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Biomedical subjects

J P Mathieu

Publications and source records attributed to J P Mathieu.

At least 37 records · Page 2Linked to original sources

Effect of glucose on the distribution of iodine-123-IHA-16 between esterification and oxidation in canine myocardium.

To evaluate the effect of glucose perfusion on the myocardial metabolism of [123I]-16-iodo-9-hexadecenoic acid (IHA), the latter was injected intravenously into six fasting dogs perfused with a solution lacking glucose (controls) and seven fasting dogs perfused with glucose and insulin. The distribution of myocardial 123I among iodides, free IHA, and esterified IHA was measured in myocardial biopsy specimens. The increase in esterification and decrease in oxidation of IHA due to glucose were quantified using a compartmental mathematical model of myocardial IHA metabolism. Subsequently, in six control and six glucose-perfused dogs, cardiac radioactivity was measured with a scintillation camera for 1 hr following i.v. injection of IHA. Four different methods were used to analyze the myocardial time-activity curves and to calculate the distribution of IHA between oxidation and esterification. Results comparable to those provided by analysis of biopsy specimens can be obtained by considering the curve to be the sum of an exponential and a constant, or by analyzing it with a compartmental mathematical model.

Animals↗

Iodomethylated fatty acid metabolism in mice and dogs.

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono beta) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono beta into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.

Animals↗

Myocardial metabolism of radioiodinated methyl-branched fatty acids.

Methylated fatty acids labeled with radioactive iodine have been proposed as a means of studying regional myocardial uptake of fatty acids in man. To investigate the methylated fatty acid that is best adapted for an assessment of uptake, we have studied the influence of the number and the position of the methyl groups of IFA intracellular metabolism; 16-iodo-2-methyl-hexadecanoic (mono-alpha), 16-iodo-2,2-methyl hexadecanoic (di-alpha), 16-iodo-3-methyl-hexadecanoic (mono-beta), and 16-iodo-3,3-methyl-hexadecanoic (di-beta) acids were injected into the coronary arteries of isolated rat hearts. Intracellular analysis shows that the degradation of mono-alpha was always lower than that of IHA and the storage was always much higher. The differences between mono-beta and IHA were similar to those observed with mono-alpha, but were much more pronounced. With the two dimethylated IFAs there was an inhibition of both oxidation and esterification which led to an accumulation of free FAs in myocardial cells. In conclusion, mono-beta, di-alpha, and di-beta are potentially suitable for studying the cellular uptake of IFA since all of them, and particularly the dimethylated IFAs, have a low oxidation rate.

Animals↗

A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.

In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.

Animals↗

Mathematical model of the metabolism of 123I-16-iodo-9-hexadecenoic acid in an isolated rat heart. Validation by comparison with experimental measurements.

The aim of the present study was to demonstrate that it is possible to estimate the intracellular metabolism of a fatty acid labelled with iodine using external radioactivity measurements. 123I-16-iodo-9-hexadecenoic acid (IHA) was injected close to the coronary arteries of isolated rat hearts perfused according to the Langendorff technique. The time course of the cardiac radioactivity was measured using an INa crystal coupled to an analyser. The obtained curves were analysed using a four-compartment mathematical model, with the compartments corresponding to the vascular-IHA (O), intramyocardial free-IHA (1), esterified-IHA (2) and iodide (3) pools. Curve analysis using this model demonstrated that, as compared to substrate-free perfusion, the presence of glucose (11 mM) increased IHA storage and decreased its oxidation. These changes were enhanced by the presence of insulin. A comparison of these results with measurements of the radioactivity levels within the various cellular fractions validated our proposed mathematical model. Thus, using only a mathematical analysis of a cardiac time-activity curve, it is possible to obtain quantitative information about IHA distribution in the different intracellular metabolic pathways. This technique is potentially useful for the study of metabolic effects of ischaemia or anoxia, as well as for the study of the influence of various substrates or drugs on IHA metabolism in isolated rat hearts.

Animals↗

Do iodinated fatty acids undergo a nonspecific deiodination in the myocardium?

The intracellular and subcellular distribution of 16-(123I)-iodo-9-hexadecenoic acid were studied in isolated rat hearts, perfused with or without glucose. At various time intervals after injection, cardiac lipids were extracted and the activity was determined for all fractions and all lipid classes. The total cardiac activity was maximal within 1 min postinjection and most of the activity was in the aqueous phase. The presence of glucose in the perfusion medium induced an increase of total cardiac and organic fraction activities. In the latter fraction, activity was very low for FFA, but high for triglycerides (TG), and especially polar lipids. The presence of an exogenous substrate, led to a more active esterification of fatty acids. Coronary effluent analysis showed, in the hydrophilic phase, a lower activity spike in the presence than in the absence of glucose. In the mitochondrial fraction most activity occurred in the organic phase, especially as polar lipids. In the nonmitochondrial fraction, activity was much higher in the aqueous phase. At 90 s postinjection of 1-14C-palmitic acid, over 80% of the myocardial activity was found in the hydrophilic fraction, which indicates, as for the iodo-fatty acid (IFA), an immediate and important oxidation, especially without glucose. These data seem to prove that IFA is taken up by the myocardial cell, subsequently enters the mitochondria and, without an early deiodination, is oxidized with iodide release. Changes in IFA metabolism, consecutive to modifications of glucose concentration in the perfusion medium can be observed by external detection of the myocardial activity curve. Omega-Iodinated fatty acids do not undergo a nonspecific deiodination and are therefore well suited for an external study of myocardial metabolism.

Animals↗

Influence on the myocardial and blood activity course of the characteristics of the labelled fatty acid injected i.v. into mice.

In order to choose a labelled fatty acid (FA) for the external study of myocardial metabolism, FAs that are different in chain length, saturation, nature and position of the radioactive label, are injected i.v. into mice. Myocardial and blood activities are measured at various times p.i. It appears that hexadecanoic and hexadecenoic acids, iodine labelled in omega position, have the highest maximal myocardial activity among all the FAs studied. Furthermore, the myocardial and blood time-activity course is similar for both FAs. As unsaturated FAs have apparently a higher myocardial fixation in man than the saturated ones, 123I 16 iodo-9 hexadecenoic acid has been selected and seems well suited for the study of myocardial metabolism.

Animals↗

Kinetics of (16 123I) iodohexadecenoic acid metabolism in the rat myocardium, influence of glucose concentration in the perfusate and comparison with (1 14C) palmitate.

External counting, intracellular and subcellular distribution of (16 123I) iodohexadecenoic acid are studied on isolated rat hearts perfused with or without glucose. The presence of an exogenous substrate reduces the fatty acid oxidation and induces an increase of total cardiac and organic fraction activities. In this fraction, activity is very low for free fatty acids, but high for triglycerides and especially for polar lipids. The presence of an exogenous substrate leads to a more active esterification of fatty acids. Coronary effluents analysis shows, in the hydrophilic phase, a lower activity rebound in the presence of glucose. In the mitochondrial fraction, activity is mostly in the organic phase, as polar lipids especially. In the non-mitochondrial fraction, activity is much higher in the aqueous phase. 90 s p.i. of (l 14C) palmitic acid, over 80% of the myocardial activity is found in the hydrophilic fraction, which indicates--as for the iodo fatty acid (IHA)--an immediate and important oxidation, especially without glucose. These data seem to prove that IHA is taken up by the myocardial cells, enters the mitochondria where it is, without an early deiodination, oxidized with iodide release. IHA metabolic changes can be seen on the external detection myocardial activity curve. Omega iodinated fatty acids do not undergo a nonspecific important deiodination and are therefore well adapted to an external study of myocardial metabolism.

Animals↗

Kinetics of iodomethylated hexadecanoic acid metabolism in the rat myocardium: influence of the number and the position of methyl radicals.

The methyl-branched fatty acids, if radioiodine labelled in alpha position, are potentially adapted to a selective study of FA myocardial uptake. To determine the position and the number of methyl radicals that are necessary to obtain a maximal uptake and a minimal degradation, we measured time-activity evolution of isolated and perfused rat hearts after an injection of iodinated fatty acids which are mono- or dimethylated in alpha or beta position. Except for dimethyl fatty acid, the uptake is similar for all fatty acids studied to that of the straight chain analogue; beta mono- or dimethyl fatty acids seem best adapted to a study of the uptake because alpha monomethyl fatty acids undergo a metabolic degradation and alpha mono- and dimethyl fatty acids induce ventricular fibrillations.

Animals↗

Date of conception and prevention of neural tube defects.

The authors studied the time of conception of 280 fetuses and liveborns with anencephaly or spina bifida seen in a French Canadian population during a period of six years. There is an evident seasonal variation in the conception of NTD fetuses. Using a wave statistical model applied to data recorded over a six year period the authors have rejected the "no variation between the six two-month intervals" hypothesis at a P less than or equal to 0.005 level. It is postulated that, in any vitamin intake or environmental program to prevent NTD in families at risk, one must take into account the annual and seasonal variations, ethnic groups identity and the date of conception in the choice of control mothers.

Canada↗

[Measurement of the right ventricular ejection fraction during the acute phase of myocardial infarction using 81m krypton infusion. Comparison with the left ejection fraction].

The right ventricular ejection fraction is rarely measured, as conventional diagnostic methods (radiology, echocardiography) are confronted with the problem of representing the right ventricle as a simple tridimensional geometrical model. This is not necessary with the radio-isotopic techniques. However, all those used for the measurement of right ventricular ejection fraction lead to important methodological problems. We have therefore developed a technique of measuring this parameter with an infusion of 81 m Kr. This radioactive gas is pure gamma-ray emitter with a 13 second period. Dissolved and infused intravenously, it is eliminated during the first passage through the lung. The continuous separation of the generator of 81 m Kr is performed with isotonic dextrose solution which is then infused for a period of 7 minutes. During this time, the activity detected by the scintillation camera inclined in the 30 degrees RAO projection is stored, together with the electrocardiogram in a computer. The precordial radioactivity of the retrocardiac lung tissue is subtracted after injection of 74 MBq of 99 mTc microspheres. A graph of right ventricular activity can then be reconstructed and the right ventricular ejection fraction calculated. The left ventricular ejection fraction is then measured with 99 mTc--labelled RBCs. This method allows the right ventricular ejection fraction to be measured in the RAO projection, the best incidence for the separation of the right atrial from the right ventricular activity without interference from left ventricular activity because of the pulmonary elimination of the Krypton radioactivity. The measurement performed on a large number of cardiac cycles allows a continuous study of the right ventricular ejection fraction. At the end of the infusion there is no circulating radioactivity so that the measurement can be repeated. This technique was used in 17 patients with acute myocardial infarction. In the 7 patients with anterior infarcts reduction of the left ventricular ejection fraction was the predominant finding (21,6 +/- 6,8%). The right ventricular ejection fraction was 34,2 +/- 6,4%. On the other hand, patients with a postero-inferior infarction had little change in left ventricular ejection fraction (59,2 +/- 12%) but those with right ventricular extension of their infarcts had very reduced right ventricular ejection fractions (less than 23%). The measurement of right ventricular ejection fraction with 81 m Kr is a reliable atraumatic method for diagnosing right ventricular infarction by the quantification of its functional impairment.

Adult↗

Psoriatic arthritis: risk factors for patients with psoriasis - a study based on histocompatibility antigen frequencies.

Histocompatibility antigen frequencies were studied in a group of 100 patients with psoriatic arthritis (PSA) and were compared to a group of 80 patients whose psoriasis was restricted to skin lesions (PSC). The antigens B13, BW57 (17), CW6 were significantly increased in PSC while BW57 (17), BW39, CW6 and CW7 were increased in PSA. No DR or MT antigen was elevated in frequency when compared to normal controls. The significant information which results from this study includes: 1) a failure to confirm previous reports on HLA-DR antigen increased frequencies; 2) an association, in this population, of BW39 with PSA and not BW38; 3) finding of a closer link of PSC and PSA with HLA-C rather than HLA-B antigens; 4) an estimate of relative risk for patients with PSC to develop PSA.

Adolescent↗

[Current indications for superior dorsal sympathectomy. Apropos of 84 cases].

Results of dorsal sympathectomy in patients (67 operations) for vasomotor disorders of the upper limbs were assessed after follow-up for between 6 months and 15 years, in order to determine the best indications for surgery. Based on clinical results, sympathectomy should be performed not only when medical treatment fails, but also in the presence of a severe clinical picture of trophic disturbances or pain of the ischemic type. Two types of investigation are essential before deciding on operative therapy:--plethysmography with a hyperemia test,--arteriography of the hand. Assessment of results as a function of etiology demonstrated that they were excellent in cases of hyperhidrosis, very satisfactory in atheromatous digital arteritis or a thoracic inlet syndrome (associated with rib resection in the latter case), but only moderately good in scleroderma or post-traumatic lesions. Finally, Raynaud's disease or thromboangiitis do not appear to be indications for this operative procedure.

Adolescent↗