bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine agonist therapy of clinically non-functioning pituitary macroadenomas. Is there a role for 123I-epidepride dopamine D2 receptor imaging?
Authors: de Herder Wouter W , Reijs Ambroos E M , Feelders Richard A , van Aken Maarten O , Krenning Eric P , Tanghe Hervé L J , van der Lely Aart-Jan , Kwekkeboom Dik J
Published: October 2006

Objective: Clinically non-functioning pituitary adenomas (NFPAs) can express functional dopamine D2 receptors. Therapy with dopamine (DA) agonists may result in a NFPA size reduction. However, DA agonist-sensitive and -resistant NFPAs are clinically indistinguishable. We have studied the correlation between in vivo imaging of D2 receptors using 123I-epidepride and the radiological response of NFPA to DA in 18 patients.

Methods: Patients were treated with either cabergoline (1–2 mg/week) or quinagolide (150–300 μg/day) for a mean period of 89.7 months (range, 34–187 months).

Results: Pituitary uptake of 123I-epidepride varied from slight uptake classified as grade 0 to very high classified as grade 3. Grade 0 uptake was found in four patients; grade 1 in three; grade 2 in ten, and grade 3 in one. NFPA stabilization or shrinkage with DA agonist therapy showed no significant difference between grade 0, 1, and 2 tumors (mean tumor stabilization or shrinkage: 31, 30, and 36% respectively). However, when we considered a decrease in tumor size ranging from 0 to 20% as tumor stabilization and >20% decrease in tumor size as true shrinkage, one out of four NFPAs with grade 1 uptake, two out of three with grade 1 uptake, and eight out of ten with grade 2 uptake showed tumor shrinkage.

Conclusion: In conclusion, there is limited clinical usefulness of dopamine D2 receptor imaging for predicting the clinical efficacy of DA agonist in selected patients with NFPAs. DA agonist therapy in NFPAs can result in tumor stabilization and shrinkage.
Hypopituitarism in childhood and adolescence following traumatic brain injury: the case for prospective endocrine investigation
Authors: Acerini Carlo L , Tasker Robert C , Bellone Simonetta , Bona Gianni , Thompson Christopher J , Savage Martin O
Published: October 2006

Pituitary dysfunction is now well recognised after traumatic brain injury (TBI) in adults; however, little except anecdotal evidence is known about this potential complication in childhood and adolescence. Histopathological evidence exists for both hypothalamic and pituitary damage, but few data specific to children have been published. We review the available paediatric data, which shows that after both mild and severe TBI, hypopituitarism may occur, with GH and gonadotrophin deficiencies appearing to be most common. Precocious puberty has also been documented. Road-traffic accidents, falls, sport and child abuse are the most common aetiological factors for paediatric TBI. There are no published data on the incidence or prevalence, neither within a population of children with TBI, of hypopituitarism, nor on its natural history or response to hormone replacement. We urge paediatric endocrinologists, in collaboration with adult endocrinologists, to perform formal prospective research studies in patients suffering from TBI to clarify these questions.
Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice
Authors: Maruyama Takaharu , Tanaka Kenichi , Suzuki Jun , Miyoshi Hiroyuki , Harada Naomoto , Nakamura Takao , Miyamoto Yasuhisa , Kanatani Akio , Tamai Yoshitaka
Published: October 2006

G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) is a novel G protein-coupled receptor for bile acid. Tissue distribution and cell-type specificity of Gpbar1 mRNA suggest a potential role for the receptor in the endocrine system; however, the precise physiological role of Gpbar1 still remains to be elucidated. To investigate the role of Gpbar1 in vivo, the Gpbar1 gene was disrupted in mice. In homozygous mice, total bile acid pool size was significantly decreased by 21–25% compared with that of the wild-type mice, suggesting that Gpbar1 contributes to bile acid homeostasis. In order to assess the impact of Gpbar1 deficiency in bile acid homeostasis more precisely, Gpbar1 homozygous mice were fed a high-fat diet for 2 months. As a result, female Gpbar1 homozygous mice showed significant fat accumulation with body weight gain compared with that of the wild-type mice. These findings were also observed in heterozygous mice to the same extent. Although the precise mechanism for fat accumulation in female Gpbar1 homozygous mice remains to be addressed, these data indicate that Gpbar1 is a potential new player in energy homeostasis. Thus, Gpbar1-deficient mice are useful in elucidating new physiological roles for Gpbar1.
Expression and function of the chemokine receptor CCR7 in thyroid carcinomas
Authors: Sancho Margarida , Vieira Joaquim Miguel , Casalou Cristina , Mesquita Marta , Pereira Teresa , Cavaco Branca Maria , Dias Sérgio , Leite Valeriano
Published: October 2006

The chemokine receptor CCR7 plays a critical role in lymphocyte and dendritic cell trafficking into and within lymph nodes, the preferential metastatic site for papillary (PTC) and medullary (MTC) thyroid carcinomas. In order to determine a possible role for CCR7 in mediating the metastatic behaviour of thyroid carcinomas, we analysed its expression in normal and tumoral thyroid tissues of different histotypes and studied the in vitro effects of its activation by the CCR7 ligand, CCL21. Using real-time quantitative-PCR, we observed that CCR7 expression was higher in PTCs and MTCs than in follicular and poorly differentiated thyroid carcinomas. CCR7 expression was ninefold higher in classic compared with follicular variants of PTCs, and its expression in MTCs was significantly correlated with lymph node metastases. Immunohistochemical staining for CCR7 showed protein expression in neoplastic thyroid cells, with higher intensity in PTCs, MTCs and their lymph node metastases (LNMs). We further showed that CCL21 stimulation of a CCR7-expressing thyroid tumour cell line (TPC-1) promotes cell proliferation and migration, and the chemotactic effect of CCL21 in these cells involves actin polymerization, increased β1-integrin expression and increased matrix metalloproteinase secretion. Taken together, our results demonstrate that CCR7 activation on thyroid carcinoma cells by CCL21 – a chemokine abundantly expressed in lymph nodes – favours tissue invasion and cell proliferation, and therefore may promote thyroid carcinoma growth and LNM.
Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct
Authors: Odau Simone , Gabler Christoph , Holder Christoph , Einspanier Ralf
Published: October 2006

The aim of the present study was to investigate the enzymes for the local prostaglandin (PG) biosynthesis present in the bovine oviduct during the estrous cycle to influence early reproductive events. Bovine oviducts were classified into four phases: pre-ovulatory, post-ovulatory, early-to-mid luteal, and late luteal phase, subdivided further into ipsi- or contralateral site and separated into ampulla or isthmus. Oviductal cells were gained by flushing the oviductal regions. Quantitative real-time reverse transcriptase-PCR was performed for the secretory and cytosolic phospholipases A2 (sPLA2IB, cPLA2α, and cPLA2β) and cyclooxygenases (COX-1 and COX-2) as the first step enzymes of PG synthesis. COX-1 and cPLA2β showed significant highest mRNA expression around and before ovulation compared with the luteal phase respectively. sPLA2IB and cPLA2α mRNA expression was unregulated during the estrous cycle. Regional differences in mRNA content were found for sPLA2IB with higher mRNA expression in the ampulla than in the isthmus. Western blot analysis revealed the highest COX-1 protein content in the early-to-mid luteal phase. Immunohistochemistry demonstrated that COX-1 was localized in epithelial and smooth muscle cells, whereas COX-2 was only localized in epithelial cells. COX-2 showed a differential distribution within the epithelial cell layer suggesting a regulation on a cellular level, although the COX-2 mRNA and protein amounts did not vary throughout the estrous cycle. A COX activity assay of oviductal cells revealed that COX activity originated predominantly from COX-1 than from COX-2. Treatment of primary oviductal cells with 10 pg/ml 17β-estradiol or 10 ng/ml progesterone resulted in a higher expression of COX-2 and cPLA2α, but not of the other enzymes. The expression pattern of these enzymes suggests that an estrous-cycle dependent and region-specific PG synthesis in the bovine oviduct may be required for a successful reproduction.
Thyroid hormone-stimulated differentiation of primary rib chondrocytes in vitro requires thyroid hormone receptor β
Authors: Rabier Bénédicte , Williams Allan J , Mallein-Gerin Frederic , Williams Graham R , Chassande O
Published: October 2006

The active thyroid hormone, triiodothyronine (T3), binds to thyroid hormone receptors (TR) and plays an essential role in the control of chondrocyte proliferation and differentiation. Hypo- and hyperthyroidism alter the structure of growth plate cartilage and modify chondrocyte gene expression in vivo, whilst TR mutations or deletions in mice result in altered growth plate architecture. Nevertheless, the particular roles of individual TR isoforms in mediating T3 action in chondrocytes have not been studied and are difficult to determine in vivo because of complex cellular and molecular interactions that regulate growth plate maturation. Therefore, we studied the effects of TRα and TRβ on chondrocyte growth and differentiation in primary cultures of neonatal rib chondrocytes isolated from TRα- and TRβ-deficient mice. T3 decreased proliferation but accelerated differentiation of rib chondrocytes from wild-type mice. T3 treatment resulted in similar effects in TRα-deficient chondrocytes, but in TRβ-deficient chondrocytes, all T3 responses were abrogated. Furthermore, T3 increased TRβ1 expression in wild-type and TRα-deficient chondrocytes. These data indicate that T3-stimulated differentiation of primary rib chondrocytes in vitro requires TRβ and suggest that the TRβ1 isoform mediates important T3 actions in mouse rib chondrocytes.
Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats
Authors: Granado M , Martín A I , Priego T , López-Calderón A , Villanúa M A
Published: October 2006

Chronic inflammation is associated with a decrease in body weight and cachexia, which is characterized by anorexia and skeletal muscle wasting. The expression of atrogens muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx) are increased in muscle atrophy and it is known that tumour necrosis factor (TNF) regulates skeletal muscle loss through TNF receptor p55 (TNFRI). The aim of this study was to examine the effect of polyethylene glycol linked to soluble TNFRI (PEG-sTNFRI) on gene expression of the atrogens MuRF-1 and MAFbx in skeletal muscle of arthritic rats. Rats were injected with Freund’s adjuvant and, 15 days later, arthritic and control rats were injected daily with PEG-sTNFRI (1 mg/kg, s.c.) or saline for 8 days. Arthritis decreased body weight gain, the weight of skeletal muscle and adipose mass. PEG-sTNFRI administration increased body weight gain and adipose mass of arthritic rats; however, it did not modify the skeletal muscle weight. The gene expression of TNF-α, MuRF1 and MAFbx, IGF-I and IGFBP-5 were increased in the skeletal muscle of arthritic rats, and the administration of PEG-sTNFRI did not modify these parameters. These data suggest that the anti-TNF agent PEG-sTNFRI did not prevent the increase in E3 ubiquitin-ligating enzymes, MuRF1 and MAFbx, gene expression in the skeletal muscle of arthritic rats.
The bi-modal effects of estradiol on gonadotropin synthesis and secretion in female mice are dependent on estrogen receptor-α
Authors: Lindzey Jonathan , Jayes Friederike L , Yates Mariana M , Couse John F , Korach Kenneth S
Published: October 2006

Depending on the estrous/menstrual cycle stage in females, ovarian-derived estradiol (E2) exerts either a negative or a positive effect on the hypothalamic–pituitary axis to regulate the synthesis and secretion of pituitary gonadotropins, LH, and FSH. To study the role of estrogen receptor-α (ERα) mediating these effects, we assessed the relevant parameters in adult wild-type (WT) and ERα-null (αERKO) female mice in vivo and in primary pituitary cell cultures. The αERKO mice exhibited significantly higher plasma and pituitary LH levels relative to WT females despite possessing markedly high levels of circulating E2. In contrast, hypothalamic GnRH content and circulating FSH levels were comparable between genotypes. Ovariectomy led to increased plasma LH in WT females but no further increase in αERKO females, while plasma FSH levels increased in both genotypes. E2 treatment suppressed the high plasma LH and pituitary Lhb mRNA expression in ovariectomized WT females but had no effect in αERKO. In contrast, E2 treatments only partially suppressed plasma FSH in ovariectomized WT females, but this too was lacking in αERKO females. Therefore, negative feedback on FSH is partially E2/ERα mediated but more dependent on ovarian-derived inhibin, which was increased threefold above normal in αERKO females. Together, these data indicate that E2-mediated negative feedback is dependent on functional ERα and acts to primarily regulate LH synthesis and secretion. Studies in primary cultures of pituitary cells from WT females revealed that E2 did not suppress basal or GnRH-induced LH secretion but instead enhanced the latter response, indicating that the positive influence of E2 on gonadotropin secretion may occur at the level of the pituitary. Once again this effect was lacking in αERKO gonadotropes in culture. These data indicate that the aspects of negative and positive effects of E2 on gonadotropin secretion are ERα dependent and occur at the level of the hypothalamus and pituitary respectively.
Identification of Novel HLA-A*0201–Restricted Epitopes in Recent-Onset Type 1 Diabetic Subjects and Antibody-Positive Relatives
Authors: Standifer Nathan E. , Ouyang Qin , Panagiotopoulos Constadina , Verchere C. Bruce , Tan Rusung , Greenbaum Carla J. , Pihoker Catherine , Nepom Gerald T.
Published: October 2006

Cytotoxic T-lymphocytes (CTLs) are considered to be essential for β-cell destruction in type 1 diabetes. However, few islet-associated peptides have been demonstrated to activate autoreactive CTLs from type 1 diabetic subjects. In an effort to identify novel epitopes, we used matrix-assisted algorithms to predict peptides of glial fibrillary acidic protein (GFAP), prepro-islet amyloid polypeptide (ppIAPP), and islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP) that likely bind to HLA-A*0201 with a strong affinity and contain a COOH-terminal proteasomal cleavage site. Seven peptides stabilized HLA-A*0201 expression in binding assays and were used to stimulate peripheral blood mononuclear cells and were evaluated for granzyme B secretion. We found that 5 of 13 type 1 diabetic subjects and 4 of 6 antibody-positive relatives exhibited greater numbers of granzyme B–secreting cells in response to at least one putative epitope compared with healthy control subjects. The most prevalent responses in antibody-positive and type 1 diabetic subjects were to ppIAPP(9-17). Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222). These data implicate peptides of ppIAPP, GFAP, and IGRP as CTL epitopes for a heterogenous CD8+ T-cell response in type 1 subjects and antibody-positive relatives.
Pubertal Timing Is an Independent Predictor of Central Adiposity in Young Adult Males
Authors: Kindblom Jenny M. , Lorentzon Mattias , Norjavaara Ensio , Lönn Lars , Brandberg John , Angelhed Jan-Erik , Hellqvist Åsa , Nilsson Staffan , Ohlsson Claes
Published: October 2006

The role of puberty and normal variations in pubertal timing for the development of obesity in men is unclear. The aim of the current study was to investigate the impact of pubertal timing and prepubertal BMI (kg/m2) for young adult BMI and fat mass distribution. Detailed growth charts from birth to age 18–20 years were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity (PHV) and BMI at age 10 years were estimated for 579 subjects, and PHV was used as an assessment of pubertal timing. The fat mass characterization and distribution were analyzed using dual X-ray absorptiometry and peripheral as well as abdominal computed tomography at age 18.9 ± 0.5 years. We demonstrate that age at PHV is an independent negative predictor of young adult BMI and whole-body fat mass. Interestingly, age at PHV is an independent negative predictor of central, but not peripheral, fat mass. In contrast, BMI at 10 years of age predicts both central and peripheral subcutaneous fat mass. In conclusion, we demonstrate that early pubertal onset specifically predicts a central fat mass distribution, while a predominantly subcutaneous obese phenotype is strongly predicted by a high prepubertal BMI.
p27 Regulates the Transition of β-Cells From Quiescence to Proliferation
Authors: Georgia Senta , Bhushan Anil
Published: October 2006

Diabetes results from an inadequate mass of functional β-cells. Such inadequacy could result from loss of β-cells due to an immune assault or the inability to compensate for insulin resistance. Thus, mechanisms that regulate the number of β-cells will be key to understanding both the pathogenesis of diabetes and for developing therapies. In this study, we show that cell cycle regulator p27 plays a crucial role in establishing the number of β-cells formed before birth. We show that p27 accumulates in terminally differentiated β-cells during embryogenesis. Disabling p27 allows newly differentiated β-cells that are normally quiescent during embryogenesis to reenter the cell cycle and proliferate. As a consequence, excess β-cells are generated in the p27−/− mice, doubling their β-cell mass at birth. The early postnatal expansion of β-cell mass was unaffected in p27−/− mice, indicating that the main function of p27 is to maintain the quiescent state of newly differentiated β-cells generated during embryogenesis. The expanded β-cell mass was accompanied by increased insulin secretion; however, the p27−/− mice were glucose intolerant, as these mice were insulin insensitive. To assess the role of p27 to affect regeneration of β-cells in models of diabetes, p27−/− mice were injected with streptozotocin (STZ). In contrast to control mice that displayed elevated blood glucose levels, p27−/− mice showed decreased susceptibility to develop STZ-induced diabetes. Furthermore, β-cells retained the ability to reenter the cell cycle at a far greater frequency in p27−/− mice after developing STZ-induced diabetes compared with wild-type littermates. These data indicate that p27 is a key regulator in establishing β-cell mass and an important target for facilitating β-cell regeneration in therapies for diabetes.
Uric Acid Restores Endothelial Function in Patients With Type 1 Diabetes and Regular Smokers
Authors: Waring W. Stephen , McKnight John A. , Webb David J. , Maxwell Simon R.J.
Published: October 2006

Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.
Differential Expression of Matrix Metalloproteinase 3 (MMP3) in Preadipocytes/Stromal Vascular Cells From Nonobese Nondiabetic Versus Obese Nondiabetic Pima Indians
Authors: Traurig Michael T. , Permana Paska A. , Nair Saraswathy , Kobes Sayuko , Bogardus Clifton , Baier Leslie J.
Published: October 2006

Prior microarray studies comparing global gene expression patterns in preadipocytes/stromal vascular cells isolated from nonobese nondiabetic versus obese nondiabetic Pima Indians showed that matrix metalloproteinase 9 (MMP9) is upregulated in obese subjects. The current study targeted analysis of nine additional MMP genes that cluster to a region on chromosome 11q22 that is linked to BMI and percent body fat. Differential-display PCR showed that MMP3 is downregulated in preadipocytes/stromal vascular cells from obese subjects, and real-time PCR showed that MMP3 expression levels are negatively correlated with percent body fat. To determine whether variants within MMP3 are responsible for its altered expression, MMP3 was sequenced, and seven representative variants were genotyped in 1,037 Pima subjects for association analyses. Two variants were associated with both BMI and type 2 diabetes, and two additional variants were associated with type 2 diabetes alone; however, none of these variants were associated with MMP3 expression levels. We propose that the MMP3 pathway is altered in human obesity, but this alteration may be the result of a combination of genetic variation within the MMP3 locus itself, as well as variation in additional factors, either primary or secondary to obesity, that regulate expression of the MMP3 gene.
No Evidence of Association of ENPP1 Variants With Type 2 Diabetes or Obesity in a Study of 8,089 U.K. Caucasians
Authors: Weedon Michael N. , Shields Beverley , Hitman Graham , Walker Mark , McCarthy Mark I. , Hattersley Andrew T. , Frayling Timothy M.
Published: October 2006

Ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) is an inhibitor of insulin-induced activation of the insulin receptor. There is strong evidence from several previous studies that a common coding variant of ENPP1 (K121Q) and a three-marker haplotype (Q121, IVS20delT-11, and G+1044TGA) are associated with type 2 diabetes and obesity. We examined the impact of ENPP1 variation on type 2 diabetes and obesity in a large U.K. genetic association study. We genotyped the three previously associated polymorphisms in 2,363 type 2 diabetic case and 4,045 control subjects, as well as 1,681 subjects from 529 type 2 diabetic families. We used the same subjects for morbid and moderate obesity association studies. For type 2 diabetes, moderate and morbid obesity, and for both the Q121 and three-marker haplotype, our results exclude with >95% confidence the effect sizes from previous studies (Q121 allele: odds ratio 1.02 [95% CI 0.93–1.12], P = 0.61; 1.00 [0.85–1.18], P = 0.99; and 0.92 [0.70–1.20], P = 0.41; three-marker haplotype: 1.10 [0.96–1.26], P = 0.17; 0.97 [0.77–1.23], P = 0.81; and 0.86 [0.57–1.30], P = 0.46 for type 2 diabetes, moderate, and morbid obesity, respectively). A K121Q type 2 diabetes meta-analysis of all previously published studies remained significant after the inclusion of this study (1.25 [1.10–1.43], P = 0.0007), although there was some evidence of publication bias. In conclusion, we find no evidence that previously associated variants of ENPP1 are associated with type 2 diabetes or obesity in the U.K. population.
Diabetes-Induced Extracellular Matrix Protein Expression Is Mediated by Transcription Coactivator p300
Authors: Kaur Harkiran , Chen Shali , Xin Xiping , Chiu Jane , Khan Zia A. , Chakrabarti Subrata
Published: October 2006

Increased fibronectin expression is a key feature of diabetic angiopathy. We have previously shown that nuclear factor-κB (NF-κB) mediates fibronectin expression in endothelial cells and in organs affected by diabetes complications. p300, a transcription coactivator, may regulate NF-κB activity via poly(ADP-ribose) polymerase (PARP) activation. Hence, we examined the role of p300 in fibronectin expression in diabetes. High glucose induced fibronectin expression in the endothelial cells, which was associated with increased p300, PARP activity, and NF-κB activation. This p300 alteration is mediated by mitogen-activated protein kinase and protein kinase C and B. We then used p300 small interfering RNA (siRNA) and showed decreased fibronectin and PARP expression, as well as NF-κB activation, in the endothelial cells. Examination of the heart tissues of streptozotocin-induced diabetic mice revealed increased fibronectin and p300 mRNA. Intravenous injection of p300 siRNA resulted in decreased p300 levels and normalized fibronectin expression in the heart. We further investigated retinal tissues from streptozotocin-induced diabetic rats treated with intravitreal p300 siRNA injection. Similar to the heart, p300 siRNA inhibited fibronectin expression in the retina of the diabetic animals. These results indicate that transcriptional coactivator p300 may regulate fibronectin expression via PARP and NF-κB activation in diabetes.
Splanchnic Cortisol Production in Dogs Occurs Primarily in the Liver
Authors: Basu Rita , Edgerton Dale S. , Singh Ravinder J. , Cherrington Alan , Rizza Robert A.
Published: October 2006

Eight dogs underwent combined hepatic/portal vein catheterization and infusion of D4-cortisol in order to determine the relative contributions of the viscera and liver to splanchnic cortisol production. D4-cortisol concentrations progressively decreased from 2.6 ± 0.1 to 2.4 ± 0.1 to 1.7 ± 0.1 μg/dl (P < 0.001 by ANOVA) from hepatic artery to portal vein to hepatic vein, respectively, indicating 8 ± 3 and 28 ± 3% extraction across the viscera and liver, respectively. On the other hand, hepatic artery, portal vein, and hepatic vein cortisol concentrations did not differ (0.31 ± 0.12 vs. 0.28 ± 0.11 vs. 0.27 ± 0.10 μg/dl, respectively), indicating zero net cortisol balance. This meant that 1.0 ± 0.1 μg/min of cortisol was produced within the splanchnic bed, all of which occurred within the liver (1.2 ± 0.1 μg/min). On the other hand, visceral cortisol production did not differ from zero (−0.2 ± 0.2 μg/min; P < 0.001 vs. liver). Flux through the 11β hydroxysteroid dehydrogenase (HSD) type 1 pathway can be measured by determining the rate of conversion of D4-cortisol to D3-cortisol. D3-cortisol concentrations were lower in the portal vein than hepatic artery (0.45 ± 0.03 vs. 0.48 ± 0.02, respectively; P < 0.01) but did not differ in the portal vein and hepatic vein, indicating net uptake across the viscera but zero balance across the liver. D3-cortisol production with the viscera and liver averaged 0.2 ± 0.1 μg/min (P = NS vs. zero production) and 0.6 ± 0.1 μg/min (P < 0.001 vs. zero production; P < 0.001 vs. viscera production), respectively. We conclude that most, if not all, of splanchnic cortisol production occurs within the liver. Taken together, these data suggest that the high local cortisol concentrations generated via the 11β HSD type 1 pathway within the liver likely contribute to the regulation of hepatic glucose, fat, and protein metabolism.
Dysregulation of the Peripheral and Adipose Tissue Endocannabinoid System in Human Abdominal Obesity
Authors: Blüher Matthias , Engeli Stefan , Klöting Nora , Berndt Janin , Fasshauer Mathias , Bátkai Sándor , Pacher Pál , Schön Michael R. , Jordan Jens , Stumvoll Michael
Published: October 2006

The endocannabinoid system has been suspected to contribute to the association of visceral fat accumulation with metabolic diseases. We determined whether circulating endocannabinoids are related to visceral adipose tissue mass in lean, subcutaneous obese, and visceral obese subjects (10 men and 10 women in each group). We further measured expression of the cannabinoid type 1 (CB1) receptor and fatty acid amide hydrolase (FAAH) genes in paired samples of subcutaneous and visceral adipose tissue in all 60 subjects. Circulating 2-arachidonoyl glycerol (2-AG) was significantly correlated with body fat (r = 0.45, P = 0.03), visceral fat mass (r = 0.44, P = 0.003), and fasting plasma insulin concentrations (r = 0.41, P = 0.001) but negatively correlated to glucose infusion rate during clamp (r = 0.39, P = 0.009). In visceral adipose tissue, CB1 mRNA expression was negatively correlated with visceral fat mass (r = 0.32, P = 0.01), fasting insulin (r = 0.48, P < 0.001), and circulating 2-AG (r = 0.5, P < 0.001), whereas FAAH gene expression was negatively correlated with visceral fat mass (r = 0.39, P = 0.01) and circulating 2-AG (r = 0.77, P < 0.001). Our findings suggest that abdominal fat accumulation is a critical correlate of the dysregulation of the peripheral endocannabinoid system in human obesity. Thus, the endocannabinoid system may represent a primary target for the treatment of abdominal obesity and associated metabolic changes.
Extraction of Re(VII) by neutral and basic extractants
Authors: Schrötterová D. , Nekovář P.
Published: October 2006

The mechanism of Re(VII) extraction from sulphate-containing solutions using primary amine Primene JMT, trioctylphosphine oxide (TOPO), tributyl phosphate (TBP), and their mixtures was investigated. It was found that the ratio of Re(VII) with Primene JMT and its sulphate in the organic phase was 1:1. The composition of Re(VII) complexes with TOPO depended on the acidity of solution ranging from about 1:1 to 2:1. When the extraction was carried out by TBP the mole ratio of TBP to Re was approximately 4. Primene JMT proved to be the most suitable agent for Re(VII) extraction with the exception of strongly acidic solutions, in which TOPO provided better results. The mixed solvents Primene JMT and TOPO as well as Primene JMT and TBP presented a slight synergism in weakly acidic solutions.
Modelling of enzymatic reaction in an internal loop airlift reactor
Authors: Sikula I. , Juraščík M. , Markoš J.
Published: October 2006

Gas-liquid reaction carried out in an internal loop airlift reactor was modelled and subjected to the scale-up procedure. Homogeneous oxidation of glucose to gluconic acid catalyzed by Gluzyme 10000 BG, a commercial product containing the enzymes glucose oxidase and catalase as active components, was chosen as the model system. The kinetic parameters were obtained using a 12-L airlift reactor considered as a CSTR. The behaviour of a large-scale internal loop airlift reactor was modelled dividing the reactor sections into a series of tank reactors. The reliability of the model was verified by comparing experimental measurements with the simulation results obtained employing 40-L and 200-L airlift reactors. The designed model could be suitable to predict the behaviour of large-scale internal loop airlift reactors.
A resistance gene in disguise for schizophrenia?
Authors: Doi Nagafumi , Itokawa Masanari , Hoshi Yoko , Arai Makoto , Furukawa Aizou , Ujike Hiroshi , Sora Ichiro , Yoshikawa Takeo
Published: October 2006

We examined the hypothesis that −485 T, a novel polymorphism in the promoter region of the neuropeptide Y gene which was shown to be associated with schizophrenia in our previous paper, confers susceptibility to the disease. For a case‐control association study, 331 unrelated Japanese schizophrenics (S1: milder cases in the previous study, n = 212; and S2: additional severer cases, n = 119) and 199 unrelated normal controls were recruited. Contribution of −485 T to the risk and the severity of the illness was examined by (1) comparing the risk in each genotype in the general population, (2) testing correlations between the gene‐dose of −485 T, and the severity of chronic outcome in S2 assessed with the Positive and Negative Symptom Scale, and (3) comparing the distribution of age at onset in S1 + S2 among the three genotypes. −485 T was significantly associated with schizophrenia in S1 + S2. Significant negative correlations were observed between the gene‐dose and the symptom assessment scores in all items. The homozygote of −485 T showed a second peak frequency in the late‐onset group both in males and females, while the homozygote of the alternative allele showed a single peak in the early‐onset group. The higher risk of schizophrenia in the heterozygote than in the homozygote of −485 T in the general population did not support the possibility of linkage disequilibrium with a susceptibility gene. −485 T most likely confers resistance but not susceptibility to schizophrenia. An interaction between a nuclear resistance gene and a presumptive pathogenic gene in the mitochondrial DNA was suggested. © 2006 Wiley‐Liss, Inc.
Synergistic association of mitochondrial uncoupling protein (UCP) genes with schizophrenia
Authors: Yasuno Katsuhito , Ando Satoshi , Misumi Shinnosuke , Makino Satoshi , Kulski Jerzy K , Muratake Tatsuyuki , Kaneko Naoshi , Amagane Hideki , Someya Toshiyuki , Inoko Hidetoshi , Suga Hidemichi , Kanemoto Kousuke , Tamiya Gen
Published: October 2006

Many studies suggest that mitochondrial dysfunction is involved in the pathophysiology of schizophrenia. We performed a case‐control study using tag SNPs in the mitochondrial uncoupling protein genes, UCP2, UCP4, and BMCP1/UCP5, to investigate their association with schizophrenia. These neuronal UCPs are expressed in various brain tissues and may exert a neuroprotective effect against increased oxidative stress. We found modest associations between schizophrenia and the four tag SNPs, rs660339 (odds ratio (OR) = 1.330; P = 0.0043) and rs649446 (OR = 0.739; P = 0.0069) in UCP2, and rs10807344 (OR = 0.622; P = 0.0029) and rs2270450 (OR = 0.704; P = 0.0043) in UCP4, all of which were statistically significant even after correcting for multiple comparisons. Moreover, we found a statistically significant synergistic interaction between UCP2 and UCP4 by using the multifactor dimensionality reduction (MDR) method. The synergistic interaction was also confirmed by the logistic regression analysis, where the maximal OR was obtained when the risk alleles at rs660339 and rs10807344 were simultaneously homozygous. Individuals possessing homozygous risk alleles at these two loci have a 7.6‐fold risk of developing schizophrenia compared with those of minimal OR. Our findings suggest that UCP2 and UCP4 have a modest but important involvement in the genetic etiology of schizophrenia. This is the first report of the association between schizophrenia and neuronal UCPs. © 2006 Wiley‐Liss, Inc.
National rates of birth defects among hospitalized newborns
Authors: Bird T.M. , Hobbs Charlotte A. , Cleves Mario A. , Tilford John M. , Robbins James M.
Published: October 2006

BACKGROUND: The Healthcare Cost and Utilization Project (HCUP) family of hospital discharge databases offer an unprecedented opportunity to generate national estimates of newborn infants with birth defects. This report estimates national hospital admissions for newborn infants diagnosed with birth defects computed from HCUP and compares them to pooled prevalence figures computed from state birth defect surveillance systems. METHODS: HCUP‐derived rates of 36 birth defects from 1997 through 2001 were compared to rates derived from pooled data reported by 26 state‐based surveillance systems stratified by inclusion of elective terminations in case definitions. Rate ratios (RRs) were calculated for each birth defect by dividing the rate derived from HCUP by the rate derived from the relevant surveillance systems. RESULTS: HCUP newborn hospitalization rates for birth defects closely approximate pooled birth defect rates for surveillance systems that do not include elective terminations. HCUP rates were not significantly different for 35 of 36 defects. Overall, 20 HCUP rates were within 10% of state rates, 11 more were within 20% of state rates, and only 1 differed by more than 50%. HCUP rates compared most closely to state rates for cardiovascular (VSD RR = 0.98, ASD = 0.96, pulmonary valve atresia and stenosis = 0.92), orofacial (cleft palate RR = 1.10, cleft lip = 1.06), and genitourinary defects (obstructive genitourinary RR = 1.01, bladder exstrophy = 0.97). HCUP rates compared less favorably to rates derived from surveillance systems that included elective terminations. CONCLUSIONS: HCUP data approximate state‐based surveillance system data for defects that are easily recognized in the newborn period and infrequently a cause for elective termination. HCUP data can be used to examine the impact of public health efforts on the number of infants born with birth defects as well as the cost and consequences of variations in the hospital management of birth defects. Birth Defects Research (Part A), 2006. © 2006 Wiley–Liss, Inc.
Microstructural and tensile properties of elastin‐based polypeptides crosslinked with Genipin and pyrroloquinoline quinone
Authors: Vieth S. , Bellingham C. M. , Keeley F. W. , Hodge S. M. , Rousseau D.
Published: October 2006

Elastin is an elastomeric, self‐assembling extracellular matrix protein with potential for use in biomaterials applications. Here, we compare the microstructural and tensile properties of the elastin‐based recombinant polypeptide (EP) EP20‐244 crosslinked with either genipin (GP) or pyrroloquinoline quinone (PQQ). Recombinant EP‐based sheets were produced via coacervation and subsequent crosslinking. The micron‐scale topography of the GP‐crosslinked sheets examined with atomic force microscopy revealed the presence of extensive mottling compared with that of the PQQ‐crosslinked sheets, which were comparatively smoother. Confocal microscopy showed that the subsurface porosity in the GP‐crosslinked sheets was much more open. GP‐crosslinked EP‐based sheets exhibited significantly greater tensile strength (P ≤ 0.05). Mechanistically, GP appears to yield a higher crosslink density than PQQ, likely due to its capacity to form short‐range and long‐range crosslinks. In conclusion, GP is able to strongly modulate the microstructural and mechanical properties of elastin‐based polypeptide biomaterials forming membranes with mechanical properties similar to native insoluble elastin. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 199–206, 2007.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
A metric for corporate environmental indicators … for small and medium enterprises in the Philippines
Authors: Rao Purba , Singh Alok Kumar , la O'Castillo Olivia , Intal Ponciano S. , Sajid Ather
Published: October 2006

This paper is an outcome of the empirical research, funded by UNDP Philippines and National Economic Development Authority (NEDA), done to establish and implement a metric of corporate environmental indicators for SMEs in the Philippines. SMEs have always played a vital role in the creation of goods and services in the country. It is therefore imperative that SMEs adhere to safe environment practices so that the greening of industries in this region is consummate. In this research we have considered SMEs operating in the food and beverage, furniture, fashion accessories, hotel and restaurant, automotive parts and electroplating sectors. The metric adopted in this research follows the framework given by the Federal Environmental Ministry in Bonn and the Federal Environmental Agency in Berlin.

  The empirical approach develops an exploratory analysis and a structural equation model to bring out statistically significant linkages between five latent constructs: environment management indicators, environment performance indicators, environmental performance, business performance and competitiveness. The research hopes to urge SMEs to implement this metric with confidence given that this would not only enhance their environmental performance but also lead to superior business performance and enhanced competitiveness. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Environmental management systems and green supply chain management: complements for sustainability?
Authors: Darnall Nicole , Jolley G. Jason , Handfield Robert
Published: October 2006

Some researchers question the legitimacy of EMSs since organizations can claim to have one when in fact they make no attempt to reduce their environmental harm. In instances where EMSs enhance an organization's environmental performance, critics argue that improvements are likely to occur within the organization's operational boundaries rather than being extended throughout the supply chain. However, previous research suggests that the organizational capabilities required to adopt an EMS may facilitate GSCM implementation and the institutional pressures to adopt both management practices are similar. Consequently, EMS adopters may have a greater propensity to expand their focus beyond their organizational boundaries and utilize GSCM practices to minimize system‐wide environmental impacts. This research illuminates the debate by empirically evaluating the relationship between EMS and GSCM practices. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Reframing applied disease stigma research: a multilevel analysis of diabetes stigma in Ghana
Authors: Aikins Ama de‐Graft
Published: October 2006

Research suggests that rural and urban Ghanaians living with uncontrolled diabetes—typified by extreme weight loss—experience HIV/AIDS‐related stigma. This paper reports a multilevel analysis of this stigma within the broader context of diabetes handicap in two rural communities. Two key findings emerge. First, the content of stigma constitutes social representations of HIV/AIDS, and to internalized and projected collective attributions of protracted illness to witchcraft or sorcery. Thus the stigma experienced by people with uncontrolled diabetes is not specific to the disease category ‘diabetes’ and distant others affected by it. Second, extreme biophysical disruption, which precipitates misperceptions, stigma and/or discrimination, is both cause and consequence of financial destitution and psychosocial neglect. Both forms of handicap have deeper pre‐stigma roots in poverty and the socio‐psychological and cultural impact of long‐term illness. Thus the actuality or threat of diabetes stigma has to be understood in terms of diabetes handicap, which in turn has to be understood as a product of shared responses to long‐term illness in communities constantly negotiating financial, health and psychological insecurities. The scope for multifaceted/multilevel intervention is considered taking into account the biophysical and psychological impact of illness and the socio‐psychological and structural realities of diabetes care in Ghana. Copyright © 2006 John Wiley & Sons, Ltd.
Antiherpetic Flavones from the Heartwood of Artocarpus gomezianus
Authors: Likhitwitayawuid Kittisak , Chaiwiriya Saowalak , Sritularak Boonchoo , Lipipun Vimolmas
Published: October 2006

The heartwood of Artocarpus gomezianus was investigated for anti‐herpetic principles. During the course of the separation, a new compound, artogomezianone (1), was isolated, along with the known compounds cycloartocarpin (2), isocyclomorusin (3), artocarpin (4), norcycloartocarpin (5), norartocarpetin (6), and oxyresveratrol (7). Evaluation of these isolates for inhibitory effects against herpes simplex virus (HSV) types 1 and 2 was carried out using the inactivation method. Compounds 2, 3, 6 and 7 showed moderate activities against both types of HSV, while 1, 4 and 5 were basically inactive (Table 2).
Electrochemical Reduction of G3‐Factor Endoperoxide and Its Methyl Ether: Evidence for a Competition between Concerted and Stepwise Dissociative Electron Transfer
Authors: Najjar Fadia , André‐Barrès Christiane , Baltas Michel , Lacaze‐Dufaure Corinne , Magri David C. , Workentin Mark S. , Tzédakis Théodore
Published: October 2006

The reduction of the bicyclic G‐factor endoperoxides G3 and G3Me was studied in N,N‐dimethylformamide using cyclic voltammetry and convolution analysis. Electron transfer leads to irreversible cleavage of the OO bond. Detailed analysis of the voltammetry curves reveals a non‐linear dependence on the transfer coefficient indicating a mechanistic transition from a stepwise mechanism to one with more concerted character with increasing potential. By using quantum calculations to estimate the OO bond dissociation energies, the experimental data was used to evaluate the standard reduction potentials and other pertinent thermochemical information.
Chiral Fluorous Dialkoxy‐Diamino Zirconium Complexes: Synthesis and Use in Stereospecific Polymerization of 1‐Hexene
Authors: Kirillov Evgueni , Lavanant Laurent , Thomas Christophe , Roisnel Thierry , Chi Yun , Carpentier Jean‐François
Published: October 2006

New catalysts for the isospecific polymerization of 1‐hexene based on cationic zirconium complexes incorporating the tetradentate fluorous dialkoxy‐diamino ligands [OC(CF3)2CH2N(Me)(CH2)2N(Me)CH2C(CF3)2O]2− [(ON2NO)2−] and [OC(CF3)2CH2N(Me)(1R,2R‐C6H10)N(Me)CH2C(CF3)2O]2− [(ONCyNO)2−] have been developed. The chiral fluorous diamino‐diol [(ONCyNO)H2, 2] was prepared by ring‐opening of the fluorinated oxirane (CF3)2COCH2 with (R,R)‐N,N′‐dimethyl‐1,2‐cyclohexanediamine. Proligand 2 reacts cleanly with [Zr(CH2Ph)4] and [Ti(OiPr)4] precursors to give the corresponding dialkoxy complexes [Zr(CH2Ph)2(ONCyNO)] (3) and [Ti(OiPr)2(ONCyNO)] (4), respectively. An X‐ray diffraction study revealed that 3 crystallizes as a 1:1 mixture of two diastereomers (Λ‐3 and Δ‐3), both of which adopt a distorted octahedral structure with trans‐O, cis‐N, and cis‐CH2Ph ligands. The two diastereomers Λ‐3 and Δ‐3 adopt a C2‐symmetric structure in toluene solution, as established by NMR spectroscopy. Cationic complexes [Zr(CH2Ph)(ON2NO)(THF)n]+ (n=0, anion=[B(C6F5)4]−, 5; n=1, anion=[PhCH2B(C6F5)3]−, 6) and [Zr(CH2Ph)(ONCyNO)(THF)]+[PhCH2B(C6F5)3]− (7) were generated from the neutral parent precursors [Zr(CH2Ph)2(ON2NO)] (H) and [Zr(CH2Ph)2(ONCyNO)] (3), and their possible structures were determined on the basis of 1H, 19F, and 13C NMR spectroscopy and DFT methods. The neutral zirconium complexes H and 3 (Λ‐3/Δ‐3 mixture), when activated with B(C6F5)3 or [Ph3C]+[B(C6F5)4]−, catalyze the polymerization of 1‐hexene with overall activities of up to 4500 kg PH mol Zr−1 h−1, to yield isotactic‐enriched (up to 74 % mmmm) polymers with low‐to‐moderate molecular weights (Mw=4800–47 200) and monodisperse molecular‐weight distributions (Mw/Mn=1.17–1.79).