Search PubMed⌕ Search

Biomedical subjects

A Syrota

Publications and source records attributed to A Syrota.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of 5-day hypoxia on cardiac adrenergic neurotransmission in rats.

Chronic hypoxia induces an overall sympathetic hyperactivation associated with a myocardial beta-receptor desensitization. The mechanisms involved in this desensitization were evaluated in 32 male Wistar rats kept in a hypobaric pressure chamber (PO2 = 40 Torr, atmospheric pressure = 450 Torr) for 5 days. In hypoxic compared with normoxic conditions, plasma norepinephrine (NE) levels were higher (2.1 +/- 0.7 vs. 0.6 +/- 0.2 ng/ml) with no difference in the plasma epinephrine levels (2.2 +/- 0.7 vs. 1.8 +/- 0.3 ng/ml). In hypoxia neuronal NE uptake measured by [3H]NE was decreased by 32% in the right ventricle (RV) and by 35% in the left ventricle (LV), and [3H]mazindol in vitro binding showed a decrease in uptake-1 carrier protein density by 38% in the RV and by 41% in the LV. In vitro binding assays with [3H]CGP-12177 indicate beta-adrenoceptor density reduced by 40% in the RV and by 32% in the LV, and this was due to reduced beta1-subtype fraction (competition binding experiments with practolol). Hypoxia reduced the production of cAMP induced by isoproterenol (36% decrease in the RV and 41% decrease in the LV), 5'-guanylylimododiphosphate (40% decrease in the RV and 42% decrease in the LV), and forskolin (39% decrease in the RV and 41% decrease in the LV) but did not alter the effect of MnCl2 and NaF. Quantitation of inhibitory G-protein alpha-subunit by immunochemical analysis showed a 46% increase in the cardiac-specific isoform Gialpha2 in hypoxic hearts. The present data demonstrate that in rats 5-day hypoxia leads to changes in pre- and postsynaptic myocardial adrenergic function. The myocardial desensitization associated with both a reduction in externalized beta1-adrenoceptor and an increase in inhibitory G-protein subunit may be caused by increased synaptic NE levels due to impaired uptake-1 system.

Adenylyl Cyclases↗
PubMed1998

[Fluorodeoxyglucose and bronchopulmonary cancer. Initial French results with positron emission tomography].

Despite recent advances, the contribution of medical imaging techniques is limited, particularly in terms of tissue characterization, in the diagnosis of pulmonary nodules and search for extension of bronchogenic cancer. The metabolic properties of the glucose analog deoxyglucose labeled with 18F1 would allow metabolic imaging. Positron emission tomography (PET) provides clinicians with quality images with an interesting sensitivity. We report the results of a feasibility study conducted in our first 17 patients. We observed 14 true positives, 1 true negative and 1 false positive and 1 false negative in patients with a malignant primary lesion. We analyzed the causes of error. Ten disseminated localizations were identified. Possible developments in terms of therapeutic strategy are discussed. The agreement between our findings and data reported in the literature prompted us to develop a study protocol using 18-fluorodeoxyglucose PET in patients with bronchogenic cancer.

Adult↗
PubMed1997

Increased myocardial muscarinic receptor density in idiopathic dilated cardiomyopathy: an in vivo PET study.

BACKGROUND: Congestive heart failure is associated with decreased stimulated myocardial adenylate cyclase activity, increased Gi-binding protein, attenuated parasympathetic tone, and increased modulation of beta-adrenergic inotropic left ventricular stimulation by parasympathetic agonists. Despite these abnormalities, changes in the density or affinity of ventricular muscarinic receptors have not been demonstrated in patients. METHODS AND RESULTS: The density and affinity constants of myocardial muscarinic receptors were evaluated noninvasively by means of positron emission tomography with 11C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, in 20 patients with congestive heart failure due to idiopathic dilated cardiomyopathy (mean left ventricular ejection fraction, 22+/-9%) and compared with values in 12 normal subjects. The mean receptor concentration was significantly higher in patients than in control subjects (B'max, 34.5+/-8.9 versus 25+/-7.7 pmol/mL, P<.005), with no changes in affinity constants. The change in heart rate after injection of 0.6 mg of cold MQNB was lower in patients than in control subjects (34+/-20% versus 55+/-36%, P<.05), and receptor density correlated negatively with maximal heart rate in the patients (r=.45, P<.05). CONCLUSIONS: Congestive heart failure is associated with an upregulation of myocardial muscarinic receptors. This may be an adaptive mechanism to beta-agonist stimulation and should increase the number of potential targets for pharmacological intervention.

Adult↗
PubMed1997

Presynaptic dopaminergic function in the striatum of schizophrenic patients.

The dopaminergic hypothesis of schizophrenia postulates increased brain dopaminergic activity. Two previous studies reported increased 18F-DOPA uptake with positron emission tomography in schizophrenic patients (n = 5, n = 7). In the present study, striatal dopaminergic function was assessed in vivo in six untreated schizophrenics and seven control subjects, comparable for age and sex. The 18F-fluoro-L-DOPA (18F-DOPA) uptake rate constant Ki was determined in the caudate and putamen using coregistered positron emission tomography and magnetic resonance imaging. No difference between groups for mean Ki was found. The variability of the 18F-DOPA uptake values was higher in the caudate (p < 0.01) and in the putamen (p < 0.001) in schizophrenic patients than in control subjects, suggesting that schizophrenia is a disorder involving heterogeneous states of the striatal presynaptic dopaminergic function.

Adolescent↗
PubMed1997

Body composition determined with MR in patients with Duchenne muscular dystrophy, spinal muscular atrophy, and normal subjects.

Magnetic resonance imaging was used to determine total fat mass of patients with neuromuscular disorders, accounting for intramuscular fat. Nineteen boys aged 9 to 12 (eight with Duchenne muscular dystrophy, three with type II spinal muscular atrophy and eight control subjects) underwent whole-body magnetic resonance imaging examination and anthropometric measurements. Whole-body fat mass was deduced from automated analysis of images normalized by a reference signal. Intramuscular and subcutaneous fat masses were deduced from manual analysis of twelve reference slices. Affected children significantly differed from control subjects for higher total fat mass, mostly related to intramuscular fat mass. Shorter protocols validated from whole-body data were shown to be more accurate than fat mass estimation derived from anthropometric measurements.

Adipose Tissue↗
PubMed1997

The right brain hemisphere is dominant in human infants.

The development of functional brain asymmetry during childhood is confirmed by changes in cerebral blood flow measured at rest using dynamic single photon emission computed tomography. Between 1 and 3 years of age, the blood flow shows a right hemispheric predominance, mainly due to the activity in the posterior associative area. Asymmetry shifts to the left after 3 years. The subsequent time course of changes appear to follow the emergence of functions localized initially on the right, but later on the left hemisphere (i.e. visuospatial and later language abilities). These findings support the hypothesis that, in man, the right hemisphere develops its functions earlier than the left.

Adolescent↗
PubMed1997

Parametric images of benzodiazepine receptor concentration using a partial-saturation injection.

The in vivo quantification of the benzodiazepine receptor concentration in human brain using positron emission tomography (PET) and 11C-flumazenil (11C-FMZ), is usually based on a three-compartment model and on PET curves measured in a small number of large regions of interest; however, it should be interesting to estimate the receptor concentration for each pixel and to build quantified images of the receptor concentration. The main advantage is to allow screening of the receptor site localization and visual observation of the possible abnormalities. Up to now, all the methods described include complex experimental protocols, difficult to use in routine examinations. In this paper, we propose the partial-saturation approach to obtain parametric images of benzodiazepine receptor concentration and FMZ affinity. It consists of a single FMZ injection with a low specific activity, followed by Scatchard analysis. Like other parametric imaging methods, this partial-saturation approach can lead to a small percentage (< 1%) of unrealistic values in receptor-poor regions; however, it is the only method that allows receptor concentration and affinity images to be obtained from a single-injection 40-min experiment without blood sampling. We also propose a second method in which the receptor concentration map is directly deduced from the PET image acquired 5 to 10 min after a partial-saturation injection. This method assumes a known and constant FMZ affinity value but requires only very simple corrections of this PET image. It is robust (negative values are never found) and quite simple to use in routine examination of patients (no blood sampling, single injection, only 10-min experiment).

Brain Chemistry↗
PubMed1997

An attempt to visualize baboon brain nicotinic receptors with N-[11C]ABT-418 and N-[11C]methyl-cytisine.

ABT-418 ((S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole) and N-methyl-cytisine, high-affinity nicotinic cholinergic agonists, were labelled with 11C and evaluated in vivo using positron emission tomography (PET) for the visualization of nicotinic cholinergic receptors in baboon brain. Both labelled compounds were synthesized by methylation to their respective precursors, A-79814 and cytisine, using [11C]methyliodide. Following the intravenous (i.v.) injection of N-[11C]ABT-418, uptake in brain was rapid but low, with a peak at 1-2 min (4.40 +/- 0.2% of injected dose per 100 ml tissue) followed by rapid washout. Clearance of radioactivity from the blood was rapid. The regional distribution of the radioactivity followed mainly the distribution of grey matter. Slightly lower uptake in the cerebellum than in the cortex was observed. The uptake and the shape of the time-activity curves were unchanged following the co-administration of labelled and of excess (1 mumol kg-1) unlabelled ABT-418. Thus the essential criteria for visualizing receptor binding with PET could not be fulfilled. Following the i.v. injection of N-[11C]methyl-cytisine, the activity in the brain was not significantly different from that of blood (0.86 +/- 0.01% and 0.96 +/- 0.1% of injected dose per 100 ml tissue, respectively). Thus N-[11C]ABT-418 and N-[11C]methylcytisine do not appear to be suitable tracers for PET studies of nicotine cholinergic receptors in primate brain.

Alkaloids↗
PubMed1997

Early single photon emission computed tomography in Sturge-Weber syndrome.

OBJECTIVES: Functional cerebral imaging PET and SPECT have shown hypometabolism and hypoperfusion in the area of vascular malformation in children with epilepsy due to Sturge-Weber syndrome. However, data are scarce in infants and do not exist in patients with Sturge-Weber disease without epilepsy. The pattern of perfusion during the first two years of life was studied including patients before the onset of seizures. METHODS: Twenty two infants with later confirmed Sturge-Weber disease underwent SPECT examination using TOMOMATIC 564 (Medimatic) and xenon-133 at ages ranging from 8 days to 25 months. Twelve had never had seizures before SPECT and seven underwent a second SPECT a mean seven months later. Cerebral blood flow (CBF) was measured in the whole hemisphere and in the part of the cortex involved in the vascular malformation on both sides as well as a "pathological to normal" index for the hemisphere and vascular malformation. These values were compared with normal age paired values. RESULTS: Compared with controls, CBF and the indices in the hemisphere and vascular malformation were significantly decreased in patients who already had had seizures before SPECT, whereas they were significantly increased in 75% of the patients who had never had any seizures. On second SPECT, the indices were decreased in all patients, including the four who still remained non-epileptic. CONCLUSIONS: SPECT therefore detects CBF asymmetry in infants with Sturge-Weber disease, which tends to shift with age. The cortex involved in the vascular malformation is hyperperfused during the first year of life before first seizures. The classic hypoperfusion appears after one year of age, even in non-epileptic patients.

Brain↗
PubMed1997

Alterations of myocardial sympathetic innervation in response to hypoxia.

UNLABELLED: The effects of altitude hypoxia on myocardial sympathetic nerve function were assessed in rats using metaiodobenzylguanidine (MIBG). METHODS: To estimate the change in uptake-1 function induced by hypoxia, three sets of rats were submitted to 5-, 7- and 21-day hypoxia (hypobaric chamber at 410 Torr) and one set of control rats was injected with 25 muCi of 123I-MIBG. Four hours later, the rats were killed and 123I activity was counted in both ventricles. The proportion of MIBG fixed in the myocardium through the norepinephrine (NE) transporter (uptake-1) was evaluated indirectly in 5-day hypoxic and controls rats by the injection of desipramine before 123I-MIBG administration. Myocardial perfusion was evaluated in 5-day hypoxic rats and controls by 201Tl injection. RESULTS: Myocardial 123I-MIBG activity was 0.253% +/- 0.036% kg dose/g-1 in controls and was decreased (0.188% +/- 0.029% kg dose/g-1, p = 0.001) in 5-day hypoxic rats. This decrease was not related to a change in cardiac perfusion. The decrease in MIBG uptake existed before the appearance of cardiac hypertrophy. Desipramine decreased MIBG uptake by 48% in controls and 17% in hypoxic rats, suggesting that the decrease predominantly affected MIBG uptake by the NE transporter. CONCLUSION: Chronic hypoxia leads to a decrease in myocardial NE-uptake-1 function. This finding suggests that altered tissue oxygen supply could play a role in the decreased cardiac MIBG uptake reported in human cardiomyopathies.

3-Iodobenzylguanidine↗
PubMed1997

Down-regulation of cardiac muscarinic receptors induced by di-isopropylfluorophosphate.

UNLABELLED: The feasability of PET determination of myocardial muscarinic acetylcholine receptor (mAChR) density has been demonstrated in dogs and humans. The results of the PET method, however, were not validated by a direct comparison with the in vitro determination of mAChR density. METHODS: Left ventricular mAChR concentrations were studied in beagle dogs at baseline and after a 5- or a 11-day treatment with the irreversible acetylcholinesterase inhibitor di-isopropylfluorophosphate (DFP). The determination of mAChR densities were performed in vivo using PET, 11C-MQNB, the three-injection protocol and the compartmental model previously described. In a parallel group of dogs, determination of mAChR density was performed in vitro using 3H-(-)-MQNB. RESULTS: In control dogs (n = 4), PET left ventricular density of mAChR was 61.1 +/- 8.1 pmol/ml tissue. In the 5-day DFP-treated animals (n = 3), Bmax decreased to 38.2 +/- 8.3 pmol/ml tissue (-38%; p = 0.005 versus control). In the 11-day DFP-treated animals (n = 3), Bmax was 34.7 +/- 5.5 pmol/ml tissue (-43%; p = 0.003). There was no change in the affinity constant either at 5 or 11 days. In control dogs, Bmax, measured in vitro, was 9.53 +/- 0.93 pmol/g tissue. In the 5-day DFP-treated animals, Bmax decreased to 6.2 +/- 0.9 pmol/g tissue (-35%; p = 0.003). In the 11-day DFP-treated animals, Bmax was 5.1 +/- 0.6 pmol/g tissue (-47%; p = 0.003 versus control). At that time, there was no change in affinity constant. On the fifth and 11th days, myocardial acetylcholinesterase activity was reduced by 88% and 90%, respectively. CONCLUSION: The in vivo and in vitro methods showed a similar decrease in mAChR density while for both methods affinity constant remained unchanged. This study validates the ability of PET and of the compartmental model to in vivo quantify changes in mAChR density.

Acetylcholinesterase↗
PubMed1996

Blunted coronary reserve in myotonic dystrophy. An early and gene-related phenomenon.

BACKGROUND: In myotonic dystrophy (DM), striated muscle is involved in relation to the size of the DNA mutation. Smooth muscle may be similarly impaired at the level of the urinary and digestive apparatus and possibly at the level of small vessels, since microangiopathy has been described in the iris and digital capillaries. Our purpose was to study the function of the myocardial microvasculature in relation to the size of the mutation in DM patients without clinical cardiac involvement and with normal left ventricular dimensions and function and normal large coronary arteries. METHODS AND RESULTS: In 6 control subjects and 10 DM patients, we investigated the coronary blood flow reserve using positron emission tomography with 15O-labeled water. Global and regional flow reserves were obtained from myocardial regions of interest manually drawn on a static FDG image encompassing, respectively, the whole left ventricle and the anterior, septal, and lateral walls. The DNA mutation size was determined on circulating lymphocytes in each DM patient. Compared with control subjects, DM patients had decreased global (2.39 +/- 0.39 versus 4.00 +/- 0.67, P = .00003) and regional (anterior, 2.39 +/- 0.64 versus 3.87 +/- 0.92, P = .002; septal, 2.60 +/- 0.48 versus 4.00 +/- 0.70, P = .0003; lateral, 2.26 +/- 0.58 versus 4.16 +/- 1.11, P = .0005) coronary reserves. In DM patients, the coronary reserve correlated strongly and inversely with the DNA mutation size (r = -.77, P = .009). CONCLUSIONS: The study demonstrated that global and regional coronary reserves are impaired, in relation to the DNA mutation size, in symptom-free DM patients with normal ventricular dimensions and function and normal large coronary vessels. We suggest that a gene-related blunted coronary reserve resulting from an impairment of vascular smooth muscle is an early component of DM cardiomyopathy.

Adult↗
PubMed1996

In vivo effect of methyl-quinuclidinyl-benzylate on myocardial beta-adrenoceptor density.

The muscarinic receptor antagonist methyl-quinuclidinyl-benzylate decreased myocardial beta-adrenoceptor density Bmax: 20.4 +/- 2.4 pmol/ml tissue versus 33.3 +/- 4 pmol/ml tissue in control dogs (P < 0.001), as assessed by using [11C]CGP-12177 (((2S)-4-(3-t-butyl-amino-2 hydroxypropoxy)-benzimidazol-2-one)) and positron emission tomography. In contrast, atropine did not induce any change in Bmax: 33.7 +/- 3.6 pmol/ml tissue. We hypothetized that methyl-quinuclidinyl-benzylate induced the release of norepinephrine from sympathetic nerve terminals, an effect which could be blocked by guanethidine. Guanethidine alone (10 mg/kg) did not change Bmax: 35.5 +/- 6 pmol/ml tissue. Guanethidine + methyl-quinuclidinyl-benzylate did not induce any significant change in Bmax: 31.5 +/- 5.1 pmol/ml tissue. Therefore, it seems likely that methyl-quinuclidinyl-benzylate acts at the presynaptic level, probably inducing the release of norepinephrine which then causes a down-regulation of beta-adrenoceptors.

Animals↗
PubMed1996

Brain functional imaging SPECT in agyria-pachygyria.

Agyria-pachygyria or lissencephaly type I, a diffuse cortical malformation, provides infantile spasms (IS) which are refractory and persisting after the first decade, an age at which IS have disappeared in the other causes. In order to study the functional postnatal development of the lissencephalic cortex, we measured regional cerebral blood flow (rCBF) using SPECT (Single photon emission computed tomography) and 133Xe in 14 children with lissencephaly, aged from 4 months to 12 years (mean = 40 months) compared to normal children of the same age range and to children with cryptogenic IS aged from 3 months to 3 years (mean = 13 months). rCBF was calculated in frontal (FR) and parieto-temporo-occipital (PTO) cortex as well as the ratio FR/PTO. FR/PTO was higher in lissencephalic patients than in controls (P < 0.001) due to higher FR rCBF (P < 0.001), particularly in patients aged less than 3 years. FR/PTO was also higher in lissencephalic patients than in patients with cryptogenic IS (P < 0.001) also due to higher FR rCBF (P < 0.001). The values of FR/PTO and FR rCBF remained stable during the first years of life and did not exhibit any age- or topography-related changes as they do in controls or in patients with cryptogenic IS. There results suggest that the normal process of postnatal development in the brain is lacking in agyria-pachygyria. That could play a role in determining the persistence of epileptic spasms, the specific seizure type of this malformation.

Aging↗
PubMed1996

MR quantification of muscle fatty replacement in McArdle's disease.

McArdle's disease is an energy-dependent disorder of skeletal muscle caused by the inability to break down glycogen. The aim of this study was to quantify fatty replacement in patients with McArdle's disease. Calf and thigh axial spin echo T1-weighted magnetic resonance (MR) images (repetition time 500 ms, echo time 25 ms) were obtained at 0.5 T in nine patients with McArdle's disease (age 51 +/- 16 years, range 26-74) and nine sex- and age-matched healthy subjects (age 52 +/- 16 years, range 29-78) to quantify intramuscular fat. Regions of interest were drawn manually, encompassing the largest cross section of muscle. A fatty replacement index (IF) was determined from histograms of signal in the regions of interest in calf and thigh muscles. In normal subjects, IF = 3.6 +/- 2.8% in calf and 4.9 +/- 2.3% in thigh. In patients, IF = 11 +/- 9.3% in calf and 13.5 +/- 10.4% in thigh, significantly different from IF values in normal subjects (p = .03). IF correlated well with age in patients (p = .03). In older patients, up to 25% of the muscle volume was replaced by fat. Patients with McArdle's disease, usually weakly disabled, exhibit significant muscle fatty replacement on MR images. These findings suggest a progressive muscle loss over time related to the disease process.

Adipose Tissue↗
PubMed1996

Error analysis on parameter estimates in the ligand-receptor model: application to parameter imaging using PET data.

Positron emission tomography and compartmental models allow the in vivo analysis of radioligand binding to receptor sites in the human brain. Benzodiazepine receptor binding was studied using a three-compartmental model and [11C]flumazenil. Four and five parameters were estimated from a single kinetic curve obtained with a multi-injection protocol, and parametric maps of receptor density and of the individual kinetic parameters were created with four-pixel sampling of the experimental images. The coefficient of variation on each estimated model parameter was calculated using the diagonal elements of the covariance matrix. However, these estimates are valid only under some statistical hypotheses which are not always verified with PET data. Thus, in order to verify the validity of the coefficient of variation of each parameter calculated with the covariance matrix, these results have been compared with the more rigorous statistical results provided by a Monte Carlo simulation. The study showed a negligible difference between the results obtained by the two methods for a low noise level in time-concentration curves encountered using large ROIs. However, this bias becomes less negligible when the noise level is high and some estimations of the coefficients of variation were unacceptable (> 100%) with the five-parameter model. Such difficulties did not occur with the four-parameter model which led to parametric images with good quality and acceptable estimates of coefficients of variation (less than 20% in about 75% of the ROIs).

Brain↗