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Biomedical subjects

A Bonnin

Publications and source records attributed to A Bonnin.

At least 19 recordsLinked to original sources

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

Cross-sectional study of the susceptibility of Candida isolates to antifungal drugs and in vitro-in vivo correlation in HIV-infected patients.

OBJECTIVES: To investigate (1) the frequency of clinical resistance to oral polyenes or azole treatment for oral candidiasis, (2) the frequency of resistant in vitro Candida strains, (3) the relationship between the susceptibilities of in vitro Candida species and in vivo status in HIV patients. DESIGN: Prospective cross-sectional study. SETTING: Tertiary care clinic at Bocage Hospital, Dijon, France. PATIENTS: HIV-infected patients with and without oral candidiasis. INTERVENTIONS: Clinical examination, oral swab for mycologic investigations. MAIN OUTCOME MEASURES: Clinical diagnosis of oral candidiasis, identification of the antifungal treatment given within the previous month, identification of Candida species, antimycogramm and determination of the minimal inhibitory concentration (MIC) for fluconazole, and measurement of T-helper cell count. RESULTS: Within a 2-month period, 154 HIV-infected patients were studied: 46 heterosexuals, 51 intravenous drug users (IVDU), 52 homosexuals and five blood transfusion recipients. The percentages of patients with oral candidiasis were: 41, 80, 44 and 20%, respectively (P < 0.05); the mean T-helper cell counts were 200, 135, 210 and 238 x 10(6)/l cells, respectively (P < 0.05). Twenty-two patients (14.3%) had received recent azole treatment and 29 (18.8%) recent oral polyene treatment. Among the 84 patients with and the 70 patients without oral candidiasis, 78 and 28 Candida strains were isolated, respectively. Although Candida albicans represented the majority of Candida species (88 strains, 83%), the non-albicans strains were isolated more frequently in patients who had received recent antifungal treatment. No strains were resistant to ketoconazole, miconazole or econazole; however, six (5.6%), 16 (15%) and 10 (9.5%) were intermediately susceptible to the three drugs, respectively. Twelve (13.6%) of the 88 C. albicans, five of the six C. (Torulopsis) glabrata, one of the five C. tropicalis and all three C. krusei strains were resistant to fluconazole. These resistant strains were separated as follows: 41.1% of C. albicans strains resistant to fluconazole were isolated from patients who had received recent azole therapy, 17.6% from patients who received recent oral polyene, and 3.7% from patients who had not received any recent antifungal treatment (P = 0.004). The mean MIC of these three categories of isolates were 3.6, 1.6 and 0.6 mg/l, respectively (P = 0.06). CONCLUSIONS: Oral candidiasis and fluconazole-resistant Candida isolates are more frequently found in IVDU. Treatments using azoles select non-albicans strains and are associated with decreased susceptibilities of C. albicans strains to fluconazole in particular. These findings show that prolonged azole treatment in severely immunocompromised patients should be avoided.

AIDS-Related Opportunistic Infections

MR imaging and CT of surgical materials currently used in ophthalmology: in vitro and in vivo studies.

PURPOSE: To assess methods of imaging postoperative changes in the eyeball by performing in vitro and in vivo studies of the main solid and fluid materials used in the treatment of cataract and retinal detachment. MATERIALS AND METHODS: The samples were analyzed in vitro with computed tomography (CT) and magnetic resonance (MR) imaging performed at 0.5 T. In vivo studies were performed in seven patients who underwent lens implantation (n = 1), scleral buckling with hydrogel or silicone (n = 6), and retinopexy with gas or silicone oil (n = 6). The attenuation and signal intensity of the materials were compared with values for anatomic structures. RESULTS: Lens implants were difficult to visualize. Each scleral buckling and retinopexy material was easily differentiated from the others and from anatomic structures at both CT and MR imaging. CONCLUSION: Postoperative CT or MR imaging may be useful after retinal detachment surgery, particularly when ultrasound is not reliable after intravitreous gas-fluid interchange.

Eye

Silent necrosis of a pituitary corticotroph adenoma revealed by timely magnetic resonance imaging: a cause of spontaneous remission of Cushing's disease.

Spontaneous necrosis of a corticotroph adenoma is rare and is a very unlikely way of curing Cushing's disease. We report hereafter a case where magnetic resonance imaging of the pituitary provided clear evidence of the event. Successive and timely pituitary magnetic resonance imaging in this patient showed first a typical microadenoma as a well-limited mass with a low signal intensity before the necrosis, then a bright signal before gadolinium injection in the T1-weighted image at the time of the event and, finally, the aspect of an empty sella turcica with a small arachnoidocele 1 year later. The necrosis of a corticotroph adenoma is more frequent in macro- than in microadenomas, and is usually heralded by headache and visual disturbances. In this case, pituitary necrosis was entirely asymptomatic, and cured the patient as well as the surgeon's knife would have. Nevertheless, this exceptional occurrence does not rule out the possibility of a recurrence.

Adenoma

A new antigen of Cryptosporidium parvum micronemes possessing epitopes cross-reactive with macrogamete granules.

Three monoclonal antibodies (mAbs) raised against purified excysted oocysts and sporozoites of Cryptosporidium parvum reacted in an immunofluorescent assay with antigens located at the apical pole of the sporozoites. On Western blots of oocyst extract, an antigen of 100 kDa was recognized by the three mAbs. Periodic acid treatment abolished this reactivity, suggesting that the corresponding epitopes are carbohydrates. As determined by immunoelectron microscopy, the three mAbs reacted with micronemes in sporozoites and merozoites and recognized a heterogeneous population of granules in the developing macrogametes. Gold particles were also detected in the parasitophorous vacuole of the macrogametes and sporulating oocysts. The detection of a microneme antigen in a family of macrogamete granules has not previously been reported in coccidia. The significance of this observation and the nature of these macrogamete inclusions are discussed.

Animals

delta 9-Tetrahydrocannabinol affects mesolimbic dopaminergic activity in the female rat brain: interactions with estrogens.

In this work, we studied the possible estrogenic modulation of the effects of delta 9-tetrahydrocannabinol (THC) on mesolimbic dopaminergic activity, by examining the effects of an acute dose of this cannabinoid: (i) during the estrous cycle; (ii) after ovariectomy, chronic estrogen-replacement and tamoxifen (TMX)-induced blockade of estrogenic receptors; and (iii) combined with a single and physiological injection of estradiol to ovariectomized rats. THC significantly decreased the density of D 1 dopaminergic receptors and non-significantly increased the L-3,4-dihydroxyphenylacetic acid (DOPAC) content in the limbic forebrain of ovariectomized rats chronically replaced with estrogens. The decrease in D 1 receptors was also produced by TMX, whereas the coadministration of both THC and TMX did not lead to a major decrease. In addition to the trend of THC increasing DOPAC content, this cannabinoid was also able to increase the ratio between DOPAC and dopamine, although this last effect only occurred after coadministration of THC and TMX, which had been ineffective administered individually. All these effects were not seen when THC was administered to normal cycling rats during each phase of estrous cycle and to ovariectomized rats without chronic estrogen replacement or only submitted to a single and acute dose of estradiol. This observation might be related to the fact that the density of limbic cannabinoid receptors increased in chronic estrogen-replaced ovariectomized rats versus normal cycling, ovariectomized or acutely estrogen-treated ovariectomized rats. Interestingly, THC administration in ovariectomized rats was followed by a slight, although significant, increase in tyrosine hydroxylase activity, which was also observed after coadministration of THC with a short-time and acute dose of estradiol. In summary, THC stimulated the presynaptic activity of mesolimbic dopaminergic neurons, but accompanied by a decrease in their postsynaptic sensitivity. These effects did not appear in normal cycling rats being only evident after ovariectomy and chronic estrogen replacement, which might be related to changes in binding characteristics of cannabinoid receptors in this area. Moreover, some of them appeared after TMX-induced blockade of estrogenic cytosolic receptors, which likely suggests the existence of a certain estrogenic modulation of the actions of THC on mesolimbic neurons. On the contrary, coadministration of THC with a single and shortly tested dose of estradiol was always ineffective in modifying THC effects.

3,4-Dihydroxyphenylacetic Acid

Efficacy and tolerance of an amphotericin B lipid (Intralipid) emulsion in the treatment of candidaemia in neutropenic patients.

The efficacy and tolerance of a new amphotericin B lipid emulsion (AmB-IL) in which amphotericin B was diluted in a lipid solution for parenteral nutrition (Intralipid) was assessed in fourteen episodes of candidaemia occurring in neutropenic patients. The strains isolated were Candida krusei (nine cases), Candida albicans (three cases), Candida parapsilosis (one case) and Candida lusitaniae (one case). An AmB-IL was administered at a mean dosage of 1.18 mg/kg/day (range 0.73-1.55) for 22 days (range 6-62). Flucytosine was added to AmB-IL in 12 patients (mean duration 10.6 days). Chills were noted in only 3/306 infusions of AmB-IL. A mild increase of serum creatinine level from 9.3 +/- 3 mg/L (baseline) to 10.9 +/- 3 mg/L (after completion of AmB-IL) and mild decrease of creatinine clearance from 83 +/- 28 mL/min to 56 +/- 21 mL/min were observed. These changes did not correlate with either daily or total dose of AmB-IL or length of therapy. Seven patients were cured and six improved (patients who subsequently died due to nonfungal cause) with AmB-IL. One patient died due to C. krusei pneumonia. In conclusion AmB-IL is a well-tolerated method of amphotericin B administration. It could facilitate the use of amphotericin B without impairing its efficacy for the treatment of candidaemia in neutropenic patients.

Adult

Presence of cannabinoid binding sites in the brain from early postnatal ages.

The present study demonstrates the presence of cannabinoid receptors in the brain from early postnatal ages. Specific and saturable binding was observed in the forebrain and remaining brain from early postnatal ages (2 and 5 days after birth). Female neonate forebrain exhibited a higher receptor density at 2 days after birth than males, but this trend was inverted at 5 days. From postnatal day 10, the receptors could be measured in more defined brain areas, i.e. the striatum, limbic forebrain and ventral mesencephalon. The ontogeny of the receptors in these three areas was relatively similar, exhibiting a progressive increase which maximised on days 30 or 40 and then subsequently decreased to adult values. Subtle sexual dimorphism was found in the striatum and ventral mesencephalon but not the limbic forebrain.

Aging

Comparison of computerized tomography and magnetic resonance imaging for the examination of the pituitary gland in patients with Cushing's disease.

OBJECTIVE: The vast majority of patients with Cushing's disease have a corticotroph adenoma, the selective removal of which, through the transsphenoidal route, has the potential to offer a definitive and complete cure. This study was designed to compare the diagnostic accuracy of computerized tomography (CT) and magnetic resonance imaging (MRI) to identify the presence, evaluate the size, and assess the topographic characteristics of pituitary corticotroph adenomas. METHODS: Forty-two patients with Cushing's disease were included in this prospective study, of whom 16 were subsequently explored transsphenoidally. Computerized tomography used a CE 12,000 CGR apparatus with 1.5-mm coronal slices and a 2-mm interslice gap. Magnetic resonance imaging used an MR Max 0.5T GE apparatus; adjacent 3-mm slices were obtained with a T1-weighted gradient echo before and after gadolinium injection. RESULTS: Lesions compatible with an adenoma were identified in 29 patients by MRI and in 21 patients by CT (69 vs 50%, P < 0.02). Seven macroadenomas were identified as well by the two methods. Eight of the 22 microadenomas detected by MRI were not identified by CT. Evidence for intracavernous tumour extension was found in nine patients: it was more frequently detected by MRI (8 patients) than by CT (4 patients). Fourteen patients with positive MRI had a pituitary examination: in one case the adenoma could not be reached because of purely suprasellar location; of the other 13 all were found by the surgeon and the surgical outcome was successful in 12 cases. CONCLUSION: MRI is superior to CT for the examination of the pituitary gland in patients with Cushing's disease.

Adolescent

Acute effects of delta 9-tetrahydrocannabinol on tuberoinfundibular dopamine activity, anterior pituitary sensitivity to dopamine and prolactin release vary as a function of estrous cycle.

The effects of delta 9-tetrahydrocannabinol (THC) on the activity of brain dopaminergic neurons might be subject to gonadal influence. In this work, we tested this hypothesis in relation to the effects of THC on tuberoinfundibular dopaminergic (TIDA) activity, the anterior pituitary sensitivity to dopamine (DA) and prolactin (PRL) secretion. To this end, we examined the effects of an acute dose of this cannabinoid administered during different phases of the estrous cycle in the morning or afternoon. The results were as follows. THC, administered during the morning of estrus, stimulated TIDA activity as reflected by increases in DA and L-3,4-dihydroxyphenylacetic acid (DOPAC) contents and tyrosine hydroxylase (TH) activity in the medial basal hypothalamus. This was accompanied by an increase in the responsiveness of the anterior pituitary to DA, as reflected by the increase in the density of D2 receptors and the corresponding decrease in PRL release. By contrast, plasma PRL levels increased when THC was administered on the afternoon of estrus, in parallel with a significant reduction in the number of D2 receptors in the anterior pituitary gland and no effects on TIDA activity. A similar decrease in the anterior pituitary density of D2 receptors, but with no changes in plasma PRL levels, was observed when THC was administered during the morning of diestrus. This effect was not accompanied by changes in TIDA activity either.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid