bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of Helicobacter pylori Infection in the Czech Republic
Authors: Bureš Jan , Kopáčová Marcela , Koupil Ilona , Voříšek Viktor , Rejchrt Stanislav , Beránek Martin , Seifert Bohumil , Pozler Oldřich , Živný Pavel , Douda Tomáš , Kolesárová Martina , Pintér Michal , Palička Vladimír , Holčík Jan ,   the European Society for Primary Care Gastroenterology
Published: January 2006

Background:  Prevalence of Helicobacter pylori infection has been estimated to range from 60 to 95% in the former communist countries of Central and Eastern Europe. The aim of this study was to evaluate H. pylori infection prevalence in a representative sample of the Czech population. The second objective was to describe difference of H. pylori prevalence between different social groups of children and adults.

Materials and Methods:  A total of 2509 persons aged 5–100 years, randomly selected out of 30,012 persons of the general population, took part in the study. H. pylori infection was investigated by means of 13C‐urea breath test. Breath samples were analyzed by isotope ratio mass spectrometry. Social and demographic characteristics were based on data from self‐completed questionnaires.

Results:  Using the total Czech population as a standard, we estimated the age‐standardized prevalence of H. pylori in males aged 5+ years at 41.9% (95% CI 39.0%, 44.8%) and in females aged 5+ years at 41.4% (95% CI 38.6%, 44.3%) in 2001. Prevalence of H. pylori increased with age but was not related to gender. Children of mothers with basic or lower education, living in crowded accommodations, without access to running warm water, and residing in smaller towns appear to be at the highest risk. Low education and heavy smoking are most strongly associated with prevalence of H. pylori positivity in adults and adolescents.

Conclusions:  This is a unique study based on a representative sample of the general population in a Central European country. The overall prevalence of H. pylori is lower than previously assumed and could partly reflect a substantial recent decrease in H. pylori prevalence in the Czech Republic. Consistent with earlier studies, H. pylori infection is strongly influenced by socioeconomic conditions and childhood poverty.
Helicobacter pylori has Stimulatory Effects on Naive T Cells
Authors: Malfitano Anna Maria , Cahill Rachel , Mitchell Peter , Frankel Gad , Dougan Gordon , Bifulco Maurizio , Lombardi Giovanna , Lechler Robert I. , Bamford Kathleen B.
Published: January 2006

Background:  Despite an apparently active host response, Helicobacter pylori infection can persist for life. Unexpectedly, T cells from apparently uninfected individuals respond to H. pylori antigen by proliferating. Also, the T‐cell proliferative response appears to be less in infected compared with uninfected individuals.

Materials and Methods:  We have investigated the T‐cell response of isolated human peripheral blood, naive, and memory CD4+ T cells to H. pylori antigen in infected and uninfected subjects.

Results:  In agreement with previous findings, the peripheral blood proliferative response was higher in uninfected compared with infected subjects. Interestingly, there was a response in CD4+CD45RO+ (memory) and CD4+CD45RA+ (naive) subsets. The RO/RA ratio of the response to H. pylori antigen was 0.8–2.1 in both H. pylori‐positive and H. pylori‐negative subjects, which was similar to that of a known superantigen (2.5 and 2.2 in Helicobacter‐positive and ‐negative subjects, respectively) whereas the RO/RA response ratio to a recall antigen (tetanus toxoid) was 9.8 and 18.7 in Helicobacter‐positive and ‐negative subjects, respectively. Mononuclear cells isolated from cord blood also responded to H. pylori antigen, whereas there was no response to tetanus toxoid. The cord blood response and CD4+CD45RA+ cell response to H. pylori antigen were inhibited predominantly by anti‐HLA‐DR and to some extent by anti‐HLA‐DQ antibodies. Investigation of the response to five different recombinant H. pylori antigens identified two that produced a response in naive T cells.

Conclusions:  These data suggest that H. pylori possesses molecules that cause higher than expected proliferation of naive T cells.
ROAT: morphology of ROAT on arm, neck and face in formaldehyde and diazolidinyl urea sensitive individuals
Authors: Zachariae Claus , Hall Barbara , Cupferman Sylvie , Andersen Klaus E. , Menné Torkil
Published: January 2006

The morphology of early allergic contact dermatitis reactions was studied in formaldehyde allergic individuals exposed to a cream product preserved with 4 different concentrations of diazolidinyl urea. The study was made using a dose‐escalating design in 3 different anatomical regions, the upper arm, neck and face. On the arm and neck, the dominant initial morphology was an eczematous papular eruption. In the face, the initial skin changes were more homogeneous and infiltrated erythema.
Characterization and chemistry of imidazolidinyl urea and diazolidinyl urea
Authors: Lehmann Søren Vig , Hoeck Ulla , Breinholdt Jens , Olsen Carl Erik , Kreilgaard Bo
Published: January 2006

For several decades, the cosmetic preservatives imidazolidinyl urea (IU) and diazolidinyl urea (DU) have not only been poorly characterized but have also had misleading chemical structures assigned to them. The most common trade names of IU and DU are Germall 115 and Germall II, respectively. This publication gives an insight into what these 2 well‐known contact allergens consist of and their degradation patterns. Approximately, 30–40% of both products can be characterized by mixtures of allantoin (synthetic starting material), (4‐hydroxymethyl‐2,5‐dioxo‐imidazolidin‐4‐yl)‐urea (compound HU) and presumably 1‐(3,4‐bis‐hydroxymethyl‐2,5‐dioxo‐imidazolidin‐4‐yl)‐1,3‐bis‐hydroxymethyl‐urea (compound BHU). A full chemical characterization of compound HU is shown. The remaining part of both IU and DU are believed to be polymers of allantoin‐formaldehyde condensation products. The analytical methods used to characterize IU and DU are capillary electrophoresis and nuclear magnetic resonance and mass spectroscopy studies.
Contact allergy and respiratory/mucosal complaints from heroin (diacetylmorphine)
Authors: Hogen Esch A. J. , Van Der Heide S. , Van Den Brink W. , Van Ree J. M. , Bruynzeel D. P. , Coenraads P. J.
Published: January 2006

After the start of heroin (diacetylmorphine)‐assisted treatment to a selected group of chronic treatment‐resistant heroin‐dependent patients in the Netherlands, we reported about work‐related eczema and positive patch tests to heroin in some nurses and nasal and respiratory complaints. To investigate the prevalence of heroin contact allergy, we started a questionnaire‐based study with follow‐up by allergological examinations. Of 120 questionnaires sent, 101 (84%) was returned: 67 from nurses and 34 from other employees. Of 101 workers, 38 (38%) had reported work‐related complaints: 33 of 67 (49%) nurses and 5 of 34 (15%) other employees. Patch tests to heroin were performed in 24 nurses and were positive in 8 (33%). All the 8 had eyelid or facial eczema and, in 6, accompanied by mucosal or respiratory complaints. The prevalence of heroin contact allergy in this study was 8% (8/101) among all employees and 12% (8/67) among nurses. Respiratory and mucosal complaints could not be ascribed to a contact allergy, and in these cases, serum was analysed for specific immunoglobulin E to heroin. A type 1 allergy to heroin could not be shown. These complaints are possibly due to the histamine‐liberating effect of heroin, to atopic constitution, to a combination of these factors or – less likely – to other non‐allergic factors.
Dermatitis and aircrew
Authors: Leggat Peter A. , Smith Derek R.
Published: January 2006

Dermatitis is a common problem both in the workplace and in the general community. Airline personnel represent a novel occupational group as they are also exposed to a wide range of potential chemical irritants and other aggravating factors, such as low relative humidity and airborne pollutants. Common skin irritants include dielectric fluids from electrodischarge machining, ‘prepreg’ materials and sealants in aircraft manufacture, kerosene and various jet‐fuel components. Commercial jet fuel is a complex mixture of aliphatic and aromatic compounds, and there is potential for dermal exposure among refueling and maintenance crew. Low relative humidity appears to exacerbate dermatitis amongst aircrew, especially on longer flight durations. Pilots may also be exposed to additional skin irritants outside of the cabin environment, such as ethylene glycol, hydraulic fluid or jet fuel, all of which may be encountered during routine inspections of aircraft before and after flight. Given these factors, preventive measures must carefully consider the undoubted potential for contact with irritants and allergens, which may lead to dermatitis in airline personnel.
Everyday Experiences of Homeless Young People in Supported Accommodation Programmes in Australia
Authors: Danby Susan , Farrell Ann , Leiminer Michele
Published: January 2006

This paper investigates young people's accounts of governance in their everyday lives within a Supported Accommodation Assistance Program (SAAP) in regional Australia. The SAAP is a joint Commonwealth and State/Territory programme for assisting people who are homeless or at risk of homelessness by providing transitional supported accommodation and support services. The paper provides accounts of how two young people, Monica and Brendan, make sense of their everyday lives in relation to how they make decisions (or have decisions made for them) everyday. The young people here are recognised as active agents who construct and negotiate their social realities. We focus, in particular, on how they describe influences that govern their everyday experiences. These two accounts present contrasting descriptions of social and interactional competence within a service that regulates their everyday lives, highlighting the challenges of policy formation on behalf of young people. Copyright © 2006 National Children's Bureau.
Desired Outcomes for Children and Adolescents with Autistic Spectrum Disorders
Authors: Beresford Bryony , Tozer Rosemary , Rabiee Parvaneh , Sloper Patricia
Published: January 2006

Within children's services, frameworks for assessing outcomes have been developed in the absence of consultation with children with autistic spectrum disorders and their parents. The research reported here worked with parents, other key adults and children with autistic spectrum disorders to identify desired outcomes. It found similarities with non‐autistic children in terms of the broad types of outcomes desired. However, the presence of autism meant either new or different sorts of outcomes were reported. Implications in terms of the ways outcomes for autistic children are defined and measured, and the role of services in achieving outcomes is discussed. © 2006 The Author(s).
Determinants of the elimination of methotrexate and 7‐hydroxy‐methotrexate following high‐dose infusional therapy to cancer patients
Authors: Joerger M. , Huitema A. D. R. , Van Den Bongard H. J. G. D. , Baas P. , Schornagel J. H. , Schellens J. H. M. , Beijnen J. H.
Published: January 2006

Aims

To characterize determinants of the elimination of methotrexate (MTX) and 7‐hydroxy‐methotrexate (7‐OH‐MTX) in patients receiving high‐dose MTX therapy (HDMTX).

Methods

24 and 48‐h blood samples from 76 patients receiving HDMTX (dose range 300 mg m−2 to 12 g m−2) were analysed, and concentration‐time data were subjected to population pharmacokinetic and covariate analysis using nonlinear mixed‐effect modelling (NONMEM).

Results

Treatment‐related mortality was 1.3% (one patient with renal failure). Values for MTX clearance (CLMTX) and 7‐OH‐MTX clearance (CL7‐OH‐MTX) were estimated at 8.85 and 2 L−1, respectively. Baseline creatinine clearance correlated with CLMTX and CL7‐OH‐MTX. Concurrent administration of benzimidazoles led to a 27% decrease in CLMTX and a 39% decrease in CL7‐OH‐MTX. Prior administration of nonsteroidal anti‐inflammatory drugs (NSAIDs) resulted in a 16% decrease in CLMTX and a 38% decrease in CL7‐OH‐MTX. Plasma MTX concentrations were significantly higher in patients also receiving benzimidazoles at 24 h (2.01 µmol L−1vs. 0.66 µmol L−1, P < 10−4) and at 48 h (0.25 µmol L−1vs. 0.12 µmol L−1, P < 10−4). 7‐OH‐MTX plasma concentrations were also significantly higher in patients with concurrent benzimidazoles as compared with patients without benzimidazoles at 24 h (4.47 µmol L−1vs. 2.52 µmol L−1, P = 0.0009) and at 48 h (1.11 µmol L−1vs. 0.72 µmol L−1, P = 0.031).

Conclusions

In patients receiving HDMTX, concurrent administration of benzimidazoles was associated with a significant decrease of CLMTX and CL7‐OH‐MTX, resulting in significantly higher plasma concentrations of MTX and 7‐OH‐MTX. The data suggest that benzimidazole treatment should be seen as a relative contraindication for HDMTX.
Phylogeography of Iurus dufoureius (Brullé, 1832) (Scorpiones, Iuridae)
Authors: Parmakelis A. , Stathi I. , Spanos L. , Louis C. , Mylonas M.
Published: January 2006

Aim  This study uses molecular data in conjunction with palaeogeography to infer the most plausible biogeographical scenario accounting for the current distributional pattern of Iurus dufoureius.

Location  North‐eastern Mediterranean region.

Methods  Sequencing of a 441‐bp segment of the mitochondrial 16S rRNA gene in seven populations covering the whole distributional range of the species. Phylogenetic analyses performed included neighbour joining, maximum parsimony and Bayesian inference.

Results  The molecular phylogeny showed that two Iurus clades are strongly supported. These clades correspond to the two subspecies Iurus dufoureius dufoureius and Iurus dufoureius asiaticus, currently recognized within the genus. The assumption of a clock‐like evolution could not be rejected, and this enabled us to estimate an approximation of the local rate of evolution for the I. dufoureius lineages. Based on the estimated evolutionary rate (0.79 ± 0.17 Myr−1), the split between the two Iurus clades occurred c. 8 Ma.

Main conclusions  Contrary to what was believed in the past, the genus Iurus is an old north‐eastern Mediterranean genus that has been differentiating in southern Greece and south‐west Turkey at least from the middle Miocene. According to the phylogenetic trees obtained and the dating of the divergence times of lineages, the genus dispersed into the Aegean Archipelago when the Aegean was still a uniform land mass. Although the phylogenetic relationships of I. d. dufoureius populations have been shaped by the most recent vicariant events, the phylogenetic relationships of I. d. asiaticus populations are mostly attributable to older palaeoevents occurring in the area.
Land hermit crab (Coenobita clypeatus) densities and patterns of gastropod shell use on small Bahamian islands
Authors: Morrison Lloyd W. , Spiller David A.
Published: January 2006

Aim  To examine patterns of abundance, density, size and shell use in land hermit crabs, Coenobita clypeatus (Herbst), occurring on three groups of small islands, and to determine how these variables change among islands.

Location  Small islands in the Central Exuma Cays and near Great Exuma, Bahamas.

Methods  Land hermit crabs were captured in baited pitfall traps and were separately attracted to baits. A mark–recapture technique was used in conjunction with some pitfall traps monitored for three consecutive days. The size of each crab and the type of adopted gastropod shell were recorded, along with physical island variables such as total island area, vegetated area, island perimeter, elevation and distance to the nearest mainland island.

Results  Relative abundances, densities and sizes of crabs differed significantly among the three island groups. Densities of land hermit crabs were as high as 46 m−2 of vegetated island area. In simple and multiple linear regressions, the only variable that was a significant predictor of the abundance of hermit crabs was the perimeter to area ratio of the island. Patterns of gastropod shell use varied significantly among the island groups, and the vast majority of adopted shells originated from gastropod species that inhabit the high intertidal and supratidal shorelines of the islands.

Main conclusions  Although densities of land hermit crabs varied, they were relatively high on many islands, and land hermit crabs may play an important role in these insular food webs. Patterns of shell use may be strongly restricted by island geomorphology: irregular shorelines provide relatively more habitat for the gastropod species that account for the majority of adopted shells and the steep sides of the islands prevent the accumulation of marine gastropod shells. The size of adult hermit crabs appears to be limited by the relatively small gastropod shells available, while the abundance of hermit crabs may be limited by the number of shells available.
Hypothalamic Pro‐GnRH‐GAP, GnRH‐I and GnRH‐II During the Onset of Photorefractoriness in the White‐Crowned Sparrow (Zonotrichia leucophrys gambelii)
Authors: Meddle S. L. , Bush S. , Sharp P. J. , Millar R. P. , Wingfield J. C.
Published: January 2006

Gambel's white‐crowned sparrow is a long distance migrant that undergoes spontaneous gonadal regression as a result of long day exposure. This termination of breeding is caused by the development of photorefractoriness and the birds become insensitive to long days, including continuous light. The present study investigated its possible mechanisms by examining the activity of the gonadotrophin‐releasing hormone (GnRH) system under different photoperiodic regimes. We investigated the localisation and distribution of GnRH‐I, its precursor pro‐GnRH‐GAP and GnRH‐II in Gambel's white‐crowned sparrow brain using immunocytochemistry with specific antibodies during photostimulation and the development of photorefractoriness. The study revealed that photoperiodic treatment, including the onset of photorefractoriness, had no significant effect on the size or number of GnRH‐I, pro‐GnRH‐GAP or GnRH II immunoreactive cells, or the density of the GnRH‐I, pro‐GnRH‐GAP immunoreactive fibres at the median eminence. GnRH‐II was not found in the median eminence, suggesting that it does not regulate pituitary gonadotrophin secretion. GnRH‐I measurement in hypothalamic extracts by radioimmunoassay did not reveal any significant difference between birds that were photostimulated or in the early stages of photorefractoriness. Furthermore, the action of the excitatory amino acid glutamate agonist N‐methyl‐D‐aspartate on GnRH neurones in photorefractory birds was demonstrated by the significant blockade of luteinising hormone release with a specific GnRH antagonist. Taken together, these results suggest that, in Gambel's white‐crowned sparrow, a decrease in GnRH‐I secretion is the initial step for the onset of photorefractoriness and not a decrease in GnRH‐I biosynthesis.
Molecular investigation and long‐term clinical progress in Greek Cypriot families with recessive distal renal tubular acidosis and sensorineural deafness due to mutations in the ATP6V1B1 gene
Authors: Feldman M , Prikis M , Athanasiou Y , Elia A , Pierides A , Deltas CC
Published: January 2006

The spectrum of distal renal tubular acidosis (dRTA) includes a genetically heterogeneous group of inherited conditions of both autosomal‐dominant and recessive mode of inheritance. The basic defect is linked to the renal part of acid–base homeostasis, which is partly achieved by the regulated luminal secretion of H+ at the apical surface of the α‐intercalated cells of renal collecting ducts. This is coupled to bicarbonate reabsorption with chloride counter transport across the basolateral membranes Here, we describe the molecular findings of the first two Greek Cypriot families with recessive dRTA and the long‐term clinical findings in four of five affected members. DNA linkage analysis with four polymorphic markers flanking the ATP6V1B1 gene on chromosome 2 gave evidence for positive linkage; direct DNA analysis by automated DNA sequencing revealed that patients in one family were homozygous for mutation 229+1G>T (IVS7+1G>T) and that patients in the second family were compound heterozygous for 229+1G>T and R157C. The mutations were found on four different haplotypes. Both the mutations were previously reported in patients of Turkish origin. Three known polymorphic variants were also identified. The five patients demonstrated the whole clinical spectrum of the disease including death in infancy, failure to thrive, rickets, nephrocalcinosis, nephrolithiasis, and episodes of hypokalemic paralysis. Some of the family members are now in their mid 30s and late 20s, and nephrolithiasis with recurrent renal colics is their main problem. Renal function has remained normal. In conclusion, early diagnosis in infancy and prompt treatment with alkali and potassium supplements is of great benefit to the patient with dRTA and ensures normal growth. The identification of responsible mutations facilitates antenatal or postnatal diagnosis in concerned families and improves the prognosis.
The electrocardiographic and hemodynamic effect of metohexital and propofol with and without esmolol
Authors: Korpinen R. , Klemola U‐M. , Simola M. , Toivonen H.
Published: January 2006

Background:  Metohexital and propofol are short‐acting induction agents, which have a tendency to prolong the QTc interval of the ECG. We studied whether this increase could be prevented by combining a beta‐blocking agent, esmolol, with these drugs. Simultaneously, we studied the hemodynamic effects of these combinations.

Methods:  In a randomized, double‐blind study, 80 ASA I–II young adults were premedicated with oxycodone and atropin and allocated to one of four groups: propofol (P), propofol + esmolol (P + E), metohexital (E) or metohexital + esmolol (M + E). The doses were 2 mg/kg propofol/metohexital and 1 mg/kg esmolol. Alfentanil 15 µg/kg was used in all groups. The hemodynamic parameters were measured non‐invasively and the electrocardiographic parameters using the signal processing method.

Result:  The highest QTc values, which often exceeded the normal upper limit of 440 ms, were recorded at the baseline or immediately after the administration of the induction drugs. The intervals were significantly shorter if esmolol was co‐administered with either propofol or metohexital. The heart rate increased in the group M and decreased in the group P + E but remained unchanged in the groups P and M + E. Systolic and diastolic arterial pressures decreased during the study in all groups, most prominently in group P + E.

Conclusions:  During the anesthesia induction, the QTc interval was significantly shorter when esmolol was co‐administered with either propofol or metohexital. The hemodynamic responses were properly controlled with the combination of metohexital and esmolol as well as with propofol alone, but the combination of propofol and esmolol tended to cause hemodynamic depression.
Isobaric bupivacaine via spinal catheter for hip replacement surgery: ED50 and ED95 dose determination
Authors: Sell A. , Olkkola K. T. , Jalonen J. , Aantaa R.
Published: January 2006

Background:  Continuous spinal anaesthesia with spinal catheters allows incremental dosing of the local anaesthetic and, consequently, less haemodynamic change. However, little is known about the required doses. Therefore, we designed a study to assess the local anaesthetic doses of isobaric bupivacaine which were effective in 50% (ED50) and 95% (ED95) of patients undergoing hip replacement surgery.

Methods:  Forty‐eight patients undergoing hip replacement surgery were randomly allocated to one of six possible groups of eight patients to receive 6, 7, 8, 9, 10 or 12 mg of isobaric bupivacaine in a double‐blind manner. The ED50 and ED95 values were calculated by a logistic regression model. The position of the spinal catheter tip was confirmed by X‐rays.

Results:  The ED50 and ED95 values were 7.1 mg (95% confidence interval, 6.0–8.4) and 12.3 mg (95% confidence interval, 8.9–15.7), respectively. The location of the tip of the intrathecal catheter had no effect on local anaesthetic requirements. Eight patients required ephedrine after anaesthesia induction and a further 11 patients required ephedrine for correction of hypotension during surgery.

Conclusion:  The observed ED50 and ED95 values may guide us to use small doses of isobaric bupivacaine for hip replacement surgery. Hypotension is still possible even if low doses of isobaric bupivacaine are used.
Effect of low‐dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block
Authors: Kanazi G. E. , Aouad M. T. , Jabbour‐Khoury S. I. , Al Jazzar M. D. , Alameddine M. M. , Al‐Yaman R. , Bulbul M. , Baraka A. S.
Published: January 2006

Background: The purpose of this study was to compare the onset and duration of sensory and motor block, as well as the hemodynamic changes and level of sedation, following intrathecal bupivacaine supplemented with either dexmedetomidine or clonidine.

Methods: In a prospective, double‐blind study, 60 patients undergoing transurethral resection of prostate or bladder tumor under spinal anesthesia were randomly allocated to one of three groups. Group B received 12 mg of hyperbaric bupivacaine, group D received 12 mg of bupivacaine supplemented with 3 µg of dexmedetomidine and group C received 12 mg of bupivacaine supplemented with 30 µg of clonidine. The onset times to reach peak sensory and motor levels, and the sensory and motor regression times, were recorded. Hemodynamic changes and the level of sedation were also recorded.

Results: Patients in groups D and C had a significantly shorter onset time of motor block and significantly longer sensory and motor regression times than patients in group B. The mean time of sensory regression to the S1 segment was 303 ± 75 min in group D, 272 ± 38 min in group C and 190 ± 48 min in group B (B vs. D and B vs. C,P < 0.001). The regression of motor block to Bromage 0 was 250 ± 76 min in group D, 216 ± 35 min in group C and 163 ± 47 min in group B (B vs. D and B vs. C,P < 0.001). The onset and regression times were not significantly different between groups D and C. The mean arterial pressure, heart rate and level of sedation were similar in the three groups intra‐operatively and post‐operatively.

Conclusions: Dexmedetomidine (3 µg) or clonidine (30 µg), when added to intrathecal bupivacaine, produces a similar prolongation in the duration of the motor and sensory block with preserved hemodynamic stability and lack of sedation.
Analgesic effects of intrathecally administered celecoxib, a cyclooxygenase‐2 inhibitor, in the tail flick test and the formalin test in rats
Authors: Nishiyama T.
Published: January 2006

Background:  The analgesic effects of celecoxib, a cyclooxygenase‐2 (COX‐2) inhibitor, on formalin‐induced pain are still controversial. The purpose of this study was to examine the analgesic effects of intrathecally administered celecoxib on inflammatory induced pain, thermal‐induced pain and hemodynamics.

Methods:  Male Sprague‐Dawley rats with lumbar intrathecal catheters were tested via their tail withdrawal response to thermal stimulation (tail flick test) and via their paw flinching and shaking response to subcutaneous formalin injection into the hind paw (formalin test) after intrathecal administration of celecoxib. The blood pressure, pulse rate and behavioral side‐effects were also examined.

Results:  Even the maximum available dose of celecoxib (200 µg/20 µl) had little effect in the tail flick test. In the formalin test, celecoxib induced a dose‐dependent decrease in the flinch response in both phases 1 and 2. The 50% effective doses were 0.025 µg (95% confidence interval, 0.007–0.082 µg) in phase 1, 0.026 µg (0.010–0.045 µg) in phase 2a and 0.001 µg (0.00009–0.010 µg) in phase 2b. With the doses used in this study, the blood pressure and pulse rate did not change and no motor disturbance or behavioral side‐effects were observed.

Conclusion:  Intrathecal administration of celecoxib decreased inflammatory acute and facilitated pain without any hemodynamic or behavioral side‐effects, but had no effect on acute thermal pain.
Changes in magnesium concentration in the serum and cerebrospinal fluid of neuropathic rats
Authors: Jeong S. M. , Hahm K. D. , Shin J. W. , Leem J. G. , Lee C. , Han S. M.
Published: January 2006

Background:  Central sensitization of neuropathic pain is associated with an influx of extracellular calcium via the opening of N‐methyl‐d‐aspartate (NMDA) receptor‐gated ion channels, which are usually blocked by magnesium plugs. As magnesium‐deficient rats develop a mechanical hyperalgesia and intrathecal or intraperitoneal magnesium suppresses neuropathic pain, the magnesium concentrations in serum and cerebrospinal fluid may be altered in neuropathic pain. We therefore compared the magnesium concentrations in serum and cerebrospinal fluid of neuropathic rats with those in injured rats without symptoms of neuropathic pain and normal rats.

Methods:  Mechanical allodynia was induced in male Sprague‐Dawley rats by tight ligature of the left lumbar fifth and sixth spinal nerves. The threshold of paw withdrawal was evaluated by the up–down method using withdrawal response to stimulus with a von Frey filament on the third, seventh and 14th days. Rats with a threshold of less than 4 g were selected as the symptomatic group and compared with an asymptomatic group, an unoperated control group and a sham‐operated group. On the 16th day, the Mg2+ concentrations in serum and cerebrospinal fluid were measured.

Results:  The magnesium concentrations in the serum and cerebrospinal fluid of symptomatic neuropathic rats did not differ from those in the injured rats without symptoms of neuropathic pain, sham‐operated rats and normal rats.

Conclusion:  Our results suggest that physiologic homeostasis is maintained by active transport through the blood–brain barrier despite the activation of NMDA receptor‐gated ion channels. However, rats with neuropathic pain may be in a magnesium‐deficient condition at the effector site, such that magnesium treatment can decrease neuropathic pain.
Ischemic preconditioning attenuates the lipid peroxidation and remote lung injury in the rat model of unilateral lower limb ischemia reperfusion
Authors: Olguner Ç. , Koca U. , Kar A. , Karci A. , İşlekel H. , Canyilmaz M. , Mavioĝlu Ö. , Kizildaĝ S. , Ünlü G. , Elar Z.
Published: January 2006

Background:  Ischemia and reperfusion of the skeletal muscle tissue may cause remote lung injury. We aimed to evaluate the protective effect of ischemic preconditioning (IP) on the lung during unilateral lower limb ischemia reperfusion (IR).

Methods:  Four groups of rats were used in this study: (i) the sham group (sham, n = 6) served as time controls, they remained anesthetized for the whole duration of the study; (ii) the ischemia and reperfusion group (IR, n = 10) underwent 4 h of left lower limb ischemia followed by 2 h of reperfusion; (iii) the ischemic preconditioning group (IP, n = 10), the left lower limbs of rats were exposed to three cycles of IP (10 min of ischemia followed by 10 min of reperfusion); and (iv) the ischemic preconditioning plus ischemia reperfusion group (IP/IR, n = 10) underwent IP followed by IR as in the IP and IR groups. Plasma and tissue samples were taken at the end of the study period for determination of lung tissue myeloperoxidase activity (MPO) and polymorphonuclear leukocyte count (PMNL), histological lung injury score and plasma thiobarbituric acid reactive substances (TBARS) level.

Results:  PMNL count and MPO activity in the lung tissue, and plasma TBARS level were higher in the IR group compared with other groups while there were no differences between the sham and the IP and between the sham and the IP/IR groups. Histological lung injury score was higher in the IR group than in the IP/IR and sham groups. The plasma TBARS level in the IP group was significantly lower than in the IP/IR group.

Conclusion:  IP pretreatment reduces lipid peroxidation and lung injury caused by lower limb IR.
Diversity of laminar connections linking periarcuate and lateral intraparietal areas depends on cortical structure
Authors: Medalla M. , Barbas H.
Published: January 2006

Lateral prefrontal and intraparietal cortices have strong connectional and functional associations but it is unclear how their common visuomotor, perceptual and working memory functions arise. The hierarchical scheme of cortical processing assumes that prefrontal cortex issues ‘feedback’ projections to parietal cortex. However, the architectonic heterogeneity of these cortices raises the question of whether distinct areas have laminar‐specific interconnections underlying their complex functional relationship. Using quantitative procedures, we showed that laminar‐specific connections between distinct prefrontal (areas 46 and 8) and lateral intraparietal (LIPv, LIPd and 7a) areas in Macaca mulatta, studied with neural tracers, varied systematically according to rules determined by the laminar architecture of the linked areas. We found that axons from areas 46 and rostral 8 terminated heavily in layers I–III of all intraparietal areas, as did caudal area 8 to area LIPv, suggesting ‘feedback’ communication. However, contrary to previous assumptions, axons from caudal area 8 terminated mostly in layers IV–V of LIPd and 7a, suggesting ‘feedforward’ communication. These laminar patterns of connections were highly correlated with consistent differences in neuronal density between linked areas. When neuronal density in a prefrontal origin was lower than in the intraparietal destination, most terminations were found in layer I with a concomitant decrease in layer IV. The opposite occurred when the prefrontal origin had a higher neuronal density than the target. These findings indicate that the neuronal density of linked areas can reliably predict their laminar connections and may form the basis of understanding the functional complexity of prefrontal–intraparietal interactions in cognition.
Macrophages and neurons are targets of retinoic acid signaling after spinal cord contusion injury
Authors: Schrage Kirsten , Koopmans Guido , Joosten Elbert A. J. , Mey Jörg
Published: January 2006

The physiological reactions after spinal cord injury are accompanied by local synthesis of the transcriptional activator retinoic acid (RA). RA exerts its effects by binding to retinoic acid receptors (RAR) which heterodimerize with retinoid X receptors (RXR) and then act as ligand‐activated transcription factors. To identify possible cellular targets of RA we investigated protein levels and cellular distribution of retinoid receptors in the rat spinal cord at 4, 7, 14 and 21 days after a contusion injury. In the nonlesioned spinal cord, immunoreactivity for RARα, RXRα, RXRβ and RXRγ was localized in the cytosol of neurons, that of RXRα and RXRβ in astrocytes and that of RARα, RXRα and RXRγ in some oligodendrocytes. After contusion injury RARα and all RXRs appeared in the cell nuclei of reactive microglia and macrophages. This nuclear staining began at 4 days, was most prominent at 7 and 14 days and had decreased at 21 days after injury. A similar nuclear translocation was also observed for the RARα, RXRα and RXRβ staining in neurons situated around the border of the contusion. These observations suggest that RA participates as a signal for the physiological responses of microglia and neurons after CNS injury.
1‐HydroxyPGE1 reduces infarction volume in mouse transient cerebral ischemia
Authors: Ahmad Muzamil , Saleem Sofiyan , Zhuang Hean , Ahmad Abdullah Shafique , Echeverria Valentina , Sapirstein Adam , Doré Sylvain
Published: January 2006

Differential neurological outcomes due to prostaglandin E2 activating G‐protein‐coupled prostaglandin E (EP) receptors have been observed. Here, we investigated the action of the EP4/EP3 agonist 1‐hydroxyPGE1 (1‐OHPGE1) in modulating transient ischemic brain damage. C57BL/6 mice were pretreated 50 min before transient occlusion of the middle cerebral artery with an intraventricular injection of 1‐OHPGE1 (0.1, 0.2, 2.0 nmol/0.2 µL). Brain damage 4 days after reperfusion, as estimated by infarct volume, was significantly reduced by more than 19% with 1‐OHPGE1 in the two higher‐dose groups (P < 0.05). To further address whether protection also was extended to neurons, primary mouse cultured neuronal cells were exposed to N‐methyl‐d‐aspartate. Co‐treatment with 1‐OHPGE1 resulted in significant neuroprotection (P < 0.05). To better understand potential mechanisms of action and to test whether changes in cyclic adenosine monophosphate (cAMP) levels and downstream signaling would be neuroprotective, we measured cAMP levels in primary neuronal cells. Brief exposure to 1‐OHPGE1 increased cAMP levels more than twofold and increased the phosphorylation of extracellular‐regulated kinases at positions Thr‐202/Tyr‐204. In a separate cohort of animals, 1‐OHPGE1 at all doses tested produced no significant effect on the physiological parameters of core body temperature, mean arterial pressure and relative cerebral blood flow observed following drug treatment. Together, these results suggest that modulation of PGE2 receptors that increase cAMP levels and activate extracellular‐regulated kinases 1/2 caused by treatment with 1‐OHPGE1 can be protective against neuronal injury induced by focal ischemia.
Identification of ventricular‐side‐enriched molecules regulated in a stage‐dependent manner during cerebral cortical development
Authors: Ajioka Itsuki , Maeda Takuya , Nakajima Kazunori
Published: January 2006

Radial glial cells are the main component of the embryonic cortical ventricular zone (VZ), producing deep‐layer excitatory neurons in the early stage and upper‐layer excitatory neurons in the late stage of development. Previous studies have suggested that the laminar fate of deep‐layer neurons might be determined by early‐stage‐specific secretory or transmembrane molecules (S/TMs) in the VZ. However, the different properties required to produce the different types of neurons in early‐stage and late‐stage VZ cells are largely unknown. Herein, we investigated the stage‐dependent transcriptional profiles of the ventricular side of the mouse cortex, which was manually dissected at embryonic day (E)12, E14 and E16, and identified 3985 ‘VZ‐enriched’ genes, regulated stage‐dependently, by GeneChip analysis. These molecules were classified into nine types based on stage‐dependent regulation patterns. Prediction programs for the S/TMs revealed 659 ‘VZ‐enriched’ S/TMs. In situ hybridization and real‐time PCR analysis for several of these molecules showed results consistent with the statistical analysis of the GeneChip experiments. Moreover, we identified 17 cell cycle‐related early‐stage and ‘VZ‐enriched’ molecules. These molecules included not only those involved in cell cycle progression, but also essential molecules for DNA double‐strand break repair, such as Rad51 and Rpa1. These results suggest that the early stage‐VZ cells, which produce both deep‐ and upper‐layer neurons, and the late‐stage VZ cells, which produce only upper‐layer neurons, are intrinsically different. The gene lists presented here will be useful for the investigation of stage‐dependent changes in VZ cells and their regulatory mechanisms in the developing cortex.
Motor learning changes GABAergic terminals on spinal motoneurons in normal rats
Authors: Wang Yu , Pillai Shreejith , Wolpaw Jonathan R. , Chen Xiang Yang
Published: January 2006

The role of spinal cord plasticity in motor learning is largely unknown. This study explored the effects of H‐reflex operant conditioning, a simple model of motor learning, on GABAergic input to spinal motoneurons in rats. Soleus motoneurons were labeled by retrograde transport of a fluorescent tracer and GABAergic terminals on them were identified by glutamic acid decarboxylase (GAD)67 immunoreactivity. Three groups were studied: (i) rats in which down‐conditioning had reduced the H‐reflex (successful HRdown rats); (ii) rats in which down‐conditioning had not reduced the H‐reflex (unsuccessful HRdown rats) and (iii) unconditioned (naive) rats. The number, size and GAD density of GABAergic terminals, and their coverage of the motoneuron, were significantly greater in successful HRdown rats than in unsuccessful HRdown or naive rats. It is likely that these differences are due to modifications in terminals from spinal interneurons in lamina VI–VII and that the increased terminal number, size, GAD density and coverage in successful HRdown rats reflect and convey a corticospinal tract influence that changes motoneuron firing threshold and thereby decreases the H‐reflex. GABAergic terminals in spinal cord change after spinal cord transection. The present results demonstrate that such spinal cord plasticity also occurs in intact rats in the course of motor learning and suggest that this plasticity contributes to skill acquisition.
Cytosolic labile zinc: a marker for apoptosis in the developing rat brain
Authors: Lee Joo‐Yong , Hwang Jung Jin , Park Mi‐Ha , Koh Jae‐Young
Published: January 2006

Cytosolic zinc accumulation was thought to occur specifically in neuronal death (necrosis) following acute injury. However, a recent study demonstrated that zinc accumulation also occurs in adult rat neurons undergoing apoptosis following target ablation, and in vitro experiments have shown that zinc accumulation may play a causal role in various forms of apoptosis. Here, we examined whether intraneuronal zinc accumulation occurs in central neurons undergoing apoptosis during development. Embryonic and newborn Sprague–Dawley rat brains were double‐stained for terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labelling (TUNEL) detection of apoptosis and immunohistochemical detection of stage‐specific neuronal markers, such as nestin, proliferating cell nuclear antigen (PCNA), TuJ1 and neuronal nuclear specific protein (NeuN). The results revealed that apoptotic cell death occurred in neurons of diverse stages (neural stem cells, and dividing, young and adult neurons) throughout the brain during the embryonic and early postnatal periods. Further staining of brain sections with acid fuchsin or zinc‐specific fluorescent dyes showed that all of the apoptotic neurons were acidophilic and contained labile zinc in their cell bodies. Cytosolic zinc accumulation was also observed in cultured cortical neurons undergoing staurosporine‐ or sodium nitroprusside (SNP)‐induced apoptosis. In contrast, zinc chelation with CaEDTA or N,N,N′,N′‐tetrakis(2‐pyridylmethyl)ethylenediamine (TPEN) reduced SNP‐induced apoptosis but not staurosporine‐induced apoptosis, indicating that cytosolic zinc accumulation does not play a causal role in all forms of apoptosis. Finally, the specific cytosolic zinc accumulation may have a practical application as a relatively simple marker for neurons undergoing developmental apoptosis.
Functional contribution of specific brain areas to absence seizures: role of thalamic gap‐junctional coupling
Authors: Proulx Éliane , Leshchenko Yevgen , Kokarovtseva Larisa , Khokhotva Vladislav , El‐Beheiry Mostafa , Snead O. Carter , Perez Velazquez Jose L.
Published: January 2006

The synchronized discharges typical of seizures have a multifactorial origin at molecular, cellular and network levels. During recent years, the functional role of gap‐junctional coupling has received increased attention as a mechanism that may participate in seizure generation. We have investigated the possible functional roles of thalamic and hippocampal gap‐junctional communication (GJC) in the generation of spike‐and‐wave discharges in a rodent model of atypical absence seizures. Seizures in this model spread throughout limbic, thalamic and neocortical areas. Rats were chronically implanted with cannulae to deliver drugs or saline, and local field potentials recordings were performed using intracerebral electrodes positioned in distinct brain areas. Initially, the effects on synaptic transmission of the gap‐junctional blockers used in this study were determined. Neither carbenoxolone (CBX) nor 18‐α‐glycyrrhetinic acid altered chemical synaptic transmission at the concentrations tested. These two compounds, when injected via cannulae into the reticular nucleus of the thalamus (NRT), decreased significantly the duration of seizures as compared with saline injections or injections of the CBX inactive derivative glycyrrhizic acid. CBX injections into the hippocampus resulted in diminished seizure activity as well. NRT injections of trimethylamine, which presumably causes intracellular alkalinization (thereby promoting gap‐junctional opening), enhanced seizures and spindle activity. These observations suggest that, in this rodent model, thalamic and limbic areas are involved in the synchronous paroxysmal activity and that GJC contributes to the spike‐and‐wave discharges.
Effects of Emx2 inactivation on the gene expression profile of neural precursors
Authors: Gangemi Rosaria M. R. , Daga Antonio , Muzio Luca , Marubbi Daniela , Cocozza Serena , Perera Marzia , Verardo Sara , Bordo Domenico , Griffero Fabrizio , Capra Maria C. , Mallamaci Antonello , Corte Giorgio
Published: January 2006

Emx2 plays a crucial role in the development of the diencephalon and dorsal telencephalon. Thus, Emx2‐null mutants have abnormal cortical lamination and a reduction in size of the caudal and medial areas of the prosencephalon. Emx2 is expressed in neural precursors of the subventricular zone in vivo and in cultured neurospheres in vitro where it controls the size of the transit‐amplifying population, affecting proliferation and clonal efficiency of neural stem cells. To identify the cellular processes mastered by Emx2, and possibly the molecular mechanisms by which the gene exerts its action, we compared the expression profile of cultured neurospheres derived from wild‐type and Emx2‐null mouse embryos. The differential expression of several genes was also confirmed by semiquantitative RT‐PCR, real‐time PCR and cytofluorimetric analysis in different preparations of neurospheres, and by in situ hybridization. The gene expression profile suggested a role for Emx2 in regulating the differentiation and migration properties of neural precursor cells. This involvement was confirmed in vitro, where the altered clonogenicity and impaired migration of Emx2‐null cells were partially corrected by transduction of the Emx2 gene. Taken together, our results indicate that Emx2 is indeed involved in the transition between resident early progenitors (perhaps stem cells) and more mature precursors capable of migrating out of the ventricular zone, becoming postmitotic and differentiating into the appropriate cell type, and help explain the alterations observed in the brains of knock‐out mice.