bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerance to allopregnanolone with focus on the GABA‐A receptor
Authors: Turkmen Sahruh , Backstrom Torbjorn , Wahlstrom Goran , Andreen Lotta , Johansson Inga‐Maj
Published: September 2010

Many studies have suggested a relationship between stress, sex steroids, and negative mental and mood changes in humans. The progesterone metabolite allopregnanolone is a potent endogenous ligand of the γ‐amino butyric acid –A (GABA‐A) receptor, and the most discussed neuroactive steroid. Variations in the levels of neuroactive steroids that influence the activity of the GABA‐A receptor cause a vulnerability to mental and emotional pathology. There are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA‐A receptor to high and continuous allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone may develop. We have shown that both acute and chronic tolerances can develop to the effects of allopregnanolone. Following the development of acute allopregnanolone tolerance, there is a decrease in the abundance of the GABA‐A receptor α4 subunit and the expression of the α4 subunit mRNA in the ventral‐posteriomedial nucleus of the thalamus. Little is known about the mechanism behind allopregnanolone tolerance and its effects on assembly of the GABA‐A receptor composition. The exact mechanism of the allopregnanolone tolerance phenomena remains unclear. The purpose of this review is to summarize certain aspects of current knowledge concerning allopregnanolone tolerance and changes in the GABA‐A receptors.
Generation of recombinant antibody fragments that target canine dendritic cells by phage display technology
Authors: Fitting J. , Killian D. , Junghanss C. , Willenbrock S. , Murua Escobar H. , Lange S. , Nolte I. , Barth S. , Tur M. K.
Published: September 2010

One of the main goals in cancer immunotherapy is the efficient activation of the host immune system against tumour cells. Dendritic cells (DCs) can induce specific anti‐tumour immune responses in both experimental animal models and humans. However, most preclinical studies using small animal models show only limited correlation with studies carried out in clinical settings, whereas laboratory dogs naturally develop tumours that are biologically and histopathologically similar to their human counterparts. Here, we describe the generation and characterization of recombinant antibodies against canine DCs, isolated using the Tomlinson phage display system. We successfully isolated highly specific single‐chain variable fragment (scFv) antibodies in a sequential three‐step panning strategy involving depletion on canine peripheral blood mononuclear cells followed by positive selection on native canine DCs. This provides the basis for an antibody‐based method for the immunological detection and manipulation of DCs and for monitoring antigen‐specific immune responses.
Rolandic epilepsy: An uncommon presentation with leg motor seizures
Authors: Fusco Lucia , Trivisano Marina , Specchio Nicola , Vigevano Federico
Published: September 2010

Rolandic epilepsy (RE) is the most common and one of the most benign epileptic syndromes of childhood. It is typically characterized by sleep‐related orofacial seizures, of brief duration, of variable frequency, in otherwise healthy children. Electroencephalography (EEG) shows typical centrotemporal spike and spike‐and‐wave complexes, often bilateral and asynchronous, activated by sleep. Therapy is often unnecessary and seizures spontaneously end at puberty. Apart from typical orofacial localization, arm or more diffuse clonic jerks are frequently described by parents. More rare and probably underestimated are sensorimotor seizure localized to one leg. When such seizures represent the only type of seizures in RE, the exact recognition of this benign epileptic syndrome appears difficult, leading to unnecessary investigation and therapy. We describe six children, among 230 with RE, who presented leg sensorimotor seizures as the mainly type of ictal manifestations.
Ictogenesis and symptomatogenesis of gelastic seizures in hypothalamic hamartomas: An ictal SPECT study
Authors: Kameyama Shigeki , Masuda Hiroshi , Murakami Hiroatsu
Published: September 2010

Purpose: To topographically localize the ictogenic zone within hypothalamic hamartomas (HHs) and the symptomatogenic zone for gelastic seizure (GS), we analyzed data from both interictal and ictal single photon emission computed tomography (SPECT).

Methods: Ictal SPECT was performed immediately after GS onset in 21 patients with HH (aged 2–36 years, mean 13.8 years) who underwent stereotactic radiofrequency thermocoagulation (SRT). SPECT data were statistically analyzed by means of subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM) and statistical parametric mapping (SPM). Topographic localization of ictal hyperperfusion areas was evaluated.

Results: SISCOM obtained in 27 studies demonstrated ictal hyperperfusion in the HH interface zone in 16 studies of 13 patients (hot HH group). In these patients, HHs were significantly larger than those without hyperperfusion of HH in 11 studies of 8 patients (21.4 ± 10.3 vs. 12.3 ± 7.3 mm in diameter, p < 0.05,t‐test). In all patients and in the hot HH group, SPM group analysis of individual differences between interictal and ictal data revealed significantly (p < 0.001) hyperperfused areas in the ipsilateral hypothalamus, mediodorsal (MD) nucleus of the thalamus and putamen, bilateral pontine tegmentum, and contralateral inferior semilunar lobule of the cerebellum. There was no hyperperfusion in the mammillothalamocingulate pathway.

Discussion: The present study confirmed that ictogenesis occurs in the HH interface zone, which should accordingly be the target for SRT. We suggest that a thalamopontocerebellar circuit plays an important role for stereotypical and automatic symptomatogenesis of GS and that the hypothalamus and MD nucleus of the thalamus are potentially involved in epileptic encephalopathy.
Neurocognitive effects of brivaracetam, levetiracetam, and lorazepam
Authors: Meador Kimford J. , Gevins Alan , Leese Philip T. , Otoul Christian , Loring David W.
Published: September 2010

Purpose:  Brivaracetam (BRV) is a new anticonvulsant under development. Although BRV is an analog of levetiracetam (LEV), in addition to being an SV2A ligand, it also inhibits sodium channels in a voltage‐dependent manner. The cognitive effects of BRV are uncertain.

Methods:  A randomized, double‐blind, placebo‐controlled, four‐way cross‐over design was employed in 16 healthy volunteers comparing acute dosing (i.e., two doses) of BRV 10 mg, LEV 500 mg, lorazepam (LZP) 2 mg, and placebo. The primary outcome was the summary score from the cognitive neurophysiologic test (CNT), which combines electrophysiologic and performance measures. Secondary outcomes included CNT cognitive and electrophysiologic subscores, traditional neuropsychological measures, and treatment‐emergent adverse events (TEAEs).

Results:  Compared to BRV, LEV, and placebo, LZP adver‐sely affected the CNT summary score and the majority of CNT subscores and neuropsychological measures. In contrast, BRV did not differ from placebo or LEV on any measure. More TEAEs occurred with LZP compared to each of the other treatment conditions.

Discussion:  The differential pattern of drug effects was consistent across multiple electrophysiologic, cognitive, and subjective measures. The profile of cognitive, subjective, and electrophysiologic effects for BRV was similar to the analog compound LEV and to placebo. The findings suggest that BRV should be tolerated well from a neuropsychological perspective, but additional studies are needed.
The Use of Individual and Societal Risk Criteria Within the Dutch Flood Safety Policy—Nationwide Estimates of Societal Risk and Policy Applications
Authors: Jonkman Sebastiaan N. , Jongejan Ruben , Maaskant Bob
Published: September 2010

The Dutch government is in the process of revising its flood safety policy. The current safety standards for flood defenses in the Netherlands are largely based on the outcomes of cost‐benefit analyses. Loss of life has not been considered separately in the choice for current standards. This article presents the results of a research project that evaluated the potential roles of two risk metrics, individual and societal risk, to support decision making about new flood safety standards. These risk metrics are already used in the Dutch major hazards policy for the evaluation of risks to the public. Individual risk concerns the annual probability of death of a person. Societal risk concerns the probability of an event with many fatalities. Technical aspects of the use of individual and societal risk metrics in flood risk assessments as well as policy implications are discussed. Preliminary estimates of nationwide levels of societal risk are presented. Societal risk levels appear relatively high in the southwestern part of the country where densely populated dike rings are threatened by a combination of river and coastal floods. It was found that cumulation, the simultaneous flooding of multiple dike rings during a single flood event, has significant impact on the national level of societal risk. Options for the application of the individual and societal risk in the new flood safety policy are presented and discussed.
Sinus Node Injury as a Result of Superior Vena Cava Isolation during Catheter Ablation for Atrial Fibrillation and Atrial Flutter
Authors: CHEN GANG , DONG JIAN ZENG , LIU XING PENG , ZHANG XIN YONG , LONG DE YONG , SANG CAI HUA , NING MAN , TANG RI BO , JIANG CHEN XI , SHENG MA CHANG
Published: September 2010

Background: The ectopic foci originating from superior vena cava (SVC) may act as triggers in the occurrence and perpetuation of atrial fibrillation (AF). Unfortunately, the SVC isolation may result in potential dysfunction of sinus node. Furthermore, little is known about the occurrence of sinus node injury complicated by the SVC isolation.

Methods:
 Patients with AF or atypical atrial flutter experienced SVC isolation. The junctional rhythm or sinus arrest could be observed, if sinus node was injured. Atropin and dopamine administration ruled out the vagal irritation of sinus node, when junctional rhythm or sinus arrest occurred.

Results:
 One hundred and thirty‐two patients who had no electrocardiogram signs of sinus node dysfunction before ablation experienced the SVC isolation. Six patients (three men, three women, mean age 62.5 ± 8.6 years) had sinus node injury (4.5%, 6/132): four patients had junctional rhythm and one male patient had junctional rhythm and sinus arrest simultaneously; another male patient required AAI mode permanent pacemaker implantation due to the persistent junctional rhythm after SVC isolation. The ablation sites of all six patients closed to the junction of right atrium and SVC during the ablation of anterolateral free wall of the SVC.

Conclusion:
 Sinus node may be damaged due to the ablation sites closer to sinus node. The definition of the junction of right atrium and SVC is very important, the ablation sites of anterolateral free wall of the SVC should not be too close to the SVC orifice. (PACE 2011; 34:163–170)
Fibrotic Tissue Growth into the Extendable Lobes of an Active Fixation Coronary Sinus Lead Can Complicate Extraction
Authors: BARANOWSKI BRYAN , YERKEY MICHAEL , DRESING THOMAS , WILKOFF BRUCE L.
Published: September 2010

Extraction of passive fixation coronary sinus (CS) leads is typically easily achieved with manual traction. The ability to readily extract active fixation leads from the CS is less clear. Our first extraction experience with an active fixation CS lead was in a 58‐year‐old man with a 13‐month‐old Medtronic 4195 lead (Medtronic Inc., Minneapolis, MN, USA). The lobes of the lead would not fully undeploy. Significant, prolonged manual traction was required to free the lead from the cardiac vein. Inspection demonstrated fibrotic tissue growth into the lead lobes. Such growth may lead to an increase in extraction complications and failures. (PACE 2010; 34:e64–e65)
A Case of Severe Gastroparesis: Indigestion and Weight Loss after Catheter Ablation of Atrial Fibrillation
Authors: CHOI SUK WON , KANG SE HUN , KWON O. SUNG , PARK HYUN WOO , LEE SEUNGBUM , KOO BON SAN , NAM GI‐BYOUNG
Published: September 2010

We describe a patient with gastroparesis after radiofrequency catheter ablation (RFCA) as a result of vagus nerve injury. A 42‐year‐old man underwent redo‐RFCA due to recurrent drug‐resistant symptomatic atrial fibrillation. The patient complained of indigestion and early satiety 2 weeks after the second procedure. There was also weight loss of approximately 5 kg for 2 months. He underwent endoscopy during which food material was noticed. In the upper gastrointestinal series, most contrast material still remained in the stomach on the 2‐hour delayed images, suggesting delayed gastric emptying time. (PACE 2010; 1–3)
Lightning Induced Inappropriate ICD Shock: An Unusual Case of Electromagnetic Interference
Authors: ANDERSON DANIEL R. , GILLBERG JEFFREY M. , TORREY JEFFREY W. , KONERU JAYANTHI N.
Published: September 2010

An unusual case of electromagnetic interference is presented. As a result of a lightning shock to a Shower House, our patient received two shocks. An elucidation of the different mechanisms for the two shocks is presented. (PACE 2012; 35:e159–e162)
Improvement in Right Ventricular Systolic Function after Cardiac Resynchronization Therapy Correlates with Left Ventricular Reverse Remodeling
Authors: AKSOY HAKAN , OKUTUCU SERCAN , AYTEMIR KUDRET , KAYA ERGUN BARIS , TULUMEN EROL , EVRANOS BANU , FATIHOGLU SEFIK GÖRKEM , KABAKCI GIRAY , TOKGOZOGLU LALE , OZKUTLU HILMI , OTO ALI
Published: September 2010

Background: Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function in heart failure (HF). However, the effects of CRT on right ventricular (RV) systolic function are not fully understood.

Objective: We aimed to determine echocardiographic correlates of improvement in RV systolic function after CRT.

Methods: Fifty‐four patients (61.9 ± 10.5 years; 43 men; LV ejection fraction 24.6 ± 4.0%; QRS duration > 120 ms) with HF were enrolled. Standard echocardiography, strain rate (SR), and tissue Doppler imaging were performed in all patients before and 6 months after CRT. Pulsed‐wave TDI‐derived systolic indices of RV included systolic (RVS) and isovolumic velocity (RVIVV) and isovolumic acceleration (RVIVA). Response to CRT was defined as decline in LV end‐systolic volume (LVESV) ≥ 10%.

Results: When indices of RV systolic function were assessed between responders and nonresponders, in responders (38 patients, 70.4%) RV end‐diastolic diameters (RVD1–3), mid‐RV strain, and mid‐RV SR improved significantly (P < 0.01, for all). RVS (10.77 ± 4.29 vs 12.62 ± 4.10 cm/sec, P = 0.005), RVIVV (14.71 ± 5.88 vs 18.52 ± 6.62 cm/sec, P < 0.001), and RVIVA (1.69 ± 0.70 vs 2.39 ± 0.77 m/sec2, P < 0.001) significantly increased among responders. There was no significant change in these parameters among nonresponders. Pearson's analyses revealed moderate positive correlations between reduction of LVESV and ΔRVIVV (r = 0.467, P = 0.001) and ΔRVIVA (r = 0.473, P = 0.001), respectively.

Conclusions: RV diameters and systolic indices after CRT improved only in the responder group. Improvement in RV systolic performance after CRT is correlated with the reduction of LVESV. (PACE 2011; 34:200–207)
Clinical Characteristics of Focal Atrial Tachycardias Arising from the Atrial Appendages during Childhood
Authors: SAKAGUCHI HEIMA , MIYAZAKI AYA , YAMAMOTO MASAKI , KUROSAKI KENICHI , OHUCHI HIDEO , SATOMI KAZUHIRO , SUYAMA KAZUHIRO , YAMADA OSAMU
Published: September 2010

Background: Focal atrial tachycardias (ATs) arising from the atrial appendages (AAT) are uncommon in adults. On the other hand, we frequently encounter AATs during childhood. However, the topographic distribution and clinical characteristics of focal ATs during childhood have not yet been clearly revealed. The aim of this study was to investigate the clinical characteristics of AATs in childhood.

Methods: The study population consisted of 16 consecutive pediatric patients with focal AT enrolled between March 1991 and June 2009. A retrospective analysis was performed. The patients with focal AT were divided into two groups: the AAT group and other AT (OAT) group, in which the foci arose from other atrial sites.

Results: Fifty percent had AAT. The AAT patients consisted of more males (88% vs 25%; P < 0.05), were more often asymptomatic at the initial visit (75% vs 25%; P < 0.05), and more often presented with an incessant form of the AT (88% vs 25%; P < 0.05) than the OAT patients. Second‐degree atrioventricular block during slow ATs of <120 beats per minute were more often observed in the AAT patients (63% vs 13%; P < 0.05). The incidence of tachycardia‐mediated cardiomyopathy was 19% out of all our subjects and 38% of the AAT patients.

Conclusions: The AATs are the major source of focal ATs in pediatric patients that are typically incessant. These characteristics probably explain why a much higher percentage of the patients are presented with TMC. (PACE 2011; 34:177–184)
Retrograde Venous Cerebral Air Embolism from Disconnected Central Venous Catheter: An Experimental Model
Authors: Fracasso Tony , Karger Bernd , Schmidt Peter F. , Reinbold Wolf D. , Pfeiffer Heidi
Published: September 2010

Abstract:  There are few reported cases of death attributed to retrograde cerebral air embolism from central venous catheter. The pathophysiological mechanism and the necessary conditions are not fully understood, also because of missing experimental data. We performed experimental simulation while working on a possible case of retrograde cerebral air embolism. A hermetic system consisting of two containers connected to each other and to an electric pump by means of rubber hoses was built. In this system, a fluid (water and blood) could continuously flow under conditions similar to those of the common jugular vein. The part of the system representing the jugular vein could be freely positioned at angles between 0 and 90°. A central venous catheter was inserted into this part. After disconnection, the behavior of the air bubbles entering the hose through the tip of the catheter was evaluated at different positions. At angles between 0 and 45°, the air bubbles followed the fluid flow. At angles >45°, the air bubbles showed the tendency to flow upstream; this phenomenon was more evident the more vertically the hose was located. We were able to demonstrate that a retrograde air embolism can be caused by a disconnected catheter and is even more likely if the neck is in a vertical position.
Cutaneous metastatic cholangiocarcinoma: a report of three cases and review of the literature
Authors: West Kelly L. , Selim Maria Angelica , Puri Puja K.
Published: September 2010

Cutaneous metastasis from cholangiocarcinoma is an extremely rare event. Herein, we present three cases with review of the literature. Case 1 is that of a young female with scalp metastasis. Cases 2 and 3 involve cutaneous metastasis to the sites of prior biliary drains, one occurring in a young female with a history of multiple biliary surgeries and one in a male with a history of sclerosing cholangitis. Review of the literature shows that the presentation of cutaneous metastases from cholangiocarcinoma can vary in terms of anatomic location and clinical features. The pathological and immunohistochemical profile of metastatic cholangiocarcinoma can be non‐specific, and accurate diagnosis relies in part on clinical correlation. In summary, metastatic disease should always be included in the differential diagnosis of cutaneous lesions in patients with known malignancy.

West KL, Selim MA, Puri PK. Cutaneous metastatic cholangiocarcinoma: a report of three cases and review of the literature.
Suppressive effect of the antimicrobial peptide LL‐37 on expression of IL‐6, IL‐8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts
Authors: Inomata Megumi , Into Takeshi , Murakami Yukitaka
Published: September 2010

Inomata M, Into T, Murakami Y. Suppressive effect of the antimicrobial peptide LL‐37 on expression of IL‐6, IL‐8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts. Eur J Oral Sci 2010; 118: 574–581. © 2010 Eur J Oral Sci

Porphyromonas gingivalis is a major periodontogenic bacterium and possesses immunostimulatory components, such as lipopolysaccharides (LPS) and fimbriae. The host antimicrobial peptide, LL‐37, suppresses proinflammatory responses of immune cells but its effect on human gingival fibroblasts (HGFs) is not known. In this study, we assessed the effect of LL‐37 on the proinflammatory responses of HGFs stimulated with P. gingivalis cells and their components. Live P. gingivalis cells did not induce proinflammatory responses of HGFs, and LL‐37 did not alter these responses. However, LL‐37 was able to suppress the killed P. gingivalis cell‐induced secretion of interleukin (IL)‐6 and IL‐8. LL‐37 also suppressed the expression of IL6, IL8, and CXCL10 genes that was induced by P. gingivalis components, including phenol–water extracts, lipid A, and fimbriae, and the induction of phosphorylation of p38 and extracellular signal‐regulated kinase (ERK) by P. gingivalis lipopolysaccharide (LPS). CAMP was found to be expressed in oral epithelial cells but not in HGFs, despite stimulation with P. gingivalis components. Therefore, LL‐37 can exert a suppressive effect on P. gingivalis‐induced proinflammatory responses of HGFs in a paracrine manner, suggesting that excess inflammatory responses to P. gingivalis in the gingival tissue are suppressed by LL‐37 in vivo.
Apoptotic and anti‐apoptotic factors in early human mandible development
Authors: Brakus Snjezana Mardesic , Govorko Danijela Kalibovic , Vukojevic Katarina , Jakus Ivana Alujevic , Carev Dominko , Petricevic Josko , Saraga‐Babic Mirna
Published: September 2010

Mardesic Brakus S, Kalibovic Govorko D, Vukojevic K, Alujevic Jakus I, Carev D, Petricevic J, Saraga‐Babic M. Apoptotic and anti‐apoptotic factors in early human mandible development. Eur J Oral Sci 2010; 118: 537–546. © 2010 Eur J Oral Sci

The regulators of apoptosis Bcl‐2, Bax, caspase‐3, p53, and Hsp70 were analyzed immunohistochemically in the developing human mandible of eight human conceptuses from weeks 5 to 10 of gestation. During this period, all proteins displayed an increased pattern of expression in the mandible ectomesenchyme and in newly formed bone, except for caspase‐3, which showed decreased expression in the ectomesenchyme, but appeared first in the ossification zone at the 7th wk of development. Simultaneously, the oral epithelium showed weak (p53) to strong (hsp70) expression of all proteins investigated, while in Meckel’s cartilage cells, bcl‐2 was expressed weakly and hsp70 was expressed moderately. Cells on the surface of the forming bone were predominantly bax positive, and only occasionally bcl‐2 positive. Only a few cells on the surface and inside the bony spicules co‐expressed bax and bcl‐2. Terminal deoxynucleotidyl transferase (TdT)‐mediated biotin–dUTP nick‐end labelling (TUNEL)‐positive cells were found to be apoptotic osteoblasts. The expression of all proteins investigated changed dynamically during early mandible development and the subsequent differentiation of Meckel’s cartilage and bone. While interactions between those factors might be associated with the survival of Meckel’s cartilage, in the ossification zone they might participate in the control of cell numbers, mineralization, and bone remodelling. Among many other factors, precise orchestration of pro‐ and anti‐apoptotic factors contributes to normal mandible development.
Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice
Authors: Ramirez‐Rodriguez Gerardo , Ortíz‐López Leonardo , Domínguez‐Alonso Aline , Benítez‐King Gloria A. , Kempermann Gerd
Published: September 2010

Abstract:  In the course of adult hippocampal neurogenesis, the postmitotic maturation and survival phase is associated with dendrite maturation. Melatonin modulates the survival of new neurons with relative specificity. During this phase, the new neurons express microtubule‐associated protein doublecortin (DCX). Here, we show that the entire population of cells expressing DCX is increased after 14 days of treatment with melatonin. As melatonin also affects microtubule polymerization which is important for neuritogenesis and dendritogenesis, we studied the consequences of chronic melatonin administration on dendrite maturation of DCX‐positive cells. Treatment with melatonin increased the number of DCX‐positive immature neurons with more complex dendrites. Sholl analysis revealed that melatonin treatment lead to greater complexity of the dendritic tree. In addition, melatonin increased the total volume of the granular cell layer. Besides its survival‐promoting effect, melatonin thus also increases dendritic maturation in adult neurogenesis. This might open the opportunity of using melatonin as an adjuvant in attempts to extrinsically stimulate adult hippocampal neurogenesis in neuropsychiatric disease, dementia or cognitive ageing.
The importance of soft tissue examination in traumatic dental injuries: a case report
Authors: Al‐Jundi Suhad Hussein
Published: September 2010

Abstract –  Traumatic dental injuries (TDIs) represent one of the main oral health problems in children, with variable prevalence rates. The issue of unmet treatment needs and inadequate emergency management of TDIs have surfaced up lately in dental literature, indicating that some TDIs present late for treatment, which may complicate management of these injuries. Soft tissue injuries usually accompany other dental injuries therefore thorough clinical and radiographic inspection of soft tissue wounds can not be over emphasized, even in late presentation cases. Tooth fragments may be embedded in soft tissues, even in late presentation cases, and may go unnoticed in the presence of urgent situations. This case report presents a child with a fractured tooth fragment embedded in the lower lip for 18 months, which went unnoticed until the child presented later for treatment of the fractured incisor, highlighting the importance of soft tissue exploration even in late presentation trauma cases.
The impact of cyclooxygenase inhibition on duodenal motility and mucosal alkaline secretion in anaesthetized rats
Authors: Nylander O.
Published: September 2010

Aim: Non‐steroidal anti‐inflammatory drugs (NSAIDs) are effective in the treatment of various human diseases. However, these drugs also have serious adverse effects in the gastrointestinal tract. In the duodenum NSAIDs inhibit mucosal alkaline secretion (DMAS), an important protective mechanism against the acid emptied from the stomach in most species, including humans. Surprisingly, NSAIDs have been shown to stimulate DMAS in an anaesthetized rat model. The aim of this review was to summarize the effects of NSAIDs and selective cyclooxygenase‐2 (COX‐2) inhibition on duodenal function in the rat and provide an explanation for why these drugs stimulate DMAS. Included are new data examining the effect of α‐adrenergic drugs on duodenal motility and DMAS.

Methods: Experiments were performed in anaesthetized rats. The proximal duodenum was perfused luminally with an isotonic NaCl solution. DMAS, motility, fluid flux and epithelial permeability were assessed in the absence and presence of various COX inhibitors.

Results: COX inhibition induced duodenal motility, increased DMAS and augmented the sensitivity as well as the maximal response of the duodenal mucosa to lidocaine‐ or hypotonicity‐induced increases in mucosal permeability. Furthermore, the ability of the duodenum to absorb water and to adjust osmolality in response to luminal hypotonicity was improved in COX‐inhibited animals. These improvements are mediated predominately via inhibition of COX‐2.

Conclusions: Inhibition of COX‐2 in rats with postoperative duodenal ileus induces muscle contractions, which in turn activate a nicotinic receptor‐dependent intramural reflex that stimulates duodenocytes to increase the activity of apical Cl−/HCO3−exchangers, resulting in a rise in DMAS.
Phylogenetic placement and population structure of Indo‐Pacific bottlenose dolphins (Tursiops aduncus) off Zanzibar, Tanzania, based on mtDNA sequences
Authors: Särnblad Anna , Danbolt Magnus , Dalén Love , Amir Omar A. , Berggren Per
Published: September 2010

Abstract

Phylogenetic placement of bottlenose dolphins from Zanzibar, East Africa and putative population differentiation between animals found off southern and northern Zanzibar were examined using variation in mtDNA control region sequences. Samples (n= 45) from animals bycaught in fishing gear and skin biopsies collected during boat surveys were compared to published sequences (n= 173) of Indo‐Pacific bottlenose dolphin, Tursiops aduncus, from southeast Australian waters, Chinese/Indonesian waters, and South African waters (which recently was proposed as a new species) and to published sequences of common bottlenose dolphin, Tursiops truncatus. Bayesian and maximum parsimony analyses indicated a close relationship between Zanzibar and South African haplotypes, which are differentiated from both Chinese/Indonesian and Australian T. aduncus haplotypes. Our results suggest that the dolphins found off Zanzibar should be classified as T. aduncus alongside the South African animals. Further, analyses of genetic differentiation showed significant separation between the T. aduncus found off northern and southern Zanzibar despite the relatively short distance (approximately 80 km) between these areas. Much less differentiation was found between southern Zanzibar and South Africa, suggesting a more recent common evolutionary history for these populations than for the northern and southern Zanzibar populations.
Results and evaluation of a survey to estimate Pacific walrus population size, 20061
Authors: Speckman Suzann G. , Chernook Vladimir I. , Burn Douglas M. , Udevitz Mark S. , Kochnev Anatoly A. , Vasilev Alexander , Jay Chadwick V. , Lisovsky Alexander , Fischbach Anthony S. , Benter R. Bradley
Published: September 2010

Abstract

In spring 2006, we conducted a collaborative U.S.–Russia survey to estimate abundance of the Pacific walrus (Odobenus rosmarus divergens). The Bering Sea was partitioned into survey blocks, and a systematic random sample of transects within a subset of the blocks was surveyed with airborne thermal scanners using standard strip‐transect methodology. Counts of walruses in photographed groups were used to model the relation between thermal signatures and the number of walruses in groups, which was used to estimate the number of walruses in groups that were detected by the scanner but not photographed. We also modeled the probability of thermally detecting various‐sized walrus groups to estimate the number of walruses in groups undetected by the scanner. We used data from radio‐tagged walruses to adjust on‐ice estimates to account for walruses in the water during the survey. The estimated area of available habitat averaged 668,000 km2 and the area of surveyed blocks was 318,204 km2. The number of Pacific walruses within the surveyed area was estimated at 129,000 with 95% confidence limits of 55,000–507,000 individuals. Poor weather conditions precluded surveying in other areas; therefore, this value represents the number of Pacific walruses within about half of potential walrus habitat.
An Animal Model of Cortical and Callosal Pathology in Multiple Sclerosis
Authors: Mangiardi Mario , Crawford Daniel K. , Xia Xiaoyu , Du Sienmi , Simon‐Freeman Rebecca , Voskuhl Rhonda R. , Tiwari‐Woodruff Seema K.
Published: September 2010

The pathological and radiological hallmarks of multiple sclerosis (MS) include multiple demyelinated lesions disseminated throughout the white matter of the central nervous system (CNS). More recently, the cerebral cortex has been shown to be affected in MS, but the elucidation of events causing cortical demyelination has been hampered by the lack of animal models reflecting such human cortical pathology. In this report, we have described the presence of cortical gray matter and callosal white matter demyelinating lesions in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Similar to the pathological lesions of MS patients, EAE lesions have been classified as type I‐leukocortical, type II‐intracortical and type III‐subpial. All of these lesions had varying degrees of demyelination, inflammatory cells and reactive astrocytes. Similar to MS, cortical layers during EAE showed demyelination, microglia activation, synaptic protein alterations and apoptotic cells. In addition, the callosal white matter during EAE had many inflammatory demyelinating lesions and axon degeneration. Functional electrophysiological conduction analysis showed deficits in both myelinated and unmyelinated callosal axons during early and late EAE. The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease.
Neuronal MCP‐1 Mediates Microglia Recruitment and Neurodegeneration Induced by the Mild Impairment of Oxidative Metabolism
Authors: Yang Guang , Meng Ya , Li Wenxia , Yong Yue , Fan Zhiqin , Ding Hanqing , Wei Youzhen , Luo Jia , Ke Zun‐Ji
Published: September 2010

Chemokines are implicated in the neuroinflammation of several chronic neurodegenerative disorders. However, the precise role of chemokines in neurodegeneration is unknown. Thiamine deficiency (TD) causes abnormal oxidative metabolism in the brain as well as a well‐defined microglia activation and neurodegeneration in the submedial thalamus nucleus (SmTN), which are common features of neurodegenerative diseases. We evaluated the role of chemokines in neurodegeneration and the underlying mechanism in a TD model. Among the chemokines examined, TD selectively induced neuronal expression of monocyte chemoattractant protein‐1 (MCP‐1) in the SmTN prior to microglia activation and neurodegeneration. The conditioned medium collected from TD‐induced neurons caused microglia activation. With a neuron/microglia co‐culture system, we showed that MCP‐1‐induced neurotoxicity required the presence of microglia, and exogenous MCP‐1 was able to activate microglia and stimulated microglia to produce cytokines. A MCP‐1 neutralizing antibody inhibited MCP‐1‐induced microglia activation and neuronal death in culture and in the thalamus. MCP‐1 knockout mice were resistant to TD‐induced neuronal death in SmTN. TD selectively induced the accumulation of reactive oxygen species in neurons, and antioxidants blocked TD‐induced MCP‐1 expression. Together, our results indicated an induction of neuronal MCP‐1 during mild impairment of oxidative metabolism caused by microglia recruitment/activation, which exacerbated neurodegeneration.
Living without psychiatrists in the Andes: Plight and resilience of the Quichua (Inca) People
Authors: Incayawar Mario , Bouchard Lise , Maldonado‐Bouchard Sioui
Published: September 2010

There is an estimated 30 million indigenous peoples in South America. Most of them live in the Andes. Regional states and governments neglect their health care needs and exclude them from the conventional Western health services in general and mental health care in particular. This review first describes this population's current situation of social exclusion, poverty and poor health. The problem of mental health care inequities in the region is illustrated through the case of the Quichua people. Indeed, for the population of over 5 million Quichua people in Ecuador, there are no psychiatric services. There are no culturally sensitive services offered in the Quichua language. The doctor–Quichua patient communication is poor and interactions are loaded with prejudice. The review provides a rationale for the Quichuas' reluctance to seek medical doctors in Ecuador. Finally, traditional healers' contribution to the mental health care of indigenous peoples is stressed, as well as their preference for a form of medical pluralism, mainly combining both traditional Quichua medicine and Western medicine. Woeful inequalities and inaccessibility to psychological and biomedical psychiatric care still widely affect the children of the sun in the Pacific Rim.
Abnormal cerebellum density in victims of rape with post‐traumatic stress disorder: Voxel‐based analysis of magnetic resonance imaging investigation
Authors: Sui Shuang‐Ge , Zhang Yan , Wu Ming‐Xiang , Xu Jian‐Min , Duan Lian , Weng Xu‐Chu , Shan Bao‐Ci , Li Ling‐Jiang
Published: September 2010

Introduction: Based on early studies of non‐motor function in the cerebellum and dysfunction in the cerebellum of post‐traumatic stress disorder (PTSD) patients, we presumed that the cerebellum was involved in the neuropathology of cognitive and emotional processing of PTSD patients, while the density of some sub‐areas of the cerebellum of PTSD patients was most likely abnormal.

Methods: Eleven female victims of rape with PTSD and 12 age‐matched female normal controls received 1.5 T 3D magnetic resonance imaging (MRI) scan. The scans were then analyzed using the voxel‐based morphometry 2 (VBM2) toolbox.

Results: Victims of rape with PTSD showed increased cerebellum density on the left side compared with normal controls (P<0.001), especially in the pyramis (x=−9, y=−72, z=−36; k=519; t=4.70), uvula (x=−4, y=−66, z=−35; k=256; t=4.02), declive (x=−6, y=−69, z=−30; k=213; t=3.84) and nodule (x=−4, y=−63, z=−31; k=147; t=3.93). In addition, compared with normal controls, the PTSD group showed significant differences in gray matter density of other brain areas, including the frontal lobe, parietal lobe, occipital lobe (P<0.001), insula, posterior cingulate, amygdala and hippocampus (P<0.005).

Discussion: These finding suggest that the cerebellum may be involved in the neuropathology and functional compensation in the neurocircuitry of PTSD.
Higher prevalence of bipolar I disorder among Asian and Latino compared to Caucasian patients receiving treatment
Authors: Hwang Sophia H.J. , Childers Meredith E. , Wang Po W. , Nam Jennifer Y. , Keller Kristine L. , Hill Shelley J. , Ketter Terence A.
Published: September 2010

Introduction: There are limited data regarding relationships between race/ethnicity and bipolar disorder. This study assessed such relationships in patients receiving treatment in a university clinic.

Methods: Demographic, illness characteristics, symptom severity, treatment, and care utilization data were collected from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP‐BD) Affective Disorders Evaluation, Mini‐International Neuropsychiatric Interview, and the STEP‐BD Clinician Rated Packet. Data were compared among 51 Asian, 35 Latino, and 86 Caucasian patients in treatment at the Stanford University Bipolar Disorders Clinic. χ2 tests and analyses of variance were used to assess between‐group differences.

Results: Asian and Latino compared to Caucasian patients had significantly higher prevalence of bipolar I disorder (58.8% and 60.0% versus 37.2%, respectively). Asian and Latino patients also had a higher prevalence of history of psychosis, but this was related to the excess of bipolar I disorder, becoming non‐significant after controlling for bipolar subtype. The racial/ethnic difference in bipolar subtype prevalence did not appear to be secondary to demographic or socioeconomic differences.

Discussion: The higher prevalence of bipolar I disorder and thus lower prevalence of bipolar II disorder and bipolar disorder not otherwise specified in Asian and Latino patients may be related to under‐diagnosis, misdiagnosis, or care underutilization of patients with milder forms of bipolar disorders. Additional research and public health efforts are warranted to further understand the effects of race and ethnicity on the management of bipolar disorders and to enhance timely and accurate diagnosis, culturally sensitive treatment, and optimal care utilization.
Saka, an ancestral possession: Malaysia
Authors: Che Ismail Hasanah , Ishak Siti Raihan , Hussein Adil , Mar Salmah Win
Published: September 2010

This report illustrates a culture‐bound disorder known as “saka” in the local population of Kelantan, as well as other states in Malaysia. It is a form of possession by the spirit of a deceased ancestor who was once a traditional healer or shaman. While in a dissociative state, the patient introduced a 7 × 3–4 cm wooden stick precisely into his inferior rectus muscle, in an attempt to identify with a blind ancestor who showed his presence momentarily and specifically to the patient. The stick remained hidden to ophthalmologists for 17 days and during this period the patient developed right orbital cellulitis, bilateral cavernous sinus thrombosis and sepsis. The stick was identified after the family took the patient home for cultural healing rites to be performed. The patient's altered behavior resolved with the removal of the stick and he returned to his premorbid personality and functioning without psychotropic medication. To date, saka has not been reported in any peer‐reviewed medical journal.
Cytokines and chemokines in inflammatory demyelinating neuropathies
Authors: Lisak Robert P.
Published: September 2010

Schwann cells are the cells that are responsible for the production and maintenance of myelin in the peripheral nervous system, as a modification of their plasma membrane. It has become clear that Schwann cells are the target of immune and inflammatory mediated reactions, and over the past 20 years studies have shown that Schwann cells might be important participants in the immune process. The interaction of Schwann cells with cytokines and chemokines, some produced by inflammatory cells but clearly some produced by the Schwann cells themselves, mediate much of these Schwann cell functions. These studies have been both in vitro and in vivo, with the latter consisting of studies of animal models as well as from patients with diseases of the peripheral nervous system. Thus, Schwann cells contribute to both pro‐inflammatory and downregulation of immune/inflammatory processes. The present review updates our current understanding of the interactions of Schwann cells with cytokines and chemokines. (Clin. Exp. Neuroimmunol. doi: 10.1111/j.1759‐1961.2010.00015.x, September 2010)
The Micromechanical Role of the Annulus Fibrosus Components Under Physiological Loading of the Lumbar Spine
Authors: Ayturk Ugur M. , Garcia Jose J. , Puttlitz Christian M.
Published: September 2010

To date, studies that have investigated the kinematics of spinal motion segments have largely focused on the contributions that the spinal ligaments play in the resultant motion patterns. However, the specific roles played by intervertebral disk components, in particular the annulus fibrosus, with respect to global motion is not well understood in spite of the relatively large literature base with respect to the local ex vivo mechanical properties of the tissue. The primary objective of this study was to implement the nonlinear and orthotropic mechanical behavior of the annulus fibrosus in a finite element model of an L4/L5 functional spinal unit in the form of a strain energy potential where the individual mechanical contributions of the ground substance and fibers were explicitly defined. The model was validated biomechanically under pure moment loading to ensure that the individual role of each soft tissue structure during load bearing was consistent throughout the physiologically relevant loading range. The fibrous network of the annulus was found to play critical roles in limiting the magnitude of the neutral zone and determining the stiffness of the elastic zone. Under flexion, lateral bending, and axial rotation, the collagen fibers were observed to bear the majority of the load applied to the annulus fibrosus, especially in radially peripheral regions where disk bulging occurred. For the first time, our data explicitly demonstrate that the exact fiber recruitment sequence is critically important for establishing the range of motion and neutral zone magnitudes of lumbar spinal motion segments.
Design of a Mechanical Larynx With Agarose as a Soft Tissue Substitute for Vocal Fold Applications
Authors: Choo J. Q. , Lau D. P. C. , Chui C. K. , Yang T. , Chng C. B. , Teoh S. H.
Published: September 2010

Mechanical and computational models consisting of flow channels with convergent and oscillating constrictions have been applied to study the dynamics of human vocal fold vibration. To the best of our knowledge, no mechanical model has been studied using a material substitute with similar physical properties to the human vocal fold for surgical experimentation. In this study, we design and develop a mechanical larynx with agarose as a vocal fold substitute, and assess its suitability for surgical experimentation. Agarose is selected as a substitute for the vocal fold as it exhibits similar nonlinear hyperelastic characteristics to biological soft tissue. Through uniaxial compression and extension tests, we determined that agarose of 0.375% concentration most closely resembles the vocal fold mucosa and ligament of a 20-year old male for small tensile strain with an R2 value of 0.9634 and root mean square error of 344.05±39.84 Pa. Incisions of 10 mm lengthwise and 3 mm in depth were created parallel to the medial edge on the superior surface of agar phantom. These were subjected to vibrations of 80, 130, and 180 Hz, at constant amplitude of 0.9 mm over a period of 10 min each in the mechanical larynx model. Lateral expansion of the incision was observed to be most significant for the lower frequency of 80 Hz. This model serves as a basis for future assessments of wound closure techniques during microsurgery to the vocal fold.
Solid-State Microrefrigeration in Conjunction With Liquid Cooling
Authors: Ezzahri Younes , Shakouri Ali
Published: September 2010

Thermal design requirements are mostly driven by the peak temperatures. Reducing or eliminating hot spots could alleviate the design requirement for the whole package. Combination of solid-state and liquid cooling will allow removal of both hot spots and background heating. In this paper, we analyze the performance of thin film Bi2Te3 microcooler and the 3D SiGe-based microrefrigerator, and optimize the maximum cooling and cooling power density in the presence of a liquid flow. Liquid flow and heat transfer coefficient will change the background temperature of the chip but they also affect the performance of the solid-state coolers used to remove hot spots. Both Peltier cooling at interfaces and Joule heating inside the device could be affected by the fluid flow. We analyze conventional Peltier coolers as well as 3D coolers. We study the impact of various parameters such as thermoelectric leg thickness, thermal interface resistances, and geometry factor on the overall system performance. We find that the cooling of a conventional Peltier cooler is significantly reduced in the presence of fluid flow. On the other hand, 3D SiGe cooler can be effective to remove high power density hot spots up to 500 W/cm2. 3D microrefrigerators can have a significant impact if the thermoelectric figure-of-merit, ZT, could reach 0.5 for a material grown on silicon substrate. It is interesting to note that there is an optimum microrefrigerator active region thickness that gives the maximum localized cooling. For liquid heat transfer coefficient between 5000 and 20,000 W m−2 K−1, the optimum is found to be between 10 μm and 20 μm.