bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL2 modulates cytokine production in cultured mouse astrocytes
Authors: Semple Bridgette D , Frugier Tony , Morganti-Kossmann M Cristina 
Published: October 2010

AbstractBackgroundThe chemokine CCL2 (also known as monocyte chemoattractant protein-1, or MCP-1) is upregulated in patients and rodent models of traumatic brain injury (TBI), contributing to post-traumatic neuroinflammation and degeneration by directing the infiltration of blood-derived macrophages into the injured brain. Our laboratory has previously reported thatCcl2-/- mice show reduced macrophage accumulation and tissue damage, corresponding to improved motor recovery, following experimental TBI. Surprisingly,Ccl2-deficient mice also exhibited delayed but exacerbated secretion of key proinflammatory cytokines in the injured cortex. Thus we sought to further characterise CCL2's potential ability to modulate immunoactivation of astrocytesin vitro.MethodsPrimary astrocytes were isolated from neonatal wild-type andCcl2-deficient mice. Established astrocyte cultures were stimulated with various concentrations of lipopolysaccharide (LPS) and interleukin (IL)-1β for up to 24 hours. Separate experiments involved pre-incubation with mouse recombinant (r)CCL2 prior to IL-1β stimulation in wild-type cells. Following stimulation, cytokine secretion was measured in culture supernatant by immunoassays, whilst cytokine gene expression was quantified by real-time reverse transcriptase polymerase chain reaction.ResultsLPS (0.1-100 μg/ml; 8 h) induced the significantly greater secretion of five key cytokines and chemokines inCcl2-/- astrocytes compared to wild-type cells. Consistently, IL-6 mRNA levels were 2-fold higher inCcl2-deficient cells. IL-1β (10 and 50 ng/ml; 2-24 h) also resulted in exacerbated IL-6 production fromCcl2-/- cultures. Despite this, treatment of wild-type cultures with rCCL2 alone (50-500 ng/ml) did not induce cytokine/chemokine production by astrocytes. However, pre-incubation of wild-type astrocytes with rCCL2 (250 ng/ml, 12 h) prior to stimulation with IL-1β (10 ng/ml, 8 h) significantly reduced IL-6 protein and gene expression.ConclusionsOur data indicate that astrocytes are likely responsible for the exacerbated cytokine response seenin vivopost-injury in the absence of CCL2. Furthermore, evidence that CCL2 inhibits cytokine production by astrocytes following IL-1β stimulation, suggests a novel, immunomodulatory role for this chemokine in acute neuroinflammation. Further investigation is required to determine the physiological relevance of this phenomenon, which may have implications for therapeutics targeting CCL2-mediated leukocyte infiltration following TBI.
Interaction of human dipeptidyl peptidase IV and human immunodeficiency virus type-1 transcription transactivator in Sf9 cells
Authors: Tansi Felista L , Blanchard Véronique , Berger Markus , Tauber Rudolf , Reutter Werner , Fan Hua 
Published: October 2010

AbstractBackgroundDipeptidyl peptidase IV (DPPIV) also known as the T cell activation marker CD26 is a multifunctional protein which is involved in various biological processes. The association of human-DPPIV with components of the human immunodeficiency virus type-1 (HIV1) is well documented and raised some discussions. Several reports implicated the interaction of human-DPPIV with the HIV1 transcription transactivator protein (HIV1-Tat) and the inhibition of the dipeptidyl peptidase activity of DPPIV by the HIV1-Tat protein. Furthermore, enzyme kinetic data implied another binding site for the HIV1-Tat other than the active centre of DPPIV. However, the biological significance of this interaction of the HIV1-Tat protein and human-DPPIV has not been studied, yet. Therefore, we focused on the interaction of HIV1-Tat protein with DPPIV and investigated the subsequent biological consequences of this interaction inSpodoptera frugiperdacells, using the BAC-TO-BAC baculovirus system.ResultsThe HIV1-Tat protein (Tat-BRU) co-localized and co-immunoprecipitated with human-DPPIV protein, following co-expression in the baculovirus-drivenSf9cell expression system. Furthermore, tyrosine phosphorylation of DPPIV protein was up-regulated in Tat/DPPIV-co-expressing cells after 72 h culturing and also in DPPIV-expressingSf9cells after application of purified recombinant Tat protein. As opposed to the expression of Tat alone, serine phosphorylation of the Tat protein was decreased when co-expressed with human-DPPIV protein.ConclusionsWe show for the first time that human-DPPIV and HIV1-Tat co-immunoprecipitate. Furthermore, our findings indicate that the interaction of HIV1-Tat and human-DPPIV may be involved in signalling platforms that regulate the biological function of both human-DPPIV and HIV1-Tat.
Biomechanical investigation of a novel ratcheting arthrodesis nail
Authors: McCormick Jeremy J , Li Xinning , Weiss Douglas R , Billiar Kristen L , Wixted John J 
Published: October 2010

AbstractBackgroundKnee or tibiotalocalcaneal arthrodesis is a salvage procedure, often with unacceptable rates of nonunion. Basic science of fracture healing suggests that compression across a fusion site may decrease nonunion. A novel ratcheting arthrodesis nail designed to improve dynamic compression is mechanically tested in comparison to existing nails.MethodsA novel ratcheting nail was designed and mechanically tested in comparison to a solid nail and a threaded nail using sawbones models (Pacific Research Laboratories, Inc.). Intramedullary nails (IM) were implanted with a load cell (Futek LTH 500) between fusion surfaces. Constructs were then placed into a servo-hydraulic test frame (Model 858 Mini-bionix, MTS Systems) for application of 3 mm and 6 mm dynamic axial displacement (n = 3/group). Load to failure was also measured.ResultsMean percent of initial load after 3-mm and 6-mm displacement was 190.4% and 186.0% for the solid nail, 80.7% and 63.0% for the threaded nail, and 286.4% and 829.0% for the ratcheting nail, respectively. Stress-shielding (as percentage of maximum load per test) after 3-mm and 6-mm displacement averaged 34.8% and 28.7% (solid nail), 40.3% and 40.9% (threaded nail), and 18.5% and 11.5% (ratcheting nail), respectively. In the 6-mm trials, statistically significant increase in initial load and decrease in stress-shielding for the ratcheting vs. solid nail (p= 0.029,p= 0.001) and vs. threaded nail (p= 0.012,p= 0.002) was observed. Load to failure for the ratcheting nail; 599.0 lbs, threaded nail; 508.8 lbs, and solid nail; 688.1 lbs.ConclusionWith significantly increase of compressive load while decreasing stress-shielding at 6-mm of dynamic displacement, the ratcheting mechanism in IM nails may clinically improve rates of fusion.
Recurrent post-partum coronary artery dissection
Authors: Rajab Taufiek K , Khalpey Zain , Kraemer Bernhard , Resnic Frederic S , Gallegos Robert P 
Published: October 2010

Abstract
Coronary artery dissection is a rare but well-described cause for myocardial infarction during the post-partum period. Dissection of multiple coronary arteries is even less frequent. Here we present a case of recurrent post-partum coronary artery dissections. This unusual presentation poses unique problems for management. A 35 year-old female, gravida 3 para 2, presented with myocardial infarction 9 weeks and 3 days post-partum. Cardiac catheterization demonstrated left anterior descending (LAD) dissection but an otherwise normal coronary anatomy. The lesion was treated with four everolimus eluting stents. Initially the patient made an unremarkable recovery until ventricular fibrillation arrest occurred on the following day. Unsynchronized cardioversion restored a normal sinus rhythm and repeat catheterization revealed new right coronary artery (RCA) dissection. A wire was passed distally, but it was unclear whether this was through the true or false lumen and no stents could be placed. However, improvement of distal RCA perfusion was noted on angiogram. Despite failure of interventional therapy the patient was therefore treated conservatively. Early operation after myocardial infarction has a significantly elevated risk of mortality and the initial dissection had occurred within 24 hours. This strategy proved successful as follow-up transthoracic echocardiography after four months demonstrated a preserved left ventricular ejection fraction of 55-60% without regional wall motion abnormalities. The patient remained asymptomatic from a cardiac point of view.
Outdoor Temperature, Age, Sex, Body Mass Index, and Diabetic Status Determine the Prevalence, Mass, and Glucose-Uptake Activity of 18F-FDG-Detected BAT in Humans
Authors: Ouellet Veronique , Routhier-Labadie Annick , Bellemare William , Lakhal-Chaieb Lajmi , Turcotte Eric , Carpentier André C. , Richard Denis 
Published: October 2010

Context: In humans, the prevalence, mass, and glucose-uptake activity of 18F-fluorodeoxyglucose (18F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled.
Objective: The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans.
Research Design and Methods: We retrospectively analyzed all 18F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for 18F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT depots was investigated.
Results: Three hundred twenty-eight of the 4842 patients (6.8%) had 18F-FDG-detected BAT. The prevalence of 18F-FDG BAT was negatively associated with outdoor temperature (P &lt; 0.0001), age (P &lt; 0.0001), BMI (P &lt; 0.0001), and diabetes status (P = 0.0003). Moreover, there was a significant age × sex interaction for the prevalence of 18F-FDG BAT (the younger the subjects, the greater the sex difference). The mass and glucose-uptake activity of 18F-FDG-detected BAT also decreased with increasing outdoor temperature (P &lt; 0.0001), age (P &lt; 0.0001), and BMI (P &lt; 0.0001). They were lower in men than in women (P &lt; 0.001) and lower in diabetic than in nondiabetic patients (P = 0.0002).
Conclusions: The present study identifies outdoor temperature, age, sex, BMI, and diabetes status as determinants of the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT.
Longitudinal Association between Growth Hormone Therapy and Obstructive Sleep Apnea in a Child with Prader-Willi Syndrome
Authors: Nixon Gillian M. , Rodda Christine P. , Davey Margot J. 
Published: October 2010

Context: Descriptions of the development of symptoms of upper airway obstruction and sudden death of children with Prader-Willi Syndrome (PWS) while on GH therapy have led to concern about GH contributing to obstructive sleep apnea (OSA), especially early in treatment. However, two studies using monitoring with polysomnography (PSG) have not shown deterioration in OSA after 6 wk on GH, except as related to upper respiratory tract infections.Objective: The aim was to describe the evolution of OSA in a girl with PWS on GH treatment in order to highlight important aspects of long-term clinical monitoring for patients with PWS on GH treatment.Patient and Research Design: GH was commenced when the patient was 2.9 yr of age. PSG was performed at baseline and 7 wk after commencing GH, plus at intervals throughout treatment based on symptoms of OSA.Intervention: GH was given at doses ranging from 4.2 to 4.7 mg/m2 · wk over a period of 3 yr.Main Outcome Measure: OSA was quantified by PSG.Results: OSA was not present at baseline or after 7 wk on GH but developed after 6 months, following a small increase in GH dose. Cessation of GH was accompanied by resolution of OSA. GH was restarted 2 yr later, again associated with the development of OSA that resolved after cessation of GH.Conclusion: This case highlights that OSA may develop late in GH treatment. Children should be monitored for the symptoms of OSA throughout GH treatment, and PSG should be repeated if symptoms develop.
Metabolomics Identifies Novel Hnf1α-Dependent Physiological Pathways in Vivo
Authors: Bonzo Jessica A. , Patterson Andrew D. , Krausz Kristopher W. , Gonzalez Frank J. 
Published: October 2010

AbstractMutations in the HNF1A gene cause maturity-onset diabetes of the young type 3, one of the most common genetic causes of non-insulin-dependent (type 2) diabetes mellitus. Although the whole-body Hnf1a-null mouse recapitulates the low insulin levels and high blood glucose observed in human maturity-onset diabetes of the young type 3 patients, these mice also suffer from Laron dwarfism and aminoaciduria, suggesting a role for hepatocyte nuclear factor 1α (Hnf1α) in pathophysiologies distinct from non-insulin-dependent (type 2) diabetes mellitus. In an effort to identify pathways associated with inactivation of Hnf1α, an ultraperformance liquid chromatography coupled to mass spectrometry-based metabolomics study was conducted on urine samples from wild-type and Hnf1a-null mice. An increase in phenylalanine metabolites is in agreement with the known regulation of the phenylalanine hydroxylase gene by Hnf1α. This metabolomic approach also identified urinary biomarkers for three tissue-specific dysfunctions previously unassociated with Hnf1α function. 1) Elevated indolelactate coupled to decreased xanthurenic acid also indicated defects in the indole and kynurenine pathways of tryptophan metabolism, respectively. 2) An increase in the neutral amino acid proline in the urine of Hnf1a-null mice correlated with loss of renal apical membrane transporters of the Slc6a family. 3) Further investigation into the mechanism of aldosterone increase revealed an overactive adrenal gland in Hnf1a-null mice possibly due to inhibition of negative feedback regulation. Although the phenotype of the Hnf1a-null mouse is complex, metabolomics has opened the door to investigation of several physiological systems in which Hnf1α may be a critical regulatory component.
Development and in-vitro evaluation of a colon-specific controlled release drug delivery system
Authors: Talukder Rahmat M , Fassihi Reza 
Published: October 2010

Abstract
The major challenges in targeting drug to various parts of the gastrointestinal tract include control of drug release with respect to its environment and transit time. These two variables should be taken into consideration in designing a rational colonic drug delivery system. To this end, a swelling matrix core containing pectin, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose and 5-aminosalicylic acid was developed. This was subjected to a dual coating operation: an inner pH-sensitive enteric and an outer semi-permeable membrane coat with a pore former. In-vitro dissolution studies were carried out in USP apparatus-I using sequential pH media. The first 2 h of dissolution studies were done in HCl buffer at pH 1.5, the next 2 h in pH 5.5 and, finally, in phosphate buffer at pH 6.8 with and without pectinolytic enzyme present. Less than 2% drug was released in the first 6 h and about 90% released in the following 12 h in a controlled manner. The stability studies of the coated systems were performed for 90 days under various conditions and it was found that drug release was not adversely affected. Results indicate that this delivery system has potential for site-specific delivery of drugs to the colon irrespective of transit time and rapid changes in the proximal pH of the gastrointestinal tract.
Lack of difference in pulmonary absorption of digoxin, a P-glycoprotein substrate, inmdr1a-deficient andmdr1a-competent mice
Authors: Manford Fergus , Riffo-Vasquez Yanira , Spina Domenico , Page Clive P , Hutt Andrew J , Moore Vanessa , Johansson Fredrik , Forbes Ben 
Published: October 2010

AbstractAlthough in-vitro experiments have suggested that P-glycoprotein (P-gp) may have an important influence on the disposition of inhaled drugs, the effect of P-gp on absorption from the lung in-vivo has not been reported previously. The aim of this study was to compare the pulmonary absorption of digoxin, a well-characterised substrate for P-gp, in mdr1a (–/–) (P-gp-deficient) and mdr1a (+/+) (P-gp-competent) mice. Digoxin was administered by intratracheal instillation over 3–4 s, a method demonstrated to result in dispersion of the dose to all regions of the lung. Drug distribution was determined in the lungs, plasma, brain, heart, liver and kidney of individual mice after 5, 10, 30, 60 and 90 min. Digoxin was cleared rapidly from the lung after intratracheal administration. No differences were observed in the maximum serum concentrations between mdr1a (+/+) and mdr1a (–/–) mice (37.8 ± 6.9 and 38.8 ± 15.8 ng mL−1, respectively). The serum concentration versus time profiles were similar in both strains; the area under the drug serum concentration versus time curve (AUC) was 2010 and 1812 ng mL−1 min in mdr1a (–/–) and mdr1a (+/+) mice, respectively. For organs harvested at the end of the experiment (90 min), the only significant difference between the strains was the markedly elevated concentration of digoxin in the brains of mdr1a (–/–) mice. In conclusion, digoxin is rapidly absorbed from the mouse lung following tracheal instillation, with no difference in the rate or extent of absorption between mdr1a-deficient and -competent mice. This suggests that, in contrast to the scenario suggested by in-vitro data, P-gp in the respiratory epithelium may have little influence on the disposition of drugs that are well absorbed from the lung.
An evaluation of the relative roles of the unstirred water layer and receptor sink in limiting the in-vitro intestinal permeability of drug compounds of varying lipophilicity
Authors: Katneni Kasiram , Charman Susan A , Porter Christopher J H 
Published: October 2010

AbstractThe roles of the unstirred water layer (UWL) and receptor sink on the in-vitro transmembrane permeability of an increasingly lipophilic series of compounds (mannitol (MAN), diazepam (DIA) and cinnarizine (CIN)) have been assessed. Altered carbogen bubbling rates were used as a means to change the UWL thickness and polysorbate-80 (PS-80), bovine serum albumin (BSA) and α-1-acid glycoprotein (AAG) were employed to alter sink conditions. After correction for solubilisation, Papp data for MAN, DIA and CIN were consistent across varying donor PS-80 concentrations suggesting that for the drugs examined here, the donor UWL did not limit in-vitro permeability. Similarly, altered bubbling rates and receptor sink conditions had no impact on the permeability of MAN. In contrast, decreasing the size of the receptor UWL or adding solubilising agents to the receptor sink resulted in modest enhancements to the permeability of the more lipophilic probe DIA. For the most lipophilic compound, CIN, very significant changes to measured permeability (&gt;30 fold) were possible, but were most evident only after concomitant changes to both the UWL and sink conditions, suggesting that the effectiveness of enhanced sink conditions were dependent on a decrease in the width of the UWL.
The anti-arthritic effect of ursolic acid on zymosan-induced acute inflammation and adjuvant-induced chronic arthritis models
Authors: Kang Suk-Yun , Yoon Seo-Yeon , Roh Dae-Hyun , Jeon Mi-Jeong , Seo Hyoung-Sig , Uh Dong-Kyu , Kwon Young-Bae , Kim Hyun-Woo , Han Ho-Jae , Lee Hye-Jung , Lee Jang-Hern 
Published: October 2010

Abstract
Ursolic acid (UA) is pentacyclic triterpenoic acid that naturally occurs in many medicinal herbs and plants. In this study, we examined the possible suppressive effect of UA extracted from Oldenlandia diffusa on zymosan-induced acute inflammation in mice and complete Freund's adjuvant (CFA)-induced arthritis in rats. UA treatment (per oral) dose-dependently (25–200 mg kg−1) suppressed zymosan-induced leucocyte migration and prostaglandin E2 (PGE2) production in the air pouch exudates. Since the maximal effective dose of UA was 50 mg kg−1 in the zymosan experiment, we used this dose of UA in a subsequent study using an adjuvant-induced rheumatoid arthritis model. UA treatment (50 mg kg−1, per oral, once a day for 10 days) was started from day 12 after adjuvant injection. UA dramatically inhibited paw swelling, plasma PGE2 production and radiological changes in the joint caused by CFA injection. Moreover, UA significantly suppressed the arthritis-induced mechanical and thermal hyperalgesia as well as the spinal Fos expression, as determined by immunohistochemistry, which was increased by CFA injection. In addition, overall anti-arthritic potency of UA was comparable with ibuprofen (100 mg kg−1, oral) while UA did not induce significant gastric lesions as compared with the ibuprofen treatment group. These findings strongly suggest that UA is a useful suppressive compound for rheumatoid arthritis treatment with low risk of gastric problems.
Microinjection of morphine into thalamic nucleus submedius depresses bee venom-induced inflammatory pain in the rat
Authors: Feng Jie , Jia Ning , Han Ling-Na , Huang Fen-Sheng , Xie Yu-Feng , Liu Jian , Tang Jing-Shi 
Published: October 2010

AbstractPrevious studies have provided evidence of the existence of a pain modulatory feedback pathway consisting of thalamic nucleus submedius (Sm)–ventrolateral orbital cortex-periaqueductal grey pathway, which is activated during acute pain and leads to depression of transmission of nociceptive information in the spinal dorsal horn. The aim of this study was to test the hypothesis that morphine microinjection into the Sm decreased spontaneous pain and bilateral thermal hyperalgesia, as well as ipsilateral mechanical allodynia, induced by subcutaneous injections of bee venom into the rat hind paw. Morphine (1.0, 2.5 or 5.0 &#x006d;̀g in 0.5 μL) injected into the Sm, contralateral to the bee venominjected paw, depressed spontaneous nociceptive behaviour in a dose-dependent manner. Furthermore, morphine significantly decreased bilateral thermal hyperalgesia and ipsilateral mechanical allodynia 2 h after bee venom injection. These morphine-induced effects were antagonized by 1.0 μg naloxone (an opioid antagonist) microinjected into the Sm 5 min before morphine administration. The results provided further support for the important role of the Sm and Sm-opioid receptors in inhibiting nociceptive behaviour and indicated for the first time that Sm opioid receptors were also effective in inhibiting the hypersensitivity provoked by bee venom-induced inflammation.