bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficiency in Lysosomal Enzyme Secretion Is Associated with Upregulation of Phosphatidylinositol 4‐Phosphate in Tetrahymena
Authors: DELI DIMITRA , LEONDARITIS GEORGE , TIEDTKE ARNO , GALANOPOULOU DIA
Published: March 2008

ABSTRACT. A variety of lower eukaryotes and certain mammalian cells are known to constitutively secrete lysosomal hydrolases. Recent studies in Tetrahymena have shown that phosphatidylinositol 3‐phosphate regulates the proper secretion of lysosomal enzymes at the level of phagolysosome formation. We extend these findings by studying the secretion‐deficient strain MS‐1 of Tetrahymena thermophila, which possess phosphatidylinositol levels similar to wild type. However, steady‐state levels of phosphatidylinositol 4‐phosphate (PtdIns4P) were found to be doubled in this strain compared with wild type as shown by in vivo [3H]inositol labeling and high‐performance liquid chromatography analysis. The increased PtdIns4P levels in MS‐1 cells were unrelated to the upregulation of total phosphatidylinositol phosphate induced by hyperosmotic stress because this treatment resulted in a similar increase of PtdIns4P in MS‐1 and wild‐type cells. Hyperosmotic stress did not affect secretion in either of the two types of cells. On the other hand, under conditions of wortmannin‐induced hypersecretion in wild‐type cells, MS‐1 cells developed a highly vacuolated phenotype while secretion was not induced. Importantly, comparative analysis of wild‐type and MS‐1 cells under wortmannin treatment showed that PtdIns4P levels were differentially regulated in the two strains. These results collectively suggest that PtdIns4P turnover in Tetrahymena is linked to lysosome secretion.
Use of Post‐heat Treatment to Obtain a 2H Solid Solution in Spark Plasma Sintering‐Processed AlN–SiC Mixtures
Authors: Kobayashi Ryota , Tatami Junichi , Wakihara Toru , Komeya Katsutoshi , Meguro Takeshi , Goto Takashi , Tu Rong
Published: March 2008

Dense aluminum nitride–silicon carbide (AlN–SiC) solid solutions with a 2H structure were fabricated by the post‐heat treatment of dense AlN–SiC composites fabricated by spark plasma sintering (SPS). The changes in the relative density, microstructure, and phases present were investigated for the compositions of 25 mol% AlN–75 mol% SiC (AlN 25), 50 mol% AlN–50 mol% SiC (AlN 50), and 75 mol% AlN–25 mol% SiC (AlN 75). The AlN–SiC composites fabricated by the SPS were dense ceramics with fine microstructures and composed of 2H and 6H AlN–SiC solid solutions. The AlN 50 samples heat treated at 2200°C and the AlN 75 samples heat treated at 2100°C were also dense ceramics and composed of only the 2H AlN–SiC solid solution. In contrast, the AlN 25 samples heat treated at 2200°C were porous ceramics and composed of several AlN–SiC solid solutions (2H, 4H, 6H, and 15R), and the AlN 75 samples heat treated at 2200°C were decomposed into an Al melt. Dense AlN–SiC solid solutions composed of only the 2H phase can be obtained by controlling the heat‐treatment temperatures, except for the AlN 25 sample.
Oxidation Resistance of Fully Dense ZrB2 with SiC, TaB2, and TaSi2 Additives
Authors: Peng Fei , Speyer Robert F.
Published: March 2008

Specimens of ZrB2 containing various concentrations of B4C, SiC, TaB2, and TaSi2 were pressureless‐sintered and post‐hot isostatic pressed to their theoretical densities. Oxidation resistances were studied by scanning thermogravimetry over the range 1150°–1550°C. SiC additions improved oxidation resistance over a broadening range of temperatures with increasing SiC content. Tantalum additions to ZrB2–B4C–SiC in the form of TaB2 and/or TaSi2 increased oxidation resistance over the entire evaluated spectrum of temperatures. TaSi2 proved to be a more effective additive than TaB2. Silicon‐containing compositions formed a glassy surface layer, covering an interior oxide layer. This interior layer was less porous in tantalum‐containing compositions.
U.S. Federal Regulations for Emergency Research: A Practical Guide and Commentary
Authors: McRae Andrew , Weijer Charles
Published: March 2008

Emergency medicine research requires the enrollment of subjects with varying decision‐making capacities, including capable adults, adults incapacitated by illness or injury, and children. These different categories of subjects are protected by multiple federal regulations. These include the federal Common Rule, the Department of Health and Human Services (DHHS) regulations for pediatric research, and the Food and Drug Administration’s (FDA) Final Rule for the Exception from the Requirements of Informed Consent in Emergency Situations. Investigators should be familiar with the relevant federal research regulations to optimally protect vulnerable research subjects, and to facilitate the institutional review board (IRB) review process. IRB members face particular challenges in reviewing emergency research. No regulations exist for research enrolling incapacitated subjects using proxy consent. The wording of the Final Rule may not optimally protect vulnerable subjects. It is also difficult to apply conflicting regulations to a single study that enrolls subjects with differing decision‐making capacities. This article is intended as a guide for emergency researchers and IRB members who review emergency research. It reviews the elements of Federal Regulations that apply to consent, subject selection, privacy protection, and the analysis of risks and benefits in all emergency research. It explores the challenges for IRB review listed above, and offers potential solutions to these problems.
Brief Screening for Adolescent Depressive Symptoms in the Emergency Department
Authors: Rutman Maia S. , Shenassa Edmond , Becker Bruce M.
Published: March 2008

Background:  Depression is the most common psychiatric disorder among adolescents and is more prevalent among those seeking care in the emergency department (ED). However, adolescents are rarely screened for depressive symptoms in the pediatric emergency department (PED).

Objectives:  To evaluate the sensitivity and specificity of one‐ and two‐item screens for depressive symptoms compared to the 20‐question Center for Epidemiologic Studies Depression Scale (CESD) among adolescents seeking care in a PED.

Methods:  This was a cross‐sectional study of a convenience sample of adolescents 12–17 years old presenting to an urban PED with subcritical illness or injury. Participants completed three screening instruments: the two‐question screen, the single‐question screen, and the CESD.

Results:  A total of 321 patients were approached to enter the study, of whom 212 (66%) agreed to participate. Seventy‐eight (37%) of the study participants screened positive for depression on the CESD using a cutoff score of ≥16. The two‐question screen had a sensitivity of 78% (95% confidence interval [CI] = 73% to 84%) and specificity of 82% (95% CI = 77% to 87%) for depressive symptoms compared with the CESD. The single‐question screen had a sensitivity of 56% (95% CI = 50% to 63%) and specificity of 93% (95% CI = 90% to 96%) compared with the CESD.

Conclusions:  The two‐question screen is a sensitive and specific initial screen for depressive symptoms in adolescents being seen in the PED. This quick, simple instrument would be ideal for use in the busy PED setting and would allow clinicians to identify adolescents who require more extensive psychiatric evaluation.
Differences in Long‐term Mortality for Different Emergency Department Presenting Complaints
Authors: Safwenberg Urban , Terént Andreas , Lind Lars
Published: March 2008

Objectives:  To characterize long‐term mortality based on previous emergency department (ED) presenting complaints.

Methods:  The authors followed, for 10 years, all of the 12,667 nonsurgical patients visiting an ED during 1995/1996. Differences in standardized mortality ratio (SMR) depending on presenting complaints were then investigated.

Results:  During follow‐up, 5,324 deaths occurred (mortality rate 6.6 per 100 person‐years at risk), giving a SMR of 1.33 (95% CI = 1.30 to 1.37, p < 0.001) when compared with the expected mortality in the catchment area. Different presenting complaints were associated with different long‐term mortality rates, independent of age and gender (p < 0.0001). The subjects with seizures had the highest SMR (2.62, 95% CI = 2.13 to 3.22) followed by intoxications (2.51, 95% CI = 2.11 to 2.98), asthmalike symptoms (1.84, 95% CI = 1.65 to 2.06), and hyperglycemia (1.67, 95% CI = 1.42 to 1.95). The largest complaint group, chest pain, had a 20% higher mortality rate than the background population (95% CI = 1.13 to 1.26). Patients with a discharge diagnosis of myocardial infarction, but without chest pain as the presenting complaint, had an increased long‐term mortality (hazard ratio [HR] 1.70, 95% CI = 1.15 to 2.42) compared to the group with chest pain. In contrast, stroke patients without strokelike symptoms had a reduced mortality (HR 0.74, 95% CI = 0.65 to 0.84) compared to patients with strokelike symptoms.

Conclusions:  Long‐term age‐ and gender‐adjusted mortality is the highest with seizures out of 33 presenting complaints and differs markedly between different ED admission complaints. Furthermore, depending on the admission complaint, long‐term mortality differs within the same discharge diagnosis. Hence, the presenting complaint adds unique information to the discharge diagnosis regarding long‐term mortality in nonsurgical patients.
Derivation of a Triage Algorithm for Chest Radiography of Community‐acquired Pneumonia Patients in the Emergency Department
Authors: Kyriacou Demetrios N. , Yarnold Paul R. , Soltysik Robert C. , Self Wesley H. , Wunderink Richard G. , Schmitt Brian P. , Parada Jorge P. , Adams James G.
Published: March 2008

Background:  Community‐acquired pneumonia (CAP) accounts for 1.5 million emergency department (ED) patient visits in the United States each year.

Objectives:  To derive an algorithm for the ED triage setting that facilitates rapid and accurate ordering of chest radiography (CXR) for CAP.

Methods:  The authors conducted an ED‐based retrospective matched case–control study using 100 radiographic confirmed CAP cases and 100 radiographic confirmed influenzalike illness (ILI) controls. Sensitivities and specificities of characteristics assessed in the triage setting were measured to discriminate CAP from ILI. The authors then used classification tree analysis to derive an algorithm that maximizes sensitivity and specificity for detecting patients with CAP in the ED triage setting.

Results:  Temperature greater than 100.4°F (likelihood ratio = 4.39, 95% confidence interval [CI] = 2.04 to 9.45), heart rate greater than 110 beats/minute (likelihood ratio = 3.59, 95% CI = 1.82 to 7.10), and pulse oximetry less than 96% (likelihood ratio = 2.36, 95% CI = 1.32 to 4.20) were the strongest predictors of CAP. However, no single characteristic was adequately sensitive and specific to accurately discriminate CAP from ILI. A three‐step algorithm (using optimum cut points for elevated temperature, tachycardia, and hypoxemia on room air pulse oximetry) was derived that is 70.8% sensitive (95% CI = 60.7% to 79.7%) and 79.1% specific (95% CI = 69.3% to 86.9%).

Conclusions:  No single characteristic adequately discriminates CAP from ILI, but a derived clinical algorithm may detect most radiographic confirmed CAP patients in the triage setting. Prospective assessment of this algorithm will be needed to determine its effects on the care of ED patients with suspected pneumonia.
Carbon Monoxide Has Direct Toxicity on the Myocardium Distinct from Effects of Hypoxia in an Ex Vivo Rat Heart Model
Authors: Suner Selim , Jay Gregory
Published: March 2008

Objectives:  Carbon monoxide (CO) toxicity causes significant central nervous system and cardiac injury. Although the neurological damage caused by CO toxicity is extensively described, the mechanisms underlying myocardial insult are unclear. The authors used an externally perfused isolated rat heart model to examine the effects of a physiological saline solution (Krebs Henseleit HEPES, KHH) aerated with CO on cardiac function.

Methods:  Fifteen rats were equally divided into three groups: the control group (KHH + 100% O2), the nitrogen control group (KHH + 70% O2, 30% N2), and the CO group (KHH + 70% oxygen, 30% CO). Left ventricular peak systolic pressure (LVPsP), end diastolic pressure (LVEdP), and coronary perfusion pressure were measured while the isolated heart was paced and perfused on a modified Langendorf apparatus.

Results:  Left ventricular generated pressure (LVGP = LVPsP − LVEdP) decreased in the nitrogen control and CO groups compared to the control group. There was higher LVGP in the recovery phase between the nitrogen control group compared to the CO group. Both groups had increased lactic acid levels in the experimental phase.

Conclusions:  Carbon monoxide with hypoxia and hypoxemic hypoxia both result in similar depression of cardiac function. Hearts poisoned with CO with hypoxia do not recover function to the extent that hearts rendered hypoxic with nitrogen do when perfused with 100% oxygen after the insult. This suggests that CO causes direct myocardial toxicity distinct from the effects of hypoxia.
Acute Ethanol Coingestion Confers a Lower Risk of Hepatotoxicity after Deliberate Acetaminophen Overdose
Authors: Waring W. Stephen , Stephen Alexandra F. , Malkowska Aleksandra M. , Robinson Oliver D.G.
Published: March 2008

Objectives:  Little is known about the clinical significance of acute ethanol coingestion around the time of acetaminophen (paracetamol) overdose. This study prospectively examined the effect of acute ethanol coingestion on risk of hepatotoxicity among patients admitted to hospital for N‐acetylcysteine (NAC) therapy after deliberate acetaminophen overdose.

Methods:  This was a prospective observational study and included sequential patients who presented within 24 hours of acute acetaminophen ingestion and required NAC therapy. Significant hepatotoxicity was defined by alanine transaminase > 1,000 U/L or the international normalized ratio > 1.3 after a standardized intravenous administration of 300 mg/kg NAC.

Results:  There were 362 patients, including 178 (49.2%) who coingested ethanol acutely. The prevalence of hepatotoxicity was 5.1% (95% CI = 2.6% to 9.5%) in those who ingested ethanol, compared to 15.2% (95% CI = 10.7% to 21.2%) in those who did not (p = 0.0027 by chi‐square proportional test). Acute ethanol intake conferred a lower risk of hepatotoxicity in patients who had acetaminophen concentrations above or below the “200‐line” and was independent of the interval between ingestion and assessment.

Conclusions:  Acute ethanol intake is associated with a lower risk of hepatotoxicity after acetaminophen overdose. This apparent protective effect cannot be explained solely by lower exposure to acetaminophen in this group, nor differences in the interval between ingestion and initiation of treatment. Further work is required to establish mechanisms by which ethanol might confer protection against hepatotoxicity, so as to identify novel strategies for reducing risk after acute acetaminophen ingestion.
The Challenge of Predicting Demand for Emergency Department Services
Authors: McCarthy Melissa L. , Zeger Scott L. , Ding Ru , Aronsky Dominik , Hoot Nathan R. , Kelen Gabor D.
Published: March 2008

Objectives:  The objective was to develop methodology for predicting demand for emergency department (ED) services by characterizing ED arrivals.

Methods:  One year of ED arrival data from an academic ED were merged with local climate data. ED arrival patterns were described; Poisson regression was selected to represent the count of hourly ED arrivals as a function of temporal, climatic, and patient factors. The authors evaluated the appropriateness of prediction models by whether the data met key Poisson assumptions, including variance proportional to the mean, positive skewness, and absence of autocorrelation among hours. Model accuracy was assessed by comparing predicted and observed histograms of arrival counts and by how frequently the observed hourly count fell within the 50 and 90% prediction intervals.

Results:  Hourly ED arrivals were obtained for 8,760 study hours. Separate models were fit for high‐ versus low‐acuity patients because of significant arrival pattern differences. The variance was approximately equal to the mean in the high‐ and low‐acuity models. There was no residual autocorrelation (r = 0) present after controlling for temporal, climatic, and patient factors that influenced the arrival rate. The observed hourly count fell within the 50 and 90% prediction intervals 50 and 90% of the time, respectively. The observed histogram of arrival counts was nearly identical to the histogram predicted by a Poisson process.

Conclusions:  At this facility, demand for ED services was well approximated by a Poisson regression model. The expected arrival rate is characterized by a small number of factors and does not depend on recent numbers of arrivals.
Heidelberg retina tomograph parameters of the optic disc in eyes with progressive retinal nerve fibre layer defects
Authors: Saarela Ville , Airaksinen P. Juhani
Published: March 2008

Purpose:  To determine the Heidelberg retina tomograph (HRT) parameters that identify glaucomatous changes in optic nerve head (ONH) topography associated with progression of retinal nerve fibre layer (RNFL) defects.

Methods:  A total of 68 eyes with open‐angle glaucoma were included in this retrospective study: 34 eyes showed progression of an RNFL defect during the follow‐up period and 34 eyes did not. Successful RNFL photographs and scanning laser tomography examinations with the HRT were taken in all patients at each of three visits. The change in HRT parameter values during follow‐up was calculated.

Results:  Progression of the RNFL defect was statistically significantly correlated (p = 0.049) with only one topographic ONH parameter, the cup shape measure. The best combination of two parameters (p = 0.009) included the maximum cup depth and the linear cup : disc area ratio; the best combination of three parameters (p = 0.007) included the maximum cup depth, the linear cup : disc area ratio and the horizontal cup : disc area ratio. Sensitivity and specificity values were 52.9% and 73.5%, respectively, for the cup shape measure, 70.6% and 73.5%, respectively, for the two‐parameter combination, and 76.5% and 79.4%, respectively, for the three‐parameter combination. The areas under the receiver operating characteristic curve were 0.617, 0.724 and 0.753, respectively.

Conclusions:  The results indicate that the HRT parameters may be used to detect small ONH changes associated with progression of the RNFL defect. With the exception of the cup shape measure, the parameters which provide the best correlation with progression differ from those considered optimal for recognizing the presence or absence of glaucoma.
Type 2 diabetes has minimal effect on osseointegration of titanium implants in Psammomys obesus
Authors: Casap Nardy , Nimri Samer , Ziv Ehud , Sela Jona , Samuni Yuval
Published: March 2008

Objectives: Dental implants are routinely used with high success rates in generally healthy individuals. In contrast, their use in patients with uncontrolled diabetes mellitus (DM) remains controversial as altered bone healing around implants has been reported. The majority of reports addressing the issue of osseointegration of implants in animals were performed in β‐cell cytotoxic‐induced Type I diabetes. In this study, we assessed the osseointegration of implants in Gerbil Psammomys obesus, a model of nutritionally induced Type 2 DM.

Materials and methods: Titanium implants were inserted into the tibial medullary space of 140 male diabetic and control animals. One, 2, 4, and 8 weeks after implantation the tibias were removed for histomorphometric evaluation, which included trabecular bone volumes (TBV) and osseointegration.

Results: Two weeks following implantation, diabetic animals had slightly less mature bone when compared with control animals. This distinction was not present 4 weeks after implantation. Interestingly, no correlation was found between ossetointegration or TBV and glucose and insulin levels. Furthermore, no difference in osseointegration and TBV values was seen between the groups. The heterogeneity of serum glucose and insulin levels in this model and the possible role of insulin in bone metabolism are discussed.

Conclusions: No significant difference in osseointegration and TBV was seen between diabetic and control P. obesus, a model of nutritionally induced Type 2 DM.
Missing osteogenic effect of expanded autogenous osteoblast‐like cells in a minipig model of sinus augmentation with simultaneous dental implant installation
Authors: Liu Yanming , Springer Ingo N. G. , Zimmermann Corinna E. , Açil Yahya , Scholz‐Arens Katharina , Wiltfang Jörg , Terheyden Hendrik
Published: March 2008

Objectives: With natural bovine bone mineral (BioOss®) as carrier, the study aimed at investigating the effect of autogenous osteoblast‐like cells on bone regeneration in an orthotopic (maxillary sinus) and an ectopic (muscle) site.

Materials and methods: Autogenous osteoblast‐like cells were isolated from iliac cancellous bone of six minipigs and expanded in an autogenous serum‐supplemented osteogenic medium. After confirmation of osteogenicity, the expanded cells were precultivated on BioOss® granules for 1 week. Four milliliter of cell‐seeded BioOss® were used for sinus augmentation of right sinus and a Straumann solid screw (dental) implant was simultaneously installed. The contralateral (control) side was filled with cell‐free BioOss®. Besides, 2 ml of the corresponding granules were placed in a pouch in the latissimus dorsi muscles bilaterally. Polychrome sequential labeling was performed postoperatively. Specimens were harvested at week 6. Undecalcified sections were evaluated with microradiography, fluorescence microscopy, histology and histomorphometry.

Results: In the test side, the coronal part of dental implant demonstrated higher bone–implant contact (BIC) than the apical part (34.88±28.86% vs. 16.68±13.80%, P=0.039), as well as higher bone density (BD) in the corresponding zone (14.88±6.37% vs. 11.10±4.54%, P=0.021). However, the test side demonstrated no advantage over control side in either BD (12.25±4.22% vs. 8.45±11.04%, P=0.473) or BIC (24.15±21.97% vs. 22.05±19.00%, P=0.270). Rare bone was formed in the muscles in both sides.

Conclusions: The expanded autogenous osteoblast‐like cells failed to enhance bone formation in the minipig model of sinus augmentation.
Histomorphometric assessment in human cadavers of the peri‐implant bone density in maxillary tuberosity following implant placement using osteotome and conventional techniques
Authors: Blanco Juan , Suárez Juan , Novio Silvia , Villaverde Gabriel , Ramos Isabel , Segade Luis Alberto G.
Published: March 2008

Objective: To evaluate and compare peri‐implant bone condensation in the maxillary tuberosity of human cadavers following the osteotome and standard drilling techniques, and to determine whether peri‐implant bone condensation following the osteotome technique is localized or homogeneous.

Material and methods: Twenty‐four cylinder‐threaded titanium implants (12 on each side) were placed in the left (standard technique) and right (osteotome technique with tapered osteotomes for bone condensation, Straumann®) maxillary tuberosities of 12 edentulous posterior maxillae of deceased people who had bequeathed their bodies to the University of Santiago de Compostela for medical‐scientific research. After surgery, the implants were removed with the surrounding bone, prepared using sawing and grinding technique and examined histomorphometrically. The bone density (bone area/analyzed area) of the entire, periapical (fifth apical) and pericylinder peri‐implant areas was calculated, statistically analyzed and compared with the bone density of the host cancellous maxillary bone.

Results: The bone density of the entire peri‐implant area was statistically found to be greater with the osteotome technique (39.38 ± 9.67) than with conventional drilling technique (31.06 ± 5.9). This difference was greatest for the periapical zone (53.32 ± 12.26 vs. 34.18 ± 6.34). Nonetheless, in the pericylinder area no significant difference was found between the two techniques (32.30 ± 8.74 vs. 30.34 ± 7.2).

Conclusion: Peri‐implant bone condensation following the osteotome technique is not homogeneously observed through the entire peri‐implant area. A greater bone density was achieved only in the fifth apical peri‐implant area.
Cytoprotective effects of melatonin on C6 astroglial cells exposed to glutamate excitotoxicity and oxidative stress
Authors: Das Arabinda , Belagodu Amogh , Reiter Russel J. , Ray Swapan K. , Banik Naren L.
Published: March 2008

Abstract:  To preserve the central nervous system (CNS) function after a traumatic injury, therapeutic agents must be administered to protect neurons as well as glial cells. Cell death in CNS injuries and diseases are attributed to many factors including glutamate toxicity and oxidative stress. We examined whether melatonin, a potent anti‐oxidant and free radical scavenger, would attenuate apoptotic death of rat C6 astroglial cells under glutamate excitotoxicity and oxidative stress. Exposure of C6 cells to 500 μm l‐glutamic acid (LGA) and 100 μm hydrogen peroxide (H2O2) for 24 hr caused significant increases in apoptosis. Apoptosis was evaluated by Wright staining and ApopTag assay. Melatonin receptor 1 appeared to be involved in the protection of these cells from excitotoxic and oxidative damage. Cells undergoing excitotoxic and oxidative stress for 15 min were then treated with 150 nm melatonin, which prevented Ca2+influx and cell death. Western blot analyses showed alterations in Bax and Bcl‐2 expression resulting in increased Bax:Bcl‐2 ratio during apoptosis. Western blot analyses also showed increases in calpain and caspase‐3 activities, which cleaved 270 kD α‐spectrin at specific sites to generate 145 kD spectrin breakdown product (SBDP) and 120 kD SBDP, respectively. However, 15‐min post‐treatment of C6 cells with melatonin dramatically reduced Bax:Bcl‐2 ratio and proteolytic activities, decreasing LGA or H2O2‐induced apoptosis. Our data showed that melatonin prevented proteolysis and apoptosis in C6 astroglial cells. The results suggest that melatonin may be an effective cytoprotective agent against glutamate excitotoxicity and oxidative stress in CNS injuries and diseases.
Suppressive action of melatonin on the TH‐2 immune response in rats infected with Trypanosoma cruzi
Authors: Santello Fabricia Helena , Frare Eduardo Osório , Dos Santos Carla Domingues , Caetano Leony Cristina , Alonso Toldo Míriam Paula , Do Prado José Clóvis
Published: March 2008

Abstract:  Control of the acute phase of Trypanosoma cruzi infection is critically dependent on cytokine‐mediated macrophage activation to intracellular killing, natural killer (NK) cells, CD4+ T cells, CD8+ T cells and B cells. Cell‐mediated immunity in T. cruzi infection is also modulated by cytokines, but in addition to parasite‐specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell‐mediated immunity of infected subjects. Here we studied the role of cytokines in the regulation of innate and adaptive immunity during the acute phase of T. cruzi infection in Wistar rats. Melatonin is an effective regulator of the immune system. Macrophages and T lymphocytes, which have melatonin receptors, are target cells for the immunomodulatory function of melatonin. In this paper melatonin was orally given via two protocols: prior to and concomitant with infection. Both treatments were highly effective against T. cruzi with enhanced action for the concomitant treatment. The data suggest an up‐regulation of the TH‐1 immune response as all analyzed parameters, interleukin (IL)‐4, IL‐10, transforming growth factor‐β1 and splenocyte proliferation, displayed reduced levels as compared with the untreated counterparts. However, the direct effects of melatonin on immune cells have not been fully investigated during T. cruzi infection. We conclude that in light of the current results, melatonin exerted important therapeutic benefits through its immune regulatory effects.
Optimized synthesis of the melatonin metabolite N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK)
Authors: Ximenes Valdecir F.
Published: March 2008

Abstract:  N
1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) is the product of oxidative pyrrole ring cleavage of melatonin. AFMK and its deformylated derivative N1‐acetyl‐5‐methoxykynuramine (AMK) are compounds for which there are increasing demands because of their antioxidant, immunomodulatory and anti‐inflammatory properties. Here, we sought to determine the best reaction conditions for preparation of AFMK using chlorpromazine (CPZ) as a co‐catalyst in the peroxidase‐mediated oxidation of melatonin. The parameters studied were pH, identity and concentration of buffers, hydrogen peroxide (H2O2) and CPZ concentrations and the presence or absence of dissolved molecular oxygen in the reaction medium. The rate and efficiency of AFMK production were compared with a noncatalyzed method which uses a high concentration of H2O2. We found that by using CPZ and bubbling molecular oxygen during the course of the reaction, the yield of AFMK was significantly increased (about 60%) and the reaction time decreased (about 30 min), as compared with the noncatalyzed reaction (yield 32% and reaction time 4 hr). Based on these data, we suggest that this could be a new, easily performed and efficient route for AFMK preparation. Additionally, we provide evidence that a radical chain reaction could be responsible for the formation of AFMK.
Dermatologic subspecialties in German inpatient dermatology:a national survey
Authors: Hensen Peter , Müller Marcel L. , Stadler Rudolf , Luger Thomas A.
Published: March 2008

Background: In German‐speaking countries, the specialty of dermatology is characterized by a large amount of subspecialties. Data providing information whether and to what extent these subspecialties are represented in German dermatology departments and clinics is not available.

Methods: A national questionnaire survey was performed to determine the extent of involvement of dermatological subspecialties in dermatologic hospitals.Methods of descriptive statistics were applied.

Results: Overall, 90 dermatologic departments participated in this survey with a response rate of 78.3 %.The subspecialties allergology, dermatooncology,and dermatologic surgery are represented in over 90 % of departments; the sub‐specialties andrology, aesthetic dermatology, dermatopathology, microbiology,phlebology,photobiology,proctology, and wound healing are represented in over 50 % of clinics. Furthermore, the subspecialties allergology, dermato‐oncology, photobiology, and dermatopathology have strong research or academic representation.

Conclusions: The present survey demonstrates that dermatologic subspecialties are widely represented in dermatologic departments and clinics not only by individuals with specialty training but also by those in higher academic posts. This demonstrated high expertise should be maintained in German dermatology and could be promoted by academic programs.
Anti‐inflammatory potential of a lipolotion containing coriander oil in the ultraviolet erythema test
Authors: Reuter Juliane , Huyke Constance , Casetti Federica , Theek Carmen , Frank Uwe , Augustin Matthias , Schempp Christoph
Published: March 2008

Background: Coriander oil is used as an antimicrobial agent and as a natural fragrance. The present study investigated the anti‐inflammatory potency of coriander oil in the ultraviolet (UV) erythema test in vivo.

Methods: 40 volunteers were enrolled in this monocentric,randomized,placebo‐controlled double‐blind study.Test areas on the back were irradiated with the 1.5 fold minimal erythema dose UV‐B. Subsequently, the test areas were treated under occlusion for 47 hours with a lipolotion containing 0.5% or 1.0% essential coriander oil. Hydrocortisone (1.0%) and betamethasone valerate (0.1%) in the vehicle served as positive controls.The vehicle was used as place‐bo.The effect of the test substances on the UV‐induced erythema was measured photometrically after 48 hours.Additionally,the skin tolerance of the test preparations was assessed on non‐irradiated skin.

Results: Compared to placebo, the lipolotion with 0.5% coriander oil significantly reduced the UV‐induced erythema, but it was not as effective as hydrocortisone. The skin tolerance of both coriander oil concentrations was excellent.

Conclusions: The lipolotion containing coriander oil displayed a mild antiinflammatory effect in this study. It could be useful in the concomitant treatment of inflammatory skin diseases.
COMPARATIVE PERFORMANCE OF PRECOOLING METHODS FOR THE STORAGE OF MANGOES (MANGIFERA INDICA L. CV. AMRAPALI)
Authors: RAVINDRA MENON REKHA , GOSWAMI T.K.
Published: March 2008

Precooling is an important postharvest unit operation for tropical fruits like mangoes because of its short postharvest life. Even though it is desirable that the precooling process be as fast as possible, the cooling should not result in any chilling injury to the fruits. Liquid nitrogen (LN2) is a cooling medium with ample potential for use in precooling operations because of its high cooling capacity and inertness of the vaporized nitrogen gas; however, its severe cold temperatures raise concerns on the possibility of chilling injury to the fruits. Hence, the present study was undertaken to compare a system where LN2 was employed in combination with mechanical refrigeration system as the cooling medium, in comparison to common precooling techniques for mangoes (cv. Amrapali) like hydrocooling and air cooling. The precooling performances were compared for the cooling rate, and cooling coefficient and fruit quality were assessed in terms of fruit firmness, color and chilling injury indices. The pH, total soluble solids and titratable acidity of the ripened fruits subjected to the different precooling techniques were also compared. The results of the study indicated that the LN2 system (LN2 flow rate: 20.5 kg/h; average gas temperature: –85C) had no adverse effect on the quality of the fruits, and improved the cooling coefficient of the air cooling process by 40%. Hence, judicious design of the system and control of exposure time would help in realizing the potential of LN2 in precooling operations for fruits, which would be practically useful in technologies like control atmosphere storage system in particular.

PRACTICAL APPLICATIONS

Liquid nitrogen (LN2) has ample potential as a refrigerant because of its excellent refrigeration capacity. The use of LN2 in cooling of horticultural produce is especially beneficial in techniques like controlled atmosphere storage, where it is desirable to have a lower oxygen concentration in the storage space. Because LN2 cooling has a high expansion ratio, during its vaporization, it also displaces the oxygen gas from the storage space. However, the use of LN2 as a refrigerant in precooling operations for fruits and vegetables is limited because of concerns of the very cold temperature of the cryogenic liquid resulting in chilling injury to the produce. The present study helps to address the same concerns and proves that if the system is so designed to avoid direct contact between LN2 and the fruits, its refrigerant potential can be successfully tapped.
Structure Function Analysis of Leishmania Sirtuin: An Ensemble of In Silico and Biochemical Studies
Authors: Kadam Rameshwar U. , Tavares Joana , M Kiran V. , Cordeiro Anabela , Ouaissi Ali , Roy Nilanjan
Published: March 2008

Novel anti‐leishmanial target LmSir2 has few subtle but prudent structural differences in ligand binding and catalytic domain as compared to its human counterpart. In silico screening and validation followed by in vitro deacetylation and cell killing assays described herein give a proof of concept for development of strategies exploiting such minor differences for screening libraries of small molecules to identify selective inhibitors.
Reconstructive cranioplasty using a porcine small intestinal submucosal graft
Authors: Sheahan D. E. , Gillian T. D.
Published: March 2008

A six‐year‐old border collie was presented with a solid mass on the dorsal cranium. Histological examination showed the mass to be a multilobular tumour of bone. A magnetic resonance imaging scan confirmed deformation of the dorsal cranium with compression of the cerebral hemispheres. A craniotomy was performed to excise the mass and overlying skin, resulting in a substantial deficit of calvarium and skin. A cranioplasty using a small intestinal submucosal (SIS) graft was performed to reconstruct the calvarial defect. A local myocutaneous advancement flap was elevated and positioned over the cranioplasty to close the skin deficit. The outcome of this reconstruction was aesthetic and functional. The small intestinal submucosal graft provided satisfactory mechanical support and was a suitable physical barrier in place of the calvarial bone. Histological examination of the small intestinal submucosal graft 128 days after implantation showed that the graft had been replaced by a dense network of collagenous tissue, with small focal areas of partially mineralised woven bone merging with a fibrocartilaginous matrix of the deeper margin. Histological examination also confirmed regrowth of the multilobular tumour of bone in the region of the small intestinal submucosal graft indicating that it is only a suitable implant if adequate surgical margins are obtained.
MicroRNAs (miRNAs) in Neurodegenerative Diseases
Authors: Nelson Peter T. , Wang Wang‐Xia , Rajeev Bernard W.
Published: March 2008

Aging‐related neurodegenerative diseases (NDs) are the culmination of many different genetic and environmental influences. Prior studies have shown that RNAs are pathologically altered during the inexorable course of some NDs. Recent evidence suggests that microRNAs (miRNAs) may be a contributing factor in neurodegeneration. miRNAs are brain‐enriched, small (∼22 nucleotides) non‐coding RNAs that participate in mRNA translational regulation. Although discovered in the framework of worm development, miRNAs are now appreciated to play a dynamic role in many mammalian brain‐related biochemical pathways, including neuroplasticity and stress responses. Research about miRNAs in the context of neurodegeneration is accumulating rapidly, and the goal of this review is to provide perspective for these new data that may be helpful to specialists in either field. An overview is provided about the normal functions for miRNAs, including some of the newer concepts related to the human brain. Recently published studies pertaining to the roles of miRNAs in NDs––including Alzheimer's disease, Parkinson's disease and triplet repeat disorders—are described. Finally, a discussion is included with theoretical syntheses and possible future directions in exploring the nexus between miRNA and ND research.
Development of Cu and Zn Isotope MC‐ICP‐MS Measurements: Application to Suspended Particulate Matter and Sediments from the Scheldt Estuary
Authors: Petit Jérôme C.J. , De Jong Jeroen , Chou Lei , Mattielli Nadine
Published: March 2008

The present study evaluates several critical issues related to precision and accuracy of Cu and Zn isotopic measurements with application to estuarine particulate materials. Calibration of reference materials (such as the IRMM 3702 Zn) against the JMC Zn and NIST Cu reference materials were performed in wet and/or dry plasma modes (Aridus I and DSN‐100) on a Nu Plasma MC‐ICP‐MS. Different mass bias correction methods were compared. More than 100 analyses of certified reference materials suggested that the sample‐calibrator bracketing correction and the empirical external normalisation methods provide the most reliable corrections, with long term external precisions of 0.06 and 0.07‰ (2SD), respectively. Investigation of the effect of variable analyte to spike concentration ratios on Zn and Cu isotopic determinations indicated that the accuracy of Cu measurements in dry plasma is very sensitive to the relative Cu and Zn concentrations, with deviations of δ65Cu from −0.4‰ (Cu/Zn = 4) to +0.4‰ (Cu/Zn = 0.2). A quantitative assessment (with instrumental mass bias corrections) of spectral and non‐spectral interferences (Ti, Cr, Co, Fe, Ca, Mg, Na) was performed. Titanium and Cr were the most severe interfering constituents, contributing to inaccuracies of −5.1‰ and +0.60‰ on δ68/64Zn, respectively (for 500 μg l−1 Cu and Zn standard solutions spiked with 1000 μg l−1 of Ti or Cr). Preliminary isotopic results were obtained on contrasting sediment matrices from the Scheldt estuary. Significant isotopic fractionation of zinc (from 0.21‰ to 1.13‰ for δ66Zn) and copper (from −0.38‰ to 0.23‰ for δ65Cu), suggest a control by physical mixing of continental and marine water masses, characterized by distinct Cu and Zn isotopic signatures. These results provide a stepping‐stone to further evaluate the use of Cu and Zn isotopes as biogeochemical tracers in estuarine environments.
Intraocular pressure control over 24 hours using travoprost and timolol fixed combination administered in the morning or evening in primary open‐angle and exfoliative glaucoma
Authors: Konstas Anastasios G. P. , Tsironi Sevasti , Vakalis Athanasios N. , Nasr Mayssa B. , Stewart Jeanette A. , Nelson Lindsay A. , Stewart William C.
Published: March 2008

Purpose:  To evaluate intraocular pressure (IOP) control over 24 hours using travoprost and timolol fixed combination (TTFC) administered in the morning or evening in primary open‐angle and exfoliative glaucoma.

Methods:  Patients were randomized to TTFC administered in either the morning or evening for 8 weeks. Previously treated patients underwent an untreated washout period of 4−6 weeks, after which baseline IOP was required to be > 25 mm Hg and < 38 mmHg (in two readings taken at 10.00 ± 1 hours). During the treatment period, IOP was measured at 10.00, 14.00, 18.00, 22.00, 02.00 and 06.00 hours. Patients were then treated with the opposite dosing regimen for 8 weeks and IOP measurements were repeated.

Results:  In 32 subjects who completed the study, the untreated baseline IOP following washout was 27.7 ± 3.5 mmHg. Both dosing regimens reduced IOP from baseline at each time‐point and throughout the 24‐hour diurnal curve (p < 0.0001). When treatments were compared directly, evening dosing (18.4 ± 3.3 mmHg) provided a statistically significant lower 24‐hour curve than morning dosing (19.2 ± 3.5 mmHg; p = 0.001). Evening dosing also resulted in a lower 24‐hour IOP fluctuation (3.8 ± 1.6 mmHg) than morning dosing (5.1 ± 1.6 mmHg; p = 0.0002) and lower peak IOP (p = 0.0003).

Conclusions:  Both morning and evening administration of TTFC provide effective 24‐hour IOP reduction, but evening dosing demonstrates better 24‐hour pressure control.
Quantitative vegetation‐environment relationships in west norwegian tall‐fern vegetation
Authors: Odland A. , Birks H. J. B. , Line J. M.
Published: March 2008

The aims of this paper are to detect floristic variation within different types of tall‐fern dominated vegetation and to interpret these patterns in terms of environmental variables. Numerical approaches have been applied to a large and varied vegetational data‐set with associated environmental data from stands dominated by Athyrium distentifolium, Thelypteris limbosperma, and Matteuccia struthiopteris in different parts of western Norway. The numerical procedures of two‐way indicator species analysis, simple discriminant functions, and canonical correspondence analysis have been used, and the strengths and weaknesses of these as tools in discerning vegetational‐environmental relationships are discussed. For each of the 96 quadrats investigated, 17 environmental variables were measured. The investigation shows that some of the observed differences in vegetational composition can be explained in terms of relatively simple soil and climatic variables measured for each quadrat. The ferns appear to be ecologically well separated. T. limbosperma‐dominaled stands are mainly characterised by low soil fertility, high January temperature, and high humidity. A. distentifolium‐dominated stands are associated with low winter temperatures, and M. struthiopteris‐dominated stands have high soil fertility and high summer temperatures.
Transcription Regulation Through Promoter-Proximal Pausing of RNA Polymerase II
Authors: Core Leighton J. , Lis John T.
Published: March 2008

Recent work has shown that the RNA polymerase II enzyme pauses at a promoter-proximal site of many genes in Drosophila and mammals. This rate-limiting step occurs after recruitment and initiation of RNA polymerase II at a gene promoter. This stage in early elongation appears to be an important and broadly used target of gene regulation.
Gene Regulation by Transcription Factors and MicroRNAs
Authors: Hobert Oliver
Published: March 2008

The properties of a cell are determined by the genetic information encoded in its genome. Understanding how such information is differentially and dynamically retrieved to define distinct cell types and cellular states is a major challenge facing molecular biology. Gene regulatory factors that control the expression of genomic information come in a variety of flavors, with transcription factors and microRNAs representing the most numerous gene regulatory factors in multicellular genomes. Here, I review common principles of transcription factor– and microRNA-mediated gene regulatory events and discuss conceptual differences in how these factors control gene expression.
Evolution of Eukaryotic Transcription Circuits
Authors: Tuch Brian B. , Li Hao , Johnson Alexander D.
Published: March 2008

The gradual modification of transcription circuits over evolutionary time scales is an important source of the diversity of life. Over the past decade, studies in animals have shown how seemingly small molecular changes in gene regulation can have large effects on morphology and physiology and how selective pressures can act on these changes. More recently, genome-wide studies, particularly those in single-cell yeasts, have uncovered evidence of extensive transcriptional rewiring, indicating that even closely related organisms regulate their genes using markedly different circuitries.
The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation
Authors: Li Long , Lok Shee-Mei , Yu I-Mei , Zhang Ying , Kuhn Richard J. , Chen Jue , Rossmann Michael G.
Published: March 2008

Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo–electron microscopy density of immature virus at neutral pH. The pr peptide β-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.
Determining Transition-State Geometries in Liquids Using 2D-IR
Authors: Cahoon James F. , Sawyer Karma R. , Schlegel Jacob P. , Harris Charles B.
Published: March 2008

Many properties of chemical reactions are determined by the transition state connecting reactant and product, yet it is difficult to directly obtain any information about these short-lived structures in liquids. We show that two-dimensional infrared (2D-IR) spectroscopy can provide direct information about transition states by tracking the transformation of vibrational modes as a molecule crossed a transition state. We successfully monitored a simple chemical reaction, the fluxional rearrangement of Fe(CO)
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, in which the exchange of axial and equatorial CO ligands causes an exchange of vibrational energy between the normal modes of the molecule. This energy transfer provides direct evidence regarding the time scale, transition state, and mechanism of the reaction.