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Biomedical subjects

W Peters

Publications and source records attributed to W Peters.

At least 181 records · Page 10Linked to original sources
PubMed1989

The chemotherapy of rodent malaria. XLIV. Studies on the mode of action of CM 6606, an indolo (3,2-c) quinoline N-oxide.

CM 6606 differs in its mode of action from chloroquine but studies on its activity against parasites resistant to other antimalarials suggest that it may have some features in common with aminoalcohols. Similarities in drug-induced pigment changes are especially striking. Only halofantrine shows a reduced activity, however, against parasites that are highly resistant to CM 6606, while such parasites are slightly hypersensitive to sulfadoxine and clindamycin. Evidence suggesting that CM 6606 may function through an active metabolite, possibly CM 6609 in which the N-oxide is reduced, is discussed.

Animals↗
PubMed1989

Changing pattern of antimalarial drug resistance.

With the current increase of international travel and increasing drug resistance, United Kingdom residents stand a high risk of contracting malaria when they visit endemic countries. The development of anti-malarial agents from old traditional plant remedies to modern synthetic drugs is briefly reviewed. Resistance to the latter has spread rapidly since the 1950s, culminating in the widespread distribution of multiple drug-resistant strains of Plasmodium falciparum in most endemic areas. There is a danger that such parasites may rapidly develop resistance even to new compounds such as mefloquine, halofantrine or artemisinin unless the use of such compounds is carefully controlled. The few developments, including new drugs and ways of reversing existing resistance, are also briefly reviewed in this paper. Emphasis is laid on the need to revert to classical methods of protection against malaria vectors since it is unlikely that a protective vaccine will become available in the near future.

Animals↗
PubMed1988

Arteether, a new antimalarial drug: synthesis and antimalarial properties.

Arteether (6) has been prepared from dihydroquinghaosu (3) by etherification with ethanol in the presence of Lewis acid and separated from its chromatographically slower moving alpha-dihydroqinghaosu ethyl ether (7). The absolute stereochemistry at C-12 has been determined by 1H NMR data (J11,12, NOESY). Ethyl ethers 6 and 7 showed potent in vitro inhibition of Plasmodium falciparum, and both compounds were highly potent antimalarials in mice infected with a drug-sensitive strain of Plasmodium berghei. Crystalline arteether (6) and its oily epimer 7 were 2-3 times more potent schizontocides than quinghaosu (1), but deoxy compounds 8, 9, and 11 were 100-300 times less potent in vitro than their corresponding peroxy precursors. Pharmacological studies have shown arteether(6) to have antimalarial activity in animals comparable to artesunate (2) and artemether (4), both of which are fast-acting blood schizontocides in humans. Arteether (6) has now been chosen for a clinical evaluation in high-risk malaria patients.

Animals↗
PubMed1988

Characterization of leukotriene B3: comparison of its biological activities with leukotriene B4 and leukotriene B5 in complement receptor enhancement, lysozyme release and chemotaxis of human neutrophils.

1. Leukotriene (LT) B3 was prepared by total chemical synthesis and its identity was confirmed by nuclear magnetic resonance analysis and proton homonuclear plot of connectivities and chemical shift assignments. The effects of LTB3 on complement receptor enhancement, chemotaxis and lysozyme release in human neutrophils (PMN) were compared with those of LTB4 and LTB5. 2. LTB3 and LTB4 elicited a virtually identical dose- and time-dependent enhancement in complement receptors type 1 (CR1) and type 3 (CR3) and release of lysozyme. LTB5 was approximately 100 times less potent than LTB4 in enhancing CR1 and CR3, whereas it was 10,000 times less potent than LTB4 in releasing lysozyme from human PMN. 3. LTB3 and LTB5 were respectively 5- and 100-fold less potent than LTB4 in eliciting chemotaxis. 4. These findings indicate that the pro-inflammatory potential of LTB3 and LTB4 are similar, whereas LTB5 is substantially less potent as an inflammatory mediator. 5. The finding that LTB5 is a weak and partial agonist relative to LTB3 and LTB4 could be due to the rigidity of the C-17-C-18 double bond in LTB5. This may interfere with the active site specificity of LTB5 to a substantial extent. 6. One approach to the development of antagonists to the LTB4 receptor may be to establish a rigid structure in the C-17-C-18 region of the LTB4 molecule.

Chemical Phenomena↗
PubMed1988

The chemotherapy of rodent malaria.XLIII. Indolo (3,2-c) quinoline-N-oxides.

A number of novel indolo (3,2-c) quinoline-N-oxides possess antimalarial activity. One of the series, compound CM 6606, has a superior blood schizontocidal action against drug-sensitive Plasmodium berghei in the mouse to that of chloroquine, although it is not fully active against strains highly resistant to chloroquine or mefloquine. It also shows some tissue schizontocidal (causal prophylactic) and gametocytocidal action in mice infected with P. yoelii nigeriensis. The structure activity of this chemical series and the possibility that CM 6606 functions through an active metabolite are discussed.

Animals↗
PubMed1988

Clinical experience with the rate responsive pacemaker Sensolog 703.

Pacemaker therapy with rate responsive systems becomes increasingly more important. Numerous clinical and experimental trials have been conducted thus far to investigate different sensors of metabolic demands of the body, functioning independently of an atrial electrogram. To transform mechanical energy into electrical energy, activity-triggered systems utilize a piezo-quartz as their sensor. Thirty five patients suffering from pathological bradyarrhythmias and therefore from an inadequate increase of the heart rate during exercise were supplied with a Sensolog 703. Clinical follow-up was first performed with the help of treadmill ergometry, later on by walking on flat ground and climbing steps. The settings due to the first test caused inadequately high stimulation rates. A 24-h-Holter-ECG was necessary to control the programming and the rate profile in the patient's daily life. Using only the histogram and the rateread function, all rate adaptive parameters of the Sensolog 703 could be set by walking on flat ground and climbing steps. We defined a frequency of 75-85 min-1 to be appropriate during walking, respectively "low work." Individual programming ranged from 2-5/8-15/high-low/very fast-medium/fast-medium (slope, threshold, gain, reaction and recovery time). Reprogramming based on 24-h-Holter ECG was only necessary if the pacemaker was formerly adjusted with the help of treadmill ergometry. Besides, we observed an increase of the stimulation rate due to vibrations not related to exercise, e.g., by driving in a car.

Aged↗
PubMed1988

[Pneumopyopericardium--a rare complication following surgical correction of an "upside-down stomach"].

The follow-up period after surgery of an upside-down stomach in a 53-year-old patient was complicated by a pneumopyopericardium due to Candida albicans and Enterococcus. Therapy was performed by pericardial drainage. Local instillations of Mezlocillin (100 mg/l) and Amphotericin B (1 mg/l, Candida-MIC = 0.1 mg/l), over a period of 10 days and followed by a systemic antimycosis with 5-Flucytosin (0.14 g/d/kg over 5 days) and Amphotericin B (0.3 mg/d/kg over 11 days) led to recovery. Six months after discharge from the hospital, echocardiography revealed only a thickened pericardium without hemodynamic disorders.

Candidiasis↗
PubMed1988

[Uni- and bipolar 2-chamber stimulation with a DDD system of programmable polarity].

In order to compare bi- (b) and unipolar (u) stimulation, sensing and electrical interference, twelve patients were followed over a period of ten months. The implanted device was the CPI Delta 925, programmable to the bi- and unipolar mode in the atrium (a) as well as in the ventricle (v). A CPI-4266 screw-in lead positioned in the atrium and a CPI-4260 hook lead placed in the ventricle were connected to the pacemaker. Intraoperatively determined were: (1) the threshold at pulse durations of 0.1 ms, of 0.5 ms and of 1.0 ms, (2) the P/QRS-amplitude, (3) the slew-rate and (4) the resistance in both the bi- and unipolar mode. Having programmed the atrial sensitivity to 0.25 mV or to 0.75 mV and the ventricular sensitivity to 0.5 mV or to 1.5 mV, we postoperatively examined and compared in the two modes of polarity the threshold (2.2 V and 5 V), the P/QRS-amplitude and finally the electrical interference triggered with the help of chest wall stimulation. All measurements were performed one day, four weeks and four months after implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Differences in binding of lectin-gold conjugates by Trypanosoma cruzi and Blastocrithidia triatomae (Trypanosomatidae) in the intestine of Triatoma infestans (Reduviidae).

Two species of trypanosomatid flagellates, Trypanosoma cruzi and Blastocrithidia triatomae which develop in the intestine of Triatoma infestans, were incubated with lectin-gold conjugates to demonstrate sugar components of the cell surface with the electron microscope. T. cruzi, strain "Chile 5" (zymodeme 1), bound SBA-gold, revealing N-acetyl-galactosamine and/or galactose residues. WGA-BSA-gold, specific for N-acetylglucosamine, did not bind to the surface of this flagellate. On the other hand, N-acetyl-glucosamine bound WGA-BSA-gold on the cell membrane of epimastigotes and cysts of B. triatomae, whereas SBA-gold was not bound by flagellates which were attached to the midgut epithelium and the rectum cuticle. Among other criteria, these differences in lectin binding may facilitate the discrimination of the two parasite species in the vector of Chagas' disease.

Animals↗
PubMed1987

Lectin binding studies on adult filariae, intrauterine developing stages and microfilariae of Brugia malayi and Litomosoides carinii.

Sections of macrofilariae of Brugia malayi and Litomosoides carinii revealed binding of the gold-labelled lectins WGA, DBA and PNA. Specificity of binding was controlled by competitive inhibition with the respective sugars. N-acetyl-glucosamine, N-acetylgalactosamine and galactose residues seem to be present in the respective tissues. The lectins were bound preferentially to parts of the reproductive organs and to the fluid contents of their lumina. The results of the chitosan test and binding experiments with WGA-gold conjugate suggest the presence of chitin in the sheath of oocytes or zygotes. Binding of WGA could not be inhibited with 0.5 M N-acetylglucosamine, but only with 10 mM triacetyl chitotriose. In older stages, binding of WGA to the sheath could be inhibited by 0.5 M N-acetylglucosamine. In mature microfilariae, the outer surface of the sheath did not show affinity for WGA, but small amounts were bound to the inner surface. Therefore, the sheath of later developmental stages and microfilariae does not contain chitin but only N-acetylglucosamine residues. The degradation of the chitin content might enable the elongation and flexibility of the sheath of microfilariae.

Animals↗
PubMed1987

Formation by the uterus of a peripheral layer of the sheath in microfilariae of Litomosoides carinii and Brugia malayi.

The eggshells of young developmental stages in the uterus are rather thin and homogenous. In the brezel stage of Brugia malayi they are 35 nm thick and 20 nm in Litomosoides carinii. In young developmental stages up to brezel stages the eggshells bind the lectins WGA, DBA and PNA labelled with colloidal gold. This shows that GlcNAc, GalNAc and Gal residues are present at the surface of the sheath. In intrauterine microfilariae of B. malayi the original sheath is reduced to a thickness of 7 nm. It is reinforced by secretions from a specialized area of the epithelium of the uterus which do not appear as a homogeneous layer but look like a string of pearls. This layer may be called the "uterine layer". It has a thickness of 40-80 nm. In the microfilaria of L. carinii, the thickness of the original sheath is reduced to 2-3 nm and the uterine layer has a thickness of 7 nm. The uterine layer does not react with any of the lectins, which shows that the surface lacks N-acetylglucosamine, N-acetylgalactosamine and galactose residues. The uterine layer appears to be an ancestral (plesiomorphic) feature which is present in free-living nematodes and the highly specialized bloodforms of filariae. The uterine layer seems to protect and disguise the original sheath against the immune reactions of the host.

Animals↗
PubMed1987

Localization of glycoconjugates at the tegument of the tapeworms Hymenolepis nana and H. microstoma with gold labelled lectins.

Gold labelled lectins were used for electron microscopic localization of carbohydrate components of the tegument surface of two tapeworm species, Hymenolepis nana and H. microstoma. WGA, succinylated WGA, SBA, APA, PNA and, to a lesser extent, Con A were preferentially bound to the spines of the microtrichs. UEA-I and DBA were not adsorbed. The results indicate that the surface coat of both species has exposed N-acetylglucosamine, galactose and perhaps glucose and/or mannose residues. The location of lectin-binding glycoconjugates within the tegument and parenchyma was found using the light microscope on sections of material embedded in Lowikryl K4M after lectin-gold labelling and silver enhancement of the gold grains. The tegument selectively adsorbs WGA and SBA and strongly; adsorbtion of PNA and Con A is less intense. Strong adsorbtion of DBA and PNA was confined to the basal lamina. The parenchyma adsorbed Con A, PNA and DBA, but little WGA and SBA. The results indicate that many glycoconjugates are present in the tegument. They have similar terminal sugar residues to those of the surface coat. The significance of these carbohydrates for host-parasite interactions is discussed.

Animals↗
PubMed1987

The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice.

Artemisinin is a novel antimalarial drug isolated in China from the wormwood plant Artemisia annua L. Studies with rodent malaria were carried out to detect antagonism and synergism with a variety of antimalarial drugs. Isobolograms of drug interaction were plotted at the ED90 level. With a normally susceptible strain of Plasmodium berghei, marked potentiative synergism was found with mefloquine, tetracycline and spiramycin. There was some synergism also with primaquine. Combinations of artemisinin with dapsone, sulfadiazine, sulfadoxine, pyrimethamine, pyrimethamine/sulfadoxine and cycloguanil showed antagonism. A high degree of potentiation was shown between artemisinin and primaquine with a primaquine-resistant strain, whilst the combination with mefloquine showed enhanced potentiation with a mefloquine-resistant strain. Combinations of artemisinin with mefloquine, primaquine, tetracycline or clindamycin showed marked potentiation with an artemisinin-resistant strain. The mechanisms underlying the drug interactions observed are discussed.

Animals↗
PubMed1987

The chemotherapy of rodent malaria. XLII. Halofantrine and halofantrine resistance.

As a blood schizontocide, halofantrine is about three times as active against a drug-sensitive line of Plasmodium berghei (N strain) as chloroquine, but it lacks any causal prophylactic effect. This activity is retained against parasites highly resistant to primaquine, cycloguanil, pyrimethamine, sulphaphenazole and menoctone. A marked resistance to halofantrine is shown by parasites resistant to mefloquine, quinine, chloroquine and amodiaquine, although the moderately chloroquine-resistant 'NS line' is sensitive. The artemisinin-resistant line shows a moderately reduced response. A high level of resistance was rapidly developed in the 'NS line' to halofantrine (NS/HAL line) but not in the N strain (N/HAL). The NS/HAL line was cross-resistant to mefloquine, amodiaquine and, to a lesser degree, artemisinin, but remained sensitive to chloroquine and quinine. The implications to a lesser degree, artemisinin, but remained sensitive to chloroquine and quinine. The implications of these observations for the possible future clinical deployment of halofantrine are discussed, and emphasis is laid on the need to find means of impeding the resistance to it of Plasmodium falciparum.

Animals↗