bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomalies of tooth formation in hypohidrotic ectodermal dysplasia
Authors: LEXNER MICHALA O. , BARDOW ALLAN , HERTZ JENS MICHAEL , NIELSEN LIS A. , KREIBORG SVEN
Published: November 2006

Objective.  The X‐linked hypohidrotic ectodermal dysplasia (HED) is the most common type of ectodermal dysplasia. The clinical identification of possible heterozygous females can be difficult because of the varying degrees of clinical signs caused by X‐chromosome inactivation. This study is the first to elaborate on anomalies of tooth formation found in a group of hemizygous males and heterozygous females with known ED1 mutations. These tooth anomalies may be used as dental biomarkers for heterozygous females, enabling an earlier diagnosis, and therefore, better treatment and genetic counselling.

Methods.  Anomalies of tooth formation were examined using panoramic radiographs, dental casts and oral photographs in hemizygous males and heterozygous females who were identified by molecular genetic analysis. The results were compared to existing controls and normative data.

Results.  All affected males had multiple missing permanent teeth and tooth malformations. The heterozygous females had a significantly higher frequency of agenesis of permanent teeth compared to normative data. The heterozygous females had an increased prevalence of tooth malformations and reduced tooth size, especially in the mesiodistal dimension.

Conclusions.  We conclude that observed anomalies of tooth formation may be used as dental biomarkers in the clinical identification of potentially heterozygous females.
Abnormal κ:λ Light Chain Ratio in Circulating Immune Complexes as a Marker for B Cell Activity in Juvenile Idiopathic Arthritis
Authors: Low J. M. , Chauhan A. K. , Moore T. L.
Published: November 2006

Patients with juvenile idiopathic arthritis (JIA) have been shown to have elevated levels of circulating immune complexes (CICs) which correlated with disease activity. Our aim was to assess B cell activity by measuring the amount of and the κ:λ chain immunoglobulin light (L) chain ratio in CICs from JIA patients and to determine potential evidence for either an antigen‐driven response or B‐cell receptor editing. We used an enzyme‐linked immunosorbent assay to measure κ and λ chains present in the CICs from the sera of patients with JIA. Statistical analysis was performed using Pearson's correlation, one‐way ANOVA and Bonferroni post hoc analysis. Sera from 44 JIA patients were examined for the concentration of L chains in CICs. Healthy controls had a κ:λ chain ratio of 1.2:1, whereas this ratio was reversed among JIA subgroups with RF‐positive polyarthritis (1:1.2), RF‐negative polyarthritis (1:1.3), oligoarthritis (1:2.3) and systemic‐onset arthritis (1:2.5). In addition, overall λ chain selection was not significantly associated with a particular immunoglobulin heavy (H) chain and occurred with all immunoglobulin isotypes. We showed preferential selection of λ chains contributing to the formation of potentially pathogenic CICs from JIA patients, of all onset types compared to healthy controls, in an H chain‐independent manner. The reversal of κ:λ chain ratio within the JIA CICs and association with all immunoglobulin isotypes demonstrated the potential for L chain editing. Furthermore, we conclude that a reversal of the normal κ:λ chain ratio in JIA CICs may be used as a marker for increased B‐cell activity.
A Comparison of the Humoral and Cellular Immune Responses at Different Immunological Sites after Split Influenza Virus Vaccination of Mice
Authors: Hauge S. , Madhun A. S. , Cox R. J. , Brokstad K. A. , Haaheim L. R.
Published: November 2006

The spleen, bone marrow and lymph nodes are all known to be important organs for the initiation and maintenance of an immune response after vaccination. To investigate the differences and similarities in the humoral and cellular immune responses between these tissues, we vaccinated mice once or twice with the conventional human dose (15 μg HA) of influenza A (H3N2) split virus vaccine and analysed the sera and lymphocytes collected from the different sites. We found that the response of antibody secreting cells (ASC) in the lymph nodes appeared to be more transient than in the spleen, possibly because the influenza‐specific IgM ASC in particular might have migrated from the lymph nodes immediately after activation. The serum antibody response was found to initially correspond with the ASC response elicited in the spleen and the lymph nodes, whereas the later serum IgG reflected the ASC response in the bone marrow. Proliferation of influenza‐specific CD4+ and CD8+ cells was predominantly observed in the spleen and was associated with higher concentrations of cytokines than in the lymph nodes. The finding of influenza‐specific CD8+ cell proliferation in the spleen indicates that a split influenza virus vaccine may stimulate a cytotoxic T‐cell response. Our results also showed that the primary response elicited a mixed Th1/Th2 profile, whereas the secondary response was skewed towards a Th2 type. Each of the three tissues had a different immunological pattern, suggesting that in preclinical vaccine studies, there is a case for investigating a range of immunological sites.
Interrater reliability of the Social Profile: Assessment of community and psychiatric group participation
Authors: Donohue Mary V.
Published: November 2006

Background/Aim:  The Social Profile was developed based on the theoretical concepts of activity group participation skills: Parallel, Associative, Basic and Supportive Cooperative and Mature activity levels. The aim of this study is to assess the interrater reliability of observations in groups of children and adults using the Social Profile.

Methods:  Two community and two hospital populations were used to determine the interrater reliability of the Social Profile as observed by clinicians and graduate students. These groups included preschool children, older adults, general, geriatric and substance abuse psychiatric patients. Observers consisted of clinicians and graduate student pairs.

Results:  Moderately high intraclass correlation coefficient (ICC) scores of interrater reliability were found in separate and combined scores from the Social Profile measurements.

Conclusion:  These ICC reliability rates indicate that the Social Profile interrater scores are adequately high for acceptable measurement of social and activity participation levels in clinical, community and school groups.
“On‐demand” therapy for gastroesophageal reflux disease: Are current proton pump inhibitors good candidates?
Authors: Goh Khean‐Lee
Published: November 2006

In the long term management of gastroesophageal reflux disease, an “on‐demand” therapy is a sensible and effective treatment strategy. Patients do not comply with continuous maintenance medications and will usually take medications only when symptoms occur. An “on‐demand” therapy is particularly useful in patients with nonerosive reflux disease or mild forms of gastroesophageal reflux disease. Currently available proton pump inhibitors provide potent acid suppression and are suitable for an on‐demand therapy. Special features required of an on‐demand therapeutic agent would include a rapid onset of action. Owing to its special characteristics, with rapid binding to the proton‐pumps, rabeprazole provides the fastest symptom relief compared to other agents. Formal trials of on‐demand therapy show that patients take medications only once in every 3 or 4 days and the majority of patients are satisfied with this treatment approach.
LA ESQUINA (THE CORNER): DAY LABORERS ON THE MARGINS OF NEW YORK'S FORMAL ECONOMY
Authors: Theodore Nik , Valenzuela Abel , Meléndez Edwin
Published: November 2006

This article presents the findings of a survey of day laborers who gather at informal hiring sites in the New York metropolitan area. Day laborers are employed by construction contractors, landscaping companies, homeowners, and small businesses to undertake manual labor jobs for low pay. The work is precarious and steady employment is rare. In addition, the day labor market is characterized by routine violations of labor and employment laws, and workers are often exposed to unsafe working conditions. These conditions prevail, in part, because day laborers largely are disconnected from workers rights' advocacy efforts. However, the creation of worker centers aims to remedy this situation. Several community organizations in the region are now actively contesting abuses in the day labor market and increasing both accountability in and transparency of the hiring process.
REPRESENTATIONS AND RIGIDITY OF Aut(F3)
Authors: HUMPHRIES STEPHEN P.
Published: November 2006

We construct some new matrix representations of Aut (F3), the automorphism group of a free group of rank 3, and show that there are infinitely many distinct irreducible representations of Aut (F3) in dimensions at most 42.
Study of physiological responses to acute carbon monoxide exposure with a human patient simulator
Authors: Cesari Whitney A. , Caruso Dominique M. , Zyka Enela L. , Schroff Stuart T. , Evans Charles H. , Hyatt Jon-Philippe K.
Published: November 2006

Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design, conduct, and present (orally and in written form) their project testing physiological adaptation to an extreme environment. This article is a student report on the physiological response to acute carbon monoxide exposure in a simulated healthy adult male and a coal miner and represents how 1) human patient simulators can be used in a nonclinical way for experiential hypothesis testing; 2) students can transition from traditional textbook learning to practical application of their knowledge; and 3) student-initiated group investigation drives critical thought. While the course instructors remain available for consultation throughout the project, the relatively unstructured framework of the assignment drives the students to create an experiment independently, troubleshoot problems, and interpret the results. The only stipulation of the project is that the students must generate an experiment that is physiologically realistic and that requires them to search out and incorporate appropriate data from primary scientific literature. In this context, the human patient simulator is a viable educational tool for teaching integrative physiology in a laboratory environment by bridging textual information with experiential investigation.
Installment options close to expiry
Authors: Alobaidi G. , Mallier R.
Published: November 2006

We use an asymptotic expansion to study the behavior of installment options close to expiry. Installment options are contracts where the price is paid over the life of the option rather than as a lump sum at the time of purchase, and where the contract can be allowed to lapse at any time. Series solutions are obtained for the location of the free boundary and the price of the option.
Analysis of natural in‐plane vibration of rectangular plates using homotopy perturbation approach
Authors: Andrianov Igor V. , Awrejcewicz Jan , Chernetskyy Vladimir
Published: November 2006

An analytical solution of the problem of free in‐plane vibration of rectangular plates with complicated boundary conditions is proposed.
Synchronous state in a fully connected phase‐locked loop network
Authors: Piqueira J. R. C. , Oliveira M. Q. , Monteiro L. H. A.
Published: November 2006

Fully connected phase‐locked networks are built with all nodes exchanging phase and frequency signals. The nodes are phase‐locked loops (PLLs) with slightly different free‐running frequencies. The synchronous state emerges from a dynamic process with the phase interactions generating a common frequency steady state. In this
work, an estimation is analytically obtained for the synchronous state in a generic N‐node network. Numerical experiments complete the analysis of the fully connected network relating free‐running frequencies, node gains, and propagation delays.
Approximate transformations for van der Pol‐type equations
Authors: Gazizov R. K. , Khalique C. M.
Published: November 2006

Classification of van der Pol‐type equations with respect to admitted approximate
transformation groups transforming a small parameter is given.
It is shown that approximate symmetries transforming the small parameter as well as the usual
approximate symmetries can be used for approximate integration (e.g., by method of
successive reduction of order) of ordinary differential equations with a small parameter.
Late-annalistic Battle Scenes in Livy
Authors: Erdkamp Paul
Published: November 2006

Livy's books 21-44 contain roughly ninety battles, about half of which are mentioned only briefly, though usually including figures on casualties, captives and booty. Livy's full-scale narratives show differences in style, nature and content, including technical matters like the terminology used for units of the Roman army. Comparison between Livy's and Polybius' narratives on the battles of Cynoscephalae, the Great Plain and Zama show that Livy closely adhered to the terminology of his sources. Differences in terminology therefore reflect Livy's use of different sources. One set of Livian battle scenes is characterised by the numbering of legions and by details concerning allied units. Various elements indicate a late-annalistic origin for these battle narratives, identified here as Valerius Antias. Battle narratives of this type are limited to particular periods and regions: Italy during the Second Punic War; Spain and Gaul from the end of the Second Punic War onwards. This shows that Livy decided on this particular source for these particular theatres of war. Outside these parts of his account, Livy briefly summarised the battle narratives he found in his predecessor's work.
Are endemic snakes with a narrow distribution more specialist than their wide-ranging counterparts? Evidence from the prey composition and morphometric correlates of the diet in Zamenis lineatus, a rat snake endemic to southern Italy
Authors: Capula Massimo , Luiselli Luca , Valenti Sophia , Ceccarelli Arianna , Rugiero Lorenzo , Aloise Gaetano
Published: November 2006

The snakes of the Mediterranean regions are in general characterised as wide
ranging with relatively unspecialised ecological traits (e.g., feeding
ecology and diet composition). The few endemic snake species with a narrow
range can be of great interest to control whether the relative ecological
non-specialization is truly general for Mediterranean snakes or if, on the
contrary, those species with a small range are so because of their more
specialised ecology. Here, we study the case of the Italian Aesulapian
snake, Zamenis lineatus, which is endemic to southern Italy and the island
of Sicily, and that has been for long time considered merely as a subspecies
of the widespread Zamenis longissimus. We studied the diet of this species
in the wild, and also examined snout-vent length and head length in several
museum vouchers in order to highlight the eventual morphometric correlates
of diet composition. Our results showed (i) a diet based on small mammals
and birds, (ii) an evident ontogenetic shift in diet composition (from
ectotherms to endotherms), and (iii) a lack of significant intersexual
difference in diet composition. In addition, morphometric data revealed no
intersexual differences in average snout-vent-length or head length. The
general implications of these results are discussed. We conclude that, based
on this study case, Zamenis lineatus feeding ecology was very similar to
that of the widespread and ecological generalist Zamenis longissimus, and
this is contrary to the hypothesis that endemic, narrowly distributed
Mediterranean snakes may be more specialist than their widespread
counterparts.
The effects of maternal size on clutch traits in a tropical invariant-clutch lizard, Carlia rubrigularis (Scincidae)
Authors: Goodman Brett Alexander
Published: November 2006

Species with an invariant or "fixed" clutch offer a unique opportunity to examine how variation in maternal size relates to key reproductive traits, such as egg size. Theoretical models of offspring size suggest selection should operate to optimize egg size and reproductive output. However, because invariant-clutch species are unable to allocate surplus resources to additional eggs (or offspring) they may exhibit different relationships than those anticipated under theoretical expectations. To test this, I examined relationships between maternal size-egg size in Carlia rubrigularis, an invariant-clutch producing scincid lizard from tropical Australia. C. rubrigularis exhibited relative clutch masses that were lower than variant clutch size species, but which were similar to other invariant clutch size species. However, maternal size (snout-vent length and post-oviposition mass) was correlated with several clutch traits (egg mass, egg width and egg volume), but females in better condition did not produce relatively heavier eggs. These results suggest mechanistic hypotheses may best explain the observed maternal size-egg size relationships in C. rubrigularis.
Seinura lii n. sp. and S. wuae n. sp. (Nematoda: Seinuridae) from pine wood in China
Authors: Huang Ren E , Ye Jian Ren
Published: November 2006

Seinura lii n. sp. and S. wuae n. sp. are described and illustrated from
dying Pinus massoniana infested with Bursaphelenchus xylophilus in China.
Seinura lii n. sp. is characterised by relatively long female and male
bodies (763-1146 and 831-1068 μm, respectively), stylet 16-20 μm long and
lacking knobs, two rows of developing oocytes in the anterior gonad,
well-developed postuterine sac (120-182 μm long), three lines or incisures
in the lateral field, four pairs of subventral papillae on the male tail
region, and an elongate-conoid female tail. Seinura wuae n. sp. is
characterised by relatively long female and male bodies (819-1179 and
787-1062 μm, respectively), stylet 15-18 μm long and with small knobs, three
lines or incisures in the lateral field, two or three rows of developing
oocytes in the anterior gonad, long postuterine sac (103-172 μm long), two
pairs of subventral papillae on the male tail region, and an elongate-conoid
female tail.
Development of an in vivo bioassay to identify sugar beet resistance to the stem nematode Ditylenchus dipsaci
Authors: Kühnhold Volker , Kiewnick Sebastian , Sikora Richard A.
Published: November 2006

A bioassay was developed to evaluate sugar beet for resistance to the stem
nematode Ditylenchus dipsaci. To produce large numbers of D. dipsaci for
inoculation of sugar beet seedlings, a protocol for a monoxenic carrot disk
culture was established. Ditylenchus dipsaci multiplication was greatest
with 125 000 nematodes per carrot disk after 72 days at 20°C with an initial
inoculum density of 75 nematodes. Higher inoculum densities resulted in more
rapid decay of carrot tissue and lower numbers of D. dipsaci. Inoculation of
200 D. dipsaci in leaf axils of sugar beet seedlings resulted in high
penetration rates. The addition of 1% carboxymethyl cellulose (CMC) as a
gelling agent resulted in a significantly increased penetration rate of 96%
compared to tap water with 34%. Soil infestation was not suitable, with only
4 and 11% of the nematodes penetrating the sugar beet seedlings when
inoculum was applied in water and CMC, respectively. The bioassay enables a
rapid screening for resistance in sugar beet to D. dipsaci.
Potential use of arugula (Eruca sativa L.) as a trap crop for Meloidogyne hapla
Authors: Melakeberhan Haddish , Xu Alex , Kravchenko Alexandra , Mennan Sevilhan , Riga Ekaterini
Published: November 2006

In the absence of resistant cultivars, the impending loss of methyl bromide
(MBr) and few sustainable alternatives available, managing the northern
root-knot nematode, Meloidogyne hapla, is a challenge in temperate vegetable
and nursery production systems. Many brassica plants, including arugula,
Eruca sativa, possess biofumigant and trap crop qualities, and thus have
been gaining popularity as potential alternatives to MBr. As part of a
project to develop alternatives to MBr, this study was conducted to
determine the effects of arugula cv. Nemat on three glasshouse populations
of M. hapla from Rhode Island (RI), New York, Geneva (NYG) and Michigan
(MI). In two glasshouse experiments conducted at 20 ± 2°C and 28 ± 2°C,
arugula and Rutgers tomato (standard susceptible) seedlings were inoculated
with either 0 (control) or 3000 eggs of 67-85% undifferentiated stages of
the three populations. Experiment 1 was terminated at 20 days and Experiment
2 at 28 days after nematode inoculation. At 20°C, 200 and 280 degree-days
(DD, base 10°C) were accumulated, while 360 and 504 DD were accumulated at
28°C in the respective experiments. Total numbers of nematodes recovered
from roots varied by host and by nematode population over the course of the
study, but the numbers of females in roots did not vary significantly. This
suggests variability in reaching the adult female stage. Egg and egg mass
production was normal in all nematode-infected tomatoes, but no eggs were
produced in more than 80% of arugula plants, and less than 17% of the
arugula samples had fewer than five loose eggs and no egg masses. The
results show that arugula interferes with development and reproduction of
populations of M. hapla and thus has potential as a trap crop to control M.
hapla.
Religious drug use in England, South Africa and the United States of America
Authors: Edge Peter
Published: November 2006

The question of whether there should be a fundamental right to sacramental use of psychotropic drugs, despite the existence of a general prohibition against the drug in question, has been considered by the courts of England, South Africa, and the United States. Despite the commonality of the issues in all three countries, the approaches taken by the courts show significant differences of interest beyond the factual situation. In particular, a consideration of the cases suggests different strategies in evaluating justificatory claims by the state when incidentally restricting religious practice; differing use of cases from other jurisdictions; and differing emphases on the importance of international law in interpreting fundamental rights.
A Lay Health Advisor Program to Promote Community Capacity and Change Among Change Agents
Authors: Plescia Marcus , Groblewski Martha , Chavis LaTonya
Published: November 2006

The Charlotte REACH 2010 project focuses on cardiovascular disease and diabetes among African Americans in a geographically defined community. The goal of the project is to create changes in individual behaviors, community capacity, change agents, and systemic policies and actions that will result in the reduction of health disparities related to cardiovascular disease and diabetes. The project consists of three main components: lay health advisors as change agents, targeted interventions (exercise, nutrition, smoking cessation, primary care), and environmental and systemic interventions. The purpose of this article is to describe the lay health advisor intervention using qualitative methodologies that were developed to document changes in community capacity and change among change agents. Lay health advisors report that they have internalized their role as a community advocate and have made positive changes in their own personal health behavior. Their understanding of the underlying causes of poor health has expanded to include social and institutional factors and they have begun to shift their emphasis toward advocacy for social and institutional change.
Generation of peripheral B cells occurs via two spatially and temporally distinct pathways
Authors: Lindsley Robert Coleman , Thomas Matthew , Srivastava Bhaskar , Allman David
Published: November 2006

We have identified a population of newly formed bone marrow (BM) B cells that shares multiple characteristics with late transitional B cells in the spleen. Both late splenic transitional B cells and cells within this uncharacterized BM population expressed the cell-surface phenotype AA4+ CD23+, yet the developmental kinetics and the renewal rate of AA4+ CD23+ BM B cells mirrored recently formed BM B cells. Further, unlike the least mature B cells in the BM and spleen, AA4+ CD23+ BM B cells expressed the homing receptor CD62L, were dependent on the antiapoptotic cytokine receptor BR3 and the tec family kinase Btk, and proliferated in response to IL-4 plus CD40 stimulation. Finally, frequencies of λ light chain-positive B cells declined among AA4+ CD23+ B cells in both the BM and spleen, suggesting that V-gene selection events correlate with CD23 expression in both compartments. These observations indicate that the first step in B-cell maturation occurs in both the BM and the periphery and suggest that recently formed B cells exit the BM as a heterogeneous pool of immature and semimature B cells.
Signal peptide peptidase (SPP) dimer formation as assessed by fluorescence lifetime imaging microscopy (FLIM) in intact cells
Authors: Nyborg Andrew C , Herl Lauren , Berezovska Oksana , Thomas Anne V , Ladd Thomas B , Jansen Karen , Hyman Bradley T , Golde Todd E
Published: November 2006

Background

Signal peptide peptidase (SPP) is an intramembrane cleaving protease identified by its cleavage of several type II membrane signal peptides. Conservation of intramembrane active site residues demonstrates that SPP, SPP family members, and presenilins (PSs) make up a family of intramembrane cleaving proteases. Because SPP appears to function without additional protein cofactors, the study of SPP may provide structural insights into the mechanism of intramembrane proteolysis by this biomedically important family of proteins. Previous studies have shown that SPP isolated from cells appears to be a homodimer, but some evidence exists that in vitro SPP may be active as a monomer. We have conducted additional experiments to determine if SPP exists as a monomer or dimerin vivo.

Results

Fluorescence lifetime imaging microscopy (FLIM) can be is used to determine intra- or intermolecular interactions by fluorescently labeling epitopes on one or two different molecules. If the donor and acceptor fluorophores are less than 10 nm apart, the donor fluorophore lifetime shortens proportionally to the distance between the fluorophores. In this study, we used two types of fluorescence energy transfer (FRET) pairs; cyan fluorescent protein (CFP) with yellow fluorescent protein (YFP) or Alexa 488 with Cy3 to differentially label the NH2- or COOH-termini of SPP molecules. A cell based SPP activity assay was used to show that all tagged SPP proteins are proteolytically active. Using FLIM we were able to show that the donor fluorophore lifetime of the CFP tagged SPP construct in living cells significantly decreases when either a NH2- or COOH-terminally YFP tagged SPP construct is co-transfected, indicating close proximity between two different SPP molecules. These data were then confirmed in cell lines stably co-expressing V5- and FLAG-tagged SPP constructs.

Conclusion

Our FLIM data strongly suggest dimer formation between two separate SPP proteins. Although the tagged SPP constructs are expressed throughout the cell, SPP dimer detection by FLIM is seen predominantly at or near the plasma membrane.
Gene Expression in the Brain from Fluoxetine‐Injected Mouse Using DNA Microarray
Authors: TAKAHASHI YASUO , WASHIYAMA KAZUO , KOBAYASHI TORU , HAYASHI SHIGENOBU
Published: November 2006

Abstract:  Previously we have examined the effects of phencyclidine and clozapine upon the gene expression in the mouse brain. Recently, fluoxetine (Prozac) has been introduced for the therapeutic purpose as an antidepressant drug. Miledi et al. reported blockage of mouse muscle and neuronal nicotinic acetylcholine receptor by various concentrations of fluoxetine. Furthermore, Kobayashi et al. discovered that fluoxetine inhibits G protein activated inwardly rectifying G protein activated K+ (GIRK) channels using Xenopus oocyte expression assay. From these experiments, we considered that it might be interesting to study the effects of fluoxetine on the gene expression in the mouse brain. After we have injected fluoxetine once a day into mouse for 20 days, we sacrificed mouse by decapitation and extracted RNA from mouse cerebral cortex. We used DNA microarray method for examining the gene expression in the brain. We found the downregulation of many spot signals in the fluoxetine‐treated mouse, for example cholecystockinin and prostaglandin D2 synthase.
Association Study of the Dihydropyrimidinase‐Related Protein 2 Gene and Methamphetamine Psychosis
Authors: UJIKE H. , SAKAI A. , NAKATA K. , TANAKA Y. , KODAKA T. , OKAHISA Y. , HARANO M. , INADA T. , YAMADA M. , KOMIYAMA T. , HORI T. , SEKINE Y. , IWATA N. , SORA I. , IYO M. , OZAKI N. , KURODA S.
Published: November 2006

Abstract:  Dihydropyrimidinase‐related protein 2 (DRP‐2 or DPYSL‐2)mediates the intracellular response to collapsin, a repulsive extracellular guidance cue or axonal outgrowth. DRP‐2 is also referred to as collapsin response mediator protein 2 (CRMP‐2). We have previously demonstrated that the DRP‐2 gene is associated with susceptibility to schizophrenia, but not to bipolar disorders. In addition, a genetic association was observed with paranoid‐type schizophrenia, but not with hebephrenic‐type schizophrenia. It has been well documented that repeated abuse of methamphetamine (METH) for a long period frequently produces psychotic symptoms, such as auditory hallucinations and delusions that are hardly distinguishable from those of paranoid‐type schizophrenia. Therefore, we hypothesized that a certain genetic variant of the DRP‐2 gene may affect individual vulnerability to the development of METH‐induced psychosis. We examined the genetic association by a case–control method. The polymorphism *2236T>C in the 3′ untranslated region of the DRP‐2 gene, which has been shown to be a negative genetic risk factor for paranoid‐type schizophrenia, was analyzed in 198 patients with METH psychosis and 221 corresponding healthy controls in a Japanese population. No significant association of the DRP‐2 gene with METH psychosis was found. Neither did we find an association with the clinical phenotype of METH psychosis, such as the age of first consumption of METH, latency to development of psychosis after METH abuse, prognosis of psychosis after detoxification from METH use, complication of spontaneous relapse of psychosis without reconsumption of the drug, or multisubstance abuse status. These findings indicate that a genetic variant of the DRP‐2 gene may not affect the risk of METH psychosis or any clinical phenotype of the disorder.
Association Study of the Tumor Necrosis Factor‐α Gene and Its 1A Receptor Gene with Methamphetamine Dependence
Authors: NOMURA A. , UJIKE H. , TANAKA Y. , KISHIMOTO M. , OTANI K. , MORITA Y. , MORIO A. , HARANO M. , INADA T. , YAMADA M. , KOMIYAMA T. , HORI T. , SEKINE Y. , IWATA N. , SORA I. , IYO M. , OZAKI N. , KURODA S.
Published: November 2006

Abstract:  Recent preclinical findings that repeated treatment with methamphetamine (METH) induced an increase in tumor necrosis factor‐α (TNF‐α) mRNA in some brain regions and that TNF‐α blocked METH neurotoxicity and rewarding effects suggest TNF‐α, a multifunctional pro‐inflammatory cytokine, may be involved in METH dependence. We hypothesized that genetic polymorphisms of the TNF‐α gene and its receptor genes may be associated with vulnerability to METH dependence. Genetic association of ‐308G>A and ‐857C>T in the promotor region of the TNF‐α gene, and 36A>G in exon 1 of the TNF receptor 1A gene (TNFR‐SF1A), were analyzed in patients with METH dependence (n= 185) and healthy controls (n= 221) in a Japanese population. No significant association of alleles or haplotypes of the TNF‐α or TNFR‐SF1A genes with METH dependence was found. Neither was any significant association of clinical phenotype with METH dependence found. These results suggest that genetic variations in the TNF‐α gene and its receptor genes may not be involved in individual vulnerability to METH dependence.
Methamphetamine, Morphine, and Their Combination
Authors: PEREIRA FREDERICO C. , LOURENÇO ELITA , MILHAZES NUNO , MORGADINHO TERESA , RIBEIRO CARLOS F. , ALI SYED F. , MACEDO TICE R.
Published: November 2006

Abstract: The co‐administration of methamphetamine (METH) and MOR (MOR)‐like compounds is becoming increasingly popular among drug abusers. Recently, it was demonstrated that rats would self‐inject METH–heroin combination and that this combination produced a greater rewarding effect than the identical doses of METH alone and it was further suggested that enhanced reward might underlie the popularity of this combination. However, there is null information on the effects of the MOR–METH combination on striatal dopaminergic transmission. In the present article,in vivobrain microdialysis was used to examine the effects of two METH doses (1 and 5 mg/kg, i.p.; [METH1: hyperlocomotion‐inducing] and [METH5: stereotypy‐inducing], respectively) and MOR (10 mg/kg, i.p. [MOR10]) either alone or in combination on dopamine (DA) and 3,4‐dihydroxyphenylacetic acid (DOPAC) release in caudate putamen (CPu) in freely moving rats. METH1 evoked a transient threefold increase in DA overflow in only one‐third of dosed rats. On the contrary, METH5 elicited a 11‐fold increase in the extracellular DA levels 30 min after dosing and stayed significantly (P< 0.05) above control levels up to 1.5 h. On the other hand, MOR10 did not significantly change DA extracellular levels. MOR10–METH1 combination prolonged DA outflow for 1 h in all rats dosed without changing peak effect compared to METH1. On the other hand, MOR10–METH5 combination did not change the peak effect nor the DA outflow profile compared to METH5 alone. Consistently, there is a concentration‐dependent decrease in DOPAC efflux evoked by METH: METH1 evoked a smaller decrease in DOPAC outflow showing a tendency for returning to basal values whereas METH5 kept DOPAC extracellular levels reduced throughout the experiment. Again, MOR10 did not significantly change DOPAC extracellular levels. MOR delayed the onset without changing METH effect on the DOPAC output. These findings provide suggestive evidence that MOR potentiated the increase in extracellular DA levels induced by a low dose of METH. Thus, this combination yields a profile of action that might underlie the reinforcing properties sought by drug addicts.
Protection by GDNF and Other Trophic Factors Against the Dopamine‐Depleting Effects of Neurotoxic Doses of Methamphetamine
Authors: CASS WAYNE A. , PETERS LAURA E. , HARNED MICHAEL E. , SEROOGY KIM B.
Published: November 2006

Abstract: Repeated methamphetamine (METH) administration to animals can result in long‐lasting decreases in striatal dopamine (DA) content. It has previously been shown that glial cell line‐derived neurotrophic factor (GDNF) can reduce the DA‐depleting effects of neurotoxic doses of METH. However, there are several other trophic factors that are protective against dopaminergic toxins. Thus, the present experiments further investigated the protective effect of GDNF as well as the protective effects of several other trophic factors. Male Fischer‐344 rats were given an intracerebral injection of trophic factor (2–10 μg) 1 day before METH (5 mg/kg, s.c., 4 injections at 2‐h intervals). Seven days later DA levels in the striatum were measured using high‐performance liquid chromatography (HPLC). Initial experiments indicated that only intrastriatal GDNF, and not intranigral GDNF, was protective. Thereafter, all other trophic factors were administered into the striatum. Members of the GDNF family (GDNF, neurturin, and artemin) all provided significant protection against the DA‐depleting effects of METH, with GDNF providing the greatest protection. Brain‐derived neurotrophic factor, neurotrophin‐3, acidic fibroblast growth factor, basic fibroblast growth factor, ciliary neurotrophic factor, transforming growth factor‐α (TGF‐α), heregulin β1 (HRG‐β1), and amphiregulin (AR) provided no significant protection at the doses examined. These results suggest that the GDNF family of trophic factors can provide significant protection against the DA‐depleting effects of neurotoxic doses of METH.
Fluoxetine as a Potential Pharmacotherapy for Methamphetamine Dependence
Authors: TAKAMATSU YUKIO , YAMAMOTO HIDEKO , OGAI YASUKAZU , HAGINO YOKO , MARKOU ATHINA , IKEDA KAZUTAKA
Published: November 2006

Abstract: The monoamine transporters are the main targets of psychostimulant drugs, including methamphetamine (METH) and cocaine. Interestingly, the rewarding effects of cocaine are retained in dopamine transporter (DAT) knockout (KO) mice, while serotonin transporter (SERT) and DAT double KO mice do not exhibit conditioned place preference (CPP) to cocaine. These data suggest that SERT inhibition decreases the rewarding effects of psychostimulants. To further test this hypothesis, in the present study, we investigated the effects of intraperitoneal (i.p.) injections of 20 mg/kg fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on 2 mg/kg METH (i.p.) CPP and locomotor sensitization to 1 mg/kg METH (i.p.) in C57BL/6J mice. Fluoxetine treatment before both the conditioning and preference tests abolished METH CPP. A two‐way analysis of variance (ANOVA) revealed that METH CPP tended to be lower in mice pretreated with fluoxetine before the preference test than in control mice pretreated with saline before the preference test. Furthermore, pretreatment with fluoxetine had inhibitory effects on METH‐induced locomotor sensitization. These results suggest that fluoxetine, a widely used medication for depression, may be also a useful tool for treating METH dependence.
Nigrostriatal Damage with 6‐OHDA
Authors: FULCERI FEDERICA , BIAGIONI FRANCESCA , LENZI PAOLA , FALLENI ALESSANDRA , GESI MARCO , RUGGIERI STEFANO , FORNAI FRANCESCO
Published: November 2006

Abstract:  The 6‐hydroxydopamine (6‐OHDA) model of Parkinson's disease in the rat represents a fundamental tool for investigating the pathophysiology of dopamine denervation. Nevertheless, 6‐OHDA can induce also noradrenergic lesions; therefore desmethylimipramine (DMI) is co‐administrated as a selective inhibitor of noradrenergic reuptake to protect noradrenaline (NA) fibers neighboring DA neurons and/or axons. The neurotoxin 6‐OHDA must be microinfused selectively into the substantia nigra pars compacta (SNpc) or into the medial forebrain bundle (MFB) to determine the nigrostriatal lesion. However, this experimental procedure is invasive and always produces a certain amount of mechanical damage that cannot be prevented by pharmacological approaches. For this reason, we have compared two types of experimental design in which we tested critical steps of the procedures, such as the flow rate. We microinfused rats in MFB with 8 μL of total volume of a solution containing the neurotoxin (infusion rate 2 μL/min in 4 min) according with general practice, and rats microinfused with an amount of 2μL of total volume with a slower rate (0.2 μL/min in 10 min) of infusion. Rats infused with a higher flow rate of infusion underwent striatal NA loss in spite of the administration of DMI. On the contrary, rats infused with a slow infusion flow rate had spared NA axons following DMI. These results suggest that the flow rate and the volume of 6‐OHDA infusion are critical to prevent the occurrence of nonspecific mechanical effects.
Induction by Cocaine of the Serotonergic 5‐HT3 Receptor in Rat Cerebellum
Authors: ARPIN‐BOTT MARIE‐PIERRE , DIETRICH JEAN‐BERNARD , DIRRIG‐GROSCH SYLVIE , AUNIS DOMINIQUE , ZWILLER JEAN
Published: November 2006

Abstract:  The expression of the 5‐HT3 receptor, a member of the serotonin receptor family, was examined in rat cerebellum of saline‐ or cocaine‐treated rats. Both immunohistochemistry and Western blot analysis were used. We found that the expression of this serotonin receptor subtype was increased in the cerebellum of rats injected either acutely or repeatedly (1 injection/day for 10 days) with cocaine. The stimulation was more pronounced after a single injection than after a series of 10 injections. Surprisingly, the expression of the 5‐HT3 receptor was mainly localized in Bergmann glial cells, as assessed from the co‐localization of the receptor with the glial cell marker glial fibrillary acidic protein (GFAP). Our data emphasize the importance of the 5‐HT3 receptor induction in the cerebellum as part of the neuroadaptations taking place in rat brain in response to the psychostimulant cocaine.
Comparison between Heroin and Heroin–Cocaine Polyabusers
Authors: BANDETTINI DI POGGIO ADOLFO , FORNAI FRANCESCO , PAPARELLI ANTONIO , PACINI MATTEO , PERUGI GIULIO , MAREMMANI ICRO
Published: November 2006

Abstract:  The concomitant use of cocaine by heroin‐dependent subjects, or by patients on methadone maintenance treatment, is a relevant phenomenon that determines the negative consequences on health, social adjustment, and outcome of opioid addiction treatment. Little is known about the patterns of co‐use of these two substances and the pathophysiological alterations following this condition. Only a few studies have evaluated the neurochemical effects in subjects carrying this specific pattern of abuse. Similarly, the impact of cocaine abuse on psychiatric and social function in subjects already affected by opioid addiction is still poorly understood and further studies are necessary to investigate this specific area that could profoundly affect methadone maintenance treatment. The aim of this article is to investigate the psychopathological symptoms of heroin–cocaine abuse in a group of heroin addicts applying for treatment. Results show a direct relationship between cocaine abuse and a higher rate of psychiatric disorders, but a negative correlation with the severity of self‐rated psychopathology.
Evaluation for the Withdrawal Syndrome from γ‐Hydroxybutyric Acid (GHB), γ‐Butyrolactone (GBL), and 1,4‐Butanediol (1,4‐BD) in Different Rat Lines
Authors: QUANG LAWRENCE S. , COLOMBO GIANCARLO , LOBINA CARLA , MACCIONI PAOLA , ORRU` ALESSANDRO , GESSA GIAN LUIGI , MAHER TIMOTHY J. , CARAI MAURO A.M.
Published: November 2006

Abstract:  A severe and life‐threatening γ‐hydroxybutyric acid (GHB) withdrawal syndrome, clinically similar to the alcohol withdrawal syndrome, is increasingly being reported in GHB addicts. We investigated for the occurrence of withdrawal in Wistar and Sprague‐Dawley rats, and in the selectively bred lines of GHB‐sensitive (GHB‐S) and Sardinian alcohol‐preferring (sP) rats, following chronic administration of GHB, γ‐butyrolactone (GBL), and/or 1,4‐butanediol (1,4‐BD). Using validated rodent alcohol withdrawal scoring scales, little to no spontaneous or pharmacologically precipitated withdrawal effects were observed in Wistar, Sprague‐Dawley, or GHB‐S rats. Conversely, sP rats displayed both spontaneous and precipitated audiogenic seizures following abrupt cessation of chronic GHB or 1,4‐BD administration and following pharmacological challenge with the GABAB receptor‐selective antagonist, SCH 50911, respectively.
γ‐Hydroxybutyrate (GHB) in Humans
Authors: ABANADES SERGIO , FARRÉ MAGI , SEGURA MIREIA , PICHINI SIMONA , BARRAL DIEGO , PACIFICI ROBERTA , PELLEGRINI MANUELA , FONSECA FRANCINA , LANGOHR KLAUS , De La TORRE RAFAEL
Published: November 2006

Abstract:  Despite γ‐hydroxybutyrate (GHB) therapeutic uses and the increasing concern about its toxicity, few studies have addressed GHB dose‐related effects under controlled administration and their relationship with its pharmacokinetics. The study design was double‐blind, randomized, crossover, and controlled. As a pilot pharmacology phase I study, increasing doses of GHB were given. Single oral sodium GHB doses (40, 50, 60, and 72 mg/kg) were administered to eight volunteers. Plasma and urine were analyzed for GHB by gas chromatography–mass spectrometry. Physiological effects, psychomotor performance, and subjective effects were examined simultaneously. GHB produced dose‐related changes in subjective effects as measured by questionnaires and VAS. GHB showed a mixed stimulant‐sedative pattern, with initially increased scores in subjective feeling of euphoria, high, and liking followed by mild‐moderate symptoms of sedation with impairment of performance and balance. Mean peak GHB plasma concentrations were 79.1, 83.1, 113.5, and 130.1 μg/L for 40, 50, 60, and 72 mg/kg, respectively. GHB‐mediated physiological and subjective effects were dose dependent and related to GHB plasma concentrations. GHB urinary excretion was mainly related to administered doses. GHB‐mediated subjective and physiological effects seem dose dependent and related to GHB plasma concentrations. Results suggest a high abuse liability of GHB in the range of dose usually consumed.
Sex- and Age-Specific Reference Curves for Serum Markers of Bone Turnover in Healthy Children from 2 Months to 18 Years
Authors: Rauchenzauner Markus , Schmid Andrea , Heinz-Erian Peter , Kapelari Klaus , Falkensammer Gerda , Griesmacher Andrea , Finkenstedt Gerd , Högler Wolfgang
Published: November 2006

Introduction: This study aimed to establish sex- and age-specific reference curves enabling the calculation of z-scores and to examine correlations between bone markers and anthropometric data.

Methods: Morning blood samples were obtained from 572 healthy children and adolescents (300 boys) aged 2 months to 18 yr. Height, weight, and pubertal stage were recorded. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), type-1 collagen degradation markers [carboxyterminal telopeptide region of type I collagen (ICTP), carboxyterminal telopeptide α1 chain of type I collagen (CTX)], and tartrate-resistant acid phosphatase (TRAP5b) were measured. Cross-sectional centile charts were created for the 3rd, 50th, and 97th centiles.

Results: Apart from TRAP5b, all bone markers were nonnormally distributed, requiring logarithmic (BALP, OC, ICTP) or square root (CTX) transformation. Back-transformed centile curves for age and sex are presented for practical use. All bone markers varied with age and pubertal stage (P < 0.001). Significant correlations were found between sd score (SDS) for bone formation markers BALP and OC (r = 0.13; P = 0.004), SDS for collagen degradation markers ICTP and CTX (r = 0.14; P = 0.002), and SDS for the phosphatases (r = 0.34, P < 0.001). Height and weight SDS correlated weakly with some bone marker SDS, particularly with lnBALP SDS (r = 0.20 and 0.24, respectively; both P < 0.001).

Conclusion: This study provides reference curves for OC, BALP, CTX, ICTP, and TRAP5b in healthy children. Taller and heavier individuals for age had greater bone marker concentrations, likely reflecting greater growth velocity. SDS for markers of bone formation, collagen degradation, and phosphatases were each independently correlated, suggesting they derive from the same biological processes. The possibility of calculating SDS will facilitate monitoring of antiresorptive therapy or disease progression in children with metabolic bone disease.