A novel glucagon receptor antagonist, NNC 25-0926, blunts hepatic glucose production in the conscious dog.

Elevated glucagon is associated with fasting hyperglycemia in type 2 diabetes. We assessed the effects of the glucagon receptor antagonist (2R)-N-[4-({4-(1-cyclohexen-1-yl)[(3,5-dichloroanilino)carbonyl]anilino}methyl)benzoyl]-2-hydroxy-b-alanine (NNC 25-0926) on hepatic glucose production (HPG) in vivo, using arteriovenous difference and tracer techniques in conscious dogs. The experiments consisted of equilibration (-140 to -40 min), control (40-0 min), and experimental [0-180 min, divided into P1 (0-60 min) and P2 (60-180 min)] periods.

Abnormal hippocampal neurochemistry in smokers: evidence from proton magnetic resonance spectroscopy at 3 T.

Objective: In animals, nicotine, the primary psychoactive constituent of tobacco smoke, reduces neurogenesis and increases cell loss in both hippocampus and cortex. Accordingly, tobacco smoking has been linked to reduced performance on cognitive paradigms requiring attention and working memory in humans. However, few prior studies have tested for evidence of structural brain alterations in human tobacco smokers.

Arginase 1 is expressed in myelocytes/metamyelocytes and localized in gelatinase granules of human neutrophils.

Arginase 1 (ARG1) metabolizes arginine, thus reducing the availability of arginine as a substrate for nitric oxide synthase (NOS). The decreased production of nitric oxide (NO) by NOS and the production of ornithine by ARG1 affect immune responses and tissue regeneration at sites of infection, respectively. We here demonstrate that ARG1 is synthesized in myelocytes/metamyelocytes and is stored in gelatinase granules.

Horizontal transfer of tet(M) and erm(B) resistance plasmids from food strains of Lactobacillus plantarum to Enterococcus faecalis JH2-2 in the gastrointestinal tract of gnotobiotic rats.

Two wild-type strains of Lactobacillus plantarum previously isolated from fermented dry sausages were analysed for their ability to transfer antibiotic resistance plasmids in the gastrointestinal tract. For this purpose, we used gnotobiotic rats as an in vivo model. Rats were initially inoculated with the recipient Enterococcus faecalis JH2-2 at a concentration of 10(10) CFU mL(-1).

Smoking and structural brain deficits: a volumetric MR investigation.

Growing evidence from animal studies indicates brain-damaging properties of nicotine exposure. Investigations in humans found a wide range of functional cerebral effects of nicotine and cigarette smoking, but studies focusing on brain damage are sparse. In 22 smokers and 23 never-smokers possible differences of the cerebral structures were investigated using magnetic resonance imaging and voxel-based morphometry.

Sublingual immunotherapy in children modulates allergen-induced in vitro expression of cytokine mRNA in PBMC.

Background: During subcutaneous immunotherapy (SCIT), there is a local mucosal shift from Th2 to Th1 type cytokine predominance and downregulation of interleukin (IL)-5 and eosinophilia. According to recent studies IL-10- and transforming growth factor (TGF)-beta-induced tolerance is another key phenomenon in SCIT. Few data to date is available on mechanisms and roles of these cytokines in sublingual immunotherapy (SLIT).

Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children.

Background: Subcutaneous immunotherapy has been the principal approach of immunotherapy in the treatment of allergic diseases. Several clinical studies with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy have been published suggesting a well-tolerated and clinically effective treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with these allergens have been published.

C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency.

Rationale: In both animals and humans, nicotine produces behavioral effects that vary across individuals. Studies examining the role of genetic variability in modulating individual response to nicotine in humans have increased, with recent work showing that genetic variation at the dopamine D2 receptor (DRD2) predicts response to pharmacotherapy for tobacco dependence.

Objectives: To determine whether a polymorphism of the DRD2 gene, C957T, that alters DRD2 binding availability in humans modifies the effects of nicotine on verbal working memory performance and on processing efficiency of brain regions that support verbal working memory.

Five-year follow-up on the PAT study: specific immunotherapy and long-term prevention of asthma in children.

Background: A 3-year course of specific immunotherapy (SIT) in children with hay fever to grass and/or birch pollen significantly reduced the risk of developing asthma. To investigate the long-term preventive effect, we performed a follow up--2 years after termination of immunotherapy.

Methods: A total of 183 children, aged 6-14 years with grass and/or birch pollen allergy could be investigated 2 years after discontinuation of SIT or no treatment.

Insulin detemir under steady-state conditions: no accumulation and constant metabolic effect over time with twice daily administration in subjects with Type 1 diabetes.

Aims: This study investigated the pharmacodynamic and pharmacokinetic characteristics of the novel long-acting insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of NPH insulin at steady state.

Methods: Twenty-five subjects with Type 1 diabetes [seven females, 18 males, mean age (+/- sd) 39 +/- 12 years, body mass index 24 +/- 3 kg/m(2)] participated in three 24-h glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses.

Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users.

Background: Cannabis remains the most widely used illicit substance by adolescents and is typically consumed by this population in the context of ongoing tobacco use. Human studies have shown that both cannabis and tobacco exert effects on cognitive function; however, little is known about possible interacting effects of these drugs on brain function and cognition during adolescent development.

Methods: Verbal learning and memory were assessed in 20 adolescent users of tobacco and cannabis and 25 adolescent tobacco users with minimal history of cannabis use.

Haptoglobin is synthesized during granulocyte differentiation, stored in specific granules, and released by neutrophils in response to activation.

Haptoglobin (Hp) is a plasma protein synthesized primarily by hepatocytes. It exerts a broad range of anti-inflammatory activities and acts indirectly as a bacteriostatic agent and an antioxidant by virtue of its ability to bind free hemoglobin (Hb) and to facilitate its immediate clearance by macrophages. We identified Hp as a novel specific granule protein of neutrophils by means of immunoelectron microscopy, subcellular fractionation, and exocytosis studies.

Visuospatial memory deficits emerging during nicotine withdrawal in adolescents with prenatal exposure to active maternal smoking.

Active maternal smoking during pregnancy elevates the risk of cognitive deficits and tobacco smoking among offspring. Preclinical work has shown that combined prenatal and adolescent exposure to nicotine produces more pronounced hippocampal changes and greater deficits in cholinergic activity upon nicotine withdrawal than does prenatal or adolescent exposure to nicotine alone. Few prior studies have examined the potential modifying effects of gestational exposure to active maternal smoking on cognitive or brain functional response to tobacco smoking or nicotine withdrawal in adolescents.

Large-area Fabry-Perot modulator based on electro-optic polymers.

We present a large-area electro-optic Fabry-Perot modulator utilizing a photoaddressable bis-azo polymer placed between two dielectric mirrors with an open aperture of 2 cm. A modulation efficiency of 1% at an effective modulation voltage of 20 V for a wavelength of 1.55 microm is demonstrated.

Intubation conditions after rocuronium or succinylcholine for rapid sequence induction with alfentanil and propofol in the emergency patient.

Background And Objective: Previous studies mainly conducted on elective patients recommend doses of 0.9-1.2 mg kg[-1] rocuronium to obtain comparable intubation conditions with succinylcholine 1.

A new mechanism for chloramphenicol, florfenicol and clindamycin resistance: methylation of 23S ribosomal RNA at A2503.

The gene product of cfr from Staphylococcus sciuri confers resistance to chloramphenicol, florfenicol and clindamycin in Staphylococcus spp. and Escherichia coli. Cfr is not similar to any other known chloramphenicol resistance determinant.

Highly glycosylated alpha1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released by activated neutrophils.

Alpha-1-acid glycoprotein (AGP) is an acute-phase protein produced by hepatocytes and secreted into plasma in response to infection/injury. We recently assessed the transcriptional program of terminal granulocytic differentiation by microarray analysis of bone marrow (BM) populations highly enriched in promyelocytes, myelocytes/metamyelocytes (MYs), and BM neutrophils. These analyses demonstrated a transient, high mRNA expression of genuine secondary/tertiary granule proteins and AGP in MYs.

Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene.

Unlabelled: A polymorphism involving a variable number of tandem repeats (VNTR) has been described in the 3' untranslated region of the gene (SLC6A3) coding for the dopamine transporter (DAT). This polymorphism has 2 common alleles, designated as 10-repeat (*10R) and 9-repeat (*9R), that have been linked with several human clinical phenotypes. Previous investigations of the effects of the SLC6A3 polymorphism on DAT availability in smaller samples of humans have yielded divergent results.

Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain.

Tomosyn was previously identified as a syntaxin-binding protein that inhibits soluble NSF (n-ethylmaleimide-sensitive fusion protein) attachment protein receptor (SNARE)-mediated secretion. We set out to investigate the distribution of tomosyn mRNA in the mammalian brain and found evidence for the presence of two paralogous genes designated tomosyn-1 and -2. In a collection of tomosyn-2 cDNA clones, we observed four splice variants (named xb-, b-, m- and s-tomosyn-2) derived from the skipping of exons 19 and 21.

Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers.

Background: In adult animals and humans, nicotine can produce short-term cognitive enhancement and, in some cases, neuroprotection. Recent work in animals, however, suggests that exposure to nicotine during adolescence might be neurotoxic. We tested for evidence of acute and chronic effects of tobacco smoking on cognition in adolescents who smoked tobacco daily and were compared with adolescent nonsmokers.

The transcriptional program of terminal granulocytic differentiation.

To characterize the transcriptional program that governs terminal granulocytic differentiation in vivo, we performed comprehensive microarray analyses of human bone marrow populations highly enriched in promyelocytes (PMs), myelocytes/metamyelocytes (MYs), and neutrophils (bm-PMNs). These analyses identified 11 310 genes involved in differentiation, of which 6700 were differentially regulated, including previously unidentified effector proteins and surface receptors of neutrophils. Differentiation of PMs toward MYs was accompanied by a marked decline of proliferative and general cellular activity as defined by down-regulation of E2 promoter binding factor (E2F) target genes; cyclin dependent kinases 2, 4, and 6; and various metabolic, proteasomal, and mitochondrial genes.

Long-term sick leave and its risk factors during pregnancy among Danish hospital employees.

Aim: The authors sought to describe risk indicators of long-term sick leave during pregnancy among hospital employees.

Methods: A register-based study was undertaken of 4,852 female hospital employees aged 20-45 years from the second largest hospital in Denmark during 1995-99 based on job titles, working time, sick leave, and births combined with a survey among a total of 773 women who had been pregnant during their employment (response rate 85%).

Results: Altogether 236 (31%) were on sick leave for at least 10% of their scheduled work time during their latest pregnancy and 169 (22%) had been absent at least 20% of the time.

Impact of cannabis use on brain function in adolescents.

Cannabis is the most common illicit substance used by adolescents. This paper reports results of a pilot study using fMRI and a working memory task to compare brain function of adolescent cannabis users to that of two control groups, one matched for tobacco use and the other for nonsmokers.

FuGENE 6 Transfection Reagent: the gentle power.

FuGENE 6 Transfection Reagent has been commercially available since 1997. Since that time, its popularity has increased due to its ease of use, minimal to no cytotoxicity, and the high level of transfection in many different cell lines. FuGENE 6 Transfection Reagent is gentle on the cells.