Argon blocks the expression of locomotor sensitization to amphetamine through antagonism at the vesicular monoamine transporter-2 and mu-opioid receptor in the nucleus accumbens

We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence.     

Ex vivo evaluation of a new neonatal/infant oxygenator: comparison of the Terumo CAPIOX Baby RX with Dideco Lilliput 1 and Polystan Safe Micro in the piglet model

OBJECTIVE: A newly developed neonatal and infant oxygenator with a nonheparin biocompatible polymer coating, low priming volume (43 mL), high oxygen transfer, wide operating range (<1.5 L/min) and low pressure drop represents a promising solution for cardiac surgery in neonates and infants. We compared the new CAPIOX Baby RX, Terumo (BRX) with two commonly used neonatal oxygenators: Dideco Lilliput 1 (DL1) and Polystan Safe Micro (PSM) in a piglet model. METHODS: Fifteen piglets (5.6 +/- 1.3kg) were placed on standardized cardiopulmonary bypass (CPB) for 6 hours using one of the three oxygenators (n = 5 in each group). After 120 min, the system was cooled to 25 degrees C for 60 min and then returned to normothermia. Arterial and venous blood gas data and temperature were recorded continuously by a CDI500 System (Terumo). Pressure drop, FiO2 and gas flow were recorded. Blood samples were taken before CBP, after 10 min, before and after cooling, and at the end. Total blood counts, thrombin-antithrombin complex and plasma-free haemoglobin (PfHb) were measured. RESULTS: All oxygenators showed acceptable performance for the duration of CPB. The BRX had lower mean gas flow (0.33 +/- 0.05 L/min) and FiO2 (0.43 +/- 0.02%) throughout CPB than the DL1 (1.14 +/- 0.25 L/min, p = 0.006 and 0.60 +/- 0.02%, p = 0.009, respectively) or the PSM (1.47 +/- 0.87 L/min and 0.54 +/- 0.08%, p = ns). Pressure drop in the BRX group ranged from 12 to 22 mmHg. This was significantly lower than in the DL1 group (39-65 mmHg, p = 0.005). In the PSM group, values ranged between 24 and 33 mmHg (p = ns). The increase in PfHb at six hours was significantly lower in the BRX (11.3 +/- 4.2 ng/dL) versus the DL1 (42.2 +/- 6.1 ng/dL, p = 0.004) and the PSM (56.7 +/- 15.5 ng/dL, p = 0.045). CONCLUSIONS: The BRX is as safe as the DL1 and the PSM, with superior performance in pressure drop, efficient blood gas management and lower haemolysis. The BRX exhibited the lowest prime, hold-up volume and breakthrough time.     

Tripe palms associated with systemic mastocytosis: the role of transforming growth factor-α and efficacy of interferon-alfa

Tripe palms are thickened, moss-like or velvety textured exaggerations of the normal dermatoglyphics. The disease belongs to the spectrum of papulosquamous paraneoplastic syndromes. Although suspected, the role of transforming growth factor-α (TGF-α) has not been clearly established. A 54-year-old man with systemic mastocytosis presented with thickening and darkening of the palms and soles. We performed skin biopsies for light microscopy (including toluidine blue), in situ hybridization and double labelling, and determination of serum tryptase, histamine and TGF-α levels. Toluidine blue stained the mast cells that had massively infiltrated the dermis. Tripe palm samples showed extensive hyperkeratosis. The TGF-α probe reacted strongly with the mast cells that also reacted with the antitryptase monoclonal antibody. Elevated tryptase, histamine and TGF-α levels prior to interferon-alfa administration decreased under treatment. The demonstration of TGF-α in infiltrating mast cells, the clinical regression of tripe palms and the lowering of the serum level and the mast cell molecular signal of the cytokine when systemic mastocytosis was controlled by interferon-alfa, suggest a key role for TGF-α in this cutaneous paraneoplastic syndrome.     

Bioavailability of ACC-9653 (Phenytoin Prodrug)

Summary: The bioavailability of phenytoin from ACC-9653 versus intravenously administered sodium phenytoin was determined using a crossover design for intravenous and intramuscular administration of ACC-9653 to healthy volunteers. Absolute bioavailability of phenytoin derived from ACC-9653 in each subject was calculated as the ratio of the phenytoin area under the plasma concentration time curve for time 0 to infinity [AUC(0-inf)] after ACC-9653 divided by the phenytoin AUC(O-inf) after intravenous sodium phenytoin. The mean absolute bioavailability of ACC-9653 was 0.992 after intravenous administration and 1.012 after intramuscular administration. These data establish that the bioavailability of ACC-9653 is complete following intravenous or intramuscular administration in single-dose volunteer studies. The absolute bioavailability of phenytoin derived from ACC-9653 in subjects with therapeutic plasma phenytoin concentrations is being studied in patients given simultaneous infusions of stable isotope-labeled tracer doses of ACC-0653 and sodium phenytoin.     

Juvenile insulin-dependent diabetes: a possible susceptibility gene in interaction with HLA

A model with a susceptibility gene unlinked to HLA but in interaction with this system is shown to fit the data on familial distribution in 30 multiplex families of juvenile insulin-dependent diabetes.     

Stability of perceived ward atmosphere over time,diagnosis and gender for patients with psychosis

In this study the focus was on patients with psychosis treated in a psychiatric rehabilitation unit in southern Sweden. The study described the stability of the ward atmosphere over 2 years, as well as differences between subgroups of patients regarding gender and diagnosis. Furthermore, the perceived ward atmosphere was compared with what has been recommended in the literature. The ward atmosphere was measured by The Community-Oriented Programs Environment Scale (COPES) five times during a 2-year period. The ward atmosphere was fairly stable over time, and in several respects it met the recommendations suggested for psychotic patients. There were few differences between schizophrenia patients and patients with other psychoses. No difference was found in perceived ward atmosphere with respect to gender. The study showed that the investigated unit, admitting almost only patients with psychosis, could provide a ward atmosphere accordance with the recommendations, probably due to a carefully planned program with a psychodynamically oriented supportive treatment milieu.     

Quantitation of the major allergen of several Parietaria pollens by an anti-Par 1 monoclonal antibody-based ELISA. Analysis of crossreactivity among purified Par j 1, Par o 1 and Par m 1 allergens

Background Plants of the genus Parietaria, Urticaceae family, represent a major cause of pollinosis in the Mediterranean area. Different Parietaria species crossreuct to a great extent, but studies on the crossreactivity among the major allergens of these pollens have not been carried out so far. Objective To develop an immunochemical method to quantify the major Parieiarin judaica allergen. Par j 1, as well as to verify the presence of Par j 1-like proteins in different Urticaceae pollens. These proteins would be purified in order to study the cross-reactivity among them. Methods Immunoaffinity chromatography with a monoclonal antibody, solid-phase enzyme-linked immunoassays and SDS-PAGE. Results A monoclonal antibody-based ELISA for the quantisation of Par j 1 has been developed. The assay has a sensitivity of 0.2 ng/mL and shows a high correlation with the allergenic activity of P. judaica extracts determined by radioallergosorbent assay (RAST) inhibition. By means of this assay, proteins homologous to Par j I were detected in P. officinalis and P. mauritanica. These proteins (Par o 1 and Par m 1, respectively) were purified by affinity chromatography using the same monoclomal antibody employed in the ELISA. Crossed-inhibition experiments demonstrated that Par j 1. Par o 1. and Par m 1, competed for the binding of specific IgE from a P. judaica-sensitive patients serum pool. Conclusion The results here described suggest that shared allergenic epitopes are present in the three main allergens investigated, which may simplify the diagnosis and therapy for Parietaria allergy.