also assayed. Comparable to the parent drug, general insignificant toxicological diferences could be attributed for III. Interestingly, III exhibited intermediate biological figures between I and II. An order of II III>I, for the other tested biochemical parameters was observed. A consideration of obtained results could indicate that, structurally, an intact glycine amide segment of the pyrazine moiety, as it is the case in both I and III, and not in II (glycine thioamide) seemed now more crucial for exhibiting an optimum antihelmintic potency as well as a more tolerant toxicity characteristics. Additionally, the obtained comparable amino acid profile of mice liver protein homogenate after the treatment by III, could suggest similar biochemical, lethal mechanistic and metabolic routes for II, III and I. The new lipophilic candidatee III seems to merit more profound chemical, biological, and pharmaceutical investigations.

Animals↗

PubMed2002

Ruthenium-based NAMI-A type complexes with in vivo selective metastasis reduction and in vitro invasion inhibition unrelated to cell cytotoxicity.

A series of analogues of NAMI-A, a reference compound active on solid tumor metastases, were synthesized (NAMI-A type complexes). They share the same chemical structure of NAMI-A, and differ from it in the nature of the coordinated nitrogen ligand, such as pyrazole, thiazole and pyrazine, which are less basic than imidazole. This modification confers to the new NAMI-A type complexes a better stability in aqueous solution compared to the parent compound, a very important characteristic for a class of compounds that, with NAMI-A, is currently completing a phase I clinical trial at the Netherlands Cancer Institute of Amsterdam. Cytotoxicity and the effects on cell cycle and invasion were investigated on TS/A, B16-F10 and MCF-7 tumor cell lines, while the inhibition of lung metastases was determined on the mouse experimental tumors Lewis lung carcinoma and MCa mammary carcinoma. The new complexes show a pharmacological activity very similar to that of the parental compound NAMI-A: in vitro they are devoid of meaningful cytotoxicity against tumor cells, and in vivo they inhibit metastasis formation and growth approximately to the same extent as NAMI-A. Thus the new NAMI-A type complexes retain the same potent characteristic of NAMI-A to selectively interact with solid tumor metastases. However, compared to NAMI-A they do not stop cell cycle progression at G2-M level and are more active in preventing the spontaneous invasion of Matrigel by tumor cells exposed for 1 h to 10(-4) M concentration. Globally, these complexes take advantage of the knowledge on NAMI-A and appear particularly interesting for future clinical handling and applications.

Animals↗

PubMedDate not supplied

High performance liquid chromatographic (HPLC) measures of hydrophobicity as determined by means of new HPLC columns.

Two new commercially available reversed phase high performance liquid chromatographic (HPLC) columns were tested from the view point of their usefulness for determination of hydrophobicity by means of partition chromatography. One column comprised a specially prepared hydrocarbon-bonded silica stationary phase material. The other column was packed with a polybutadiene-coated alumina (PBCA) phase. As reference served a regular commercial octadecylsilica (ODS) column. A series of test solutes were pyrazine CH- and NH-acids--the compounds which are able to take part in specific as well as in nonspecific intermolecular interactions. Unique properties of the new hydrocarbonaceous column manifested themselves in regular linear relationships between logarithms of capacity factors and volume percent of methanol in aqueous eluent. The main advantage of the PBCA column is a possibility of performing chromatography at alkaline pH. Both new columns are superior to regular ODS columns in respect of providing reliable chromatographic measures of hydrophobicity. It was observed that hydrophobicity parameters determined in individual HPLC systems are not highly intercorrelated and hence can reflect different structural features of solutes.

Aluminum↗

PubMed1992

Self propagation of injured tissue by localized changes of free radicals in the central nervous system.

To examine the role of free radicals in the pathogenesis of injured tissue in the central nervous system (CNS), we developed a new technique for mapping superoxide free radicals, vascular permeability, and energy metabolism simultaneously. The distribution of superoxide anions in the CNS is based upon the 380 nm chemiluminescence of 2-methyl-6-phenyl-3,7-dihydroimidazo[1,2a] pyrazin-3-one (CLA-phenyl) when it reacts with superoxide anions in frozen tissue sections. This new CLA-phenyl hybrid--paper technique show clear relationships between the regional production of superoxide free radicals, increased vascular permeability, and changes of energy metabolism in the self propagating phenomena occurring in the various lesions in the CNS.

Adenosine Triphosphate↗

PubMed2004

Reduction of in vivo lung metastases by dinuclear ruthenium complexes is coupled to inhibition of in vitro tumour invasion.

Mononuclear ruthenium-dmso compounds showed interesting antimetastatic properties on experimental models of solid tumours. In line with the interesting results with multinuclear platinum complexes, which proved to overcome cisplatin resistance, we thought it worthwhile to test the pharmacological properties of some dinuclear ruthenium complexes to ascertain the possible advantages due to the introduction of a second metal centre over NAMI-A and its mononuclear analogues. These compounds belong to the general formula X2[[RuCl4(dmso-S)]2(mu-L)] or [X][[RuCl4(dmso-S)](mu-L)[RuCl3(dmso-S)(dmso-O)]] where L is a nitrogen donor ligand (pyrazine; pyrimidine; 4,4'-bipyridine; 1,2-bis(4-pyridyl)ethane; 1,2-bis(4-pyridyl) ethylene; 1,3-bis(4-pyridyl)propane) and X a counterion. We focused on parameters related to metastatic ability such as gelatinase activity, detected by zymography, and invasive potential, measured by means of a transwell chamber. These activities were correlated to the ability to inhibit tumour metastases in vivo. All dinuclear complexes, except compound D8 ([NH4]2[[RuCl4(dmso-S)]2(mu-pyz]), decrease the number of tumour cells that cross a matrigel barrier, and inhibit MMP-9 gelatinolytic activity at concentrations lower than that of NAMI-A and of other mononuclear ruthenium complexes. In vivo compounds D5 (Na2[[RuCl4(dmso-S)]2(mu-ethylbipy)]) and D7 ([NH4][[RuCl4(dmso-S)](mu-pyz)[RuCl3(dmso-S) (dmso-O)]]) show anti-metastasis activity, at two dose levels, with mild or null effect on primary tumour growth; compound D8 is the weakest active. All compounds tend to accumulate in liver and kidneys, rather than in tumour and lungs. However, compound D5, the most active in vitro on invasion and gelatinases and active in vivo on metastasis, is better concentrated in the lungs than compound D8 which is less active or inactive in vitro and in vivo. Histological analysis show liver, as well as kidney toxicities that limit in vivo activity. These data thus suggest dinuclear ruthenium complexes as promising anti-invasive agents for cancer treatment.

Animals↗