bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioural equivalents of anxiety in children with fragile X syndrome: parent and teacher report
Authors: Sullivan Kelly , Hooper Stephen , Hatton Deborah
Published: November 2006

Background Identifying many of the diagnostic criteria for anxiety and depression in individuals with intellectual disability (ID) can be challenging because they may be unable to recognize and communicate their emotional experiences accurately. The purpose of this study is to identify behavioural equivalents of anxiety in children with fragile X syndrome (FXS), the leading inherited cause of ID.

Methods Parents and teachers of 43 children (aged 6–14 years) with full mutation FXS completed two standardized questionnaires on children’s problem behaviour and psychiatric symptoms. Items from the questionnaires thought to be possible behavioural equivalents of anxiety were identified and grouped into four domains: Avoidance Behaviours – Confrontational; Avoidance Behaviours – Non‐confrontational; Anxiety Continuum Behaviours; and Behavioural Dysregulation. The mean rating for the four groups of items was used to predict the children’s status for exhibiting significant problems with anxiety as defined by the Diagnostic and Statistical Manual of Mental Disorders‐oriented Anxiety Subscale from the problem behaviour scale.

Results The predictor variables classified 81% (parent rating) and 86% (teacher rating) of the children correctly. Avoidance Behaviours – Confrontational and Avoidance Behaviours – Non‐confrontational (teacher rating) and Anxiety Continuum Behaviours (parent and teacher rating) made unique contributions to the models.

Conclusions Children who are unable to identify and communicate that they worry about general day‐to‐day events may exhibit more observable behaviours resembling active and passive avoidance (e.g. arguing, avoiding difficult tasks, staring off) or have specific phobias and compulsions. These findings suggest that there are behavioural equivalents for anxiety disorder in children with FXS and, more generally, support the notion of behavioural equivalents in ID.
Learning from health system reforms: lessons from Burkina Faso
Authors: Haddad Slim , Nougtara Adrien , Fournier Pierre
Published: November 2006

Objectives Burkina Faso has implemented a macroeconomic adjustment programme (MAP) along with an ambitious reform of the health care system. Our aim was (1) to verify whether MAPs led to a reduction in health resources, and (2) to analyze the consequences of health policies implemented.

Method Cross‐sectional and retrospective study, spanning the years 1983–2003. The macro aspect is based upon documents from national and international sources, a database of secondary socioeconomic data, and interviews of key informants working in upper management. Household and health facility surveys were conducted in three regions covering 53 communities.

Results Within the reforms, the health sector benefited from an important flow of resources. There were significant increases in public expenditures, health care staff, the number of primary care facilities and the availability of generic drugs. However, health facilities in the public sector remain underused and major inequities subsist. Access to health care is constrained by the population's ability to pay. Health expenditures impoverish households, creating new poor and impoverishing the already poor.

Conclusions The success of reforms depends largely on the extent to which they remove financial barriers to access to services. The experience of Burkina Faso also reveals the need for fundamental changes that will motivate staff, improve productivity, and ensure good quality services. Integrating health development policies with strategic plans for poverty reduction can provide new opportunities for African countries to redesign their health systems within this type of perspective.
Differential expression of glycans in the hippocampus of rats trained on an inhibitory learning paradigm
Authors: Hidalgo Alejandra , Burgos Valeria , Viola Haydée , Medina Jorge , Argibay Pablo
Published: November 2006

The glycan chains of glycoconjugates play important roles in cell–cell and cell–matrix interactions. In the CNS, previous studies on learning and memory suggest the importance of oligosaccharides attached to glycoconjugates in the modulation of synaptic connections. We studied the hippocampal glycan distribution of rats subject to an inhibitory avoidance task. The expression of glycans was examined by lectin‐histochemistry using Vicia villosa lectin (VVL) for terminal α/β N‐acetylgalactosamine (α/β GalNAc); Galanthus nivalus lectin (GNL) for terminal mannose α‐1,3 (Man α‐1,3); Peanut agglutinin (PNA) for galactose β‐1,3N‐acetylgalactosamine (Gal β‐1,3 GalNAc); Erythrina cristagalli lectin (ECL) for galactose β‐1,4 N‐acetylglucosamine (Gal β‐1,4 GlcNAc); Sambucus nigra lectin (SNA) for sialic acid α‐2.6 galactose (SA α‐2,6 Gal); Maackia amurensis lectin II (MAL II) for sialic acid α‐2,3 (SA α‐2,3); Wheat germ agglutinin (WGA) for terminal N‐acetylglucosamine with/without sialic acid (GlcNAc wo SA); succynilated WGA (sWGA) for terminal N‐acetylglucosamine without sialic acid (terminal GlcNAc without SA); Griffonia simplicifolia lectin II (GSL II) for terminal α/β N‐acetylglucosamine (α/β GlcNAc terminal); and Lotus tetragonolobus lectin (LTL) α–fucose. Two groups of 10 animals were examined: non‐trained (Control) and Trained rats. ECL, sWGA and GSL II were negative for both groups in all the hippocampal subfields studied. For both groups, VVL was negative in CA4 and granular cells of the Dentate Gyrus (DG) and LTL was negative in the CA4 subfield. Expression of α/β GalNAc, α ‐fucose and GlcNAc in other hippocampal subfields was positive, with no differences between groups. However, expression of Man α‐1,3 was significantly higher in the CA1, CA2, CA3, and CA4 subfields in the Trained group. On the other hand, expression of Gal β‐1,3 GalNAc was significantly low in CA4 and DG in the Trained group. In conclusion, the results here presented indicate that the exposure of rats to an associative behavioral paradigm related to declarative memory, involves some regulatory mechanism/s for the differential patterns of glycan expression.
Quantitative analysis of neurofibrillary pathology in a general population to reappraise neuropathological criteria for senile dementia of the neurofibrillary tangle type (tangle‐only dementia): The Hisayama study
Authors: Noda Kazuhito , Sasaki Kensuke , Fujimi Kohei , Wakisaka Yoshinobu , Tanizaki Yumihiro , Wakugawa Yoshiyuki , Kiyohara Yutaka , Iida Mitsuo , Aizawa Hisamiti , Iwaki Toru
Published: November 2006

Senile dementia of the neurofibrillary tangle type (SD‐NFT) is characterized by numerous neurofibrillary tangles (NFT) in the hippocampal region and the absence or minimal presence of senile plaques throughout the brain. We analyzed 207 demented subjects and 68 non‐demented subjects autopsied in the Hisayama study to investigate the clinicopathological aspects of SD‐NFT in the general Japanese population. The prevalence of SD‐NFT in the consecutive autopsy cases was 8/207 (3.9%), comprising three men and five women. The average age at onset and death was 83.8 ± 6.8 (mean ± SD; standard deviation) and 88.1 ± 7.6 years, respectively. A mild memory disturbance preceded a decrease in the ability to undertake the activities of daily living and the diagnosis of dementia. Focal cerebral symptoms, such as aphasia and paralysis, did not appear during the disease course of any subject. Gross examination of the brains showed moderate to severe diffuse cerebral atrophy with brain weight loss (mean ± SD; standard deviation: 1118.1 ± 124.0 g). Histologically, there were abundant NFT and neuropil threads predominantly in or limited to the limbic cortex. The density of NFT in the CA1/subiculum in SD‐NFT was much higher than the densities in the other hippocampal regions. The average density of NFT in CA1 in SD‐NFT subjects was 115.4 per 100× field (range 23–247), that in Alzheimer disease (AD) subjects was 80.1 (range 1–227), and that in non‐demented elderly subjects was 37.2 (range 0–203). Although many previous papers have reported that the densities of NFT in the limbic system in SD‐NFT were significantly higher than those in AD, there was considerable overlap of NFT densities in CA1 among the non‐demented elderly, AD subjects and SD‐NFT subjects.
Autopsy case of sporadic Creutzfeldt–Jakob disease presenting with signs suggestive of brainstem and spinal cord involvement
Authors: Iwasaki Yasushi , Iijima Masahiro , Kimura Seigo , Yoshida Mari , Hashizume Yoshio , Yamada Masahito , Kitamoto Tetsuyuki , Sobue Gen
Published: November 2006

We describe an autopsy case of MM1‐type sporadic Creutzfeldt–Jakob disease (CJD), the duration of which was 93 days. The patient was a 59‐year‐old Japanese man with no family history of prion disease or known iatrogenic exposure to CJD. His first symptom was dysesthesia in the left arm, suggestive of cervical cord involvement, and he showed rapidly progressive neurologic signs, such as dysarthria, dysphagia, lethargy, sleep apnea and respiratory failure, suggestive of brainstem involvement. Progressive mental deterioration combined with episodes of myoclonic seizure and periodic synchronous discharges on the electroencephalogram were observed in the later disease stage. Autopsy showed typical spongiform change to be widespread in the cerebral and cerebellar cortices, thalamus and basal ganglia. Synaptic‐type PrP deposition was marked in the cerebral cortex, thalamus and basal ganglia. In the cerebellum, although the granular, molecular and Purkinje cell layers were well preserved from neuronal loss and gliosis, PrP deposition was marked in the molecular and granular cell layers. Spongiform degeneration and neuronal loss were not seen in the brainstem and spinal cord, but relatively marked PrP deposition was observed in the quadrigeminal body, substantia nigra, pontine nucleus, inferior olivary nucleus and posterior horn. Immunohistochemical staining for HLA‐DR showed proliferation of activated microglia in the cerebral and cerebellar cortices, pontine nucleus, inferior olivary nucleus and posterior horn. The mechanisms underlying the neurologic symptoms and signs were unclear, but we speculate that, in addition to widespread involvement of the cerebral cortex, PrP deposition and microglial activation in the brainstem and spinal cord were responsible.
Expression of Ki‐67, Topoisomerase IIα and c‐MYC in astrocytic tumors: Correlation with the histopathological grade and proliferative status
Authors: Faria Mário H. G. , Gonçalves Bronner P. A. , Patrocínio Régia M. do S. V. do , Moraes‐Filho Manoel O. de , Rabenhorst Silvia H. B.
Published: November 2006

Astrocytomas represent the most frequent primary tumors of the central nervous system. Recently, the determination of the proliferative index of astrocytic tumors by different methods has been proposed as a valuable tool for tumor grading and also as a prognostic marker. The aim of the present study was to evaluate the expression of cell proliferation‐related proteins in human astrocytic tumors of different histopathological grades (WHO). An immunohistochemical study of the Ki‐67, Topoisomerase IIα (Topo IIα) and c‐MYC proteins using the avidin‐biotin‐peroxidase method was performed in 55 astrocytomas (13 grade I, 14 grade II, 7 grade III and 21 grade IV) and five samples of non‐tumor brain tissue (control group). Ki‐67, Topo IIα and c‐MYC positive indices tended to increase according to malignant progression, were absent in non‐tumor brain tissue and showed maximum values in high‐grade astrocytomas (III and IV). A gradual increase in Ki‐67 antigen expression was observed in agreement with mitotic index and histopathological classification. The same was not observed for Topo IIα and c‐MYC. Ki‐67 antigen detection in more than 8.0% of the tumor cells distinguished astrocytoma grade IV, while a labeling index between 1.5 and 8.0% characterized astrocytomas grade III and values below 1.5% discriminated low‐grade tumors (I and II). These results indicate that Topo IIα and c‐MYC expression is associated with cell proliferation in astrocytomas, although not in an exclusive way. Moreover, Ki‐67 antigen was found to be the best marker of cellular proliferation, and its expression predicts the grade of astrocytic tumors.
Solitary fibrous tumor of the orbit: Morphological, cytogenetic and molecular features
Authors: Cerdá‐Nicolás Miguel , López‐Gines Concha , Gil‐Benso Rosario , Benito Rafael , Pellin Antonio , Ruiz‐Saurí Amparo , Sanchos‐Garcia Juan , Roldan Pedro , Talamantes Fernando , Barberá José
Published: November 2006

Solitary fibrous tumor (SFT), a benign neoplasm arising in mesenchymal structures, was initially described in the pleura but subsequently has also been documented in other locations. It is uncommon in the orbit, where it closely resembles other benign spindle‐shaped mesenchymal tumors of this area such as schwannoma, meningioma or hemangiopericytoma. We present a case of orbital SFT in a 34‐year‐old woman. The radiological study showed the presence of an enhanced uptake lesion measuring 2 cm in major diameter. The histopathological evaluation revealed alternating cellular and hypocellular areas with spindle‐shaped cells. The cellular organization displayed a broad variety of irregular morphological patterns. The neoplastic cells were intensely positive for CD34 and vimentin, while S100, epithelial membrane antigen (EMA), Caldesmon, Calretinin and WT‐1 proved negative. The pericellular matrix exhibited strong positivity for CD44 and collagen IV. Scarce mitotic figures, a Ki‐67 nuclear labeling index of <5%, and focal expression of p53 were also observed. Measurement of DNA content revealed a DNA index of 1, indicating a diploid peak in 95% of the tumor cells. A normal 46,XX karyotype was present. No TP53 (exons 5–8) mutations or MDM2 and CDK4 amplifications were observed. No p14ARF, p15INK4B and p16INK4A deletions or hypermethylation were observed in this benign tumor. Following surgical resection and radiotherapy, the patient showed no tumor relapse after one year of follow‐up.
Causes of neuronal heterotopia other than migration disturbances
Authors: Hori Akira
Published: November 2006

A differentiated form of cerebellocortical fragments (case 1) in the white matter or even in the cerebellar dentate nucleus, found in a fetus with trisomy 13, may be due to an auto‐transplantation accompanied by a penetrating vessel. A similar condition was observed in the Ammon’s horn (case 2) incidentally as a heterotopic tissue fragment of the dentate fascia. Further cause of heterotopia may be speculated as a mechanical separation by a surrounding and developing tissue part in case of organized, differentiated cerebellocortical heterotopia in the white matter (cases 3–5) which were clinically silent. Migration disturbances are not the only cause of neuronal heterotopia since the structure of heterotopia is differentiated and organized by tissue components.
Low‐grade follicular lymphoma in the dura: Rare mimic of meningioma
Authors: Low Irene , Allen Jonathan
Published: November 2006

Lymphomas rarely present as a localized mass within the dura. We report a case of a 72‐year‐old woman, normally fit and well, who presented with a sudden episode of grand mal seizure. Imaging studies showed an extra‐axial mass arising from the dura, with radiologic features characteristic of a meningioma. The mass was surgically excised, and the histologic features were of a grade 1 follicular lymphoma. Analysis using fluorescent in situ hybridization (FISH) demonstrated t(14:18) translocation. A bone marrow aspirate showed focal infiltration of lumbar vertebra by low‐grade follicular lymphoma. Intracranial meningeal involvement by non‐Hodgkin lymphoma usually occurs in the form of diffuse leptomeningeal spread. It is seen in high‐grade lymphomas, often in association with widespread systemic disease. The majority of cases of dural lymphomas reported in the literature have been primary mucosa‐associated lymphoid tissue (MALT)‐type lymphomas. Most of these presented as localized dural masses mimicking meningiomas. Low‐grade follicular lymphoma, either primary or secondarily involving the dura, appears to be an exceedingly rare occurrence.
Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat
Authors: Holland P. R. , Akerman S. , Goadsby P. J.
Published: November 2006

Migraine pathophysiology is thought to involve the trigeminal innervation of the dura mater and intracranial blood vessels. Electrical stimulation of dural blood vessels is painful in humans and causes activation of neurons in the caudal‐most portion of the trigeminal nucleus in experimental animals. The hypothalamic neuropeptides orexin A and B are selectively synthesized in the lateral and posterior hypothalamus, and recent findings have implicated their involvement in nociceptive processing. To evaluate the potential for orexin receptor modulation of trigeminovascular nociceptive afferents, we examined the effects of intravenous orexin A and B on responses of neurons in the trigeminal nucleus caudalis. To dissect the receptor pharmacology of responses to stimulation we utilized the novel orexin 1 receptor (OX1R) antagonist N‐(2‐methyl‐6‐benzoxazolyl)‐N′′‐1,5‐naphthyridin‐4‐yl urea (SB‐334867). Orexin A 30 µg/kg (F1.9,9.8 = 21.93,P < 0.001) and 50 µg/kg (F3.2,16.4 = 3.28,P < 0.045) inhibited the A‐fibre responses to dural electrical stimulation over 60 min. Maximum inhibition was achieved at 25 min for both 30 µg/kg (t5 = 19.83,n = 6,P < 0.001) and 50 µg/kg (t5 = 7.74,n = 6,P < 0.001). The response with orexin A 30 µg/kg was reversed by pretreatment with the OX1R antagonist SB‐334867 (F3.5,17.5 = 0.49,P = 0.73), which had no effect when given alone. Orexin B and control vehicle administration had no significant effect on trigeminal neuronal firing. The current study demonstrates that orexin A is able to inhibit A‐fibre responses to dural electrical stimulation via activation of the OX1R.
Visual functions without the occipital lobe or after cerebral hemispherectomy in infancy
Authors: Werth Reinhard
Published: November 2006

This paper investigates whether and to what extent vision with awareness is still possible in the whole visual field after loss of the occipital lobe of one or both cerebral hemispheres or after hemispherectomy in childhood. The visual functions of four children who suffered from unilateral or bilateral loss of the occipital lobe or who had been hemispherectomized were examined. The results show that even after unilateral loss of the striate and prestriate cortex the extent of the visual field may still be in the normal range. The residual visual functions may be mediated by intact extrastriate areas such as V5 and LO of the damaged cerebral hemisphere. It is also shown that even after complete hemispherectomy in early life the visual field may have a normal extent and that conscious visual perception in the whole visual field may be preserved. In hemispherectomized children, the remaining cerebral hemisphere or neural structures in the midbrain, including the superior colliculi and the praetectum, may be able to mediate these visual functions.
Telencephalon and geometric space in goldfish
Authors: Vargas Juan Pedro , Bingman Verner Peter , Portavella Manuel , López Juan Carlos
Published: November 2006

Neuroanatomical evidence indicates that the lateral pallium (LP) of ray‐finned fishes could be homologous to the hippocampus of mammals and birds. Recent studies have found that hippocampus of mammals and birds is critical for learning geometric properties of space. In this work, we studied the effects of lesions to the lateral pallium of goldfish on the encoding of geometric spatial information. Goldfish with telencephalic lesions were trained to search for a goal in a rectangular‐shaped arena containing one different wall that served as the only distinctive environmental feature. Although fish with lateral pallium lesions learned the task even faster than sham and medial pallium (MP)‐lesioned animals, subsequent probe trials showed that they were insensitive to geometric information. Sham and medial pallium‐lesioned animals could use both geometric and feature information to locate the goal. By contrast, fish with lateral palium lesions relied exclusively on the feature information provided by the wall of a different colour. These results indicate that lesions to the lateral pallium of goldfish, like hippocampal lesions in mammals and birds, selectively impair the encoding of geometric spatial information of environmental space. Thus, the forebrain structures of teleost fish that are neuroanatomically equivalent to the mammalian and avian hippocampus also share a central role in supporting spatial cognition. Present results suggest that the presence of a hippocampal‐dependent memory system implicated in the processing of geometric spatial information is an ancient feature of the vertebrate forebrain that has been conserved during the divergent evolution of different vertebrate groups.
Difference in organization of corticostriatal and thalamostriatal synapses between patch and matrix compartments of rat neostriatum
Authors: Fujiyama Fumino , Unzai Tomo , Nakamura Kouichi , Nomura Sakashi , Kaneko Takeshi
Published: November 2006

The neostriatum, which possesses a mosaic organization consisting of patch and matrix compartments, receives glutamatergic excitatory afferents from the cerebral cortex and thalamus. Differences in the synaptic organization of these striatopetal afferents between the patch and matrix compartments were examined in the rat using confocal laser scanning and electron microscopes. Thalamostriatal terminals immunopositive for vesicular glutamate transporter (VGluT) 2 were less dense in the patch than in the matrix compartment, although the density of VGluT1‐immunopositive corticostriatal terminals was almost evenly distributed in both the compartments. Quantitative analysis of ultrastructural images revealed that 84% of VGluT2‐positive synapses in the patch compartment were formed with dendritic spines, whereas 70% in the matrix compartment were made with dendritic shafts. By contrast, VGluT1‐positive terminals display a similar preference for specific synaptic targets in both compartments: about 80% made synapses with dendritic spines. In addition, VGluT2‐positive axospinous synapses in the patch compartment were larger than the VGluT1‐positive axospinous synapses in both compartments. As axospinous synapses are generally found in neuronal connections showing high synaptic plasticity, the present findings suggest that the thalamostriatal connection requires higher synaptic plasticity in the patch compartment than in the matrix compartment.
Absence of carotid rete mirabile in small tropical ruminants: implications for the evolution of the arterial system in artiodactyls
Authors: Fukuta Katsuhiro , Kudo Hiroshi , Sasaki Motoki , Kimura Junpei , Ismail Dahlan bin , Endo Hideki
Published: November 2006

The intracranial carotid rete (or rete mirabile epidurale) is a unique blood vascular system supplying the brain of artiodactyls, which have either an involuted or no internal carotid artery. Although the lesser and greater mouse deer (Tragulus javanicusandT. napu, respectively) are ruminants, the rete mirabile epidurale is absent. In these animals, as in non‐artiodactyls, such as canines, equines and humans, the complete internal carotid artery supplies the brain. It is currently uncertain whether the absence of the rete is confined to mouse deer among ruminants. The absence of the rete in mouse deer provides new insights into the evolution of the arterial system in artiodactyls.
Activity patterns of springhares from the Eastern Cape Province, South Africa
Authors: Brown C. R. , Peinke D. M.
Published: November 2006

The activity patterns of springhares Pedetes capensis (Rodentia: Pedetidae) from the Eastern Cape Province, South Africa, were investigated by counting the number of springhares active above ground at regular intervals throughout the night at different times of the year and under different weather conditions and phases of the moon. A combination of time of year, time of night and level of illumination best explained springhare activity, accounting for 43% of the variation in springhare numbers. Springhare activity generally reached its peak soon after dark, thereafter remaining fairly constant throughout most of the night and only decreasing in the 2–4‐h period before sunrise. On those nights when the moon either rose or set during the night, this pattern was modified by the level of illumination. Springhares responded to moonlight by reducing above‐ground activity, shifting activity to dark, moonless periods of the night, and by reducing their use of open space. Except for extremes, other weather conditions had no significant effect on springhare activity.
Challenging the New Military History: The Case of Eighteenth‐Century British Army Studies
Authors: Tatum William P.
Published: November 2006

Since the 1950s, academic military history has experienced an explosion in the quantity and quality of its scholarship. Historians have traditionally attributed this expansion to the advent of the “New Military History.” This article challenges the conventional account of academic military history's expansion by examining the past thirty years of work on the eighteenth‐century British Army. The results of this analysis will be used to suggest replacing the traditional divide between new and old military history with the more utilitarian subfields of the History of War and the History of the Army.
Characterization of the antioxidant profile of human saliva in peri‐implant health and disease
Authors: Liskmann Stanislav , Vihalemm Tiiu , Salum Olev , Zilmer Kersti , Fischer Krista , Zilmer Mihkel
Published: November 2006

Objectives: Peri‐implant disease is considered to be an inflammatory disease, but many aspects of its pathogenesis remain unknown. At present, peri‐implant disease is considered to be initiated and perpetuated by a small group of predominantly Gram‐negative, anaerobic, or micro‐aerophilic bacteria that colonize the subgingival area. Bacteria cause the observed tissue destruction directly by toxic products and indirectly by activating host defence systems, i.e. inflammation. A variety of molecular species appears in the inflamed tissues, among them are reactive species such as free radicals and reactive oxygen species (ROS). The purpose of this study was to assess levels of various antioxidants in saliva to identify differences between the saliva of patients with healthy peri‐implant tissues and patients with peri‐implant disease, and to examine whether the whole saliva of those with peri‐implant disease conditions might have lower levels of antioxidants than that of healthy individuals.

Materials and Methods: Thirty healthy adult volunteers (14 men and 16 women) with implant‐supported overdentures (Ankylos® Biofunctional Implants) were selected from the group of patients from Tallinn Dental Clinic. Biochemical and clinical parameters evaluated were the following ones: the levels of urate, ascorbate, myeloperoxidase in saliva, total antioxidant status of saliva, pocket probing depth (mm), gingival index (0, 1, 2, or 3), and bleeding on probing (0 or 1).

Results and conclusion: Total antioxidant status (TAS) of saliva and concentration of uric acid and ascorbate, which are the main salivary antioxidants, are significantly decreased in patients with peri‐implant disease. TAS in healthy subjects was 0.41±0.10 for resting saliva and 0.31±0.09 for stimulated saliva; in diseased subjects TAS was 0.19±0.07 and 0.12±0.03, respectively. In healthy subjects, the concentration of urate was 307.2±78.06 μM/l in resting saliva and 241.5±89.09 μM/l in stimulated saliva. In diseased patients, the concentration of urate was 120±36.13 and 91.60±39.35 μM/l, respectively. The concentration of ascorbate did not differ in resting and stimulated saliva. In healthy subjects, it was 2.79±0.81 mg/l and in diseased subjects, it was 1.54±0.30 mg/l. This may indicate that excessive ROS production in peri‐implant disease is leading to the situation of excessive oxidative stress, which may be an important factor contributing the destruction of peri‐implant tissues.

The importance of these findings may be the better understanding of the processes involved in the pathogenesis of peri‐implant disease and that the treatment of peri‐implant disease may involve adjuvant anti‐oxidants supplementation together with cumulative interceptive supportive therapy concept introduced by Mombelli & Lang.
Decontamination of rough titanium surfaces with diode lasers: microbiological findings on in vivo grown biofilms
Authors: Sennhenn‐Kirchner Sabine , Klaue Sören , Wolff Nadine , Mergeryan Hamparsum , Borg von Zepelin Margarete , Jacobs Hans Georg
Published: November 2006

Objectives: The bactericidal efficacy of diode lasers has already been demonstrated in vitro. We investigated the reduction of aerobe bacteria – colonizing rough titanium samples in biofilms intraorally grown – by diode lasers of different wave lengths.

Material and methods: Twenty‐two volunteers participated in the trial. They were fitted for 10 days with custom‐made intraoral plastic splints carrying titanium sleeves. A part of the sleeves was then irradiated with diode lasers in different modes. The other part remained non‐irradiated and served as control. Directly after irradiation, the sleeves were swabbed and the gained bacteria were first examined microscopically and then were cultured under aerobic conditions.

Results: The bacteria in the controls and in the treated samples were quantified. A comparison with the controls revealed a marked overall reduction of bacterial colonization in all irradiated sleeves. Continuous irradiation for 20 s reduced bacteria counts by 99.67% at 810 nm and 99.58% at 980 nm. Repeating the 20 s exposure five times reduced counts by 99.98% at 810 nm and by 99.39% at 980 nm. A 98.86% reduction was seen after irradiation in pulsed mode. A further analysis in respect of different isolated bacteria revealed that the streptococci group was reduced by 99.29–99.99%, while the staphylococci group was reduced to a lesser extent in the range 94.67–99.99%.

Conclusion: The results are of clinical relevance. In comparison with the mean bacterial counts of the untreated samples, all irradiation programs studied in this investigation reduced mean bacterial colonization in a biofilm on intraoral rough titanium surfaces by more than 98%. The actual extent of reduction was dependent on the bacteria species as well as on the irradiation mode.
Cementable implant crowns composed of cast superstructure frameworks luted to electroformed primary copings: an in vitro retention study
Authors: Di Felice Roberto , Rappelli Giorgio , Camaioni Emanuele , Cattani Maria , Meyer Jean‐Marc , Belser Urs C.
Published: November 2006

Objective: The aim of this in vitro study was to investigate, on ITI solid abutments, the retention values of single crowns fabricated using an alternative prosthetic solution: secondary cast superstructure luted to an electroformed primary coping.

Materials and methods: Fifty standard 4.1 mm ITI implants and 5.5 mm high ITI machined abutments were assembled and mounted in acrylic resin. Implant/abutment assemblies were randomly divided into two groups. In the test group, primary galvanic caps were directly fabricated on implant abutments (A.G.C. Micro machine), and a secondary cast noble alloy superstructure was luted on each primary galvanic cap with a resin cement (Nimetic Cem). In the control group, prefabricated burn‐out caps were used for casting the metal frameworks. Test and control crowns were cemented using a resin cement (Panavia 21). After storage at 37° for 24 h, the specimens were subjected to a pull‐out test using an Instron universal testing machine. The load required to dislodge each sample and the respective mode of failure were recorded. Means and standard deviations of loads at failure were analyzed using ANOVA. Statistical significance was set at P≤0.05.

Results: The retention values (±SD) of loads at failure were 67.26 (±16.61) for the test group and 44.03 (±9.45) for the control group. In the test group no separation occurred between the electroformed (galvanic) primary cap and the secondary superstructure.

Conclusions: The results showed that this prosthetic solution is superior on retentive performance than the conventional cast framework. An added clinical advantage of this novel method is its potential to provide a totally passive fit.

Further in vitro and in vivo studies involving multiple‐unit restorations are needed in order to more generally validate this prosthetic concept.
Bone regeneration in dehiscence‐type defects at chemically modified (SLActive®) and conventional SLA titanium implants: a pilot study in dogs
Authors: Schwarz Frank , Herten Monika , Sager Martin , Wieland Marco , Dard Michel , Becker Jürgen
Published: November 2006

Objectives: The aim of the present study was to evaluate bone regeneration in dehiscence‐type defects at titanium implants with chemically modified (mod) and conventional sand‐blasted/acid‐etched (SLA) surfaces.

Material and Methods: Standardized buccal dehiscence defects (height: 3 mm, width: 3 mm) were surgically created following implant site preparation in both the upper and lower jaws of four beagle dogs. modSLA and SLA implants were inserted bilaterally according to a split‐mouth design. The animals were sacrificed after 2 and 12 weeks (n=2 animals each). Dissected blocks were processed for histomorphometrical analysis: defect length, new bone height (NBH), percent linear fill (PLF), percent of bone‐to‐implant contact (BIC‐D) and area of new bone fill (BF).

Results: Wound healing at SLA implants was predominantly characterized by the formation of a dense connective tissue at 2 and 12 weeks, without significant increases in mean NBH, PLF, BIC‐D or BF values. In contrast, modSLA implants exhibited a complete defect fill at 12 weeks following implant placement. In particular, histomorphometrical analysis revealed the following mean values at 12 weeks: NBH (3.2±0.3 mm), PLF (98%), BIC‐D (82%) and BF (2.3±0.4 mm2).

Conclusion: Within the limits of the present study, it was concluded that modSLA titanium surfaces may promote bone regeneration in acute‐type buccal dehiscence defects at submerged implants.
Melatonin increases stress fibers and focal adhesions in MDCK cells: participation of Rho‐associated kinase and protein kinase C
Authors: Ramírez‐Rodríguez Gerardo , Ortiz‐López Leonardo , Benítez‐King Gloria
Published: November 2006

Abstract:  Melatonin cyclically modifies water transport measured as dome formation in MDCK cells. An optimal increase in water transport, concomitant with elevated stress fiber (SF) formation, occurs at nocturnal plasma melatonin concentrations (1 nm) after 6 hr of incubation. Blockage in melatonin‐elicited dome formation was observed with protein kinase C (PKC) inhibitors. Despite, this information on the precise mechanism by which melatonin increases SF formation involved in water transport is not known. Focal adhesion contacts (FAC) are cytoskeletal structures, which participate in MDCK membrane polarization. SF organization and vinculin phosphorylation are involved in FAC assembly and both processes are mediated by PKC, an enzyme stimulated by melatonin; in these processes also involved is Rho‐associated kinase (ROCK). Thus, we studied FAC formation and the ROCK/PKC pathway as the mechanism by which melatonin increases SF formation and water transport. The results showed that 1 nM melatonin and the PKC agonist phorbol‐12‐miristate‐13‐acetate increased FAC. The PKC inhibitor GF109203x, and the ROCK inhibitor Y27632, blocked increased FAC caused by melatonin. ROCK and PKC activities, vinculin phosphorylation and FAC formation were increased with melatonin. The PKC inhibitor, GF109203x, abolished both melatonin stimulated FAC in whole cells and ROCK activity, indicating that ROCK is a downstream kinase in the melatonin‐stimulated PKC pathway in MDCK cultured cells that causes an increase in SF and FAC formation. Data also document that melatonin modulates water transport through modifications of the cytoskeletal structure.
Review article: the role of sleep in the pathogenesis of gastro‐oesophageal reflux disease
Authors: ORR W. C.
Published: November 2006

Night‐time heartburn is common in patients with gastro‐oesophageal reflux disease and its consequences in terms of sleep disturbance and subsequent effects on daytime functioning are substantial.

Most patients with night‐time heartburn indicate that it is more bothersome than daytime heartburn. A significant odds ratio has been described between night‐time heartburn and daytime sleepiness and fatigue.

Sleep‐related gastro‐oesophageal reflux has characteristics that distinguish it from waking reflux and that have been shown to enhance the risk of the development of reflux oesophagitis. Swallowing and salivary flow are markedly diminished during sleep and behavioural arousal responses to acid mucosal contact are blunted due to the depressed consciousness of the sleeping state. These sleep‐related changes conspire to prolong acid mucosal contact, which in turn increases the likelihood of significant hydrogen ion back‐diffusion and the risk of oesophageal damage.

An awareness of the presence of night‐time heartburn suggests significant sleep‐related gastro‐oesophageal reflux and this should be assessed in order to optimally treat gastro‐oesophageal reflux disease patients.

Consideration of PPI treatment should involve an assessment of its effectiveness in maintaining acid suppression throughout the sleeping interval.
Systemic, cellular and molecular analysis of chemoreflex‐mediated sympathoexcitation by chronic intermittent hypoxia
Authors: Prabhakar Nanduri R. , Dick Thomas E. , Nanduri Jayasri , Kumar Ganesh K.
Published: November 2006

Patients with recurrent apnoeas exhibit autonomic abnormalities manifested as persistent increase in sympathetic nerve activity (SNA). Several studies suggest that chronic intermittent hypoxia (CIH) resulting from recurrent apnoeas is a major stimulus for evoking autonomic morbidity. Although it has been proposed that CIH, by way of activating the chemoreceptor reflex, leads to sympathetic excitation, the underlying mechanisms are incompletely understood. Studies on experimental models have provided new insights into the mechanisms associated with CIH‐evoked sympathoexcitation. The purpose of this article is to highlight recent information on systemic, cellular and molecular analysis of the effects of CIH on chemoreceptor‐mediated sympathoexcitation. Chronic intermittent hypoxia exerts two major effects on the chemoreceptor reflex: (a) augmentation of the carotid body and sympathetic effector responses to acute hypoxia; and (b) induction of long‐lasting activation of both the sensor and the effector that persists several hours after termination of CIH. Available evidence indicates that CIH may facilitate processing of chemoreceptor afferent information at the central nervous system. Recent studies suggest that reactive oxygen species‐mediated signalling is a major cellular mechanism, and transcriptional activation by hypoxia‐inducible factor‐1 is one of the critical molecular mechanisms underlying chemoreceptor‐mediated sympathoexcitation by CIH.
Simultaneous measurement of current and calcium in the ultraviolet‐sensitive cones of zebrafish
Authors: Leung Yiu Tak , Fain Gordon L. , Matthews Hugh R.
Published: November 2006

In rods and visible cone photoreceptors, multiple measurements cannot be made of intracellular Ca2+ concentration from the same cell using fluorescent dyes, because a single exposure of the measuring light bleaches too large a fraction of the rod or cone photopigment. We have therefore identified and characterized UV‐sensitive cones of the zebrafish, whose wavelength of maximum sensitivity is at 360 nm which is far enough from the wavelength of our measuring light (514.5 nm) so that it has been possible to make multiple determinations of photocurrent and Ca2+ concentration from the same cells. We show that for a limited number of measurements, for which the bleaching of the cone photopigment is too small to affect flash kinetics, the outer segment Ca2+ concentration closely follows the wave form of the flash response convolved with the dominant time constant for Ca2+ removal by Na+–Ca2+–K+ exchange. For a larger number of measurements, significant acceleration of the response kinetics by pigment bleaching inevitably occurs, but the Ca2+ concentration nevertheless rises and falls in approximate agreement with the flash wave form. During exposure to steady background light, the Ca2+ concentration falls in proportion to the steady‐state current for dim backgrounds at all times and for bright backgrounds at steady state. At early times following the onset of bright backgrounds, however, the Ca2+ concentration is markedly higher than expected from the current of the cone. We show this to be the result of light‐dependent Ca2+ release by bright background light, which can be abolished by pre‐exposure of the cone to the membrane‐permeant acetoxymethyl ester of the Ca2+ chelator BAPTA. Our results therefore demonstrate that the cone outer segment Ca2+ concentration is predominantly a function of the rate of influx and efflux of Ca2+ across the plasma membrane, but that a release of Ca2+ in bright light most probably from buffer sites within the cell can transiently elevate the Ca2+ concentration above the level expected from the open probability of the light‐dependent channels.
Protease‐activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice
Authors: Grant Andrew D. , Cottrell Graeme S. , Amadesi Silvia , Trevisani Marcello , Nicoletti Paola , Materazzi Serena , Altier Christophe , Cenac Nicolas , Zamponi Gerald W. , Bautista‐Cruz Francisco , Lopez Carlos Barajas , Joseph Elizabeth K. , Levine Jon D. , Liedtke Wolfgang , Vanner Stephen , Vergnolle Nathalie , Geppetti Pierangelo , Bunnett Nigel W.
Published: November 2006

Exacerbated sensitivity to mechanical stimuli that are normally innocuous or mildly painful (mechanical allodynia and hyperalgesia) occurs during inflammation and underlies painful diseases. Proteases that are generated during inflammation and disease cleave protease‐activated receptor 2 (PAR2) on afferent nerves to cause mechanical hyperalgesia in the skin and intestine by unknown mechanisms. We hypothesized that PAR2‐mediated mechanical hyperalgesia requires sensitization of the ion channel transient receptor potential vanilloid 4 (TRPV4). Immunoreactive TRPV4 was coexpressed by rat dorsal root ganglia (DRG) neurons with PAR2, substance P (SP) and calcitonin gene‐related peptide (CGRP), mediators of pain transmission. In PAR2‐expressing cell lines that either naturally expressed TRPV4 (bronchial epithelial cells) or that were transfected to express TRPV4 (HEK cells), pretreatment with a PAR2agonist enhanced Ca2+and current responses to the TRPV4 agonists phorbol ester 4α‐phorbol 12,13‐didecanoate (4αPDD) and hypotonic solutions. PAR2‐agonist similarly sensitized TRPV4 Ca2+signals and currents in DRG neurons. Antagonists of phospholipase Cβ and protein kinases A, C and D inhibited PAR2‐induced sensitization of TRPV4 Ca2+signals and currents. 4αPDD and hypotonic solutions stimulated SP and CGRP release from dorsal horn of rat spinal cord, and pretreatment with PAR2agonist sensitized TRPV4‐dependent peptide release. Intraplantar injection of PAR2agonist caused mechanical hyperalgesia in mice and sensitized pain responses to the TRPV4 agonists 4αPDD and hypotonic solutions. Deletion of TRPV4 prevented PAR2agonist‐induced mechanical hyperalgesia and sensitization. This novel mechanism, by which PAR2activates a second messenger to sensitize TRPV4‐dependent release of nociceptive peptides and induce mechanical hyperalgesia, may underlie inflammatory hyperalgesia in diseases where proteases are activated and released.
Neurotransmitter mechanisms mediating low‐glucose signalling in cocultures and fresh tissue slices of rat carotid body
Authors: Zhang Min , Buttigieg Josef , Nurse Colin A.
Published: November 2006

The mammalian carotid body (CB) is a polymodal chemosensor which can detect low blood glucose (hypoglycaemia), leading to increased afferent discharge and activation of counter‐regulatory autonomic pathways. The underlying neurotransmitter mechanisms are unknown and controversy surrounds whether the action of low glucose is direct or indirect. To address this, we used a coculture model containing functional chemosensory units of rat CB receptor (type I) cell clusters and afferent petrosal neurones (PN). During perforated‐patch, whole‐cell recordings, low glucose (0–2 mm) stimulated sensory discharge in cocultured PN. When the background P was lowered to levels typical of arterial blood (∼90 mmHg), robust PN chemoexcitation could be induced by physiological hypoglycaemia (3.3–4 mm glucose). These sensory responses were reversibly inhibited by a combination of purinergic (suramin, 50 μm) and nicotinic (mecamylamine, 1 μm) receptor blockers, suggesting that transmission depended on corelease of ATP and ACh. Hypoglycaemic responses were additive with those evoked by hypoxia or hypercapnia; further, they could be potentiated by the GABAB receptor blocker (CGP 55845) and inhibited by 5‐HT2A receptor blockers (ketanserin or ritanserin). During paired simultaneous recordings from a PN and a type I cell in an adjacent cluster, the afferent PN response coincided with type I cell depolarization, which was associated with a decrease in input resistance. In fresh tissue slices of rat CB, low glucose stimulated ATP secretion as determined by the luciferin–luciferase assay; this secretion was cadmium sensitive, potentiated by CGP 55845, and inhibited by ketanserin. Taken together these data indicate that CB receptors act as direct glucosensors, and that processing of hypoglycaemia utilizes similar neurotransmitter and neuromodulatory mechanisms as hypoxia.
Maturation of rat cerebellar Purkinje cells reveals an atypical Ca2+ channel current that is inhibited by ω‐agatoxin IVA and the dihydropyridine (−)‐(S)‐Bay K8644
Authors: Tringham Elizabeth W. , Payne C. Elizabeth , Dupere Jonathan R. B. , Usowicz Maria M.
Published: November 2006

To determine if the properties of Ca2+ channels in cerebellar Purkinje cells change during postnatal development, we recorded Ca2+ channel currents from Purkinje cells in cerebellar slices of mature (postnatal days (P) 40–50) and immature (P13–20) rats. We found that at P40–50, the somatic Ca2+ channel current was inhibited by ω‐agatoxin IVA at concentrations selective for P‐type Ca2+ channels (∼85%; IC50, <1 nm) and by the dihydropyridine (–)‐(S)‐Bay K8644 (∼70%; IC50, ∼40 nm). (−)‐(S)‐Bay K8644 is known to activate L‐type Ca2+ channels, but the decrease in current was not secondary to the activation of L‐type channels because inhibition by (−)‐(S)‐Bay K8644 persisted in the presence of the L‐type channel blocker (R,S)‐nimodipine. By contrast, at P13–20, the current was inhibited by ω‐agatoxin IVA (∼86%; IC50, ∼1 nm) and a minor component was inhibited by (R,S)‐nimodipine (∼8%). The dihydropyridine (−)‐(S)‐Bay K8644 had no clear effect when applied alone, but in the presence of (R,S)‐nimodipine it reduced the current (∼40%), suggesting that activation of L‐type channels by (−)‐(S)‐Bay K8644 masks its inhibition of non‐L‐type channels. Our findings indicate that Purkinje neurons express a previously unrecognized type of Ca2+ channel that is inhibited by ω‐agatoxin IVA, like prototypical P‐type channels, and by (−)‐(S)‐Bay K8644, unlike classical P‐type or L‐type channels. During maturation, there is a decrease in the size of the L‐type current and an increase in the size of the atypical Ca2+ channel current. These changes may contribute to the maturation of the electrical properties of Purkinje cells.