The effect of the plasticizer di-2-ethylhexyl phthalate on the survival of stored RBCs

Recent in vitro studies have shown that di-2-ethylhexyl-phthalate (DEHP) inhibits the deterioration of RBCs during refrigerated storage in containers that use this compound as a plasticizer. The experiments described in this report were designed to assess whether this in vitro protective effect of DEHP would result in a prolonged in vivo survival of RBCs infused into normal human recipients. Whole blood collected from ten normal donors was stored for 35 days in citrate-phosphate- dextrose-adenine (CPDA-1) anticoagulant contained in polyvinylchloride (PVC) bags plasticized with DEHP or a trimellitate compound that is known to have low leachability. Aliquots of RBCs from each container were then labeled with chromium-51 and were reinfused into the original donors. For blood stored in DEHP-plasticized PVC bags, 24% more red cells survived in vivo 24 hours after reinfusion than was observed when the blood had been stored in trimellitate-plasticized bags (P less than .001). Whole blood stored in glass bottles showed a similar improvement in in vivo survival when DEHP was added in weekly increments to mimic the accumulation of this plasticizer seen during storage in plastic containers. Survival of packed red cells stored in the presence of DEHP increased by 14% compared with storage in trimellitate-plasticized bags (P less than .05). In agreement with previous studies, hemolysis and microvesicle formation were also reduced in the presence of DEHP. These results suggest that proposed new storage systems lacking DEHP should be carefully evaluated to determine whether adequate post-transfusion survival of RBCs may be achieved.     

Testing for the safety, reactogenicity and antigenic properties of a live thermostable mumps vaccine made from the Leningrad-3 strain]

A live mumps vaccine (LMV) from strain Leningrad-3 with a new stabilizer LS-18 was tested for reactogenicity and antigenic potency. Examinations of vaccinated children for vaccination reactions showed its complete areactogenicity and safety. LMV induced synthesis of virus-neutralizing antibodies in 78-82% of the vaccinees. Determinations of the dynamics, intensity and duration of circulation of specific antihemagglutinating, antineuraminidase and virus-neutralizing antibodies demonstrated marked antigenic potency of the LMV and established production of earliest specific antineuraminidase antibodies in 75% of the vaccinees. EIA was found to be the most sensitive test.     

INITIAL LOADING (400 μg TWICE DAILY) VERSUS STATIC (400 μg NOCTE) DOSE BUDESONIDE FOR ASTHMA MANAGEMENT

SUMMARY This double-blind study aimed to determine whether superior asthma control is achieved with budesonide (Pulmicort® Turbohaler®) at a loading dose (LD) (400 μg b.d.) for 6 weeks, followed by step down to 400 μg nocte for 12 weeks, compared with a static dose (SD) (400 μg nocte) for 18 weeks. A total of 682 patients (mean peak expiratory flow rate (PEFR) 413 l/min), who demonstrated ≥15% reversibility in PEFR, were randomised into the study. After 18 weeks, patients experienced improvements in morning PEFR (+45 l/min, both groups), symptom score (LD -0.57, SD -0.49, on a scale of 0-3), sleep disturbance (LD -1.21 nights/week, SD -1.06 nights/week) and to-agonist use (LD -1.36 puffs/day, SD -1.06 puffs/day), within both groups (each p=0.0001). At 18 weeks, 82% (LD) and 84% (SD) of patients benefited from no nocturnal wakening in the previous 7 days. Overall, at 18 weeks, asthma control was not significantly different between the groups. After 6 weeks, improvements in morning PEFR (LD +36 l/min, SD +26 l/min) and β₂-agonist use (LD -1.10 puffs/day, SD -0.94 puffs/day) were greater in the loading dose than in the static dose group (each p<0.05). The greater improvement in morning PEFR in the loading dose group was significant by day 7 (p<0.05). While both regimens are equally effective in achieving asthma control at 18 weeks, early clinical advantage is gained with initial loading dose budesonide (400 μg b.d.).     

Altered spatial learning, cortical plasticity and hippocampal anatomy in a neurodevelopmental model of schizophrenia-related endophenotypes

Adult rats exposed to the DNA‐methylating agent methylazoxymethanol on embryonic day 17 show a pattern of neurobiological deficits that model some of the neuropathological and behavioral changes observed in schizophrenia. Although it is generally assumed that these changes reflect targeted disruption of embryonic neurogenesis, it is unknown whether these effects generalise to other antimitotic agents administered at different stages of development. In the present study, neurochemical, behavioral and electrophysiological techniques were used to determine whether exposure to the antimitotic agent Ara‐C later in development recapitulates some of the changes observed in methylazoxymethanol (MAM)‐treated animals and in patients with schizophrenia. Male rats exposed to Ara‐C (30 mg/kg/day) at embryonic days 19.5 and 20.5 show reduced cell numbers and heterotopias in hippocampal CA1 and CA2/3 regions, respectively, as well as cell loss in the superficial layers of the pre‐ and infralimbic cortex. Birth date labeling with bromodeoxyuridine reveals that the cytoarchitectural changes in CA2/3 are a consequence rather that a direct result of disrupted cortical neurogenesis. Ara‐C‐treated rats possess elevated levels of cortical dopamine and DOPAC (3,4‐didyhydroxypheylacetic acid) but no change in norepinephrine or serotonin. Ara‐C‐treated rats are impaired in their ability to learn the Morris water maze task and showed diminished synaptic plasticity in the hippocampocortical pathway. These data indicate that disruption of neurogenesis at embryonic days 19.5 and 20.5 constitutes a useful model for the comparative study of deficits observed in other gestational models and their relationship to cognitive changes observed in schizophrenia.     

GluA3-deficiency in mice is associated with increased social and aggressive behavior and elevated dopamine in striatum

Glutamate signaling has been implicated in the regulation of social behavior. AMPA-glutamate receptors are assembled from four subunits (GluA1-4) of mainly GluA1/2 and GluA2/3 tetramers that form ion channels of distinct functional properties. Mice lacking GluA1 showed a reduced anxiety and male aggression. To understand the role of GluA3 in modulating social behavior, we investigated GluA3-deficient mice (Gria3-/Y) on C57BL/6J background. Compared to wild type (WT) littermates (n=14), Gria3-/Y mice (n=13) showed an increase in isolation-induced male aggression (p=0.011) in home cage resident-intruder test; an increase in sociability (p=0.01), and increase in male-male social interactions in neutral arena (p=0.005); an increase in peripheral activities in open field test (p=0.037) with normal anxiety levels in elevated plus maze and light-dark box; and minor deficits in motor and balance function in accelerating rotarod test (p=0.016) with normal grip strength. Gria3-/Y mice showed no significant deficit in spatial memory function in Morris-water maze and Y-maze tests, and normal levels of testosterone. Increased dopamine concentrations in stratum (p=0.034) and reduced serotonin turnover in olfactory bulb (p=0.002) were documented in Gria3-/Y mice. These results support a role of GluA3 in the modulation of social behavior through brain dopamine and/or serotonin signaling and different AMPA receptor subunits affect social behavior through distinct mechanisms.