bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of the oxysterol, 24(S), 25-epoxycholesterol, parallels cholesterol production and may protect against cellular accumulation of newly-synthesized cholesterol
Authors: Wong Jenny , Quinn Carmel M , Brown Andrew J 
Published: May 2007

Abstract

Aim
The effects of 24(S),25-epoxycholesterol (24,25EC) on aspects of cholesterol homeostasis is well-documented. When added to cells, 24,25EC decreases cholesterol synthesis and up-regulates cholesterol efflux genes, including ABCA1. Synthesis of 24,25EC occurs in a shunt of the mevalonate pathway which also produces cholesterol. Therefore, 24,25EC synthesis should be subject to the same negative feedback regulation as cholesterol synthesis. To date, no role has been ascribed to 24,25EC in light of the fact that increased accumulation of cholesterol should decrease formation of this oxysterol through feedback inhibition. This leads to the intriguing paradox: why inhibit production of an apparently important regulator of cholesterol homeostasis when it is needed most?

Methods
We used a combination of pharmacological and genetic approaches in Chinese Hamster Ovary cell-lines to investigate this paradox. Endogenous synthesis of 24,25EC was manipulated using partial inhibition of the enzyme, Oxidosqualene Cyclase. Changes in cholesterol and 24,25EC synthesis were determined using metabolic labelling with [1-14C]-acetate, thin-layer chromatography and phosphorimaging. Transcriptional effects mediated via SREBP and LXR were analysed by luciferase reporter assays.

Results
We showed that cholesterol addition to cells lead to a rapid and preferential inhibition of 24,25EC synthesis. Addition of 24,25EC resulted in parallel inhibition of 24,25EC and cholesterol synthesis. Furthermore, we used a variety of approaches to examine the relationship between cholesterol and 24,25EC synthesis, including cell-lines with different rates of cholesterol synthesis, varying cholesterol synthetic rates by pre-treatment with a statin, or lipoprotein cholesterol loading of macrophages. In all cases, we showed that 24,25EC synthesis faithfully tracked cholesterol synthesis. Moreover, changes in 24,25EC synthesis exerted downstream effects, reducing SREBP transcriptional activity whilst increasing ABCA1 and LXR transcriptional activity.

Conclusion
Our results show that 24,25EC synthesis parallels cholesterol synthesis, consistent with this oxysterol functioning as a safety valve to protect against the accumulation of newly-synthesised cholesterol (as opposed to exogenously-derived cholesterol). Considering that 24,25EC is capable of being produced in all cholesterogenic cells, we propose that production of 24,25EC may represent a ubiquitous defence mechanism.
The lipid lowering effect of plant sterol ester capsules in hypercholesterolemic subjects
Authors: Acuff Robert V , Cai David J , Dong Zhi-Ping , Bell Doris 
Published: May 2007

Abstract

Background
Foods enriched with phytosterols have been proven to be an effective therapy to improve blood lipid profiles. However, none of the studies have investigated the efficacy in lipid lowering of plant sterol esters (PSE) in capsule form. The objective of this study is to determine if the plant sterol esters (PSE) in capsule form (1.3 grams of PSE/day) lowered plasma cholesterol levels and lipid ratios in free-living hypercholesterolemic subjects during a 4-week intervention period.

Methods
Sixteen subjects participated in a double-blind, placebo-controlled, sequential study with a 4-week placebo phase followed by a 2-week wash-out period and a 4-week treatment phase. Subjects were instructed to maintain stable diet pattern and physical activities. Blood samples were collected at 7, 21 and 28 days of each phase. The primary measurements were change in plasma total cholesterol (TC), HDL-cholesterol (HDL) and LDL-cholesterol (LDL) between phases and within each phase. The secondary measurements were change in triglycerides, lipoprotein ratios (TC/HDL, LDL/HDL) and C-reactive protein (CRP).

Results
In comparison to placebo, LDL-cholesterol was significantly reduced by 7% and 4% (P < 0.05) at both week 3 and week 4; HDL at week 3 of the treatment was significantly increased by 9% (P < 0.01), but not at week 4 (4%); total cholesterol was not significantly different from placebo throughout the period, TC/HDL and LDL/HDL were significantly reduced by (8%, 8%, 6%, 10%, respectively) (P < 0.01) at both week 3 and week 4. CRP and triglycerides did not differ either between the two phases or during the treatment phase.

Conclusion
In conclusion, plant sterol ester capsule is effective in improving lipid profiles among hypercholesterolemic subjects in a free-living setting at the minimum dosage recommended by FDA. The significant improved lipid profiles were reached after three weeks of administration. To achieve better lipid lowering results, higher dosages and combination with diets low in saturated fat and cholesterol are recommended.
The influence of obesity on calf blood flow and vascular reactivity in older adults
Authors: Acree Luke S , Comp Philip C , Whitsett Thomas L , Montgomery Polly S , Nickel Kevin J , Fjeldstad Anette S , Fjeldstad Cecilie , Gardner Andrew W 
Published: May 2007

AbstractObjectiveTo determine whether differences in vascular reactivity existed among normal weight, overweight, and obese older men and women, and to examine the association between abdominal fat distribution and vascular reactivity.MethodsEighty-seven individuals who were 60 years of age or older (age = 69 ± 7 yrs; mean ± SD) were grouped into normal weight (BMI < 25; n = 30), overweight (BMI ≥ 25 and < 30; n = 28), or obese (BMI ≥ 30; n = 29) categories. Calf blood flow (BF) was assessed by venous occlusion strain-gauge plethysmography at rest and post-occlusive reactive hyperemia.ResultsPost-occlusive reactive hyperemia BF was lower (p = 0.038) in the obese group (5.55 ± 4.67 %/min) than in the normal weight group (8.34 ± 3.89 %/min). Additionally, change in BF from rest to post-occlusion in the obese group (1.93 ± 2.58 %/min) was lower (p = 0.001) than in the normal weight group (5.21 ± 3.59 %/min), as well as the percentage change (75 ± 98 % vs. 202 ± 190 %, p = 0.006, respectively). After adjusting for age, prevalence in hypertension and calf skinfold thickness, change in BF values remained lower (p < 0.05) in obese subjects compared to the normal weight subjects. Lastly, the absolute and percentage change in BF were significantly related to BMI (r = -0.44, p < 0.001, and r = -0.37, p < 0.001, respectively) and to waist circumference (r = -0.36, p = 0.001, and r = -0.32, p = 0.002).ConclusionObesity and abdominal adiposity impair vascular reactivity in older men and women, and these deleterious effects on vascular reactivity are independent of conventional risk factors.
The role of the purinergic P2X7 receptor in inflammation
Authors: Lister Martin F , Sharkey John , Sawatzky Deborah A , Hodgkiss Joseph P , Davidson Donald J , Rossi Adriano G , Finlayson Keith 
Published: May 2007

AbstractThe inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X7receptor (P2X7R) is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X7R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X7R in inflammation, immunity and its potential role in disease will be reviewed and discussed.
Anti-inflammatory potential of a malleable matrix composed of fermented whey proteins and lactic acid bacteria in an atopic dermatitis model
Authors: Beaulieu Josée , Dupont Claude , Lemieux Pierre 
Published: May 2007

Abstract

Background
Over the last 10 years, whey proteins have received considerable attention in the area of functional foods and nutraceuticals. In this paper, a novel fermented whey protein-based product described as a gel-like Malleable Protein Matrix (MPM) has been tested for its anti-inflammatory activity. Preliminary in vitro results have already indicated that MPM could exert such an anti-inflammatory activity.

Methods
The systemic anti-inflammatory activity of the MPM was explored using the oxazolone-induced atopic contact dermatitis mouse model (ACD). Parameters including ear thickness, side effects as well as neutrophil extravasation were monitored.

Results
In the ACD model, the MPM exhibited an anti-inflammatory effect comparable to that of hydrocortisone (positive control). Mice fed with MPM showed strong reduction of the ear inflammation while no side effects, as compared to hydrocortisone, were observed. The MPM seemed to reduce neutrophil extravasation in tissue as evidenced by blood polymorphonuclear cells and ear myeloperoxidase content.

Conclusion
The anti-inflammatory activity demonstrated in the ACD model suggests that the mechanism of action of the MPM is different than that of hydrocortisone and could become a relevant product for people suffering from dermatological manifestations associated with immune dysfunctions such as allergies, eczema, dermatitis, and autoimmune diseases.
Psycho-education programme for temporomandibular disorders: a pilot study
Authors: Jerjes Waseem , Madland Geir , Feinmann Charlotte , El Maaytah Mohammed , Kumar Mahesh , Hopper Colin , Upile Tahwinder , Newman Stanton 
Published: May 2007

Abstract

Background
Temporomandibular disorders (TMDs) are by far the most predominant condition affecting the temporomandibular joint (TMJ), however many patients have mild self-limiting symptoms and should not be referred for specialist care.
The aim of this pilot study was to develop a simple, cost-effective management programme for TMDs using CD-ROM. 41 patients (age 18–70) participated in this study, patients were divided into three groups: the 1st group were involved in an attention placebo CD-ROM (contain anatomical information about the temporomandibular system), the 2nd group received information on CD-ROM designed to increase their control and self efficacy, while the 3rd group received the same programme of the 2nd group added to it an introduction to self-relaxing techniques followed by audio tape of progressive muscle relaxation exercises. Each of the groups was asked to complete a number of questionnaires on the day of initial consultation and six weeks afterwards.

Results
The two experimental groups (2nd & 3rd) were equally effective in reducing pain, disability and distress, and both were more effective than the attention placebo group (1st), however the experimental groups appeared to have improved at follow-up relative to the placebo-group in terms of disability, pain and depressed mood.

Conclusion
This pilot study demonstrates the feasibility and acceptability of the design. A full, randomized, controlled trial is required to confirm the efficacy of the interventions developed here.
Vacuum-assisted closure therapy in ureteroileal anastomotic leakage after surgical therapy of bladder cancer
Authors: Denzinger Stefan , Luebke Lars , Burger Maximilian , Kessler Sigurd , Wieland Wolf F , Otto Wolfgang 
Published: May 2007

Abstract

Background
Vacuum-assisted closure (VAC) is an acknowledged method of treating wound healing disorders, but has been viewed as a contraindication in therapy of intraabdominal fistulas.

Case presentation
We present the case of an 83-year old patient with ureteroileal anastomotic insufficiency following cystectomy and urinary diversion by Bricker ileal conduit due to urothelial bladder cancer. After developing an open abdomen on the 16th postoperative day a leakage of the ureteroileal anastomosis appeared that cannot be managed by surgical means. To stopp the continued leakage we tried a modified VAC therapy with a silicon covered polyurethane foam under a suction of 125 mmHg. After 32 days with regularly changes of the VAC foam under general anesthesia the fistula resolved without further problems of ureteroileal leakage.

Conclusion
We present the first report of VAC therapy successfully performed in urinary tract leakage after surgical treatment of bladder cancer. VAC therapy of such disorders requires greater care than of superficial application to avoid mechanical alterations of internal organs but opens new opportunities in cases without surgical alternatives.
Ubp43 gene expression is required for normal Isg15 expression and fetal development
Authors: Rempel Lea A , Austin Kathleen J , Ritchie Kenneth J , Yan Ming , Shen Meifeng , Zhang Dong-Er , Henkes Luiz E , Hansen Thomas R 
Published: May 2007

AbstractBackgroundIsg15 covalently modifies murine endometrial proteins in response to early pregnancy. Isg15 can also be severed from targeted proteins by a specific protease called Ubp43 (Usp18). Mice lacking Ubp43 (null) form increased conjugated Isg15 in response to interferon. The Isg15 system has not been examined in chorioallantoic placenta (CP) or mesometrial (MM) components of implantation sites beyond 9.5 days post coitum (dpc). It was hypothesized that deletion of Ubp43 would cause disregulation of Isg15 in implantation sites, and that this would affect pregnancy rates.MethodsHeterozygous (het) Ubp43 mice were mated and MM and CP implantation sites were collected on 12.5 and 17.5 days post-coitum (dpc).ResultsFree and conjugated Isg15 were greater on 12.5 versus 17.5 dpc in MM. Free and conjugated Isg15 were also present in CP, but did not differ due to genotype on 12.5 dpc. However, null CP had greater free and conjugated Isg15 when compared to het/wt on 17.5 dpc. Null progeny died in utero with fetal genotype ratios (wt:het:null) of 2:5:1 on 12.5 and 2:2:1 on 17.5 dpc. Implantation sites were disrupted within the junctional zone and spongiotrophoblast, contained less vasculature based on lectin B4 staining and contained greater Isg15 mRNA and VEGF protein in Ubp43 null when compared to wt placenta.ConclusionIt is concluded that Isg15 and its conjugates are present in implantation sites during mid to late gestation and that deletion of Ubp43 causes an increase in free and conjugated Isg15 at the feto-maternal interface. Also, under mixed genetic background, deletion of Ubp43 results in fetal death.
An exploration of socioeconomic variation in lifestyle factors and adiposity in the Ontario Food Survey through structural equation modeling
Authors: Ward Heather , Tarasuk Valerie , Mendelson Rena , McKeown-Eyssen Gail 
Published: May 2007

Abstract

Title
An exploration of socioeconomic variation in lifestyle factors and adiposity in the Ontario Food Survey through structural equation models.

Background
Socioeconomic indicators have been inversely associated with overweight and obesity, with stronger associations observed among women. The objective of the present secondary analysis was to examine the relationships among socioeconomic measures and adiposity for men and women participating in the Ontario Food Survey (OFS), and to explore lifestyle factors as potential mediators of these associations.

Methods
The cross-sectional 1997/98 OFS collected anthropometric measurements, a food frequency questionnaire, data on socio-demographics (age, sex, income, and education) and physical activity from 620 women and 467 men, ages 18 to 75. Based on the 2003 Health Canada guidelines, waist circumference and BMI values were used to derive least risk, increased risk, and high risk adiposity groups. Structural equation modeling was conducted to examine increased risk and high risk adiposity in relation to education and income, with leisure time physical activity, fruit and vegetable intake, and smoking status included as potential mediators of these associations.

Results
The probability of high risk adiposity was directly associated with education (β-0.19, p < 0.05) and income (β-0.22, p < 0.05) for women, but not for men. Fruit and vegetable intake was a marginally significant mediator of the relationship between education and high risk adiposity for women. Increased risk adiposity was not associated with income or education for men or women.

Conclusion
The socioeconomic context of adiposity continues to differ greatly between men and women. For women only in the OFS, fruit and vegetable intake contributed to the inverse association between education and high risk adiposity; however, additional explanatory factors are yet to be determined.
Specific targeting of whole lymphoma cells to dendritic cells ex vivo provides a potent antitumor vaccine
Authors: Adam Christian , Mysliwietz Josef , Mocikat Ralph 
Published: May 2007

AbstractBackgroundDendritic cells (DC) pulsed with tumor-derived antigenic material have widely been used in antitumor vaccination protocols. However, the optimal strategy of DC loading has not yet been established. Our aim was to define requirements of optimal DC vaccines in terms ofin vivoprotection in a murine B-cell lymphoma model.MethodsWe compare various loading reagents including whole parental and modified tumor cells and a single tumor-specific antigen, namely the lymphoma idiotype (Id). Bone marrow-derived DC were pulsedin vitroand used for therapy of established A20 lymphomas.ResultsWe show that a vaccine with superior antitumor efficacy can be generated when DC are loaded with whole modified tumor cells which provide both (i) antigenic polyvalency and (ii) receptor-mediated antigen internalization. Uptake of cellular material was greatly enhanced when the tumor cells used for DC pulsing were engineered to express an anti-Fc receptor immunoglobulin specificity. Upon transfer of these DC, established tumor burdens were eradicated in 50% of mice. By contrast, pulsing DC with unmodified lymphoma cells or with the lymphoma Id, even when it was endowed with the anti-Fc receptor binding arm, was far less effective. A specific humoral anti-Id response could be detected, particularly following delivery of Id protein-pulsed DC, but it was not predictive of tumor protection. Instead a T-cell response was pivotal for successful tumor protection. Interaction of the transferred DC with CD8+T lymphocytes seemed to play a role for induction of the immune response but was dispensable when DC had received an additional maturation stimulus.ConclusionOur analyses show that the advantages of specific antigen redirection and antigenic polyvalency can be combined to generate DC-based vaccines with superior antitumor efficacy. This mouse model may provide information for the standardization of DC-based vaccination protocols.
Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila
Authors: Hall Dayna J , Grewal Savraj S , de la Cruz Aida Flor A , Edgar Bruce A 
Published: May 2007

Abstract

Background

The Ras-related GTPase, Rheb, regulates the growth of animal cells. Genetic and biochemical tests place Rheb upstream of the target of rapamycin (TOR) protein kinase, and downstream of the tuberous sclerosis complex (TSC1/TSC2) and the insulin-signaling pathway. TOR activity is regulated by nutritional cues, suggesting that Rheb might either control, or respond to, nutrient availability.

Results

We show that Rheb and TOR do not promote the import of glucose, bulk amino acids, or arginine in Drosophila S2 cells, but that both gene products are important regulators of ribosome biogenesis, protein synthesis, and cell size. S2 cell size, protein synthesis, and glucose import were largely insensitive to manipulations of insulin signaling components, suggesting that cellular energy levels and TOR activity can be maintained through insulin/PI3K-independent mechanisms in S2 cell culture. In vivo in Drosophila larvae, however, we found that insulin signaling can regulate protein synthesis, and thus may affect TOR activity.

Conclusion

Rheb-TOR signaling controls S2 cell growth by promoting ribosome production and protein synthesis, but apparently not by direct effects on the import of amino acids or glucose. The effect of insulin signaling upon TOR activity varies according to cellular type and context.
The pathology of embryo death caused by the male-killing Spiroplasma bacterium in Drosophila nebulosa
Authors: Bentley Joanna K , Veneti Zoe , Heraty Joseph , Hurst Gregory DD 
Published: May 2007

Abstract

Background

Inherited bacteria that kill male offspring, male-killers, are known to be common in insects, but little is understood about the mechanisms used by male-killing bacteria to kill males. In this paper we describe the tempo and changes that occur during male-killing by Spiroplasma bacteria in the host Drosophila nebulosa.

Results

Spiroplasma infected D. nebulosa males were developmentally retarded from 6–8 h into embryonic development at 25°C, and arrested at between stages 12 and 13 of embryogenesis (10–12 h). Dying males were characterized by a failure to form segments, and ultimately disintegration of the normal oval embryonic shape. Prior to death, dying males exhibited widespread apoptosis, as testified by TUNEL staining.

Conclusion

The Spiroplasma kills male Drosophila in a narrow developmental period, shortly after the formation of the host dosage compensation complex that is required for male-killing. Male death is preceded by widespread apoptosis, but it is uncertain if this is primary or secondary apoptosis.