bluuebunny/crossref_metadata_2025 huggingface dataset:
Distant effects of nitric oxide inhalation in lavage‐induced lung injury in anaesthetised pigs
Authors: NILSSON M. C. A. , HAMBRAEUS‐JONZON K. , ALVING K. , WIKLUND P. , BERGQUIST M. , FREDÉN F.
Published: November 2012

Background

Inhalation of nitric oxide (INO) exerts both local and distant effects. INO in healthy pigs causes down‐regulation of endogenous nitric oxide (NO) production and vasoconstriction in lung regions not reached by INO, especially in hypoxic regions, which augments hypoxic pulmonary vasoconstriction. In contrast, in pigs with endotoxemia‐induced lung injury, INO causes increased NO production in lung regions not reached by INO. The aim of this study was to investigate whether INO exerts distant effects in surfactant‐depleted lungs.

Methods

Twelve pigs were anaesthetised, and the left lower lobe (LLL) was separately ventilated. Lavage injury was induced in all lung regions, except the LLL. In six pigs, 40 ppm INO was given to the LLL (INO group), and the effects on endogenous NO production and blood flow in the lavage‐injured lung regions were studied. Six pigs served as a control group. NO concentration in exhaled air (ENO), NO synthase (NOS) activity and cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured.

Results

The calcium (Ca2+)‐dependent NOS activity was lower (P < 0.05) in the lavage‐injured lung regions in the INO group than in the control group. There were no measurable differences between the groups for Ca2+‐independent NOS activity, cGMP, ENO, or regional pulmonary blood flow.

Conclusions

Regional INO did not increase endogenous NO production in lavage‐injured lung regions not directly reached by INO, but instead down‐regulated the constitutive calcium‐dependent nitric oxide synthase activity, indicating that NO may inhibit its own synthesis.
Medical practice and legal background of decisions for severely ill newborn infants: viewpoints from seven European countries
Authors: Sauer PJJ , Dorscheidt JHHM , Verhagen AAE , Hubben JH ,   On behalf of the European Neonatal EoL Study group 2010
Published: November 2012

Aim

To comparing attitudes towards end‐of‐life (EOL) decisions in newborn infants between seven European countries.

Methods

One paediatrician and one lawyer from seven European countries were invited to attend a conference to discuss the practice of EOL decisions in newborn infants and the legal aspects involved.

Results

All paediatricians/neonatologists indicated that the best interest of the child should be the leading principle in all decisions. However, especially when discussing cases, important differences in attitude became apparent, although there are no significant differences between the involved countries with regard to national legal frameworks.

Conclusion

Important differences in attitude towards neonatal EOL decisions between European countries exist, but they cannot be explained solely by medical or legal reasons.
Treatment with the cytochrome P450 ω‐hydroxylase inhibitor HET0016 attenuates cerebrovascular inflammation, oxidative stress and improves vasomotor function in spontaneously hypertensive rats
Authors: Toth Peter , Csiszar Anna , Sosnowska Danuta , Tucsek Zsuzsanna , Cseplo Peter , Springo Zsolt , Tarantini Stefano , Sonntag William E , Ungvari Zoltan , Koller Akos
Published: November 2012

Background and Purpose

Hypertension increases cerebrovascular oxidative stress and inflammation and impairs vasomotor function. These pathological alterations lead to dysregulation of cerebral blood flow and exacerbate atherogenesis, increasing the morbidity of ischaemic cerebrovascular diseases and promoting vascular cognitive impairment. We aimed to test the hypothesis that increased production of the arachidonic acid metabolite 20‐hydroxy‐5,8,11,14‐eicosatetraenoic acid (20‐HETE) contributes to hypertension‐induced cerebrovascular alterations.

Experimental Approach

We treated male spontaneously hypertensive rats (SHR) with HET0016 (N‐hydroxy‐N′‐(4‐butyl‐2‐methylphenyl)‐formamidine), an inhibitor of 20‐HETE synthesis. In middle cerebral arteries (MCAs) of SHRs, we focused on vasomotor responses and end points that are highly relevant for cellular reactive oxygen species (ROS) production, inflammatory cytokine expression and NF‐κB activation.

Key Results

SHRs treated with HET0016 remained hypertensive (SHR + HET0016: 149 ± 8 mmHg, Wistar‐Kyoto rat: 115 ± 4 mmHg; P < 0.05.), although their systolic blood pressure was decreased compared to untreated SHRs (191 ± 6 mmHg). In MCAs of SHRs, flow‐induced constriction was increased, whereas ACh‐ and ATP‐induced dilations were impaired. This functional impairment was reversed by treatment with HET0016. Treatment with HET0016 also significantly decreased oxidative stress in MCAs of SHRs (as shown by dihydroethidium staining and analysis of vascular 5‐nitrotyrosine, 4‐hydroxynonenal and carbonyl content) and inhibited cerebrovascular inflammation (shown by the reduced mRNA expression of TNFα, IL‐1β and IL‐6). Treatment of SHRs with HET0016 also attenuated vascular NF‐κB activation. In vitro treatment with 20‐HETE significantly increased vascular production of ROS and promoted NF‐κB activation in cultured cerebromicrovascular endothelial cells.

Conclusions and Implications

Taken together, treatment with HET0016 confers anti‐oxidative and anti‐inflammatory effects in the cerebral arteries of SHRs by disrupting 20‐HETE‐mediated autocrine/paracrine signalling pathways in the vascular wall. It is likely that HET0016‐induced decreases in blood pressure also potentiate the cerebrovascular protective effects of the drug.
Purple corn color inhibition of prostate carcinogenesis by targeting cell growth pathways
Authors: Long Ne , Suzuki Shugo , Sato Shinya , Naiki‐Ito Aya , Sakatani Keisuke , Shirai Tomoyuki , Takahashi Satoru
Published: November 2012

Purple corn color is a widely used food colorant that was reported to have attenuating effects on hypertension, diabetes, and to have anti‐cancer effects on colon and breast cancer. Our study is the first on its possible chemoprevention effects against prostate cancer. For this purpose an androgen‐dependent prostate cancer cell line, LNCaP, was used to examine effects in vitro. Purple corn color inhibited the proliferation of LNCaP cells by decreasing the expression of Cyclin D1 and inhibiting the G1 stage of the cell cycle. Thirty‐six male transgenic rats for adenocarcinoma of prostate were fed basic diet or diet with purple corn color for 8 weeks. Purple corn color decreased the incidence of adenocarcinoma in the lateral prostate and slowed down the progression of prostate cancer. A lower Ki67 positive rate, a decrease of the expression of Cyclin D1, and downregulation of the activation of Erk1/2 and p38 MAPK were observed in the group consuming purple corn color in the diet. Since purple corn color is a mixture, determining its active component should help in the understanding and usage of purple corn color for prostate cancer chemoprevention. Therefore, the three major anthocyanins in purple corn color, cyanidin‐3‐glucoside, pelargonidin‐3‐glucoside and peonidin‐3‐glucoside, were tested with LNCaP cells. The results suggested that cyanidin‐3‐glucoside and pelargonidin‐3‐glucoside are the active compounds.
Discrimination Concerns and Expectations as Explanations for Gendered Socialization in African American Families
Authors: Varner Fatima , Mandara Jelani
Published: November 2012

Discrimination concerns and parental expectations were examined as mediators of the relations between gender and parenting practices among 796 African American mothers of 11‐ to 14‐year‐olds from the Maryland Adolescent Development in Context Study. Mothers of sons had more concerns about racial discrimination impacting their adolescents' future, whereas mothers of daughters had more gender discrimination concerns. Racial discrimination concerns, but not gender discrimination concerns, were related to lower maternal academic and behavioral expectations. Maternal expectations were related to mothers' responsiveness, rule enforcement, monitoring, and parent–adolescent conflict. The relations between gender and parenting practices were partially explained through mothers' racial discrimination concerns and expectations. These findings demonstrate the importance of contextual factors on African American family processes.
Low faecal haemoglobin concentration potentially rules out significant colorectal disease
Authors: McDonald P. J. , Digby J. , Innes C. , Strachan J. A. , Carey F. A. , Steele R. J. C. , Fraser C. G.
Published: November 2012

Aim

The study aimed to determine whether faecal haemoglobin (Hb) concentration can assist in deciding who with lower abdominal symptoms will benefit from endoscopy.

Method

Faecal Hb concentrations were measured on single samples from 280 patients referred for lower gastrointestinal tract endoscopy from primary care in NHS Tayside who completed a faecal immunochemical test (FIT) for Hb and underwent subsequent endoscopy.

Results

Among 739 invited patients, FIT and endoscopy were completed by 280 (median age 63 (18–84) years; 59.6% women), with a median time between FIT and endoscopy of 9 days. Six (2.1%) participants had cancer, 23 (8.2%) had high‐risk adenoma (HRA) (more than three adenomas or any > 1 cm), 31 (11.1%) low‐risk adenoma (LRA) and 26 (9.3%) inflammatory bowel disease (IBD) as the most serious diagnosis. Those with cancer had a median faecal Hb of > 1000 ng Hb/ml buffer. Those with cancer + HRA + IBD had a median faecal Hb concentration of 75 ng Hb/ml buffer (95% CI 18–204), which was significantly higher than that of all remaining participants without significant colorectal disease (P < 0.0001). Using a cut‐off faecal Hb concentration of 50 ng Hb/ml buffer, negative predictive values of 100.0%, 94.4%, 93.4% and 93.9% were found for cancer, HRA, LRA and IBD. Patients with reasons for referral other than rectal bleeding and family history did not have high faecal Hb concentrations.

Conclusion

Faecal Hb concentration measurements have considerable potential to contribute to reducing unnecessary endoscopy for the majority of symptomatic patients.
Do developmental orthopaedic disorders influence future jumping performances inWarmblood stallions?
Authors: Verwilghen D. R. , Janssens S. , Busoni V. , Pille F. , Johnston C. , Serteyn D.
Published: November 2012

Reasons for performing the study

Few reports are available on the relationship between developmental orthopaedic diseases (DOD) and future performances inWarmblood horses.

Objectives

To investigate the relationship between performance and the presence ofDODlesions.

Methods

Records ofWarmblood stallions for which radiographic and performance data were available were collected. Showjumping performances were expressed as scores derived from the final ranking of horses in each competition. These scores are available in an established performance database. The relationship between radiographic findings and both performance scores and number of performances was analysed using a linear regression model.

Results

Two hundred and fifteen horses met the inclusion criteria. There was no difference in either the number of performances or performance score between horses categorised as affected withDODlesions (independent of joint location) compared with controls. Significantly lower numbers of performances were recorded for horses with osteochondral fragments (OCD) located at the dorsal aspect of the sagittal ridge of the metacarpo/metatarsophalangeal bone. No significant difference was found between horses affected withDODlesions of the tarsocrural joint and controls. Horses with osteochondrosis of the lateral trochlear ridge of the femur had both significantly lower performance scores and numbers of performances compared with controls.

Conclusion

This study demonstrated that specificDODlocation and site within the joint have an influence on performance. Osteochondral fragments in the femoropatellar and at the dorsal aspect of the sagittal ridge of the metacarpo/metatarsophalangeal joint resulted in lowered performance. Fragmentation in the tarsocrural joint had no influence on performance.

Potential relevance

The future athletic performance ofWarmblood jumping horses may be limited as a result ofOCDin the femoropatellar joint and to a certain extent the metacarpo/metatarsophalangeal joint.
Neutrophil–lymphocyte ratio predicts overall and recurrence‐free survival after liver transplantation for hepatocellular carcinoma
Authors: Limaye Alpna R. , Clark Virginia , Soldevila‐Pico Consuelo , Morelli Giuseppe , Suman Amitabh , Firpi Roberto , Nelson David R. , Cabrera Roniel
Published: November 2012

Aim

The goal of this study is to evaluate whether an elevated neutrophil–lymphocyte ratio (NLR) at the time of diagnosis predicts survival of patients with hepatocellular carcinoma (HCC) after liver transplantation (LT). We hypothesize that the NLR is predictive of overall survival (OS) and recurrence‐free survival (RFS) in patients with HCC who undergo LT.

Methods

This is a retrospective analysis of adult patients undergoing LT for HCC between 2000 and 2008 at our institution. We define an elevated NLR as a ratio of 5 or greater.

Results

We included 160 patients who underwent LT for HCC in the time period, of whom 28 had an elevated NLR. Seventeen subjects experienced recurrent HCC during the study period. The cumulative survival among subjects with an elevated NLR was significantly lower than among subjects with a normal NLR. On univariate analysis, several factors (including an elevated NLR) predicted decreased OS and RFS. However, after multivariate analysis, only three factors (including elevated NLR) remained significant as predictors of OS. Additionally, multivariate analysis revealed that an elevated NLR was the only significant independent predictor of RFS.

Conclusion

Preoperative NLR is a powerful independent predictor of OS and RFS in patients undergoing LT for HCC. Measurement of NLR could serve as a useful and easily obtained adjunct to the Model for End‐Stage Liver Disease score and Milan criteria when evaluating this patient population and determining which patients will gain the most survival benefit from transplantation.
Expression of OV‐6 in primary colorectal cancer and rectal cancer with preoperative chemoradiotherapy: a clinicopathological study
Authors: Lin Chih‐Hung , Liu Chia‐Hsing , Tsai Hsiang‐Lin , Wang Jaw‐Yuan , Tsai Hung‐Pei , Chai Chee‐Yin
Published: November 2012

Aims

OV‐6 is among the best available markers of liver stem cells. The aim of this study was to investigate OV‐6 expression and its clinical implications in colorectal cancer.

Methods and results

Expression of OV‐6 and its clinical implications were investigated in 94 patients with American Joint Committee on Cancer (AJCC) stage I–III primary colorectal cancer and in 37 rectal cancer patients who had received preoperative chemoradiotherapy. The two main expression patterns of OV‐6 were cytoplasmic and membranous. Overexpression of OV‐6, which was identified on the basis of overall staining intensity, was associated with perineural invasion, lymphovascular invasion, and early relapses. Membranous OV‐6 overexpression was also significantly associated with depth of tumour invasion, AJCC stage, lymphovascular and perineural invasion, and postoperative early relapse. Disease‐free survival and overall survival were significantly poorer in patients with high overall OV‐6 expression than in those with low overall OV‐6 expression (P = 0.015 and P = 0.029, respectively), and significantly poorer in patients with high membranous OV‐6 expression than in those with low membranous OV‐6 expression (P < 0.001 and P < 0.001, respectively). Membranous OV‐6 expression was a more reliable prognostic marker than overall expression.

Conclusions

OV‐6 is not unique to the hepatobiliary system, and may be a novel prognostic marker in colorectal cancer.
The infarct‐limiting effect of cerebral ischaemic postconditioning in rats depends on the middle cerebral artery branching pattern
Authors: Shcherbak Natalia , Popovetsky Maxim , Galagudza Michael , Barantsevitch Eugene , Shlyakhto Eugene
Published: November 2012

Cerebral ischaemic postconditioning (PostCon) is a recently discovered endogenous neuroprotective phenomenon that occurs after several brief bouts of reperfusion/ischaemia instituted immediately after prolonged cerebral ischaemia. Data on the extent of PostCon‐mediated infarct size limitation in models of focal cerebral ischaemia–reperfusion are controversial. In this study, we investigated the infarct‐limiting effect of PostCon in the rat model of focal cerebral ischaemia–reperfusion. The relationship between anatomic pattern of the middle cerebral artery (MCA) and infarct size was also studied. The protocol of PostCon consisting of five episodes each of 10‐s ischaemia and 10‐s reperfusion was protective in terms of infarct size limitation only in animals with the typical bifurcating MCA branching pattern. The anatomic pattern of the MCA should be considered as one of the important factors influencing the outcome of neuroprotection studies.
Social rank‐dependent expression of arginine vasotocin in distinct preoptic regions in male Oryzias latipes
Authors: Kagawa N.
Published: November 2012

This study examined arginine vasotocin (AVT) expression in the brains of dominant and subordinate male medaka Oryzias latipes after short‐ and long‐term competition. High AVT expression in distinct preoptic regions was found in dominants and subordinates within minutes of encountering each other. During long‐term competition, AVT expression remained high in dominants but not in subordinates.
Evolution of the biochemistry of the photorespiratory C2 cycle
Authors: Hagemann M. , Fernie A. R. , Espie G. S. , Kern R. , Eisenhut M. , Reumann S. , Bauwe H. , Weber A. P. M.
Published: November 2012

Oxygenic photosynthesis would not be possible without photorespiration in the present day O2‐rich atmosphere. It is now generally accepted that cyanobacteria‐like prokaryotes first evolved oxygenic photosynthesis, which was later conveyed via endosymbiosis into a eukaryotic host, which then gave rise to the different groups of algae and streptophytes. For photosynthetic CO2 fixation, all these organisms use RubisCO, which catalyses both the carboxylation and the oxygenation of ribulose 1,5‐bisphosphate. One of the reaction products of the oxygenase reaction, 2‐phosphoglycolate (2PG), represents the starting point of the photorespiratory C2 cycle, which is considered largely responsible for recapturing organic carbon via conversion to the Calvin–Benson cycle (CBC) intermediate 3‐phosphoglycerate, thereby detoxifying critical intermediates. Here we discuss possible scenarios for the evolution of this process toward the well‐defined 2PG metabolism in extant plants. While the origin of the C2 cycle core enzymes can be clearly dated back towards the different endosymbiotic events, the evolutionary scenario that allowed the compartmentalised high flux photorespiratory cycle is uncertain, but probably occurred early during the algal radiation. The change in atmospheric CO2/O2 ratios promoting the acquisition of different modes for inorganic carbon concentration mechanisms, as well as the evolutionary specialisation of peroxisomes, clearly had a dramatic impact on further aspects of land plant photorespiration.
The ‘green whistle’: A novel method of analgesia for transrectal prostate biopsy
Authors: Grummet Jeremy , Huang Sean , Konstantatos Alex , Frydenberg Mark
Published: November 2012

What's known on the subject? and What does the study add?

Periprostatic infiltration of local anaesthetic (PILA) is accepted as the current ‘gold standard’ of analgesia for TRUS‐guided biopsy. However, it does not account for discomfort of anal probe insertion and has not received wide uptake amongst clinicians. A better method is therefore sought. PenthroxTM (methoxyflurane) is an effective systemic analgesic that is self‐administered via a hand‐held inhaler. Its use in TRUS‐guided biopsy has not been previously reported.

An initial experience with a novel analgesic for TRUS‐guided biopsy, which appears to be safe and effective. It has led to the planning of a randomised control trial, which will compare Penthrox with PILA for TRUS‐guided biopsy.

Objectives

To determine the feasibility of using a novel inhaled analgesic agent (PenthroxTM, methoxyflurane)) for transrectal ultrasonography (TRUS)‐guided biopsies of the prostate.

Patients and methods

Patients undergoing TRUS‐guided biopsies were each given a Penthrox inhaler to self‐administer during the procedure and instructed in its use.

Immediately after the procedure, patients were asked to rate their pain using a verbal rating scale from 0 to 10.

Results

In all, 42 consecutive men underwent a TRUS‐guided biopsy.

The median pain score was 3.

All 42 patients stated they would be happy to undergo the same procedure again. The only adverse effects reported by patients were brief light‐headedness and a sickly sweet taste.

Conclusion

This study of our initial experience using Penthrox suggests that it may have a role in analgesia for TRUS‐guided biopsy.

It may provide safe, adequate analgesia that is easy for urologists to use and avoids excessive use of resources.

Planning for a randomised control trial comparing Penthrox to the current ‘gold standard’ of prostatic infiltration of local anaesthetic is presently underway.
Renal angiomyolipoma
Authors: Lienert Andrew R. , Nicol David
Published: November 2012

What's known on the subject? and What does the study add?

Renal angiomyolipomas (AMLs) were first described in 1900 by Grawitz when he published a description of a large renal tumour composed of fat, muscle and blood vessels. Over the subsequent 100 years a lot has been discovered about the AML of the kidney. Initially, it was thought to be a hamartoma, an abnormal proliferation of tissues that are normally present in the kidney. More recent studies and observations have led to these lesions being classed a form of neoplasm of the renal parenchyma.

The present paper is a review of the presenting features of renal AMLs, as well as an overview of how they are diagnosed and some of the difficulties in diagnosis. It is aimed as a brief overview of the presenting features and diagnostics of renal AMLs. We hope it will be useful to refresh the knowledge of practicing urologists and as a study aid for training urologists.

Renal angiomyolipomas (AMLs) are usually easy to diagnose with imaging alone. They have unique characteristics on ultrasonography, computerised tomography and magnetic resonance imaging that usually allow AMLs to be differentiated from other renal masses.

If this is not possible on imaging criteria then biopsy can be performed and AMLs have unique immunohistochemical staining that allows them to be accurately differentiated from other renal tumours.
SOCIAL ENTERPRISE: SPECIAL REPORT
Authors: Crainer Stuart
Published: November 2012

The rise of social enterprise seeks to tackle some of the world's most intractable problems. It might also re‐invent capitalism.
VITAL STATISTICS
Authors: Crainer Stuart
Published: November 2012

Could social enterprise reform capitalism and solve some of the world's biggest problems?
TWIN PEAKS: CHANGING LIVES IN NEPAL
Authors: Crainer Stuart
Published: November 2012

The Dolma Development Fund is changing lives in Nepal. Its founder Tim Gocher explains how.
SOCIAL FINANCING
Authors: Walker John
Published: November 2012

John Walker examines the financing opportunities and challenges facing social ventures.
ENTERPRISE OXYGEN
Authors: Peters Georgina
Published: November 2012

The Social Stock Exchange may help propel social enterprise to the next level by providing the oxygen of capital. Georgina Peters takes the air.
APPEARANCE IS EVERYTHING
Authors: Cable Daniel , Elsbach Kimberly
Published: November 2012

Non‐traditional work arrangements, such as telecommuting, have effects that are often not recognised, according to Daniel Cable and Kimberly Elsbach. Their research over the last decade shows that merely showing up at the office affects your standing at work.
STAKEHOLDERS: THREAT OR OPPORTUNITY
Authors: Crilly Donal
Published: November 2012

Firms that operate in the same industry with similar stakeholders and organisational pressures could be expected to respond to stakeholders in the same way. But they don't. Donal Crilly set out to discover why.
RESPONSIBLE READING
Authors: Crainer Stuart
Published: November 2012

If you are taking social responsibility seriously, what should you be reading?
FACE VALUES: BETH COMSTOCK
Authors: Crainer Stuart
Published: November 2012

In 2003, Beth Comstock was named General Electric's (GE) first Chief Marketing Officer (CMO) in more than 20 years. Today, she leads GE's growth and market‐innovation initiatives as well as the sales, marketing and communications functions. Comstock previously held roles at NBC, CBS, and Turner Broadcasting. She is a member of Nike's Board of Directors and Trustee President of the Smithsonian's Cooper‐Hewitt National Design Museum.
EXECUTIVE SUMMARY: USAGE AND ABUSAGE: FREE REIN
Authors: Ascarza Eva , Lambrecht Anja , Vilcassim Naufel
Published: November 2012

Eva Ascarza, Anja Lambrecht and Naufel Vilcassim, “When Talk is ‘Free’: The Effect of Tariff Structure on Usage under Two – and Three‐Part Tariffs’, Journal of Marketing Research (Working Paper: http://ssrn.com/abstract=1444757).
EXECUTIVE SUMMARY: OLD PROBLEMS: WOMEN AT THE GATES
Authors: Fernandez‐Mateo Isabel , King Zella
Published: November 2012

Isabel Fernandez‐Mateo and Zella King, ‘Anticipatory Sorting and Gender Segregation in Temporary Employment’, Management Science 57, no.6, June 2011.
MY DAY: A DAY WITH PIPPA WICKS OF ALIX PARTNERS
Authors: Wicks Pippa
Published: November 2012

Pippa Wicks is Managing Director and London office head of AlixPartners, a global firm of operational and financial professionals. What does her day look like?
Plane Registration Leveraged by Global Constraints for Context‐Aware AEC Applications
Authors: Feng Chen , Kamat Vineet R.
Published: November 2012

Abstract:  In this article, we propose a new registration algorithm and computing framework, the KEG tracker, for estimating a camera's position and orientation for a general class of mobile context‐aware applications in Architecture, Engineering, and Construction (AEC). By studying two classic natural marker‐based registration algorithms, Homography‐from‐detection and Homography‐from‐tracking, and by overcoming their specific limitations of jitter and drift, our method applies two global constraints (geometric and appearance) to prevent tracking errors from propagating between consecutive frames. The proposed method is able to achieve an increase in both stability and accuracy, while being fast enough for real‐time applications. Experiments on both synthesized and real‐world test cases demonstrate that our method is superior to existing state‐of‐the‐art registration algorithms. The article also explores several AEC applications of our method in context‐aware computing and desktop‐augmented reality.
Pelvic Limb Kinetic and Kinematic Analysis inLabradorRetrievers Predisposed or at a Low Risk for Cranial Cruciate Ligament Disease
Authors: Ragetly Chantal A. , Griffon Dominique J. , Klump L. Michaela , Hsiao‐Wecksler Elizabeth T.
Published: November 2012

Objective

To compare kinematics, net moments, powers, ground and joint reaction forces (GRF,JRF) across the hock, stifle and hip joints inLabradorRetrievers at low risk or predisposed to cranial cruciate ligament disease (CCLD).

Study Design

Cross‐sectional clinical study.

Animals

Clinically normalLabradors predisposed (n = 11) or at low risk forCCLD(n = 9).

Methods

Right pelvic limbs were classified as predisposed or not toCCLDusing a predictive score equation based on combining tibial plateau angle (TPA) and femoral anteversion angle (FAA) measured on radiographs. Kinematic,GRF, and morphometric data were combined in an inverse dynamics approach to compute hock, stifle and hip kinematics, net moments, powers, and JRF while trotting.

Results

The extensor moment of the hock joint was greater in predisposed limbs compared with nonpredisposed limbs (0.37 versus 0.28 Nm/kg). The power generated around the hock and stifle joints in predisposed limbs was increased (0.69 versus 0.44 W/kg for the hock, 1.59 versus 1.05 W/kg for the stifle). Trotting velocity, stance time, vertical and craniocaudalGRFandJRFdid not differ between groups.

Conclusions

Extensor moment at the hock was increased in predisposed limbs compared with nonpredisposed limbs. Predisposed limbs generated more energy than nonpredisposed limbs around the hock and stifle joints.
Minimally Invasive Transxiphoid Approach to the Cardiac Apex and Caudoventral Intrathoracic Space
Authors: Nelson David A. , Miller Matthew W. , Gordon Sonya G. , Saunders Ashley , Fossum Theresa W.
Published: November 2012

Objective

To describe a minimally invasive surgical technique for procedures involving the caudoventral compartment of the thoracic cavity.

Study Design

Case series.

Animals

Dogs (n = 13).

Methods

Thirteen dogs; undergoing epicardial pacemaker implantation (9), palliative pericardial window (2), perforated right ventricle repair with epicardial pacemaker implantation (1), and peritoneopericardial diaphragmatic hernia (1) were operated by a transxiphoid approach. Dogs were positioned in dorsal recumbency and the bony xiphoid process was dissected free of adjoining tissue and transected proximally and distally. The distal transection was proximal to the cartilaginous junction of the process and the diaphragm. Entry to the thoracic cavity without penetration of the abdomen provided access for surgical treatment.

Results

All dogs recovered without complication. No dogs required thoracostomy tube placement.

Conclusions

Transxiphoid approach is minimally invasive and provides adequate exposure for disorders of the caudoventral thoracic cavity.
Expression of cell proliferation cycle negative regulators in fibroblasts of an ischemic diabetic foot ulcer. A clinical case report
Authors: Berlanga‐Acosta Jorge , Mendoza‐Mari Yssel , Martínez María Daniela , Valdés‐Perez Calixto , Ojalvo Ariana G , Armstrong David G
Published: November 2012

Wound chronification and opportunistic infections stand as major factors leading to lower extremities amputations in diabetes. The molecular mechanisms underlying diabetic's torpid healing have not been elucidated. We present the case of a female diabetic patient that after a plantar abscess surgical drainage, tight glycaemia control and infection clearance; the wound bed evolved to chronification with poor matrix accumulation, scant angiogenesis and no evidence of dermo‐epidermal contours contraction. Ulcer fibroblasts yet cultured under ‘physiological’ conditions exhibited a slow and declining proliferative response. Diabetic fibroblasts cycle arrest occurred earlier than non‐diabetic counterparts. This in vitro premature arrest‐senescence phenotype appeared related to the transcriptional upregulation of p53 and the proto‐oncogene c‐myc; with a concomitant expression reduction of the survival and cellular growth promoters Akt and mTOR. Importantly, immunocytochemistry of the diabetic ulcer‐derived fibroblasts proved nuclear over expression of potent proliferation inhibitors and pro‐senescence proteins as p53 phosphorylated on serine‐15 and p21Cip(1). In line with this, cyclin D1 appeared substantially underexpressed in these cells. We postulate that the downregulation of the Akt/mTOR/cyclin D1 axis by the proximal activation of p53 and p21 due to stressor factors, impose an arrest/pro‐senescence programme that translated in a torpid and slow healing process.
Evaluation of Pumping Induced Flow in Observation Wells During Aquifer Testing
Authors: Székely Ferenc
Published: November 2012

The vertical variation of drawdown around pumping wells generates an induced flow in the observation wells. A set of governing equations is presented to couple the drawdown variation and the vertical flux distribution in observation wells. A numerical example is performed to justify the governing equations and to verify the solution methods used by the simulation software WT. The example analyzes the effect of skin loss, wellbore storage, and vertical segmentation on the drawdown and induced flow in observation well during pumping. The evaluation of the Fairborn pumping test involves a vertically homogeneous and anisotropic water table aquifer, uniform well‐face drawdown conditions in the pumping well and simulation of the drawdown evolution in the observation well with and without the effect of induced flow. The computer calibrations resulted in small differences between the measured and simulated drawdown curves.
Peer Group Influence on Urban Preadolescents' Attitudes Toward Material Possessions: Social Status Benefits of Material Possessions
Authors: SHI BING , XIE HONGLING
Published: November 2012

This study explores peer influence on urban preadolescents' perceptions of social status benefits of material possessions. A longitudinal design is used. Natural, interaction‐based peer groups are identified through the Social Cognitive Map procedure. Findings indicate that high‐status rather than low‐status peers in a group are influential on individuals. Strong influence of high‐status peers is observed in both boys' and girls' groups. High‐status peers are particularly influential on low‐status individuals in girls' groups and on high‐status individuals in boys' groups. Additionally, high‐status peers' influence is stronger on African Americans than on Hispanic Americans and tends to be stronger on Hispanic Americans than on White Americans. These findings imply that special attention should be given to high‐status youth in groups who highly endorse social benefits of material possessions. Characteristics of the target youth (e.g., gender, ethnicity and individual status) should be considered in future efforts for reducing the pervasiveness of materialism.
Study in 1790 Baltic men:FSHRAsn680Ser polymorphism affects total testes volume
Authors: Grigorova M. , Punab M. , Poolamets O. , Sõber S. , Vihljajev V. , Žilaitienė B. , Erenpreiss J. , Matulevičius V. , Tsarev I. , Laan M.
Published: November 2012

Follicle‐stimulating hormone receptor (FSHR) contains two common linked polymorphisms, Thr307Ala (rs6165) and Asn680Ser (rs6166), shown to modulate ovarian function in women. The effect on male fertility and reproductive parameters has been inconclusive. We studiedFSHRAsn680Ser polymorphism in a large study group (n = 1790) from the Baltic countries. The population‐based Baltic male cohort (Estonians, Latvians, Lithuanians;n = 1052) and Estonian oligo‐/azoospermic (sperm concentration <20 × 106/mL) idiopathic infertile patients (n = 738) were genotyped for the FSHR Asn680Ser using PCR‐RFLP. Genetic associations were tested using linear regression under additive model and results were combined in meta‐analysis. No statistical difference was detected in allelic distribution of the FSHR Asn680Ser between the Baltic cohort and Estonian male infertility group. A consistent significant association was detected between the FSHR Ser680 allele and lower total testes volume in both, the Baltic cohort (p = 0.010, effect = −1.16 mL) and Estonian idiopathic infertility group (p = 0.007, effect = −1.77 mL). In meta‐analysis, the statistical significance was enhanced (p = 0.000066, effect = −1.40 mL). Meta‐analysis supported further associations with moderate effect between the FSHR Ser680 variant and higher serum FSH (p = 0.072), lower Inhibin B (p = 0.037) and total testosterone (p = 0.034). No statistically significant associations were identified with serum LH and estradiol, and sperm parameters. In conclusion, the study in 1790 Baltic men shows statistically highly significant association of theFSHRAsn680Ser with total testes volume and supportive association with serum reproductive hormone levels indicative to the functional effect of the alternativeFSHRvariants on male reproductive physiology.
Partial loss of contractile marker proteins in human testicular peritubular cells in infertility patients
Authors: Welter H. , Kampfer C. , Lauf S. , Feil R. , Schwarzer J. U. , Köhn F.‐M. , Mayerhofer A.
Published: November 2012

Fibrotic remodelling of the testicular tubular wall is common in human male infertility caused by impaired spermatogenesis. We hypothesized that this morphological change bears witness of an underlying fundamentally altered state of the cells building this wall, that is, peritubular smooth muscle‐like cells. This could include a loss of the contractile abilities of these cells and thus be a factor in male infertility. Immune cells are increased in the tubular wall in these cases, hence local immune cell‐related factors, including a prostaglandin (PG) metabolite may be involved. To explore these points in the human, we used testicular biopsies, in which tubules with normal spermatogenesis and impaired spermatogenesis are next to each other [mixed atrophy (MA)], normal biopsies and cultured human testicular peritubular cells. Proteins essential for contraction, myosin heavy chain (MYH11), calponin (Cal) and relaxation, cGMP‐dependent protein kinase 1 (cGKI), were readily detected by immunohistochemistry and were equally distributed in all peritubular cells of biopsies with normal spermatogenesis. In all biopsies, vascular smooth muscle cells also stained and served as important intrinsic controls, which showed that in MA samples when spermatogenesis was impaired, staining was restricted to only few peritubular cells or was absent. When spermatogenesis was normal, regular peritubular staining became obvious. This pattern suggests complex regulatory influences, which in face of the identical systemic hormonal situation in MA patients, are likely caused by the local testicular micromilieu. The PG metabolite 15dPGJ2 may represent such a factor and it reduced Cal protein levels in peritubular cells from patients with/without impaired spermatogenesis. The documented phenotypic switch of peritubular, smooth muscle‐like cells in MA patients may impair the abilities of the afflicted seminiferous tubules to contract and relax and must now be considered as a part of the complex events in male infertility.
Orally applied doxazosin disturbed testosterone homeostasis and changed the transcriptional profile of steroidogenic machinery, cAMP/cGMP signalling and adrenergic receptors in Leydig cells of adult rats
Authors: Stojkov N. J. , Janjic M. M. , Kostic T. S. , Andric S. A.
Published: November 2012

Doxazosin (Doxa) is an α1‐selective adrenergic receptor (ADR) antagonist widely used, alone or in combination, to treat high blood pressure, benign prostatic hyperplasia symptoms, and recently has been suggested as a potential drug for prostate cancer prevention/treatment. This study was designed to evaluate the effect of in vivo Doxa po‐application, in clinically relevant dose, on: (i) steroidogenic machinery homeostasis; (ii) cAMP/cGMP signalling; (iii) transcription profile of ADR in Leydig cells of adult rats. The results showed that po‐application of Doxa for once (1×Doxa), or for two (2×Doxa) or 10 (10×Doxa) consecutive days significantly disturbed steroidogenic machinery homeostasis in Leydig cells. Doxa po‐application significantly decreased circulating luteinizing hormone and androgens levels. The level of androgens in testicular interstitial fluid and that extracted from testes obtained from 1×Doxa/2×Doxa rats decreased, although it remained unchanged in 10×Doxa rats. Similarly, the ex vivo basal androgen production followed in testes isolated from 1×Doxa/2×Doxa rats decreased, while remained unchanged in 10×Doxa rats. Differently, ex vivo testosterone production and steroidogenic capacity of Leydig cells isolated from 1×Doxa/2×Doxa rats was stimulated, while 10×Doxa had opposite effect. In the same cells, cAMP content/release showed similar stimulatory effect, but back to control level in Leydig cells of 10×Doxa. 1×Doxa/2×Doxa decreased transcripts for cAMP specific phosphodiesterases Pde7b/Pde8b, whereas 10×Doxa increased Pde4d. All types of treatment reduced the expression of genes encoding protein kinase A (PRKA) regulatory subunit (Prkar2b), whereas only 10×Doxa stimulated catalytic subunit (Prkaca). Doxa application more affected cGMP signalling: stimulated transcription of constitutive nitric oxide synthases (Nos1, Nos3) in time‐dependent manner, whereas reduced inducible Nos2. 10×Doxa increased guanylyl cyclase 1 transcript and PRKG1 protein in Leydig cells. Orally applied Doxa significantly disturbed the transcriptional ‘signature’ of steroidogenic machinery, cAMP/cGMP signalling and ADRs and β‐ADRs kinases in Leydig cells, thus giving new molecular insights into the role of cAMP/cGMP/adrenalin signalling in Leydig cells homeostasis.
Parallel and nonparallel ecological, morphological and genetic divergence in lake–stream stickleback from a single catchment
Authors: Ravinet M. , Prodöhl P. A. , Harrod C.
Published: November 2012

Parallel phenotypic evolution in similar environments has been well studied in evolutionary biology; however, comparatively little is known about the influence of determinism and historical contingency on the nature, extent and generality of this divergence. Taking advantage of a novel system containing multiple lake–stream stickleback populations, we examined the extent of ecological, morphological and genetic divergence between three‐spined stickleback present in parapatric environments. Consistent with other lake–stream studies, we found a shift towards a deeper body and shorter gill rakers in stream fish. Morphological shifts were concurrent with changes in diet, indicated by both stable isotope and stomach contents analysis. Performing a multivariate test for shared and unique components of evolutionary response to the distance gradient from the lake, we found a strong signature of parallel adaptation. Nonparallel divergence was also present, attributable mainly to differences between river locations. We additionally found evidence of genetic substructuring across five lake–stream transitions, indicating that some level of reproductive isolation occurs between populations in these habitats. Strong correlations between pairwise measures of morphological, ecological and genetic distance between lake and stream populations supports the hypothesis that divergent natural selection between habitats drives adaptive divergence and reproductive isolation. Lake–stream stickleback divergence inLoughNeagh provides evidence for the deterministic role of selection and supports the hypothesis that parallel selection in similar environments may initiate parallel speciation.
Neuregulin 1 up‐regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade in adult autonomic ganglion neurons
Authors: Kim Han‐Gyu , Lee Choong‐Ku , Cho Sung‐Min , Whang Kum , Cha Byong‐Ho , Shin Ju‐Hyun , Song Ki‐Hak , Jeong Seong‐Woo
Published: November 2012

We investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat. MPG neurons were found to express transcripts for type I and III NRG1s as well as α and β‐type epidermal growth factor (EGF)‐like domains. Of the four ErbB receptor isoforms, ErbB1, ErbB2, and ErbB3 were expressed in MPG neurons. Treating MPG with NRG1β significantly increased the transcript and protein level of the nAChR α3 and β4 subunits. Consistent with these molecular data, nicotinic currents (IACh) were significantly up‐regulated in NRG1β‐treated sympathetic and parasympathetic MPG neurons. In contrast, the type III NRG1 and the α form of the NRG1 failed to alter the IACh. Inhibition of the ErbB2 tyrosine kinase completely abolished the effects of NRG1β on the IACh. Stimulation of the ErbB receptors by NRG1β activated the phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK). Immunoblot analysis revealed that PI3K‐mediated activation of Akt preceded Erk1/2 activation in NRG1β‐treated MPG neurons. Furthermore, specific PI3K inhibitors abrogated the phosphorylation of Erk1/2, while inhibition of MEK did not prevent the phosphorylation of Akt. Taken together, these findings suggest that NRG1 up‐regulates nAChR expression via the ErbB2/ErbB3‐PI3K‐MAPK signaling cascade and may be involved in maintaining the ACh‐mediated synaptic transmission in adult autonomic ganglia.
Enhanced expression of the Flt‐1 and Flk‐1 receptor tyrosine kinases in a newborn piglet model of ischemic tolerance
Authors: Ara Jahan , Shukla Panchanan , Frank Melissa
Published: November 2012

Vascular endothelial growth factor (VEGF), an angiogenic factor induced by hypoxia, also exerts direct effects on neural tissues. VEGF up‐regulation after hypoxia coincides with expression of its two tyrosine kinase receptors Flt‐1(VEGFR‐1) and Flk‐1 (KDR/VEGFR‐2), which are the key mediators of physiological angiogenesis. We have recently shown that hypoxic‐preconditioning (PC) leading to tolerance to hypoxia–ischemia in neonatal piglet brain resulted in increased expression of VEGF. In this study, we used a hypoxic‐preconditioning model of ischemic tolerance to analyze the expression and cellular distribution of VEGF receptors and phosphorylation of cAMP‐response element‐binding protein (CREB) in newborn piglet brain. The response of Flt‐1 and Flk‐1 mRNA to PC alone was biphasic with peaks early (6 h) and late (1 week) after PC. The mRNA expression of Flt‐1 and Flk‐1 in piglets preconditioned 24 h prior to hypoxia–ischemia was significantly higher than non‐preconditioned piglets and remained up‐regulated up to 7 days. Furthermore, PC prior to hypoxia–ischemia significantly increased the protein levels of Flt‐1 and Flk‐1 compared with hypoxia–ischemia in a time‐dependent manner. Double‐immunolabeling indicated that both Flt‐1 and Flk‐1 are expressed in neurons and endothelial cells with a similar time course of expression following PC and that PC leads to the growth of new vessels. Finally, our data demonstrate that PC significantly phosphorylated and activated cAMP‐response element‐binding protein in nucleus. These results suggest that mechanism(s) initiated by PC can induce VEGF receptor up‐regulation in newborn brain and that VEGF–VEGF receptor‐coupled signal transduction pathways could contribute to the establishment of tolerance following hypoxia–ischemia.
Effects of sirtuin 1 activation on nicotine and lipopolysaccharide‐induced cytotoxicity and inflammatory cytokine production in human gingival fibroblasts
Authors: Park G‐J. , Kim Y‐S. , Kang K‐l. , Bae S‐J. , Baek H‐S. , Auh Q‐S. , Chun Y‐H. , Park B‐H. , Kim E‐C.
Published: November 2012

Background and Objective

Although sirtuin 1 (SIRT1) over‐expression and resveratrol exert anti‐inflammatory and proinflammatory effects, their effects and the mechanism of action on human gingival fibroblast (HGF)‐mediated inflammation are unknown. The aim of this study was to demonstrate the effects of activating SIRT1 using resveratrol and recombinant adenovirus encoding SIRT1 (Ad‐SIRT1) on the expression of proinflammatory cytokines and to elucidate its mechanism of action of lipopolysaccharide (LPS) and nicotine stimulated‐HGF.

Material and Methods

Cytotoxicity and the production of reactive oxygen species (ROS) were measured using the 3‐(4,5‐dimethylthiazolyl‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. The amount of prostaglandin E2 (PGE2) released into the culture medium was measured by radioimmunoassay. mRNA and protein levels were analyzed using RT‐PCR and western blotting, respectively.

Results

Nicotine and LPS up‐regulated the expression of SIRT1 mRNA and SIRT1 protein in a time‐ and concentration‐dependent manner. Resveratrol and Ad‐SIRT1 decreased LPS and nicotine‐induced cytotoxicity, ROS and PGE2 production, and expression of cyclooxygenase‐2 in HGFs. Resveratrol and Ad‐SIRT1 inhibited nicotine and LPS‐mediated protein kinase C (PKC), phosphatidylinositol 3‐kinase (PI3K), p38, ERK, JNK, MAPK and nuclear factor‐kappa B (NF‐κB) activation.

Conclusion

This study is the first to show that the anti‐inflammatory and cytoprotective effects of SIRT1 activation in HGFs occur through the PKC, PI3K, MAPK and NF‐κB pathways.