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Biomedical subjects

O Michel

Publications and source records attributed to O Michel.

At least 145 records · Page 8Linked to original sources

Effect of inhaled endotoxin on bronchial reactivity in asthmatic and normal subjects.

Endotoxins are released from the membrane of Gram-negative bacteria present in the environment and in oral and nasal cavities. They are proinflammatory substances that could participate in bronchial obstruction and hyperreactivity in asthmatic patients. This hypothesis was tested by using bronchial challenge tests with inhaled lipopolysaccharides (LPS) from Escherichia coli 026:B6 (22.2-micrograms total dose) followed by a histamine nonspecific challenge test and compared with a placebo procedure, in which the diluent was substituted for the LPS solution. In doing so we showed that LPS induces a slight but significant (P less than 0.01) bronchial obstruction (measured as forced expiratory volume in 1 s) in asthmatics (n = 8) but not in normal subjects (n = 6). The histamine hyperresponsiveness, expressed as the dosage of histamine necessary to decrease the bronchial specific conductance by 50%, was increased 5 h after LPS inhalation in asthmatics (P less than 0.05) but not in normal subjects. This effect of LPS on bronchial obstruction and hyperresponsiveness was observed in extrinsic (n = 6) as well as in intrinsic (n = 2) asthma.

Administration, Inhalation↗

[Comparison of the effect of 2 methods of histamine administration on the bronchomotor response in asthmatics].

Bronchial provocation tests are useful for the detection of subclinical bronchial hyper-reactivity. Their standardisation is vital, in particular the method of administration of the bronchoconstrictor agent. Our study compares two systems of histamine delivery: an aerosol propellant with freons and a jet nebuliser linked to a dosimeter. Ten allergic asthmatics underwent bronchial provocation by each of these two systems at 8 days interval. The forced expired volume in one second FEV1 (VEMS) and specific conductance (sGAW) were measured during both tests. The dose of histamine inducing a reduction of VEMS of 20% (PD VEMS) or of sGAW of 40% (PD sGAW) was calculated. The comparison of the two methods showed a lower threshold of sensitivity when histamine was administered by dosimetry whether it was in terms of PD 20 VEMS (p less than 0.01) or PD 40 sGAW (p less than 0.05). The threshold of sensitivity expressed as PD 20 VEMS and PD 40 sGAW are superimposable by the dosimetric technique but on the other hand, using the aerosol dosage method, the threshold of sensitivity expressed in PD 40 sGAW is significantly lower than that for PD 20 VEMS (p less than 0.02). The 2 differences of bronchial response as a function of the method of administration of histamine could be explained by a better bronchial penetration, accompanied by a more central depot of the drug when histamine is administered by dosimetry.

Adult↗

Platypnea induced by worsening of VA/Q inhomogeneity in the sitting position in chronic obstructive lung disease.

We report a patient with COPD who experienced severe dyspnea with a decreased PaO2 in the sitting position, largely improved in the ventral prone position (platypnea). By using an isotopic method, we showed that this phenomenon is the result of a deleterious effect of the sitting position on regional ventilation/perfusion matching. We speculated that hypoxic vascular pulmonary constriction was deficient in our patient. This hypothesis is supported by a dramatically better matching of the VA/Q ratio after treatment with almitrine bismesilate, a drug that could potentiate hypoxic pulmonary vasoconstrictive reflexes.

Aged↗

Failure to demonstrate complement activation during bronchial challenge test.

In order to demonstrate a possible complement activation during early bronchospastic reaction in asthma, we have measured plasmatic C3d (a split product of C3) and the C3d/C3 index, both of which are sensitive indices of complement activation. Twenty-nine allergenic bronchial challenge tests were accomplished, with an absence of response in six cases, an early reaction in sixteen cases and a dual reaction in seven cases. Changes in plasmatic C3d or C3d/C3 five min after an early reaction, or five min after the last dose of allergen (in the six cases without bronchial response) were insignificant. However, complement activation in the lungs during asthmatic reaction cannot be completely excluded without studies using the bronchoalveolar technique.

Adolescent↗

[Asthma and complement].

The complement system has an important place in the development of the inflammatory reaction. The complement may be activated by the classical pathway (itself activated by immune complexes, CRP etc.) or the alternative pathway (activated by bacterial endotoxins, different lung allergens etc.). This activation culminates in the release of opsonising, chemotactic, smooth muscle constrictor, and mast cell activating factors. The complement system is present locally at the level of the bronchi and could participate in the development of bronchial inflammation narrowly associated with asthma. Study of the complement system in the plasma in asthmatics has not shown a relation between its state of activation and bronchomotor tone. However, in view of recent studies of the complement in the bronchi, analysed on broncho-alveolar lavage, the potential role of complement in asthma should be re-evaluated.

Asthma↗

Comparative effects of 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'-isopropylthyroacetic acid (IpTA2) on body weight gain and lipid metabolism in genetically obese Zucker rats.

3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT) and 3,5-diiodo-3'-isopropylthyroacetic acid (IpTA2), two thyroid hormone analogs, have been tested in genetically obese Zucker rats and their lean littermates, in comparison with thyroxine (T4) and triiodothyronine (T3) for their thyromimetic activities on body weight gain and lipid levels in serum and liver. The compounds were administered for 9 weeks by orogastric tube to 6- to 8-week-old animals. While body weight gain remained practically unchanged in the lean rats, it decreased significantly in the obese individuals, especially with IpTA2. The serum lipid concentrations were also decreased in the obese rats in comparison with their lean littermates, especially with DIMIT. The connection observed between the structure of DIMIT and IpTA2 on one hand and their effects on the other is in good agreement with previous studies. Our results confirm that the iodine substituents are not necessary for thyromimetic activity and demonstrate that the isopropyl substituent in 3' plays an important role in the serum lipid-lowering effect of the thyroid hormone analogs tested.

Animals↗

Complement activation in bronchial asthma evaluated by the C3d/C3 index.

In order to demonstrate a suspected complement activation in bronchial asthma, we measured the C3d (split product of C3) and the C3d/C3 ratio in 73 adults. Both are considered to be a sensitive index of complement activation. Compared with the value obtained in 47 normal subjects, the C3d level and the C3d/C3 ratio level were found significantly higher in asthmatic subjects. Fourteen asthmatics presented an increased C3d/C3 above the calculated limit of normality. These 14 subjects differed from the other asthmatics by a significantly lower C4 plasmatic level, suggesting an activation of the classical pathway of the complement system. Nevertheless, the clinical significance of these observations remains difficult to interpret in view of the absence of significant differences of clinical, allergologic and respiratory functional parameters between asthmatics with low or high C3d/C3 index.

Adolescent↗

[Interaction between asthma and maxillary sinusitis].

We have studied atopic status and respiratory function in 69 asthmatics in relation to possible radiological changes in the sinuses. These alterations were classified under four headings: normal, mucosal thickening (greater than 3 mm), polyp or opaque films. The bronchial obstruction, evaluated by FEV1/FVC ratio was compared in the 4 groups. The reversibility of airflow obstruction by beta-2-sympathomimetics (Fenoterol) was the same with or without changes in the sinuses. The atopic trait (RAST or immediate prick tests) or non-atopic asthma was not associated with any sinus abnormalities. In conclusion, if a close association between asthma and radiological disease of the sinuses exists (60% of cases), it does not seem that chronic sinusitis worsens bronchial obstruction or reduces sensitivity to beta-2-sympathomimetics. The changes in the sinus mucosa may be induced by the same aetiologic agent (allergic or non allergic) as asthma.

Adult↗

[Anti-anginal effect of transdermally applied nitroglycerin as dependent on the size of the plaster].

Nitroglycerin plaster (in 5 cm2, 10 cm2 or 20 cm2 sizes) was applied to 12 patients with coronary heart disease, angina and exercise-induced ischemic reactions in the course of a simple-blind trial with intra-individual crossover in a randomized sequence over one week each. A 15 cm2 plaster served as a placebo. In the placebo phase the mean number of angina attacks was 9.3 per week. It decreased to 6.2 with the 10 cm2 plaster (P less than 0.05), to 2.6 per week with the 20 cm2 plaster (P less than 0.001). The ischemia reaction in the exercise ECG (sum of ST segment depressions), recorded on day 7 of the treatment phase, was improved three hours after plaster application, dependent on the size of the plaster: placebo 6.0 +/- 1.2 mm; 5 cm2 plaster 5.1 +/- 1.0 mm; 10 cm2 4.6 +/- 1.0 mm (P less than 0.05); 20 cm2 3.4 +/- 0.9 mm (P less than 0.001). The angina-free period during ergometry showed dose-dependent improvement 3 and 24 hours after application. Arterial blood pressure was decreased only after 20 cm2 plaster by 8% after three hours, as compared with the placebo (P less than 0.05). There was no effect on heart rate, at rest or on exercise, after any plaster. The results indicate that significant decrease in ischemia reaction occurred with a plaster of 10 cm2 or larger. A 24-hour effect was demonstrable only with respect to the duration of symptom-free exercise.

Administration, Topical↗

[Effect of hypothyroidism on mitochondrial energy metabolism and nuclear synthesis of RNA in the liver of Cynomolgus monkeys].

The effects of hypothyroidism and of replacement therapy with T4 or T3 were studied on the enzymatic activities of liver subcellular fractions isolated from Cynomolgus monkeys. Animals were sacrificed 20 days after thyroidectomy. In mitochondria, thyroidectomy decreased significantly the respiratory chain activity (succinate cytochrome c-reductase), the transfer of cytosolic reducing equivalents (glycerol-3-phosphate dehydrogenase) and the phosphorylating capacity (oligomycin-sensitive ATPase and state 3 respiratory rate). The activity of nucleolar and nucleoplasmic RNA polymerases dropped by about 50% in hypothyroid monkeys. In T4 (2.5 micrograms/kg/d) or T3 (1 microgram/kg/d) treated thyroidectomized animals, the iodothyronine concentrations and the activity of mitochondria and nuclei enzymes were halfway between normal and hypothyroid values. Thus, the mitochondrial effects of thyroidectomy in monkey are, as in rat, at least partly secondary to a decrease in nucleocytoplasmic protein synthesis.

Animals↗

Comparative effects of thyroid hormone analogs on the activities of brain and liver mitochondria and nuclei in thyroidectomized rats.

Several thyroid hormone analogs have been tested for thyromimetic activity on rat brain and liver subcellular organelles. The compounds were administered immediately after thyroidectomy to 90 g male S-D rats for 10 days, by daily s.c. injection. In cerebral cortex and liver we measured the activities of mitochondrial succinate cytochrome c reductase and alpha-GPD, and nuclear RNA polymerase I. Brain mitochondrial enzymes were unchanged in thyroidectomized (Tx) and in Tx-treated rats, whereas the activities of these enzymes in liver mitochondria were partially restored by the treatments. RNA polymerase I activity in brain and liver dropped significantly 10 days after thyroidectomy and daily injection of thyroid hormones or analogs maintained the nuclear activity at a normal level. Correlation between the structure of thyroid hormone analogs and their subcellular effects is in good agreement with previous binding and in vivo studies. Enzyme activities stimulated by T3 were lowered by replacing the T3 side-chain by an acetic acid group or by substituting the bridged oxygen atom by atom by CO. In contrast, the activity was enhanced by substituting iodine with a 3' isopropyl group. Although less active than iodine, the 3,5-dimethyl substituents may be introduced without a complete loss of nuclear activity.

Animals↗

Effects of chronic aspirin ingestion in aspirin-intolerant asthmatic patients.

The effects of regular aspirin ingestion after aspirin-desensitization were evaluated in 10 aspirin-intolerant asthmatic patients. Chronic aspirin ingestion was not observed to be associated with either a significant improvement of mean FEV1 values or with a decrease in daily corticosteroid requirements. This study suggests that regular aspirin ingestion in aspirin-intolerant asthmatic patients does not induce a measurable improvement of the respiratory status.

Administration, Oral↗

[Indications for the aspirin provocation test in the asthmatic].

Oral provocation tests using aspirin (n = 55), tartrazine (n = 37) and benzoate (n = 28) were performed in 55 asthmatic patients. A positive aspirin provocation test was observed in 15 patients (27%). These patients often had a past history of aspirin intolerance, 53% of them also had nasal polyposis and 5 out of 12 had associated tartrazine intolerance, while 2 out of 8 had associated benzoate intolerance. The authors consider that these features may help the clinician to detect the asthmatic patient at high risk of aspirin intolerance in whom a provocation test should be performed.

Adult↗

Decreased sensitivity to tartrazine after aspirin desensitization in an asthmatic patient intolerant to both aspirin and tartrazine.

An aspirin- and tartrazine-sensitive asthmatic patient underwent a desensitization to the adverse effects of aspirin by oral aspirin challenges. After a month of daily aspirin ingestion, the patient's reactivity to tartrazine, tested by oral challenge, was observed to the blunted. This report suggests that desensitization to the adverse effects of aspirin might protect the patient against the adverse effects of tartrazine.

Adult↗