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Biomedical subjects

I Winkler

Publications and source records attributed to I Winkler.

At least 73 records · Page 4Linked to original sources
PubMed1992

Antibacterial activity in vitro of cefpirome against clinical isolates causing sexually transmitted diseases.

The in-vitro activity of cefpirome was compared with other antibiotics against organisms causing sexually transmitted diseases (STD). The excellent activity of cefpirome against Neisseria gonorrhoeae (MIC90 1.0 mg/L), Haemophilus ducreyi (MIC90 0.5 mg/L), and Gardnerella vaginalis (MIC90 1.0 mg/L) suggests that this agent might be useful in the empirical treatment of a variety of venereal diseases.

Cephalosporins↗
PubMed1992

Can echoic memory store two traces simultaneously? A study of event-related brain potentials.

The mismatch negativity, a component of the event-related brain potential elicited by infrequent deviants in sequences of auditory stimuli, is presumably generated by an automatic mismatch process in a mechanism that compares the current stimulus to the trace of the previous one. The present study addressed the possible simultaneous existence of two such traces. Two equiprobable (45% each) frequent stimuli ("standards"), one of 600 Hz and the other of 700 Hz, were presented together with an infrequent (10%), "deviant" stimulus which was of different frequency in different blocks. These deviants elicited a mismatch negativity, though a smaller one than that obtained in corresponding blocks with only one standard stimulus. Two aspects of the present results from the blocks with two standard stimuli implicate two parallel stimulus traces in these blocks: 1) deviants elicited a mismatch negativity (MMN) of approximately the same amplitude when preceded by sequences of four identical standards as when preceded by sequences of four stimuli containing both standards; 2) in contrast to the one-standard condition, the magnitude of stimulus deviance did not affect the MMN component elicited by the different deviants.

Adult↗
PubMed1990

Antiviral activity and pharmacokinetics of HOE 602, an acyclic nucleoside, in animal models.

The acyclic nucleoside derivative HOE 602 (2-amino-9-[1,3-bis(isopropoxy)-2-propoxymethyl]purine) was evaluated for its antiviral activity in cell culture and for its therapeutic efficacy in mice infected with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) or with murine cytomegalovirus (MCMV). HOE 602 was inactive in vitro against a variety of DNA- and RNA-viruses. However it prevented symptoms and mortality in mice systemically infected with HSV-1, HSV-2 or MCMV when administered intraperitoneally or orally at a dosage of 100 mumol/kg twice per day. Pharmacokinetic studies in mice and macaques revealed that HOE 602 was converted via three metabolic steps to ganciclovir, which seemed to be the antivirally active compound. The bioavailability of ganciclovir after oral administration of HOE 602 or ganciclovir was similar in mice, while in rhesus monkeys much higher serum levels of ganciclovir were reached with HOE 602. After intraperitoneal or intravenous administration higher drug levels were obtained with ganciclovir. The excellent therapeutic efficacy in animal models, the high enteral absorption in monkeys, and the favourable physical properties will hopefully lead to an orally active drug against cytomegalovirus and severe herpes infections in man.

Acyclovir↗
PubMed1990

Steady-state responses from the cat auditory cortex.

Responses to 350 ms trains of clicks with 10-100 Hz repetition rate were recorded from the auditory cortices of six cats. Click trains of 30-50 and 90-100 Hz elicited a clear steady-state response (SSR) in awake state. SSRs were small or absent below 30 Hz and in 60-70 Hz stimulus range. In slow wave sleep the optimal rate to elicit SSR shifted towards lower frequencies. 90 Hz SSR was largest in paradoxical sleep. SSRs were strongly suppressed by barbiturate anesthesia. The amplitude of the SSR from the medial geniculate body (MGB) in two cats gradually decreased from 20 to 100 Hz and was more resilient to barbiturate anesthesia than the cortical SSRs. Only low amplitude or no SSRs could be recorded from vertex, visual and association cortices and from the hippocampus in control recordings. The results suggest different generation mechanisms for SSRs recorded from cat auditory cortex and MGB. Human auditory SSRs resemble cat auditory cortical SSRs more than those recorded from cat MGB. The results imply that auditory SSRs in humans are generated in the cortex.

Acoustic Stimulation↗
PubMed1990

Polyclonal antibodies to mannan from yeast also recognize the carbohydrate structure of gp120 of the AIDS virus: an approach to raise neutralizing antibodies to HIV-1 infection in vitro.

This study initiates a new method of developing an antigen which might be useful in the prevention of HIV-1 infection. Using a mannan preparation from Saccharomyces cerevisiae neutralizing antiserum was raised in rabbits which prevents HIV-1 infection in vitro up to a titre of 1:128. The corresponding antibody preparation neutralized the in vitro infectivity down to a concentration of 5 micrograms/ml. Analytical studies suggest that the antibodies are directed against the mannose residues of the HIV-1 glycoprotein (gp) 120 and its precursor gp 160.

Acquired Immunodeficiency Syndrome↗
PubMed1990

The effect of small variation of the frequent auditory stimulus on the event-related brain potential to the infrequent stimulus.

We investigated whether the mismatch process between a rare stimulus and the trace of the frequent stimulus, which generates the mismatch-negativity component of the event-related potential, can tolerate a small variation in the intensity of the frequent stimulus. Series of short tone pips were presented to 10 subjects while they were reading a book and ignoring the auditory stimuli. The intensity (mean 80dB) of the frequent stimulus (600 Hz) varied within a range that was different in different blocks. The probability of the infrequent stimuli which were, in different blocks, either intensity deviants (600 Hz/70dB) or frequency deviants (650 Hz/80dB) was 10%. Both deviant stimuli elicited mismatch negativity even when the intensity of the frequent stimulus varied, although the amplitude of this component decreased with the increasing variability of the frequent stimulus. These results show that the generator process of mismatch negativity tolerates some variation in the repetitive stimulus, thus indicating that this process is also activated in ecologically more valid conditions. This is crucial to the interpretation of the generator process of mismatch negativity as a biologically vital warning mechanism.

Adult↗
PubMed1988

Intracortical auditory evoked potentials during classical aversive conditioning in cats.

Auditory evoked potentials (EPs) were recorded simultaneously from six different depths of the auditory cortex of freely moving cats. In a classical aversive learning paradigm the change of the pitch of regularly given acoustic stimuli served as warning signal. With conditioning the amplitude of a middle latency negative component increased and its latency decreased. Based on laminar analysis of EP profiles we propose that the observed EP changes were generated within the upper cortical layers and reflected a temporary aurousal reaction induced by the signal as a result of discrimination learning. For the description of this effect the term "learned aversive arousal" is suggested.

Animals↗
PubMed1988

Inhibition of HIV and virus replication by polysulphated polyxylan: HOE/BAY 946, a new antiviral compound.

Xylanpoly-(hydrogen sulphate) disodium salt with a molecular weight of about 6000 daltons (HOE/BAY 946) completely inhibited syncytium formation induced by the infection of T lymphocytes with HIV as well as viral replication at concentrations above 25 micrograms/ml. This dose was found to be inhibitory for several strains of HIV-1 and HIV-2. Low molecular weight fractions of the compound were less active against HIV, and high molecular derivatives were as active as HOE/BAY 946. A direct influence of the drug on the infectivity of the virus could not be demonstrated. The drug inhibited the reverse transcriptase of HIV. Treatment of permanently HIV-infected U937 cells resulted in a drastic reduction of virus particles released into the supernatant and points to an additional mode of action. A therapeutic effect of HOE/BAY 946 against retroviruses in vivo could be demonstrated in Friend leukaemia virus-infected mice. A clinical pilot study with the compound was started recently in Germany with AIDS patients who did not tolerate or refused to take zidovudine and with asymptomatic virus carriers.

Animals↗
PubMed1988

The D-mannose-specific lectin from Gerardia savaglia blocks binding of human immunodeficiency virus type I to H9 cells and human lymphocytes in vitro.

The new D-mannose-specific lectin from Gerardia savaglia is shown to prevent infection of H9 cells with human immunodeficiency virus type 1 (HIV-1; strain HTLV-IIIB). At a concentration of 0.2 microM, complete protection was achieved. Even at a 50-fold higher concentration, this lectin is not toxic for the cells. Moreover, the lectin inhibits syncytium formation in the HTLV-IIIB/H9-Jurkat cell system to 100% at 0.2 microM. This effect was abolished by coaddition of D-mannose at a stoichiometric ratio of lectin to sugar of 1:500. The lectin-caused inhibition of syncytia formation was observed also in the HIV-1/human lymphocyte system. Perhaps more importantly, it is shown that the lectin reacts with the oligosaccharide side chains of the HIV-1 gp120 env molecule, which very likely can be classified to the high-mannose oligosaccharides. These data provide the basis for a rational screening for compounds interfering with gp120-CD4 interactions.

Antigen-Antibody Complex↗
PubMed1988

New prodrugs of acyclic nucleosides with antiviral activity.

More than 130 acyclic purine and pyrimidine nucleoside derivatives have been synthesized. Structure-activity relationships among a selected group of 6- and 9-substituted guanine derivatives will be discussed. By introduction of secondary aliphatic (e.g. isopropyl or secondary butyl) ether groups into acyclic nucleosides such as aciclovir and ganciclovir new lipophilic prodrugs with modified physical and improved pharmacokinetic properties have been obtained. Several compounds with isopropylether groups in the side-chain and/or in the 6-position (among these the 6-deoxy derivative Hoe 602) of the purine moiety displayed excellent antiviral activity when tested in vivo against herpes simplex virus type 1 infection in mice.

Acyclovir↗
PubMed1986

Chemotherapeutic effects of ofloxacin (HOE 280) and other quinolone-carboxylic derivates in the treatment of experimental lung infections due to Klebsiella pneumoniae DT-S in mice.

The chemotherapeutic activity of ofloxacin (HOE 280), a new pyridone-carboxylic acid derivative, was compared with that of other drugs in the same group, including norfloxacin, ciprofloxacin, enoxacin and in some cases pipemidic acid and nalidixic acid. The test model used was experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. In the treatment of pneumonic mice, ofloxacin was 4 to 18 times more effective than norfloxacin and enoxacin and in most cases slightly more effective than ciprofloxacin. Pipemidic acid and nalidixic acid showed only low activity or proved to be inactive. In studies on the bactericidal activity of the compounds in vivo, ofloxacin produced a more pronounced effect than ciprofloxacin. With norfloxacin and enoxacin, a bactericidal effect in the infected tissue of the animals was only observed during the first hours after treatment.

Animals↗
PubMed1986

Absence of renal 25-hydroxycholecalciferol-1-hydroxylase activity in a pig strain with vitamin D-dependent rickets.

Cholecalciferol-1-hydroxylase activities were estimated in renal cortex homogenates and mitochondrial preparations from three groups of 6- to 12-week-old pigs. Five animals suffering from an inherited form of vitamin D-deficiency rickets showed symptoms of florid rickets when used for this study. Six pigs were normocalcemic heterozygous litter mates of the rachitic strain and three pigs were normal controls (German land-race and wild pigs). The renal cortex homogenates and mitochondrial preparations were incubated for 5-30 min at 37 degrees C with 25-(26-27-methyl-3H) OHD3 as substrate. 1,25(OH)2D3 was subsequently identified in normal phase (Zorbax-Sil) and reversed phase (Zorbax-ODS) HPLC eluates. 1-hydroxylase activities were demonstrated in both normal controls and heterozygote offspring and were ten times above minimum detectability of the assay. The km was 255 +/- 74 (SD) and 278 +/- 85 nmol X 1(-1) in controls and heterozygote offspring, respectively. The Vmax in the two groups was between 0.11 and 0.794 and decreased with age of the animals. Km and Vmax did not differ between the two groups. In homozygous, hypocalcemic rachitic animals no 1-hydroxylase activity was detectable in either homogenates or mitochondrial preparations. Addition of kidney homogenate from a rachitic animal to a homogenate from a normal pig did not specifically depress 1-hydroxylase activity in the mixture. Treatment of rachitic pigs with 1.0 microgram/day of 1,25(OH)2D3 for 4 weeks also had no effect on 1-hydroxylase activity. It is concluded that the rachitic pigs suffer from an inborn error of renal 1,25(OH)2D3 production.(ABSTRACT TRUNCATED AT 250 WORDS)

24,25-Dihydroxyvitamin D 3↗
PubMed1986

Comparative effects of cefpirome (HR 810) and other cephalosporins on experimentally induced pneumonia in mice.

The chemotherapeutic efficacy of cefpirome (HR 810), a new polar aminothiazolylcephalosporin and that of ceftazidime, cefotaxime, cefoperazone, latamoxef and cefodizime were examined against experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. When compared in terms of MIC values against the infecting organism and the pharmacokinetic pattern, cefpirome showed equal activity and a similar pharmacokinetic behavior to ceftazidime and cefotaxime in mice. Trials to assess the bactericidal activity in vivo, however, showed that cefpirome displayed a more marked bactericidal effect in pneumonic mice than the other cephalosporins tested. Only cefodizime, a cephalosporin with extremely high and prolonged blood and tissue levels in experimental animals exerted chemotherapeutic effects similar to cefpirome. After cefpirome or cefodizime medication (50 mg/kg), the viable counts in the lungs of experimental animals fell steadily to 1/10,000 of the pretreatment level and, in contrast to the reference compounds, no regrowth of the challenge organisms could be observed with both drugs. Moreover, with ED50s ranging from 1.1 to 59.1 mg/kg in treatment studies, cefpirome as well as cefodizime were two to ten times more effective than ceftazidime and cefotaxime, whereas cefoperazone and latamoxef were considerably less effective.

Animals↗
PubMed1986

Evoked potential components in the layers of the auditory cortex of the cat.

The intracortical distribution of evoked potentials was studied by seven-contact multielectrodes implanted into the primary auditory cortex of freely moving cats. The aim of the study was to compare the intracortical profiles of the responses evoked by click stimuli and by electrical stimulation of the medial geniculate body in different states of alertness and in Nembutal anesthesia. Only the early surface positive component showed phase reversal in the depth of the cortex. The middle latency components which were faithful indicators of vigilance appeared without phase reversal. Nembutal wiped out these components. A negative component of about 50 ms latency appeared in the attentive animal which had the highest amplitude close to the surface and decreased toward the depth indicating that it was generated in the most superficial layers of the cortex. The stimulation of the last nucleus of the specific auditory pathway elicited evoked potential patterns including also the middle latency components, which were closely similar to those induced by click stimuli.

Animals↗
PubMed1986

Comparison of evoked potential changes during classical and instrumental conditioning in cats.

The waveform changes of cortical evoked potentials to click conditioned stimuli were analyzed by a complex computer program developed for sorting nonhomogeneous series of evoked potentials. The changes of evoked responses manifested themselves mainly in the middlelatency waves, while the first components showed only a slight fluctuation during the whole conditioning. A late negative component of 40-50 ms latency was clearly related to the attentive state of the animal. The evoked potentials with increased negative component appeared in different sequences in 'the two conditioning paradigms and in the different phases of the learning process.

Animals↗