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Biomedical subjects

R Pauwels

Publications and source records attributed to R Pauwels.

At least 181 records · Page 10Linked to original sources
PubMed1987

Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitro.

The combined antiviral effects of various 2',3'-dideoxynucleosides and ribavirin on the replication of human immunodeficiency virus type 1 in MT-4 cells have been examined. Ribavirin antagonized the antiviral activity of the pyrimidine 2',3'-dideoxynucleosides (3'-azido-2',3'-dideoxythymidine, 2',3'-dideoxythymidin-2'-ene, 2',3'-dideoxycytidine, and 2',3'-dideoxycytidin-2'-ene), but enhanced the antiviral activity of the purine 2',3'-dideoxynucleosides (2',3'-dideoxyadenosine and 2',3'-dideoxyguanosine). Combinations of the 2',3'-dideoxynucleosides with each other were also examined. These combinations resulted in an additive to subsynergistic effect.

Cytopathogenic Effect, Viral↗
PubMed1987

Effect of inhaled substance P and neurokinin A on the airways of normal and asthmatic subjects.

The neuropeptides substance P and neurokinin A are present in sensory airway nerves. Their effect on airway calibre was compared in six healthy non-smoking subjects and six asthmatic subjects. On separate days increasing concentrations (from 10(-9) to 10(-6) mol/ml) of each neuropeptide were administered by nebuliser and the airway response measured as change in specific airway conductance (sGaw). Substance P and neurokinin A caused no change in sGaw in the healthy subjects. Inhalation of substance P up to the highest concentration of 10(-6) mol/ml caused no change in sGaw in the asthmatic subjects. Neurokinin A, however, caused bronchoconstriction with a mean fall in sGaw of 48% (SEM 12%) after 5 x 10(-7) mol/ml. The onset of bronchoconstriction was rapid, but sGaw had returned to baseline values within one hour in all but one patient.

Administration, Inhalation↗
PubMed1987

The effects of theophylline on airway inflammation.

One of the important modes of action of theophylline in asthma and chronic obstructive airway disease may be the inhibition of airway inflammation. This hypothesis is based on in vitro and in vivo studies demonstrating that theophylline at therapeutic concentrations has an inhibitory activity on airway inflammation induced by allergic and nonallergic stimuli. Indirect evidence suggests that airway inflammation is an important determinant in the long-term outcome of chronic obstructive airway disease. The effect of theophylline on the long-term evolution of chronic obstructive lung disease remains to be proven.

Adult↗
PubMed1987

Intravenous versus nebulized terbutaline in patients with acute severe asthma; a double-blind randomized study.

Twenty-three patients with acute severe asthma were treated in a randomized double-blind way by either intravenous terbutaline two times at an hour interval 6 micrograms/kg or inhaled terbutaline two times 0.1 mg/kg. Peak expiratory flow rate in percent of expected value rose from 89 L/min to 128 L/min (P less than .01) in the intravenous group and from 97 L/min to 122 L/min (P less than .02) in the inhalation group; this was comparable for both groups. PaO2 initially was 7.55 kPa in the intravenous group and rose by 1.4 after 60 minutes (P less than .02) and by 1.33 after 120 minutes (P less than .01). The mean PaO2 did not change in the inhalation group. The pulse rate and blood pressure did not vary significantly in either of the two groups. We conclude that both the intravenous and inhalational administration of terbutaline are effective in acute severe asthma, but that the intravenous route is possibly better for increasing PaO2.

Acute Disease↗
PubMed1986

Glycosylation inhibitors block the expression of LAV/HTLV-III (HIV) glycoproteins.

The glycosylation inhibitors 2-deoxy-D-glucose (2-dGlc) and, to a lesser extent, beta-hydroxynorvaline blocked the formation of syncytia in HIV (LAV/HTLV-III)-infected cells. Using monospecific polyclonal antibodies against recombinant envelope proteins gp110 and gp41 or monoclonal antibodies against env gp110, we could demonstrate a marked reduction in the immunoreactivity of these antigens in HIV-infected cells exposed to the glycosylation inhibitors. There was concomitant accumulation of core proteins p15 and p24, as shown by a solid phase radio-immunoassay, and a decreased oligosaccharide synthesis of env proteins, as monitored by the incorporation of [6-3H]GlcNAc. The reverse transcriptase was not affected by the compounds. Glycosylation inhibitors may be considered for the chemotherapy of AIDS or AIDS-related complex, or chemoprophylaxis of HIV-positive individuals.

Deoxy Sugars↗
PubMed1986

Potent and selective anti-HTLV-III/LAV activity of 2',3'-dideoxycytidinene, the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine.

2',3'-Dideoxycytidinene (ddeCyd), the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine (ddCyd) is, like ddCyd itself, a potent and selective inhibitor of HTLV-III/LAV in vitro. This conclusion is based on the relatively high ratio of effective antiviral dose (0.3 microM) versus cell growth inhibitory concentration (20-35 microM) and the lack of any appreciable inhibitory activity against a series of non-oncogenic RNA and DNA viruses. Both compounds were considerably more inhibitory to human lymphoid cell lines than human nonlymphoid or murine cell lines. They were highly dependent on prior activation by deoxycytidine kinase to exert their anti-HTLV-III/LAV and cytostatic effects. In contrast with ddCyd, ddeCyd lost part of its anti-retrovirus effect upon prolonged incubation (10 days) with the virus-infected cells in culture.

Animals↗
PubMed1986

Efficacy and safety of pefloxacin in the treatment of patients with complicated urinary tract infections.

One hundred and four patients with complicated urinary tract infections (prolonged severe chronic infections or with complicated postoperative conditions) were treated for ten days with pefloxacin 400 mg bid. Bacteriological eradication of the initial pathogen was achieved in 98% of the patients. After six weeks 93% of the patients were still free of the initial infecting microorganism. Clinical improvement was achieved in 77% of the patients five to seven days after cessation of treatment. The side-effects which were definitely related to pefloxacin occurred in 9% of patients and were mostly of a gastro-intestinal, a neurological, or an allergic nature. No significant biochemical or haematological adverse reactions occurred.

Adolescent↗
PubMed1986

A comparison of the clinical and bronchodilating effects of plain and slow-release tablets of terbutaline at steady state.

The clinical efficacy, the bronchodilating effect and the side effects of two oral forms of terbutaline were compared in a double-blind, cross-over study involving ten patients with chronic reversible airways obstruction. The administration of plain-tablets, containing 2.5 mg terbutaline sulphate, three times daily at 6 h intervals was compared to the administration of slow-release (SR) tablets, containing 5 mg terbutaline sulphate, every 12 h. Each course of treatment lasted for 7 days. Treatment with SR-tablets resulted in significantly higher lung function values in the morning (PEFR at home and FEV1 at the lung function laboratory on day 7). There were no significant differences between the two forms with regard to symptom score, extra use of rimiterol aerosol, heart rate or blood pressure. The plasma terbutaline concentration in the morning of the seventh treatment day was significantly higher during SR-tablet treatment. The plasma terbutaline concentration curve showed a smaller peak/trough ratio for the SR-tablets.

Administration, Oral↗
PubMed1986

Is there a functional heterogeneity among IgE-type mast-cell-sensitizing antibodies?

It has recently been established that mast cells display functional heterogeneity. The question then arises whether the IgE-type of antibody, which avidly binds to and thereby sensitizes mast cells and basophils for allergen-induced release of mediators, also expresses functional heterogeneity. In the present article we bring together several experimental observations, mainly from the rat system, which are difficult to explain unless one postulates that mast cell/basophil-sensitizing antibodies of the IgE-type are heterogeneous in their cell-binding properties.

Allergens↗
PubMed1986

A multicentre trial with bacampicillin (Penglobe) in the treatment of respiratory tract infections in general practice.

Nine hundred and eleven patients were admitted to a multicentre trial with bacampicillin (Penglobe) in respiratory tract infections. Of these it was possible to evaluate 830 with respect to efficacy and side-effects. In most cases a dosage of 400 mg X 2 was used but in severe cases 800 mg X 2 was used. The clinical outcome was assessed as good for 79% of the patients, while 17% showed an improvement and 3% a failure. The tolerance was good with an over-all incidence of 8% side-effects, of which dyspepsia was the most common.

Ampicillin↗
PubMed1986

The effect of tachykinins on the conducting airways of the rat.

We studied the bronchial effects of intravenously administered tachykinins in inbred rats. Substance P and related tachykinins caused a dose-dependent bronchoconstriction. The bronchial reactivity to substance P differed significantly between different inbred rat strains. Substance K, eledoisin and kassinin were more potent than substance P in causing bronchoconstriction. This suggests a predominance in the bronchi of SP-E receptors. The bronchial effects of substance P and eledoisin were largely inhibited by atropine and slightly enhanced by hexamethonium. In addition to a direct effect on airway smooth muscle, tachykinins interfere with the cholinergic airway innervation of the rat at the ganglionic and postganglionic level.

Airway Resistance↗
PubMed1986

The respiratory effects of neuropeptides.

Several peptides have been localised to pulmonary nerves and endocrine cells. The neuropeptides vasoactive intestinal polypeptide (VIP) and substance P have potent effects on the airway smooth muscle, bronchial glands and blood vessels. There is increasing evidence that VIP and substance P are neurotransmitters of the non-adrenergic, non-cholinergic nervous (NANC) system. Non-adrenergic inhibitory nerves are the predominant inhibitory nervous system of the human airways. The presence of VIP in the innervation of the airways and the demonstration that it can mimick the effect of NANC nerve stimulation supports the hypothesis that it could be a mediator of the NANC system in the lungs. Sensory nerve fibers containing substance P can contribute to the smooth muscle contraction and mucosal oedema seen in asthma, by local axon reflexes that are initiated by noxious stimuli, such as for example cigarette smoke. A rat model for study of the bronchial reaction to substance P and related tachykinins, is described. In addition to a direct effect on airway smooth muscle, a large part of the broncho-constrictory actions of tachykinins in the rat is mediated by interaction with cholinergic nerves.

Airway Resistance↗
PubMed1986

The bronchial effects of adenosine in the rat.

The in vivo intravenous administration of adenosine caused bronchoconstriction in the rat. There were significant differences between inbred rat strains with regard to bronchial reactivity to adenosine. Inosine caused bronchoconstriction in the rat but was a less potent bronchoconstrictor than adenosine and there was no correlation between the bronchial reactivity to inosine and the reactivity to adenosine. Theophylline, DSCG and nedocromil were potent inhibitors of the adenosine-induced bronchoconstriction. Bilateral vagotomy and the ganglion blocker hexamethonium had no effect on the adenosine-induced bronchoconstriction. High doses of atropine had a small inhibitory effect. The bronchial adenosine receptor has the characteristics of the A2 type.

Adenosine↗
PubMed1986

The clinical relevance of airway inflammation.

Inflammation forms an integral part of the normal defence mechanisms of the airways. Airway inflammation is therefore in essence beneficial, although prolonged exposure to noxious stimuli, overwhelming damage or insufficient control of the inflammatory process may lead to clinical disease. However, the factors contributing to the type and magnitude of airway inflammation, including the level at which damage occurs, the individual difference in sensitivity and inflammatory response to noxious stimuli and the evolution from acute to chronic inflammation, are insufficiently characterized. Clinical, pathological and experimental investigations clearly show that airway inflammatory disorders are heterogeneous. Mucus hypersecretion and bronchial hyperresponsiveness are different characteristics of airway diseases with distinct clinical manifestations and prognostic significance. Epidemiological studies have shown that bronchial hyperresponsiveness is associated with a worse prognosis in obstructive airway disease. Further efforts are needed to understand the impact of different parts of the airway inflammatory process on the physiological and clinical manifestations of airway diseases. Understanding the mode of action of existing and newly developed therapeutic agents on airway inflammation will teach us more about its role in these frequent disorders.

Adult↗