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A Prigent

Publications and source records attributed to A Prigent.

At least 19 recordsLinked to original sources

In vivo upregulation of endogenous NGF in the rat brain by the alpha2-adrenoreceptor antagonist dexefaroxan: potential role in the protection of the basalocortical cholinergic system during neurodegeneration.

We have previously reported that the alpha2-adrenoceptor antagonist dexefaroxan protects against the degeneration of nucleus basalis magnocellularis (NbM) cholinergic neurons following cortical devascularization in the adult rat. Since nerve growth factor (NGF) is critical to the survival of NbM cholinergic neurons in the adult brain and its synthesis is known to be regulated by noradrenergic mechanisms, we examined whether the protective effect of dexefaroxan in the devascularization model was associated with regional induction of NGF biosynthesis. Dexefaroxan or vehicle was administered to rats via subcutaneous minipumps for 28 days following devascularization or sham operation procedures. In vehicle-treated devascularized rats, NGF protein levels in the cortex were increased at 5 days but had normalized by 2 weeks postoperation; NGF levels in NbM remained unchanged during this time. In dexefaroxan-treated devascularized rats, increases in NGF protein levels (2-fold) and immunoreactivity were maintained in both the cortex and NbM over the entire 28-day postoperation period; these increases were coincident with changes in functional markers characteristic of NGF's actions, including increases in choline acetyltransferase (ChAT), p75 and TrkA immunoreactivities, and a preservation of NbM cholinergic cell numbers. Dexefaroxan also increased NGF protein levels in sham-operated rats, but without any significant consequence to the otherwise normal NbM cholinergic phenotype in these animals. Results indicate that activation of endogenous NGF systems could contribute to the cholinergic protective effect of dexefaroxan in the cortical devascularization model, and provide further support for a potential therapeutic utility of dexefaroxan in neurodegenerative diseases where central cholinergic function is progressively compromised.

Acetylcholine↗

Animal models of Parkinson's disease in rodents induced by toxins: an update.

The development of animal models of Parkinson's disease is of great importance in order to test substitutive or neuroprotective strategies for Parkinson's disease. Such models should reproduce the main characteristics of the disease, such as a selective lesion of dopaminergic neurons that evolves over time and the presence of neuronal inclusions known as Lewy bodies. Optimally, such models should also reproduce the lesion of non-dopaminergic neurons observed in a great majority of patients with Parkinson's disease. From a behavioral point of view, a parkinsonian syndrome should be observed, ideally with akinesia, rigidity and rest tremor. These symptoms should be alleviated by dopamine replacement therapy, which may in turn lead to side effects such as dyskinesia. In this review, we analyze the main characteristics of experimental models of Parkinson's disease induced by neurotoxic compounds such as 6-hydroxydopamine, MPTP and rotenone. We show that, whereas MPTP and 6-hydroxydopamine induce a selective loss of catecholaminergic neurons that in most cases evolves over a short period of time, rotenone infusion by osmotic pumps can induce a chronically progressive degeneration of dopaminergic neurons and also of non-dopaminergic neurons in both the basal ganglia and the brainstem.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The basics of renal imaging and function studies.

Many radiotracers are available for kidney studies. They are classified into glomerular tracers (DTPA, EDTA), tubular tracers (OIH, MAG3) and cortical tracers (DMSA, GHA). Renal function is best assessed by glomerular filtration rate. Camera studies provide a relative function assessment, whereas clearance techniques provide a precise and reliable assessment of absolute renal function. The combination of both therefore gives a comprehensive study of glomerular function. Attempts to assess absolute function from camera studies only resulted in gross inaccuracy. Tubular tracers have a higher extraction rate. This could be used to estimate renal plasma flow (by assessing the effective renal plasma flow), or to determine relative function when renal function is low, or to study the urine flow in the urinary tract. Cortical tracers provide a high imaging quality. They are more adapted to infection assessment and relative function measurements. This paper reviews the most commonly used tracers and their relationship with renal physiology. Techniques for camera static and dynamic studies and plasma and urinary clearances are detailed. Procedures follow the recommendations of the most recent international consensus conferences on the topics.

Humans↗

[Respiratory bronchiolitis with diffuse interstitial lung disease].

Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) is a disease that exclusively affects cigarette smokers. Long-term prognosis is good with cessation of smoking, in combination or not with corticosteroid therapy. We report here the case of a 50-year-old patient with RB-IL diagnosed on lung biopsy. Despite corticosteroid and cyclophosphamide therapy, no functional or radiological improvement was obtained. In contrast, cessation of smoking was associated with the disappearance of the infiltrative opacities. Clinical and radiological parameters remained stable during follow-up (13 years) while a moderate obstructive pattern appeared.

Adrenal Cortex Hormones↗

Clinical impact of (18)F-FDG PET in thyroid carcinoma patients with elevated thyroglobulin levels and negative (131)I scanning results after therapy.

UNLABELLED: 18F-FDG PET has been shown to effectively detect differentiated thyroid carcinoma (DTC) metastases with impaired iodine-trapping ability. This article evaluates the potential contribution of FDG PET in the follow-up of patients with differentiated thyroid carcinoma, elevated thyroglobulin (Tg) levels, and negative whole-body scan results obtained after high doses of (131)I. METHODS: We prospectively assessed the ability of FDG to detect metastases in 37 DTC patients who had undergone total thyroidectomy and radioactive ablation and presented with persistent disease, as assessed from elevated Tg levels and negative results of whole-body scans performed after therapeutic doses of (131)I. Additional conventional imaging procedures were performed to detect residual disease, and the patients were divided into 2 groups: group 1, with positive conventional imaging findings (n = 10), and group 2, with negative conventional imaging findings (n = 27). RESULTS: FDG PET showed positive findings in 28 patients and accurately localized tumor sites in 89% of them. In group 1, FDG PET confirmed 17 of 18 previously known tumor sites and detected 11 additional sites. In group 2, FDG PET findings were positive in 19 of 27 patients with no previously detected metastases. PET was effective for both low- and high-stage tumors. The FDG data led to a change in the clinical management of 29 of 37 patients with further surgical resection in 23 patients, 14 of whom achieved disease-free status, and external radiation therapy in 4 patients. CONCLUSION: FDG PET is able to detect metastases undetected by (131)I posttherapy whole-body scanning in patients with elevated Tg levels. It should be proposed as a first-line investigation in patients with persistent disease but negative findings on (131)I whole-body scans after treatment.

Adult↗

Can dimercaptosuccinic acid renal scintigraphy be used to assess global renal function?

Use of dimercaptosuccinic acid (DMSA) has been proposed for the assessment of both relative and absolute renal function. Our aim was to test whether the renal absolute DMSA uptake (ADU) can reflect the absolute renal function from a theoretical point of view. A simple model was used to compute the ADU in the case of injury to one kidney. It was found that the assumption that ADU correctly reflects the absolute renal function may lead to a more than 50% overestimation of the function of both the normal and the impaired kidney. The later the measurement is made and the more impaired is the kidney, the more important is the error. Although DMSA can reliably quantify the relative renal function, it should not be used to assess absolute renal function lest major overestimation should occur.

Humans↗

Distribution of semaphorin IV in adult human brain.

The semaphorins comprise a family of secreted and membrane bound proteins that influence development of the nervous system as well as non-neural organs. H.SemaIV was originally isolated from a homozygously deleted region involving a subset of small cell lung cancers, a neuroendocrine derived neoplasm. To investigate H.SemaIV expression, specific polyclonal antibodies directed against a unique polypeptide (amino acids 758-773) were developed and their specificity confirmed. In cell lines, H.SemaIV staining was observed in cytoplasmic granules. In the normal adult human brain, we noted three general characteristics of H.SemaIV expression. H.SemaIV was strongly present in specific nuclei or in neuronal regions arranged in defined subnuclear structures. It was also present in neurons but not glial cells or ependymocytes. Lastly, H.SemaIV was not present in cell bodies, but rather in fibers and nerve terminals. Interestingly, an altered pattern of staining was detected in brains of three patients with Alzheimer's disease.

Adult↗

Quantitation in planar renal scintigraphy: which mu value should be used?

The attenuation coefficient value mu used by different authors for quantitation in planar renal scintigraphy varies greatly, from the theoretical value of 0.153 cm-1 (appropriate for scatter-free data) down to 0.099 cm-1 (empirical value assumed to compensate for both scatter and attenuation). For a 6-cm-deep kidney, such variations introduce up to 30% differences in absolute measurement of kidney activity. Using technetium-99m phantom studies, we determined the mu values that would yield accurate kidney activity quantitation for different energy windows corresponding to different amounts of scatter, and when using different image analysis approaches similar to those used in renal quantitation. With the 20% energy window, it was found that the mu value was strongly dependent on the size of the region of interest (ROI) and on whether background subtraction was performed: the mu value thus varied from 0.119 cm-1 (loose ROI, no background subtraction) to 0.150 cm-1 (kidney ROI and background subtraction). When using data from an energy window that could be considered scatter-free, the mu value became almost independent of the image analysis scheme. It is concluded that: (1) when performing background subtraction, which implicitly reduces the effect of scatter, the mu value to be used for accurate quantitation is close to the theoretical mu value; (2) if the acquired data were initially corrected for scatter, the appropriate mu value would then be the theoretical mu value, whatever the image analysis scheme.

Humans↗

Consensus report on quality control of quantitative measurements of renal function obtained from the renogram: International Consensus Committee from the Scientific Committee of Radionuclides in Nephrourology.

Among all the physiological indices that can be quantified using renography, measurement of renal function is the most basic. These measurements are used to make critical clinical management decisions and, as such, their reliability needs to be quality assured. This article seeks to address each aspect of the renography procedure, with particular emphasis on the effect on measurement of relative renal function. Estimation of individual kidney function is mentioned, but only briefly. A consensus approach was adopted, overseen, and directed by a chairman appointed by the Scientific Committee of the International Radionuclides in Nephro-Urology Group. The chairman selected the panel of experts from eight different countries based on their practical experience in the field. Where evidence exists to support the various recommendations it is given. Otherwise, the stated guidance represents the considered opinion of a body of experts, based on long experience and unpublished data. Some necessary compromises were made to account for the fact that renography is seldom performed solely with the purpose of measuring relative renal function. The technicalities of renography have always been a source of debate in nuclear medicine, which is reflected by the fact that a consensus could simply not be reached on a small number of issues. The structure of the report ensures that these are clearly indicated. This should serve to highlight gaps in our current knowledge, thus helping to direct future research. It is envisaged that the recommendations will be revised on a 2-year cycle to ensure that they remain up to date. An "open" process will be used to encourage participation and ownership. It is hoped that promotion of these guidelines, suitably complemented by audit processes, will raise standards in the practice of gamma camera renography.

Adult↗

Concordance between dobutamine Doppler tissue imaging echocardiography and rest reinjection thallium-201 tomography in dysfunctional hypoperfused myocardium.

OBJECTIVE: To evaluate the efficiency of the new technique colour Doppler tissue imaging (DTI) by studying the concordance between dobutamine DTI, standard grey scale echocardiography (SE), and rest-reinjection TI-201 tomography (TI) in dysfunctional myocardium. PATIENTS: 23 patients with chronic wall motion abnormalities and proven coronary artery disease (> 70% diameter stenosis of at least one major coronary artery at angiogram). METHODS: The contractile reserve and the resting perfusion characteristics of dysfunctional myocardial segments were assessed with low dose dobutamine SE and/or DTI (2.5 up to 20 gamma/kg/min) and TI on a semiquantitative basis. The DTI or SE data were separately compared with TI, on the basis of a 13 segment ventricular model. The resulting score of combined DTI and SE was also compared with TI. Finally the results obtained from DTI were compared with SE. RESULTS: A total of 142 severely hypokinetic or akinetic segments were visualised. The viability study was feasible in 127 (89%) and 121 (85%) segments with DTI and SE, respectively. TI detected viability more frequently than DTI (84 v 61, p < 0.001) and SE (80 v 50, p < 0.001). However, as many viable segments were detected with combined DTI and SE as with TI (78 v 84, NS). The kappa values between TI and SE, DTI or combined SE and DTI were 0.38, 0.45, and 0.57, respectively, and increased to 0.52 and 0.76, respectively, for SE and DTI versus TI when mid-anterior and mid-inferior segments only were considered. The kappa value between SE and DTI was 0.34. CONCLUSIONS: DTI is a helpful adjunct to SE, when using low dose dobutamine. This combination revealed as many viable segments as TI and showed a better agreement than DTI or SE alone for the assessment of myocardial viable segments evidenced by TI.

Adrenergic beta-Agonists↗

Enalapril plus frusemide MAG3 scintigraphy in hypertensive patients with atherosclerosis and moderate renal insufficiency.

We performed a retrospective study on 26 patients with moderate renal failure (mean GFR = 51 +/- 21 ml min-1 1.73 m-2), hypertension and atherosclerosis. Apart from three patients who had completely normal renal Doppler ultrasonography, all patients underwent renal angiography. Three groups of kidneys with different atherosclerotic renal artery involvement were identified: Group 1, 24 kidneys with no renal artery stenosis (RAS); Group 2, 18 kidneys with mild (> 25% and < 50% diameter) RAS; and Group 3, 10 kidneys with moderate (> 50% diameter) RAS. We used a two-day protocol with frusemide plus enalapril 99Tcm-MAG3 scintigraphy. The mean parenchymal transit time (MPTT), time to the maximum activity (time to peak) of the renal curve (Tmax), residual activity and split renal uptake were evaluated. The measured parameters did not differ before and after enalapril in Group 1 or in Group 2. In Group 3, MPTT and residual activity differed significantly (P < 0.025) before and after enalapril. The Tmax before and after enalapril, MPTT before and after enalapril and residual activity after enalapril differed significantly (P < 0.05) between Groups 1 and 3 and between Groups 2 and 3. Threshold values were obtained to maximize diagnostic accuracy. The Tmax, MPTT and residual activity after enalapril gave satisfactory results, and MPTT performed best with a 75% positive predictive value and a 98% negative predictive value for the diagnosis of renal artery stenosis. We conclude that MPTT, measured after enalapril administration, is a useful parameter to detect renal artery stenosis in patients with hypertension, atherosclerosis and moderate renal insufficiency.

Adult↗

Is differential regulation of mitochondrial transcripts in Parkinson's disease related to apoptosis?

A cDNA library of substantia nigra pars compacta from a patient with Parkinson's disease (PD) was differentially screened with probes of normal and parkinsonian substantia nigra enriched in neuronal transcripts. Fifty-eight clones were isolated; 39 were subunits of mitochondrial respiratory complexes I and IV. Parallel screening of a cDNA library derived from normal substantia nigra confirmed differential representation of the transcripts in the substantia nigra pars compacta. In situ hybridization in postmortem brain from parkinsonian and control subjects, with representative complex I and complex IV probes, showed increased labeling, at the cellular level, of the complex I subunit ND1 in neurons of the lateral substantia nigra, where cell death is greatest in PD, but decreased labeling in the medial substantia nigra where fewer cells die. Expression of a complex IV subunit, COXI, increased, however, in both parts of the structure. Increased expression of ND1 and COXI was also observed in nerve growth factor-differentiated PC12 cells undergoing apoptosis induced by tumor necrosis factor-alpha, suggesting that the differential regulation of certain mitochondrial mRNAs may be associated with this form of cell death. This in vitro model of apoptosis is potentially relevant to the death of dopaminergic neurons in PD, because these cells express the tumor necrosis factor-alpha receptor, and neighboring microglial cells in patients synthesize the cytokine.

Aged↗

Prostaglandin E2 production by uterine stromal cell line UIII: regulation by estradiol and evidence of an ethanol action.

We have recently established a uterine stromal cell line (UIII). The purpose of the present study was to determine whether these cells have retained the ability to produce and release prostaglandins after several passages and whether this production was regulated. UIII cells, grown in basal conditions, released a very low amount (40.6 +/- 2.9 pg/24h/10(6) cells) of prostaglandin E2 (PGE2) though cellular content was more elevated (192 +/- 23 pg/10(6) cells). Ethanol increased the cellular content but decreased the release of PGE2, whereas estradiol 17 beta (E2) increased it in a dose-dependent manner, but had no effect on the cellular content. The PGE2 release by cells grown in medium containing 10 microM arachidonate (AA) reached 1.39 +/- 0.05 ng/24h/10(6) cells, and was further increased to 2.1 +/- 0.1 ng/24 h/10(6) cells by the addition of ethanol. Under the latter condition, E2 was ineffective. This study also showed that UIII cells expressed an immunoreactive pancreatic type 14 kD PLA2. A substantial increased 14 kD PLA2 expression was observed in ethanol-treated cells, suggesting that ethanol-effect on prostaglandin production might be partly mediated by PLA2 increase. Medium supplementation with arachidonate also resulted in a significant increase of intracellular 14 kD PLA2 expression. The present results showed that uterine stromal UIII cells have retained the enzymatic machinery to produce PGE2. Moreover these data demonstrate that ethanol and E2 affect differently uterine PGE2 production.

Animals↗

[Measurement of global and separate renal blood flow using cine-computed tomography].

EBCT flow study offer a promising new approach to measure the renal blood flow. In vitro and in vivo studies were performed to resolve methological problems such as checking the linear relation between contras concentration and Hounsfield units or determination of the Treshold used for the mapping. First measurements of renal volumes and flow performed in patients showed expected values.

Aged↗