bluuebunny/crossref_metadata_2025 huggingface dataset:
WATER CHANNEL ACTIVITY OF PLASMA MEMBRANE AFFECTS CHONDROCYTE MIGRATION AND ADHESION
Authors: Liang Hai‐Tao , Feng Xue‐Chao , Ma Tong‐Hui
Published: October 2007

Recent studies indicate that the aquaporin‐1 (AQP1) water channel is expressed in human and equine articular chondrocytes. The role of AQP1 in chondrocyte function has not been characterized. In the present study, we investigated the expression of the AQP1 water channel in cultured articular chondrocytes from wild‐type (AQP1+/+) and AQP1‐knockout (AQP1−/–) mice and characterized its function in chondrocyte proliferation, migration and adhesion.

Expression of AQP1 mRNA and protein was identified in freshly isolated neonatal AQP+/+ chondrocytes. Immunofluorescence localized the AQP1 protein to the plasma membrane of AQP+/+ chondrocytes in primary cultures. Relative plasma membrane water permeability of AQP1+/+ chondrocytes was approximately 1.6‐fold higher than that of AQP1−/– chondrocytes.

The condrocyte proliferation rate was not affected by AQP1 deletion. However, the serum‐induced transwell migration rate of AQP1−/– chondrocytes was markedly reduced compared with AQP1+/+ chondrocytes (16.2 ± 0.2 vs 27.1 ± 0.3%, respectively; P < 0.01). Cell adhesion to type II collagen‐coated plates was also significantly reduced in AQP1−/– chondrocytes compared with AQP1+/+ chondrocytes (38.1 ± 0.3 vs 51 ± 1%, respectively; P < 0.01).

The results provided direct evidence that AQP1‐mediated plasma membrane water permeability plays an important role in chondrocyte migration and adhesion.
EFFECTS OF CHRONIC ACARBOSE TREATMENT ON ADIPOCYTE INSULIN RESPONSIVENESS, SERUM LEVELS OF LEPTIN AND ADIPONECTIN AND HYPOTHALAMIC NPY EXPRESSION IN OBESE DIABETIC WISTAR RATS
Authors: Pérez Coralia , Fernández‐Agulló Teresa , De Solís Alain J , Ros Manuel , Andrés Antonio , Carrascosa José M
Published: October 2007

Inhibitors of intestinal glucosidases have been shown to improve glycaemic control in diabetic and obese humans and animals. In the present study, we have investigated the effect of 3 months treatment with acarbose on adiposity, food intake and the modulation of hypothalamic neuropeptide Y (NPY) in obese diabetic Wistar (WDF) rats and the possible correlation between changes in overall insulin sensitivity and the level of circulating adipokines, leptin and adiponectin. In addition, we investigated the effect of acarbose on adipocyte insulin signalling.

Mature male WDF rats were randomly distributed to one of three treatment groups (no acarbose or 20 or 40 mg of acarbose/100 g diet). After 3 months, blood glucose, cholesterol, triglyceride, insulin, leptin and adiponectin were analysed. Insulin signalling was determined in isolated adipocytes as the stimulation of mitogen‐activated protein kinase (MAPK) and Akt phosphorylation; the level of hypothalamic NPY was assessed by immunohistochemistry.

Acarbose‐treated rats had lower levels of blood glucose, cholesterol, triglyceride, insulin and leptin and an increase in adiponectin compared with untreated animals. There were no changes in bodyweight and adiposity. Stimulation of adipocyte MAPK activity by insulin was higher in rats treated with both doses of acarbose, whereas higher stimulation of Akt phosphorylation was observed with the highest dose of acarbose. Although food intake was not significantly reduced in rats treated with acarbose, the acarbose‐treated rats had lower NPY expression in the arcuate nucleus.

We conclude that the improvement in overall insulin sensitivity in WDF rats after prolonged acarbose treatment is paralleled by increases in circulating adiponectin and adipocyte insulin responsiveness. Acarbose neither decreases food intake nor reverts obesity, but decreases leptin levels and the expression of the orexigenic NPY in the hypothalamus.
α‐LIPOIC ACID PROTECTS AGAINST RENAL ISCHAEMIA–REPERFUSION INJURY IN RATS
Authors: Şehirli Özer , Şener Emre , Çetinel Şule , Yüksel Meral , Gedik Nursal , Şener Göksel
Published: October 2007

Oxygen free radicals are important components involved in the pathophysiological processes observed during ischaemia–reperfusion (I/R). The present study was designed to assess the possible protective effect of a‐lipoic acid (ALA) on renal I/R injury.

Wistar albino rats were unilaterally nephrectomized and subjected to 45 min renal pedicle occlusion followed by 24 h reperfusion. Saline or ALA (100 mg/kg, i.p.) was administered 15 min prior to ischaemia and immediately before the reperfusion period. At the end of 24 h, rats were decapitated and trunk blood was collected. Creatinine, blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) activity were measured in serum samples, whereas tumour necrosis factor (TNF)‐a, interleukin (IL)‐1b, IL‐6, 8‐hydroxydeoxyguanosine (8‐OHdG) and total anti‐oxidant capacity (AOC) were assayed in plasma samples.

Kidney samples were taken for the determination of tissue malondialdehyde (MDA) and glutathione (GSH) levels, as well as Na+/K+‐ATPase and myeloperoxidase (MPO) activity. The formation of reactive oxygen species in renal tissue samples was monitored using a chemiluminescence (CL) technique with luminol and lucigenin probes. Oxidant‐induced tissue fibrosis was determined by tissue collagen content and the extent of tissue injury was analysed microscopically.

Ischaemia–reperfusion caused a significant increases in blood creatinine, BUN, LDH, IL‐1b, IL‐6, TNF‐a and 8‐OHdG, whereas AOC was decreased. In kidney samples from the I/R group, MDA, MPO, collagen and CL levels were found to be increased significantly; however, glutathione levels and Na+/K+‐ATPase activity were decreased. Conversely, ALA treatment reversed all these biochemical indices, as well as histopathological alterations induced by I/R.

In conclusion, these data suggest that ALA reverses I/R‐induced oxidant responses and improves microscopic damage and renal function. Thus, it seems likely that ALA protects kidney tissues by inhibiting neutrophil infiltration, balancing the oxidant–anti‐oxidant status and regulating the generation of inflammatory mediators.
HYDROGEN SULPHIDE‐INDUCED HYPOTHERMIA ATTENUATES STRESS‐RELATED ULCERATION IN RATS
Authors: Lou Li‐Xia , Geng Bin , Du Jun‐Bao , Tang Chao‐Shu
Published: October 2007

Hydrogen sulphide (H2S) acts as a gaseous cellular messenger and has recently been reported to induce a suspended animation‐like state in mice. The aim of the present study was to investigate the protective role of H2S exposure in stress gastric ulcer.

In the present study, we used a rat model of water immersion and restraint stress (WRS) to induce the typical stress disease, namely stress gastric ulcer. Rats were treated with WRS for 4 h, with or without pre‐exposure to H2S (160 p.p.m. H2S for 2.5 h).

In H2S‐exposed rats, body temperature was significantly reduced by 2.5C (P < 0.01) and oxygen consumption was reduced by 37.1% (P < 0.01) compared with control rats. Plasma levels of H2S were increased by 20.8% (P < 0.01) following pre‐exposure. Pre‐exposure to H2S significantly reduced the gastric ulcer index, from 24 ± 9 to 9 ± 2 (P < 0.01), in WRS rats. In addition, WRS increased plasma levels of adrenocorticotropin (ACTH) and corticosterone 4.7‐ and 4.8‐fold, respectively (both P < 0.01). Pre‐exposure to H2S markedly suppressed plasma ACTH and corticosterone level by 34.4 and 53.2%, respectively (both P < 0.01), and reduced WRS‐elevated myeloperoxidase (MPO) activity by 19%. In the present study, WRS increased gastric malondialdehyde and conjugated diene content by 42 and 68%, respectively (both P < 0.01), and H2S exposure reduced lipid peroxide production. Finally, H2S exposure inhibited the WRS‐elevated expression of glucose‐regulated protein 78 and caspase 12, markers of endoplasmic reticulum stress.

In conclusion, a low concentration of H2S may be a new pharmacological tool for induced hypothermia to prevent severe stress‐induced diseases and multifarious trauma in the clinical setting.
CHANGES IN REDOX RATIO AND PROTEIN GLYCATION IN PRECATARACTOUS LENS FROM FRUCTOSE‐FED RATS: EFFECTS OF EXOGENOUSl‐CARNITINE
Authors: Balasaraswathi K , Rajasekar P , Anuradha CV
Published: October 2007

Rats fed high dietary fructose are documented to form an acquired model of insulin resistance. The present study measured the effects of administration ofl‐carnitine (CA) on lens protein glycation, oxidative stress and redox homeostasis in rats fed a high‐fructose diet.

Animals were divided into four groups: (i) an untreated control group (fed starch diet); (ii) an untreated fructose‐group (fed a high‐fructose diet); (iii) a CA‐treated (300 mg/kg per day), fructose‐fed group; and (iv) a CA‐treated, starch‐fed group. After 60 days treatment, lenses were dissected and multiple oxidative stress markers, glycation of proteins and the ratio of oxidized to reduced glutathione (GSSG/GSH) were determined.

A significant decline in enzyme and non‐enzyme anti‐oxidants and an increase in lipid peroxidation products, protein oxidation, protein glycation, GSSG/GSH ratio and aldehyde formation were observed in lens samples obtained from fructose‐fed rats. Administration of CA to fructose‐fed rats significantly attenuated oxidative damage and protein glycation and returned levels of anti‐oxidants to near those seen in the control group.

The results of the present study indicate that dietary fructose disturbs lens integrity and exogenous CA may safeguard the lens by preventing glycation and oxidative stress.
GABAA RECEPTOR EXPRESSION AND INHIBITORY POST‐SYNAPTIC CURRENTS IN CEREBELLAR PURKINJE CELLS IN DYSTROPHIN‐DEFICIENT mdx MICE
Authors: Kueh SLL , Head SI , Morley JW
Published: October 2007

Duchenne muscular dystrophy (DMD) is the second most common fatal genetic disease and arises as a consequence of an absence or disruption of the protein dystrophin. In addition to wasting of the skeletal musculature, boys with DMD have a significant degree of cognitive impairment.

We show here that there is no difference between littermate control and mdx mice (a murine model of DMD) in the overall expression of the GABAA receptor a1‐subunit, supporting the suggestion that it is the clustering at the synapse that is affected and not the expression of the GABAA receptor protein.

We report a significant reduction in both the frequency and amplitude of spontaneous inhibitory post‐synaptic currents in cerebellar Purkinje cells of mdx mice compared with littermate controls, consistent with the reported reduction in the number and size of GABAA receptor clusters immunoreactive for a1‐ and a2‐subunits at the post‐synaptic densities.

These results may explain some of the behavioural problems and cognitive impairment reported in DMD.
DIETARY SESAMIN SUPPRESSES AORTIC NADPH OXIDASE IN DOCA SALT HYPERTENSIVE RATS
Authors: Nakano Daisuke , Kurumazuka Daisuke , Nagai Yukiko , Nishiyama Akira , Kiso Yoshinobu , Matsumura Yasuo
Published: October 2007

Dietary sesamin, a sesame lignan, is known to suppress the development of experimental hypertension in rats partly through its inhibitory effect on vascular production. Therefore, in the present study, we examined whether sesamin feeding had any effect on vascular NADPH oxidase using aortas from deoxycorticosterone acetate (DOCA) salt hypertensive rats.

After a 5 week feeding and treatment period, aortic production and NADPH oxidase activity were measured using the lucigenin assay. Reverse transcription–polymerase chain reaction was performed to analyse aortic expression of NADPH oxidase subunit (p22phox, gp91phox, Nox1 and Nox4) mRNA.

Sesamin feeding markedly suppressed DOCA salt‐induced hypertension and significantly decreased aortic production. DOCA salt treatment increased NADPH oxidase activity and elevated aortic mRNA expression of p22phox, gp91phox, Nox1 and Nox4. Sesamin feeding abolished the increase in NADPH oxidase activity and, furthermore, significantly suppressed increases in p22phox, gp91phox and Nox1 mRNA expression.

In conclusion, dietary sesamin prevented DOCA salt‐induced increases in NADPH oxidase activity and subunit mRNA expression. These effects seem to be involved in the anti‐oxidant and antihypertensive effects of sesamin.
Disruption of tissue‐type plasminogen activator gene in mice aggravated liver fibrosis
Authors: Hsiao Yao , Zou Tie , Ling Chang‐Chun , Hu Hua , Tao Xian‐Mei , Song Hou‐Yan
Published: October 2007

Background and Aim:  Tissue‐type plasminogen activator (tPA) is one of the major components in the matrix proteolytic network whose role in the pathogenesis of liver fibrosis remains unknown. The aim of this study is to investigate the role of tPA in carbon tetrachloride (CCl4)‐induced liver fibrosis.

Methods:  Wild‐type and tPA knockout mice (8 mice per group) were injected interperitoneumly with 25% CCl4 2 ml/kg twice per week as CCl4 administration groups and olive oil 2 ml/kg as controls. After 4 weeks, the livers of mice were removed under deep anesthesia and prepared for further studies such as histology, immunostaining, hydroxyproline assay, zymography and western blot analysis.

Results:  Mice lacking tPA developed more severe morphological injury and displayed an increased deposition of collagen in the liver after CCl4 administration compared with wild‐type counterparts. Deficiency of tPA increased α‐smooth muscle actin expression in the mice livers. On the other hand, the decrease of matrix metalloproteinase‐2 (MMP‐2), matrix metalloproteinase‐9 (MMP‐9) activities, metalloproteinase‐13 (MMP‐13) expression and a marked increase of tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐1) expression were found in the liver of CCl4 administrated tPA−/− mice compared with wild‐type counterparts.

Conclusions:  Deficiency of tPA aggravated liver fibrosis through promoting hepatic stellate cells (HSCs) activation and inhibiting ECM degradation by decreasing MMP‐2, MMP‐9 activities and disrupting the balance between MMP‐13 and TIMP‐1.
Mycophenolate mofetil prevents lethal acute liver failure in mice induced by bacille Calmette‐Guérin and lipopolysaccharide
Authors: Yang Yong‐Feng , Tan De‐Ming , Xie Yu‐Tao , Zhao Wei , Hou Zhou‐Hua , Zhong Yan‐Dan
Published: October 2007

Background/Aims:  To investigate the effect of mycophenolate mofetil (MMF) on acute liver injury induced by bacille Calmette‐Guérin (BCG) and lipopolysaccharide (LPS).

Methods:  Acute liver failure was induced in male Kunming strain mice by injecting the animals with BCG 2.5 mg per mouse, and LPS 10 μg per mouse 10 days later. The mice in the treatment groups were given MMF 2 h before, simultaneous with, or 2 h after administration of LPS, and the mice in the control group were given the same dose of saline. The 24‐h survival rate, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were compared. Serum levels of tumor necrosis factor alpha (TNF‐α), interferon gamma (IFN‐γ), and interleukin 6 (IL‐6) were measured and the expressions of TNF‐α, IFN‐γ, and IL‐6 mRNA in the liver tissue were determined by reverse transcription–polymerase chain reaction (RT‐PCR). Concanavalin A (Con A)–induced splenocyte proliferation were determined by methods of methyl thiazolyl tetrazolium.

Results:  Injecting a small dose of LPS into BCG‐primed mice caused a lethal hepatic injury mimicking acute hepatitis, from which 16 of the 20 mice died within 24 h (20% survival rate). Massive necrosis of parenchymal hepatocytes with marked inflammatory cell infiltration was observed by histological examination. In parallel, serum ALT and TNF‐α, IFN‐γ, and IL‐6 levels were increased. Expression of TNF‐α, IFN‐γ, and IL‐6 mRNA in the liver were significantly increased also. Treatment with MMF markedly reduced the death rate in a dose‐dependent manner. It reached its maximal effect at the dosage of 150 mg per kg of body weight when pretreated 2 h before LPS injection, with improvement of histological feather and survival rate (84.2%, 16/19). MMF significantly inhibited serum levels of TNF‐α, IFN‐γ, and IL‐6, and significantly reduced TNF‐α, IFN‐γ, and IL‐6 expression in the liver, which increased after BCG and LPS injection. Moreover, splenocyte proliferation response induced by Con A was also inhibited by MMF treatment.

Conclusions:  Treatment with MMF has a protective effect on endotoxin‐induced fatal liver failure by regulating the production of inflammatory cytokines and T‐cell proliferation.
Cholecystokinin receptor A gene polymorphism in gallstone disease and gallbladder cancer
Authors: Srivastava Anvesha , Pandey Sachchida Nand , Dixit Manjusha , Choudhuri Gourdas , Mittal Balraj
Published: October 2007

Background and Aim:  Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease which may be causatively related to decreased gallbladder contractility. Cholecystokinin receptor A (CCK‐AR) mediates signals resulting in gallbladder contraction. Deteriorating gallbladder contraction promotes gallstone formation. A common genetic polymorphism of CCK‐AR may be causatively associated with the risk of gallstone and GBC. This study aimed to understand the association of CCK‐AR Pst I polymorphism in gallstone disease with gallbladder cancer.

Method:  This study included 165 gallstone patients, 139 GBC patients, and 190 healthy subjects. Genotyping was done using the polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) method.

Results:  The frequency of the A1A1 genotype of CCK‐AR was significantly higher in gallstone patients than healthy individuals (P = 0.008 odds ratio [OR] = 2.25, and 95% confidence interval [CI]:1.2–4.1). However, there was a significant difference in the frequency of A1A1 genotype when gallstone patients were compared to GBC patients (P = 0.041, OR = 0.49, and 95% CI: 0.3–0.9). On stratification of GBC patients according to presence or absence of gallstones, GBC patients without stones were compared to controls and GBC patients with stones were compared to stone patients; however, no significant differences in frequencies were observed.

Conclusion:  The results suggest that the A1A1 genotype of CCK‐AR is an independent genetic risk factor for gallstone disease and does not modulate the susceptibility of gallbladder cancer.
Outcomes of bleeding peptic ulcers: A prospective study
Authors: Liu Nai‐Jen , Lee Ching‐Song , Tang Jui‐Hsiang , Cheng Hao‐Tsai , Chu Yin‐Yi , Sung Kai‐Feng , Lin Cheng‐Hui , Tsou Yung‐Kuan , Lien Jau‐Min , Chen Pang‐Chi , Chiu Cheng‐Tang , Cheng Chi‐Liang
Published: October 2007

Background and Aim:  Bleeding peptic ulcers can be due to Helicobacter pylori (H. pylori) infection, use of non‐steroidal anti‐inflammatory drugs (NSAIDs), or idiopathic causes. The aim of this prospective study was to identify the clinical outcomes of bleeding peptic ulcers related to different causes.

Methods:  A total of 390 patients with bleeding ulcers were evaluated consecutively between June 2005 and August 2006. The diagnosis of H. pylori infection was made at index endoscopy, using histology and the rapid urease test. If both endoscopic diagnostic tests were not performed, a serological test was applied to detect the presence of H. pylori infection in a previously untreated patient. The prevalence and outcome of bleeding ulcers are related to H. pylori infection, NSAID use, and non‐H. pylori idiopathic causes. The outcome between patients who were admitted for ulcer bleeding (outpatient bleeder) and those who bled while hospitalized (in‐hospital bleeder) was also compared.

Results:  NSAID ulcers were noted in 223 patients, H. pylori ulcers in 102, and non‐H. pylori idiopathic ulcers in 65. In total, 298 patients had outpatient bleeders, and 92 had in‐hospital bleeders. The overall 3‐day rebleeding rate was 11.8% and the mortality rate was 5.4%. Eighteen of the 21 mortality cases died of their underlying comorbid illness. Patients with non‐H. pylori idiopathic ulcers had a significantly higher mortality rate than NSAID and H. pylori ulcers (12.3% vs 4.5% vs 2.9%, P = 0.02). Patients with H. pylori ulcers had significantly favorable outcomes than patients with NSAID ulcers (less blood transfusion and a shorter hospital stay) and non‐H. pylori idiopathic ulcers (shorter hospital stay and a lower mortality). Patients with in‐hospital bleeders had an adverse outcome as compared to outpatient bleeders, including a 3‐day rebleeding rate (25.0% vs 7.7%, P < 0.0001), 30‐day rebleeding rate (32.6% vs 12.1%, P < 0.0001), and higher mortality rate (16.3% vs 2.0%, P < 0.0001).

Conclusion:  This study emphasizes the role of non‐H. pylori idiopathic ulcers and in‐hospital bleeders as the determining high‐risk predictors for bleeding peptic ulcers.
Neural cadherin overexpression is a predictive marker for early postoperative recurrence in hepatocellular carcinoma patients
Authors: Seo Dong Dae , Lee Han Chu , Kim Ha Jung , Min Hyun Ju , Kim Kang Mo , Lim Young Suk , Chung Young‐Hwa , Lee Yung Sang , Suh Dong Jin , Yu Eunsil , Chun Sun Young
Published: October 2007

Background and Aim:  Recent studies have disclosed alterations in neural and/or epithelial cadherin (E‐cadherin) expression in several epithelial tumors. However, the clinical relevance of these phenomena in hepatocellular carcinoma (HCC) remains to be established. In this study, we investigated the expression patterns of neural and epithelial cadherins and their clinical implications in HCC.

Methods:  Immunohistochemical staining for neural and epithelial cadherins was performed on tumor and adjacent non‐tumor tissue sections of 52 HCC patients subjected to curative surgical resection. Clinical, radiological, and histopathological characteristics were analyzed, relative to the degree of neural and E‐cadherin expression.

Results:  The neural cadherin (N‐cadherin) expression was upregulated in 67% of HCC tissues, compared to adjacent non‐tumoral liver tissues. Patients expressing high levels of N‐cadherin experienced more frequent tumor recurrences within 2 years (50% vs 12.5%; P = 0.01) after surgical resection. Consequently, the cumulative overall survival rate tended to be lower in patients overexpressing N‐cadherin (P = 0.08). The N‐cadherin overexpression was the only independent predictive factor for postoperative recurrence within 2 years in both univariate and multivariate analyses (odds ratio: 8.5; 95% confidence interval: 1.625–44.46; P = 0.011). No correlation was evident between E‐cadherin expression patterns and clinicopathological parameters.

Conclusion:  The overexpression of N‐cadherin is significantly related to postoperative recurrence within 2 years after surgical resection in HCC. Therefore, immunohistochemical staining for N‐cadherin may be effectively applied as a predictive marker for early postoperative recurrence in HCC.
Spindle cell lipoma of the spermatic cord
Authors: Ide Hisamitsu , Nakagawa Takashi , Kamiyama Yutaka , Muto Satoru , Imamura Tetsuo , Horie Shigeo
Published: October 2007

Abstract:  Spindle cell lipoma usually occurs as a solitary, subcutaneous, circumscribed lesion in the back, posterior neck or shoulders of older men. As a paratesticular tumor, spindle cell lipoma is extremely rare. Herein we report the second case of spindle cell lipoma of the spermatic cord in the published reports. The tumor comprised mature adipocytes and uniform spindle cells within thick ropey collagen bundles and mast cells. Immunohistochemical studies showed spindle cells positive for CD34, a diagnostic feature of this tumor.
The time course of transmitter release in mouse motor nerve terminals is differentially affected by activation of muscarinic M1 or M2 receptors
Authors: Dudel J.
Published: October 2007

At endplates of mouse diaphragms the effects of activation of presynaptic muscarinic M1 and M2 autoreceptors on the time courses of monoquantal releases have been investigated at 20 °C. Quantal excitatory postsynaptic currents (qEPSCs) were elicited and recorded with a perfused macropatch electrode, through which control‐ and drug‐containing solutions were applied to 10 µm φ regions of a neuromuscular junction. M2 receptors were activated with muscarine, while the M1 receptors were blocked by pirenzepine. M2 activation presented a slight, but highly significant augmentation of early releases. Analogously, M1 receptors were activated with muscarine, while M2 receptors were blocked by methoctramine. M1 activation elicited a highly significant small shift of the time course of release towards longer delays. In controls, the number of late releases decayed with a time constant of 0.3 ms. This time constant did not change appreciably when methoctramine or methoctramine + muscarine were applied. However, methoctramine + muscarine reduced the amplitude of qEPSCs and shortened their decay by a partial block of postsynaptic channels. Double blocks with pirenzepine + methoctramine allowed no presynaptic effect of muscarine, showing that the blocker concentrations were sufficient. Neither the addition of methoctramine to pirenzepine, nor the further addition of muscarine changed the time constant of decay of the number of late releases. The results are very similar to that of autoreceptor activations in the glutamatergic crayfish synapse: activation of inhibitory receptors augmented early releases, and that of facilitatory receptors depressed early releases [J. Dudel (2006a) Eur. J. Neurosci., 23, 2695–2700], which may suggest a general presynaptic mechanism.
Enhancement of synaptic transmission and nociceptive behaviour in HPC‐1/syntaxin 1A knockout mice following peripheral nerve injury
Authors: Takasusuki T. , Fujiwara T. , Yamaguchi S. , Fukushima T. , Akagawa K. , Hori Y.
Published: October 2007

Our previous analysis of HPC‐1/syntaxin 1A knockout (KO) mice indicated that HPC‐1/syntaxin 1A plays an important role in the synaptic plasticity of the hippocampus in vitro and learning behaviour in vivo. In order to gain further insights into the physiological functions of HPC‐1/syntaxin 1A, we studied the changes in the plasticity of synaptic transmission in the superficial dorsal horn of the spinal cord following a peripheral nerve injury in HPC‐1/syntaxin 1A KO and wild‐type (WT) mice. The von Frey filament test revealed that partial ligation of the sciatic nerve caused neuropathic pain in both WT and KO mice. However, KO mice showed significant enhancement of mechanical allodynia as compared with WT mice. Tight‐seal whole‐cell recordings were obtained from neurons in the superficial dorsal horn of the spinal cord slices. Electrical stimulus‐evoked excitatory postsynaptic currents (EPSCs), asynchronous EPSCs (aEPSCs) in the presence of strontium, and spontaneously occurring miniature EPSCs (mEPSCs) were analysed. Prior to peripheral nerve ligation, no significant differences were observed in the properties of evoked EPSCs, aEPSCs and mEPSCs in KO and WT mice. Seven−14 days after partial ligation, the amplitude of evoked EPSCs and the frequency of aEPSCs and mEPSCs in KO mice were significantly greater than those in WT mice; however, the amplitude of aEPSCs and mEPSCs remained unchanged in both groups. Enhanced allodynia behaviour and significant enhancement of excitatory synaptic transmission following peripheral nerve ligation in KO mice suggest that HPC‐1/syntaxin 1A might play a role in synaptic plasticity in the nociceptive pathway.
Pre‐ and postsynaptic excitation and inhibition at octopus optic lobe photoreceptor terminals; implications for the function of the ‘presynaptic bags’
Authors: Piscopo Stefania , Moccia Francesco , Di Cristo Carlo , Caputi Luigi , Di Cosmo Anna , Brown Euan R.
Published: October 2007

Synaptic transmission was examined in the plexiform zone of Octopus vulgaris optic lobes using field‐potential recording from optic lobe slices. Stimulation of the optic nerve produced pre‐ and postsynaptic field potentials. Transmission was abolished in calcium‐free seawater, L‐ glutamate or the AMPA/Kainate receptor blocker CNQX (EC50, 40 µm), leaving an intact presynaptic field potential. ACh markedly reduced or blocked and d‐tubocurarine augmented both pre‐ and postsynaptic field potentials, while α‐bungarotoxin and atropine were without effect. Paired‐pulse stimulation showed short‐term depression of pre‐ and postsynaptic components with a half‐time of recovery of ∼ 500 ms. The depression was partially relieved in the presence of d‐tubocurarine (half‐time of recovery, 350 ms). No long‐term changes in synaptic strength were induced by repetitive stimulation. A polyclonal antibody raised against a squid glutamate receptor produced positive staining in the third radial layer of the plexiform zone. No positive staining was observed in the other layers. Taking into account previous morphological data and our results, we propose that the excitatory terminations of the photoreceptors are in the innermost layer of the plexiform zone where the transmitter is likely to be glutamate and postsynaptic receptors are AMPA/kainate‐like. Thus, the function of the terminal bags is to provide a location for a presynaptic cholinergic inhibitory shunt. The results imply that this arrangement provides a temporal filter for visual processing and enhances the perception of moving vs. stationary objects.
The formation of trajectories during goal‐oriented locomotion in humans. I. A stereotyped behaviour
Authors: Hicheur Halim , Pham Quang‐Cuong , Arechavaleta Gustavo , Laumond Jean‐Paul , Berthoz Alain
Published: October 2007

Human locomotion was investigated in a goal‐oriented task where subjects had to walk to and through a doorway starting from a fixed position and orientation in space. The door was located at different positions and orientations in space, resulting in a total of 40 targets. While no specific constraint was provided to subjects in terms of the path they were to follow or the expected walking speeds, all of them generated very similar trajectories in terms of both path geometry and velocity profiles. These results are reminiscent of the stereotyped properties of the hand trajectories observed in arm reaching movements in studies over the last 20 years. This observation supports the hypothesis that common constraining mechanisms govern the generation of segmental and whole‐body trajectories. In contrast, we observed that the subjects placed their feet at different spatial positions across repetitions, making unlikely the hypothesis that goal‐oriented locomotion is planned as a succession of steps. Rather, our results suggest that common planning and/or control strategies underlie the formation of the whole locomotor trajectory during a spatially oriented task.
Translin‐associated factor‐X (Trax) is a molecular switch of growth‐associated protein (GAP)‐43 that controls axonal regeneration
Authors: Schröer Uwe , Volk Gerd Fabian , Liedtke Tomas , Thanos Solon
Published: October 2007

The ability of neurons to form axons requires the choreographed assembly of growth cones. We show that there is a time window from postnatal day 14 (P14) until P21/22 when axons of rat retinal ganglion cells will regenerate under serum‐free culture conditions. In contrast, no outgrowth occurred before P13, and growth declined from P22 and ceased after P30. Using proteomics, we have identified translin‐associated factor X (Trax), a DNA‐binding factor that is expressed during this period of postnatal development. Trax is shown to coexpress with growth‐associated protein GAP‐43. Small interfering RNA‐mediated inhibition of Trax expression resulted in downregulation of both Trax and GAP‐43 transcripts and protein both before and during the period of regeneration (P8) and (P16). In contrast, silencing of Trax at P30 resulted in significant upregulation of the GAP‐43 transcript and protein and induced outgrowth of axons. These data suggest that Trax regulates GAP‐43 transcription and regeneration‐promoting effects during the postnatal maturation period. Trax may represent a new potent therapeutic target gene for optic nerve and spinal cord injuries.
Audition differently activates the visual system in neonatally enucleated mice compared with anophthalmic mutants
Authors: Chabot Nicole , Robert Stéphane , Tremblay Robin , Miceli Dom , Boire Denis , Bronchti Gilles
Published: October 2007

The occipital cortex, normally visual, can be activated by auditory or somatosensory tasks in the blind. This cross‐modal compensation appears after early or late onset of blindness with differences in activation between early and late blind. This could support the hypothesis of a reorganization of sensory pathways in the early blind that does not occur in later onset blindness. Using immunohistochemistry of the c‐Fos protein following a white noise stimulus and injections of the anterograde tracer dextran‐biotin in the inferior colliculus, we studied how the occurrence of blindness influences cross‐modal compensation in the mutant anophthalmic mouse strain and in C57BL/6 mice enucleated at birth. We observed, in mutant mice, immunolabeled nuclei in the visual thalamus – the dorsal lateral geniculate nucleus – in the primary visual area (V1) and a few labeled nuclei in the secondary visual area (V2). In enucleated mice, we observed auditory activity mainly in V2 but also sparsely in V1. No labeled cells could be found in the visual thalamus. Tracing studies confirmed the difference between anophthalmic and birth‐enucleated mice: whereas the first group showed inferior colliculus projections entering both the dorsal lateral geniculate and the latero‐posterior nuclei, in the second, auditory fibers were found only within the latero‐posterior thalamic nucleus. None was found in controls with intact eyes. We suggest that the prenatal period of spontaneous retinal activity shapes the differences of the sensory reorganization in mice.
Role of the corticotropin‐releasing factor receptor type 2 in the control of food intake in mice: a meal pattern analysis
Authors: Tabarin A. , Diz‐Chaves Y. , Consoli D. , Monsaingeon M. , Bale T. L. , Culler M. D. , Datta R. , Drago F. , Vale W. W. , Koob G. F. , Zorrilla E. P. , Contarino A.
Published: October 2007

The actions of corticotropin‐releasing factor (CRF) and related peptides are mediated by two receptors (CRF1and CRF2). The respective role of each subtype in the control of food intake remains poorly known. In the present study, we examined the quantity and microstructure of ingestive behavior of knockout (KO) mice lacking CRF2receptors and their wild‐type (WT) littermates. Under basal conditions, CRF2KO mice showed increased nocturnal food intake, evident as an increased zenith in circadian cosinor analysis of food intake. Microstructure analysis revealed that this greater food intake reflected increased meal size, rather than meal frequency, suggesting a decreased satiating value of food. Following acute restraint stress, CRF2KO mice showed an intact immediate anorectic response with increased latency to eat and decreased meal size. However, CRF2deletion abolished the prolonged phase of restraint‐induced anorexia. CRF2KO mice did not differ from WT controls in feeding responses to food deprivation or injection of ghrelin receptor agonists. Independent of genotype, food deprivation increased food intake, with dramatic changes in meal size, meal frequency, water : food ratio and eating rate. Acyl‐ghrelin or BIM‐28131, a potent ghrelin analog, dose‐dependently stimulated food intake by increasing meal size (ghrelin, BIM‐28131) and meal number (BIM‐28131), while slowing the average eating rate (BIM‐28131) similarly in WT and KO mice. These results suggest that the CRF2receptor is involved in the control of meal size during the active phase of eating and following acute exposure to stress.
Slow oscillation of membrane currents mediated by glutamatergic inputs of rat somatosensory cortical neurons: in vivo patch‐clamp analysis
Authors: Doi Atsushi , Mizuno Masaharu , Katafuchi Toshihiko , Furue Hidemasa , Koga Kohei , Yoshimura Megumu
Published: October 2007

Using in vivo patch‐clamp technique, the slow oscillation of membrane currents was characterized by its synaptic nature, correlation with electroencephalogram (EEG) and responses to different anesthetic agents, in primary somatosensory cortex (SI) neurons in urethane‐anesthetized rats. In more than 90% of the SI neurons, the slow oscillation of the inward currents (0.1–2.5 Hz) with the duration of several hundreds of a millisecond was observed at the holding membrane potential of −70 mV. The reversal potential of the inward currents was approximately 0 mV and was suppressed by application of an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) receptor antagonist. In most cases (> 90%) the inward current was synchronized with positive wave of the surface EEG recorded from ipsilateral and even contralateral cortical regions. The frequency as well as duration of the slow oscillation decreased by a volatile anesthetic agent, isoflurane (1.5–5.0%), and excitatory postsynaptic currents (EPSCs) were almost abolished at the highest concentration. Intraperitoneal injection of pentobarbital (25 mg/kg) also decreased the frequency of the slow oscillation without affecting short EPSCs. When γ‐aminobutyric acid A (GABAA) receptors were activated by local microinjection of muscimol (3 × 10−3 m, 1–10 µL) into the thalamus, the frequency of the slow oscillation markedly decreased, but was not abolished completely. These findings suggest that the slow oscillation of the inward currents is generated by the summation of glutamatergic EPSCs, and affected by isoflurane and pentobarbital differently. In addition, GABAergic system in the thalamus can affect the frequency, but is not essentially implicated in the genesis of the slow oscillation.
A simple method to reduce the inspiratory oxygen fraction for high pulmonary blood flow patients in an operating room
Authors: ASAKURA AYAKO , MIYASHITA TETSUYA , FUJIMOTO JUNICHI , MORIMURA NAOTO , KURAHASHI KIYOYASU , YAMADA YOSHITSUGU
Published: October 2007

Background:  Low inspired oxygen acutely increases pulmonary vascular resistance and decreases pulmonary‐systemic blood flow ratio. We present a simple method to lower inspired oxygen fraction (FIO2 < 0.21) without supplemental nitrogen, during mechanical ventilation by an anesthesia machine.

Methods:  After institutional approval, seven healthy adult volunteers and three infants (0–12 month old) scheduled for congenital heart surgery were enrolled in this study. All the infants were diagnosed with congestive heart failure because of high pulmonary blood flow and were thought to benefit from low FIO2. The volunteers performed spontaneous ventilation (fresh air flow rate = 10 l·min−1, tidal volume = 600 ml, frequency = 10 br·min−1). The infants were mechanically ventilated with air (fresh air flow rate = 6 l·min−1, tidal volume = 10 ml·kg−1, 15 < frequency < 30 br·min−1 to adjust PaCO2 between 5.8 kPa and 6.5 kPa (45–50 mmHg), after induction of general anesthesia and tracheal intubation. The fresh gas flow rates were determined by the following formula. Fresh gas flow rate = (FIO2 − FEO2) EVE/(0.21 + FIO2 − FEO2 − target FIO2). We recorded FIO2 every 5 min for 30 min. When arterial oxygen saturation decreased >15%, fresh gas flow rates were increased to adjust FIO2 to 0.21.

Results:  In all of the seven volunteers and three infants target FIO2 was achieved in <10 min. FIO2 was kept at 0.18 ± 0.01 (SD) by calculated fresh air flow rates. In one infant, SpO2 decreased >15% 20 min after lowering FIO2, we had to discontinue this study, and increase fresh gas flow to ventilate the infant with FIO2 0.21. In the other two infants, FIO2 was maintained throughout the study.

Conclusions:  This simple and convenient method to decrease FIO2, has a utility in clinical situations, in which pulmonary vascular resistance is to be increased to improve systemic oxygen delivery in patients with high pulmonary blood flow during cardiac surgery.
Multidrug intravenous anesthesia for children undergoing MRI: a comparison with general anesthesia
Authors: SHORRAB AHMED A. , DEMIAN ATEF D. , ATALLAH MOHAMED M.
Published: October 2007

Background:  We used a multidrug intravenous anesthesia regimen with midazolam, ketamine, and propofol to provide anesthesia for children during magnetic resonance imaging (MRI). This regimen was compared with general anesthesia in a randomized comparative study. Outcome measures were safety, side effects and recovery variables in addition to adverse events in relation to age strata.

Methods:  The children received either general anesthesia with propofol, vecuronium and isoflurane [general endotracheal anesthesia (GET) group; n = 313] or intravenous anesthesia with midazolam, ketamine, and propofol [intravenous anesthesia (MKP) group; n = 342]. Treatment assignment was randomized based on the date of the MRI. Physiological parameters were monitored during anesthesia and recovery. Desaturation (SpO2 < 93%), airway problems, and the need to repeat the scan were recorded. The discharge criteria were stable vital signs, return to baseline consciousness, absence of any side effects, and ability to ambulate.

Results:  With the exception of two children (0.6%) in the MKP group, all enrolled children completed the scan. A significantly greater number (2.3%) required a repeat scan in the MKP group (P < 0.05) and were sedated with a bolus dose of propofol. The total incidence of side effects was comparable between the MKP (7.7%) and GET groups (7.0%). Infants below the age of 1 year showed a significantly higher incidence of adverse events compared with the other age strata within each group. Within the MKP group, risk ratio was 0.40 and 0.26 when comparing infants aged below 1 year with the two older age strata, respectively. Recovery characteristics were comparable between both groups.

Conclusions:  Intravenous midazolam, ketamine and propofol provides safe and adequate anesthesia, comparable with that obtained from general endotracheal anesthesia, for most children during MRI.
Use of the ProSeal™ laryngeal mask airway in an infant with a repaired H‐type tracheoesophageal fistula and tracheomalacia
Authors: OLOMU PATRICK N. , KIDD JOSEPH N. , KOSTER KIM R.
Published: October 2007

The ProSeal™ laryngeal mask airway (PLMA) is a relatively new airway device with design features that improve the quality of positive pressure ventilation (PPV) and may decrease the risk of gastric aspiration. We describe the use of this device for the anesthesia management of an infant with an esophagocutaneous fistula following repair of an H‐type tracheoesophageal fistula and tracheomalacia, in which avoidance of tracheal intubation was desired. This case report demonstrates that the PLMA may be a useful and practical alternative to tracheal intubation in an infant with a tenuous airway.
Awake tracheal intubation through the laryngeal mask in neonates with upper airway obstruction
Authors: ASAI TAKASHI , NAGATA ATSUSHI , SHINGU KOH
Published: October 2007

Neonates with Pierre Robin or Treacher‐Collins syndrome are at risk of upper airway obstruction and may require surgical fixation of the tongue to the mandible. Such neonates are at high risk of hypoxia during induction of anesthesia and thus awake fiberoptic intubation would be required. We experienced neonates in whom awake fiberoptic intubation could not be carried out, because of severe hypoxia. Awake insertion of the laryngeal mask solved this problem. A 1‐month‐old neonate with Pierre Robin syndrome and another with Treacher‐Collins syndrome were scheduled for surgical fixation of the tongue to the mandible, for constant upper airway obstruction. In both patients, awake fiberoptic intubation was attempted but abandoned, because SpO2 rapidly decreased during the attempts. Awake insertion of the laryngeal mask relieved upper airway obstruction and facilitated oxygenation. Fiberoptic intubation through the laryngeal mask was easily achieved. Anesthesia was then induced. No hypoxia occurred after insertion of the laryngeal mask. In a further two neonates with Treacher‐Collins syndrome and in one neonate with Pierre Robin syndrome, awake fiberoptic intubation through the laryngeal mask was also successful. We believe that in neonates with predicted difficult intubation, who are at risk of upper airway obstruction and awake fiberoptic intubation could aggregate hypoxia, awake insertion of the laryngeal mask can be useful in facilitating oxygenation (by relieving upper airway obstruction) and in facilitating fiberoptic intubation.
The electroencephalograph during anesthesia and emergence in infants and children
Authors: DAVIDSON ANDREW J. , SALE STEVEN M. , WONG CONNIE , MCKEEVER STEPHEN , SHEPPARD SUZETTE , CHAN ZEKE , WILLIAMS CHRIS
Published: October 2007

Background:  The characteristics of the electroencephalogram (EEG) during anesthesia in children are poorly described. An understanding of the EEG during anesthesia may help explain and predict the performance of EEG‐derived depth of anesthesia monitors in children. This study aims to describe the association between age and some basic characteristics of the EEG during nonstandardized anesthesia in children and infants.

Methods:  Sixty‐four children aged 9 days to 12 years were enrolled in this observational physiological study. Anesthesia was given at the discretion of the anesthetist. EEG was recorded from after induction to emergence using a BRM2 brain monitor ’’BrainZ Instruments, Auckland, New Zealand‘‘ in parietal and frontal montages. For comparison, 90% spectral edge frequency (SEF‐90) and power were determined at three points (equilibrium during anesthesia, when the volatile agent was discontinued and at emergence), and children were divided into three age groups (0–6 months, 6–24 months and 2–12 years).

Results:  Fifty‐seven children had artifact‐free EEG data. From equilibrium to emergence the mean forehead power decreased substantially in children aged 2–12 years (3171–153 μV2, P < 0.001) and 6–24 months (756–140 μV2, P < 0.001) but no difference was found in infants aged 0–6 months (93–63 μV2, P = 0.4). From equilibrium to emergence mean forehead spectral edge frequency increased in children aged 2–12 years (10.8–13.7 Hz, P = 0.01) but no change was found in children aged 6–24 months (12.7–12.7 Hz, P = 0.9) or 0–6 months (9.45–7.26 Hz, P = 0.08). Throughout emergence, infants demonstrated a discontinuous EEG pattern with intermittent bursts separated with low amplitude.

Conclusions:  During anesthesia, the EEG in infants is fundamentally different from the EEG in older children. This study supports the need for specific infant‐derived algorithms if EEG‐derived anesthesia depth monitors are to be used in infants.
Does the Italian pediatric anesthesia training program adequately prepare residents for future clinical practice? What should be done?
Authors: ASTUTO MARINELLA , LAURETTA DANIELA , MINARDI CARMELO , DISMA NICOLA , SALVO IDA , GULLO ANTONINO
Published: October 2007

Background:  Pediatric anesthesia should be considered a subspecialty addressing the complete pediatric population (from preterm to teenager) and requiring particular anatomical, pathophysiological, pharmacological and anesthesiological knowledge. A survey was conducted to evaluate the training in pediatric anesthesia performed by Medical Schools of Anesthesia in Italy and to assess if the European Federation of Associations of Pediatric Anesthesia (FEAPA) guidelines for training in pediatric anesthesia had been adopted.

Methods:  The survey was addressed to the Directors of the Departments of Anesthesia and Intensive Care of the Medical Schools throughout Italy using a questionnaire.

Results:  We contacted all 37 Schools of Anesthesia, but only 26 of these (70 %) answered all the questions. A specific training program exists in 24 (92%). The duration of the training is variable: in 40% of the schools it lasts 2 months, in 27% 3 months and in 33% more than 3 months (3–6 months). Only 29% of the Schools required a minimum number of procedures to be performed during the training period. A final test is performed in 46% of the Schools. A dedicated staff for pediatric anesthesia exists in 70% of the Italian Schools.

Conclusions:  In Italy, the FEAPA guidelines have not yet been completely adopted. The experience of a dedicated unit for pediatric anesthesia will be invaluable to define operative guidelines, courses and to establish the minimum equipment necessary for pediatric management in nonspecialist hospitals.