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Selected AbstractsInduction of avian musculoaponeurotic fibrosarcoma proteins by toxic bile acid inhibits expression of glutathione synthetic enzymes and contributes to cholestatic liver injury in mice,HEPATOLOGY, Issue 4 2010Heping Yang We previously showed that hepatic expression of glutathione (GSH) synthetic enzymes and GSH levels fell 2 weeks after bile duct ligation (BDL) in mice. This correlated with a switch in nuclear anti-oxidant response element (ARE) binding activity from nuclear factor erythroid 2,related factor 2 (Nrf2) to c,avian musculoaponeurotic fibrosarcoma (c-Maf)/V-maf musculoaponeurotic fibrosarcoma oncogene homolog G (MafG). Our current aims were to examine whether the switch in ARE binding activity from Nrf2 to Mafs is responsible for decreased expression of GSH synthetic enzymes and the outcome of blocking this switch. Huh7 cells treated with lithocholic acid (LCA) exhibited a similar pattern of change in GSH synthetic enzyme expression as BDL mice. Nuclear protein levels of Nrf2 fell at 20 hours after LCA treatment, whereas c-Maf and MafG remained persistently induced. These changes translated to ARE nuclear binding activity. Knockdown of c-Maf or MafG individually blunted the LCA-induced decrease in Nrf2 ARE binding and increased ARE-dependent promoter activity, whereas combined knockdown was more effective. Knockdown of c-Maf or MafG individually increased the expression of GSH synthetic enzymes and raised GSH levels, and combined knockdown exerted an additive effect. Ursodeoxycholic acid (UDCA) or S-adenosylmethionine (SAMe) prevented the LCA-induced decrease in expression of GSH synthetic enzymes and promoter activity and prevented the increase in MafG and c-Maf levels. In vivo knockdown of the Maf genes protected against the decrease in GSH enzyme expression, GSH level, and liver injury after BDL. Conclusion: Toxic bile acid induces a switch from Nrf2 to c-Maf/MafG ARE nuclear binding, which leads to decreased expression of GSH synthetic enzymes and GSH levels and contributes to liver injury during BDL. UDCA and SAMe treatment targets this switch. (HEPATOLOGY 2010.) [source] Differential roles of two major brain structures, mushroom bodies and central complex, for Drosophila male courtship behaviorDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2006Takaomi Sakai Abstract Drosophila male courtship is a complex and robust behavior, the potential for which is genetically built into specific neural circuits in the central nervous system. Previous studies using male-female mosaics and the flies with defects in particular brain structures implicated the critical central regions involved in male courtship behavior. However, their acute physiological roles in courtship regulation still largely remain unknown. Using the temperature-sensitive Dynamin mutation, shibirets1, here we demonstrate the significance of two major brain structures, the mushroom bodies and the central complex, in experience-independent aspects of male courtship. We show that blocking of synaptic transmission in the mushroom body intrinsic neurons significantly delays courtship initiation and reduces the courtship activity by shortening the courtship bout length when virgin females are used as a sexual target. Interestingly, however, the same treatment affects neither initiation nor maintenance of courtship toward young males that release courtship-stimulating pheromones different from those of virgin females. In contrast, blocking of synaptic transmission in a central complex substructure, the fan-shaped body, slightly but significantly reduces courtship activity toward both virgin females and young males with little effect on courtship initiation. Taken together, our results indicate that the neuronal activity in the mushroom bodies plays an important role in responding to female-specific sex pheromones that stimulate initiation and maintenance of male courtship behavior, whereas the fan-shaped body neurons are involved in maintenance of male courtship regardless of the nature of courtship-stimulating cues. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Uncertainty analysis of single-concentration exposure data for risk assessment,introducing the species effect distribution approachENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2006Janeck J. Scott-fordsmand Abstract In recent years, the inclusion of uncertainty analysis in risk assessment has been much debated. One pertinent issue is the translation of the effects observed with a limited number of test species to a general protection level for most or all species present in the environment. In a number of cases, toxicity data may consist of data from tests employing only a control and one treatment. Given that more species (or processes) have been tested with the same treatment, the treatment can be considered as fixed, and the effect level of the individual species (or processes) can be considered as variable. The distribution of effects can be viewed as a species effect distribution for that treatment. The distribution will represent all organisms and may be used to predict the maximum impact on any fraction of all organisms (e.g., 95% of all species). Hence, it is possible to predict the maximum effect level, with a selected certainty, for a given fraction of all species. [source] New drug combinations for the treatment of murine AIDS and macrophage protectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2001A. Fraternale The failure of highly active antiretroviral therapies (HAART) is mainly due to the existence of latent infected reservoirs, such as macrophages and resting CD4+ T cells. In this paper, we report the results that we obtained in a murine model of AIDS by alternating the administration of the lympholitic drug 2-Fluoro-ara-AMP (Fludarabine) to eliminate the infected cells, with that of Azidothymidine (AZT) plus reduced glutathione (GSH) encapsulated in erythrocytes, to protect lymphocytes and macrophages not yet infected, respectively. Two groups of infected mice were treated as follows: one group was treated by alternating the administration of Fludarabine and AZT (treatment A), while the other group received the same treatment plus GSH-loaded erythrocytes given with AZT (treatment A + L,RBC). Fludarabine was administered intraperitoneally, AZT in the drinking water and GSH was encapsulated in erythrocytes by a procedure of hypotonic dialysis and isotonic resealing. The results obtained show that GSH-loaded erythrocytes provide additive effects in all the parameters examined. Alternation of a lympholitic drug and antiretroviral drug is effective in reducing the progression of murine AIDS. Addition of a system to protect macrophages provides additive effects in almost all the parameters considered, confirming that combination therapies aimed at protecting different infectable cell compartments are better than treatments protecting mainly lymphocytes. [source] Cooperation between toll-like receptor,2 and,4 in the brain of mice challenged with cell wall components derived from gram-negative and gram-positive bacteriaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2003Nathalie Laflamme Abstract In this study we investigated whether induction of toll-like receptor,2 (TLR2) amplifies the effect of a cell wall component derived from gram-positive bacteria, namely peptidoglycan (PGN). Mice received a first systemic lipopolysaccharide (LPS) injection to pre-induce TLR2 in various regions of the brain, and 6,h later, a second administration of either LPS or PGN. The data show a robust transcriptional activation of TLR2, TNF-, and monocyte chemotactic protein-1 (MCP-1) in microglial cells of mice challenged twice with LPS, whereas PGN essentially abolished this response. TLR4 plays a critical role in this process, because C3H/HeJ mice no longer responded to LPS but exhibited a normal reaction to PGN. Conversely, a robust signal for genes encoding innate immune proteinswas found in the brain of TLR2-deficient mice challenged with LPS. However, the second LPS bolus failed to trigger TNF-, and IL-12 in TLR2-deficient mice, while the same treatment caused a strong induction of these genes in the cerebral tissue of wild-type littermates. The present data provide evidence that cooperation exists between TLR4 and TLR2. While TLR4 is absolutely necessary to engage the innate immune response in the brain, TLR2 participates in the regulation of genes encoding TNF-, and IL-12 during severe endotoxemia. Such collaboration between TLR4 and TLR2 may be determinant for the transfer from the innate to the adaptive immunity within the CNS of infected animals. [source] Individual differences in the effects of chronic prazosin hydrochloride treatment on hippocampal mineralocorticoid and glucocorticoid receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Mohamed Kabbaj Abstract The aim of this study was to investigate the noradrenergic regulation of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in high responder (HR) and low responder (LR) male rats, an animal model of individual differences in hypothalamo-pituitary-adrenal axis activity and vulnerability to drugs of abuse. The effects of a chronic treatment with the noradrenergic ,1 antagonist (1-[4-amino-6,7-dimethoxy-2-quinazolinyl]-4-[2-furanylcarbonyl] piperazine) hydrochloride (prazosin) (0.5 mg/kg, i.p., 35 days) were assessed on stress-induced corticosterone (CORT) secretion and on hippocampal MRs and GRs in adrenally intact rats. In order to ascertain whether the effects of chronic prazosin treatment on hippocampal MRs and GRs were direct or indirect, through prazosin-induced CORT secretion, we also assessed the effects of the same treatment on adrenalectomized rats with CORT substitutive therapy. When compared with LR rats, HR rats exhibited a delayed return to the basal level of CORT following acute restraint stress; this was associated with a lower binding of MRs and GRs in HR rats than in LR rats. Chronic prazosin treatment had no effect in HR animals but markedly reduced hippocampal MRs and GRs, and increased stress-induced CORT secretion in LR rats. In LR adrenalectomized rats, prazosin reduced hipppocampal MRs but did not change GRs. Our results provide evidence of a differential regulation by noradrenaline of hippocampal MRs and GRs in HR and LR rats. These data could have clinical implications in terms of individual differences in the resistance to antidepressant treatments and individual differences in drug abuse. [source] Studying spatial and temporal dynamics of sward structure at low stocking densities: the use of an extended rising-plate-meter methodGRASS & FORAGE SCIENCE, Issue 4 2003O. Correll Abstract An extended rising-plate-meter method was used to study the spatial and temporal variability of the sward structure of extensively managed pastures over a grazing season. Two treatments of a long-term grazing experiment with heifers were investigated: extensive continuous grazing (EG) with a target sward height of 10 cm and intensive continuous grazing (IG) with a target sward height of 5 cm. Compressed sward height and related herbage mass (HM), dominant plant species and stage of development of phenology were determined at weekly or twice weekly intervals at fixed measuring points. The results demonstrated a strong variability in sward height and HM, especially on the EG treatment. The botanical composition of the standing herbage differed between treatments and between patches of different heights within the same treatment. In areas with a short sward, the herbage was predominantly composed of Agrostis capillaris, Festuca rubra and Trifolium repens. It was more evenly composed and also included taller growing species, such as Alopecurus pratensis and Galium mollugo, in areas with a tall sward. The area potentially available for reproductive development was high in the EG treatment and low in the IG treatment. The method employed proved suitable to provide a detailed description of the dynamics of the sward structure. [source] Effect of Autogenic Training on Drug Consumption in Patients With Primary Headache: An 8-Month Follow-up StudyHEADACHE, Issue 3 2003Terezia Zsombok MD Objective.,To examine the effects of Schultz-type autogenic training on headache-related drug consumption and headache frequency in patients with migraine, tension-type, or mixed (migraine plus tension-type) headache over an 8-month period. Background.,Behavioral treatments often are used alone or adjunctively for different types of headache. There are, however, only a few studies that have compared the efficacy and durability of the same treatment in different types of primary headache, and the effects of treatment on headache-related drug consumption rarely have been assessed even in these studies. Methods.,Twenty-five women with primary headache (11 with mixed headache, 8 with migraine, and 6 with tension-type headache) were evaluated via an open-label, self-controlled, 8-month, follow-up study design. After an initial 4 months of observation, patients began learning Schultz-type autogenic training as modified for patients with headache. They practiced autogenic training on a regular basis for 4 months. Based on data from headache diaries and daily medication records, headache frequencies and the amounts of analgesics, "migraine-specific" drugs (ergots and triptans), and anxiolytics taken by the patients were compared in the three subgroups over the 8-month period. Results.,From the first month of implementation of autogenic training, headache frequencies were significantly reduced in patients with tension-type and mixed headache. Significant reduction in frequency was achieved in patients with migraine only from the third month of autogenic training. Decreases in headache frequencies were accompanied by decreases in consumption of migraine drugs and analgesics resulting in significant correlations among these parameters. Reduction in consumption of anxiolytic drugs was more rapid and robust in patients with tension-type headache compared to patients with migraine, and this outcome failed to show any correlation with change in headache frequency. Conclusion.,Schultz-type autogenic training is an effective therapeutic approach that may lead to a reduction in both headache frequency and the use of headache medication. [source] Survival in Danish patients with breast cancer and inflammatory bowel disease: A nationwide cohort study,INFLAMMATORY BOWEL DISEASES, Issue 4 2008Kirstine Kobberøe Søgaard BA Abstract Background: Incidences of inflammatory bowel disease (IBD) and of breast cancer have increased over the last decades. The influence of IBD on breast cancer prognosis, however, is unknown. We therefore examined the impact of IBD on treatment receipt and survival in breast cancer patients. Methods: Information on breast cancer patients (stage and treatment) diagnosed between 1980 and 2004 was sourced from the Danish Cancer Registry. Data on IBD and potential confounders were extracted from the Danish National Registry of Patients covering all Danish hospitals. Cox regression was used to compute mortality rate ratios (MRRs) among breast cancer patients with IBD, compared to their non-IBD counterparts, adjusting for age, stage, comorbidity measured by the Charlson Index, and calendar year. Results: We identified 71,148 breast cancer cases; 67 also had Crohn's disease (CD) and 216 had ulcerative colitis (UC). Patients with CD had more advanced stage and received radiotherapy less, and chemotherapy more, frequently than patients without IBD. In the adjusted analyses there was no substantial survival difference in breast cancer patients with and without IBD (MRRCD = 1.22; 95% confidence interval [CI] = 0.85,1.75; MRRUC = 1.09; 95% CI = 0.86,1.38). In a stratified analysis, chemotherapy was associated with poorer survival in patients with CD (MRRCD = 1.93; 95% CI = 1.00,3.72). Conclusions: Breast cancer patients with UC receive the same treatment and have similar survival to breast cancer without IBD. In contrast, breast cancer patients with CD are treated with radiotherapy less often. Survival of breast cancer in patients with CD treated with chemotherapy is poorer compared to survival in patients without IBD. (Inflamm Bowel Dis 2007) [source] Quantitative two-dimensional analysis of facial wrinkles of Japanese women at various agesINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2002K. Tsukahara Synopsis To evaluate individual differences in the recognition of facial wrinkles, we asked 40 Japanese female observers to identify wrinkles using transparent sheets over frontal facial photos of four females aged 20, 39, 55 or 75 years. We then measured the number and length of those wrinkles by image analysis. Wrinkles identified by those 40 observers showed aged-related increases in the standard deviation (SD) values for number and length but age-related decreases in the coefficient of variation (CV)%. Therefore, to clarify factors affecting the degree of wrinkle detection, wrinkles were identified by two groups of age-matched male and female observers, by two groups that differed by age, and by two other groups, one of which who felt that there was an improvement in their wrinkles after application of an antiwrinkle agent and another group who did not feel that there was any improvement after the same treatment. Improvement was observed by replica image analysis in all groups. The degree of wrinkles identified was not affected by the age or by the sex of the observer group. However, the group who felt that there was an improvement in their wrinkles after treatment with the antiwrinkle agent identified a significantly higher number of wrinkles than did the group who did not feel that there was an improvement. These results suggest marked individual differences in the recognition of wrinkles. Fine wrinkles in relatively young subjects are difficult to detect, but moderate to marked wrinkles in middle-aged and in aged subjects can easily be detected. Concerning the cause of individual differences in the extent of wrinkle detection, observers who identified a large number of wrinkles tended to recognize not only pronounced wrinkles but also recognized fine wrinkles as ,wrinkles'. This seems to have also affected their feelings about the success of treatment with the antiwrinkle agent. Résumé Pour pouvoir évaluer les différences individuelles dans la l'identification des rides faciale, nous avons demandéà 40 femmes japonaises d'identifier des rides en utilisant des feuilles transparentes sur des photos faciales frontales de quatre femmes, âgées respectivement de 20, 39, 55 et 75 ans. Nous avons alors mesuré le nombre et la longueur de ces rides par analyse d'images. Les rides identifiées par ces 40 femmes montraient que le vieillissement qui s'y rattachait augmentait selon les valeurs d'un écart standard (ES) pour le nombre et la longueur, mais que le vieillissement qui s'y rattachait diminuait dans le pourcentage du coefficient de variation. Par conséquent, pour clarifier les facteurs affectant le degré de détection des rides, ces dernières furent identifiées par deux groupes d'hommes et de femmes dont l'âge coïncidait, âgés de 26,6 ans et de 44,5 ans, et par deux autres groupes. Un groupe qui a estimé qu'il y avait eu une amélioration dans les rides après une application de 6 semaines d'un agent antirides aux coins des yeux et un autre groupe qui a considéré qu'après le même traitement il n'y avait pas eu d'amélioration. Une amélioration fut remarquée par la copie d'une analyse d'images dans tous les groupes. Le degré d'importance des rides identifiées n'était pas affecté par l'âge ou le sexe des groupes étudiés. Cependant, le groupe qui a estimé qu'il y avait eu une amélioration concernant leurs rides après un traitement avec un agent antirides a identifié un nombre significativement plus élevé de rides que le groupe qui estimait qu'il n'y avait pas eu d'amélioration. Ces résultats suggèrent des différences individuelles notoires dans l'identification de rides. De minces rides dans les groupes relativement jeunes sont difficiles à déceler. Mais des rides modérées remarquées dans les groupes de personnes d'un,ge moyen et, âgées peuvent être facilement localisées. Concernant la cause de ces différences individuelles dans l'importance d'un décèlement des rides, les sujets qui identifièrent un grand nombre de rides avaient tendance à ne pas prononcer le mot ,rides', mais trouvaient que de fines rides n'étaient que des ,rides'. Cela semblait aussi affecter leurs sentiments après le succès du traitement avec des agents antirides. [source] Accounting Standards, Implementation Guidance, and Example-Based ReasoningJOURNAL OF ACCOUNTING RESEARCH, Issue 4 2007SHANA CLOR-PROELL ABSTRACT This paper examines interpretation of accounting standards that provide implementation guidance via affirmative or counter examples. Based on prior psychology research, we predict that practitioners engage in "example-based reasoning" such that they are more likely to conclude that their case qualifies for the same treatment as the example. We test our predictions in two experiments in which participants judge the appropriateness of income-statement recognition. Experiment 1 uses Masters of Business Administration (MBA) students and varies example type (affirmative, counter) and case (revenue recognition, expense recognition) in a 2 × 2 design. Experiment 1 supports our predictions. Experiment 2 uses more experienced practitioners, and varies example type (affirmative, counter, both) in a 1 × 3 design. Experiment 2 supports the use of example-based reasoning, and indicates that practitioners in the "both" condition respond as if they had only received an affirmative example. These results have implications for understanding how guidance that accompanies accounting standards can result in aggressive or conservative application of standards. [source] Differential sensitivity to apoptosis between the human small and large intestinal mucosae: Linkage with segment-specific regulation of Bcl-2 homologs and involvement of signaling pathways,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2001Rémy Gauthier Abstract The small and large intestines differ in their expression profiles of Bcl-2 homologs. Intestinal segment-specific Bcl-2 homolog expression profiles are acquired as early as by mid-gestation (18,20 weeks) in man. In the present study, we examined the question whether such distinctions underlie segment-specific control mechanisms of intestinal cell survival. Using mid-gestation human jejunum and colon organotypic cultures, we analyzed the impact of growth factors (namely insulin; 10 ,g/ml) and pharmacological compounds that inhibit signal transduction molecules/pathways (namely tyrosine kinases, Fak, PI3-K/Akt, and MEK/Erk) on cell survival and Bcl-2 homolog expression (anti-apoptotic: Bcl-2, Bcl-XL, Mcl-1; pro-apoptotic: Bax, Bak, Bad). The relative activation levels of p125Fak, p42Erk-2, and p57Akt were analyzed as well. Herein, we report that (1) the inhibition of signal transduction molecules/pathways revealed striking differences in their impact on cell survival in the jejunum and colon (e.g., the inhibition of p125Fak induced apoptosis with a significantly greater extent in the jejunum [,43%] than in the colon [,24%]); (2) sharp distinctions between the two segments were noted in the modulatory effects of the various treatments on Bcl-2 homolog steady-state levels (e.g., inhibition of tyrosine kinase activities in the jejunum down-regulated all anti-apoptotics analyzed while increasing Bax, whereas the same treatment in the colon down-regulated Bcl-XL only and increased all pro-apoptotics); and (3) in addition to their differential impact on cell survival and Bcl-2 homolog expression, the MEK/Erk and PI3-K/Akt pathways were found to be distinctively regulated in the jejunum and colon mucosae (e.g., insulin in the jejunum increased p42Erk-2 activation without affecting that of p57Akt, whereas the sa e treatment in the colon decreased p42Erk-2 activation while increasing that of p57Akt). Altogether, these data show that intestinal cell survival is characterized by segment-specific susceptibilities to apoptosis, which are in turn linked with segmental distinctions in the involvement of signaling pathways and the regulation of Bcl-2 homolog steady-state levels. Therefore, these indicate that cell survival is subject to segment-specific control mechanisms along the proximal-distal axis of the intestine. J. Cell. Biochem. 82: 339,355, 2001. © 2001 Wiley-Liss, Inc. [source] Effect of enamel matrix proteins (Emdogain®) on healing after re-implantation of "periodontally compromised" rootsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2003An experimental study in the dog Abstract Objective: The present experiment was performed to assess whether Emdogain® applied on the root surface of extracted teeth or teeth previously exposed to root planning can protect the tooth from ankylosis following re-implantation. Material and Methods: The experiment included two groups of dogs, including five animals each. The root canals of all mandibular third premolars (3 P 3) were reamed and filled with gutta-percha. A crestal incision was placed from the area of the second to the fourth premolar. Buccal and lingual full thickness flaps were elevated. With the use of a fissure bur, the crown and furcation area of 3 P 3 were severed in an apico-coronal cut. The distal and mesial tooth segments were luxated with an elevator and extracted with forceps. Group A: The mesial and distal segments of 3 P 3 were air dried on a glass surface for 60 min. The roots from the right side were conditioned and exposed to Emdogain® application. The roots from the left side received the same treatment with the exception of Emdogain® application. The mesial and distal tooth segments were re-implanted and the crown portions were severed with a horizontal cut and removed. The buccal and lingual flaps were mobilized and sutured to obtain complete coverage of the submerged roots. Group B: A notch was prepared in each root, 4,5 mm apical of the cemento-enamel junction. The area of the root that was located coronal to the notch was scaled and planned. The roots in the right side of the mandible were treated with Emdogain®, while the roots in the left side served as controls. After 6 months of healing, the dogs were killed and blocks containing one root with surrounding tissues were harvested, and prepared for histological examination, which also included morphometric assessments. Thus, the proportions of the roots that exhibited signs of (i) replacement (ii) inflammatory and (iii) surface resorption were calculated. Results and Conclusion: It was demonstrated that healing of a re-implanted root that had been extracted and deprived of vital cementoblasts was characterized by processes that included root resorption, ankylosis and new attachment formation. It was also demonstrated that Emdogain® treatment, i.e. conditioning with EDTA and placement of enamel matrix proteins on the detached root surface, failed to interfere with the healing process. Zusammenfassung Zielsetzung: Untersuchung, ob Emdogain®, wenn es auf die Wurzeloberfläche extrahierter Zähne oder von Zähnen, die zuvor eine Wurzelglättung bekommen haben, appliziert wird, die Zähne nach Reimplantation vor Ankylose schützen kann. Material und Methoden: Die Studie wurde bei 2 Gruppen von Hunden durchgeführt, die je 5 Tiere umfasste. Die Wurzelkanäle aller 3. Prämolaren des Unterkiefers (3 P 3) wurden aufbereitet und mit Guttapercha gefüllt. Ein Schnitt auf dem Limbus alveolaris wurde vom 2. zum 4 Prämolaren geführt. Bukkal und lingual wurde ein Vollschichtlappen mobilisiert. Mit einem Fissurenbohrer wurden die 3 P 3 mit einem Schnitt in koronoapikaler Richtung im Bereich der Krone und der Furkation geteilt. Die distalen und mesialen Zahnsegmente wurden mit einem Elevator luxiert und mit einer Zange extrahiert. Gruppe A: Die mesialen und distalen Segmente von 3 P 3 wurden auf einer Glasoberfläche 60 min lang luftgetrocknet. Die Wurzeln der rechten Seite wurden konditioniert und mit Emdogain® beschickt. Die Wurzeln der linken Seite erhielten die gleiche Behandlung mit der Ausnahme, dass keine Applikation von Emdogain® erfolgte. Die mesialen und distalen Wurzeln wurden reimplantiert und die Kronenanteile durch einen horizontalen Schnitt getrennt und entfernt. Die bukkalen und lingualen Lappen wurden mobilisiert und durch Naht ein vollständiger Verschluss der reimplantierten Wurzeln erreicht. Gruppe B: In jede Wurzel wurde 4,5 mm apikal der Schmelz-Zement-Grenze eine Kerbe präpariert. Der Bereich der Wurzel, der koronal dieser Kerbe lag, wurde gescalt und wurzelgeglättet. Die Wurzeln der rechten Unterkieferseite wurden mit Emdogain® behandelt, während die Wurzeln der linken Seite als Kontrolle dienten. Nach einer Heilung von 6 Monaten wurden die Hunde getötet und Blöcke, die eine Wurzel und das umgebende Gewebe enthielten, gewonnen und für die histologische Untersuchung präpariert, die auch morphometrische Befunde einschloss. Es wurden also die Anteile der Wurzeln berechnet, die Zeichen von (i) Ersatz- (ii) entzündlicher und (iii) Oberflächenresorption zeigten. Ergebnisse und Schlussfolgerungen: Es wurde gezeigt, dass die Heilung von reimplantierten Wurzeln, die extrahiert und von vitalen Zementoblasten befreit worden waren, durch Prozesse charakterisiert war, die Wurzelresorption, Ankylose und die Bildung neuen Attachments umfassten. Es wurde gezeigt, dass die Behandlung mit Emdogain®, d.h. Konditionierung mit EDTA und Applikation des Schmelz-Matrix-Proteins auf die freie Wurzeloberfläche diesen Heilungsprozess nicht beeinflussen konnte. Résumé Objectif: Cette expérimentation fut réalisée pour déterminer si Emdogain® appliqué sur la surface radiculaire de dents extraites ou de dents préalablement soumises à un surfaçage radiculaire pouvait protéger la dent de l'ankylose après réimplantation. Matériel et Méthodes: L'expérience comprenait 2 groupes de 5 chiens. Les canaux radiculaires de toutes les troisièmes premolaires mandibulaires (3 P 3) furent alésés et bouchés à la gutta-percha. Une incision crestale de la deuxième à la quatrième prémolaire permit de soulever un lambeau de pleine épaisseur vestibulaire et lingual. La couronne et la zone de furcation de 3 P 3 furent découpées à l'aide d'une fraise fissure d'apical en coronaire. Les segments distaux et mésiaux furent luxés avec un élévateur et extraits avec un davier. Groupe A: Les segments mésiaux et distaux de 3 P 3 furent séchés à l'air sur une plaque de verre pendant 60 min. Les racines du coté droit furent préparées et imprégnées d' Emdogain®. Les racines gauches reçurent le même traitement sans application d'Emdogain ®. Les segments mésiaux et distaux furent alors réimplantés et les couronnes découpées par un trait horizontal et éliminées. Les lambeaux vestibulaires et linguaux furent déplacés et suturés pour obtenir un recouvrement complet des racines enfouies. Groupe B: Une entaille a été préparée sur chaque racine, à 4,5 mm en apical de la jonction amélo-cémentaire. La surface de racine située coronairement à cette entaille fut alors détartrée et surfacée. Les racines du coté droit furent traitées par Emdogain® alors que les racines du coté gauche firent office de contrôle. Après 6 mois de cicatrisation, les chiens furent sacrifiés et des blocs contenant une racine et les tissus environnant furent prélevés pour un examen histologique et morphométrique. Ainsi, les proportions de racine présentant des signes de (i) remplacement (ii) d'inflammation et (iii) de résorption furent calculées. Résultats et conclusion: Nous avons démontré que la cicatrisation de racine réimplantées après extraction et élimination des cémentoblastes se caractérisait par un processus qui comprenait résorption radiculaire, ankylose et formation d'une nouvelle attache. Nous avons aussi démontré que le traitement par Emdogain®, c'est à dire conditionnement à l'EDTA et mise en place de protéines de la matrice améllaire sur la surface radiculaire, ne pouvait pas interférer avec le processus de cicatrisation. [source] Effect of Temperature (,5 to 130 °C) and Fiber Direction on the Dielectric Properties of Beef Semitendinosus at Radio Frequency and Microwave FrequenciesJOURNAL OF FOOD SCIENCE, Issue 6 2008N. Basaran-Akgul ABSTRACT:, The dielectric properties must be defined to design efficient radio frequency (RF) and microwave (MW) processes by the food manufacturers. The objective of this study was to understand how frequency, temperature, and muscle fiber orientation influence the dielectric properties. The eye of round (Semitendinosus) muscle was selected because it contains large, relatively uniform muscle cells with similar muscle fiber orientation and relatively uniform chemical composition throughout the tissue. Dielectric properties were measured using an open-ended coaxial probe technique at 27, 915, and 1800 MHz and temperatures between ,5 and 130 °C. Power penetration depth was calculated. Since many commercially prepared, thermally processed, ready-to-eat entrees are made with frozen meat, dielectric property measurements were started from ,5 °C. The dielectric constant and dielectric loss factors were often higher for muscle with the muscle fiber measured in a parallel orientation to the probe compared to samples of the same treatment (for example, fresh or frozen) in a perpendicular tissue orientation at the same frequency and temperature. Dielectric constant and loss values for frozen beef tended to be higher than fresh beef at the same temperature and frequency. Tissue orientation appeared to have a greater effect on dielectric loss values at lower frequencies. Penetration depth tended to be greater when the direction of propagation was perpendicular to the muscle fiber. [source] Involvement of ,, Subunits of Gq/11 in Muscarinic M1 Receptor Potentiation of Corticotropin-Releasing Hormone-Stimulated Adenylyl Cyclase Activity in Rat Frontal CortexJOURNAL OF NEUROCHEMISTRY, Issue 1 2000Maria C. Olianas Abstract : In the present study, we investigated the involvement of ,, subunits of Gq/11 in the muscarinic M1 receptor-induced potentiation of corticotropin-releasing hormone (CRH)-stimulated adenylyl cyclase activity in membranes of rat frontal cortex. Tissue exposure to either one of two ,, scavengers, the QEHA fragment type II adenylyl cyclase and the GDP-bound form of the , subunit of transducin, inhibited the muscarinic M1 facilitatory effect. Moreover, like acetylcholine (ACh), exogenously added ,, subunits of transducin potentiated the CRH-stimulated adenylyl cyclase activity, and this effect was not additive with that elicited by ACh. Western blot analysis indicated the expression in frontal cortex of both type II and type IV adenylyl cyclases, two isoforms stimulated by ,, subunits in synergism with activated Gs. The M1 receptor-induced enhancement of the adenylyl cyclase response to CRH was counteracted by the Gq/11 antagonist GpAnt-2A but not by GpAnt-2, a preferential Gi/o antagonist. In addition, the muscarinic facilitatory effect was inhibited by membrane preincubation with antiserum directed against the C terminus of the , subunit of Gq/11, whereas the same treatment with antiserum against either Gi1/2 or Go was without effect. These data indicate that in membranes of rat frontal cortex, activation of muscarinic M1 receptors potentiates CRH-stimulated adenylyl cyclase activity through ,, subunits of Gq/11. [source] Investigation of Protective Reactions Against Cadmium Toxicity in the Cells Established from a Transgenic Mouse Deficient in the Metallothionein GenesJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 2 2003Tetsuya Abe Objective:, To characterize a fibroblast cell strain which we established from an metallothionein (MT) knock-out (KO) mouse and to determine whether expression of the Hsp genes induced by cadmium is related to expression of the MT-I and -II genes. Methods:, We established a fibroblast cell strain (named "MT-KO2") derived from the peritoneum of an MT-KO mouse which is deficient in the MT-I and -II genes. We determined an expression of MT-I, Hsp32 and Grp 78 genes by Northern blot analysis. Results:, The mRNA level of MT-I, an isoform of the MT gene products, was induced dose-dependently in responce to increasing concentrations of CdCl2 (5,25 µM) in a fibroblast cell strain derived from the peritoneum of an MT wild type mouse (named "MT-W3"). But it was not induced in MT-KO2 cells after the same treatment. There was no significant difference between MT-KO2 and MT-W3 cells in a concentration of intracellular glutathione (reduced form) under normal conditions. MT-KO2 cells were not more sensitive to cytotoxicity of CdCl2 than in MT-W3 cells. Expression of the Hsp32 gene was more extensively enhanced in MT-KO2 cells than in MT-W3 cells after treatment with 5,10 µM CdCl2 for 5 hours. Furthermore, the cellular concentration of reduced glatathione (GSH) was also more increased in MT-KO2 cells than in MT-W3 cells after treatment with 50 µM CdCl2 for 3 hours. Conclusions:, Expression of the Hsp32 gene tends to be increased in MT-KO2 cells in response to cadmium exposure. The expression of the Hsp32 gene and increase in the cellular concentration of GSH may be augmented to compensate for the impaired expression of the MT genes in MT-KO2 cells. [source] Amelioration of disease severity by intraarticular hylan therapy in bilateral canine osteoarthritisJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2000K. W. Marshall Because of its high molecular weight, the glycosaminoglycan molecule hyaluronan is responsible for the viscoelastic properties of normal synovial fluid. In osteoarthritis, the concentration and molecular weight of hyaluronan in synovial fluid is diminished; this impairs the ability of synovial fluid to effectively lubricate joints, absorb loads, and exert anti-inflammatory effects. Using a bilateral anterior cruciateligament transection and partial neurectomy canine model of osteoarthritis, this study examined the effect of viscosupplementation with hylan G-F 20 as a treatment for osteoarthritis, this study examined the effect of viscosupplementation with hylan G-F 20 as a treatment for osteoarthritis. Twelve dogs underwent bilateral arthroscopic anterior cruciate-ligament transections and partial neurectomy of the knee joints. Beginning 1 week after the operation, six dogs received three weekly 500-,l injections of hylan G-F 20 in one knee and a sham injection of saline solution in the contralateral knee (early-treatment group). The remaining six animals underwent the same treatment 2 months following the procedure (late-treatment group). All dogs were killed at 8 months, and both knees were evaluated for gross pathology, histology, and proteoglycan content. In addition, with use of 500-MHz [1H] magnetic resonance spectroscopy, the synovial fluid from both knees was assessed for changes in metabolic profile. Differences in outcome were analyzed with paired t tests. Gross pathological and histological examination revealed significantly less severe changes of osteoarthritis in knees treated with hylan G-F 20 2 months after surgery than in the contralateral untreated knees. Magnetic resonance spectroscopy of the specimens in this late-treatment group showed significantly decreased glucose concentrations and significantly elevated isoleucine levels in the synovial fluid from knees treated with hylan G-F 20 compared with the controls. Previous magnetic resonance spectroscopy had shown that glucose concentrations increase with the onset of osteoarthritis and eventually diminish in end-stage osteoarthritis. The three injections of hylan were given after osteoarthritis was established, and the severity of the disease was ameliorated in the treated knees 6 months after treatment. This occurred although hylan G-F 20 is almost certainly cleared from joints by lymphatics within 4 weeks of injection, suggesting that hylan therapy can retard the progression of osteoarthritis for periods of time extending beyond the intraarticular residence time of the injected molecules and that hylan injections given at relatively early stages of osteoarthritis may have a chondroprotective effect. No changes in outcome were noted in the animals that received hylan G-F 20 immediately following surgery. [source] Expression of receptor activator of NF-kappa B ligand and osteoprotegerin in culture of human periodontal ligament cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2002Tomokazu Hasegawa The receptor activator of NF-kappa B ligand (RANKL) and its decoy receptor, osteoprotegerin (OPG), are the important proteins implicated in osteoclastogenesis. In this study, we investigated the expressions of RANKL and OPG in cultured human periodontal ligament (PDL) cells and their roles in osteoclastogenesis. Northern blotting revealed that the OPG mRNA was down-regulated remarkably by application of 10,8 m one-alpha, 25-dihydroxyvitamin D3[1,25-(OH)2D3] and 10,7 m dexamethasone (Dex). In contrast, RANKL mRNA was up-regulated by the same treatment. Western blotting demonstrated decrease of OPG by the application of 1,25-(OH)2D3 and Dex. Tartrate-resistant acid phosphatase-positive multinuclear cells were markedly induced when the PDL cells were cocultured with mouse bone marrow cells in the presence of an anti-OPG antibody together with 1,25-(OH)2D3 and Dex. These results indicate that PDL cells synthesize both RANKL and OPG and that inactivation of OPG may play a key role in the differentiation of osteoclasts. [source] Ethanol Attenuates Spatial Memory Deficits and Increases mGlu1a Receptor Expression in the Hippocampus of Rats Exposed to Prenatal StressALCOHOLISM, Issue 8 2009Vincent Van Waes Background:, Although it is generally believed that chronic ethanol consumption impairs learning and memory, results obtained in experimental animals are not univocal, and there are conditions in which ethanol paradoxically improves cognitive functions. In the present work, we investigated the effects of prenatal stress and of chronic ethanol exposure during adulthood on spatial memory in rats. Methods:, Rats were subjected to a prenatal stress delivered as 3 daily 45-minute sections of restraint stress to the mothers during the last 10 days of pregnancy (PRS rats). After 7 months of ethanol exposure (ethanol 10%, oral intake), memory performances were evaluated in a spatial discrimination test in control and PRS male rats. Then, the oxidative damages and the expression of metabotropic glutamate (mGlu) receptors were assessed in their hippocampus. Results:, Chronic ethanol exposure resulted in a reduced performance in a spatial recognition task in control animals. Unexpectedly, however, the same treatment attenuated spatial memory deficits in rats that had been subjected to prenatal stress. This paradigm of ethanol administration did not produce detectable signs of oxidative damage in the hippocampus in either unstressed or PRS rats. Interestingly, ethanol intake resulted in differential effects in the expression of mGlu receptor subtypes implicated in mechanisms of learning and memory. In control rats, ethanol intake reduced mGlu2/3 and mGlu5 receptor levels in the hippocampus; in PRS rats, which exhibited a constitutive reduction in the levels of these mGlu receptor subtypes, ethanol increased the expression of mGlu1a receptors but did not change the expression of mGlu2/3 or mGlu5 receptors. Conclusion:, Our findings support the idea that stress-related events occurring before birth have long-lasting effects on brain function and behavior, and suggest that the impact of ethanol on cognition is not only dose- and duration-dependent, but also critically influenced by early life experiences. [source] Cultural Variations in the Placebo Effect: Ulcers, Anxiety, and Blood PressureMEDICAL ANTHROPOLOGY QUARTERLY, Issue 1 2000Daniel E. Moerman An analysis of the control groups in double-blind trials of medicines demonstrates broad variation,from 0 to 100 percent,in placebo effectiveness rates for the same treatment for the same condition. In two cases considered here, drug healing rates covary with placebo healing rates; placebo healing is the ultimate and inescapable "complementary medicine. " Several factors can account for the dramatic variation in placebo healing rates, including cultural ones. But because variation differs by illness, large placebo effects for one condition do not necessarily anticipate large placebo effects for other conditions as well. Deeper understanding of the intimate relationship between cultural and biological processes will require close ethnographic scrutiny of the meaningfulness of medical treatment in different societies, [placebo effect, ulcer disease, anxiety, hypertension, cross-cultural variation] [source] Effects of sodium benzoate on the complications of 1.ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 20045% glycine solution using two different intravesical pressures during bladder irrigation Background:, In this experimental study we researched the effects of sodium benzoate on the complications of 1.5% glycine solution using with two different intravesical pressures during bladder irrigation. Methods:, Thirty-six male adult New Zealand rabbits with body weight ranging from 1500 to 2800 g were used in the experiments. The rabbits were randomly allocated to four groups. In groups 1 and 2, 500 ml of 1.5% gylcine was used as irrigating fluid during 30 min, but only group 2 received 500 mg kg,1 of sodium benzoate treatment by oral route immediately after irrigation. In groups 3 and 4, 500 ml of 1.5% glycine was used as irrigating fluid during 60 min, but only group 4 received the same treatment as group 2. Ammonia, urea, sodium, potassium, hemoglobin, hemotocrit and platelet levels were studied at preirrigation and postirrigation on the 4 h and 24 h. Also electrocardiographic (ECG) changes were monitored at the same time with blood parameters. Results:, At 4 h postirrigation, Na+ levels were decreased significantly in group 1 and non-significantly in group 3 when compared with preirrigation levels. But these levels were not changed in groups 2 and 4. Both at 4 h and 24 h, ammonia and urea levels were significantly increased in groups 1 and 3. Ammonia level was decreased but the urea level was not changed in groups 2 and 4 at the same time points. K+ level was significantly changed only in group 1 at 4 h and 24 h. Hemoglobin and hemotocrit concentrations were decreased both at 4 h and 24 h compared with preirrigation levels in all groups. Also there were ECG changes between the treated and untreated groups. Conclusion:, Sodium benzoate was very effective against the complications of 1.5% glycine during bladder irrigation experimentally. But this needs further investigation, especially for the applicability of this new treatment model in human TURP syndrome. [source] Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: A report from the HLH studyl centerPEDIATRIC BLOOD & CANCER, Issue 2 2003Shinsaku Imashuku MD Abstract Background Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), also known as EBV-associated hemophagocytic syndrome, develops mostly in children and young adults and may be fatal. Early etoposide treatment has been confirmed to be effective in children. However, it is unclear whether the same treatment is useful in adults. Procedure To assess whether etoposide is effective in treating young adult cases, we retrospectively studied the therapeutic measures taken and outcomes in 20 young adult cases of EBV-HLH. Eleven cases were registered in our HLH study center in Kyoto and nine derived from the literature. The patients were between 17 and 33 years old and eight were males. The influence of gender, cell lineage (T- or natural killer-), EBV serology pattern, jaundice and treatment on the outcome was assessed. Results and Conclusions Patients receiving etoposide within four weeks after diagnosis had a good prognosis as five of the seven patients survived compared to one of 13 not treated with etoposide or treated late (chi-square test for survival, P,=,0.0095). The Kaplan,Meier analysis showed the 2.5-year survival of 85.7,±,13.2% in the early etoposide-treated patients, compared to 10.3,±,9.4% in the remaining patients (log-rank test, P,=,0.0141). Thus, early etoposide treatment is effective in treating EBV-HLH in young adults as well as in children. Med Pediatr Oncol 2003;41:103,109. © 2003 Wiley-Liss, Inc. [source] Assessment of lovastatin application as tool in probing cytokinin-mediated cell cycle regulationPHYSIOLOGIA PLANTARUM, Issue 2 2005Katja Hartig Lovastatin, a potent inhibitor of the mevalonate pathway, has been used in plant cell cycle studies to eliminate the cytosolic cytokinin biosynthesis. However, several implications can blur the results, as cytokinins may be alternatively formed from isopentenylpyrophosphate produced by the plastid 1-deoxy-xylulose 5-phosphate pathway and because the endogenous cytokinin levels oscillate considerably in the course of a cell cycle. In the work presented here, short- and long-term effects of lovastatin on suspension- cultured Nicotiana tabacum (L.) BY-2 cells were differentiated. The short-term experiments revealed a fast action of lovastatin, resulting in a significantly, though not completely, decreased content of endogenous cytokinins that became visible already after 10 min and was most pronounced after 30 min. But the impact of lovastatin on cell cycle progression depended also on the phase of the cell cycle at which it was administered. Lowering of the cytokinin level during the early S phase, when the endogenous cytokinin levels increased, delayed the S/G2 transition, whereas the same treatment in the late S phase, when the cellular cytokinin concentrations had already started to decrease, promoted it. Incubation periods longer than 48 h resulted in about 50% loss of viable of the cells and also in a reduced capability of division of the survivors. These cells later on resumed cell division. A second treatment with lovastatin of that culture again killed about 50% of the cells, but the surviving cells showed faster re-growth. In conclusion, lovastatin appears as a useful inhibitor of cytokinin biosynthesis in short-term studies, but its use in long-term experiments may create complex effects and therefore requires substantial caution. [source] Promotion of 5-aminolevulinic acid on photosynthesis of melon (Cucumis melo) seedlings under low light and chilling stress conditionsPHYSIOLOGIA PLANTARUM, Issue 2 2004Liang Ju Wang When melon seedlings (Cucumis melo L. Ximiya No. 1) were cultured in a growth chamber with about 150 µmol m,2 s,1 photon flux density, the leaf photosynthetic ability reduced dramatically as leaf position decreased from the top. The application of 5-aminolevulinic acid (ALA) solutions significantly increased the net photosynthetic rate (Pn) as well as apparent quantum yield (AQY), carboxylation efficiency (CE) and stomata conductance (Gs). After irrigation with 10 ml of ALA solution (10 mg l,1 or 100 mg l,1) per container filled with approximately 250 g clean sand for 3 days, the leaf Pn was about 40,200% higher than that of controls, and AQY, CE and Gs increased 21,271%, 55,210% and 60,335%, respectively. Furthermore, ALA treatments increased leaf chlorophyll content and soluble sugar levels, as well as the rate of dark respiration, but decreased the rate of respiration under light. On the other hand, after melon seedlings that had been cultured in the chamber suffered chilling at 8°C for 4 h and then recovered at 25,30°C for 2 and 20 h, the Pn of the water-irrigated plants was only 12,18% and 37,47%, respectively, compared with the initial Pn before chilling treatment. If the seedlings underwent the same treatment but with ALA (10 mg l,1), the respective Pn was 22,38% and 76,101%, compared with that of the control before chilling stress. If chilling was prolonged for 6 h, the ALA-pre-treated plants only showed a few symptoms in the leaf margins whereas all water-irrigated plants died, which suggested that ALA presumably promoted chilling tolerance of the plants under low light. [source] Water relations under root chilling in a sensitive and tolerant tomato speciesPLANT CELL & ENVIRONMENT, Issue 8 2004A. J. BLOOM ABSTRACT The shoots of cultivated tomato (Lycopersicon esculentum cv. T5) wilt if their roots are exposed to chilling temperatures of around 5 °C. Under the same treatment, a chilling-tolerant congener (Lycopersicon hirsutum LA 1778) maintains shoot turgor. To determine the physiological basis of this differential response, the effect of chilling on both excised roots and roots of intact plants in pressure chambers were investigated. In excised roots and intact plants, root hydraulic conductance declined with temperature to nearly twice the extent expected from the temperature dependence of the viscosity of water, but the response was similar in both species. The species differed markedly, however, in stomatal behaviour: in L. hirsutum, stomatal conductance declined as root temperatures were lowered, whereas the stomata of L. esculentum remained open until the roots reached 5 °C, and the plants became flaccid and suffered damage. Grafted plants with the shoots of one genotype and roots of another indicated that the differential stomatal behaviour during root chilling has distinct shoot and root components. [source] Overexpression of bacterial catalase in tomato leaf chloroplasts enhances photo-oxidative stress tolerancePLANT CELL & ENVIRONMENT, Issue 12 2003E.-A. MOHAMED ABSTRACT The Escherichia coli gene katE, which is driven by the promoter of the Rubisco small subunit gene of tomato, rbcS3C, was introduced into a tomato (Lycopersicon esculentum Mill.) by Agrobacterium tumefaciens -mediated transformation. Catalase activity in progeny from transgenic plants was approximately three-fold higher than that in wild-type plants. Leaf discs from transgenic plants remained green at 24 h after treatment with 1 µm paraquat under moderate light intensity, whereas leaf discs from wild-type plants showed severe bleaching after the same treatment. Moreover, ion leakage from transgenic leaf discs was significantly less than that from wild-type leaf discs at 24 h after treatment with 1 µm paraquat and 10 mm H2O2, respectively, under moderate light intensity. To evaluate the efficiency of the E. coli catalase to protect the whole transgenic plant from the oxidative stress, transgenic and wild-type plants were sprayed with 100 µm paraquat and exposed to high light illumination (800 µmol m,2 s,1). After 24 h, the leaves of the transgenic plants were less damaged than the leaves of the wild-type plants. The catalase activity and the photosynthesis activity (indicated by the Fv/Fm ratio) were less affected by paraquat treatment in leaves of transgenic plants, whereas the activities of the chloroplastic ascorbate peroxidase isoenzymes and the ascorbate content decreased in both lines. In addition, the transgenic plants showed increased tolerance to the oxidative damage (decrease of the CO2 fixation and photosystem II activity and increase of the lipid peroxidation) caused by drought stress or chilling stress (4 °C) under high light intensity (1000 µmol m,2 s,1). These results indicate that the expression of the catalase in chloroplasts has a positive effect on the protection of the transgenic plants from the photo-oxidative stress invoked by paraquat treatment, drought stress and chilling stress. [source] Towards the best model for H atoms in experimental charge-density refinementACTA CRYSTALLOGRAPHICA SECTION A, Issue 4 2009Anna A. Hoser The consequences of different treatments of H atoms in experimental charge-density studies are discussed. Geometric and topological parameters obtained after applying four different H-atom models in multipolar refinement on high-resolution X-ray data only were compared with the results obtained for a reference joint high-resolution X-ray/neutron refinement. The geometry and the topological critical point and integrated parameters closest to the reference values were obtained after a mixed refinement (high-order refinement of heavy atoms, low-angle refinement of H atoms and elongation of the X,H distance to the average neutron bond lengths) supplemented by an estimation of the anisotropic thermal motions of H atoms using the SHADE program. Such a procedure works very well even for strong hydrogen bonds. The worst fit to the reference results for both critical point and integrated parameters was obtained when only the standardization to the average neutron X,H distances was applied. The non-H-atom parameters are also systematically influenced by the H-atom modeling. In order to compare topological and integrated properties calculated for H and non-H atoms in multipolar refinement when there are no neutron data, the same treatment of H atoms (ideally the mixed refinement + estimated anisotropic atomic displacement parameters for H atoms) should be applied. [source] Latest news and product developmentsPRESCRIBER, Issue 11 2008Article first published online: 18 JUN 200 New asthma guideline The BTS/SIGN guideline for the management of asthma has been updated. The diagnosis section has been rewritten, there is a new section on difficult asthma and the treatment sections have been updated. A new option at Step 3 (initial add-on therapy) is now the use of a combined budesonide/formoterol inhaler (Symbicort) as a reliever in addition to regular use as a preventer. This reflects evidence from the SMART trials, which showed that an average of one extra puff per day significantly reduced exacerbations and admissions (Br Med J 2007;335:513). Metformin matches insulin in pregnancy Metformin does not worsen perinatal outcomes compared with insulin in gestational diabetes and mothers prefer it, a study from Australia and New Zealand shows (N Engl J Med 2008;358:2003,15). Of the women randomised to metformin treatment, 93 per cent were still taking it at term and 46 had supplemental insulin. The combined incidence of neonatal hypoglycaemia, respiratory distress, need for phototherapy, birth trauma, five-minute Apgar score less than 7 or prematurity was 32 per cent with both treatments. There were no serious adverse events. More women said they would choose the same treatment again for metformin than insulin (77 vs 27 per cent). Same CV protection with antihypertensives There is no difference in protection against major cardiovascular events between different types of antihypertensives in young or older (65 or over) adults, according to the Blood Pressure Lowering Treatment Trialists' Collaboration. Its meta-analysis of 31 trials involving over 190 000 patients (BMJ Online 2008; doi:10.1136/bmj.39548.738 368.BE) found no significant difference by age on blood pressure reduction or risk reduction. Treatment may be chosen according to tolerability and cost as long as effective blood pressure reduction is achieved, the authors conclude. Older people are at greater absolute risk and treatment therefore offers larger reductions in serious vascular events. HPV vaccination starts in September Vaccination against human papilloma virus will be part of the national immunisation programme from the start of the new school year in September. The vaccine, administered as three doses over six months, will initially be offered to girls aged 12,13 (school year 8) to reduce their risk of cervical cancer. A two-year catch-up campaign for all girls up to 18 years old will begin in 2009. MHRA: pancreatitis with exenatide warning The incretin mimetic exenatide (Byetta), licensed for the treatment of type 2 diabetes, may rarely be associated with pancreatitis, warns the MHRA (Drug Safety Update 2008;1:Issue 10). One case has been reported in the UK and 89 in the USA and Germany. The MHRA advises that patients should be warned of the symptoms of pancreatitis (severe abdominal pain, back pain). Treatment should be discontinued if pancreatitis is suspected and the case reported on a yellow card. 2007 prescribing bill Primary-care expenditure on drugs in England in 2007 totalled £8.37 billion, only 2 per cent more than in 2006, according to the latest statistics from the Information Centre (www.ic.nhs.uk). Prescription numbers increased by almost 6 per cent. Prescribing increased in most BNF categories but changed little in musculoskeletal drugs and immunological products and vaccines. Calceos: calcium/ vitamin D3 price match Manufacturer Galen has pledged to continue to price-match its calcium/vitamin D3 supplement Calceos with Adcal-D3 or Calcichew D3 Forte. If the price of either product falls below that of Calceos chewable tablets, Galen will match it within six months. The company says it will honour the pledge until at least 2011. Copyright © 2008 Wiley Interface Ltd [source] Latest news and product developmentsPRESCRIBER, Issue 3 2007Article first published online: 14 MAR 200 PPIs and hip fracture Treatment with a PPI may increase the risk of hip fracture, with longer use associated with higher risk according to a study in UK patients (J Am Med Assoc 2006;297:2947-53). The case control study compared use of PPIs by 13 556 patients with hip fracture and 135 386 controls in the UK General Practice Research Database. Use of a PPI for more than one year was associated with an increase of 44 per cent in the odds of hip fracture. The risk was higher for longer- term use (59 per cent after four years) and at higher doses (more than doubled with long-term high doses). The mechanism for this possible effect may be impaired calcium absorption associated with hypochlorhydria and reduced bone resorption. CHD NSF Statin prescribing has increased by 30 per cent every year since the publication of the Coronary Heart Disease NSF, the Department of Health says. The estimated number of lives saved attributable to statins had risen to 9700 in 2005. The proportion of patients with acute MI who were given thrombolysis within 30 minutes of admission has increased to 83 per cent. Flu jabs cut pneumonia deaths A US study suggests that flu vaccine protects against death during the flu season in patients admitted with community-acquired pneumonia (Arch Intern Med 2007;167:53-9). Nineteen per cent of patients admitted with pneumonia during the winters of 1999-2003 were known to have been vaccinated against flu. Their risk of death during their hospital stay was 70 per cent lower than that of nonvaccinated individuals. After adjustment for antipneumococcal vaccination and comorbidity, the odds of death were still 39 per cent lower. Model to predict admissions The King's Fund, together with New York University and Health Dialog, has published a model that predicts the risk of emergency hospital admission (see www.kingsfund.org.uk). The model is intended for use by PCTs and draws on data from secondary and primary care to define clinical profiles, allowing patients whose condition is deteriorating to be identified before they need admission. Problem drinking The National Treatment Agency for Substance Misuse (NTA), a special authority within the NHS, has published a critical appraisal of the evidence for various treatments for alcohol problems (www.nta.nhs.uk). The 212-page document estimates that over seven million hazardous or harmful drinkers may benefit from brief interventions by any health workers, and over one million dependent drinkers may benefit from specialist intervention. It concludes that cognitive behavioural approaches to specialist treatment are most effective and that treatment probably accounts for about one-third of improvements made in problem drinking. of patients remained on the same treatment after one year, falling to half at two years and about 40 per cent at three years. Treatment was more frequently stopped for lack of efficacy than for adverse effects. Stopping anti-TNFs Discontinuation of treatment with anti-TNF agents is more common in clinical practice than in clinical trial populations, a French study has found (J Rheumatol 2006;33:2372-5). The retrospective analysis of a single centre's experience of treating 770 patients with etanercept (Enbrel), infliximab (Remicade) or adalimumab (Humira) found that fewer than two-thirds of patients remained on the same treatment after one year, falling to half at two years and about 40 per cent at three years. Treatment was more frequently stopped for lack of efficacy than for adverse effects. There were no statistically significant differences between the three agents but there was a trend for infliximab to be least well tolerated. Generic statin savings The Department of Health has estimated that prescribing simvastatin and pravastatin generically would save £85 million per year. Its analysis of the ,Better care, better value' indicators (see www.productivity.nhs.uk) shows that statin prescribing has increased by 150 per cent in the past five years, with costs totalling £600 million in 2005. The Department says that if every PCT prescribed pravastatin and simvastatin by generic name in only 69 per cent of cases ,the level achieved by the top quarter of trusts ,the savings would be over £85 million a year. Herceptin reporting Press reports of a two-year trial of trastuzumab (Herceptin) were generally accurate in reporting its effectiveness but few reported an increased risk of adverse effects, according to the NHS National Library for Health (www.library.nhs.uk). The Herceptin Adjuvant (HERA) trial (Lancet 2007;369:29-36) found that, after an average follow-up of two years, 3 per cent of women treated with trastuzumab died compared with 5 per cent of controls; estimated three-year survival rates were 92.4 and 89.7 per cent respectively. All four press articles reported these findings accurately, but only two mentioned the increased risk of adverse effects. Updated guidance on CDs The Department of Health has published updated guidance on the strengthened governance requirements for managing controlled drugs, taking into account new regulations that came into force on 1 January (seewww.dh.gov.uk/asset Root/04/14/16/67/04141667.pdf). Statin adherence lowers MI mortality Patients with acute myocar- dial infarction (MI) who take their statins as prescribed are significantly more likely to survive for two to three years than those with low adherence (J Am Med Assoc 2007;297: 177-86). The four-year observational study of 31 455 patients with acute MI found that, compared with those who had taken at least 80 per cent of prescribed daily doses, the risk of death in those with less than 40 per cent adherence was 25 per cent greater over 2.4 years. For individuals with intermediate adherence (40-79 per cent), the risk was 12 per cent greater. Both differences were statistically significant after adjustment for potential confounding factors. The authors believe their finding is explained by differences in adherence rather than healthier behaviour because the excess risk of low adherence was less marked with beta-blockers and not significant for calcium-channel blockers. Improving community medicines management Mental health trusts need to improve medicines management by their community teams and improve information sharing with GPs, the Healthcare Commission has found (www.healthcare commission.org.uk). Its national report revealed limited evidence of pharmacist involvement in community mental health teams, even though 90 per cent of patients were cared for in the community. Only 11 per cent of assertive outreach patients had the tests necessary to ensure safe use of their medicines. Medication reviews found that 46 per cent of patients in mental health trusts and 12 per cent of those in acute trusts were not taking their medication appropriately. The Commission also reported that acute trusts received a complete drug history from GPs for fewer than half of audited patients when they were admitted to hospital, and only 30 per cent of PCTs reported that GPs received adequate information on patients' medicines on discharge. Copyright © 2007 Wiley Interface Ltd [source] Ultrastructural Study of Encystation and Excystation in Acanthamoeba castellaniiTHE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 2 2005BIBIANA CHÁVEZ-MUNGUÍA Abstract. Encystation and excystation of Acanthamoeba castellanii were studied by transmission electron microscopy. The differentiation process was induced in asynchronous cultures grown axenically. Cytoplasmic vesicles containing a dense fibrous material very similar in appearance to the cyst wall were observed in trophozoites induced to encyst. When these trophozoites were incubated with calcofluor white m2r, fluorescence was observed in cytoplasmic vesicles, suggesting that the material contained in these vesicles corresponded to cyst wall precursors. Semithin cryosections of mature cysts with the same treatment showed fluorescence in the ectocyst and a less intense fluorescence in the endocyst, suggesting the presence of cellulose in both structures of the cyst wall. In mature cysts induced to excystation, small structures very similar to electron-dense granules (EDG) previously described in other amoebae were frequently observed. The EDGs were either sparsely distributed in the cytoplasm or associated with the cytoplasmic face of the plasma membrane. Many of them were located near the ostiole. In advanced phases of excystation, endocytic activity was suggested by the formation of endocytic structures and the presence of vacuoles with fibrous content similar to that of the cyst wall. Electron-dense granules in the process of dissolution were also observed in these vacuoles. Furthermore, the formation of a pseudopod suggests a displacement of the amoeba toward the ostiole. [source] | ||||||||||||||||||||||||||||||||||||||||