bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does Reimportation Reduce Price Differences for Prescription Drugs? Lessons from the European Union
Authors: Kyle Margaret K. , Allsbrook Jennifer S. , Schulman Kevin A. 
Published: March 2008

Objective. To examine the effect of parallel trade on patterns of price dispersion for prescription drugs in the European Union.Data Sources. Longitudinal data from an IMS Midas database of prices and units sold for drugs in 36 categories in 30 countries from 1993 through 2004.Study Design. The main outcome measures were mean price differentials and other measures of price dispersion within European Union countries compared with within non‐European Union countries.Data Collection/Extraction Methods. We identified drugs subject to parallel trade using information provided by IMS and by checking membership lists of parallel import trade associations and lists of approved parallel imports.Principal Findings. Parallel trade was not associated with substantial reductions in price dispersion in European Union countries. In descriptive and regression analyses, about half of the price differentials exceeded 50 percent in both European Union and non‐European Union countries over time, and price distributions among European Union countries did not show a dramatic change concurrent with the adoption of parallel trade. In regression analysis, we found that although price differentials decreased after 1995 in most countries, they decreased less in the European Union than elsewhere.Conclusions. Parallel trade for prescription drugs does not automatically reduce international price differences. Future research should explore how other regulatory schemes might lead to different results elsewhere.
Short‐term ferrous sulfate supplementation in female blood donors
Authors: Maghsudlu Mahtab , Nasizadeh Soheila , Toogeh Gholam Reza , Zandieh Tahereh , Parandoush Siavash , Rezayani Maryam 
Published: March 2008

BACKGROUND: Iron deficiency is a public problem in women, which contributes to the high percentage of deferred blood donations in this group. This study evaluated the effect of iron supplementation in improving iron stores to promote safe blood donation in women.STUDY DESIGN AND METHODS: A total of 412 female blood donors were randomly recruited for the study. The volunteers were scheduled for an initial visit and three subsequent visits at 4‐month intervals for possible repeat donation. Each volunteer was given 21 tablets of 150 mg of ferrous sulfate or placebo to be taken three times daily for 1 week after each blood donation. Their hemoglobin (Hb) concentration, hematocrit (Hct), serum ferritin, total iron‐binding capacity (TIBC), and percent saturation of the TIBC were tested throughout the course of the study.RESULTS: The group taking ferrous sulfate showed no significant difference between the mean initial and final result for any of the values other than Hb values, whereas there was a significant decline in mean Hb, Hct, serum iron, serum ferritin, and percent saturation in the group taking placebo. Hb concentrations declined significantly in both groups; however, it was more severe in the placebo group when compared to the ferrous sulfate group. The relative risk of iron deficiency in placebo group was 3.6 (95% confidence interval = 1.73‐7.74).CONCLUSION: The results indicate that supplementation therapy can be considered as one of the strategies to promote safe blood donation in women. A quantity of 150 mg of elemental iron per day as ferrous sulfate, however, is not the correct dose for Iranian female donors.
Cell secretion: an update
Authors: Jeremic A. 
Published: March 2008

Introduction
An update
AbstractThis past decade has witnessed the publication of a flurry of scientific papers and reports on the subject of cell secretion, following discovery of a permanent plasma membrane structure termed ‘porosome’ and its determination as the universal secretory machinery in cells. This discovery has led to a paradigm shift in our understanding of the secretory process, demonstrating that membrane‐bound secretory vesicles transiently dock and fuse at the porosome base to release their contents to the cell exterior. The regulated release of intravesicular contents during cell secretion is governed by dilation of the porosome opening to the outside, and the extent of vesicle swelling. In agreement, a great number of articles have been written and studies performed, which are briefly discussed in this article.
GTRAP3‐18 serves as a negative regulator of Rab1 in protein transport and neuronal differentiation
Authors: Maier S. , Reiterer V. , Ruggiero A. M. , Rothstein J. D. , Thomas S. , Dahm R. , Sitte H. H. , Farhan H. 
Published: March 2008

AbstractGlutamate transporter associated protein 3–18 (GTRAP3‐18) is an endoplasmic reticulum (ER)‐localized protein belonging to the prenylated rab‐acceptor‐family interacting with small Rab GTPases, which regulate intracellular trafficking events. Its impact on secretory trafficking has not been investigated. We report here that GTRAP3‐18 has an inhibitory effect on Rab1, which is involved in ER‐to‐Golg trafficking. The effects on the early secretory pathway in HEK293 cells were: reduction of the rate of ER‐to‐Golgi transport of the vesicular stomatitis virus glycoprotein (VSVG), slowed accumulation of a Golgi marker plasmid in pre‐Golgi structures after Brefeldin A treatment and inhibition of cargo concentration of the neuronal glutamate transporter excitatory amino‐acid carrier 1 (EAAC1) into transpor complexes in HEK293 cells, an effect that could be completely reversed in the presence of an excess of Rab1. In accordance with the known role of Rab1 in neurite formation, overexpression of GTRAP3‐18 significantly inhibited the length of outgrowing neurites in differentiated CAD cells. The inhibitory effect of GTRAP3‐18 on neurite growth was rescued by co‐expression with Rab1, supporting the conclusion that GTRAP 3‐18 acted by inhibiting Rab1 action. Finally, we hypothesized that expression of GTRAP3‐18 in the brain shoul be lower at stages of active synaptogenesis compared to early developmental stages. This was the case as expression of GTRAP3‐18 declined from E17 to P0 and adult rat brains. Thus, we propose a model where protein trafficking and neuronal differentiation are directly linked by the interaction of Rab1 and its regulator GTRAP3‐18.
Discovery of a phosphatidylserine‐recognizing peptide and its utility in molecular imaging of tumour apoptosis
Authors: Thapa Narendra , Kim Soyoun , So In‐Sup , Lee Byung‐Heon , Kwon Ick‐Chan , Choi Kuiwon , Kim In‐San 
Published: March 2008

AbstractThe exposure of phosphatidylserine (PS) molecules from the inner to the outer leaflet of the plasma membrane has been recognized as a well‐defined molecular epitope of cells undergoing apoptosis. Examination and monitoring of PS exposure is an extensively used molecular marker in non‐invasive apoptosis imaging under a variety of clinical conditions, including the assessment of therapeutic anti‐cancer agents and myocardial infarction. Herein, we report the identification of a PS‐recognizing peptide which was identified by the screening of an M13 phage display peptide library onto PS‐coated ELISA plates. Repeated biopanning for a total of four rounds revealed a predominant enrichment of the phage clone displaying peptide sequence, CLSYYPSYC (46%). The identified phage clone evidenced enhanced binding to a number of apoptotic cells over non‐apoptotic cells, and this binding was inhibited by both annexin V and synthesized peptide displayed on the phage. The binding of the fluorescein‐labelled CLSYYPSYC peptide to apoptotic versus normal cells was assessed by both FACS analysis and fluorescence microscopy. Optical imaging after the systemic administration of fluorescein‐labelled CLSYYPSYC peptide to tumour‐bearing nude mice (H460 cells xenograft model) treated with a single dose of an anticancer drug (camp‐tothecin) indicated peptide homing to the tumour. The histological examination of tumour tissues showed intense staining of the tumour vasculature and apoptotic tumour cells. With these results, the CLSYYPSYC peptide is recognized as a novel PS‐recognizing moiety which may possibly be developed into a molecular probe for the imaging of apoptosis in vivo. This application would clearly be relevant to assessments of the efficacy of anticancer therapy in tumours.
Polymorphisms in the 5′ flanking region of IL12RB2 are associated with susceptibility to periodontal diseases in the Japanese population
Authors: Takeuchi‐Hatanaka Kazu , Ohyama Hideki , Nishimura Fusanori , Kato‐Kogoe Nahoko , Soga Yoshihiko , Matsushita Sho , Nakasho Keiji , Yamanegi Koji , Yamada Naoko , Terada Nobuyuki , Takashiba Shogo 
Published: March 2008

AbstractObjectives: The expression of interleukin (IL)‐12Rβ2 molecule is a crucial regulatory factor in the T‐helper type (Th) 1 differentiation of T cells. To elucidate the role of the cell‐mediated immune (CMI) response in the pathogenesis of periodontitis, Japanese periodontal patients were subjected to single nucleotide polymorphism (SNP) analyses of the 5′ flanking region of IL12RB2, whose variants are frequently detected in lepromatous leprosy patients, in which the very weak cellular immune response is caused by low expression of IL‐12Rβ2.Material and Methods: The gene polymorphisms of the 5′ flanking region of IL12RB2 were examined in subjects with several types of periodontal disease and in healthy controls. Serum immunoglobulin (Ig) G antibody titres against periodontopathic bacteria were measured and compared in periodontal patients with and without variant alleles of IL12RB2.Results: The frequencies of variant alleles of IL12RB2 were significantly higher in aggressive periodontitis patients as compared with healthy controls or chronic periodontitis patients. Serum IgG titres against all periodontal bacteria examined in subjects carrying variant alleles were higher than those in subjects without variant alleles.Conclusion: IL‐12Rβ2 SNPs could be useful as genetic markers to access the susceptibility of the general population to periodontal disease. Low CMI responses or high humoral responses are associated with the pathogenesis of inflammatory periodontal diseases.
Tissue alterations after tooth extraction with and without surgical trauma: a volumetric study in the beagle dog
Authors: Fickl Stefan , Zuhr Otto , Wachtel Hannes , Bolz Wolfgang , Huerzeler Markus 
Published: March 2008

AbstractObjectives: The aim of this study is to evaluate whether tooth extraction without the elevation of a muco‐periosteal flap has advantageous effects on the resorption rate after tooth extraction.Material and Methods: In five beagle dogs polyether impressions were taken before the surgery. The roots of the first and second pre‐molars (P1 and P2) were extracted and the sites were assigned to one of the following treatments: treatment group (Tx) 1, no treatment; Tx 2, surgical trauma (flap elevation and repositioning); Tx 3, the extraction socket was filled with BioOss Collagen® and closed with a free soft‐tissue graft; Tx 4, after flap elevation and repositioning, the extraction socket was treated with BioOss Collagen® and a free soft‐tissue graft. Impressions were taken 2 and 4 months after surgery. The casts were scanned, matched together with baseline casts and evaluated with digital image analysis.Results: The “flapless groups” demonstrated significant lower resorption rates both when using socket‐preservation techniques and without. Furthermore, socket‐preservation techniques yielded better results compared with not treating the socket.Conclusion: The results demonstrate that leaving the periosteum in place decreases the resorption rate of the extraction socket. Furthermore, the treatment of the extraction socket with BioOss Collagen® and a free gingival graft seems beneficial in limiting the resorption process after tooth extraction.
Longitudinal study on the relationship between serum albumin and periodontal disease
Authors: Iwasaki Masanori , Yoshihara Akihiro , Hirotomi Toshinobu , Ogawa Hiroshi , Hanada Nobuhiro , Miyazaki Hideo 
Published: March 2008

AbstractAim: The purpose of this study was to evaluate the relationship between periodontal disease and the general health status in community‐dwelling elderly using the serum albumin concentration as a criterion index of the severity of underlying disease and nutrition.Material and Methods: Six hundred subjects aged 70 years underwent a baseline examination. Dental examinations were carried out at baseline and once a year for 4 years. Periodontal conditions were estimated for subjects with at least one remaining tooth. Clinical attachment levels at six sites of all teeth present were measured. A change in loss of attachment of 3 mm or greater in 1 year at each site was defined as periodontal disease progression. Data were analysed in subjects for whom data were available for 4 years.Results: Serum albumin concentration at baseline ranged from 3.4 to 5.0 g/dl with a mean of 4.3±0.2. When the analysis was stratified by smoking status, we found that serum albumin concentration had a significant effect on periodontal disease progression among non‐smokers (standardized regression coefficient=−0.16; p=0.017), using multiple regression analysis.Conclusions: The findings of the present study suggest that serum albumin concentration is a significant risk predictor of periodontal disease progression among elderly non‐smokers.
Transforming growth factor‐β1 gene expression and cyclosporine A‐induced gingival overgrowth: a pilot study
Authors: Radwan‐Oczko Małgorzata , Boratyńska Maria , Ziętek Marek , Dobosz Tadeusz 
Published: March 2008

AbstractAims: The relationship between gingival overgrowth (GO) induced by cyclosporine A (CsA) and transforming growth factor‐β1 (TGF‐β1) remains unclear. The aims of the present study were to evaluate TGF‐β1 gene expression under different immunosuppressive treatments and its association with TGF‐β1 gene functional polymorphism and GO in renal transplant recipients.Material and Methods: The study included 98 CsA‐treated renal transplant recipients (with and without GO) and 44 tacrolimus‐treated transplant patients (without GO). TGF‐β1 mRNA expression was measured using a real‐time quantitative polymerase chain reaction assay. The levels were correlated with TGF‐β1 gene polymorphisms at codons 10 and 25, with different immunosuppressive treatment and GO.Results: The level of TGF‐β1 gene expression was insignificantly lower in the CsA‐treated group compared with the tacrolimus group, and significantly lower in the group with GO compared with patients without GO. In tacrolimus‐ and CsA‐treated patients, but not in patients with GO, the level of TGF‐β1 gene expression was associated with functional phenotypes of TGF‐β1. The incidence, degree and extent of GO were higher in recipients with lower TGF‐β1 gene expression.Conclusions: Lower level TGF‐β1 gene expression, not functional polymorphism, in patients treated with CsA may be considered to be a risk factor for GO.
The methylenetetrahydrofolate reductase 677C>T gene polymorphism is not associated with chronic plaque psoriasis
Authors: Weger Wolfgang , Hofer Angelika , Stanger Olaf , Wolf Peter , El‐Shabrawi Yosuf , Renner Wilfried , Kerl Helmut , Salmhofer Wolfgang 
Published: March 2008

AbstractBackground:  Methylenetetrahydrofolate reductase (MTHFR) is involved in the formation of methyl donors, which contribute to DNA methylation. DNA methylation is an essential epigenetic feature playing a critical role in gene regulation and cellular differentiation. In addition, MTHFR activity affects plasma homocysteine levels. A functional polymorphism in the MTHFR gene (677C>T, rs1801133) leading to reduced enzyme activity has been associated with chronic plaque psoriasis in a Chinese population. This finding, however, has not yet been either confirmed or refuted in other populations. The purpose of the present study was to investigate a hypothesized association between the MTHFR 677C>T polymorphism and the presence of chronic plaque psoriasis in a Caucasian population.Methods:  Genotypes for the MTHFR 677C>T polymorphism were determined in 310 patients and 247 control subjects. In a subgroup of 33 patients and 33 sex‐ and age‐matched control subjects, fasting plasma homocysteine concentrations were determined by high‐performance liquid chromatography and immunological assays were used for the measurement of folate and vitamin B12.Results:  Prevalence of the homozygous MTHFR 677TT genotype did not significantly differ between patients and controls (15.2% vs 11.7%, P = 0.24). Mean plasma homocysteine concentrations were significantly higher in psoriasis patients than among control subjects (13.5 ± 5.3 μmol/l vs 11.0 ± 2.2 μmol/l, P = 0.026). No significant differences between either mean plasma folate or vitamin B12 concentrations were observed between both groups.Conclusion:  Our data suggest that the MTHFR 677C>T gene polymorphism is not associated with chronic plaque psoriasis among Caucasians.
Topical isoflavones provide effective photoprotection to skin
Authors: Lin Jing‐Yi , Tournas Joshua A. , Burch James A. , Monteiro‐Riviere Nancy A. , Zielinski Jan 
Published: March 2008

SummaryBackground/purpose: Isoflavones, one main group of phytoestrogens, have antioxidative and photoprotective effects in cellular and mouse studies. The aim of this study is to obtain a more comprehensive understanding of the isoflavone‐mediated photoprotection with the pig skin model, a more human‐resembling model.Methods: The pig skin was treated with five well‐known isoflavone compounds (genistein, equol, daidzein, biochanin A, and formononetin) and one antioxidant combination solution of 15% vitamin C and 1% vitamin E and 0.5% ferulic acid (CEF) daily for 4 days. Skin was irradiated with solar‐simulated UV irradiation, 1 to 5 minimal erythema dose (MED) at 1‐MED intervals. Evaluation was carried out 24 h later by colorimeter‐measured erythema and sunburn cell numbers.Results: Topical application of 0.5% solutions of three individual phytoestrogens – genistein, daidzein, biochanin A – are better than similar solutions of equol or formononetin in protecting pig skin from solar‐simulated ultraviolet (SSUV)‐induced photodamage, as measured by sunburn cell formation and/or erythema. However, the protection was less than that provided by a topical combination antioxidant standard containing 15% L‐ascorbic acid, 1%α‐tocopherol, and 0.5% ferulic acid.Conclusion: Isoflavones provide effective photoprotection and are good candidate ingredients for protection against ultraviolet (UV) photodamage.
The effect of ultraviolet B‐induced vitamin D levels on host resistance to Mycobacterium tuberculosis: a pilot study in immigrant Asian adults living in the United Kingdom
Authors: Yesudian Paul Devakar , Berry Jacqueline Lesley , Wiles Siouxsie , Hoyle Stefan , Young Douglas Brownlie , Haylett Ann Katarina , Rhodes Lesley Elizabeth , Davies Peter 
Published: March 2008

SummaryAsian immigrants to the United Kingdom demonstrate much higher tuberculosis rates than the indigenous population. This is postulated to be because of their low vitamin D levels, consequent upon a combination of diet and their reduced ultraviolet (UV) exposure in the United Kingdom, because vitamin D enhances antimycobacterial activity in in vitro systems. The aim of this study was to examine the relationship between UVB exposure, vitamin D levels and tuberculo‐immunity in Asian immigrants in the United Kingdom. Suberythemal UVB treatments were given to eight subjects on 3 consecutive days, using broadband UVB fluorescent lamps. Blood was sampled for 25‐hydroxyvitamin D (25‐OH D) and whole blood functional assays were performed for antimycobacterial immunity. The mean 25‐OH D level increased from a baseline of 11.23 ng/ml (95% CI 6.7–20.39) to 20.39 ng/ml (95% CI 16.6–20) following UVB treatment, P<0.01. However, no significant change in antimycobacterial immunity occurred following UVB exposure. This pilot study in Asian subjects with good baseline tuberculo‐immunity has not supported a role for UVB‐induced 25‐OH D in the immune response to Mycobacterium tuberculosis.
Effect of ultraviolet adaptation on the ultraviolet absorption spectra of human skin in vivo
Authors: Meinhardt Merve , Krebs Ronald , Anders Angelika , Heinrich Ulrike , Tronnier Hagen 
Published: March 2008

SummaryBackground: The absorption spectrum of human skin provides a basis for the estimation of the possible photobiological impact of ultraviolet (UV) radiation. The optical properties of human skin in the UV spectral range have so far mainly been measured ex vivo due to a lack of an appropriate in vivo technique and the change of optical properties during the course of adaptation to higher UV doses has hardly been addressed.Methods: We have determined the absorption spectra of human skin in vivo in the wavelength range from 290 to 341 nm in 3 nm steps using laser optoacoustics. In this technique, optical properties are derived from the pressure profile generated by absorbed light energy in the sample. Spectra from the volar and dorsal aspects of the forearm of 20 subjects were compared, i.e. sites with native and various facultative pigmentation.Results: UV adaptation shows as an increase in absorption coefficients over the entire measured UV range and especially in short‐range UVB. Subject groups with high vs. low UV exposure can be discriminated by analyzing the difference absorption spectra between dorsal and volar aspects of the forearm. No dependence on the subject's phototype was seen in the degree of adaptation.Conclusion: The difference between native and facultative pigmentation may be explained by the absorption properties of the two prime chromophores responsible for adaptation to higher UV exposure: melanin and keratin. Stronger pigmentation, i.e. a higher melanin concentration, is found as an increase of absorption coefficients over the entire UVA‐II/UVB range. The thickening of the horny layer and accordingly, a higher influence of keratin on the absorption spectra is prominent especially in the UVB region.
Role of hyperinflation vs. deflation on dyspnoea in severely to extremely obese subjects
Authors: Romagnoli I. , Laveneziana P. , Clini E. M. , Palange P. , Valli G. , De Blasio F. , Gigliotti F. , Scano G. 
Published: March 2008

AbstractAim:  To test the hypothesis that obese individuals may either hyperinflate or deflate the lung when exercising. In both cases breathlessness is an inescapable consequence.Methods:  Ventilatory variables, end‐expiratory lung volume and end‐inspiratory lung volume, and dyspnoea score (Borg scale) were studied in 20 class II‐III obese subjects and 14 healthy controls during incremental symptom‐limited cycle exercise.Results:  Ventilation increased with increasing work rate, in obese and in control subjects; most obese subjects had to increase end‐expiratory lung volume to escape from flow limitation; in contrast, like controls, a few subjects deflated the lung on heavy‐to‐peak exercise. Dyspnoea was equal in degree at anaerobic threshold and peak exercise in obese as in control subjects, and in obese who hyperinflated as in those who deflated the lung. In particular, end‐expiratory lung volume at baseline (r = −0.84, P = 0.04) was negatively correlated with changes in Borg score in obese who did not hyperinflate: the lower the former the higher the latter. On the other hand, tidal volume (r = 0.54, P = 0.045) and decrease in inspiratory reserve volume (r = 0.59, P = 0.028) were positively correlated with the Borg score in obese subjects who hyperinflated. No other independent variable correlated with the Borg score.Conclusions:  We conclude that not all obese subjects had to increase end‐expiratory lung volume on heavy‐to‐peak exercise. Changes in dyspnoea for unit changes in ventilation were similar in obese who did hyperinflate as well as in those who did not, suggesting that the increase in respiratory neural drive, associated with an increase in ventilation, is an important source of dyspnoea in obese as well as in control subjects.