Impact of neurocognitive function on academic difficulties in pediatric bipolar disorder: A clinical translation.

BACKGROUND: Previous research has demonstrated that academic and neuropsychological functions are compromised in pediatric bipolar disorder (PBD). Investigation of the degree to which neuropsychological deficits might contribute to those academic problems is needed to aid in the recognition and intervention for school achievement difficulties in PBD. METHODS: A sample of 55 children and adolescents with PBD with and without attention-deficit/hyperactivity disorder (ADHD) (PBD group, n = 28; PBD+ADHD group, n = 27) were tested with a computerized neurocognitive battery and standardized neuropsychological tests. Age range of subjects was 7-17 years, with the mean age of 11.97 (3.18) years. Parents completed a structured questionnaire on school and academic functioning. RESULTS: Logistic regression analyses indicated that executive function, attention, working memory, and verbal memory scores were poorer in those with a history of reading/writing difficulties. A separate logistic regression analysis found that attentional dysfunction predicted math difficulties. These relationships between neuropsychological function and academic difficulties were not different in those with PBD+ADHD than in those with PBD alone. CONCLUSIONS: In PBD neuropsychological deficits in the areas of attention, working memory, and organization/problem solving skills all contribute to academic difficulties. Early identification and intervention for these difficulties might help prevent lower academic achievement in PBD.     

Ferrocene-containing cationic lipids for the delivery of DNA: oxidation state determines transfection activity.

The ability of two redox-active, ferrocene-containing cationic lipids [11-(ferrocenylundecyl)trimethylammonium bromide (FTMA) and bis(11-ferrocenylundecyl)dimethylammonium bromide (BFDMA)] to transfect mammalian cells was investigated. This study sought to determine the range of conditions over which these lipids were capable of transfecting cells and whether the oxidation state of the ferrocenyl groups in these materials could be used to influence the extent of transfection. Experiments conducted in the COS-7 cell line demonstrated that reduced and oxidized FTMA were substantially cytotoxic and did not transfect cells. Subsequent experiments conducted using BFDMA and reporter plasmids encoding enhanced green fluorescent protein (EGFP) and firefly luciferase demonstrated that BFDMA was able to transfect cells. However, the extent of transfection depended significantly upon both the concentration of BFDMA and the oxidation state of the lipid. Quantitative characterization of cytotoxicity and gene expression demonstrated that a window of concentration existed over which reduced BFDMA was non-cytotoxic and yielded high levels of transfection, but over which electrochemically oxidized BFDMA yielded very low (background) levels of transfection. Characterization of lipoplexes using dynamic light scattering demonstrated that reduced and oxidized BFDMA formed small aggregates (ca. 90 to 250nm) at concentrations of lipid ranging from 2 to 10 microM. Taken together, these results demonstrate that the oxidation state of BFDMA, which can be controlled electrochemically, can be used to control the extent of cell transfection. These results could form the basis of transfection procedures that exploit the redox behavior of ferrocene-containing lipids to achieve active spatial and temporal control over transfection using electrochemical methods.     

Quantification of vitamin C in the rat brain in vivo using short echo-time 1H MRS.

Both ultrashort echo-time STEAM and MEGA-PRESS-edited spectroscopy were used to validate noninvasive quantification of vitamin C (ascorbate) in the developing rat brain, where changes in ascorbate concentration have been reported. Despite strong overlap with resonances from glutamine, glutamate, glutathione, and macromolecules, reliable quantification of ascorbate (Cramer-Rao lower bounds<0.2 micromol/g) by LCModel analysis of STEAM (TE=2 ms) spectra was possible at 9.4 T. Ascorbate concentrations quantified from the STEAM spectra were in very good agreement with concentrations calculated from fully resolved ascorbate resonances in MEGA-PRESS-edited spectra measured from identical volumes of interest. Ascorbate concentrations measured using STEAM decreased with increasing postnatal rat age, in agreement with published brain ascorbate concentrations measured in vitro using high-performance liquid chromatography (HPLC).     

The combination of prazosin and verapamil in the treatment of essential hypertension

An exaggerated fall in blood pressure has been reported with the combination of an alpha 1-blocker and a calcium antagonist. This study investigated, in a placebo-controlled, randomized crossover trial, the clinical usefulness of the combination of prazosin (2 mg b.i.d.) and verapamil (160 mg b.i.d.). Therapeutic efficacy was monitored at regular outpatient visits: average supine and erect blood pressures were, respectively, 175/99 and 176/103 mm Hg with placebo, 160/91 and 164/96 mm Hg with single drug treatment, and 152/84 and 152/89 mm Hg with combination therapy. This significant and clinically useful reduction in blood pressure had an overall magnitude of approximately 28/18 mm Hg (supine) and 29/19 mm Hg (erect). Further measurements were made during a series of intensive study days, and the most important additional finding was a pharmacokinetic interaction that resulted in increased peak concentrations and bioavailability of prazosin. In conclusion, the combination of prazosin and verapamil proved effective in the treatment of 12 patients with essential hypertension who had been poorly responsive to conventional treatment with a beta-blocker and thiazide diuretic.     

Ocular changes in the mouse embryo following acute maternal ethanol intoxication

The development of the eye was investigated in the mouse embryo following a single administration of ethanol plus [3H]thymidine to the dam on day 13 of gestation. After 1 hr there was no difference in the number of labelled cells/100 micron 2 in the neural layer of the retina compared to controls, but there was an alcohol-related reduction in labelling density. After 24 hr there was an increase in the numbers of both pyknotic cells and mitotic figures, breaks occurred in the inner surface of the retina and cell debris was being extruded into the posterior chamber. At 48 hr the increase in pyknotic cells persisted, but there was less evidence of cell debris and the borders had been repaired. The estimated cell cycle time in the neural progenitor cells following maternal alcohol administration was increased 7-fold compared to controls. Morphometric analysis revealed that after 48 hr there were significant alcohol-related reductions in the width and depth of the eye, in the thickness of the neural layer and in the interocular distance. It appears that many of the ophthalmic abnormalities reported in human fetal alcohol syndrome can be produced in the mouse embryo following a single episode of acute maternal intoxication during a critical period of ocular ontogeny, and that they evolve primarily from disturbances in the normal patterns of recruitment and loss of neural progenitor cells in the developing retina.     

Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.     

Regulation of NGF gene expression in CNS glia by cell-cell contact.

Nerve growth factor (NGF) gene expression in central nervous system (CNS) glia appears to be associated with active glial growth. To study the underlying molecular mechanisms, we examined the effects of a number of growth-related factors on NGF mRNA expression in glial cultures. Our results suggest that glial membrane interaction, as a consequence of growth, actively inhibits NGF gene expression in CNS glia.     

An experimental collagen-impregnated dacron graft: Potential for endothelial seeding

This study evaluates the potential for endothelial seeding of a collagen-impregnated Dacron graft with or without surface modifiers (fibronectin, heparin) to attach and retain these cells during flow. Human umbilical endothelial cells were harvested, cultured, labeled with Indium111-oxine and seeded onto 30 mm X 4 mm diameter grafts. Six graft surfaces were studied: 1) a collagen-impregnated Dacron graft, HemashieldR (C); 2) C + fibronectin (C + F); 3) C + heparin (C + H); 4) C + F + H; 5) HytrelR + F (Hyt + F); and 6) Hyt + F + H. Radioactive loss determined the percentage attachment and then percentage retention of labeled inoculum after a one-hour in vitro perfusion. Scanning electron and light microscopy demonstrated the endothelium on the graft surface following perfusion. Fibronectin-coated grafts had a significantly higher percentage attachment than those without fibronectin (ANOVA, P less than 0.05). However, the percentage retention following perfusion was similar for all Dacron grafts and statistically inferior to the HytrelR grafts studied (ANOVA, P less than 0.05). SEM evaluation of the C + F + H graft surface was qualitatively the most impressive Dacron surface for seeding, yet was inferior to the HytrelR graft. We conclude that fibronectin benefits the initial attachment of endothelium to collagen-coated Dacron rivaling the HytrelR surface. Fibronectin does not improve percentage retention of the HemashieldR surface during perfusion, therefore, some of its initial benefit is lost.