bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis
Authors: Shvedova A. A. , Kisin E. , Murray A. R. , Johnson V. J. , Gorelik O. , Arepalli S. , Hubbs A. F. , Mercer R. R. , Keohavong P. , Sussman N. , Jin J. , Yin J. , Stone S. , Chen B. T. , Deye G. , Maynard A. , Castranova V. , Baron P. A. , Kagan V. E.
Published: July 2008

Nanomaterials are frontier technological products used in different manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNT) are finding numerous applications in electronics, aerospace devices, computers, and chemical, polymer, and pharmaceutical industries. SWCNT are relatively recently discovered members of the carbon allotropes that are similar in structure to fullerenes and graphite. Previously, we ( 47 ) have reported that pharyngeal aspiration of purified SWCNT by C57BL/6 mice caused dose-dependent granulomatous pneumonia, oxidative stress, acute inflammatory/cytokine responses, fibrosis, and decrease in pulmonary function. To avoid potential artifactual effects due to instillation/agglomeration associated with SWCNT, we conducted inhalation exposures using stable and uniform SWCNT dispersions obtained by a newly developed aerosolization technique ( 2 ). The inhalation of nonpurified SWCNT (iron content of 17.7% by weight) at 5 mg/m3, 5 h/day for 4 days was compared with pharyngeal aspiration of varying doses (5–20 μg per mouse) of the same SWCNT. The chain of pathological events in both exposure routes was realized through synergized interactions of early inflammatory response and oxidative stress culminating in the development of multifocal granulomatous pneumonia and interstitial fibrosis. SWCNT inhalation was more effective than aspiration in causing inflammatory response, oxidative stress, collagen deposition, and fibrosis as well as mutations of K- ras gene locus in the lung of C57BL/6 mice.
Flagellin-stimulated Cl− secretion and innate immune responses in airway epithelia: role for p38
Authors: Illek Beate , Fu Zhu , Schwarzer Christian , Banzon Tina , Jalickee Stephen , Miller Sheldon S. , Machen Terry E.
Published: July 2008

Activation of an innate immune response in airway epithelia by the human pathogen Pseudomonas aeruginosa requires bacterial expression of flagellin. Addition of flagellin (10−7 M) to airway epithelial cell monolayers (Calu-3, airway serous cell-like) increased Cl− secretion ( ICl) beginning after 3–10 min, reaching a plateau after 20–45 min at Δ ICl = 15–50 μA/cm2. Similar, although 10-fold smaller, responses were observed in well-differentiated bronchial epithelial cultures. Flagellin stimulated ICl in the presence of maximally stimulating doses of the purinergic agonist ATP, but had no effects following forskolin. IL-1β (produced by both epithelia and neutrophils during infections) stimulated ICl similar to flagellin. Flagellin-, IL-1β-, ATP-, and forskolin-stimulated ICl were inhibited by cystic fibrosis transmembrane conductance regulator (CFTR) blockers GlyH101, CFTRinh172, and glibenclamide. Neither flagellin nor IL-1β altered transepithelial fluxes of membrane-impermeant dextran (10 kDa) or lucifer yellow (mol wt = 457), but both activated p38, NF-κB, and IL-8 secretion. Blockers of p38 (SB-202190 and SB-203580) reduced flagellin- and IL-1β-stimulated ICl by 33–50% but had smaller effects on IL-8 and NF-κB. It is concluded that: 1) flagellin and IL-1β activated p38, NF-κB, IL-8, and CFTR-dependent anion secretion without altering tight junction permeability; 2) p38 played a role in regulating ICl and IL-8 but not NF-κB; and 3) p38 was more important in flagellin- than IL-1β-stimulated responses. During P. aeruginosa infections, flagellin and IL-1β are expected to increase CFTR-dependent ion and fluid flow into and bacterial clearance from the airways. In cystic fibrosis, the secretory response would be absent, but activation of p38, NF-κB, and IL-8 would persist.
Neuromechanical control of the isolated upper airway of mice
Authors: Liu Audrey , Pichard Luis , Schneider Hartmut , Patil Susheel P. , Smith Philip L. , Polotsky Vsevolod , Schwartz Alan R.
Published: July 2008

We characterized the passive structural and active neuromuscular control of pharyngeal collapsibility in mice and hypothesized that pharyngeal collapsibility, which is elevated by anatomic loads, is reduced by active neuromuscular responses to airflow obstruction. To address this hypothesis, we examined the dynamic control of upper airway function in the isolated upper airway of anesthetized C57BL/6J mice. Pressures were lowered downstream and upstream to the upper airway to induce inspiratory airflow limitation and critical closure of the upper airway, respectively. After hyperventilating the mice to central apnea, we demonstrated a critical closing pressure (Pcrit) of −6.2 ± 1.1 cmH2O under passive conditions that was unaltered by the state of lung inflation. After a period of central apnea, lower airway occlusion led to progressive increases in phasic genioglossal electromyographic activity (EMGGG), and in maximal inspiratory airflow (V̇imax) through the isolated upper airway, particularly as the nasal pressure was lowered toward the passive Pcrit level. Moreover, the active Pcrit fell during inspiration by 8.2 ± 1.4 cmH2O relative to the passive condition ( P < 0.0005). We conclude that upper airway collapsibility (passive Pcrit) in the C57BL/6J mouse is similar to that in the anesthetized canine, feline, and sleeping human upper airway, and that collapsibility falls markedly under active conditions. Active EMGGG and V̇imax responses dissociated at higher upstream pressure levels, suggesting a decrease in the mechanical efficiency of upper airway dilators. Our findings in mice imply that anatomic and neuromuscular factors interact dynamically to modulate upper airway function, and provide a novel approach to modeling the impact of genetic and environmental factors in inbred murine strains.
Double-Balloon Enteroscopy to Remove a Strangulated Enteroclysis Catheter from the Small Bowel
Authors: Moreels Tom G. , Op de Beeck Bart , Pelckmans Paul A.
Published: July 2008

We present the case of a 77-year-old male who was referred for magnetic resonance (MR) enteroclysis because of small bowel subobstruction. To optimise small bowel distention during MR, a nasojejunal balloon catheter was placed to perfuse iso-osmotic water solution into the small bowel. However, after deflation of the balloon, the catheter could not be removed by gentle traction. Subsequently, computed tomography (CT) of the abdomen revealed that the catheter was strangulated deep in the jejunum and traction resulted in painful backward intussusception of the small bowel. In order to avoid surgical intervention, we decided to perform urgent proximal double-balloon enteroscopy to remove the enteroclysis catheter. Under fluoroscopic guidance, the enteroscope was introduced into the jejunum until the tip of the enteroscope reached the tip of the catheter. By straightening the enteroscope, the catheter could then be retracted from the jejunum, using the enteroscope as a guide wire along the catheter. Urgent surgical intervention was avoided and the patient completely recovered the same day.
Clinical Heterogeneity of Pseudohypoparathyroidism: From Hyper- to Hypocalcemia
Authors: Shalitin Shlomit , Davidovits Miriam , Lazar Liora , Weintrob Naomi
Published: July 2008

Pseudohypoparathyroidism (PHP) is a rare inherited syndrome characterized by parathyroid hormone (PTH) resistance and is frequently associated with Albright’s hereditary osteodystrophy and resistance to other cAMP-mediated hormones. The usual neonatal presentation is mild primary hypothyroidism secondary to resistance to thyroid-stimulating hormone; hypocalcemia usually develops after age 3–5 years. This work describes the diversity in the clinical expression and course of PHP, with emphasis on calcium levels by age and treatment, in 8 children under long-term follow-up at our pediatric tertiary center. The calcium levels at presentation ranged from transient neonatal hypocalcemia to infantile hypercalcemia to childhood/adolescence hypocalcemia. Interestingly, relative hypocalciuria at diagnosis and during therapy, in the presence of renal PTH resistance, was the rule. These findings indicate that transient neonatal hypocalcemia associated with other clinical features or a family history of PHP may be a flag for clinicians to screen for PTH resistance later in life. In addition, PTH resistance may be missed by surveying calcium levels only; thus the PTH levels have to be checked as well. In addition, the recommendation for patients with hypoparathyroidism that strict low-normal calcium levels be maintained during therapy in order to prevent hypercalciuria is probably not applicable in PHP.
Abnormal Growth in Noonan Syndrome: Genetic and Endocrine Features and Optimal Treatment
Authors: Padidela Raja , Camacho-Hübner Cecilia , Attie Kenneth M. , Savage Martin O.
Published: July 2008

Noonan syndrome (NS) is a phenotypically heterogeneous syndrome which is frequently associated with short stature. Recent genetic investigations have identified mutations in five genes, namely PTPN11, KRAS, SOS1, NF1 and RAF1 in patients with the NS phenotype. PTPN11 is the commonest, being present in approximately 50% of cases. The degree of short stature in children does not associate closely with the presence of mutations, however some PTPN11-positive patients have decreased GH-dependent growth factors consistent with mild GH insensitivity. GH therapy, using doses similar to those approved for Turner syndrome (TS), induced short-term increases in height velocity over 1–3 years, and may improve final adult height with longer-term treatment.
Growth Hormone Treatment Completely Normalizes Adult Height and Improves Body Composition in Prader-Willi Syndrome: Experience from KIGS (Pfizer International Growth Database)
Authors: Lindgren A.C. , Lindberg A.
Published: July 2008

Background: Abnormal body composition, with low muscle mass and increased fat mass, as well as short adult stature are common features in Prader-Willi syndrome (PWS), as in growth hormone (GH) deficiency. Methods: We followed a cohort of 22 genetically verified patients with PWS from the start of GH (Genotropin®) treatment at the median age of 6.9 years (4.9–11.3) to near-adult height at 18.1 years (16.4–21.2). The patients were treated with a median GH dose of 0.03 mg/kg/day (0.02–0.03) for a median duration of 10.2 years (6.9–11.5). Results: All patients reached near-adult height within midparental height median –0.5 SDS (–1.4 to 0.7) and 0.9 SDS (0.1–1.9) for girls and boys, respectively. The body composition improved but did not normalize. Only 7 of the 22 patients were reported to be in puberty. None of the patients were reported to be on sex hormone substitution which might contribute to not reaching a normal body composition. No serious side effects were reported when the caloric intake was controlled to maintain an appropriate body weight. Conclusion: GH treatment in children with Prader-Wili syndrome normalizes adult height and improves body composition.
Outcomes of Stage 3–5 Chronic Kidney Disease before End-Stage Renal Disease at a Single Center in Taiwan
Authors: Chiu Yen-Ling , Chien Kuo-Liong , Lin Shuei-Liong , Chen Yung-Ming , Tsai Tun-Jun , Wu Kwan-Dun
Published: July 2008

Background: Taiwan has the highest incidence of end-stage renal disease (ESRD) in the world, but little is known about the outcomes of patients with chronic kidney disease (CKD) before ESRD in Taiwan. This study investigated the rate of renal progression and predictors for ESRD and death in a prospective cohort of patients under usual nephrologic care at a single center. Methods: A total of 433 patients at CKD stage 3–5 short of dialysis were recruited from nephrology clinics. Patients were monitored for up to 36 months or until ESRD, death or loss to follow-up. Glomerular filtration rates (GFR) were calculated by the Modification of Diet in Renal Disease abbreviated formula. Results: At baseline, mean age was 65.6 years, 61.7% were male, 33.3% were diabetic and 29.1% had cardiovascular diseases (CVD). At the end of follow-up, 123 patients (28.4%) had advanced to ESRD and 41 (9.5%) had died. Mean annual declines in GFR were 2.24, 4.22, and 3.23 ml/min/1.73 m2 for stages 3, 4, and 5, respectively. By Cox regression model, patients with CVD, lower BMI and higher systolic BP were more likely to develop ESRD. Older patients with CVD and lower systolic BP were more likely to die. Conclusion: In this CKD cohort, patients were more likely to develop ESRD than cardiovascular death. The rate of GFR decline and predictors of ESRD were comparable to those reported in Western countries. Thus, the high incidence of ESRD in Taiwan may be attributed, at least in part, to lower cardiovascular mortality.
Microscopic Hematuria and Diabetic Glomerulosclerosis – Clinicopathological Analysis of Type 2 Diabetic Patients Associated with Overt Proteinuria
Authors: Akimoto Tetsu , Ito Chiharu , Saito Osamu , Takahashi Hideaki , Takeda Shinichi , Ando Yasuhiro , Muto Shigeaki , Kusano Eiji
Published: July 2008

Background/Aims: The information available concerning the qualitative and quantitative clinical variables in cases with pathologically defined diabetic glomerulosclerosis (DGs) has been insufficient so far. In addition, the prevalence and composition of nondiabetic renal disease (NDRD) among proteinuric diabetics still remain to be delineated. Methods: The glomerular pathology, clinical correlates, and the prevalence of NDRD were retrospectively analyzed in 50 type 2 proteinuric diabetics who underwent a renal biopsy between 1990 and 2006. The patients were divided into two groups according to clinical and pathological features. Thereafter, the diagnostic contribution of the laboratory and clinical variables that were significant between the two groups were determined by logistic regression analysis. Results: There were 34 cases with pure DGs and 15 cases (30%) had NDRD with or without DGs. Although the difference in the prevalence of microscopic hematuria between these two groups was significant, it was no longer statistically significant when the patients were limited to nephrotic cases. We identified 14 hematuric cases with pathologically defined DGs, and they all had a significantly lower renal function than nonhematuric patients with DGs. The prevalence of nephrotic syndrome and retinopathy were significantly higher in the cases with hematuric DGs than in the cases with nonhematuric DGs. Based on a logistic regression analysis, the presence of nephrotic syndrome and known duration of diabetes were identified to be significant predictors for hematuria with DGs. Conclusions: Our observations suggest that the presence of hematuria may be a common feature for DGs with nephrotic syndrome.
Validation of the Toronto Formula to Predict Progression in IgA Nephropathy
Authors: Mackinnon Bruce , Fraser Emily P. , Cattran Daniel C. , Fox Jonathan G. , Geddes Colin C.
Published: July 2008

Background/Aim: Predicting outcome in IgA nephropathy (IgAN) is difficult. The Toronto formula uses average mean arterial blood pressure and proteinuria during the first 2 years of follow-up (MAP0–2, UP0–2) to predict the subsequent slope of estimated creatinine clearance (eCrCl). We aimed to validate the Toronto formula in a Scottish cohort and test the hypothesis that adding the slope eCrCl over the first 2 years of follow-up (eCrCl0–2) would improve the predictive utility of a similar multivariate model. Methods: Adultsfrom our centre with biopsy-proven IgAN (n = 169) and at least 2 years of follow-up (median 129.4 months) were included. Clinical data were used to calculate MAP0–2,UP0–2,slope eCrCl0–2 and predicted slope eCrCl (using the Toronto formula). Results: There was a significant correlation between predicted slope eCrCl using the Toronto formula and actual slope eCrCl (R2 = 0.21; p < 0.001). The formula predicted the actual rate of progression to within 4 ml/min/year in 75% of subjects, predicting patients with the most rapid deterioration with the greatest accuracy. The multivariate linear regression model created in our cohort using the same independent variables as the Toronto formula to predict the overall slope eCrCl had an R2 of 0.22 (p < 0.001) and adding the slope CrCl0–2 only increased this to 0.25. Conclusions: The Toronto formula is valid in a European population and useful for identifying patients at high risk of future deterioration in renal function. Adding slope eCrCl0–2 to a predictive model containing MAP0–2, andUP0–2 does not appear to improve prediction of the overall slope of eCrCl.
Characteristics of Pruritus in Children on Peritoneal Dialysis
Authors: Senturk Nilgun , Ozkaya Ozan , Aytekin Sevil , Bek Kenan , Açıkgöz Yonca , Aydin Fatma , Bek Yuksel , Turanli Ahmet Yaşar
Published: July 2008

Background/Aims: The aim of this study was to evaluate the characteristics of pruritus in pediatric patients undergoing peritoneal dialysis. Patients and Methods: Twenty-seven patients (16 females, 11 males), aged between 5 and 18 years, were evaluated for the presence, intensity, onset, activation time, duration, characteristics, localization and increasing factors for pruritus. The intensity of pruritus was scored using a visual analog scale. Patients were grouped according to the existence of pruritus and other clinical and laboratory parameters (dialysis duration, dialysis adequacy, hemoglobin, blood urea nitrogen, creatinine, Ca, P, albumin, bicarbonate, parathyroid hormone (PTH), C-reactive protein (CRP)) were compared between the 2 groups. Results: The mean age of patients was 11.85 ± 4.4 years. There were 21 patients (77.7%) without pruritus and 6 patients with pruritus (22.2%). Serum P, PTH, CRP levels and Ca×P product were significantly higher in patients with pruritus compared to patients without pruritus (p = 0.027, p = 0.03, p < 0.026, p = 0.031, respectively). In a stepwise logistic regression model, P (p = 0.01), Ca×P product (p = 0.09), PTH (p = 0.03) and CRP (p = 0.02) were independently associated with pruritus. Conclusion: Our study indicates that pruritus remains a common but not troublesome symptom in children on peritoneal dialysis. Higher serum P, Ca×P product, PTH and CRP concentrations appear to be important factors associated with uremic pruritus in this group.
Personality Traits Predict Treatment Outcome in Alcohol-Dependent Patients
Authors: Müller Sandra E. , Weijers Heinz-Gerd , Böning Jobst , Wiesbeck Gerhard A.
Published: July 2008

Personality traits are important individual characteristics modifying responses to therapy in various diseases. The aim of this study was to identify personality traits that may predict treatment outcome in alcohol-dependent patients. The present analysis was based on a total of 146 alcohol-dependent patients (109 male, 37 female) after detoxification. The variable of interest was treatment outcome (abstinence/relapse) after a 1-year follow-up. To identify personality traits as predictors of treatment outcome, 5 personality questionnaires (NEO 5-Factor Inventory, Temperament and Character Inventory, Eysenck Personality Questionnaire, Eysenck Impulsiveness-Venturesomeness-Empathy Scale and Sensation-Seeking Scale) were applied. Data analysis was performed by using a classification and regression tree analysis (CART; a nonparametric technique for data with a complex structure) in order to find a decision rule to predict treatment outcome from personality traits. The CART model identified psychoticism and persistence as the 2 most relevant discriminatory parameters, of which psychoticism was used as the first node in the model, classifying 64% of the patients correctly as relapsed and 12% correctly as abstinent. In addition, the risk of relapse was even higher in patients with a substantial score in psychoticism and a low score in persistence. When comparing relapsed and abstinent patients, further variables, such as scores for novelty seeking (20.9 ± 5.5 vs. 18.5 ± 5.9) and impulsiveness (8.4 ± 3 vs. 7.2 ± 3.5), showed significance. In addition, relapsed patients lived alone more often than abstinent patients (52 vs. 25%, p = 0.004). In conclusion, this analysis demonstrated that specific personality characteristics, namely psychoticism and persistence, are usable predictors for the risk of relapse in alcohol-dependent patients.
Dance Clubbing on MDMA and during Abstinence from Ecstasy/MDMA: Prospective Neuroendocrine and Psychobiological Changes
Authors: Parrott A.C. , Lock J. , Conner A.C. , Kissling C. , Thome J.
Published: July 2008

Background/Aims: The present study is the first to prospectively compare a group of recreational Ecstasy users when dance clubbing on 3,4-methylenedioxymethamphetamine (MDMA) and when clubbing during abstinence from Ecstasy/MDMA. Methods: Twelve normal healthy volunteers (mean age = 23.2 years) were assessed at a Saturday night dance club under self-administered MDMA. On the other weekend they went to the same dance club without taking MDMA (order counterbalanced). Both conditions involved 5 test sessions conducted at similar times: pre-drug baseline, 1 h post-drug clubbing, 2.5 h post-drug clubbing, and 2 and 4 days later. The assessments included body and ambient temperature, physical activity (pedometer), as well as self-ratings for mood state, physical activity, thermal comfort and thirst. Saliva samples were analyzed for MDMA, cortisol and testosterone. Results: The cortisol levels increased significantly by 800% when dance clubbing on MDMA, while testosterone increased significantly by 75%; neither neuroendocrine measure was altered during abstinence. Saliva analyses confirmed the presence of MDMA when dancing on Ecstasy and its absence when dancing off Ecstasy. The pedometer values and self-rated levels of dancing were similar at both weekends. Hot and cold flushes and feeling hot increased significantly under MDMA. The mean body temperature did not change significantly, although there was a borderline trend for increased values after MDMA. Feelings of happiness and excitement increased under MDMA, although they were not significantly greater than when clubbing during abstinence. Conclusions: Neurohormonal release may be an important part of the acute MDMA experience. The large cortisol increase provides further data on the bioenergetic stress model of recreational Ecstasy/MDMA.
Activation of the Prefrontal Cortex in Working Memory and Interference Resolution Processes Assessed with Near-Infrared Spectroscopy
Authors: Schreppel Theresa , Egetemeir Johanna , Schecklmann Martin , Plichta Michael M. , Pauli Paul , Ellgring Heiner , Fallgatter Andreas J. , Herrmann Martin J.
Published: July 2008

Background/Aims: The present study investigated cortical correlates of top-down processes in visual-object working memory with multi-channel near-infrared spectroscopy. Methods: The activity of the prefrontal cortex (PFC) was investigated while performing an n-back task with sequentially presented task-relevant and task-irrelevant faces. The activation patterns in the PFC associated with working memory and interference resolution were examined in 20 healthy adults. Results: We found a bilateral enhancement of oxygenated haemoglobin in the lateral PFC for remembering relevant faces and in the right lateral PFC for ignoring irrelevant faces. Oxygenation for relevant and irrelevant faces did not differ significantly, indicating that memory pro- cesses and interference resolution were interdependent functions, which were subserved by comparable prefrontal regions. Conclusion: This supports the notion that the prefrontal activity during working memory tasks reflects not only maintenance processes but also attentional monitoring and selection processes.
Fluoroscopic Registration and Localization for Image-Guided Cranial Neurosurgical Procedures: A Feasibility Study
Authors: Henderson Jaimie M. , Hill Bruce C.
Published: July 2008

Background/Aims: Frameless image-guided neurosurgical techniques can achieve high degrees of accuracy when skull-implanted fiducials are used for registration. However, fiducial placement is invasive and uncomfortable for patients. Development of a noninvasive registration method for accurate image-guided functional neurosurgery such as deep brain stimulator placement would therefore be highly desirable. We performed an initial series of experiments using a commercially available fluoroscopic registration package to assess the feasibility of this approach for image-guided functional neurosurgery. We also evaluated the accuracy of landmark placement in the fluoroscopic images using the navigational capability of the software. Methods: A fluoroscopic target was created by etching a hexagonal pattern of 1-mm diameter holes on a copper-clad board (0.0254-mm copper cladding on fiberglass). The target was then mounted in a plastic phantom skull, oriented in a mid-sagittal plane. Five implantable fiducial markers were screwed into the phantom in positions which approximated those commonly used clinically. 1.25-mm CT slices were obtained, uploaded to a Stealthstation neuronavigational system and were displayed using the Fluoromerge software package. Lateral and AP images were generated with 2 approximately orthogonal views of the phantom. Registration was carried out both fluoroscopically and using the implanted fiducials. Targets were localized using both methods and the localization errors recorded. Results: Localization error was less than 1 mm using fiducial-based registration, and between 0.8 and 2.9 mm using fluoroscopic registration. Error varied depending on location within the volume of the phantom. Conclusion: Initial experiments show that fluoroscopic registration is feasible for the performance of frameless functional neurosurgical procedures, although accuracy is still insufficient. Intraoperative verification of lead location was also shown to be feasible in one case.
Influence of Microparticles on the Homogeneity of Distribution of Topically Applied Substances
Authors: Lademann J. , Richter H. , Golz K. , Zastrow L. , Sterry W. , Patzelt A.
Published: July 2008

The uppermost layer of the skin – the stratum corneum – represents a barrier of the human organism to the environment. It prevents the penetration of substances coming into contact with the skin into the human body. In cases of strong exposure, the skin has to be protected additionally by barrier creams. In the present study, the influence of microparticles on the homogeneity of distribution of the protection cream on the skin was investigated by laser scanning microscopy. The protection cream contained antioxidant substances with a high radical protection factor for the prevention of palmar-plantar erythema often occurring during chemotherapy with doxorubicin. In this case, the chemotherapeutic substance comes out with the sweat onto the skin surface, from which it penetrates into the skin like topically applied. It was found that particles increase the homogeneity of distribution and, thus, the protection efficacy is significantly increased. The obtained results are important, not only for the prevention of side effects during chemotherapy, but also for the development and application of sunscreens and all types of topically applied drugs and cosmetics, which should form an efficient protection film on the skin.
Modelling the Bilateral Symmetry of Caries Incidence
Authors: Burnside G. , Pine C.M. , Williamson P.R.
Published: July 2008

Background/Aims: Past caries experience has been shown to be the best predictor of the development of caries in the future, and clinical observations suggest that caries develops symmetrically in similar teeth on each side of the mouth. This study investigates whether caries on a given surface can be used as a predictor of future caries on the corresponding surface on the other side of the mouth. Methods: The data come from a 3-year trial examining the caries-preventive efficacy of chlorhexidine varnish on adolescents. A logistic multilevel model was fitted with 3 levels; participant, tooth and surface. The outcome variable was the development of caries into enamel or dentine, after 3 years. Covariates were tooth position, the caries status of the contralateral surface at baseline, the caries status of the corresponding surface in the opposing jaw at baseline, the caries status of adjacent teeth and the total number of decayed, missing, filled surfaces at baseline. Results: The effect of caries at baseline on the contralateral surface was highly significant (odds ratio = 4.80, 95% CI = 4.38–5.38). The effect of caries at baseline on the corresponding surface in the opposing jaw was also significant, but smaller in magnitude (odds ratio = 1.66, 95% CI = 1.49–1.83). Conclusion: Multilevel modelling provides a clinically useful method of estimating the probability of a surface developing caries over a period of time, based on the caries status of the contralateral surface and the corresponding surface in the opposing jaw, while controlling for the natural clustering in tooth surface data.
Fluoride Uptake and Remineralisation of Enamel Lesions after Weekly Application of Differently Concentrated Fluoride Gels
Authors: Altenburger M.J. , Schirrmeister J.F. , Wrbas K.-T. , Klasser M. , Hellwig E.
Published: July 2008

There is only little information on the remineralising capability of regularly applied highly concentrated fluoride gels. The aim of this in situ study was to test the hypothesis that weekly application of a 1.25% fluoride gel results in a significantly higher fluoride uptake and a significantly higher mineral gain compared to a 0.5% fluoride or a placebo gel, respectively. Thirty-six subjects were included in this double-blind, three-way, crossover, placebo-controlled study and randomly assigned to a treatment scheme. Two weeks before the study, between treatment periods as well as during the study periods, subjects were instructed to abstain from any fluoride source other than the study medication. At the beginning of each of three 4-week periods specimen holders, each containing 10 bovine enamel slabs, were placed in the subjects’ mouths. During the experimental periods the volunteers brushed the specimens with placebo gel, 0.5% fluoride gel or 1.25% fluoride gel once a week. Fluoride uptake was significantly higher after treatment with the 1.25% fluoride gel than after treatment with the 0.5% fluoride gel (p = 0.007) or the placebo gel (p < 0.001). Treatment with 0.5% fluoride gel led to a significantly higher fluoride uptake compared to placebo treatment (p < 0.001). Changes in mineral gain and lesion depth were not statistically significantly different between the three groups. Under the present experimental conditions repeated application of highly concentrated fluoride gels did not promote remineralisation significantly.
Association of Serum α-Tocopherol, Retinol and Ascorbic Acid with the Risk of Cataract Development
Authors: Nourmohammadi I. , Modarress M. , Khanaki K. , Shaabani M.
Published: July 2008

Objective: Several studies on cataract have suggested that antioxidant micronutrients such as α-tocopherol, retinol and ascorbic acid may help to protect against cataractogenesis. Our objective was to determine the serum concentration of these antioxidant vitamins in subjects with cataract to see if there is any correlation between the levels of essential vitamins and the development of cataract. Methods: The study was performed on a total of 88 patients and healthy controls who were given physical examinations that included a complete eye examination. Ascorbic acid was measured in serum with UV/Vis spectrophotometry, and fat-soluble vitamins were measured in serum by high-performance liquid chromatography according to previously published methods. Results: The mean serum concentration of α-tocopherol in patients (9.16 ± 2.53.µg/ml) with cataract was lower than in the control group (p < 0.001). Patients had a moderately lower ascorbic acid concentration than the control group, which was not statistically significant. The subjects’ serum retinol levels were similar to control group levels and not statistically significant. Conclusion: While this is a small-scale case study it can nonetheless be viewed as presenting support to help narrow the possibility that antioxidative agents may play a role in delaying cataract formation.
fMRI Activation Changes during Successful Episodic Memory Encoding and Recognition in Amnestic Mild Cognitive Impairment Relative to Cognitively Healthy Older Adults
Authors: Trivedi Mehul A. , Murphy Christopher M. , Goetz Celine , Shah Raj C. , Gabrieli John D.E. , Whitfield-Gabrieli Susan , Turner David A. , Stebbins Glenn T.
Published: July 2008

Background/Aims: Previous functional MRI studies in individuals with amnestic mild cognitive impairment (AMCI), a putative, prodromal form of Alzheimer’s disease, reveal substantial regional changes in brain activation during episodic memory function. Methods: Functional MRI was applied to examine changes in brain activation during different stages of episodic memory function using a subsequent memory task in individuals with AMCI relative to older normal controls. Results: We found that the AMCI group displayed greater activation in the right hippocampus but less activation in the frontal cortex relative to the older normal control group during intentional encoding of items that were subsequently recognized. We observed nearly the opposite pattern of results for successful recognition. The AMCI group displayed less activation in the medial temporal cortex but greater activation in the frontal cortex. In addition, the AMCI group showed reduced activation in the medial temporal and frontal cortices during incidental encoding of novel information during recognition. Conclusion: The results of the present study suggest that brain activation differences in individuals with AMCI are modulated by the stage of episodic memory examined (i.e. intentional vs. incidental encoding vs. recognition). These observations may help to clarify some of the conflicting findings regarding brain activation changes in AMCI.
In vitro Antiviral Activity of Distamycin A against Clinical Isolates of Herpes Simplex Virus 1 and 2 from Transplanted Patients
Authors: Matteoli Barbara , Bernardini Sara , Iuliano Rodolfo , Parenti Silvia , Freer Giulia , Broccolo Francesco , Baggiani Angelo , Subissi Alessandro , Arcamone Federico , Ceccherini-Nelli Luca
Published: July 2008

Objective(s): Herpes simplex virus (HSV) infections in immunocompromised individuals may require prolonged antiviral therapy resulting in the emergence of viral strains resistant to the currently employed antiviral drugs. Distamycin A (DA), a basic antibiotic belonging to the lexitropsin DNA minor groove binding drugs, exhibits antiviral properties. In this study we evaluated the in vitro cytotoxicity and antiviral activity of DA against HSV type 1 and HSV type 2 clinical isolates from transplanted patients and compared them with those of acyclovir (ACV) in search of alternative antiviral drugs. Methods: Viral detection and typing was performed by multiplex PCR and immunofluorescence assay; the in vitro cytotoxicity of DA and the antiviral activity of ACV and DA was evaluated respectively by neutral red uptake assay and plaque reduction assay for HSV2 isolates and fluorescence reduction assay for HSV1 isolates. Results: Tissue culture 50% cytotoxic concentration of DA was 58 µM. Tissue culture 50% inhibitory concentration values ranged from 0.16 to 7.4 µM for the ACV-sensitive and from 5.4 to 32 µM for the ACV-resistant viral strains. Conclusions: In spite of the lower activity against ACV-resistant strains, DA may be used as an antiherpetic drug.
Dermoscopic Findings of Pilomatricomas
Authors: Zaballos Pedro , Llambrich Álex , Puig Susana , Malvehy Josep
Published: July 2008

Background: To the best of our knowledge, no specific dermoscopic criteria have been described in the medical literature for the diagnosis of pilomatricomas. Objectives: To evaluate the morphological findings of pilomatricomas under dermoscopic observation. Material and Methods: Dermoscopic examination (using the Dermlite Foto; 3Gen, LLC, Dana Point, Calif., USA) of 10 patients with pilomatricomas was performed to evaluate specific dermoscopic criteria and patterns. Results: The most frequently occurring dermoscopic features were found to be: irregular white structures (80%) and white streaks (70%); vascular structures in all lesions (reddish homogeneous area in 90%, hairpin vessels in 70%, linear-irregular vessels in 70% and dotted vessels in 40%); ulceration (60%), and structureless gray-blue areas in 20% of cases. The results of our study reveal that the absence of specific dermoscopic criteria for other skin tumors and the presence of irregular white structures and polymorphous/atypical vessels is the most frequent dermoscopic pattern in pilomatricomas. Conclusions: Dermoscopy may be a useful tool for improving the recognition of pilomatricomas. However, dermoscopy does not assure 100% diagnostic accuracy and pilomatricomas may represent in some cases, above all in elderly patients, a dermoscopic pitfall, being difficult to differentiate dermoscopically from other lesions, such as melanoma or basal cell carcinoma.
Relationship between Serum Pre-B Cell Colony-Enhancing Factor/Visfatin and Atherosclerotic Parameters in Chronic Hemodialysis Patients
Authors: Kato Akihiko , Odamaki Mari , Ishida Junko , Hishida Akira
Published: July 2008

Pre-B cell colony-enhancing factor (PBEF)/visfatin is produced by adipose tissue, skeletal muscle, bone marrow, the liver and lymphocytes. Although serum PBEF/visfatin is related to the pathogenesis of atherosclerosis, and its level is elevated in patients with chronic kidney disease, it remains unclear whether increased PBEF/visfatin is associated with atherosclerotic parameters in hemodialysis (HD) patients. In this study, we measured serum PBEF/visfatin in 68 chronic HD patients (age 66 ± 14 years, time on HD 76 ± 76 months, 41 males, 27 females) and examined the association of serum PBEF/visfatin with serum asymmetric dimethylarginine, arteriosclerotic parameters such as pulse wave velocity, ankle brachial pressure index and the percent of abdominal aortic wall calcification in a cross-sectional fashion. Serum PBEF/visfatin was significantly correlated with time on HD (r = 0.29, p = 0.02), but not with age, gender and diabetes. There was no association between PBEF/visfatin and body mass index, abdominal visceral and subcutaneous fat mass area, and total adiponectin. Serum PBEF/visfatin was significantly positively correlated with log-transformed highly sensitive C-reactive protein (r = 0.26, p < 0.05) but negatively with serum albumin (r = –0.33, p < 0.01). In contrast, there was no association between serum PBEF/visfatin and asymmetric dimethylarginine, aortic pulse wave velocity, brachial ankle pressure index and percent of abdominal aortic wall calcification. It follows from these findings that serum PBEF/visfatin may reflect the inflammatory status rather than atherosclerotic changes in chronic HD patients.
Nephrogenic Systemic Fibrosis
Authors: Nainani Neha , Panesar Mandip
Published: July 2008

Nephrogenic systemic fibrosis is a recently diagnosed disease that occurs in patients with chronic kidney disease and acute renal failure. The patients develop skin thickening and fibrosis which is usually symmetrical, and typically of the upper and lower extremities. In some cases the progression is rapid leading to joint contractures confining the patient to a wheelchair. Systemic involvement may occur, leading to cardiomyopathy, pulmonary fibrosis, pulmonary hypertension, diaphragmatic paralysis and in severe cases death. The pathophysiology of the disease still remains unclear, but recent studies have demonstrated gadolinium deposits in tissues of patients diagnosed with nephrogenic systemic fibrosis. The prevalence of nephrogenic systemic fibrosis after exposure to gadolinium has been reported to be up to 12% in CKD stage 5 patients after a single exposure. No single treatment has been shown to be effective, although there are some patients shown to have improvement of their clinical symptoms with regaining of renal function especially after transplantation. In this article we review the current literature of this disease.
Gender-Specific Differences in the Kinetics of Nonfasting TRL, IDL, and LDL Apolipoprotein B-100 in Men and Premenopausal Women
Authors: Matthan Nirupa R. , Jalbert Susan M. , Barrett P. Hugh R. , Dolnikowski Gregory G. , Schaefer Ernst J. , Lichtenstein Alice H.
Published: July 2008

Objective—

To investigate mechanisms underlying gender differences in serum lipoprotein concentrations, the kinetic behavior of apoB-100 was assessed.

Methods and Results—

Twenty subjects (<50 years; 12 men and 8 premenopausal women) were provided a Western diet for 4 to 6 weeks, after which the kinetics of apoB-100 in triglyceride-rich, intermediate-density, and low-density lipoprotein (TRL, IDL, and LDL) were determined in the fed state. Nonfasting plasma TC, LDL-C, and triglyceride concentrations were 23%, 34%, and 57% lower, respectively, in the women compared with men. Plasma TRL and LDL apoB 100 pool sizes were lower by 40% and 30%, respectively. These differences were accounted for by higher TRL and LDL apoB 100 fractional catabolic rates (FCR), rather than differences in production rates (PR). Plasma TRL-C and LDL-C were positively correlated with TRL and LDL apoB 100 concentrations and pool size, and negatively correlated with TRL and LDL apoB 100 FCR (women:
r
=−0.59,
P
<0.01 and
r
=−0.54,
P
<0.04, and men:
r
=−0.43,
P
<0.05 and
r
=−0.44,
P
<0.05). No significant associations were observed between plasma TRL-C and LDL-C and PR.

Conclusions—

These data suggest the mechanism for lower TRL-C and LDL-C concentrations in women was determined predominantly by higher TRL and LDL FCR rather than lower PR. This could explain, in part, the lower CVD risk in premenopausal women relative to men.
Transcriptional Activation of HIF-1 by RORα and its Role in Hypoxia Signaling
Authors: Kim Eun-Jin , Yoo Young-Gun , Yang Woo-Kyeom , Lim Young-Soun , Na Tae-Young , Lee In-Kyu , Lee Mi-Ock
Published: July 2008

Objective—

Hypoxia-inducible factor 1α (HIF-1α) is primarily involved in the adapting of cells to changes in oxygen levels, which is essential for normal vascular function. Recently, physiological roles for retinoic acid–related orphan receptor α (RORα) have been implicated in cardiovascular diseases such as atherosclerosis. In this study, we have investigated the potential roles of RORα in the hypoxia signaling pathway in connection with activation of HIF-1α.

Methods and Results—

Under hypoxic conditions, expression of RORα was induced. When RORα was introduced exogenously, protein level as well as transcriptional activity of HIF-1α was enhanced. Putative ligands of RORα, such as melatonin and cholesterol sulfate, induced transcriptional activity for HIF-1α, which was abolished by RNA interference against RORα. RORα was physically associated with HIF-1α through DNA binding domain, which was required to the RORα-induced stabilization and transcriptional activation of HIF-1α. Finally, either infection with adenovirus encoding RORα or treatment with ROR ligands enhanced the formation of capillary tubes by human umbilical vascular endothelial cells.

Conclusions—

Our results provide a new insight for the function of RORα in amplification of hypoxia signaling and suggest a potential application of RORα ligands for the therapy of hypoxia-associated vascular diseases.
Integrins
Authors: Silva Rita , D'Amico Gabriela , Hodivala-Dilke Kairbaan M. , Reynolds Louise E.
Published: July 2008

Angiogenesis, the formation of new blood vessels from preexisting vasculature, contributes to the pathogenesis of many disorders, including ischemic diseases and cancer. Integrins are cell adhesion molecules that are expressed on the surface of endothelial cells and pericytes, making them potential targets for antiangiogenic therapy. Here we review the contribution of endothelial and mural cell integrins to angiogenesis and highlight their potential as antiangiogenesis targets.
Heterogeneity of Left Ventricular Wall Thickening Mechanisms
Authors: Cheng Allen , Nguyen Tom C. , Malinowski Marcin , Daughters George T. , Miller D. Craig , Ingels Neil B.
Published: July 2008

Background—

Myocardial fibers are grouped into lamina (or sheets) 3 to 4 cells thick. Fiber shortening produces systolic left ventricular (LV) wall thickening primarily by laminar extension, thickening, and shear, but the regional variability and transmural distribution of these 3 mechanisms are incompletely understood.

Methods and Results—

Nine sheep had transmural radiopaque markers inserted into the anterior basal and lateral equatorial LV. Four-dimensional marker dynamics were studied with biplane videofluoroscopy to measure circumferential, longitudinal, and radial systolic strains in the epicardium, midwall, and endocardium. Fiber and sheet angles from quantitative histology allowed transformation of these strains into transmural contributions of sheet extension, thickening, and shear to systolic wall thickening. At all depths, systolic wall thickening in the anterior basal region was 1.6 to 1.9 times that in the lateral equatorial region. Interestingly, however, systolic fiber shortening was identical at each transmural depth in these regions. Endocardial anterior basal sheet thickening was >2 times greater than in the lateral equatorial region (epicardium, 0.16±0.15 versus 0.03±0.06; endocardium, 0.45±0.40 versus 0.17±0.09). Midwall sheet extension was >2 times that in the lateral wall (0.22±0.12 versus 0.09±0.06). Epicardial and midwall sheet shears in the anterior wall were ≈2 times higher than in the lateral wall (epicardium, 0.14±0.07 versus 0.05±0.03; midwall, 0.21±0.12 versus 0.12±0.06).

Conclusions—

These data demonstrate fundamentally different regional contributions of laminar mechanisms for amplifying fiber shortening to systolic wall thickening. Systolic fiber shortening was identical at each transmural depth in both the anterior and lateral LV sites. However, systolic wall thickening of the anterior site was much greater than that of the lateral site. Fiber shortening drives systolic wall thickening, but sheet dynamics and orientations are of great importance to systolic wall thickening. LV wall thickening and its clinical implications pivot on different wall thickening mechanisms in various LV regions. Attempts to implant healthy contractile cells into diseased hearts or to surgically manipulate LV geometry need to take into account not only cardiomyocyte contraction but also transmural LV intercellular architecture and geometry.