Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes

meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter.     

The effects of shivering on oxygen consumption and carbon dioxide production in patients rewarming from hypothermic cardiopulmonary bypass

Oxygen consumption (VO2), carbon dioxide production (VCO2), end-tidal carbon dioxide partial pressure (PETCO2), mixed venous oxygen saturation (SvO2) and haemodynamic variables were recorded every 30 min for four hours in 15 patients recovering from hypothermic cardiopulmonary bypass (CPB). All patients had been anaesthetised with fentanyl 40 micrograms.kg-1, supplemented with isoflurane, and pancuronium 0.15 mg.kg-1 for muscle relaxation. Three of the 15 patients (20 per cent) shivered, defined as intermittent or continuous, vigorous movements of chest or limb muscles. Patients who shivered had a VO2 of 159 +/- 16.4 ml.min-1.m-2 on arrival in the ICU which rose to a maximum value of 254 +/- 28.3 ml.min-1.m-2 by 150 min post-CPB. In contrast, patients who did not shiver had a significantly lower VO2 of 93.1 +/- 6.9 ml.min-1.m-2 on arrival in the ICU which rose to a maximal value of only 168 +/- 11.5 ml.min-1.m-2 by 180 min post-CPB. Maximal VO2 in both groups was reached when the nasopharyngeal temperature (NPT) was approaching normal. VCO2 paralleled the increase in VO2 in both groups. By four hours there was no significant difference between the two groups; however, the VO2 in both groups (160.5 +/- 21.3 ml.min-1.m-2 and 173.9 +/- 12.3 ml.min-1.m-2 respectively) was approximately twice values commonly measured in anaesthetized patients. Patients who shivered had a significantly higher heart rate and cardiac index and significantly lower SvO2. We conclude that the high VO2 and VCO2 associated with shivering causing increased myocardial work may be detrimental to patients who have impaired cardiac function post-coronary artery surgery (CAS).     

Ontogeny of B lymphocytes in mice. Quantification of surface membrane immunoglobulins by immunoperoxidase assay.

Surface membrane immunoglobulins (SmIg) of splenic lymphocytes were investigated by immunoperoxidase assay in newborn Swiss mice, their mothers and adult controls. The mean number of SmIg + cells in adult mice was 45-8% and the mean number of antigenic sites per positive cells was 108,500. In newborn mice during the first 7 days of life, values for both parameters were low (24-25--28-5% and 38,000-45,773 respectively) and began to rise after the 10th day to reach adult levels between the ages of 2 and 3 weeks. A peak above adult levels for the mean number of sites per cell was observed on day 21 with a subsequent drop to adult levels on day 28. Post-partum females were found to have consistently fewer sites per positive cell (69,000-86,600) during the 14 days following delivery than their adult control counterparts, though the difference was not statistically significant.     

Increased dopamine receptor sensitivity in the rat following acute administration of sufentanil,U50,488H and d-Ala2-d-Leu5-enkephalin

Summary The effects of acutely administered opioid receptor agonists sufentanil, U50,488H and [d-Ala², d-Leu⁵]-enkephalin (DADL) were observed upon dopamine D₁ and D₂ binding site density in the striatum of the rat. In addition, the functional implications of opioid-induced changes in dopamine receptor sensitivity were studied using the behavioural profile elicited by apomorphine in the rat. The -agonist sufentanil (1 or 20 Erg/kg, i. p.), the -agonist U50,488H (10 mg/kg, i. p.) and DADL (1 g/animal, i. c. v.) all significantly elevated D₂ but not D₁ binding site density in rat striatum. Pretreatment with sufentanil (1 g/kg, i. p.) induced an elevation in apomorphine-induced sterotyped behaviour, but attenuated locomotor activity. Following administration of U50,488H (10 mg/kg, i. p.), both the degree of stereotypy and the intensity of the locomotor activity were enhanced. Contralateral rotation was observed in animals pretreated with DADL (1 g/animal, i. c. v.) following challenge with apomorphine. It is concluded that the opioid agonists studied induce a significant elevation in functional D₂ sites to the exclusion of D₁ sites. However, the precise mechanism by which this effect is elicited remains to be established. Send offprint requests to R. D. E. Sewell at the above address     

Differences in the response of Sprague-Dawley and Lewis rats to bezafibrate: The hypolipidemic effect and the induction of peroxisomal enzymes

The effects of bezafibrate administered at 10 and 50 mg/kg/day for 7 days to male Sprague-Dawley (SD) and Lewis rats were investigated in order to determine the interrelation between the changes in serum and hepatic lipid contents and activities of selected peroxisomal, microsomal and mitochondrial enzymes in the two rat strains. In both strains, bezafibrate effectively reduced serum and hepatic lipids, increased the liver weight, induced a proliferation of peroxisomes, and selectively elevated the activities of carnitine acetyltransferase and of the enzymes of the peroxisomal -oxidation system. Moreover, immunoblotting revealed that the drug specifically enhanced the concentration of only those peroxisomal enzymes involved in fatty acid -oxidation. The data obtained demonstrate that although the responses initiated by bezafibrate are qualitatively similar in both strains, they differ in their magnitude in a dose-dependent manner, with the Lewis strain exhibiting a more pronounced response than the SD rats. These results show that dose-dependent strain differences as well as the generally known species differences should be taken into account in pharmacological and toxicological evaluations of fibrates in rodents. Furthermore, generalization and extrapolation from rodent studies should be treated with great caution.     

Shifting Cerebral Dominance in a Woman with Schizoaffective Psychosis: A Case Study

We describe a case of an intelligent, artistic 50-year-old woman with schizoaffective disorder with a long history of delusional preoccupation with laterality and episodes of reported shifts in handedness. Investigations including dichotic listening and lateralised visual imagery tasks indicated unusual patterns of asymmetry. Executive functions were found to be intact, and EEG and CT scan were normal. Interview schedules revealed high scores for schizotypy, and no evidence of a dissociative disorder, whereas psychotic symptoms with mood lability were evident on mental status examination. The subject's preoccupations are illustrated with a selection of her artistic productions. The case is discussed in the context of reports of a relationship between schizophrenia and ambiguous handedness. A cognitive neuropsychiatric formulation briefly explores the possibility of alternative cerebral hemispheres affecting cognitive-perceptual operations.     

Community-acquired methicillin-resistant Staphylococcus aureus clones circulating in Belgium from 2005 to 2009: changing epidemiology

The present study reports the evolution of the demographic characteristics and the molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in Belgium from 2005 to 2009. Four hundred and ten CA-MRSA isolates were prospectively collected and screened for the presence of Panton–Valentin leucocidin (PVL) and toxic shock syndrome toxin 1 (TSST-1) encoding genes, while clinical information were recorded. PVL- and TSST-1-positive isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Staphylococcal cassette chromosome mec (SCCmec) type, spa type and multilocus sequence type (MLST) were determined on representative isolates. One hundred and fifty-nine (39 %) isolates were PVL-positive. PVL-positive isolates were significantly more frequently isolated from skin or soft tissue than PVL-negative isolates, causing mainly subcutaneous abscesses and furuncles. Patients with PVL-positive CA-MRSA were significantly younger than patients with PVL-negative CA-MRSA. Eighty-seven percent of the PVL-positive isolates belonged to a limited number (n?=?7) of PFGE types belonging to sequence types (ST) ST80, ST8, ST30, ST5, ST152, ST338 and a new ST, a single-locus variant of ST1. A temporal evolution of the distribution of these PFGE types was observed, characterised by (1) the dissemination of the ST8-SCCmecIV arcA-positive (USA300) genotype and (2) a genetic diversification. Forty-seven (11 %) strains were TSST-1-positive, of which 65 % clustered into four PFGE types, all belonging to ST5. The epidemiology of CA-MRSA in Belgium is changing, as the rapid diffusion of the USA300 clone seems to occur, together with a clonal diversification.