Severe bradycardia following fluoxetine administration: A case report in a young HIV-1 infected woman

Some reports in the literature suggest that fluoxetine can produce bradycardia in elderly people or in subjects with cardiovascular diseases, thus indicating that the drug should be used with caution in this kind of patient. The aim of this case report is to notify that the same adverse effect could be found in HIV-1 infected patients. The HIV-1 infected patient we describe is a young woman not affected by cardiovascular pathologies who nevertheless developed severe bradycardia following fluoxetine administration. Therefore, we recommend caution not only when administering this drug to elderly people or subjects with cardiovascular diseases, but also to HIV-1 infected patients.     

Analysis of trough serum growth hormone concentrations: comparison of an immunoradiometric assay and a sensitive ELISA for growth hormone

OBJECTIVES: We compared a sensitive assay for GH (ELISA) with a conventional immunoradiometric (IRMA) assay with particular reference to the oscillatory activity detected by Fourier transformation and the estimation of trough concentrations using occupancy analysis. DESIGN: Eight healthy adult male volunteers underwent 24-hour profiles during which samples were drawn at 20-minute intervals. Samples were analysed by an ELISA and an IRMA system. MEASUREMENTS: The 24-hour serum GH concentration profiles were subjected to Fourier transformation and to occupancy analysis. RESULTS: No additional GH periodicities could be determined in the ELISA data other than the well documented 180-200-minute periodicity. Median observed concentrations (OC) at 5% occupancy were 0.035 mU/l (range 0.004-0.22) for the ELISA and 0.035 mU/l (range 0.001-0.50) for the IRMA. For all OC parameters, 5, 50 and 95%, there was a good correlation between the ELISA and IRMA systems. The mean difference (bias) between the ELISA and IRMA were -0.05, -0.28 and -1.40 mU/l at OC values of 5, 50 and 95% respectively and the standard deviations of the difference at the same OC values were 0.10, 0.50 and 1.61 mU/l. CONCLUSION: Although there is a qualitative improvement on visual inspection of individual 24-hour serum GH profiles obtained using the ELISA system, there is little additional information gained in terms of pulse periodicity or occupancy analysis.     

Induction of DNA double-strand breaks by 8-methoxycaffeine: cell cycle dependence and comparison with topoisomerase II inhibitors

We have studied the ability of 8-methoxycaffeine (8-MOC)—oneof the most effective caffeine derivatives in inducing chromosomalaberrations—to induce DNA double strand breaks (DSB) inpurified human T lymphocytes during the cell cycle. Etoposide-or ellipticine-mediated DNA break frequency was used as a parameterof topoiso merase II activity. DNA-DSB induced by either 8-MOCor VP16 or ellipticine rose co-ordinately with the level ofDNA topoisomerase II and with the onset of DNA replication.At concentrations between 10 and 50 .µM 8-MOC was     

Hyperforin contributes to the hepatic CYP3A-inducing effect of Hypericum perforatum extract in the mouse.

This study in mice investigated whether hyperforin accounts for the inductive effects on cytochrome P4503A enzymes of St. John's wort extracts (SJW; Hypericum perforatum), one of the most popular herbal preparations because of its alleged activity in mild to moderate depression. A hydroalcoholic extract containing 4.5% hyperforin was given at a dose of 300 mg/kg, bis in die (b.i.d.), for 4 and 12 days. Hyperforin, its main phloroglucinol component, was given as dicyclohexylammonium (DCHA) salt (18.1 mg/kg, b.i.d.) on the basis of its content in the extract, to ensure comparable exposure to hyperforin. The extract increased hepatic erythromycin-N-demethylase (ERND) activity, which is cytochrome P450 enzyme (CYP) 3A-dependent, about 2.2-fold after 4 days of dosing, with only slightly greater effect after 12 days (2.8 times controls). Hyperforin too increased ERND activity within 4 days, much to the same extent as the extract (1.8 times the activity of controls), suggesting that it behaves qualitatively and quantitatively like the extract as regards induction of CYP3A activity. This effect was confirmed by Western blot analysis of hepatic CYP3A expression. Exposure to hyperforin at the end of the 4-day treatment was still similar to that with SJW extract, although it was variable and lower than after the first dose in both cases, further suggesting that hyperforin plays a key role in CYP3A induction by the SJW extract in the mouse. Standardization of the extracts based on the hyperforin content can be proposed for further evaluation of their potential action on first-pass metabolism and clearance of coadministered CYP3A substrates.     

Intraimage reproducibility of measurements in the macular area using a computerized system

An accurate analysis of the morphological changes which take place during pathological processes of the posterior pole is important for a correct diagnosis and therapeutic approach. The purpose of the study was to determine the intraobserver and interobserver reproducibility of the Image-net system 100 (Topcon, Japan) to take measurements on the retina. The program ’Linear/Areal Measurement functions‘ of Image-net system 100 which is an image digitalization technique, was tested. Twelve patients were consecutively selected from the patients of the Retina Center of the Department of Ophthalmology, University of Genoa. Three images of each eye were taken from each subject and only the best image was used in this study. The intraobserver and interobserver reproducibility of both the distance between two pre-set points (linear measurement), and the perimeter and area of preselected retinal zones were calculated. The repeatability (or intraobserver reproducibility) of the linear sizes was measured by the coefficient of variation and ranged from 0.32% to 7.38%, while the interobserver reproducibility ranged from 0.46% to5.22%. The repeatability and reproducibility of the perimeters ranged from 0.72% to 9.63% and from0.6%to 5.7%, respectively, while the repeatability and reproducibility of the areas ranged from 0.72% to 9.63%and from 0.6% to 5.7%, respectively. Although the results were quite good, the quality of the image of the fundus and the number of observers influenced the coefficient of variation; furthermore, the anatomy of the areas to be measured and the computer’mouse‘ could increase the value of the coefficient of variation. This revised version was published online in August 2006 with corrections to the Cover Date.     

Silica supported zirconocenes and Al-based cocatalysts: surface metal loading and catalytic activity

The Zr surface loading from Cp₂ZrCl₂ toluene solutions on different kinds of commercial silicas (Grace 948, 952 and 956) was determined by Rutherford backscattering spectrometry. In all silicas, a saturation trend was observed with increasing amount of metal in the initial solution, the largest Zr loading value (1 wt.-%) being observed for silica Grace 948. Solid surface areas were determined by the BET method before and after metallocene immobilization, revealing that the values do not change after zirconocene impregnation. Two different kinds of cocatalyst were used, methylaluminoxane and trimethylaluminium. The aluminium loading on silica Grace 948 was determined using the ²⁷Al(p,γ)²⁸Si nuclear reaction and titrometry, both showing that methylaluminoxane leads to an “Al grafting” four times more efficient than does trimethylaluminium. Finally, the catalytic activity of these systems was tested in the polymerization of ethylene. The supported catalysts were shown to be active, specially using the low cost trimethylaluminium as a cocatalyst. The polymers obtained with the supported systems exhibited a higher molecular weight than those obtained with the homogeneous system.     

Effects of ondansetron administration on opioid withdrawal syndrome observed in rats

This study tested whether a 5-HT₃ receptor antagonist could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days. After the four days, half of the rats in each group received naloxone and half received saline. Each animal also received one of four doses of ondansetron (0, 1, 2 and 4 mg/kg i.p.). Administration of ondansetron to rats receiving naloxone after chronic morphine decreased the intensity of withdrawal signs such as increased defecation, jumping and wet-dog shakes, elevated the nociceptive threshold values which were decreased by precipitated withdrawal, but produced no change in urination, rectal temperature or salivation. The effects exhibited by ondansetron administration may be explained through interference of its 5-HT₃ receptor antagonist activity with serotoninergic mechanisms involved in the regulation of these withdrawal symptoms. The use of this drug is thus suggested as a possible treatment of opioid withdrawal signs in heroin addicts.