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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Cannabinoid receptors and the endocannabinoids anandamide and 2-arachidonoylglycerol have been suggested to regulate food intake in several animal phyla. Orthologs of the mammalian cannabinoid CB1 and CB2 receptors have been identified in fish. We investigated the presence of this endocannabinoid system in the brain of the goldfish Carassius auratus and its role in food consumption. CB1-like immunoreactivity was distributed throughout the goldfish brain. The prosencephalon showed strong CB1-like immunoreactivity in the telencephalon and the inferior lobes of the posterior hypothalamus. Endocannabinoids were detected in all brain regions of C. auratus and an anandamide-hydrolysing enzymatic activity with features similar to those of mammalian fatty acid amide hydrolase was found. Food deprivation for 24 h was accompanied by a significant increase of anandamide, but not 2-arachidonoylglycerol, levels only in the telencephalon. Anandamide caused a dose-dependent effect on food intake within 2 h of intraperitoneal administration to satiated fish and significantly enhanced or reduced food intake at low (1 pg/g body weight) or intermediate (10 pg/g) doses, respectively, the highest dose tested (100 pg/g) being inactive. We suggest that endocannabinoids might variously contribute to adaptive responses to food shortage in fish.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1460-9592
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Craniopagus conjoining represents a complex and challenging issue for neurosurgeons as well as for anesthesiologists. A rare face-to-face case of conjoined twins underwent surgical separation and presented peculiar differences compared with those already reported in the literature. Even in cases lacking large cerebrovascular sinus connections, the impending risk of large blood loss and hemorrhagic shock in the infant requires a high level of surveillance and the institution of invasive monitoring.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1433-9285
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We carried out a population-based prevalence study to assess the association between the presence of alcohol-related problems within the family and the risk of disorders in the children's global functioning level. We enrolled 394 children attending nursery, primary and secondary schools and their parents living in two municipalities in Central Italy. Alcohol-related problems within the family were reported by registered records obtained from general practitioners and teachers, who were considered as preference raters. The childrens level of functioning was assessed by teachers, who attributed to each school child a score according to the Children Global Assessment Scale (CGAS). The number of reports of alcohol-related problems within the family and the CGAS scores were considered, respectively, as independent and dependent variables in a multiple logistic regression model for ordinal outcome variables. The children's sex and age, and the age of their parents, the duration of the parents' education and family size were considered as covariates. We found a strong association between a poor level of functioning in the children in the social environment and alcohol-related problems within the family. The pravalence odds ratio (and 95% confidence interval) decreased from 0.5 (range 0.2–1.3) for children whose families were reported by one rater to 0.4 (range 0.2–0.8) for children whose families were reported by two raters, the non-reported families being the reference category, suggesting that the level of functioning of the child decreased as reports of alcohol-related problems in the family increased.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract During a survey of the mutations of the low density lipoprotein receptor (LDL-R) gene in Italian patients with familial hypercholesterolemia (FH), we identified a novel point mutation, that creates a new EcoRI site at the 5′ end of exon 7, in a heterozygous FH subject (FH-100). The sequence of a cDNA fragment encompassing exon 7 showed the presence of a G→T transversion in codon 297; this created a new EcoRI site and produced a missense mutation, leading to a Cys297→Phe substitution in repeat A of the epidermal growth factor (EGF) precursor homology domain of LDL-R. Since the substitution of Cys297 disrupts the intracellular transport of the LDL-R protein, as previously demonstrated by site-directed mutagenesis, we suggest that this mutation is the cause of FH in the FH-100 proband. We screened the DNA of 303 Italian FH patients by amplification of exon 7 from genomic DNA followed by digestion with EcoRI or by Southern blotting. Two individuals (FH-64 and FH-127) were found to be carriers of the Cys297→Phe mutation. Restriction fragment length polymorphism analysis demonstrated that, in two kindreds (FH-64 and FH-100), the haplotype in linkage with the Cys297→Phe mutation was the same, suggesting the presence of a common ancestor. The Cys297→Phe mutation has been designated FHTrieste after the name of the city in Northern Italy from which probands FH-100 and FH-127 originate.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 617-619 
    ISSN: 1432-1041
    Keywords: clotiazepam ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the single dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets in a cross-over study in 6 healthy volunteers (median age 28 years). The formulations had similar systemic availability. Compared with oral tablets the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-5233
    Keywords: Key words Family history ; Insulin-dependent diabetes mellitus ; Case-control study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Insulin-dependent diabetes mellitus (type 1) is a common chronic disease of childhood occurring throughout the world. In the literature, its most important determinants include genetic, environmental and familial factors. We evaluated family history as a determinant of the risk of type 1 diabetes mellitus with a population-based case-control study. Information about type 1 patients was taken from the dedicated register of the Abruzzo Region; the register has been collecting incident cases in the age group 0–14 years, diagnosed between 1 January 1990 and 31 December 1996. The control group was taken from the lists of patients attending family pediatricians. The family history data for type 1 and type 2 patients was obtained by a questionnaire, administered to their parents. The risk of type 1 diabetes mellitus associated with its occurrence in first- and second-degree relatives was estimated using logistic regression methods. Our results show that the risk is indeed increased with a positive family history (OR=3.96; 95% CI 1.54–10.14). This shows that the risk of type 1 diabetes mellitus for children whose fathers are affected by the disease is 11 times higher with respect to controls. Moreover, the risk for children whose brothers are affected by the disease is 20 times higher with respect to controls. In contrast, a family history for type 2 diabetes mellitus does not influence the risk.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-5233
    Keywords: Key words Type 1 diabetes mellitus ; Management ; Cross-sectional study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The main objectives of type 1 diabetes mellitus (DM) management include keeping glycemia levels within the euglycemic range to prevent complications. Daily self-monitoring is an important problem for many diabetic patients, particularly for adolescents. The aim of this study was to evaluate the determinants of poor daily self-monitoring, focusing on the patients' parents' perception of the problem. In order to evaluate parents' awareness of their children's disease-monitoring status, we carried out a cross-sectional investigation of a sample of children and adolescents from a population-based register, with the corresponding population of parents. To collect our data, we used a 33-item questionnaire, separately administered by diabetologists to both parents and children. We estimated the concordance with respect to patients' and parents' answers. Adolescents followed their overall medical prescriptions more regularly (48.8%) than children (29.7%), but mostly frequently they forgot to use glycemic tests (adolescents 42.4%, children 29,7%). A major duration of disease affected HbA1c levels (values 〉: 8%) of patients younger than 14 years (pFisher = 0.016). Our results indicate a worse compliance of adolescents with respect to children in attending to daily self-monitoring, not just regarding daily glycemic levels but also the course of daily activities such as going to school, studying, working, and simulating symptoms and signs of hypo-hyperglycemia. Parents mostly ignored their child's self-monitoring status and the related motivations.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-7284
    Keywords: Alcohol consumption ; Cirrhosis ; Coffee consumption ; Tobacco smoking
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to assess the interaction between alcohol intake, tobacco smoking and coffee con sumption in determining the risk of liver cirrhosis we carried out a hospital-based case-control study involving 115 patients at their first diagnosis of cirrhosis and 167 control patients consecutively enrolled in the General Hospitals of the Province of L'Aquila (Central Italy). The mean life-time daily alcohol intake (as g ethanol consumed daily) was measured by direct patient interviews, whose reproducibility was 〉0.80 and similar for cases and controls, as checked by interviewing the relatives of a sample of 50 cases and 73 controls. During the same patient's interview we also measured the mean consumption of coffee (daily number of cups of filtered coffee) and tobacco (life-time daily number of cigarettes smoked). A dose-effect relationship on the risk of cirrhosis was present both for alcohol intake — for which the risk was significantly increased above 100 g of daily intake — and for cigarette consumption. The latter did not however improve the goodness-of-fit of a logistic regression model including alcohol intake as covariate. By contrast, coffee consumption had a protective effect on the risk of cirrhosis and significantly improved the goodness-of-fit of such a model. Abstaining from coffee consumption determined both a significantly increased risk of cirrhosis, even for daily alcohol intake below 100 g, and a multiplicative effect with alcohol intake on this risk. In patients drinking ⩾101 g ethanol daily the relative risk increased from 5.5 (95% confidence interval: 1.4–22.0) for coffee consumers to 10.8 (95% confidence interval: 1.3–58.1) for coffee abstainers. We conclude that: (1) tobacco smoking is likely to be a faint risk factor for cirrhosis, and studies on wider patients series should be performed for confirmation; (2) coffee drinking is associated with a reduced risk of cirrhosis. Whether coffee contains some hitherto unknown protective substances, or is just a marker of other life-style or dietary protective factors, deserves further clarification.
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  • 9
    Publication Date: 2013-11-02
    Description: Purpose: To provide rationale for using phosphoinositide 3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathway inhibitors to treat rhabdomyosarcomas, a major cause of pediatric and adolescent cancer deaths. Experimental Design: The prevalence of PI3K/MAPK pathway activation in rhabdomyosarcoma clinical samples was assessed using immunohistochemistry. Compensatory signaling and cross-talk between PI3K/MAPK pathways was determined in rhabdomyosarcoma cell lines following p110α short hairpin RNA–mediated depletion. Pharmacologic inhibition of reprogrammed signaling in stable p110α knockdown lines was used to determine the target-inhibition profile inducing maximal growth inhibition. The in vitro and in vivo efficacy of inhibitors of TORC1/2 (AZD8055), MEK (AZD6244), and P13K/mTOR (NVP-BEZ235) was evaluated alone and in pairwise combinations. Results: PI3K pathway activation was seen in 82.5% rhabdomyosarcomas with coactivated MAPK in 36% and 46% of alveolar and embryonal subtypes, respectively. p110α knockdown in cell lines over the short and long term was associated with compensatory expression of other p110 isoforms, activation of the MAPK pathway, and cross-talk to reactivate the PI3K pathway. Combinations of PI3K pathway and MAP–ERK kinase (MEK) inhibitors synergistically inhibited cell growth in vitro . Treatment of RD cells with AZD8055 plus AZD6244 blocked reciprocal pathway activation, as evidenced by reduced AKT/ERK/S6 phosphorylation. In vivo , the synergistic effect on growth and changes in pharmacodynamic biomarkers was recapitulated using the AZD8055/AZD6244 combination but not NVP-BEZ235/AZD6244. Pharmacokinetic analysis provided evidence of drug–drug interaction with both combinations. Conclusions: Dual PI3K/MAPK pathway activation and compensatory signaling in both rhabdomyosarcoma subtypes predict a lack of clinical efficacy for single agents targeting either pathway, supporting a therapeutic strategy combining a TORC1/2 with a MEK inhibitor. Clin Cancer Res; 19(21); 5940–51. ©2013 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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  • 10
    Publication Date: 2017-10-28
    Description: Author(s): P. Schütz, D. V. Christensen, V. Borisov, F. Pfaff, P. Scheiderer, L. Dudy, M. Zapf, J. Gabel, Y. Z. Chen, N. Pryds, V. A. Rogalev, V. N. Strocov, C. Schlueter, T.-L. Lee, H. O. Jeschke, R. Valentí, M. Sing, and R. Claessen The spinel/perovskite heterointerface γ − Al 2 O 3 / SrTiO 3 hosts a two-dimensional electron system (2DES) with electron mobilities exceeding those in its all-perovskite counterpart LaAlO 3 / SrTiO 3 by more than an order of magnitude, despite the abundance of oxygen vacancies which act as electron donors as w... [Phys. Rev. B 96, 161409(R)] Published Fri Oct 27, 2017
    Keywords: Surface physics, nanoscale physics, low-dimensional systems
    Print ISSN: 1098-0121
    Electronic ISSN: 1095-3795
    Topics: Physics
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