bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction in Mitral Regurgitation in Patients Undergoing Cardiac Resynchronization Treatment: Assessment of Predictors by Two‐Dimensional Radial Strain Echocardiography
Authors: Goland Sorel , Rafique Asim M. , Mirocha James , Siegel Robert J. , Naqvi Tasneem Z.
Published: April 2009

Background: We utilized the novel approach of 2D radial strain (2‐DRS) to evaluate whether left ventricular (LV) mechanical dyssynchrony in mid‐LV segments corresponding to papillary muscles insertion sites can predict early mitral regurgitation (MR) reduction post–cardiac resynchronization therapy (CRT). Methods: We evaluated 32 patients undergoing CRT (mean age 64 ± 17 years, 54% males) with MR grade ≥3 determined by the MR jet area/left atrial area ratio (JA/LAA). Results: Fifteen (47%) patients responded to CRT (JA/LAA) < 25%). Sixty‐seven percent of responders had mild or no residual MR and 33% had mild‐to‐moderate MR, while 70% of nonresponders had grade 3 or 4 MR (P = 0.0001) post CRT. The percent reduction in LV end‐systolic volume was significantly higher in responders (P = 0.03), as was improvement in LVEF (P = 0.007). Significant delay of time‐to‐peak 2‐DRS in the midposterior and inferior segments prior to CRT was found in responders compared with nonresponders (580 ± 58 vs. 486 ± 94, P = 0.002 and 596 ± 79 vs. 478 ± 127 ms, P = 0.005, respectively). Responders also had higher peak positive systolic 2‐DRS in the posterior and inferior segments compared to nonresponders (22 ± 13 vs. 12 ± 7%, P = 0.01 and 17 ± 9 vs. 9 ± 7%, P = 0.02, respectively). Logistic regression analysis showed that the differences in pre‐CRT inferoanterior time‐to‐peak 2‐DRS of >110 ms and MRJA/LAA <40% as well as 2‐DRS >18% in the posterior wall were significant predictors of post‐CRT improvement in MR. Conclusion: The presence of a significant time‐to‐peak delay on 2‐DRS between inferior and anterior LV segments, preserved strain of posterior wall, and MRJA/LAA <40% were found to be associated with significant MR reduction in patients post‐CRT.
A New Pan‐Nitinol Occluder for Transcatheter Closure of Ventricular Septal Defects in a Canine Model
Authors: DING ZHONG‐RU , QIN YONG‐WEN , HU JIAN‐QIANG , ZHAO XIAN‐XIAN , YANG ZHI‐HONG , HONG‐WU   M.D.  , CAO JIANG
Published: April 2009

Background: The Amplatzer ventricular septal defect (VSD) occluder has a fixed stainless steel pin bottom protruding out of the surface at the center of the discs on both sides. Theoretically, this protruding bottom may interfere with epithelialization or, in some cases, cause thrombosis.

Objective: To evaluate a new type of pan‐nitinol VSD occluder without the protruding stainless steel pin bottom on both sides in a canine VSD model designed to ensure safety, effectiveness, and feasibility.

Methods and Results: VSDs were successfully created by transseptal ventricular septal puncture with a Brockenbrough needle and dilation with an 8‐mm‐diameter balloon via the right jugular vein in 9 out of 12 canines. The new type VSD occluder was successfully implanted in 8 of the 9 modeled canines. No procedure‐ or device‐related complication was observed. Transthoracic echocardiography and MRI 2 months after device implantations showed that there was no device dislocation or heart valve dysfunction in 6 of the 8 tested canines. In addition, gross and pathological examinations 3–6 months after implantation showed no corrosion of the devices or serious inflammatory reactions in the modeled animals. Complete endothelialization was seen over the surface of the discs.

Conclusions: The new pan‐nitinol VSD device can be successfully implanted in a canine VSD model via a transcatheter approach featuring high success rate, low risk of procedure‐related complications, and sound biocompatibility. The result suggests that this new VSD occluder could be used safely in future clinical trials for further test.
Formation of single electron transistors in single-walled carbon nanotubes with low energy Ar ion irradiation technique
Authors: Mori Takahiro , Sato Shunsuke , Omura Kazuo , Yajima Shota , Tsuruoka Yasuhiro , Achiba Yohji , Ishibashi Koji
Published: April 2009

The single electron transistor (SET) fabrication process on the individual single-walled carbon nanotubes (SWCNTs) using low energy Ar ion irradiation technique has been demonstrated. The individual SWCNT was partly irradiated through the protection resist with the two opening windows, whose width was 50 nm, fabricated by electron beam lithography. The irradiated segments had higher resistance and worked as barriers. The SWCNT-SET successfully operated up to 100 K.
First-principles calculation of electron transport in Si atom wire
Authors: Kusaka Hiroyuki , Kobayashi Nobuhiko
Published: April 2009

The authors report a theoretical analysis of electron transport in a Si atom wire at a finite bias voltage using a first-principles method. Electronic states and transport properties are calculated using the Lippmann-Schwinger equation using the Laue representation in the framework of the density functional theory. They analyzed the transport properties of the Si wires between the metallic electrodes, and elucidated potential drop, transmission spectra, and the dependence on the bias voltage.
Soft processing for formation of self-assembled monolayer on hydrogen-terminated silicon surface based on visible-light excitation
Authors: Sano Hikaru , Yaku Tomohiro , Ichii Takashi , Murase Kuniaki , Sugimura Hiroyuki
Published: April 2009

Visible-light irradiation has been employed to promote a chemical reaction of 1-hexadecene with hydrogen-terminated silicon, yielding alkyl chains directly immobilized on bulk silicon surface. The resulting monolayer, that is, one type of self-assembled monolayer, was examined with water contact angle measurements, x-ray photoelectron spectroscopy, atomic force microscopy, and ellipsometry. While a part of the silicon surface was oxidized during the reaction, it was demonstrated that a compact monolayer was successfully formed both on p- and n-typed silicon substrates regardless of doping density.
Enhanced ultraviolet electroluminescence from p-Si∕n-ZnO nanorod array heterojunction
Authors: Sun Minghua , Zhang Qi-Feng , Sun Hui , Zhang Junyan , Wu Jin-Lei
Published: April 2009

The authors report enhanced ultraviolet electroluminescence at room temperature from a diode structure consisting of vertically oriented ZnO nanorod arrays grown on a p-typed silicon substrate. Excitonic emitting peak at wavelength of 385nm with a full width at half maximum (FWHM) of 23nm and a defect-related visible emitting peak at the wavelength of 546nm with a FWHM of 124nm are observed from this structure under forward-bias voltage. The intensity ratio of the ultraviolet peak and the visible peak reaches 4.7. The scanning electron microscope, x-ray diffraction, energy dispersive x ray, I-V, and electroluminescence measurements demonstrate that good crystal structure and rectifying diodelike behavior are obtained and defect-related visible light emission is greatly restrained.
Visualizing the surface structure of immunochromatography test strips using dynamic force microscopy
Authors: Yarkov S. P. , Shilenko I. V. , Valiev H. H. , Karnet Yu. N. , Kovalev G. N. , Snegireva N. S. , Yanovsky Yu. G. , Bogdanov E. V.
Published: April 2009

The surface structure of immunochromatography indicator elements, designed for the detection of vegetative forms of Bacillus Anthracis, was visualized using the Easy Scan dynamic force microscope. It is shown that such microscopy can serve as a useful support to immunochemical determinations of pathogenic bacteria in field conditions.
Distilling Free-Form Natural Laws from Experimental Data
Authors: Schmidt Michael , Lipson Hod
Published: April 2009

For centuries, scientists have attempted to identify and document analytical laws that underlie physical phenomena in nature. Despite the prevalence of computing power, the process of finding natural laws and their corresponding equations has resisted automation. A key challenge to finding analytic relations automatically is defining algorithmically what makes a correlation in observed data important and insightful. We propose a principle for the identification of nontriviality. We demonstrated this approach by automatically searching motion-tracking data captured from various physical systems, ranging from simple harmonic oscillators to chaotic double-pendula. Without any prior knowledge about physics, kinematics, or geometry, the algorithm discovered Hamiltonians, Lagrangians, and other laws of geometric and momentum conservation. The discovery rate accelerated as laws found for simpler systems were used to bootstrap explanations for more complex systems, gradually uncovering the “alphabet” used to describe those systems.
Gender Ideology: Components, Predictors, and Consequences
Authors: Davis Shannon N. , Greenstein Theodore N.
Published: April 2009

The purpose of this article is to review research on the construction of gender ideology and its consequences. The article begins with a summary of research focused on measuring gender ideology—individuals' levels of support for a division of paid work and family responsibilities that is based on the belief in gendered separate spheres. We describe the ways this concept has been operationalized in widely available data sources and provide a categorization schema for the items used to measure gender ideology. We also review the research predicting gender ideology, focusing on social and demographic characteristics while concurrently examining studies using cross-sectional, trend, and panel data. Finally, this article summarizes research focused on the consequences of gender ideology, both in families and family-related behaviors and in other areas of social life where beliefs about gender are relevant, such as the workplace. We conclude with implications for future research for measurement tools, predictors of gender ideology, and consequences of ideology in individuals' lives.
Models and Mechanisms of Hyperalgesia and Allodynia
Authors: Sandkühler Jürgen
Published: April 2009

Hyperalgesia and allodynia are frequent symptoms of disease and may be useful adaptations to protect vulnerable tissues. Both may, however, also emerge as diseases in their own right. Considerable progress has been made in developing clinically relevant animal models for identifying the most significant underlying mechanisms. This review deals with experimental models that are currently used to measure (sect. ii) or to induce (sect. iii) hyperalgesia and allodynia in animals. Induction and expression of hyperalgesia and allodynia are context sensitive. This is discussed in section iv. Neuronal and nonneuronal cell populations have been identified that are indispensable for the induction and/or the expression of hyperalgesia and allodynia as summarized in section v. This review focuses on highly topical spinal mechanisms of hyperalgesia and allodynia including intrinsic and synaptic plasticity, the modulation of inhibitory control (sect. vi), and neuroimmune interactions (sect. vii). The scientific use of language improves also in the field of pain research. Refined definitions of some technical terms including the new definitions of hyperalgesia and allodynia by the International Association for the Study of Pain are illustrated and annotated in section i.
Catecholaminergic Systems in Stress: Structural and Molecular Genetic Approaches
Authors: Kvetnansky Richard , Sabban Esther L. , Palkovits Miklos
Published: April 2009

Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct stressful stimuli.
Downstream Genes of Sox8 That Would Affect Adult Male Fertility
Authors: Singh A.P. , Harada S. , Mishina Y.
Published: April 2009

Sertoli cells provide nutritional and physical support to germ cells during spermatogenesis. Sox8 encodes a high mobility group transcription factor closely related to Sox9 and Sox10. Sertoli cells produceSOX8 protein, and its elimination results in an age-dependent deregulation of spermatogenesis resulting in male infertility. This suggests that Sox8 is a critical regulator of Sertoli cell function for the maintenance of male fertility beyond the first wave of spermatogenesis. To better understand the roles of Sox8 in testicular development and maintenance of male fertility, we have performed a detailed analysis to explore its downstream genes. We have used mRNA expression profiling to identify affected genes in Sertoli cells in the mutant testes of 2-month-old mice. Expression profiling of the heterozygous and homozygous Sox8 mutant testes indicates alterations in several important spermatogenesis and blood-testis barrier genes, providing insight into the molecular basis of the defects in Sox8–/– testes beyond the first wave of spermatogenesis.
Relationship of Neurovascular Elements to Neuron Injury during Ischemia
Authors: del Zoppo Gregory J.
Published: April 2009

Occlusion of flow to the brain regions identifies regions of vulnerability within the vascular territory at risk, which coalesce to become the mature ischemic lesion. A large number of unsuccessful clinical trials have focused on neuron and extravascular targets in humans that have shown apparent salvage in preclinical models. However, the observation that microvessel and neuron responses to ischemia occur simultaneously in these regions suggest that the responses could be coordinated. This presentation examines evidence in support of the conceptual ‘neurovascular unit’ and its application to the setting of acute intervention trials in ischemic stroke. There are no uniform reasons for which nonvascular interventions, as a class, have not been successful in clinical trials, but both the clinical observations and the hypothesis imply the need to understand interactions with the neurovascular unit as a prelude to further neuron protectant trials.
Sleep-Disordered Breathing and Acute Stroke
Authors: Cardona Portela Pere , Campdelacreu Fumadó Jaume , Quesada García Helena , Rubio Borrego Francisco
Published: April 2009

Background: Sleep-disordered breathing (SDB) is a disease of increasing importance and it is frequent in stroke patients. SDB is being recognized as an independent risk factor for several clinical consequences, including cardiovascular and cerebrovascular disease. Methods: The present review summarizes the current evidence for an independent association between SDB and stroke, defining SDB subgroups, mechanisms, confounding factors and other epidemiological aspects. We analyze stroke outcome and prognosis in SDB patients. A search for recent data on this issue was made in several population-based studies and reference lists of articles. Results: Many recent studies have shown an association between SDB and stroke. Moreover, there is a high prevalence of sleep apnea in patients with stroke. The pathogenesis of stroke in obstructive sleep apnea syndrome is not completely understood and likely to be multifactorial. Several mechanisms like hemodynamic disturbances and inflammatory or endothelial dysfunction could be involved. The presence of SDB in stroke patients may lead to a poor outcome and recurrence. Noninvasive treatments such as continuous positive airway pressure may decrease the risk of stroke in terms of secondary, and possibly, primary prevention. Conclusions: SDB is associated with cerebrovascular morbidity and an unfavorable clinical course. The presence of SDB should be systematically screened in patients with acute stroke. Further studies are needed to determine whether continuous positive airway pressure treatment ameliorates stroke outcome and prognosis.
Quality of Life after Stroke: The Importance of a Good Recovery
Authors: Carod-Artal Francisco Javier , Egido José Antonio
Published: April 2009

Background: Health-related quality of life (HRQoL) is a recognized and important outcome after stroke. An increased survival and the presence of moderate impairment in long-term stroke survivors impact their HRQoL. Methods: HRQoL measures and HRQoL determinants in stroke survivors are reviewed. Results: Stroke is the leading cause of long-term disability in western countries. Specific HRQoL scales have been developed in the last years, such as the Stroke Impact Scale, the Stroke Specific Quality of Life Scale, the Stroke and Aphasia HRQoL Scale, and the Burden of Stroke Scale. Disability and poststroke depression are consistent determinants of HRQoL. Other determinants include female sex, coping strategies, and social support. Poststroke depression affects HRQoL, functional recovery, cognitive function and healthcare use in stroke survivors. Stroke caregivers have lower HRQoL, greater prevalence of stress and depression, economical burden, and changes in social relationships. Advancing age and anxiety in patients and caregivers, high dependency and poor family support identify caregivers at risk of adverse outcomes. Conclusions: Physical and psychosocial well-being is greatly affected in stroke survivors and their caregivers.
Genetics of Hypertensive Syndrome
Authors: Martinez-Aguayo Alejandro , Fardella Carlos
Published: April 2009

The knowledge of the genetic bases of hypertension has improved over the last decade; this area of research has high priority due to the high incidence of hypertension and its impact on public health. Monogenetic mineralocorticoid hypertension syndromes are associated with suppressed plasma renin activity due to excessive activation of the mineralocorticoid pathway. We review the pathophysiology, phenotype, and method of diagnosis for familial hyperaldosteronism type I and type II, hypertensive forms of congenital adrenal hyperplasia, 11β-hydroxysteroid dehydrogenase type 2 deficiency, Liddle’s syndrome, an activating mutation of the MR, and glucocorticoid resistance. We also review some genes that could contribute to essential hypertension.
Triiodothyronine Is an Indicator of Nutritional Status in Adolescent Girls with Eating Disorders
Authors: Swenne Ingemar , Stridsberg Mats , Thurfjell Barbro , Rosling Agneta
Published: April 2009

Aim: Circulating thyroid hormone concentrations are influenced by nonthyroidal disease and changes in nutritional status. We studied thyroid hormones as possible indicators of nutrition in adolescent girls with eating disorders. Method: Blood samples for analyses of thyroid hormones were obtained at 360 assessments of 298 patients and biweekly during 42 treatment periods in 36 patients. Results: At assessment, when most of the girls were on a weight losing course, serum triiodothyronine (T3) concentrations were low. Great weight loss and rapid rate of weight loss were the most important predictors of low T3 concentrations. Serum free thyroxine concentrations were in the lower normal range. In premenarcheal girls, weight loss was the most important predictor of free thyroxine but this relationship was weaker in postmenarcheal girls. Serum TSH concentrations were within the normal range and only weakly related to weight changes. During treatment, T3 increased in parallel with weight but was also influenced by the short-term weight trend. Conclusion: Serum T3 concentration is an indicator of nutritional status in adolescent girls with eating disorders. It is sensitive to short-term weight changes and could be used to monitor progress throughout nutritional rehabilitation.
A Case of X-Linked Adrenal Hypoplasia Congenita, Central Precocious Puberty and Absence of the DAX-1 Gene: Implications for Pubertal Regulation
Authors: Loke Kah-Yin , Poh Larry Kok-Seng , Lee Warren Wei-Rhen , Lai Poh-San
Published: April 2009

Background/Aims: X-linked adrenal hypoplasia congenita (AHC) is typically associated with DAX-1 mutations and hypogonadotropic hypogonadism. However, atypical cases of X-linked AHC in association with central precocious puberty and even normal puberty have rarely been reported, although the mechanism of action remains unknown. Case Report: This is a case report of a boy with X-linked AHC associated with Duchenne muscular dystrophy, whose clinical presentation led to analysis of the DAX-1, glycerol kinase (GK1) and dystrophin genes, which were amplified by polymerase chain reaction, with Southern blot analysis of the AHC locus. Results: There was a non-contiguous deletion of the DAX-1 and GK1 genes, with deletion of the dystrophingene from exons 3 to 79. Conclusion: This is the first report of X-linked AHC, central precocious puberty in the absence of the DAX-1 gene. The fact that a ‘loss of function’ DAX-1 mutation can be associated with hypogonadotropic hypogonadism, precocious and normal puberty, suggests that DAX-1 is but one of several transcription factors which regulate puberty, and provides further evidence that other transcription factors may interact with DAX-1 and influence gonadal regulation in a complex, but hierarchical fashion.
The Spectrum of Motor Function Abnormalities in Gastroesophageal Reflux Disease and Barrett’s Esophagus
Authors: Ang D. , Blondeau K. , Sifrim D. , Tack J.
Published: April 2009

Barrett’s esophagus has traditionally been regarded as the most severe end of the spectrum of gastroesophageal reflux disease and is of great clinical importance in view of the association with esophageal adenocarcinoma. Studies have documented high levels of esophageal acid exposure in Barrett’s esophagus. Various pathogenetic mechanisms underlie this phenomenon. These include abnormalities in esophageal peristalsis, defective lower esophageal sphincter pressures, gastric dysmotility and bile reflux. Whilst these factors provide evidence for an acquired cause of Barrett’s esophagus, an underlying genetic predisposition cannot be ruled out. Although the past decade has brought about many new discoveries in the pathogenesis of Barrett’s esophagus, it has also added further controversy to this complex disorder. A detailed analysis of the gastrointestinal motor abnormalities occurring in Barrett’s esophagus follows, with a review of the currently available literature and an update on this condition that continues to be of interest to the gastroenterologist.
Elevated Peripheral Allergen-Specific T Cell Response Is Crucial for a Positive Atopy Patch Test Reaction
Authors: Johansson Catharina , Ahlborg Niklas , Andersson Anna , Lundeberg Lena , Karlsson Maria A. , Scheynius Annika , Tengvall Linder Maria
Published: April 2009

Background: Atopic eczema is a chronic inflammatory skin disease in which several subgroups of cases can be identified. Atopy patch testing (APT) reveals allergen sensitization also in atopic eczema patients devoid of detectable allergen-specific IgE, suggesting the importance of factors other than IgE in the reaction. Here we investigate the relationship between APT reactions and allergen-specific peripheral IgE and T cell reactivity in atopic eczema patients. Methods: Adult patients with atopic eczema (n = 64) and healthy controls (n = 24) were analyzed for reactivity to Malassezia sympodialis extract by APT, measurement of specific plasma IgE and in vitro determination of the frequency of allergen-reactive peripheral blood mononuclear cells producing interleukin-4 and interleukin-5 using the ELISpot method. Results: When combining the results of the APT, IgE measurements and the ELISpot analyses, reactivity to M. sympodialis was found in a majority of the atopic eczema patients (69%), whereas the healthy controls were negative throughout. T cell reactivity to M. sympodialis, manifested by production of both interleukins 4 and 5, was highly predictive for a positive APT reaction and displayed a strongly positive correlation with the APT score. In contrast, the allergen-specific IgE levels did not predict the APT outcome, and no correlation could be found between the IgE levels and the APT score. Conclusion: Peripheral allergen-specific T helper 2 cell-mediated reactivity appears to be required for a positive APT reaction to M. sympodialis. The diagnostic potential of measuring peripheral allergen-specific T cell responses should be considered in atopic eczema.
Time Trends in Allergic Sensitisation and Helicobacter pylori Prevalence in Finnish Pregnant Women
Authors: Seiskari Tapio , Viskari Hanna , Kaila Minna , Haapala Anna-Maija , Koskela Pentti , Hyöty Heikki
Published: April 2009

Background: An increase in the prevalence of allergic conditions has been documented in Finland, correlating with the diminishing prevalence of Helicobacter pylori infections. We investigated whether the increase of allergic sensitisation still continues and correlates with the prevalence of H. pylori infections. Methods: The sera from 958 pregnant women in 1983, 1989, 1995 and 2001 were analysed for the presence of antibodies against H. pylori. In addition, allergen-specific IgE antibodies and total levels of IgE antibodies were measured. Results: A clear birth cohort effect was found in the prevalence of allergic sensitization: allergen-specific IgE was more frequent among recent birth cohorts than earlier ones (p = 0.001). The frequency of H. pylori antibodies followed the opposite trend (p < 0.001) and the increase in allergic sensitisation was only seen among H. pylori-negative women. A modest increase was also seen in allergic sensitisation between the 4 time series among the H. pylori-negative subjects (p = 0.04). Total IgE levels did not differ between birth cohorts or time series. Conclusion: The results suggest that hygiene-related environmental factors have played a role in the increase of allergic sensitisation during the last decades.
Long-Term Results of Bare Sclera, Limbal-Conjunctival Autograft and Amniotic Membrane Graft Techniques in Primary Pterygium Excisions
Authors: Özer Ahmet , Yıldırım Nilgün , Erol Nazmiye , Yurdakul Sumru
Published: April 2009

Purpose: To compare the long-term follow-up results of the bare sclera technique (BST), limbal-conjunctival autograft technique (LCAT) and amniotic membrane graft technique (AMGT) in primary pterygium excisions. Materials and Methods: In this study, 48 eyes of 48 patients who underwent pterygium surgery using BST (group 1), 63 eyes of 63 patients who underwent pterygium surgery using LCAT (group 2) and 52 eyes of 52 patients who underwent pterygium surgery using AMGT (group 3) were compared with respect to corneal epithelialization, recurrence and complication of the procedures. The mean ages of the groups were 47.88 ± 14.21 years in group 1, 49.63 ± 14.42 years in group 2 and 47.92 ± 15.52 years in group 3. Patients were followed up to 72.39 ± 11.03 months in group 1, 69.91 ± 12.41 months in group 2 and 61.43 ± 9.83 months in group 3. Results: Postoperative corneal epithelialization was completed in 5.62 ± 1.74 days in group 1, 4.33 ± 0.91 days in group 2 and 4.79 ± 1.39 days in group 3. Corneal epithelialization time was earlier in group 2 than in groups 1 (p < 0.01) and 3 (p < 0.05). Recurrences were detected in 19 eyes (39.58%) in group 1, 11 eyes (14.29%) in group 2 and 12 eyes (23.08%) in group 3. The recurrence rate was significantly lower in group 2 than in groups 1 and 3 (p < 0.001). Postoperative complications were not seen in any of the groups. Graft retraction and necrosis were not detected in the LCAT and AMGT groups during the follow-up period. Conclusions: LCAT was found to be a more effective procedure than BST and AMGT, with decreased recurrence rates after pterygium excision. Limbal-conjunctival autograft seems to be a useful treatment in pterygium surgery due to higher success rates and lower recurrence rates. Amniotic membrane grafts may be an alternative surgical technique for pterygium treatment for patients with or without glaucoma who might need glaucoma surgery in the future.
Outward Transcutaneous Chemical Migration: Implications for Diagnostics and Dosimetry
Authors: Peck Carl C. , Conner Dale P. , Bolden Brenda J. , Almirez Ramona G. , Kingsley Thomas E. , Mell Leroy D. , Murphy Gail , Hill Vincent E. , Rowland Laura M. , Ezra David , Kwiatkowski Terease E. , Bradley Charles R. , Abdel-Rahim Maged
Published: April 2009

Chemical substances migrate outwards from within the body to the skin surface by diffusion from cutaneous capillaries across the epidermis. Heretofore, study of transepidermal chemical emissions have been restricted to substances which are in the vapor phase at skin surface temperature. We have investigated outward transcutaneous chemical migration of nongaseous chemicals by devising an occlusive transcutaneous chemical collection system, consisting of a tape-encased plug of gelled saline in which activated carbon is dispersed. Investigations of nine chemicals in ‘fuzzy’ rats, rhesus monkeys, and man provide data which are consistent with a general theory of outward transcutaneous chemical migration. This noninvasive continuous transcutaneous sampling technique provides a new method for investigating skin permeability in vivo and may provide a basis for convenient diagnosis and monitoring of chemical exposure.
15-Hydroxyeicosatetraenoic Acid (15-HETE) Specifically Inhibits LTB4-Induced Chemotaxis of Human Neutrophils
Authors: Ternowitz Thomas , Fogh Karsten , Kragballe Knud
Published: April 2009

15-Hydroxyeicosatetraenoic acid (15-HETE), a 15-lipoxygenase (15-LO) product of arachidonic acid has the potential to inhibit leukotriene formation. In the present study the effect of 15-HETE on leukotriene B4 (LTB4)-induced polymorphonuclear leukocytes (PMN) and monocyte chemotaxis was investigated. LTB4-induced chemotaxis of PMNs was inhibited in a dose-dependent manner by 15-HETE. Maximum inhibition (68%) occurred at a 15-HETE concentration of 10-4M. The 15-LO product of eicosapentaenoic acid (15-HEPE) was approximately 10 times less potent in inhibiting LTB4-induced PMN chemotaxis. LTB4-induced chemotaxis of monocytes was unaffected by both 15-HETE and 15-HEPE. Using N-formyl-methionyl-leucyl-phenylalanine (FMLP) and complement split product C5a as chemoattractants, 15-HETE did not decrease PMN chemotaxis. Furthermore, 15-HETE itself did not affect random migration of leukocytes. The present results demonstrate that 15-HETE inhibits LTB4-induced chemotaxis of PMNs in vitro in a specific and selective way. Because 15-HETE not only inhibits formation, but also the effect of LTB4, it may be important in regulating LTB4-induced inflammation.
Topical Ciclosporin for Psoriasis: In vitro Skin Penetration and Clinical Study
Authors: Hermann Richard C. , Taylor Robert S. , Ellis Charles N. , Williams Adeyinka , Weiner Norman D. , Flynn Gordon L. , Annesley Thomas M. , Voorhees John J.
Published: April 2009

In contrast to oral administration, topical ciclosporin is not effective in the treatment of psoriasis. This may be due to the drug’s inability to penetrate the stratum corneum or to a need for systemic metabolism of ciclosporin to active metabolites. We conducted a preliminary evaluation of the ability of ciclosporin, in a variety of vehicles, to penetrate excised human skin in a two-compartment diffusion cell, a standard in vitro technique for evaluating percutaneous drug delivery. A high-pressure liquid chromatography assay for ciclosporin did not detect the passage of ciclosporin through skin. This finding was consistent through multiple trials, some of which evaluated Azone or liposomal formulations, which are reported to enhance the penetrability of certain compounds. These results indicate that ciclosporin is unable to penetrate human skin in the vehicles tested. This may explain the lack of clinical efficacy we demonstrated in 5 patients with psoriasis treated with topical ciclosporin for 14–16 days.
Autoradiographic Study of the Effects of Psoralen and Ultraviolet Light on DNA, RNA and Protein Synthesis in Cultured Keratinocytes and Psoriatic Skin
Authors: Bertaux B. , Moreno G. , Vinzens F. , Dubertret L.
Published: April 2009

DNA, RNA and protein synthesis were studied by autoradiography in cultured keratinocytes, immediately, 24 and 48 h after 8-methoxypsoralen and ulraviolet light, (PUVA) treatment. Using the same technique, the immediate and long-term effects of PUVA therapy on DNA, RNA and protein synthesis were analysed in skin biopsies from psoriatic patients. In the cultures, immediately after irradiation, DNA and RNA syntheses were similarly inhibited in a dose-dependent manner, while protein synthesis was slightly affected only for the highest dose. After 24 h, RNA synthesis recovered whereas DNA synthesis was more severely inhibited suggesting that other cell components may be damaged by PUVA. In patients, DNA and RNA syntheses decreased immediately after PUVA sessions. During all the sessions until the psoriatic plaques had cleared, an impairment of DNA synthesis was observed in comparison with the synthesis in involved and uninvolved skin before treatment. These results suggest that the therapeutic efficiency of PUVA is based on the inhibition of DNA replication due to direct effects on nucleic acids but also to photoreactions with other cell components.
Modulatory Effects of Glycosaminoglycans and Histamine on Lymphocyte Mitogenesis
Authors: Czarnetzki Beate M. , Wüllenweber Imke
Published: April 2009

Since mast cells have previously been shown to be potent modulators of lymphocyte function, the effect of varying concentrations of three mast cell- or basophil- as well as skin ground substance-derived glycosaminoglycans (GAG; heparin, chondroitin sulfate, hyaluronic acid) and of histamine was investigated on rat spleen cell 3H-thymidine incorporation in the absence and presence of mitogens. Modulation proved to be different for the three GAG: chondroitin sulfate was inhibitory and hyaluronic acid enhancing, while heparin exhibited a more complex pattern, with inhibition in control and phytohemagglutinin-stimulated cultures and enhancement in concanavalin A-driven cultures, in parallel to histamine. The data suggest that ground substance GAG as well as mast cell- and basophil-derived mediators in the skin can have a marked and complex modulatory effect on the function of lymphocytes.
Epidermal Keratin Levels during Oral 1-Alpha-Hydroxyvitamin D3 Treatment for Psoriasis
Authors: Holland D.B. , Wood E.J. , Roberts S.G. , West M.R. , Cunliffe W.J.
Published: April 2009

Recently the treatment of psoriasis with vitamin D3, its metabolites or analogues, has been reported to be clinically effective and free from side effects. We have quantified the changes in the levels of epidermal lesional keratins in 15 psoriatic patients receiving oral 1Α(OH)D3 treatment. Lesions were sampled before treatment commenced and at monthly intervals for 4–6 months. Clinical resolution occurred in 7 patients within this time; 3 other patients showed incomplete lesion resolution and the remaining 5 patients showed a complete lack of response within the treatment period. Lesion resolution, as judged by clinical criteria, was accompanied by significant changes in the levels of three of the keratin polypeptides and smaller changes in others. Keratin 2 increased to levels greater than those in normal epidermis, while keratins 16 and 18 decreased to normal levels. Changes in the levels of keratins 1 and 5 were small and those of keratins 7, 10 and 14 minimal. These changes were compared with values found during lesion resolution with other therapies used in psoriasis, i.e. topical dithranol, PUVA, oral etretinate and hydroxyurea and were highly reminiscent of those observed during PUVA therapy but contrasted with those during etretinate treatment. The decrease in level of keratin 16, a hyperproliferation marker, suggests that 1Α(OH)D3 inhibits keratinocyte proliferation, but at the same time the overproduction of keratin 2, a major keratin of the granular cells, indicates that there is an increase in the number of cells in the later stages of differentiation.
Evidence for Autoregulation of Cell Division and Cell Transit in Keratinocytes Grown on Collagen at an Air-Liquid Interface
Authors: MacCallum Donald K. , Lillie John H.
Published: April 2009

Oral and epidermal rat keratinocytes when cultured on a matrix of type I collagen fibrils at the interface between the gaseous and liquid phases of a culture form a highly ordered stratified squamous epithelium. Autoradiographic studies of cells labeled by tritiated thymidine indicate that the keratinocytes are capable of autoregulating cell division. Early confluent cultures exhibit 51 % of basal cells labeled, a percentage that decreases to 18% when a fully differentiated stratified squamous epithelium is formed. Such a decrease in labeling occurs in cultures where the mitotically active basal cells have unimpeded access to culture medium supplied from below and when no cell type other than the keratinocyte is present in the culture. Additionally, the transit of keratinocytes from the basal cell layer through other viable cell strata to the layer of terminally differentiated cells can be followed by tracking cells labeled with tritiated thymidine. In cultures of oral keratinocytes, cells move from the basal cell layer to the cornified layer at a maximum rate of 7 days, while virtually all labeled cells (91 %) are localized in the terminally differentiated cell layer 14 days following labeling. Keratinocyte cultures grown in culture at an air-liquid interface exhibit tissue organization that closely resembles the native, parent tissue. Such cultures can be useful in studying the effects of pharmacologic mediators of cell division and cell transit.
Characterization of Skin Reconstructed on a Chitosan-Cross-Linked Collagen-Glycosaminoglycan Matrix
Authors: Shahabeddin Lili , Berthod François , Damour Odile , Collombel Christian
Published: April 2009

Reconstruction of skin requires both the dermal and epidermal equivalent of the skin. We have developed a reconstructed skin composed of two compartments: (1) a dermal equivalent comprising an acellular dermal substrate populated by foreskin fibroblasts and (2) an epidermis regenerated from normal human keratinocytes seeded onto the dermal equivalent. The dermal substrate contains type I and III collagen and glycosaminoglycans (GAGs) cross-linked by chitosan. Fibroblasts seeded into the porous structure of the dermal substrate provide a dermal equivalent suitable to support epidermal cells. Keratinocytes attach quickly, exhibit mitotic activity and form a continuous and stratified epidermis. After 2 weeks of culture, histological sections show a basal layer with cuboidal cells attached to the dermal equivalent and several suprabasal cell layers including the stratum corneum. Transmission electron microscopy revealed the cell membrane densification (hemidesmosomes) at the dermoepidermal junction; however, the lamina densa was found discontinuous at this stage. We noted the presence of lipid vesicles in spinous layer and keratohyalin granules in granular layer. The epidermal differentiation was complete terminal with the stratum corneum containing several layers of corneocytes filled with tonofilaments. Reconstructed skin, based on our chitosan-cross-linked collagen-GAG matrix is moφhologically equivalent to normal human skin and should thus provide a useful tool for in vitro toxicological studies as well as a suitable wound covering for the treatment of patients with severe burns.
Irritant Patch Testing: Penetration of Sodium Lauryl Sulphate into Human Skin
Authors: Agner Tove , Fullerton Ann , Broby-Johansen Urs , Batsberg Walther
Published: April 2009

To clarify the sources of variation in irritant patch testing, variability in delivery of the test substance from the patch test system was studied. An in vitro model was used to study the penetration of sodium lauryl sulphate (SLS) from a patch test system into the skin. Different formulations of SLS applied to the skin for 24 h were studied (aqueous solution and gels), but irrespective of the vehicle used permeation of SLS into the recipient phase was poor. Results were compared to in vivo patch testing in 12 subjects. Approximately 70% of the applied SLS in aqueous soltion was released from the patch test system. Release from gels was poorer. High concordance between the in vivo and the in vitro model was found. No correlation was found between the amount of SLS left in the filter disc and the strentgh of the clinical reaction in vivo.
Inhibitory Effects of Prostanoids on the Proliferation of Transformed Human Epidermal Cells in Culture
Authors: Ikai Kouichi , Sone Rie , Fukushima Masanori
Published: April 2009

The cytotoxic action of various prostanoids was examined on a transformed human epidermal cell line (HSC-1), and methyl(5S,6S,7Z)-5,6-diacetoxy-7-((2S)-4-chloro-2-hydroxy-2-((2Z)-2-octenyl)-5-oxo-3-cyclopentenylidene)heptanoate (YM-11), which is a punaglandin compound, was found to be most active. YM-11 exerted a dose-dependent inhibition of HSC-1 cell growth over 0.03 µM (0.01 µg/ml), and at 0.3 µM(0.1 µg/ml) its growth was completely inhibited. The IC50 value of YM-11 on HSC-1 cell growth was calculated as 0.15 µM(0.05 µg/ml). Methyl(E)-7-(5-chloro-2-hydroxy-2-octyl-5-oxo-3-cyclopentenylidene)heptanoate (YM-3), which is also a punaglandin derivative, showed remarkable cytotoxicity on HSC-1 cells with an IC50 of 0.24 µM(0.08 µg/ml). Concerning other cytotoxic prostaglandins (PGs), the IC50 values of Δ7-PGA1, Δ12-PGJ2 and PGD2 were 1.5 µM (0.5 µg/ml), 2.1 µM(0.75 µg/ml) and 5.7 µM (2 µg/ml), respectively. On the basis of the present data and previous in vitro and in vivo evidence, punaglandin derivatives may be useful antineoplastic agents for skin cancer.
Ciclopirox Nail Lacquer 8%: In vivo Penetration into and through Nails and in vitro Effect on Pig Skin
Authors: Ceschin-Roques C.G. , Hänel H. , Pruja-Bougaret S.M. , Luc J. , Vandermander J. , Michel G.
Published: April 2009

This report presents original methods to assess the bioavailability of an antifungal drug from a varnish preparation in finger nails. For the studies with human volunteers a ciclopirox 8 % nail lacquer was used to determine its efficacy in the treatment of onychomycoses. In vivo studies were performed on the fingernails of healthy volunteers by determining the total amount of ciclopirox penetrated per milligram of nail and the partition of the drug in the plate of the nails (technically divided into four layers). Ciclopirox concentrations were evaluated by measuring the inhibition of Candida pseudotropicalis growth in vitro. The ciclopirox concentration after 30 days treatment was determined as 3.35 ± 0.82 µg/mg nail material. This is a sufficient amount to kill the fungal pathogens. In addition, in vitro penetration experiments were carried out with excised pig skin. Lacquer formulations from 0.5 to 8 % were used to inhibit the growth of Trichophyton mentagrophytes. Formulations from 2 to 8% led to a strong to total inhibition of the dermatophyte after 30 min treatment time.
Efficacy of Topical Dimetindene in Experimentally Induced Pruritus and Weal and Flare Reactions
Authors: Lever L.R. , Hill S. , Dykes P.J. , Marks R.
Published: April 2009

Double-blind, placebo-controlled studies were performed to assess the effect of 0.1 % dimetindene gel on the itch threshold to intracutaneous histamine and on the weal and flare reaction after intracutaneous injection of histamine in normal volunteer subjects. Treatment of the forearm skin in 20 volunteers resulted in an increase in itch threshold with dimetindene gel compared to placebo. Treatment of the forearm skin with dimetindene gel in 32 volunteers had no significant effect on weal thickness in subjects treated for 10, 30 or 60 min, but there was a significant reduction in weal thickness in those subjects treated for 120 min. Topical dimetindene may be of value in treating conditions mediated through histamine release.
Modulation of Human Immune Functions in vitro by Temarotene and Its Metabolite
Authors: Bollag Werner , Peck Richard
Published: April 2009

The arotinoid temarotene (Ro 15–0778) and its metabolite Ro 14–6113 were examined in a variety of in vitro assays quantitating parameters of human immune functions. Both immunosuppressive and immunostimulatory activities of these compounds were identified. These activities were compared with those of the known immunomodulatory compound ciclosporin A (CsA) at concentrations corresponding to clinically effective plasma concentrations. Like CsA, Ro 14–6113 inhibited the mitogen- or alloantigen-induced proliferation of T cells as well as their capacity to secrete interleukin-2 (IL-2), interferon-Γ and tumor necrosis factor Α. Ro 15–0778 showed no activity in inhibiting cytokine secretion and was considerably less effective than Ro 14–6113 in inhibiting T cell proliferation. Ro 14–6113 was more effective than CsA in inhibiting IL-2 receptor expression. Ro 14–6113 modulated both positively or negatively the proliferation of B cells, depending on the concentration. Ro 14–6113 inhibited the secretion of IgM, IgG, and IgA, while stimulating IgE secretion. A different profile of activity for Ro 14–6113 and CsA was observed, suggesting differing effectiveness in immunologically mediated diseases.
Retinol Uptake and Metabolism to 3,4-Didehydroretinol in Human Keratinocytes at Various Stages of Differentiation
Authors: Törmä Hans , Vahlquist Anders
Published: April 2009

The concentration of 3,4-didehydroretinol, an epidermal metabolite of retinol, is changed both in association with keratinizing disorders and during treatment with certain synthetic retinoids. To delineate further the factors regulation biosynthesis of 3,4-didehy-droretinol, keratinocytes from three different layers of normal epidermis were prepared by trypsinization and incubated with [3H]-retinol for 20 h. Cell-bound [3H]-retinol and 3,4-[3H]-didehydroretinol were separated by high-performance liquid chromatography. The results indicate that the uptake of retinol and the synthesis of 3,4-didehydroretinol occur predominantly in undifferentiated cells from the basal and spinous layers of the epidermis.