Search PubMed⌕ Search

Biomedical subjects

A Bonnin

Publications and source records attributed to A Bonnin.

At least 55 records · Page 3Linked to original sources

Immunocytochemical localization of neurons expressing 5-HT-moduline in the mouse brain.

The localization of 5-HT-moduline, an endogenous cerebral tetrapeptide (LSAL) which specifically interacts with 5-HT1B receptors (Rousselle et al., 1996; Massot et al., 1996) was examined in mouse brain using an immunocytochemistry technique with a polyclonal anti-peptide antibody highly specific for this tetrapeptide. Highest levels of 5-HT-moduline immunoreactivity were observed in the cerebral cortex including cingulate, retrosplenial, parietal and pyriform cortical areas and in the basal ganglia. Intense immunoreactivity also occurred in the hippocampus, subiculum, various hypothalamic and thalamic nuclei and in some midbrain regions such as the substantia nigra and the superior colliculi. Immunoreactive neurons generally showed intense and extensive labelling of the perikarya and dendritic arborizations with moderate to heavy characteristic deposits of reaction product along plasma membranes and within cytoplasm while the nuclei were devoid of reaction product. The results obtained indicated that 5-HT-moduline immunoreactivity was heterogenously distributed in neuronal structures of mouse brain. The distribution of 5-HT-moduline immunoreactivity closely correlated with that of 5-HT-moduline specific binding sites as visualized by autoradiography (Massot et al., 1996). Moreover, it seems to overlap with the distribution of serotonergic innervation and also with that of 5-HT1B receptors in mouse brain (Boschert et al., 1994; Bruinvels et al., 1994; Chopin et al., 1994; Langlois et al., 1995). These data provide evidence that 5-HT-moduline immunoreactivity is located in cells with the morphological appearance of neurones. Its localization in brain areas which also contain 5-HT1B receptors, is in good agreement with previous demonstrations that this peptide specifically interacts with 5-HT1B receptors to regulate their functional activity and accordingly controls the modulatory activity of the serotoninergic system on various CNS functions.

Animals↗

In-vivo activity and tolerance of conventional formulation versus fat emulsion formulation of amphotericin B in experimental disseminated candidiasis in neutropenic rabbits.

Amphotericin B can cause significant toxicity but this can be reduced by direct dilution into a fat emulsion (Intralipid). To investigate the potential use of amphotericin B diluted in Intralipid, a study was made of its activity in the treatment of subacute disseminated candidiasis in persistently granulocytopenic rabbits, compared with the same dose of amphotericin B diluted in dextrose. Amphotericin-B-fat emulsion was at least as effective as amphotericin-B-dextrose. Amphotericin-B-fat emulsion was significantly more effective than amphotericin-B-dextrose therapy in reducing candida colony counts in both kidney and liver tissues (P < 0.05). Furthermore, amphotericin-B-fat emulsion was found less toxic on the renal function than conventional amphotericin B (P < 0.05). From these experimental results, we conclude that amphotericin-B-fat emulsion (Intralipid) was at least as effective and less toxic than conventional amphotericin B.

Amphotericin B↗

Detection of Cryptosporidium parvum DNA in formed human feces by a sensitive PCR-based assay including uracil-N-glycosylase inactivation.

We developed a PCR-based method that can be used to identify Cryptosporidium parvum in human feces. Fecal oocysts were concentrated by centrifugation on a sodium chloride gradient and filtration on a nitrocellulose filter prior to DNA extraction and PCR amplification of a 452-bp C. parvum-specific DNA sequence with a protocol including dUTP and uracil-N-glycosylase. All samples obtained from naturally infected humans (n = 10), calves (n = 4), and goats (n = 2) were positive. A 100% detection rate was achieved with both formed and solid stools (n = 10) seeded with 1,000 C. parvum oocysts per g. Procedures based on stool concentration by a modified Ritchie method and subsequent oocyst identification by immunofluorescent labeling or acid-fast staining require concentrations of 50,000 to 500,000 oocysts per g to achieve a 100% detection rate with formed stools. The described PCR-based assay thus has a 50- to 500-fold increase in sensitivity compared to those of the methods commonly used to analyze formed feces.

Animals↗

Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery.

PURPOSE: The prognosis of invasive pulmonary aspergillosis (IPA) occurring in neutropenic patients remains poor. We studied whether new strategies for early diagnosis could improve outcome in these patients. PATIENTS AND METHODS: Twenty-three histologically proven and 14 highly probable IPAs in 37 hematologic patients (neutropenic in 36) were analyzed retrospectively. RESULTS: The most frequent clinical signs associated with IPA were cough (92%), chest pain (76%), and hemoptysis (54%). Bronchoalveolar lavage (BAL) was positive in 22 of 32 cases. Aspergillus antigen test was positive in 83% of cases when tested on BAL fluid. Since October 1991, early thoracic computed tomographic (CT) scans were systematically performed in febrile neutropenic patients with pulmonary x-ray infiltrates. This approach allowed us to recognize suggestive CT halo signs in 92% of patients, compared with 13% before this date, and the mean time to IPA diagnosis was reduced dramatically from 7 to 1.9 days. Among 36 assessable patients, 10 failed to respond (amphotericin B [AmB] plus fluorocytosyne, n = 2; itraconazole + AmB, n = 8) and died of aspergillosis. Twenty-six patients were cured or improved by antifungal treatment (itraconazole with or without AmB, n = 22; voriconazole, n = 4). In 15 of 16 cases, surgical resection was combined successfully with medical treatment. Achievement of hematologic response, early diagnosis, unilateral pulmonary involvement, and highest level of fibrinogen value < 9 g/L were associated with better outcome. CONCLUSION: In febrile neutropenic patients, systematic CT scan allows earlier diagnosis of IPA. Early antifungal treatment, combined with surgical resection if necessary, improves IPA prognosis dramatically in these patients.

Antigens, Fungal↗

Technetium-99m sestamibi scintigraphy, magnetic resonance imaging and venous blood sampling in persistent and recurrent hyperparathyroidism.

Surgical treatment for primary hyperparathyroidism (HPT) is effective in 90% of cases. Recurrent or persistent HPT occurs in 10% of cases. Parathyroid imaging is indicated to confirm and locate an abnormal gland before reoperation. The aim of this study was to evaluate whether the combination of 99Tcm sestamibi scintigraphy, MRI and venous blood sampling (VBS) improved the overall sensitivity for abnormal parathyroid gland detection. 18 patients with recurrent or persistent HPT underwent sestamibi scintigraphy (n = 18), MRI (T1 weighted and STIR sequences) (n = 18) and venous blood sampling (n = 12) at different sites (internal jugular veins, innominate veins, and superior vena cava). All patients underwent surgical exploration. MRI yielded positive results in 15 cases (sensitivity 88%), sestamibi scintigraphy in 14 cases (83%) and VBS in 10 cases out of 12 (83%). Combined results of MRI, sestamibi and VBS yielded positive results in 16 cases (94%). The combination of MRI, sestamibi scintigraphy and VBS improved accuracy in detecting abnormal parathyroid glands before reoperation.

Adenoma↗

[Imaging of pituitary adenoma].

Direct visualization of pituitary parenchyma and lesions has been made possible by progress in imaging. CT scan and magnetic resonance imaging, which has become the imaging method of choice in pituitary diseases, allow detection of 2 to 3 mm pituitary microadenomas, with a sensitivity of 60 and 85% respectively. The ability to establish the extent of the tumor using these techniques has made them indispensable to preoperative assessment of macroadenomas. Nevertheless, cavernous sinus involvement is often difficult to evaluate, and the smallest adenomas still escape detection.

Adenoma↗

Genotyping human and bovine isolates of Cryptosporidium parvum by polymerase chain reaction-restriction fragment length polymorphism analysis of a repetitive DNA sequence.

In order to define transmission routes of cryptosporidiosis and develop markers that distinguish Cryptosporidium parvum isolates, we have identified 2 polymorphic restriction enzyme sites in a C. parvum repetitive DNA sequence. The target sequence was amplified by polymerase chain reaction from 100 to 500 oocysts and the amplified product was subjected to restriction enzyme digestion. Typing of 23 isolates showed that 10/10 calf isolates had the same profile. In contrast, 2 patterns were observed among human isolates: 7/13 displayed the calf profile, and 6/13 presented another pattern. The PCR-RFLP assay described here is a sensitive tool to distinguish C. parvum isolates.

Animals↗

Effects of perinatal exposure to delta 9-tetrahydrocannabinol on the fetal and early postnatal development of tyrosine hydroxylase-containing neurons in rat brain.

The exposure of pregnant rats to delta 9-tetrahydrocannabinol (delta 9-THC), the main psychoactive constituent of Cannabis sativa, during the perinatal period affects the gene expression and the activity of tyrosine hydroxylase (TH) in the brains of their offspring at peripubertal and adult ages. In the present work we explored whether these effects also appear during fetal and early neonatal periods, when TH expression plays an important role in neural development. To this end, the mRNA amounts for TH and the amounts and activity of this enzyme, in addition to catecholamine (CA) contents, were analyzed in the brain of fetuses at different gestational days (GD) and of newborns at two postnatal ages, which had been daily exposed to delta 9-THC or vehicle from d 5 of gestation. Results were as follows. The exposure to delta 9-THC markedly affected the expression of the TH gene in the brain of fetuses at GD 14. Thus, the amounts of its mRNA at this age were higher in delta 9-THC-exposed fetuses than in controls. This corresponded with a marked rise in the amounts of TH protein and in the activity of this enzyme at this age. Normalization was found in these parameters at GD16. However, a marked sexual dimorphism in the response of TH gene to cannabinoid exposure appeared from GD18 and was particularly evident at GD21, when TH-mRNA amounts increased in developing female brains, but decreased in developing male brains exposed to delta 9-THC, effects that were mostly prolonged to early postnatal ages. However, these changes did not correspond always with parallel changes in the amounts and activity of TH and in CA contents, as occurred in GD14, suggesting that delta 9-THC would not be affecting the basal capability to synthesize CAs in TH-containing neurons, but would affect the responsiveness of TH gene. We found only a marked increase in the production of L-3,4-dihydroxyphenylacetic acid, the main intraneuronal dopamine metabolite, in female newborns exposed to delta 9-THC. Collectively, our results support the belief that the perinatal exposure to delta 9-THC affects the expression of the TH gene and, sometimes, the activity of this enzyme in brain catecholaminergic neurons in certain critical periods of fetal and early neonatal brain development. These results support the notion that cannabinoids are able to affect the gene expression of specific key proteins for catecholaminergic development, and that these alterations might be the origin of important long-term neurobehavioral effects caused by perinatal cannabinoid exposure at peripubertal and adult ages.

3,4-Dihydroxyphenylacetic Acid↗

Contrast material injection for hepatic helical computed tomography. Comparative study of five protocols.

RATIONALE AND OBJECTIVES: The authors develop and compare contrast material injection protocols suitable for hepatic helical computed tomography. METHODS: One hundred twenty-one patients who underwent contrast-enhanced computed tomography (CT) of the liver with spiral CT imaging were evaluated for enhancement of the liver parenchyma and for post-enhancement attenuation of the aorta and portal vein with iohexol. Patients were assigned randomly to five protocols with different flow rates, volume of contrast material, and scan delays. RESULTS: Mean parenchymal contrast enhancement was statistically significantly higher with protocol 5 (biphasic injection of 100 mL of iohexol 300 (g/100 mL) at a flow rate of 1.5 mL/second followed by 25 mL at 2 mL/second; total iodine load = 37.5 g, with a scan delay of 70 seconds). The highest aortic enhancement and the second highest portal vein enhancement were obtained with this protocol. CONCLUSION: The authors suggest an easily tolerated injection protocol able to ensure high parenchymal liver enhancement and satisfactory aortic and portal vein enhancement. This protocol includes a long scan delay (70 seconds), biphasic low flow injection rate, and a relatively low iodine load.

Adult↗

Perinatal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) leads to changes in opioid-related behavioral patterns in rats.

Perinatal exposure to cannabinoids has been shown to elicit central nervous system impairment in rodents. This includes changes in monoaminergic and neuropeptidergic activities. We have examined the effect of perinatal exposure to delta 9-tetrahydrocannabinol (delta 9-THC) on sensitivity to radiant heat in both male and female rats on days 24, 50 and 70 after birth. Animals used in this experiment were born of mothers that received delta 9-THC (5 mg/kg; p.o.) daily from day 5 of pregnancy until day 24 after offspring birth. delta 9-THC perinatally treated males, but not females, showed higher baseline tail-flick values than controls on days 24 and 50 (Day 24, controls: 3.88 +/- 0.18 s; delta 9-THC group: 4.51 +/- 0.18 s; Day 50, controls: 3.16 +/- 0.17 s; delta 9-THC group: 4.38 +/- 0.38 s). In addition, adult males were found to be tolerant to the analgesic effect of morphine (5 mg/kg; i.p.; % analgesia: controls 71.75 +/- 10.20; delta 9-THC 35.5 +/- 10.59). Moreover, recently weaned pups that received 5 mg/kg of naloxone (i.p.) developed an opioid-like withdrawal syndrome. Taken together all these results suggest that perinatal treatment with delta 9-THC may alter the functionality of the endogenous opioid system, including changes in pain sensitivity.

Analgesics↗

The prenatal exposure to delta 9-tetrahydrocannabinol affects the gene expression and the activity of tyrosine hydroxylase during early brain development.

We have previously reported that the exposure of pregnant female rats to delta 9-tetrahydrocannabinol (THC) during the perinatal period affected the gene expression and the activity of tyrosine hydroxylase (TH) in the brain of their male offspring. Those studies were done in animals perinatally exposed to THC but tested at peripubertal and adult ages. In the present work, we explored whether these effects also appear during early fetal brain development, when TH expression plays an important role in neuronal development. To this end, TH-mRNA concentrations were measured by Northern blot analysis with a specific TH probe in the brain of fetuses at gestational days 14 and 16 which had been prenatally exposed to THC or vehicle from day 5 of gestation. In parallel, measurements of TH activity and catecholamine contents by HPLC were also done. The results obtained were as follows. The prenatal exposure to THC markedly affected the expression of the TH gene in the brain of fetuses at gestational day 14. Thus, the amounts of TH-mRNA at this age were higher (2-fold) in THC-exposed fetuses than in controls. This corresponded with a marked increase in the activity of this enzyme (3-fold) at this age. Normalization was found in both parameters at gestational day 16. In summary, the prenatal exposure to THC affected the expression of the TH gene and the activity of this enzyme in brain catecholaminergic neurons during early fetal brain development. These results support the notion that cannabinoids are able to act at the level of the gene expression of specific key proteins for brain development.

Animals↗

Hepatic artery thrombosis after liver transplantation: diagnosis with spiral CT.

OBJECTIVE: The purpose of this study was to prospectively evaluate spiral CT with maximum-intensity projection in the diagnosis of hepatic artery thrombosis in patients with liver transplants. SUBJECTS AND METHODS: Thirty liver transplant recipients (19 men, 11 women; mean age, 49 years) underwent Doppler sonography and spiral CT with maximum-intensity projection to evaluate both hepatic parenchyma and hepatic vessels. In five cases, these examinations were followed by angiography for suspected hepatic artery thrombosis. RESULTS: Among the 30 patients, results of both Doppler sonography and spiral CT were abnormal in five patients. In all five patients, Doppler sonography revealed an absence of intrahepatic arterial signal (sensitivity, 100%). Spiral CT showed the hepatic artery to be patent from its origin to the anastomosis and then occluded distally in four patients and showed occlusion of the entire hepatic artery in one patient (sensitivity, 100%). Aortography and/or selective arteriography of the celiac axis confirmed the diagnosis of hepatic artery thrombosis in all five cases. The other 25 patients had a normal clinical outcome, 24 with normal findings on Doppler sonograms (specificity, 96%), and 23 with normal findings on spiral CT. Two patients had false-positive CT studies because of technical failures (specificity, 92%). CONCLUSION: Spiral CT with maximum-intensity projection is highly accurate in identifying hepatic artery thrombosis after liver transplantation.

Adult↗

[Invasive pulmonary aspergillosis in neutropenic patients. Analysis of a series of 36 cases: contribution of thoracic scanners and itraconazole].

In neutropenic patients, one way of improving invasive pulmonary aspergillosis (IPA) prognosis is an earlier initiation of the antifungal treatment. We report our experience with 36 cases of IPA in 35 patients with haematological malignancies. When aspergillosis was diagnosed, all but 2 patients were neutropenic (PMN < 500; median duration = 20 days). The most frequent clinical signs were cough (100%), chest pain (78%) and haemoptysis (58%). Before the diagnosis of IPA, Aspergillus antibody test was positive in 60% of cases. A thoracic CT-scan was performed in 23 patients and demonstrated highly suggestive images in 22 cases (96%) with presence of CT halo sign (n = 13) or CT air-crescent sign (n = 9). Moreover, Aspergillus antigen test was positive in 13 of 28 tested patients. IPA diagnosis was determined to be definite in 23 cases and probable or possible in 13 cases. Thirty-five patients were treated: in 3 cases with amphotericin B (2 failures) and in 32 cases with itraconazole (7 failures and 25 successes or improvements). In 7 cases (including 5 emergencies) surgical resection was successfully combined with the medical treatment. In neutropenic patients with fever, we consider that thoracic CT-scan and repeated biological tests (Aspergillus antibody and antigen tests) can be used to establish the diagnosis of aspergillosis. Early treatment with itraconazole and surgical resection appears to improve prognosis.

Adult↗

Terminal protein-primed DNA amplification.

By using appropriate amounts of four bacteriophage phi 29 DNA replication proteins--terminal protein, DNA polymerase, protein p6 (double-stranded DNA-binding protein), and protein p5 (single-stranded DNA-binding protein)--it has been possible to amplify limited amounts of the 19,285-bp-long phi 29 DNA molecule by three orders of magnitude after 1 hr of incubation at 30 degrees C. Moreover, the quality of the amplified material was demonstrated by transfection experiments, in which infectivity of the synthetic (amplified) phi 29 DNA, measured as the ability to produce phage particles, was identical to that of the natural phi 29 DNA obtained from virions. The results presented in this paper establish some of the requisites for the development of isothermal DNA amplification strategies based on the bacteriophage phi 29 DNA replication machinery that are suitable for the amplification of very large (> 70 kb) segments of DNA.

Bacillus Phages↗

Possible role of the cytochrome P450-linked monooxygenase system in preventing delta 9-tetrahydrocannabinol-induced stimulation of tuberoinfundibular dopaminergic activity in female rats.

The administration of delta 9-tetrahydrocannabinol (THC) or related cannabinoids markedly affected neurobehavioral and neuroendocrine indices in male rodents but usually failed to affect those indices in females. We examined whether inhibition of the cytochrome P450-linked monooxygenase system in female rats is able to elicit the effects of THC on one of the most characteristic targets of cannabinoid action, tuberoinfundibular dopaminergic neurons, whose activity is known to increase after cannabinoid exposure in males. It was found that the administration of THC to ovariectomized rats acutely replaced with estradiol (to discard problems derived from differences in the estrogenic status) did not affect either dopamine and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents and tyrosine hydroxylase activity in the medial basal hypothalamus or the density of D2-dopaminergic receptors in the anterior pituitary. However, the administration of THC to estrogen-replaced ovariectomized rats that had been pretreated with two separately administered inhibitors of cytochrome P450, piperonyl butoxide or metyrapone, significantly increased DOPAC content in the medial basal hypothalamus, with no changes in the other parameters. Collectively, these results indicate that the metabolism of THC to inactive compounds might play a protective role in females, counteracting the effects of this cannabinoid on tuberoinfundibular dopaminergic activity because pharmacological inhibition of cytochrome P450-linked monooxygenase system elicited a significant stimulation of these neurons by THC.

3,4-Dihydroxyphenylacetic Acid↗

Changes in tyrosine hydroxylase gene expression in mesencephalic catecholaminergic neurons of immature and adult male rats perinatally exposed to cannabinoids.

We have previously reported that the perinatal exposure of pregnant rats to cannabinoids affected the activity of tyrosine hydroxylase (TH) in the striatum of their male offspring at peripubertal ages. In the present work, we examined whether this effect was accompanied by modifications in TH gene expression. The amount of TH-mRNA--measured by Northern blot analysis with a specific TH probe--in the mesencephalon of 15- and 20-day-old male rats perinatally exposed to hashish extracts was higher than that measured in aged-matched controls. No differences appeared at 30 and 40 days after birth, a priori because they correspond to ages after the hashish withdrawal occurring on day 24 after birth. However, a significant decrease in the amount of TH-mRNA was observed in adult animals (70 days of life) perinatally exposed to hashish. The increase in TH-mRNA concentrations observed in hashish-exposed 15-day-old animals corresponded to an increase in the amount of TH protein, measured by Western blot analysis, in the mesencephalon, with no differences in the striatum. However, the amount of TH protein in both tissues was not modified by perinatal hashish treatment in adult animals, where TH-mRNA amounts had been decreased. In summary, perinatal cannabinoid exposure enhances the expression of the TH gene in mesencephalic catecholaminergic neurons during early peripubertal ages, coinciding with hashish treatment. Normality was found after hashish withdrawal and an interesting decrease in the amount of TH-mRNA appeared in adulthood, although with no reflection on the amount of TH protein.

Animals↗

[Spontaneous unilateral adrenal hematomas. 10 cases].

Spontaneous unilateral adrenal haematoma is a very rare condition. We report 10 such cases in which the pathological examination confirmed the diagnosis and for which computed tomography (CT) (n = 10) and magnetic resonance imaging (MRI) (n = 5) were performed. The diagnosis of this condition was difficult because there was no specific clinical setting nor any specific functional disorder. CT most often revealed a large mass (> 4 cm) of one of the adrenal glands, most often displaying soft-tissue attenuation and thus not specific. However, MRI suggested the diagnosis, showing foci of hypersignal on T1-weighted images and heterogeneous masses on T2-weighted images, predominantly displaying hypersignal and not enhancing, after Gd-DTPA dynamic perfusion study. Pathologic examination of the surgical specimen confirmed either idiopathic haematoma (n = 5) or haematoma possibly associated with a small benign tumour (n = 5). The diagnosis of adrenal haematoma must be considered when an unilateral isolated large adrenal mass is discovered in an asymptomatic patient. MRI with Gd-DTPA dynamic perfusion study has to be performed and one may suggest waiting and repeat imaging (so as to follow decrease in size or signal changes) in order to avoid surgery.

Adrenal Gland Diseases↗