bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of a pre‐formulated amphotericin B lipid emulsion for the treatment of Indian Kala‐azar
Authors: Sundar S. , Chakravarty J. , Agarwal D. , Shah A. , Agrawal N. , Rai M.
Published: August 2008

Amphotericin B (AB) deoxycholate is highly effective in antimony refractory cases for the treatment of visceral leishmaniasis (VL) in Bihar. But the need for prolonged hospitalisation and frequent, occasionally serious, adverse events are its major drawbacks. Lipid formulations of AB are devoid of these problems, but very expensive. We evaluated the safety and efficacy of a commercial standardised amphotericin B emulsion, a product of AB formulated in lipid emulsion vehicle (ABLE) in the treatment of Indian VL. In this open label, non‐comparative study, 15 patients in each group were given three daily intravenous infusions each of 3, 4 or 5 mg/kg. All 45 patients (15 in each group) completed the treatment. The drug was tolerated well. Infusion reactions occurred in 5 (11%) patients and vomiting in 2 (4.4%). No nephrotoxicity or other organ toxicity was observed. At the end of treatment all patients of every group were clinically and parasitologically cured. However, during 6 months follow up, three patients from the 5 mg/kg group and one from the 4 mg/kg group tested positive for splenic aspirate. Thus 41 (91.1%; 95% CI 78–97) of 45 patients were cured with a total dose ranging between 9 and 15 mg/kg. There was no dose response linear correlation. In this preliminary study, AB formulated in a lipid emulsion vehicle was safe and effective for the treatment of VL in India.
Retrovirus vector‐mediated gene transfer into the chick optic vesicle by in ovo electroporation
Authors: Sakuta Hiraki , Suzuki Ryoko , Noda Masaharu
Published: August 2008

Owing to its external position in the embryo, the chick eye has been used as a readily accessible model for studying the molecular mechanisms behind the patterning of the central nervous system. Although methods of genetic analysis have not been established as in the mouse, the chick is convenient for analyzing the functions of genes by in ovo electroporation of retroviral vectors. In this review, we describe the retroviral vector‐mediated transfer of genes into the chick optic vesicle by in ovo electroporation. A rapid, efficient, and sustained expression of transgenes is achieved by this approach.
Enhancer analysis by chicken embryo electroporation with aid of genome comparison
Authors: Uchikawa Masanori
Published: August 2008

The identification of the enhancers associated with each developmentally regulated gene is a first step to clarify the regulatory mechanisms underlying embryogenesis. The electroporation technique using chicken embryo is a powerful tool to identify such enhancers. The technique enables us to survey a large genomic region and to analyze the enhancers in great detail. Comparison of the genomic sequences of the chicken and other vertebrate species identifies conserved non‐coding sequence blocks to which the functionally identified enhancers often correspond. In this review, I describe in detail the methods to analyze the enhancers using the chicken embryo electroporation and genome comparison.
Mammalian testis: A target of in vivo electroporation
Authors: Yomgogida Kentaro
Published: August 2008

Mammalian spermatogenesis consists of three biologically significant processes: stem cell self‐renewal and differentiation, meiosis, and haploid cell morphogenesis. Understanding the molecular mechanisms behind these processes might provide clues to the puzzle of species preservation and evolution, and to treatments for male infertility. However, few useful in vitro systems exist to investigate these processes at present. To elucidate these mechanisms, in vivo electroporation of the testis might be a convenient option. Since DNA solution can be injected into the seminiferous tubule via the rete testis, similar to germ cell transplantation, it is easy to transfect expression vectors into various differentiated germ cells and supporting Sertoli cells with adequate electric shock. Unfortunately, it is difficult to create transgenic animals using this method because of its low efficiency. However, gain‐ and loss‐of‐function assays, promoter assays, and tagged‐protein behavior assays can be conducted with this technique, as in in vitro culture systems.
Gene application with in utero electroporation in mouse embryonic brain
Authors: Shimogori Tomomi , Ogawa Masaharu
Published: August 2008

Mouse genetic manipulations, such as the production of gene knock‐out, knock‐in, and transgenic mice, have provided excellent systems for analysis of numerous genes functioning during development. Nevertheless, the lack of specific promoters and enhancers that control gene expression in specific regions and at specific times, limits usage of these techniques. However, progress in in utero systems of electroporation into mouse embryos has opened a new window, permitting new approaches to answering important questions. Simple injection of plasmid DNA solution and application of electrical current to mouse embryos results in transient area‐ and time‐dependent transfection. Further modification of the technique, arising from variations in types of electrodes used, has made it possible to control the relative size of the region of transfection, which can vary from a few cells to entire tissues. Thus, this technique is a powerful means not only of characterizing gene function in various settings, but also of tracing the migratory routes of cells, due to its high efficiency and the localization of gene expression it yields. We summarize here some of the potential uses and advantages of this technique for developmental neuroscience research.
Novel method for the nuclear transfer of adult somatic cells in medaka fish (Oryzias latipes): Use of diploidized eggs as recipients
Authors: Wakamatsu Yuko
Published: August 2008

Until recently, the nuclear transfer of adult somatic cell nuclei in fish has been unsuccessful. This is primarily because of chromosomal aberrations in nuclear transplants, which are thought to arise due to asynchrony between the cell cycles of the recipient egg and donor nucleus. We recently succeeded in circumventing this difficulty by using a new nuclear transfer method in medaka fish (Oryzias latipes). Instead of enucleated eggs, the method uses non‐enucleated and diploidized eggs, obtained by retention of the second polar body release, as recipients in the nuclear transfer of primary culture cells from the caudal fin of an adult green fluorescent protein gene (GFP)‐transgenic strain. We found that 2.7% of the reconstructed embryos grew into diploid and fertile adults exhibiting donor expression characteristics and transmission of the GFP marker gene to progeny. The mechanism underlying the generation of nuclear transplants using this method is unknown at present; however, analyses of donor and recipient nuclei behavior and the cytoskeletal mechanisms involved in the early developmental stages, as well as the special ability of diploidized eggs to facilitate reprogramming of the donor nuclei will result in elucidation of the mechanism.
Production of a maternal‐zygotic medaka mutant using hybrid sterility
Authors: Shimada Atsuko , Takeda Hiroyuki
Published: August 2008

Taking advantage of the characteristics that make hybrids between Japanese and Chinese medaka grow well, albeit sterile, we have developed a method of germ‐line replacement in which these hybrids are used as hosts for the production of a maternal‐zygotic mutant. The protocol is described herein.
Lymphovascular invasion is an independent predictor of prostate‐specific antigen failure after radical prostatectomy in patients with pT3aN0 prostate cancer
Authors: Yamamoto Shinya , Kawakami Satoru , Yonese Junji , Fujii Yasuhisa , Ohkubo Yuhei , Suyama Taisuke , Komai Yoshinobu , Kijima Toshiki , Ishikawa Yuichi , Fukui Iwao
Published: August 2008

Objectives:  To investigate the association of lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens with prostate‐specific antigen (PSA) failure in patients with pT3aN0 prostate cancer (PCA).

Methods:  We retrospectively reviewed the clinical records of 94 patients with pT3aN0 PCA treated with RP alone. All of the 94 patients were prospectively observed without any treatment until PSA failure was confirmed. We investigated the association of LVI with the adverse pathological findings in RP specimens and the PSA failure‐free survival rate. The Cox proportional hazard model was used to elucidate predictors of PSA failure.

Results:  Median follow up was 47.4 months (quartile range 9.1 to 146.8). LVI was found in 26 (27.7%) of the 94 patients. In a multivariate analysis, PSA (P = 0.0054) and LVI (P = 0.015) were significant and independent predictors of PSA failure. Stratifying patients into four risk groups by LVI status and PSA level, the PSA failure‐free survival rate in patients with negative LVI and PSA ≤10 ng/mL was significantly better than any other groups (positive LVI and/or PSA >10 ng/mL).

Conclusions:  Adjuvant therapy would not be indicated to patients with pT3aN0 PCA with negative LVI and PSA ≤10 ng/mL.
Endogenous oxalogenesis after acute intravenous loading with ethylene glycol or glycine in rats receiving standard and vitamin B6‐deficient diets
Authors: Teerajetgul Yaovalak , Hossain Rayhan Zubair , Machida Noriko , Sugaya Kimio , Ogawa Yoshihide
Published: August 2008

Objectives:  The effect on endogenous oxalate synthesis of acute intravenous loading with ethylene glycol or glycine was investigated in rats on a standard or a vitamin B6‐deficient diet.

Methods:  Twenty‐four male Wistar rats weighing approximately 180 g were randomly divided into ethylene glycol and glycine groups of 12 animals each. These groups were further divided into two subgroups of six animals each that were fed either a standard or a vitamin B6‐deficient diet for 3 weeks. Animals of these two subgroups received an intravenous infusion of 20 mg (322.22 µmol) of ethylene glycol or 100 mg (1332.09 µmol) of glycine, respectively. Urine samples were collected just before intravenous infusion of each substance and at hourly intervals until 5 h after receiving the infusion. Urinary oxalate, glycolate, and citrate levels were measured by capillary electrophoresis.

Results:  Urinary oxalate and glycolate excretion was significantly increased after ethylene glycol administration. Significant differences between the control and vitamin B6‐deficient groups were found. In contrast, there were only small changes of oxalate and glycolate excretion after glycine administration. Recovery of the given dose of ethylene glycol as oxalate in 5‐h urine was 0.31% and 7.15% in the control and vitamin B6‐deficient groups, respectively, whereas recovery of glycolate was 0.68% and 7.22%, respectively.

Conclusions:  Ethylene glycol loading has a significant effect on urinary oxalate excretion in both normal and vitamin B6‐deficient rats, whereas glycine loading only has a small effect. Oxalate and glycolate excretion after ethylene glycol loading were respectively 23‐fold and 11‐fold higher in vitamin B6‐deficient rats than in controls.
Efficacy of bacillus Calmette‐Guérin in the treatment of superficial bladder cancer: The impact of previous intravesical treatment
Authors: Okamura Takehiko , Akita Hidetoshi , Imura Makoto , Kaneko Tomoyoshi , Mizuno Kentaro , Tozawa Keiichi , Kohri Kenjiro
Published: August 2008

Objective:  To clinically evaluate the role of intravesical bacillus Calmette‐Guérin (BCG) in the management of superficial bladder cancer, focusing on dose, age, high grade/stage, and pretreatment episodes with other therapies in long‐term follow‐up patients.

Methods:  A total of 213 patients with superficial (Ta‐T1) transitional cell carcinoma of the bladder received 6–8 weekly instillations of 40, 60 or 80 mg of Tokyo strain BCG. Further 6–8 monthly applications were given in some cases.

Results:  Recurrence‐free and progression‐free survival rates were compared with reference to dose, age, previous treatment, grade, stage, and high risk categories. Overall recurrence‐free rates for 3, 5, and 10 years were 70.8%, 67.1%, and 57.6%, with progression‐free survival rates of 94.5%, 93.6%, 90.6%, respectively. In univariate analyses, younger cases demonstrated higher recurrence‐free survival rates, but without statistical significance (P = 0.1229). Recurrence‐free rates were significantly higher for cases without previous intravesical treatment (P = 0.0010). There was no significant BCG dose‐dependence. High grade and high stage patients were confirmed as having higher recurrence and progression rates.

Conclusions:  Intravesical instillation of BCG is the most effective in the long term when chosen as the initial prophylactic therapy for the prevention of recurrence in superficial bladder cancer.
Surface area of chorionic villi of placentas: An index of intrauterine growth restriction of fetuses
Authors: Biswas Sharmistha , Ghosh Samit K. , Chhabra Shakuntala
Published: August 2008

Aim:  Histomorphometric studies of placentas from idiopathic intrauterine growth restricted (IUGR) fetuses as well as normal‐weight (control) fetuses were performed to determine surface area of chorionic villi (mostly terminal and few intermediate) using stereological technique. The results were compared to determine the difference in the values of surface area of chorionic villi, and to establish any relationship between placental histomorphometric changes and IUGR.

Methods:  Placentas from fifty (50) full‐term, uncomplicated deliveries were collected; twenty eight (28) of them were associated with IUGR babies and twenty two (22) were from normal‐weight babies. Placental weights and volumes were measured. Pieces of placental tissues were formalin‐fixed, processed and embedded in paraffin. Seven‐micron sections were cut and stained with HE stain. Histomorphometric and stereological studies were performed.

Results:  IUGR placental weights and volumes were lower than those of controls. Surface areas of villi of IUGR placentas had a mean of 8.19 m2 (SD ± 2.88). For control placentas, the mean was 10.02 m2 (SD ± 1.83). The mean value of the surface area of villi of the IUGR group was significantly lower than that of the control group.

Conclusion:  These findings pointed to a defect in the normal interaction between trophoblast and maternal tissue, leading to a reduced surface area of villi. Because the surface area of the villi presents the interface between maternal and fetal circulation, its reduction might be the cause of idiopathic intrauterine growth restriction.
Maternal mortality in India: A 20‐year study from a large referral medical college hospital, West Bengal
Authors: Bhattacharyya Subir Kumar , Majhi Arup Kumar , Seal Subrata Lall , Mukhopadhyay Sima , Kamilya Gourisankar , Mukherji Joydev
Published: August 2008

Aim:  The present study was carried out to analyze the maternal death rate and its changing trends over a 20‐year period in a large referral/teaching institution in Eastern India.

Methods:  A retrospective analysis of maternal deaths was carried out from January 1986 to December 2005 at the Department of Obstetrics and Gynaecology, R. G. Kar Medical College and Hospital, Kolkata, India. Records were divided into four 5‐yearly periods: 1986–1990; 1991–1995; 1996–2000; and 2001–2005, for comparison of the trends. The initial interval from 1986 to 1990 was chosen as the reference period.

Results:  The cumulative maternal mortality ratio (MMR) was 599.3 per 100 000 live births. Comparison between the first 5‐year period (1986–1991) and the last (2001–2005) showed a statistical significant downward trend in MMR (683.6 vs 474.3; P < 0.001). Deaths due to direct causes are still the leading cause, accounting for 82.09% of total deaths. Hypertensive disorders (36.14%), hemorrhage (21.91%) and sepsis (19.54%) were still the major causes of direct obstetric deaths throughout the study period. Hypertensive disorders alone showed a substantial decline after the introduction of magnesium sulphate.

Conclusion:  The fall in maternal mortality has been very slow.
Treatment of cervical cancer with adjuvant chemotherapy versus adjuvant radiotherapy after radical hysterectomy and systematic lymphadenectomy
Authors: Hosaka Masayoshi , Watari Hidemichi , Takeda Mahito , Moriwaki Masashi , Hara Yoko , Todo Yukiharu , Ebina Yasuhiko , Sakuragi Noriaki
Published: August 2008

Aim:  To compare the clinical efficacy focused on post‐treatment morbidity between adjuvant chemotherapy (CT) and pelvic radiotherapy (RT) after radical hysterectomy for patients with cervical cancer.

Methods:  A total of 125 patients with cervical squamous cell carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy at Hokkaido University Hospital between 1991 and 2002 were enrolled in the study for retrospective analysis. Seventy patients with recurrent risk factors, including deep stromal invasion, lymph vascular space invasion, parametrial invasion, lymph node metastasis (LNM), and bulky tumor (≥4 cm), received adjuvant therapy; 42 were treated with RT, and 28 were treated with CT. Almost all patients with multiple LNM received RT. Analyses were also performed on a subgroup of 50 patients without multiple LNM (23 RT, 27 CT). Clinical efficacy of post‐treatment morbidity and survival was evaluated.

Results:  Because there were more patients with multiple LNM in the RT group, we analyzed disease‐free survival in 50 patients without multiple LNM. The 3‐year disease‐free survival rate was 82.6% with RT and 96.3% with CT (P = 0.16). Postoperative bowel obstruction was significantly more frequent in the RT group versus the CT (P = 0.007) and no‐therapy (P = 0.0026) groups. Urinary disturbance was also more frequent in the RT group than in the CT (P = 0.0016) and no‐therapy (P = 0.089) groups.

Conclusion:  CT has the equivalent therapeutic effect as RT with fewer postoperative complications for patients with intermediate risks. A prospective randomized trial is needed to compare CT combined with radical hysterectomy and pelvic lymphadenectomy to RT or chemoradiotherapy.
Prediction of fetal birthweight in Taiwanese women with pre‐eclampsia and gestational hypertension using an equation based on maternal characteristics
Authors: Liu Ching‐Ming , Chang Shuenn‐Dyh , Cheng Po‐Jen
Published: August 2008

Aim:  The purpose of the present study was to develop a method for predicting the birthweight of newborns in women with pre‐eclampsia and gestational hypertension based on maternal characteristics and pregnancy‐related factors.

Methods:  A total of 661 consecutive pregnant women with pre‐eclampsia and gestational hypertension who delivered at Chang Gung Memorial Hospital from 1994 to 2003 were included in the analysis. Multivariate regression formulas (Models I and II) were derived from maternal characteristics to predict low infant birthweight. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated and tested for these formulas.

Results:  The Model I formula was as follows:

image

Using a cut‐off value of 2210 g, the equation predicts the occurrence of a low birthweight baby with 90.9% sensitivity. If higher specificity is required, increasing the cut‐off value to 2488 g yields a specificity of 95.2%. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve of 93.7 (95% confidence interval [CI], 0.88 to 0.99) for low birthweight baby prediction in Model I.

Conclusion:  The results suggest that these regression formulas based on maternal characteristics may accurately predict low birthweight babies in pregnant women with pre‐eclampsia and gestational hypertension. The cut‐off values were determined and cross‐validated by ROC curve analysis.
Gamma‐glutamyltransferase level in pregnancy is an independent risk factor for gestational diabetes mellitus
Authors: Tan Peng C. , Mubarak Sarah , Omar Siti Z.
Published: August 2008

Aim:  To evaluate the relationship between gamma‐glutamyltransferase (GGT) level in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of gestational diabetes (GDM).

Methods:  Blood was taken for analyzing GGT level from women at high risk of GDM at the time of their scheduled OGTT. GDM was diagnosed according to World Health Organization 1999 criteria.

Results:  GGT level correlated positively with the 2‐hour glucose level (Spearman's rho = 0.112: P < 0.05). GGT values that were stratified into quartiles demonstrated a significant trend with diagnosis of GDM (χ2 for trend; P = 0.03). Multivariable logistic regression analysis taking into account maternal age, gestational age at OGTT, body mass index and a positive 50‐g glucose challenge test (GCT) indicated that high GGT was an independent risk factor for GDM (adjusted odds ratio [AOR] 2.1 95% CI 1.2–3.8: P = 0.01). In the subset of women identified by a positive GCT, on multivariable logistic regression analysis, only high GGT was an independent risk factor for GDM (AOR 2.3 95% CI 1.3–4.2: P = 0.007).

Conclusion:  Raised GGT level is an independent risk factor for GDM in high risk pregnant women undergoing OGTT.
Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line
Authors: Watanabe Mari , Kobayashi Yoichi , Takahashi Noriyuki , Kiguchi Kazushige , Ishizuka Bunpei
Published: August 2008

Aim: To determine the receptor subtypes of melatonin in estrogen receptor‐positive endometrial cancer cell line, Ishikawa, and the influence of melatonin on chemosensitivity.

Methods: To confirm the subtype of melatonin on Ishikawa cells, cells were treated with melatonin alone and with antagonists against melatonin receptor luzindole and 4‐phenyl‐2‐propionamidotetralin (4‐P‐PDOT). Expression of MT1/MT2 mRNA was analyzed by reverse transcriptase‐polymerase chain reaction (RT‐PCR). Immunocytochemistry of MT1/MT2 was also performed. The effect of melatonin against expression of MT1, MT2, and ERα‐receptors mRNA was compared with RT‐PCR. To determine whether melatonin enhances the effect of anticancer agents, chemosensitivity test was performed with or without melatonin.

Results: Our study revealed that Ishikawa cells express MT1 by both RT‐PCR and immunocytochemistry. In contrast, expression of MT2 mRNA was not found. Furthermore, ERα mRNA expression was attenuated at melatonin level of 1 × 10−9 M. Chemosensitivity test revealed that melatonin enhanced anti‐tumor effects of paclitaxel among anticancer drugs tested.

Conclusion: Based on the above results, MT1 receptor, but not MT2, is expressed in Ishikawa cells. It was also revealed that the cytostatic effect of melatonin is partly an action mediated by MT1 receptor, and attenuation of ERα expression was predicted as the mechanism of action. Clinical application of melatonin to biochemotherapy might be also expected.
Denitrifying bacteria anaerobically oxidize methane in the absence of Archaea
Authors: Ettwig Katharina F. , Shima Seigo , Van De Pas‐Schoonen Katinka T. , Kahnt Jörg , Medema Marnix H. , Op Den Camp Huub J. M. , Jetten Mike S. M. , Strous Marc
Published: August 2008

Recently, a microbial consortium was shown to couple the anaerobic oxidation of methane to denitrification, predominantly in the form of nitrite reduction to dinitrogen gas. This consortium was dominated by bacteria of an as yet uncharacterized division and archaea of the order Methanosarcinales. The present manuscript reports on the upscaling of the enrichment culture, and addresses the role of the archaea in methane oxidation. The key gene of methanotrophic and methanogenic archaea, mcrA, was sequenced. The associated cofactor F430 was shown to have a mass of 905 Da, the same as for methanogens and different from the heavier form (951 Da) found in methanotrophic archaea. After prolonged enrichment (> 1 year), no inhibition of anaerobic methane oxidation was observed in the presence of 20 mM bromoethane sulfonate, a specific inhibitor of MCR. Optimization of the cultivation conditions led to higher rates of methane oxidation and to the decline of the archaeal population, as shown by fluorescence in situ hybridization and quantitative MALDI‐TOF analysis of F430. Mass balancing showed that methane oxidation was still coupled to nitrite reduction in the total absence of oxygen. Together, our results show that bacteria can couple the anaerobic oxidation of methane to denitrification without the involvement of Archaea.
Comparison of pre‐ vs. postmeal administration of miglitol for 3 months in type 2 diabetic patients
Authors: Aoki K. , Nakajima S. , Nezu U. , Shinoda K. , Terauchi Y.
Published: August 2008

Aim:  α‐Glucosidase inhibitors (αGIs) primarily modify postprandial plasma glucose levels and should be taken just before meals. We previously demonstrated that a single administration of miglitol within 30 min after the start of a meal was equally effective as when administered just before a meal. We here compared pre‐ vs. postmeal administration of miglitol for 3 months in type 2 diabetic patients.

Methods:  Thirty‐one type 2 diabetic outpatients who had never been treated with insulin injections or αGIs were randomized to two groups: patients in group A were asked to take miglitol just before meals, while patients in group B were asked to take miglitol after meals. We measured 1,5‐anhydroglucitol (1,5‐AG) and HbA1C levels in these patients.

Results:  The administration of miglitol after meals for a 3‐month period decreased HbA1C and increased 1,5‐AG levels to the same extent as when administered just before meals. The incidence of adverse effects seemed to be unrelated to the timing of the miglitol administration.

Conclusions:  Our results suggest that if patients have difficulty remembering to take miglitol just before meal, they should be instructed to take the medicine together with other medicine(s) after the meal; this instruction may improve the treatment compliance of diabetic patients.
Relationship between soluble CD40 ligand and γ‐glutamyltransferase concentrations in non‐drinking, young Type 1 diabetic individuals
Authors: Zoppini G. , Targher G. , Trombetta M. , Lippi G. , Muggeo M.
Published: August 2008

Aims  To assess the association between circulating levels of soluble CD40 ligand (sCD40L), an emerging cardiovascular risk factor, and γ‐glutamyltransferase (GGT) activity concentrations in Type 1 diabetic subjects.

Methods  Plasma concentrations of sCD40L and GGT activity, a marker of liver dysfunction, were measured in 54 non‐smoking, non‐drinking, young Type 1 diabetic patients, who were free of diagnosed cardiovascular disease.

Results  When participants were grouped according to tertiles of GGT, plasma sCD40L concentrations steadily increased across GGT tertiles (P = 0.007 for trend). Similarly, plasma sCD40L concentrations were positively correlated with plasma GGT levels in the whole group of participants (r = 0.532; P < 0.0001). In multivariate linear regression analysis, plasma GGT activity levels were positively associated with sCD40L (standardized beta coefficient = 0.342; P = 0.027) independently of age, gender, diabetes duration, glycated haemoglobin, total cholesterol and systolic blood pressure. Further adjustment for the presence of diabetic retinopathy and microalbuminuria did not appreciably attenuate this association.

Conclusions  Our findings suggest that there is a strong, graded, relationship between plasma GGT activity and sCD40L concentrations in non‐smoking, non‐drinking, young Type 1 diabetic individuals. This association appears to be independent of numerous confounding factors. Further studies are required to confirm the reproducibility of these results.
A critical review of the cannabinoid receptor as a drug target for obesity management
Authors: Akbas F. , Gasteyger C. , Sjödin A. , Astrup A. , Larsen T. M.
Published: August 2008

The discovery of cannabinoids, with the well‐known stimulatory effect of Cannabis sativa on appetite, has offered a new drug target for obesity treatment. Cannabinoids act on two different receptors: CB1 receptors which are sited in the brain and many peripheral tissues, and CB2 receptors which are primarily found in immune system cells. Cannabinoid receptor antagonists act centrally by blocking CB1 receptors, thereby reducing food intake. Moreover, they probably also act peripherally by increasing thermogenesis and therefore energy expenditure, as has been suggested by animal experiments. Despite these promising mechanisms of action, recent clinical studies examining the effect of the two CB1 receptor antagonists rimonabant and taranabant showed that the attained weight loss did not exceed that attained with other currently approved anti‐obesity medications. Moreover, potentially severe psychiatric adverse effects limit their clinical use. As several new CB1 receptor antagonists are presently undergoing development, it remains to be elucidated to what extent they differ in terms of efficacy and safety. This review primarily discusses how close cannabinoid receptor antagonists are to the ideal anti‐obesity drug, with respect to their mechanisms of action, clinical effectiveness and safety.
On the Foundations of Law: Religion, Nature, Morals
Authors: ROTHKAMM JAN
Published: August 2008

Abstract. The article discusses the importance of three extra‐legal sources—divine inspiration, natural law, and morality—for a full understanding and effective application of law. Each source is seen as vital due to its ability to compensate for the shortcomings of the other two sources. No source, including belief, is seen as necessarily incompatible with the doctrinal pluralism characteristic of modern societies.
Sanction and Obligation in Hart's Theory of Law
Authors: PRIEL DANNY
Published: August 2008

Abstract.  The paper begins by challenging Hart's argument aimed to show that sanctions are not part of the concept of law. It shows that in the “minimal” legal system as understood by Hart, sanctions may be required for keeping the legal system efficacious. I then draw a methodological conclusion from this argument, which challenges the view of Hart (and his followers) that legal philosophy should aim at discovering some general, politically neutral, conceptual truths about law. Instead, the aim should be to discover the values because of which certain things in the world are classified as law and others as non‐law. Focusing on those would give us a more insight to the roles law plays in society, as well as more illuminating answers to traditional jurisprudential questions like the status of law in evil regimes.
THE DEONTOLOGICAL DEFENSE OF DEMOCRACY: AN ARGUMENT FROM GROUP RIGHTS
Authors: ALTMAN ANDREW , HEATH WELLMAN CHRISTOPHER
Published: August 2008

Abstract: Democracy is regularly heralded as the only form of government that treats political subjects as free and equal citizens. On closer examination, however, it becomes apparent that democracy unavoidably restricts individual freedom, and it is not the only way to treat all citizens equally. In light of these observations, we argue that the non‐instrumental reasons to support democratic governance stem, not from considerations of individual freedom or equality, but instead from the importance of respecting group self‐determination. If this is correct, it implies that a state may choose democracy, but its right to self‐determination means that it is also free, in principle, to decide in favor of some nondemocratic alternative.
ON THE CORRECT TREATMENT OF INVERTED EARTH
Authors: BARTLETT GARY
Published: August 2008

Abstract:The Inverted Earth case has seen fierce debate between Ned Block, who says it defeats the causal‐covariational brand of wide representationalism about qualia, and Michael Tye and Bill Lycan, who say it does not. The debate has generated more heat than light because of a failure to get clear on who is supposed to be proving what, and what premises can be deployed in doing so. I argue that a correct understanding of the case makes it clear that the causal covariation theory is in deeper trouble over Inverted Earth than is generally supposed even by the theory's detractors.
REPRESENTATIONALISM AND THE ARGUMENT FROM HALLUCINATION
Authors: THOMPSON BRAD
Published: August 2008

Abstract:Representationalism is sometimes advertised as providing a novel response to the argument from hallucination, one that accepts the presence of a ‘common factor’ between veridical and hallucinatory experience without positing sensory intermediaries between the mind and the world. I argue that much of the attractiveness of representationalism stems from a failure in the literature to distinguish between two distinct possible versions of representationalism, what I call ‘content‐based representationalism’ and ‘vehicle‐based representationalism’. Generically, representationalism appears to have a response to the argument from hallucination that avoids a commitment to qualia or sense‐data. But once the distinction between content‐based representationalism and vehicle‐based representationalism is recognized, this response to the argument from hallucination fails.
Denying Foreign State Immunity on the Grounds of the Unavailability of Alternative Means
Authors: Tomonori Mizushima
Published: August 2008

Granting immunity from suit to a foreign state or an international organisation, deprives the plaintiff of access to court and appears incompatible with the rule of law. Since the European Court of Human Rights judgment in Waite v Germany (1999), the availability of alternative means for dispute settlement has been emphasised in the context of international organisation immunity. However in the case of foreign state immunity, this approach was not taken by the European Court of Human Rights in Al‐Adsani v United Kingdom (2001) nor by the House of Lords in Jones v Ministry of the Interior of Saudi Arabia (2006). Likewise, foreign state immunity would be granted under the UN State Immunity Convention of 2004, regardless of whether there are alternative means. This Convention, rather than enhancing the rule of law, could lead to its attenuation. That several of these cases involve immunity in cases of torture sharpens their sensitivity.
International Co‐operation in Cross‐Border Insolvency: HIH Insurance
Authors: Townsend John
Published: August 2008

The House of Lords decision in HIH Insurance raised important questions about the pari passu principle of distribution in cross‐border insolvency. This comment examines the case in light of academic debate, arguing that Lord Hoffmann's application of the principle of (modified) universalism achieved distributive justice amongst HIH group creditors.
Differential mortality of wintering shorebirds on the Banc d’Arguin, Mauritania, due to predation by large falcons
Authors: VAN DEN HOUT PIET J. , SPAANS BERNARD , PIERSMA THEUNIS
Published: August 2008

Predators may influence many aspects of the daily life and seasonal movements of their prey. Here we quantify direct, and evaluate indirect effects of predation by three falcon species (Lanner FalconFalco biarmicus, Barbary FalconFalco pelegrinoidesand Peregrine FalconFalco peregrinus) on coastal shorebirds wintering on the Banc d’Arguin, Mauritania, an area hosting approximately 30% of the East Atlantic Flyway population of shorebirds. On the basis of 754 h of observation over five winters, 97 witnessed attacks and 585 collected prey remains, we show that shorebirds were safer in larger flocks, which tended to be attacked less often. Furthermore, species that forage relatively close to shore and in small flocks were depredated more often than expected from their relative abundance. In three species, Red KnotCalidris canutus canutus, Bar‐tailed GodwitLimosa lapponica taymyrensisand DunlinCalidris alpina, the juveniles were more vulnerable than adults. We estimated that on average 1% of the juvenile and 0.1% of the adult Red Knots present were killed by large falcons each winter. For Red Knots we simultaneously quantified annual survival on the basis of an individual colour‐marking programme: mortality due to predation by falcons accounted for an estimated 6.2% (juveniles) and 0.8% (adults) of annual mortality. We suggest that juvenile Red Knots are 10 times as likely to be killed by falcons because they use riskier habitats, i.e. early and late tide foraging areas closer to shores where surprise attacks are both more common and more successful. These results indicate that the strength of indirect effects of predation operating in a shorebird population largely outweigh the effects of mortalityper se.
Intraguild predation in raptor assemblages: a review
Authors: SERGIO FABRIZIO , HIRALDO FERNANDO
Published: August 2008

Intraguild predation, the killing of species that use similar resources, has been largely overlooked in raptor investigations. To help fill this gap in knowledge, we conducted a literature review, focusing on studies that tested the behavioural and demographic impact of intraguild predation on individuals, populations, and assemblages of diurnal and nocturnal raptorial species. Overall, data were available for 39 empirical and experimental studies on 63 populations belonging to 11 killer species and 15 victim species. An overview of these studies suggested that intraguild predation was a widespread, size‐based phenomenon. Results from multiple studies on the same species at different locations were usually consistent across wide geographical areas. Individual‐level demographic impacts included reduced site‐occupancy, breeding success and survival. Individuals of the prey species responded to predation pressure through direct spatial avoidance, risk‐sensitive habitat selection, short‐term behavioural avoidance (e.g. reduced vocal activity and escape to refugia after predator detection) and, possibly, temporal segregation. Population‐level effects were common but mainly examined as spatio‐temporal correlations between the abundance of killer and victim species. Correlative evidence also suggested that intraguild predation may have the potential to structure whole raptor assemblages. More studies on other species and different geographic areas are needed to increase our understanding of the causes and consequences of this widespread interaction. From a conservation point of view, intraguild predation may limit the success of raptor preservation programmes and could be used as a management tool through its effect on mesopredator release and its potentially positive, indirect effects on game species.
Identifying predators of eggs and chicks of Lapwing Vanellus vanellus and Black‐tailed Godwit Limosa limosa in the Netherlands and the importance of predation on wader reproductive output
Authors: TEUNISSEN WOLF , SCHEKKERMAN HANS , WILLEMS FRANK , MAJOOR FRANK
Published: August 2008

Farmland bird populations in the Netherlands have shown an accelerating decline in recent years, despite extensive conservation efforts including reserves, agri‐environment schemes and protection of nests by volunteers. Although agricultural intensification is the main cause underlying these declines, there is a growing concern that the ongoing decline of grassland‐breeding shorebirds in recent years is caused or aggravated by increasing predation. Although Red Fox Vulpes vulpes and Carrion Crow Corvus corone are often accused of causing widespread breeding losses, and calls for management of these species are made, very few field data are available on the incidence of predation on grassland shorebirds and the relative importance of different predators. To obtain such data, we identified egg predators using temperature loggers and continuous video recordings of 792 clutches, and chick predators by radiotagging 662 chicks of Black‐tailed Godwit Limosa limosa and Northern Lapwing Vanellus vanellus. In total, 22 species were identified as predators of eggs or chicks, of which Red Fox, Common Buzzard Buteo buteo, Grey Heron Ardea cinerea and Stoat Mustela erminea were the most frequent. Eggs were taken primarily by mammals and chicks more often by birds. There was great variation in predation levels and species involved in predation of clutches between sites and years, but less in chick predation. Hence, there was no correlation between predation levels on clutches and those on chicks within the same sites. In sites where more then 50% of clutches were lost to predation, however, nocturnal predators took the larger share. As temporal and spatial variation on a small scale significantly influences predation levels, a site‐specific approach based on sound knowledge of the local situation will be more effective in reducing predation on farmland birds than general, country‐wide measures. Calculations based on our data indicate that eliminating only one loss factor at a time will often not reverse a local population decline, and provide a strong argument for targeting several locally limiting factors simultaneously instead of focusing on mitigation of predation alone.
The usefulness of sensitivity analysis for predicting the effects of cat predation on the population dynamics of their avian prey
Authors: MACLEAN MAIREAD M. , CARSLAKE DAVID J. , EVANS MATTHEW R. , TOWNLEY STUART , HODGSON DAVID J.
Published: August 2008

Sensitivity analyses of population projection matrix (PPM) models are often used to identify life‐history perturbations that will most influence a population's future dynamics. Sensitivities are linear extrapolations of the relationship between a population's growth rate and perturbations to its demographic parameters. Their effectiveness depends on the validity of the assumption of linearity. Here we assess whether sensitivity analysis is an appropriate tool to investigate the effect of predation by cats on the population growth rates of their avian prey. We assess whether predation by cats leads to non‐linear effects on population growth and compare population growth rates predicted by sensitivity analysis with those predicted by a non‐linear simulation. For a two‐stage, age‐classified House Sparrow Passer domesticus PPM slight non‐linearity arose when PPM elements were perturbed, but perturbation to the vital rates underlying the matrix elements had a linear impact on population growth rate. We found a similar effect with a slightly larger three‐stage, age‐classified PPM for a Winter Wren Troglodytes troglodytes population perturbed by cat predation. For some avian species, predation by cats may cause linear or only slightly nonlinear impacts on population growth rates. For these species, sensitivity analysis appears to be a useful conservation tool. However, further work on multiple perturbations to avian prey species with more complicated life histories and higher‐dimension PPM models is required.
Predation on wader nests in Europe
Authors: MACDONALD MICHAEL A. , BOLTON MARK
Published: August 2008

The population declines of waders in Europe are widely considered to have resulted from habitat loss and degradation due to agricultural changes. However, recent empirical evidence suggests that levels of predation on wader nests are unsustainably high in many cases, even in some situations where breeding habitat is otherwise favourable. We review the published and ‘grey’ literature on nest predation on waders in Europe and quantify the relative importance of the major predators. Nest cameras offer the least biased method of identifying and quantifying nest predators. A small number of camera studies, in combination with others utilizing nest temperature loggers, indicate that nocturnal/mammalian predators make the largest contribution to wader nest predation. More than half of site‐years or studies reviewed reported clutch failure rates of over 50% attributable to predation alone, a rate that is likely to be associated with declining populations, although parameters such as chick and adult survival will also affect population trends. Correlates of wader nest predation are documented, with time of season, field type and management, distance to habitat/field edge, wader nest density, and abundance of mammalian predators being most consistently identified. Future directions of research into wader productivity are discussed, and we suggest that studies quantify additional life‐history parameters such as chick survival, as well as examining the predator community, wherever possible.
Biofilms in chronic wounds
Authors: James Garth A. , Swogger Ellen , Wolcott Randall , Pulcini Elinor deLancey , Secor Patrick , Sestrich Jennifer , Costerton John W. , Stewart Philip S.
Published: August 2008

Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg ulcers are a worldwide health problem. It has been speculated that bacteria colonizing chronic wounds exist as highly persistent biofilm communities. This research examined chronic and acute wounds for biofilms and characterized microorganisms inhabiting these wounds. Chronic wound specimens were obtained from 77 subjects and acute wound specimens were obtained from 16 subjects. Culture data were collected using standard clinical techniques. Light and scanning electron microscopy techniques were used to analyze 50 of the chronic wound specimens and the 16 acute wound specimens. Molecular analyses were performed on the remaining 27 chronic wound specimens using denaturing gradient gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens evaluated by microscopy, 30 were characterized as containing biofilm (60%), whereas only one of the 16 acute wound specimens was characterized as containing biofilm (6%). This was a statistically significant difference (p<0.001). Molecular analyses of chronic wound specimens revealed diverse polymicrobial communities and the presence of bacteria, including strictly anaerobic bacteria, not revealed by culture. Bacterial biofilm prevalence in specimens from chronic wounds relative to acute wounds observed in this study provides evidence that biofilms may be abundant in chronic wounds.
Temporal and quantitative profiles of growth factors and metalloproteinases in acute wound fluid after mastectomy
Authors: Baker Elizabeth A. , Kumar Senthil , Melling Andrew C. , Whetter Deborah , Leaper David J.
Published: August 2008

Seventy‐three samples of acute wound fluid were collected from 47 patients during the first 3 postoperative days (POD) following mastectomy for cancer (n=47 on POD‐1, n=19 on POD‐2, and n=7 POD‐3). Samples were analyzed by enzyme‐linked immunosorbent assay for growth factor levels (epidermal [EGF], platelet‐derived [PDGF], basic fibroblast [bFGF], transforming growth factor‐β1 [TGF‐β1], vascular endothelial [VEGF]), interleukin‐6 (IL‐6), matrix metalloproteinases (MMPs‐2, ‐3, ‐9), and the tissue inhibitor of metalloproteinase 1 (TIMP‐1). The levels of EGF, bFGF, PDGF, and interleukin‐6 peaked on POD‐1, with a significant decrease by POD‐3, while total and active MMP‐2, MMP‐3, and tissue inhibitor of metalloproteinase 1 showed a progressive and significant increase from days 1 to 3. The wounds that later developed an infection (11%) were found to have a significantly lower PDGF and EGF on day 1 (PDGF, median 169 pg/mL [range, 86–2,595]) than the noninfected wounds (2,098 [17–66,506] p<0.05, Mann–Whitney U‐test). Sixty‐two percent patients developed a seroma and the levels of bFGF were significantly less in these patients (441 pg/mL [45–4,108]) than in those patients where there was no seroma (807 [245–3,133] p<0.05). The levels of certain growth factors in acute wound fluid may be important markers for wound outcomes.