bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short term hypothyroidism affects ovarian function in the cycling rat
Authors: Hapon María Belén , Gamarra-Luques Carlos , Jahn Graciela A 
Published: February 2010

Abstract

Background
Rats made hypothyroid with propilthyouracil start showing abnormal cycling on the second cycle after the start of the treatment, with a high proportion of spontaneous pseudopregnancies and reduced fertility.

Methods
To investigate some of the mechanisms involved in these reproductive abnormalities, hypothyroidism was induced in virgin rats by propilthyouracil (0.1 g/L in the drinking water) and we determined circulating hormones by radioimmunoassay and whole ovary expression of ovarian hormone receptors, growth factors and steroidogenic enzymes using semi-quantitative RT-PCR.
The study was performed on days 6 to 9 of treatment, corresponding to diestrus I (at 20.00-22.00 h), diestrus II (at 20.00-22.00 h), proestrus and estrus (both at 8.00-10.00 h and 20.00-22.00 h) of the second estrous cycle after beginning propilthyouracil treatment. Another group of rats was mated on day 8 and the treatment continued through the entire pregnancy to evaluate reproductive performance.

Results
Hypothyroidism increased circulating prolactin and estradiol on estrus 5 to 7-fold and 1.2 to 1.4-fold respectively. Growth hormone and insulin-like growth factor 1 diminished 60 and 20% respectively on proestrus morning. Hypothyroidism doubled the ovarian mRNA contents of estrogen receptor-beta on proestrus and estrus evenings, cyp19A1 aromatase mRNA on estrus evening and of growth hormone receptor on proestrus evening. Hypothyroidism did not influence ovulation rate or the number of corpora lutea at term, but a diminished number of implantation sites and pups per litter were observed (Hypothyroid: 11.7 +/- 0.8 vs. Control: 13.9 +/- 0.7).

Conclusions
Short term hypothyroidism alters normal hormone profile in the cycling rat increasing the expression of estrogen receptor-beta and cyp19A1 aromatase on estrus, which in turn may stimulate estradiol and prolactin secretion, favouring corpus luteum survival and the subsequent instauration of pseudopregnancy.
Effects of collagen membranes enriched with in vitro-differentiated N1E-115 cells on rat sciatic nerve regeneration after end-to-end repair
Authors: Amado Sandra , Rodrigues Jorge M , Luís Ana L , Armada-da-Silva Paulo AS , Vieira Márcia , Gartner Andrea , Simões Maria J , Veloso António P , Fornaro Michele , Raimondo Stefania , Varejão Artur SP , Geuna Stefano , Maurício Ana C 
Published: February 2010

AbstractPeripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-Endgroup), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMembgroup); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiatedin vitrofrom N1E-115 cells (End-to-EndMembCellgroup). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat.
Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of salt-loading
Authors: Chen Qixuan , Gruber Heidi , Swist Eleonora , Coville Kara , Pakenham Catherine , Ratnayake Walisundera MN , Scoggan Kylie A 
Published: February 2010

Abstract

Background
There are safety concerns regarding widespread consumption of phytosterol and phytostanol supplemented food products. The aim of this study was to determine, in the absence of excess dietary salt, the individual effects of excess accumulation of dietary phytosterols and phytostanols on blood pressure in Wistar Kyoto (WKY) inbred rats that have a mutation in the Abcg5 gene and thus over absorb phytosterols and phytostanols.

Methods
Thirty 35-day old male WKY inbred rats (10/group) were fed a control diet or a diet containing phytosterols or phytostanols (2.0 g/kg diet) for 5 weeks. The sterol composition of the diets, plasma and tissues were analysed by gas chromatography. Blood pressure was measured by the tail cuff method. mRNA levels of several renal blood pressure regulatory genes were measured by real-time quantitative PCR.

Results
Compared to the control diet, the phytosterol diet resulted in 3- to 4-fold increases in the levels of phytosterols in plasma, red blood cells, liver, aorta and kidney of WKY inbred rats (P < 0.05). The phytostanol diet dramatically increased (> 9-fold) the levels of phytostanols in plasma, red blood cells, liver, aorta and kidney of these rats (P < 0.05). The phytosterol diet decreased cholesterol levels by 40%, 31%, and 19% in liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet decreased cholesterol levels by 15%, 16%, 20% and 14% in plasma, liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet also decreased phytosterol levels by 29% to 54% in plasma and tissues (P < 0.05). Both the phytosterol and phytostanol diets produced significant decreases in the ratios of cholesterol to phytosterols and phytostanols in plasma, red blood cells, liver, aorta and kidney. Rats that consumed the phytosterol or phytostanol diets displayed significant increases in systolic and diastolic blood pressure compared to rats that consumed the control diet (P < 0.05). The phytosterol diet increased renal angiotensinogen mRNA levels of these rats.

Conclusion
These data suggest that excessive accumulation of dietary phytosterols and phytostanols in plasma and tissues may contribute to the increased blood pressure in WKY inbred rats in the absence of excess dietary salt. Therefore, even though phytosterols and phytostanols lower cholesterol levels, prospective clinical studies testing the net beneficial effects of dietary phytosterols and phytostanols on cardiovascular events for subgroups of individuals that have an increased incorporation of these substances are needed.
Maintenance of Sorafenib following combined therapy of three-dimensional conformal radiation therapy/intensity-modulated radiation therapy and transcatheter arterial chemoembolization in patients with locally advanced hepatocellular carcinoma: a phase I/II study
Authors: Zhao Jian-Dong , Liu Jin , Ren Zhi-Gang , Gu Ke , Zhou Zhen-Hua , Li Wen-Tao , Chen Zhen , Xu Zhi-Yong , Liu Lu-Ming , Jiang Guo-Liang 
Published: February 2010

Abstract

Background
Three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with or without transcatheter arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma (HCC) has shown favorable outcomes in local control and survival of locally advanced HCC. However, intra-hepatic spreading and metastasis are still the predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would probably prevent or delay the intrahepatic and extrahepatic spread of HCC after radiotherapy, which provides the rationale for the combination of these treatment modalities.

Methods and design
Patients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. If no more than 3 patients discontinue Sorafenib treatment who experience dose-limiting toxicity after necessary dose modification and delay and/or radiation-induced liver disease in the first 15 enrolled patients, the study will recruit second fifteen patients for further evaluating safety and efficacy of treatment. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data.

Discussion
A recent meta-analysis showed TACE in combination with radiotherapy, improved the survival and the tumor response of patients, and was thus more therapeutically beneficial. In this study, local therapy for HCC is the combination of TACE and radiotherapy. Radiation exposure as a kind of stress might induce the compensatory activations of multiple intracellular signaling pathway mediators, such as PI3K, MAPK, JNK and NF-kB. Vascular endothelial growth factor (VEGF) was identified as one factor that was increased in a time- and dose-dependent manner after sublethal irradiation of HCC cells in vitro, translating to enhanced intratumor angiogenesis in vivo. Therefore, Sorafenib-mediated blockade of the Raf/MAPK and VEGFR pathways might enhance the efficacy of radiation, when Sorafenib is followed sequentially as a maintenance modality. (ClinicalTrials.gov number, NCT00999843.)
Occult small bowel perforation in a patient with Ehlers Danlos syndrome: a case report and review of the literature
Authors: Leake Tessa Frances , Singhal Tarun , Chandra Aninda , Ashcroft Alexandra , Doddi Sudeendra , Hussain Abdulzahra , Smedley Frank 
Published: February 2010

Abstract
Patients who present with a co-existing connective tissue disorder add a degree of complexity to operative intervention. We present an unusual case of a 53-year-old Caucasian female patient with Ehlers Danlos syndrome who presented with an occult perforation of the distal ileum. The patient had known small bowel diverticulae yet the perforation occurred within the normal bowel wall. The pre-operative CT only showed malrotation of the large bowel and did not correlate with the intra-operative findings. Our case has highlighted that although small bowel perforation is a rare occurrence, it may be more common in Ehlers Danlos and may present with atypical features. Perforation may also occur alongside normal bowel as well as diverticulae within the bowel. Where diverticulae exists within a patient with Ehlers Danlos syndrome and there is some diagnostic uncertainty, there should be a lower threshold for operative intervention. We present in the discussion a number of salient features and learning points.
Differential expression level of cytokeratin 8 in cells of the bovine nucleus pulposus complicates the search for specific intervertebral disc cell markers
Authors: Gilson Audrey , Dreger Mathias , Urban Jill PG 
Published: February 2010

Abstract
Introduction
Development of cell therapies for repairing the intervertebral disc is limited by the lack of a source of healthy human disc cells. Stem cells, particularly mesenchymal stem cells, are seen as a potential source but differentiation strategies are limited by the lack of specific markers that can distinguish disc cells from articular chondrocytes.

Methods
We searched for markers using the differential in-gel electrophoresis proteomic technology to compare proteins of bovine nucleus pulposus cells, phenotypically similar to mature human nucleus cells, with those of bovine articular chondrocytes. In the cohort of the differentially expressed proteins identified by mass spectrometry, cytokeratin 8 (CK8) was further validated by immunostaining of freshly isolated cells and frozen tissue sections using monoclonal antibodies.

Results
We identified a set of 14 differentially expressed proteins. Immunohistochemistry showed that only a subset of cells (approximately 10%) was positive for one of these proteins, CK8, an intermediate filament protein present in epithelial but not mesenchymal cells. In tissue sections, CK8-positive cells were seen in all discs examined and appeared as small isolated clusters surrounded by gelatinous matrix. Notochordal nucleus pulposus cells from pig, phenotypically similar to human infant nucleus pulposus cells, were all CK8-positive. The mesenchymal intermediate filament protein vimentin was present in all bovine and porcine nucleus pulposus cells.

Conclusions
The notochordal cell population is reported to disappear from the nucleus pulposus of bovine discs before birth and from human discs in childhood. However our finding of the co-expression of vimentin and CK8 in small isolated clusters of the bovine nucleus pulposus cells indicates that a subpopulation of notochordal-like cells remains in the mature bovine disc. This finding agrees with reports in the literature on co-expression of cytokeratins and vimentin in adult human discs. As notochordal cells produce factors that promote matrix production, the CK8-positive subpopulation could have important implications for activity and survival of the nucleus pulposus, and should be considered in development of cell therapies for disc repair. In addition, the finding of differential expression of proteins in the cell population of nucleus pulposus has implications with regard to the search for specific markers.
Diffusion-weighted magnetic resonance imaging for predicting the clinical outcome of comatose survivors after cardiac arrest: a cohort study
Authors: Choi Seung Pill , Park Kyu Nam , Park Hae Kwan , Kim Jee Young , Youn Chun Song , Ahn Kook Jin , Yim Hyeon Woo 
Published: February 2010

Abstract
Introduction
The aim of this study was to examine whether the patterns of diffusion-weighted imaging (DWI) abnormalities and quantitative regional apparent diffusion coefficient (ADC) values can predict the clinical outcome of comatose patients following cardiac arrest.

Methods
Thirty-nine patients resuscitated from out-of-hospital cardiac arrest were prospectively investigated. Within five days of resuscitation, axial DWIs were obtained and ADC maps were generated using two 1.5-T magnetic resonance scanners. The neurological outcomes of the patients were assessed using the Glasgow Outcome Scale (GOS) score at three months after the cardiac arrest. The brain injuries were categorised into four patterns: normal, isolated cortical injury, isolated deep grey nuclei injury, and mixed injuries (cortex and deep grey nuclei). Twenty-three subjects with normal DWIs served as controls. The ADC and percent ADC values (the ADC percentage as compared to the control data from the corresponding region) were obtained in various regions of the brains. We analysed the differences between the favourable (GOS score 4 to 5) and unfavourable (GOS score 1 to 3) groups with regard to clinical data, the DWI abnormalities, and the ADC and percent ADC values.

Results
The restricted diffusion abnormalities in the cerebral cortex, caudate nucleus, putamen and thalamus were significantly different between the favourable (n = 13) and unfavourable (n = 26) outcome groups. The cortical pattern of injury was seen in one patient (3%), the deep grey nuclei pattern in three patients (8%), the cortex and deep grey nuclei pattern in 21 patients (54%), and normal DWI findings in 14 patients (36%). The cortex and deep grey nuclei pattern was significantly associated with the unfavourable outcome (20 patients with unfavourable vs. 1 patient with favourable outcomes, P < 0.001). In the 22 patients with quantitative ADC analyses, severely reduced ADCs were noted in the unfavourable outcome group. The optimal cutoffs for the mean ADC and the percent ADC values determined by receiver operating characteristic (ROC) curve analysis in the cortex, caudate nucleus, putamen, and thalamus predicted the unfavourable outcome with sensitivities of 67 to 93% and a specificity of 100%.

Conclusions
The patterns of brain injury in early diffusion-weighted imaging (DWI) (less than or equal to five days after resuscitation) and the quantitative measurement of regional ADC may be useful for predicting the clinical outcome of comatose patients after cardiac arrest.
The Incidence of Ischemic Heart Disease and Mortality in People with Subclinical Hypothyroidism: Reanalysis of the Whickham Survey Cohort
Authors: Razvi Salman , Weaver Jola U. , Vanderpump Mark P. , Pearce Simon H. S. 
Published: February 2010

Abstract
Context: The Whickham Survey evaluated vascular events over 20 yr in community-dwelling subjects stratified by thyroid function and thyroid autoantibody status. No association between ischemic heart disease (IHD) and a composite autoimmune thyroid disease group, comprising individuals with subclinical hypothyroidism (SCH), with positive thyroid antibodies or those using levothyroxine, was found. This result appears to be at odds with the findings of other cohort studies.
Objective: The objective of the study was to evaluate incident IHD and mortality in participants in relation to their thyroid status.
Outcomes, Design, and Participants: Data were reanalyzed assessing incident IHD events and mortality during 20 yr of follow-up in individuals with endogenous SCH (n = 97; TSH 6.0–15 mIU/liter) vs. the euthyroid group (n = 2279), who were IHD free at baseline.
Results: Incident IHD was significantly higher in the SCH group [adjusted hazard ratio 1.76 (95% confidence interval 1.15–2.71); P = 0.01]. IHD mortality was also increased in the SCH group [hazard ratio of 1.79 (1.02–3.56); P = 0.05]. These findings lost their significance when subsequent treatment with levothyroxine was excluded from the regression model. There was no difference in all-cause mortality between the groups.
Conclusion: In the Whickham Survey, there is an association between incident IHD events and IHD-related mortality with SCH over the 20 yr of follow-up. Furthermore, subsequent treatment of SCH with levothyroxine appears to attenuate IHD-related morbidity and mortality, and this may explain why some other longitudinal studies of SCH have not shown such an association; properly designed controlled trials of treatment of SCH are required to answer this question definitively.
The Association of Mitochondrial Content with Prevalent and Incident Type 2 Diabetes
Authors: Reiling Erwin , Ling Charlotte , Uitterlinden André G. , van't Riet Esther , Welschen Laura M. C. , Ladenvall Claes , Almgren Peter , Lyssenko Valeriya , Nijpels Giel , van Hove Els C. , Maassen Johannes A. , de Geus Eco J. C. , Boomsma Dorret I. , Dekker Jacqueline M. , Groop Leif , Willemsen Gonneke , 't Hart Leen M. 
Published: February 2010

Abstract
Context: It has been shown that mitochondrial DNA (mtDNA) content is associated with type 2 diabetes (T2D) and related traits. However, empirical data, often based on small samples, did not confirm this observation in all studies. Therefore, the role of mtDNA content in T2D remains elusive.
Objective: In this study, we assessed the heritability of mtDNA content in buccal cells and analyzed the association of mtDNA content in blood with prevalent and incident T2D.
Design and Setting: mtDNA content from cells from buccal and blood samples was assessed using a real-time PCR-based assay. Heritability of mtDNA content was estimated in 391 twins from the Netherlands Twin Register. The association with prevalent T2D was tested in a case control study from The Netherlands (n = 329). Incident T2D was analyzed using prospective samples from Finland (n = 444) and The Netherlands (n = 238).
Main Outcome Measures: We measured the heritability of mtDNA content and the association of mtDNA content in blood with prevalent and incident T2D.
Results: A heritability of mtDNA content of 35% (19–48%) was estimated in the twin families. We did not observe evidence of an association between mtDNA content and prevalent or incident T2D and related traits. Furthermore, we observed a decline in mtDNA content with increasing age that was male specific (P = 0.001).
Conclusion: In this study, we show that mtDNA content has a heritability of 35% in Dutch twins. There is no association between mtDNA content in blood and prevalent or incident T2D and related traits in our study samples.
Mixed Lineage Kinase-3/JNK1 Axis Promotes Migration of Human Gastric Cancer Cells following Gastrin Stimulation
Authors: Mishra Prajna , Senthivinayagam Subramanian , Rangasamy Velusamy , Sondarva Gautam , Rana Basabi 
Published: February 2010

AbstractGastrin is a gastrointestinal peptide hormone, secreted by the gastric G cells and can exist as a fully processed amidated form (G17) or as unprocessed forms. All forms of gastrin possess trophic properties towards the gastrointestinal mucosa. An understanding of the signaling pathways involved is important to design therapeutic approaches to target gastrin-mediated cellular events. The studies described here were designed to identify the signaling pathways by which amidated gastrin (G17) mediates cancer cell migration. These studies indicated a time- and dose-dependent increase in gastric cancer cell migration after G17 stimulation, involving cholecystokinin 2 receptor. G17-induced migration was preceded by activation of MAPK pathways and was antagonized after pretreatment with SP600125, a pharmacological inhibitor of c-Jun-NH2-terminal kinase (JNK) pathway. Knockdown of endogenous JNK1 expression via small interference RNA (JNK1-siRNA) inhibited G17-induced phosphorylation of c-Jun and migration, and overexpression of wild-type JNK1 or constitutive active JNK1 promoted G17-induced migration. Studies designed to identify the MAPK kinase kinase member mediating JNK activation indicated the involvement of mixed lineage kinase-3 (MLK3), which was transiently activated upon G17 treatment. Inhibition of MLK3 pathway via a pan-MLK inhibitor or knockdown of MLK3 expression by MLK3-siRNA antagonized G17-induced migration. Incubation with G17 also resulted in an induction of matrix metalloproteinase 7 promoter activity, which is known to mediate migration and invasion pathways in cancer cells. Modulation of MLK3, JNK1, and c-Jun pathways modulated G17-induced matrix metalloproteinase 7 promoter activation. These studies indicate that the MLK3/JNK1 axis mediates G17-induced gastric cancer cell migration, which can be targeted for designing novel therapeutic strategies for treating gastric malignancies.