Distinct multivariate structural brain profiles are related to variations in short- and long-delay memory consolidation across children and young adults.

From early to middle childhood, brain regions that underlie memory consolidation undergo profound maturational changes. However, there is little empirical investigation that directly relates age-related differences in brain structural measures to memory consolidation processes. The present study examined memory consolidation of intentionally studied object-location associations after one night of sleep (short delay) and after two weeks (long delay) in normally developing 5-to-7-year-old children (n = 50) and young adults (n = 39).

Subretinal Stimulation Chip Set with 3025 Electrodes, Spatial Peaking Filter, Illumination Adaptation and Implant Lifetime Optimization.

A subretinal stimulator chip has been designed and tested, which combines high pixel number with highest simulation voltages, lowest power consumption, spatial peaking and illumination adaptation. A supporting ASIC completes the implantable device electronics. Blind mouse retina has successfully been stimulated in vitro.

Alcohol induces programmed death receptor-1 and programmed death-ligand-1 differentially in neuroimmune cells.

Engagement of programmed death-1 (PD-1) receptor by its ligands (PD-L1/PD-L2) in activated immune cells is known to be involved in inflammatory neurological disease via a co-inhibitory signal pathway. Interaction of PD-1/PD-L1 is believed to occur only in activated neuroimmune cells because there are undetectable levels of PD-1/PD-L1 in normal physiological conditions. Here, we evaluated whether activation of neuroimmune cells such as human macrophage, brain endothelial cells (hBECs), astrocytes, microglia, and neurons by non-toxic concentrations of ethanol (EtOH) exposure can alter PD-1/PD-L1 expression.

Antiretroviral drug-S for a possible HIV elimination.

Although the combination of highly active antiretroviral therapy (cART) can remarkably control human immunodeficiency virus type-1 (HIV-1) replication, it fails to cure HIV/AIDS disease. It is attributed to the incapability of cART to eliminate persistent HIV-1 contained in latent reservoirs in the central nervous system (CNS) and other tissue organs. Thus, withdrawal of cART causes rebound viral replication and resurgent of HIV/AIDS.

Impairment of Thiamine Transport at the GUT-BBB-AXIS Contributes to Wernicke's Encephalopathy.

Wernicke's encephalopathy, a common neurological disease, is caused by thiamine (vitamin B1) deficiency. Neuropathy resulting from thiamine deficiency is a hallmark of Wernicke-Korsakoff syndrome in chronic alcohol users. The underlying mechanisms of this deficiency and progression of neuropathy remain to be understood.

Activation of NLRP3 inflammasome by cholesterol crystals in alcohol consumption induces atherosclerotic lesions.

Epidemiological studies showed a strong association between alcoholism and incidence of stroke, for which the underlying causative mechanisms remain to be understood. Here we found that infiltration of immune cells and deposition of cholesterol at the site of brain artery/capillary injury induced atherosclerosis in chronic alcohol (ethanol) consumption in the presence or absence of high-fat diet. Conversion of cholesterol into sharp edges of cholesterol crystals (CCs) in alcohol intake was key to activation of NLRP3 inflammasome, induction of cerebral atherosclerosis, and development of neuropathy around the atherosclerotic lesions.

The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

Background: Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described.

Objective: To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions.

Primary blast causes mild, moderate, severe and lethal TBI with increasing blast overpressures: Experimental rat injury model.

Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0-450 kPa (0-800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP.

Differential induction of PD-1/PD-L1 in Neuroimmune cells by drug of abuse.

Interaction of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) plays a critical role in regulating the delicate balance between protective immunity and tolerance. Human neuroimmune cells express very low or undetectable levels of PD-1/PD-L1 in normal physiological condition.We seek to examine if exposure of these cells to drug of abuse such as methamphetamine (METH) alters the profile of PD-1/PD-L1 levels, thereby dampens the innate immune response of the host cells.

The direct renin inhibitor aliskiren localizes and persists in rat kidneys.

The aims of this study were to 1) determine whether renal localization of aliskiren and its antihypertensive and renoprotective effects persist after administration of the drug is stopped and 2) define the renal localization of aliskiren by light microscopy autoradiography. Hypertensive double transgenic rats (dTGR) overexpressing genes for human renin and angiotensinogen were treated with aliskiren (3 mg·kg(-1)·day(-1) sc; osmotic minipumps) or enalapril (18 mg/l in drinking water). After a 2-wk treatment, dTGR were assigned to either continued treatment with aliskiren ("continued"), or to cessation of their respective treatment ("stopped") for a 3-wk washout.

When precaution creates misunderstandings: the unintended effects of precautionary information on perceived risks, the EMF case.

In the past decade, growing public concern about novel technologies with uncertain potential long-term impacts on the environment and human health has moved risk policies toward a more precautionary approach. Focusing on mobile telephony, the effects of precautionary information on risk perception were analyzed. A pooled multinational experimental study based on a 5 × 2 × 2 factorial design was conducted in nine countries.

Induction of oxidative and nitrosative damage leads to cerebrovascular inflammation in an animal model of mild traumatic brain injury induced by primary blast.

We investigate the hypothesis that oxidative damage of the cerebral vascular barrier interface (the blood-brain barrier, BBB) causes the development of mild traumatic brain injury (TBI) during a primary blast-wave spectrum. The underlying biochemical and cellular mechanisms of this vascular layer-structure injury are examined in a novel animal model of shock tube. We first established that low-frequency (123kPa) single or repeated shock wave causes BBB/brain injury through biochemical activation by an acute mechanical force that occurs 6-24h after the exposure.

Pharmacokinetic and technical comparison of Sandostatin® LAR® and other formulations of long-acting octreotide.

Background: Sandostatin® LAR® (Novartis Pharma AG) is a long-acting repeatable formulation of the somatostatin analogue octreotide, the safety and efficacy of which has been established through 15 years of clinical experience. Recently, other formulations of octreotide using polymer poly(lactic-co-glycolic acid) technology have been developed. This study compares the composition and pharmacokinetic (PK) profile of Sandostatin LAR with three other versions of the depot delivery system (formulations A, B and C, available in selected countries).

Biocompatibility of an injectable in situ forming depot for peptide delivery.

Poly(ethyleneglycol) 500 dimethylether (PEG500DME) was tested as a novel solvent for the manufacture of an injectable in situ forming depot (ISFD) containing poly(D,L-lactide-co-glycolide) (PLGA). The sustained release of pasireotide from the ISFD was evaluated in vitro and in vivo. Furthermore, the local tolerability of the delivery system using PEG500DME was investigated in subcutaneous (s.

Pharmacokinetics of the oral direct renin inhibitor aliskiren in combination with digoxin, atorvastatin, and ketoconazole in healthy subjects: the role of P-glycoprotein in the disposition of aliskiren.

This study investigated the potential pharmacokinetic interaction between the direct renin inhibitor aliskiren and modulators of P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Aliskiren stimulated in vitro P-glycoprotein ATPase activity in recombinant baculovirus-infected Sf9 cells with high affinity (K(m) 2.1 micromol/L) and was transported by organic anion-transporting peptide OATP2B1-expressing HEK293 cells with moderate affinity (K(m) 72 micromol/L).

Effects of aliskiren on blood pressure, albuminuria, and (pro)renin receptor expression in diabetic TG(mRen-2)27 rats.

The aim of this study was to explore the effects of the renin inhibitor aliskiren in streptozotocin-diabetic TG(mRen-2)27 rats. Furthermore, we investigated in vitro the effect of aliskiren on the interactions between renin and the (pro)renin receptor and between aliskiren and prorenin. Aliskiren distributed extensively to the kidneys of normotensive (non)diabetic rats, localizing in the glomeruli and vessel walls after 2 hours exposure.

Changing pattern of brain hemorrhage during 12 years of computed axial tomography.

Background And Purpose: We examined whether the pattern of cerebral hemorrhage changed after the introduction of computed tomography.

Methods: Using a prospective data base we analyzed the case-fatality ratio, early mortality, and the incidences of hypertension and anticoagulant medication in 488 consecutive cases with supratentorial hemorrhage between 1978 and 1989. Blood pressure at admission of all patients for the years 1978-1979 and 1988-1989 and the Mathew and activities of daily living scores for the years 1978-1979, 1982-1983, and 1988-1989 were assessed retrospectively.

Amphotericin B and amphotericin B methylester: effect on brush border membrane permeability.

In order to explain the nephrotoxicity of polyene antibiotics such as Amphotericin B (AM), an effect on the tubule membrane permeability has been postulated. However, studies on the action of AM have been complicated by the use of sodium deoxycholate (DOC), a membrane dissociating detergent as a solvent. Recently, a derivative, the methylester aspartate salt of Amphotericin B (AME) has been synthesized, which is highly water soluble in the absence of organic solvents.

Degradation of NAD(H) by endogenous enzymes of yeasts and Clostridia.

The time courses of degradation of exogenous NAD and NADH (2.5 mM) catalyzed by endogenous enzymes present in Saccharomyces cerevisiae, Candida utilis, Clostridium spec. La 1, Clostridium kluyveri, and Clostridium sporogenes have been determined.

Synthesis and properties of acrylamide-substituted base pair specific dyes for deoxyribonucleic acid template mediated synthesis of dye polymers.

We have tried to construct synthetic polymers for sequence-specific recognition and complexation of longer deoxynucleotide sequences. For this purpose, we developed a method of template-directed polymerization of basic pair specific DNA ligands such as basic dyes. The template-directed polymerization consists in a copolymerization of various dyes of different specificities staying simultaneously in a binding equilibrium with DNA.

Polyethylene glycol derivatives of base and sequence specific DNA ligands: DNA interaction and application for base specific separation of DNA fragments by gel electrophoresis.

Various base pair specific DNA ligands comprising a phenyl phenazinium dye, a triphenylmethan dye and Hoechst 33258 were covalently bound to polyethylene glycol (PEG) via ester or ether bonds. The DNA interactions of the PEG derivatives formed were shown to exhibit the same base pair specificity as the parent compounds. Since the PEG chains thus bound to the DNA could be expected to increase drastically the frictional coefficient of the DNA, the PEG derivatives were used for base specific DNA separations in agarose and polyacrylamide gel electrophoresis.

Size fractionation of DNA fragments by liquid-liquid chromatography.

A method for the fractionation of double-stranded DNA fragments from 150 to 22000 b.p. in size by liquid-liquid chromatography is described.