[Ultrastructure of the myocardium in the calcium channel blocker withdrawal syndrome].

Changes in the ultrastructure of rat myocardial cells were investigated after withdrawal of therapy with the calcium entry blockers diltiazem, nifedipine, and verapamil. Two hours after the last administration the ultrastructure was without significant changes in comparison to the control group. However the incidence of contracture bands, dehiscence of intercalated discs and lesions of mitochondria observed 30 hours after therapy withdrawal demonstrated serious damage of myocardial tissue.

[The effect of verapamil and nifedipine on acid-base and electrolyte disorders induced by cholesterol in rabbits].

The influence of cholesterol atherogenic diet on the acid-base balance and electrolyte profile was investigated in rabbit blood and the effect of simultaneous administration of verapamil and nifedipine on the induced changes was evaluated. Cholesterol diet resulted in significant metabolic acidosis, hyperkalemia, and a slight decrease in plasma ionized calcium. On the other hand, longterm treatment with verapamil and nifedipine exhibited their protective effect, with the acid-base status and electrolyte profile maintained within the normal range.

[Changes in myocardial sensitivity after sudden with withdrawal of calcium channel blockers].

Our previous experiments have suggested that besides the receptor cont and/or sensitivity a decrease of intracellular calcium level significantly participates in the mechanism of beta-blocker withdrawal 'rebound' phenomenon. This suggestion initiated studies in which possible changes in myocardial responsibility to cardioactive drugs were investigated in the condition of withdrawal of treatment with calcium entry blockers. The results showed increased cardiotoxicity of ouabain, aconitine and CaCl2, as well as an increased response of the heart to isoprenaline 24 hours after sudden cessation of treatment with verapamil (2 mg.

[Changes in the relative levels of fatty acids in blood and myocardium in the Prague breed of rats with hereditary hypercholesteremia after administration of slow calcium channel blockers].

The present paper describes the effect of six-week oral administration of verapamil and diltiazem (1 mg.kg-1 of weight two times daily in 12 hour intervals) on the content of fatty acids of the serum and myocardium of PHHC rats. A cholesterol diet changes the content of fatty acids of the serum and myocardium of PHHC rats in comparison with control rats without the cholesterol diet.

[Anti-inflammatory and antipyretic activity of aqua-dihydroxybenzoate copper complexes].

Using screening methods, the anti-inflammatory and antipyretic activities of mononuclear otahedral complexes [composition:Cu(2,YDHB)2.H2O;dihydroxybenzoate ion - DHB; Y(n)-4(8).5(4) and 6(8)] and the corresponding carboxylic acids were studied.

[Local anesthetics. 99. Synthesis and local anesthetic actions of alkoxyphenylcarbamates].

Within the framework of studying the influence of alterations of the connecting chain in the group of local anaesthetics a series of 24 compounds of 1-propoxymethyl-2-(1-pyrrolidinyl), 2-(1-piperidino)-, and 2-(1-perhydroazepinyl)-ethyl esters of o- and m-alkoxyphenylcarbamic acid were prepared. Studied compounds show a high index of relative local anaesthetic activity as compared to the standards cocaine and procaine, at a relatively low acute toxicity.

Acid-base balance disturbance following toxic doses of local anesthetics.

The effect of equitoxic doses of three carbamate local anesthetics (pentacaine, carbisocaine and heptacaine), and a derivative of lidocaine (trimecaine) on the acid-base balance of blood was studied in conscious rabbits. In addition, changes in arterial blood pH induced by local anesthetics in relation to lipophilicity of the respective drugs were evaluated. All the drugs administered at the dose of half of LD50 induced a significant decrease in the arterial blood pH as well as in the plasma bicarbonate level and in the blood base excess.

Cloning and nucleotide sequence of a chromosomally encoded tetracycline resistance determinant, tetA(M), from a pathogenic, methicillin-resistant strain of Staphylococcus aureus.

This report describes the cloning and sequencing of a chromosomally encoded tetracycline resistance determinant from a clinical isolate of methicillin-resistant Staphylococcus aureus. On the basis of the sequence, the gene is in the tet(M) class, and it was shown that the S. aureus tetA(M) gene is induced at the level of transcription.

Pharmacological evaluation of new alkylesters of 4-[(2-hydroxy-3-alkylamino)propoxy]phenylcarbamic acids with beta-adrenolytic properties.

The basic relationship between the chemical structure and pharmacological activities of new alkylesters of 4-[(2-hydroxy-3-alkylamino)propoxy]phenylcarbamic acids were evaluated. The efficiency of compounds was compared with those of metipranolol and practolol, respectively. The majority of 4-substituted derivatives of aryloxypropanolamines have shown antiisoprenaline (beta-adrenolytic) and local anesthetic (membrane stabilizing) activities.

The effect of carbamate local anesthetics on artificial lipid membrane.

The influence of phenylcarbamic acid basic esters with local anesthetic activity on the phase transition temperature (Tc) of a model dipalmitoylphosphatidylcholine (DPPC) membrane from gel to liquid crystalline state was studied. It was found that (Tc) in the presence of carbamate anesthetics decreases. The decrease of Tc (delta Tc) correlated well with the biological activity of the compounds studied.

An Escherichia coli cis-acting antiterminator sequence: the dnaG nut site.

The Escherichia coli rpsU-dnaG-rpoD operon contains an internal transcription terminator T1 located in the intergenic region between the rpsU and dnaG genes (Smiley et al. 1982). By cloning T1 as a small 127 bp fragment into the terminator probe plasmid pDR720 between the trp operator promoter and the assayable galK gene, it was shown that T1 acts as a strong transcription terminator, comparable in strength to the 3' operon terminator T2.

[Local anesthetics. 90. Asymmetric dibasic alkyl esters of alkoxyphenylcarbamic acids].

The synthesis of 24 compounds belonging to the group of dibasic substituted alkoxy phenyl carbamic acids is described. The compounds are characterized by relatively low acute toxicity and good local anaesthetic as well as antiarrhythmic activity.

Possible new genes as revealed by molecular analysis of a 5-kb Escherichia coli chromosomal region 5' to the rpsU-dnaG-rpoD macromolecular-synthesis operon.

The complete nucleotide sequence of 5-kb DNA fragment immediately 5' to the rpsU-dnaG-rpoD macromolecular-synthesis operon in Escherichia coli has been determined. It encodes for six open reading frames. Transcriptional and translational analysis have shown that three of them (orfx, orfz1 and orfz2) are expressed in exponentially growing E.

Pharmacological properties of a new local anaesthetic, carbisocaine.

During the systematic analysis of the relationship between chemical structure and local anaesthetic activity of basic esters of alkoxyphenylcarbamic acids, the diethylamino-isopropylester of 2-heptyloxyphenylcarbamic acid (carbisocaine) was synthesised and later extensively studied. This drug has been shown to be as active as procaine in skin anaesthesia in molar concentrations 416 times lower, and in corneal anaesthesia the drug parallels the standard agent cocaine in molar concentrations 251 times lower. The high relative local anaesthetic potency of carbisocaine and its low subcutaneous toxicity prompted wider pharmacological investigations in which the effects of carbisocaine on the central nervous system and the circulation were studied.

Diversity of circumsporozoite antigen genes from two strains of the malarial parasite Plasmodium knowlesi.

The complete nucleotide sequence of the coding region of the circumsporozoite antigen gene (CS gene) of the Nuri strain of the malarial parasite Plasmodium knowlesi is presented. The gene from the Nuri strain exhibits a novel form of sequence diversity when compared to the CS gene from the H strain. Instead of the 12 tandem repeating 36-base pair units of the H strain, the Nuri strain contains 16 tandem repeating 27-base pair units of a different nucleotide sequence that encodes a different repeating peptide.

Comparison of left-end DNA sequences of bacteriophages Mu and D108.

The nucleotide sequences of the left ends of bacteriophage Mu DNA and that of its close relative D108 have been determined. The first 100 bp of phages Mu and D108 are substantially the same except for an octanucleotide change from bp 53 to 61 and other small interspersed base-pair changes from bp 61 to 200. The first five host nucleotides preceding the host-phage junction are generally, but not always, G + C-rich and these five nucleotides display no obvious consensus sequence.

Structure and organization of genes for sporozoite surface antigens.

The major surface antigen (circumsporozoite-protein) of the sporozoite stage of Plasmodium knowlesi has been cloned and characterized. The gene is notable for the presence of a 36 base pair unit repeated in tandem 12 times. These repeats may function at the DNA level in regulating gene expression and at the protein level in providing multiple copies of a single epitope (repitope) as part of a protein designed to evade and decoy the immune system.

Structure of the plasmodium knowlesi gene coding for the circumsporozoite protein.

The gene that codes for the surface antigen of Plasmodium knowlesi sporozoites (CS protein) is unsplit and present in the genome in only one copy. The CS protein, as deduced from DNA sequence analysis of the structural gene, has an unusual structure with the central 40% of the polypeptide chain present as 12 tandemly repeated amino acid peptide units flanked by regions of highly charged amino acids. The protein has an amino-terminal hydrophobic amino acid signal sequence and a hydrophobic carboxy-terminal anchor sequence.

Identification and chemical synthesis of a tandemly repeated immunogenic region of Plasmodium knowlesi circumsporozoite protein.

Complementary DNA clones that code for the immunogenic region of the Plasmodium knowlesi circumsporozoite protein were shown to contain a tandemly repeating 36-base pair unit. A synthetic dodecapeptide corresponding to the predicted reading frame of the repeating nucleotide unit behaved, in an immunoradiometric assay, identically with the native P. knowlesi circumsporozoite protein.

Sequences of the Escherichia coli dnaG primase gene and regulation of its expression.

The nucleotide sequence of a cloned section of the Escherichia coli chromosome containing the dnaG primase gene [Lupski, J., Smiley, B., Blattner, F.