bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased cholesterol 7α-hydroxylase expression and size of the bile acid pool in the lactating rat
Authors: Wooton-Kee Clavia Ruth , Cohen David E. , Vore Mary
Published: February 2008

Maximal bile acid secretory rates and expression of bile acid transporters in liver and ileum are increased in lactation, possibly to facilitate increased enterohepatic recirculation of bile acids. We determined changes in the size and composition of the bile acid pool and key enzymes of the bile acid synthetic pathway [cholesterol 7α-hydroxylase (Cyp7a1), sterol 27-hydroxylase (Cyp27a1), and sterol 12α-hydroxylase (Cyp8b1)] in lactating rats relative to female virgin controls. The bile acid pool increased 1.9 to 2.5-fold [postpartum (PP) days 10, 14, and 19–23], compared with controls. A 1.5-fold increase in cholic acids and a 14 to 20% decrease in muricholic acids in lactation significantly increased the hydrophobicity index. In contrast, the hepatic concentration of bile acids and small heterodimer partner mRNA were unchanged in lactation. A 2.8-fold increase in Cyp7a1 mRNA expression at 16 h (10 h of light) demonstrated a shift in the diurnal rhythm at day 10 PP; Cyp7a1 protein expression and cholesterol 7α-hydroxylase activity were significantly increased at this time and remained elevated at day 14 PP but decreased to control levels by day 21 PP. There was an overall decrease in Cyp27a1 mRNA expression and a 20% decrease in Cyp27a1 protein expression, but there was no change in Cyp8b1 mRNA or protein expression at day 10 PP. The increase in Cyp7a1 expression PP provides a mechanism for the increase in the bile acid pool.
Endocannabinoids and Liver Disease. IV. Endocannabinoid involvement in obesity and hepatic steatosis
Authors: Kunos George , Osei-Hyiaman Douglas
Published: February 2008

Endocannabinoids are endogenous lipid mediators that interact with the same receptors as plant-derived cannabinoids to produce similar biological effects. The well-known appetitive effect of smoking marijuana has prompted inquiries into the possible role of endocannabinoids in the control of food intake and body weight. This brief review surveys recent evidence that endocannabinoids and their receptors are involved at multiple levels in the control of energy homeostasis. Endocannabinoids are orexigenic mediators and are part of the leptin-regulated central neural circuitry that controls energy intake. In addition, they act at multiple peripheral sites including adipose tissue, liver, and skeletal muscle to promote lipogenesis and limit fat elimination. Their complex actions could be viewed as anabolic, increasing energy intake and storage and decreasing energy expenditure, as components of an evolutionarily conserved system that has insured survival under conditions of starvation. In the era of plentiful food and limited physical activity, pharmacological inhibition of endocannabinoid activity offers benefits in the treatment of obesity and its hormonal/metabolic consequences.
Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism
Authors: Seth A. , Yan Fang , Polk D. Brent , Rao R. K.
Published: February 2008

Probiotics promote intestinal epithelial integrity and reduce infection and diarrhea. We evaluated the effect of Lactobacillus rhamnosus GG-produced soluble proteins (p40 and p75) on the hydrogen peroxide-induced disruption of tight junctions and barrier function in Caco-2 cell monolayers. Pretreatment of cell monolayers with p40 or p75 attenuated the hydrogen peroxide-induced decrease in transepithelial resistance and increase in inulin permeability in a time- and dose-dependent manner. p40 and p75 also prevented hydrogen peroxide-induced redistribution of occludin, ZO-1, E-cadherin, and β-catenin from the intercellular junctions and their dissociation from the detergent-insoluble fractions. Both p40 and p75 induced a rapid increase in the membrane translocation of PKCβI and PKCε. The attenuation of hydrogen peroxide-induced inulin permeability and redistribution of tight junction proteins by p40 and p75 was abrogated by Ro-32-0432, a PKC inhibitor. p40 and p75 also rapidly increased the levels of phospho-ERK1/2 in the detergent-insoluble fractions. U0126 (a MAP kinase inhibitor) attenuated the p40- and p75-mediated reduction of hydrogen peroxide-induced tight junction disruption and inulin permeability. These studies demonstrate that probiotic-secretory proteins protect the intestinal epithelial tight junctions and the barrier function from hydrogen peroxide-induced insult by a PKC- and MAP kinase-dependent mechanism.
Activation of innate immunity (NK/IFN-γ) in rat allogeneic liver transplantation: contribution to liver injury and suppression of hepatocyte proliferation
Authors: Shen Kezhen , Zheng Shu-Sen , Park Ogyi , Wang Hua , Sun Zhaoli , Gao Bin
Published: February 2008

Liver transplantation is presently the only curative treatment for patients with end-stage liver disease. However, the mechanisms underlying liver injury and hepatocyte proliferation posttransplantation remain obscure. In this investigation, liver injury and hepatocyte proliferation in syngeneic and allogeneic animal models were compared. Male Lewis and Dark Agouti (DA) rats were subjected to orthotopic liver transplantation (OLT). Rat OLT was performed in syngeneic (Lewis-Lewis) and allogeneic (Lewis-DA or DA-Lewis) animal models. Allogeneic liver grafts exhibited greater injury and cellular apoptosis than syngeneic grafts but less hepatocyte proliferation after OLT. Expression of IFN-γ mRNA and activation of the downstream signal transducer and activator of transcription 1 (STAT1) and genes (interferon regulatory factor-1 and cyclin-dependent kinase inhibitor p21CDKN1A) were also greater in the allogeneic grafts compared with the syngeneic grafts. In contrast, STAT3 activation was lower in the allogeneic grafts. Furthermore, in the allogeneic grafts, depletion of natural killer (NK) cells decreased IFN-γ/STAT1 activation but enhanced hepatocyte proliferation. These findings suggest that, compared with syngeneic transplantation, innate immunity (NK/IFN-γ) is activated after allogeneic transplantation, which likely contributes to liver injury and inhibits hepatocyte proliferation.
Translation inhibition during cell cycle arrest and apoptosis: Mcl-1 is a novel target for RNA binding protein CUGBP2
Authors: Subramaniam Dharmalingam , Natarajan Gopalan , Ramalingam Satish , Ramachandran Ilangovan , May Randal , Queimado Lurdes , Houchen Courtney W. , Anant Shrikant
Published: February 2008

CUGBP2, a translation inhibitor, induces colon cancer cells to undergo apoptosis. Mcl-1, an antiapoptotic Bcl-2 family protein, interferes with mitochondrial activation to inhibit apoptosis. Here, we have determined the effect of CUGBP2 on Mcl-1 expression. We developed a HCUG2 cell line by stably expressing CUGBP2 in the HCT-116 colon cancer cells. HCUG2 cells demonstrate decreased levels of proliferation and increased apoptosis, compared with HCT-116 cells. Flow cytometry analysis demonstrated higher levels of cells in the G2-M phase. Western blot analyses demonstrated that there was decreased Bcl-2 and Mcl-1 protein but increased expression of Bax, cyclin B1, and Cdc2. Immunocytochemistry also demonstrated increased levels of cyclin B1 and Cdc2 in the nucleus of HCUG2 cells. However, there was colocalization of phosphorylated histone H3 with transferase-mediated dUTP nick-end labeling (TUNEL). Furthermore, immunostaining for α-tubulin demonstrated that there was disorganization of microtubules. These data suggest that CUGBP2 expression in HCUG2 cells induces the cells to undergo apoptosis during the G2-M phase of the cell cycle. We next determined the mechanism of CUGBP2-mediated reduction in Mcl-1 expression. Mcl-1 protein, but not Mcl-1 mRNA, was lower in HCUG2 cells, suggesting translation inhibition. CUGBP2 binds to Mcl-1 3′-untranslated region (3′-UTR) both in vitro and in HCUG2 cells. Furthermore, CUGBP2 increased the stability of both endogenous Mcl-1 and luciferase mRNA containing the Mcl-1 3′-UTR. However, luciferase protein expression from the luciferase-Mcl-1 3′-UTR mRNA was suppressed. Taken together, these data demonstrate that CUGBP2 inhibits Mcl-1 expression by inhibiting Mcl-1 mRNA translation, resulting in driving the cells to apoptosis during the G2phase of the cell cycle.
20-HETE increases superoxide production and activates NAPDH oxidase in pulmonary artery endothelial cells
Authors: Medhora Meetha , Chen Yuenmu , Gruenloh Stephanie , Harland Daniel , Bodiga Sreedhar , Zielonka Jacek , Gebremedhin Debebe , Gao Ying , Falck John R. , Anjaiah Siddam , Jacobs Elizabeth R.
Published: February 2008

Reactive oxygen species (ROS) signal vital physiological processes including cell growth, angiogenesis, contraction, and relaxation of vascular smooth muscle. Because cytochrome P-450 family 4 (CYP4)/20-hydroxyeicosatetraenoic acid (20-HETE) has been reported to enhance angiogenesis, pulmonary vascular tone, and endothelial nitric oxide synthase function, we explored the potential of this system to stimulate bovine pulmonary artery endothelial cell (BPAEC) ROS production. Our data are the first to demonstrate that 20-HETE increases ROS in BPAECs in a time- and concentration-dependent manner as detected by enhanced fluorescence of oxidation products of dihydroethidium (DHE) and dichlorofluorescein diacetate. An analog of 20-HETE elicits no increase in ROS and blocks 20-HETE-evoked increments in DHE fluorescence, supporting its function as an antagonist. Endothelial cells derived from bovine aortas exhibit enhanced ROS production to 20-HETE quantitatively similar to that of BPAECs. 20-HETE-induced ROS production in BPAECs is blunted by pretreatment with polyethylene-glycolated SOD, apocynin, inhibition of Rac1, and a peptide-based inhibitor of NADPH oxidase subunit p47phox association with gp91. These data support 20-HETE-stimulated, NADPH oxidase-derived, and Rac1/2-dependent ROS production in BPAECs. 20-HETE promotes translocation of p47phox and tyrosine phosphorylation of p47phox in a time-dependent manner as well as increased activated Rac1/2, providing at least three mechanisms through which 20-HETE activates NADPH oxidase. These observations suggest that 20-HETE stimulates ROS production in BPAECs at least in part through activation of NADPH oxidase within minutes of application of the lipid.
Coronary venous retroperfusion: an old concept, a new approach
Authors: Kassab Ghassan S. , Navia Jose A. , March Keith , Choy Jenny Susana
Published: February 2008

The potential of the coronary veins for revascularization has been evaluated by many investigators for more than a century. The major hurdle has been the damage of veins during sudden exposure to arterial pressure. The solution to this problem has typically involved the use of intricate and complicated apparatus and devices, which has prevented routine clinical utility in the catheterization laboratory. This review examines this old concept from a new perspective and proposes a novel hypothesis to address previous shortcomings. We speculate on an approach that may serve to eliminate the edema and hemorrhage that result during venous retroperfusion as the pressure is suddenly increased to arterial values. We propose the rationale to increase the venous pressure to arterial values more gradually to allow prearterializations of the veins before full exposure of arterial pressure. Finally, we discuss various possible indications for this selective autoretroperfusion strategy to combat myocardial ischemia in cardiogenic shock patients, ST-elevation myocardial infarct patients, no-option patients, and beyond.
Effects of hypoxia on genioglossus and scalene reflex responses to brief pulses of negative upper-airway pressure during wakefulness and sleep in healthy men
Authors: Eckert Danny J. , McEvoy R. Doug , George Kate E. , Thomson Kieron J. , Catcheside Peter G.
Published: February 2008

Hypoxia can depress ventilation, respiratory load sensation, and the cough reflex, and potentially other protective respiratory reflexes such as respiratory muscle responses to increased respiratory load. In sleep-disordered breathing, increased respiratory load and hypoxia frequently coexist. This study aimed to examine the effects of hypoxia on the reflex responses of 1) the genioglossus (the largest upper airway dilator muscle) and 2) the scalene muscle (an obligatory inspiratory muscle) to negative-pressure pulse stimuli during wakefulness and sleep. We hypothesized that hypoxia would impair these reflex responses. Fourteen healthy men, 19–42 yr old, were studied on two separate occasions, ∼1 wk apart. Bipolar fine-wire electrodes were inserted orally into the genioglossus muscle, and surface electrodes were placed overlying the left scalene muscle to record EMG activity. In random order, participants were exposed to mild overnight hypoxia (arterial oxygen saturation ∼85%) or medical air. Respiratory muscle reflex responses were elicited via negative-pressure pulse stimuli (approximately −10 cmH2O at the mask, 250-ms duration) delivered in early inspiration during wakefulness and sleep. Negative-pressure pulse stimuli resulted in a short-latency activation followed by a suppression of the genioglossus EMG that did not alter with hypoxia. Conversely, the predominant response of the scalene EMG to negative-pressure pulse stimuli was suppression followed by activation with more pronounced suppression during hypoxia compared with normoxia (mean ± SE suppression duration 64 ± 6 vs. 38 ± 6 ms, P = 0.006). These results indicate differential sensitivity to the depressive effects of hypoxia in the reflex responsiveness to sudden respiratory loads to breathing between these two respiratory muscles.
Targeting human CD34+ hematopoietic stem cells with anti-CD45 × anti-myosin light-chain bispecific antibody preserves cardiac function in myocardial infarction
Authors: Zhao Ting C. , Tseng Andy , Yano Naohiro , Tseng YiTang , Davol Pamela A. , Lee Randall J. , Lum Lawrence G. , Padbury James F.
Published: February 2008

We have previously shown that targeting human CD34+ hematopoietic stem cells (HSC) with a bispecific antibody (BiAb) directed against myosin light chain (MLC) increases delivery of cells to the injured hearts and improves cardiac performance in the nude rat. In this study, we have sought to validate our previous observations and to perform more detailed determination of ventricular function in immunocompetent mice with myocardial infarction (MI) that were treated with armed CD34+ HSC. We examined whether armed CD34+ HSC would target the injured heart following MI and restore ventricular function in vitro. MI was created by ligation of the left anterior descending artery. After 48 h, adult ICR mice received either 0.5 × 106 human CD34+ HSC armed with anti-CD45 × anti-MLC BiAb or an equal volume of medium through a single tail vein injection. Two weeks after stem cell administration, ventricular function of hearts from mice receiving armed CD34+ HSC was significantly greater compared with the same parameters from control mice. Immunohistochemistry confirmed the accumulation of CD34+ HSC in MI hearts infused with stem cells. Angiogenesis was significantly enhanced in CD34+ HSC-treated heart as determined by vascular density per area. Furthermore, histopathological examination revealed that the retained cardiac function observed in CD34+ HSC-treated mice was associated with decreased ventricular fibrosis. These results suggest that peripheral administration of armed CD34+ HSC results in localization of CD34+ HSC to injured myocardium and restores myocardial function.
Training at high exercise intensity promotes qualitative adaptations of mitochondrial function in human skeletal muscle
Authors: Daussin Frédéric N. , Zoll Joffrey , Ponsot Elodie , Dufour Stéphane P. , Doutreleau Stéphane , Lonsdorfer Evelyne , Ventura-Clapier Renée , Mettauer Bertrand , Piquard François , Geny Bernard , Richard Ruddy
Published: February 2008

This study explored mitochondrial capacities to oxidize carbohydrate and fatty acids and functional optimization of mitochondrial respiratory chain complexes in athletes who regularly train at high exercise intensity (ATH, n = 7) compared with sedentary (SED, n = 7). Peak O2uptake (V̇o2max) was measured, and muscle biopsies of vastus lateralis were collected. Maximal O2uptake of saponin-skinned myofibers was evaluated with several metabolic substrates [glutamate-malate (V̇GM), pyruvate (V̇Pyr), palmitoyl carnitine (V̇PC)], and the activity of the mitochondrial respiratory complexes II and IV were assessed using succinate (V̇s) and N, N, N′, N′-tetramethyl- p-phenylenediamine dihydrochloride (V̇TMPD), respectively. V̇o2maxwas higher in ATH than in SED (57.8 ± 2.2 vs. 31.4 ± 1.3 ml·min−1·kg−1, P < 0.001). V̇GMwas higher in ATH than in SED (8.6 ± 0.5 vs. 3.3 ± 0.3 μmol O2·min−1·g dry wt−1, P < 0.001). V̇Pyrwas higher in ATH than in SED (8.7 ± 1.0 vs. 5.5 ± 0.2 μmol O2·min−1·g dry wt−1, P < 0.05), whereas V̇PCwas not significantly different (5.3 ± 0.9 vs. 4.4 ± 0.5 μmol O2·min−1·g dry wt−1). V̇Swas higher in ATH than in SED (11.0 ± 0.6 vs. 6.0 ± 0.3 μmol O2·min−1·g dry wt−1, P < 0.001), as well as V̇TMPD(20.1 ± 1.0 vs. 16.2 ± 3.4 μmol O2·min−1·g dry wt−1, P < 0.05). The ratios V̇S/V̇GM(1.3 ± 0.1 vs. 2.0 ± 0.1, P < 0.001) and V̇TMPD/V̇GM(2.4 ± 1.0 vs. 5.2 ± 1.8, P < 0.01) were lower in ATH than in SED. In conclusion, comparison of ATH vs. SED subjects suggests that regular endurance training at high intensity promotes the enhancement of maximal mitochondrial capacities to oxidize carbohydrate rather than fatty acid and induce specific adaptations of the mitochondrial respiratory chain at the level of complex I.
Effect of Laser Spot Diameter on the Reproducibility of Visual Field Analysis in Diabetic Patients with Upper Temporal Retinal Vein Occlusion
Authors: Akar Yusuf , Apaydin K. Cemil , Metinsoy Mehmet
Published: February 2008

Aim: To evaluate the effect of the laser spot diameter on the reproducibility of the visual field analysis in diabetic patients with upper temporal retinal vein occlusion. Material and Methods: Thirty-six eyes of 36 consecutive type-2 diabetes mellitus patients with upper temporal retinal vein occlusion who required sectoral retinal photocoagulation (SRP) treatment were enrolled for the study. Patients with a history of previous retinal laser photocoagulation, significant lenticular opacities and those whose perimetric test reliability criteria were low (fixation loss >20% and false-positive or false-negative responses >33%) were excluded from the study. SRP was applied to the upper temporal retinal quadrant. Nineteen eyes received SRP treatment with 500-µm laser spots (group 1) while the rest of the eyes (n = 17) received SRP with 300-µm laser spots (group 2). Patients underwent five consecutive visual field analyses, each on a different day during a 2-week period, both before and 6 weeks after SRP. The Humphrey field analyzer central 30–2 threshold test using SITA Standard strategy was applied for visual field testing. Results: The mean age of the patients in groups 1 and 2 were 58.6 ± 6.7 and 59.1 ± 7.1 years, respectively (p > 0.05). Pre-SRP mean retinal sensitivities of the lower nasal quadrant in groups 1 and 2 were not different statistically (p > 0.05). Post-SRP mean retinal sensitivity of the lower nasal quadrant was significantly higher in group 2 than group 1. Moreover, mean defect has been found to be lower in group 2 (p < 0.05). The coefficient of variation for pre-SRP retinal sensitivity measurements were 7.9 and 7.6% for groups 1 and 2, respectively (p > 0.05). The coefficient of variation for post-SRP retinal sensitivity measurements were 3.8 and 2.1% for groups 1 and 2, respectively (p < 0.05). Conclusion: SRP treatment with 300-µm diameter laser spots may yield more reproducible visual field data than that with 500-µm diameter laser spots. Moreover, the improvement in the retinal sensitivity of the patients with branch retinal vein occlusion is more marked in case where 300-µm laser spots are used.
CO2, Excimer and Erbium:YAG Laser in Deep Sclerectomy
Authors: Klink Thomas , Schlunck Günther , Lieb Wolfgang , Klink Janine , Grehn Franz
Published: February 2008

Purpose: Deep sclerectomy is a non-penetrating filtering procedure that is not generally accepted, as tissue dissection is difficult and varying success rates have been reported. The purpose of the present study was to compare the use of CO2, excimer and erbium:YAG lasers in dissection of the deep corneoscleral lamella. Methods: In enucleated porcine eyes a superficial lamellar scleral flap of 5 × 5 mm was surgically dissected. The deep lamella was removed using a pulsed erbium:YAG, a CO2 or an excimer laser (10 eyes/group). All eyes were analysed histologically and 3 in each group by scanning electron microscopy (SEM). Results: It is feasible to ablate the deep corneoscleral lamella with the CO2, excimer and erbium:YAG lasers without perforating the anterior chamber. The following histology and SEM showed a smoother surface after dissection with the CO2 and excimer lasers compared to the erbium:YAG laser. There was no thermal damage after excimer laser treatment, compared to a damage zone of 10–30 µm using the erbium laser and one of 70–100 µm with the CO2 laser. Conclusions: Excimer,erbium:YAG and CO2 lasers allow the microsurgical dissection of the deep lamella. The excimer and CO2 lasers achieve a more regular and smoother tissue surface. The excimer laser has the advantage to dissect without thermal tissue damage.
Comparison of the Infiniti Vision and the Series 20,000 Legacy Systems
Authors: Fernández de Castro Luis E. , Solomon Kerry D. , Hu Daniel J. , Vroman David T. , Sandoval Helga P.
Published: February 2008

Purpose: To compare the efficiency of the Infiniti vision system and the Series 20,000 Legacy system phacoemulsification units during routine cataract extraction. Methods: Thirty-nine eyes of 39 patients were randomized to have their cataract removed using either the Infiniti or the Legacy system, both using the Neosonix handpiece. System settings were standardized. Ultrasound time, amount of balanced salt solution (BSS) used intraoperatively, and postoperative visual acuity at postoperative days 1, 7 and 30 were evaluated. Results: Preoperatively, best corrected visual acuity was significantly worse in the Infiniti group compared to the Legacy group (0.38 ± 0.23 and 0.21 ± 0.16, respectively; p = 0.012). The mean phacoemulsification time was 39.6 ± 22.9 s (range 6.0–102.0) for the Legacy group and 18.3 ±19.1 s (range 1.0–80.0) for the Infiniti group (p = 0.001). The mean amounts of intraoperative BSS used were 117 ± 37.7 ml (range 70–195) in the Legacy group and 85.3 ± 38.9 ml (range 40–200) in the Infiniti group (p = 0.005). No differences in postoperative visual acuity were found. Conclusion: The ability to use higher flow rates and vacuum settings with the Infiniti vision system allowed for cataract removal with less phacoemulsification time than when using the Legacy system.
Phacoemulsification in Pseudoexfoliation Syndrome
Authors: Akinci Arsen , Batman Cosar , Zilelioglu Orhan
Published: February 2008

Purpose: To compare the incidence of intraoperative and early postoperative complications (IEPC), visual outcomes, and change in intraocular pressure (IOP) between eyes with and without pseudoexfoliation syndrome (PEX) having cataract extraction by phacoemulsification. Material and Method: 800 eyes with PEX and 1,600 eyes without PEX having cataract extraction by phacoemulsification were included in this retrospective study. Evaluated parameters were incidence of IEPC, visual outcomes and change in IOP. χ2 and Student’s t test were used for statistical analysis. Results: There were no significant differences in the incidence of IEPC and visual acuity gain between the two groups (p > 0.05). Rise in IOP in the early postoperative period was significantly higher in the PEX group (p < 0.02). Conclusion: Patients with PEX who have phacoemulsification can achieve results similar to patients without PEX. IOP control in the early postoperative period seems to be more important in patients with PEX.
A Rare Case of Conjunctival Myxoma and a Review of the Literature
Authors: Chen Ching-Long , Tai Ming-Cheng , Chen Jiann-Torng , Chen Chiao-Hong , Jin Jong-Shiaw , Lu Da-Wen
Published: February 2008

Background: To report on an 11-year-old boy with a painless slow-growing temporal bulbar conjunctival mass of his left eye. Methods: A case report and review of the literature. Results: An 11-year-old boy presented with a painless slow-growing mass in the temporal bulbar conjunctiva of his left eye, which had been noted for 1 year. After ophthalmic and systemic evaluations, the clinical differential diagnosis at the time included amelanotic naevus, amelanotic melanoma, myxoma, fibrous histiocytoma, reactive lymphoid hyperplasia and lipoma. This lesion was excised under local anaesthesia. From the histopathological features, conjunctival myxoma was confirmed. After 12 months, the patient remained healthy, with no recurrence or metastasis of the conjunctival lesion or evidence of a systemic abnormality. Conclusion: We report this case to emphasize that conjunctival myxoma can appear as a well-circumscribed, translucent, yellow-pink conjunctival mass in teenage patients. Successful healing is usually achieved by complete surgical resection. Cardiac, endocrine, and family screening is required to reduce the risk of morbidity and mortality.
Effect of Different Concentrations of Fluoride in Dentifrices on Dentin Erosion Subjected or Not to Abrasion in situ/ex vivo
Authors: Magalhães A.C. , Rios D. , Moino A.L. , Wiegand A. , Attin T. , Buzalaf M.A.R.
Published: February 2008

This in situ/ex vivo study assessed the effect of different concentrations of fluoride in dentifrices on dentin subjected to erosion or to erosion plus abrasion. Ten volunteers took part in this crossover and double-blind study performed in 3 phases (7 days). They wore acrylic palatal appliances containing 4 bovine dentin blocks divided in two rows: erosion and erosion plus abrasion. The blocks were subjected to erosion by immersion ex vivo in a cola drink (60 s, pH 2.6) 4 times daily. During this step, the volunteers brushed their teeth with one of three dentifrices D (5,000 ppm F, NaF, silica); C (1,100 ppm F, NaF, silica) and placebo (22 ppm F, silica). Then, the respective dentifrice slurry (1:3) was dripped on dentin surfaces. While no further treatment was performed in one row, the other row was brushed using an electric toothbrush for 30 s ex vivo. The appliances were replaced in the mouth and the volunteers rinsed with water. Dentin loss was determined by profilometry and analyzed by 2-way ANOVA/Bonferroni test (a = 0.05). Dentin loss after erosive-abrasive wear was significantly greater than after erosion alone. Wear was significantly higher for the placebo than for the D and C dentifrices, which were not significantly different from each other. It can be concluded that the presence of fluoride concentrations around 1,100 ppm in dentifrices is important to reduce dentin wear by erosion and erosion + abrasion, but the protective effect does not increase with fluoride concentration.
Pulse Wave Velocity Is Associated with Metabolic Syndrome Components in CAPD Patients
Authors: Zhe Xing-wei , Zeng Jing , Tian Xin-kui , Chen Wei , Gu Yue , Cheng Li-tao , Chen Hui-min , Axelsson Jonas , Lindholm Bengt , Wang Tao
Published: February 2008

Background: Overall, the proportion of deaths due to cardiovascular disease (CVD) reached 40–50% in dialysis patients. Pulse wave velocity (PWV) reflects arterial stiffness and may provide an integrated index of vascular status and CVD risk. Individual components of the metabolic syndrome (MetS) are well-established cardiovascular risk factors. Thus we conducted a cross-sectional study in continuous ambulatory peritoneal dialysis (CAPD) patients to explore the association of MetS components with PWV. Methods: Prevalent CAPD patients (n = 148, 63 M/85 F) were categorized according to the number of traits of the MetS into one of three groups (No MetS, Risk of MetS, MetS). Due to the effect of peritoneal dialysis (PD), waist circumference was not assessed. Aortic stiffness was assessed by carotid-femoral PWV (C-F PWV). Results: Patients’ MetS trait numbers were positively associated with C-F PWV (r = 0.301, p < 0.01), pulse pressure (r = 0.256, p < 0.01), systolic blood pressure (r = 0.233, p < 0.01), and serum albumin (r = 0.205, p < 0.05). In a multivariate regression analysis, PWV was independently determined by age (p < 0.01) and MetS score (p = 0.01). Adjusted R2 of the model was 0.24. Conclusion: MetS traits were closely associated with an increased C-F PWV, even after adjustment for confounders. This suggests that commonly recognized MetS criteria are useful also when predicting CVD in CAPD patients.
Somatostatin Receptor in Human Hepatocellular Carcinomas: Biological, Patient and Tumor Characteristics
Authors: Verhoef C. , van Dekken H. , Hofland L.J. , Zondervan P.E. , de Wilt J.H.W. , van Marion R. , de Man R.A. , IJzermans J.N.M. , van Eijck C.H.J.
Published: February 2008

Background/Aim: The evidence on the efficacy of somatostatin analogues in the treatment of hepatocellular carcinoma (HCC) in humans is conflicting. A variety of human tumors demonstrate somatostatin receptors. All subtypes bind human somatostatin with high affinity, while somatostatin analogues bind with high affinity to somatostatin receptor subtype 2 (sst2). We investigated the sst2 expression in HCC and examined whether HCCs expressing sst2 are a distinct subgroup. Patients and Methods: Forty-five human HCCs were tested for sst2 expression and biological alterations. The proliferative capacity was determined with Ki67 immunostaining and the DNA ploidy status was measured by fluorescent in situ hybridization with a chromosome 1-specific repetitive DNA probe. Expression of tumor suppressor genes (p16, p53 and Rb1) was measured by immunohistochemistry. Results: sst2 expression was detected in 30 tumors (67%). No correlation existed between sst2 expression and the immunoprofiles of the tumor suppressor genes, aneuploidy, proliferation, age, gender, α-fetoprotein levels, tumor size, tumor grade and underlying liver disease. Conclusion: In 67% of the patients with HCC, sst2 could be detected in the tumor. No clinical, pathological or biological characteristics were specific for sst2-positive tumors.
Role of Medial Pancreatectomy in the Management of Intraductal Papillary Mucinous Neoplasms and Islet Cell Tumors of the Pancreatic Neck and Body
Authors: Shimada Kazuaki , Sakamoto Yoshihiro , Esaki Minoru , Kosuge Tomoo , Hiraoka Nobuyoshi
Published: February 2008

Background/Aim: Medial pancreatectomy has been applied as a safe and effective alternative in benign diseases located in the pancreatic neck or body. However, the role of this procedure remains controversial. We investigate outcomes using this method in 14 patients. Methods: Fourteen consecutive patients underwent medial pancreatectomy. The surgical indications, postoperative outcomes, and pathologic characteristics were retrospectively analyzed. Results: Among 10 patients with intraductal papillary mucinous neoplasms, 3 patients had minimally invasive adenocarcinoma, and 3 had adenocarcinoma in situ. Four patients required an additional resection of the pancreatic remnant because of a positive surgical margin. A medial pancreatectomy was converted to a distal pancreatectomy in 1 patient with adenocarcinoma in situ. Three patients with islet cell tumor and 1 patient with solid pseudopapillary tumor had no malignant disease. Postoperative complications occurred in 6 patients (43%): 5 had pancreatic fistulas and 1 had a gastric ulcer. All of the patients are doing well without recurrence. Conclusions: A medial pancreatectomy is a safe and effective alternative for the treatment of intraductal papillary mucinous neoplasm, islet cell tumor, or solid pseudopapillary tumor located in the neck or body of the pancreas. However, a precise preoperative and intraoperative assessment including an examination of frozen sections is mandatory to select the appropriate surgical procedure.
Incidence and Management of Bile Leakage after Partial Liver Resection
Authors: Erdogan D. , Busch O.R.C. , van Delden O.M. , Rauws E.A.J. , Gouma D.J. , van Gulik T.M.
Published: February 2008

Background/Aims: Bile leakage after partial liver resection still is a common complication and is associated with substantial morbidity and even mortality. Methods: A total of 234 consecutive liver resections without biliary reconstruction, performed between January 1992 and December 2004, were analyzed for postoperative bile leakage. Results: Postoperative bile leakage occurred in 6.8% of patients (16/234). In univariate analysis, male gender (p = 0.037), major liver resection (p = 0.004), right-sided hepatectomy (p = 0.005), prolonged operation time (p = 0.001), intraoperative blood loss >500 ml (p = 0.009), red cell transfusion (p = 0.02), tumor size (p = 0.026), duration of vascular occlusion (p = 0.03) and surgical irradicality (p = 0.001) were risk factors. No independent risk factors were associated with bile leakage after liver resection. Bile leakage originated from the resection plane in 10 patients (63%). Endoscopic biliary decompression was performed in 9 patients as initial treatment, and percutaneous drainage of the bile collection was used in 4 patients. Bile leakage resolved spontaneously in 3 patients. Conclusions: Bile leakage is a persisting complication and in this study occurred in 6.8% of patients after partial liver resection. Percutaneous drainage of bile collection with or without endoscopic biliary decompression are effective interventions in the management of most cases of bile leakage.
Extended Extrahepatic Bile Duct Resection to Avoid Performing Pancreatoduodenectomy in Patients with Mid Bile Duct Cancer
Authors: Hwang Shin , Lee Sung-Gyu , Kim Ki-Hun , Ahn Chul-Soo , Moon Deok-Bog , Ha Tae-Yong , Song Gi-Won , Jung Dong-Hwan
Published: February 2008

Background/Aims: Since proximal-to-mid bile duct (BD) cancers often involve the proximal portion of the intrapancreatic BD, resection of the extrahepatic BD can result in a tumor-positive distal resection margin. It is essential that a surgical procedure is developed to obtain a tumor-free distal BD resection margin during extrahepatic BD resection, in which R0 resection can be achieved without performing pancreatoduodenectomy. Methods: Based on preparatory clinicopathological analyses, excavation of the proximal intrapancreatic BD was designed to resemble a 2- to 3-cm-long funnel. The surgical procedure was a combination of the usual extrahepatic BD resection and funnel-shaped excavation of the proximal intrapancreatic BD. Results: This unique procedure, called extended extrahepatic BD resection, was performed on 3 patients aged over 70 years with mid BD cancer. Deep intrapancreatic BD excavation per se required about 1 h. A tumor-free intrapancreatic BD resection margin was obtained in all 3 patients. Only minor complications occurred. Two patients are doing well without recurrence, at 20 and 14 months, respectively, and one is alive at 12 months with lymph node metastasis detected 1 month earlier. Conclusion: By achieving R0 resection, this extended extrahepatic BD resection seems to benefit some proximal-to-mid BD cancer patients in whom pancreatoduodenectomy has a high operative risk.
Maximizing Venous Outflow after Right Hepatic Living Donor Liver Transplantation with a Venous Graft Patch
Authors: Mizuno Shugo , Sanda Ryo , Hori Tomohide , Yagi Shintaro , Iida Taku , Usui Masanobu , Sakurai Hiroyuki , Tabata Masami , Isaji Shuji , Uemoto Shinji
Published: February 2008

Between March 2002 and September 2004, 36 patients at Mie University Hospital underwent living donor liver transplantation (LDLT) of a right lobe graft without the middle hepatic vein. The patients were divided into two groups: group I (n = 25) received ordinary hepatic vein anastomoses, and group II (n = 11) received a venous graft patch in the subsequent procedure. Between groups, we compared hepatic vein blood flow (ultrasound), liver volume (CT scan), laboratory data, and ascitic fluid volume. Outflow block developed as a complication in 1 patient in group I. Hepatic vein blood flow on postoperative day (POD) 3 was significantly better in group II, and hepatic vein waveforms of most group II patients showed the triphasic pattern, especially on PODs 3 and 5. The total bilirubin and aspartate aminotransferase values on POD 1 were significantly better in group II, and daily ascitic fluid volume on PODs 3 and 5 was significantly lower in group II. Thus, modified venoplasty with a graft patch in the right hepatic LDLT not only improved hepatic vein hemodynamics (based on the ultrasound findings), but also improved liver function and decreased daily ascitic fluid volume.
Improving Outcome after Stroke: Overcoming the Translational Roadblock
Authors: Endres Matthias , Engelhardt Britta , Koistinaho Jari , Lindvall Olle , Meairs Stephen , Mohr Jay P. , Planas Anna , Rothwell Nancy , Schwaninger Markus , Schwab Martin E. , Vivien Denis , Wieloch Tadeusz , Dirnagl Ulrich
Published: February 2008

Stroke poses a massive burden of disease, yet we have few effective therapies. The paucity of therapeutic options stands contrary to intensive research efforts. The failure of these past investments demands a thorough re-examination of the pathophysiology of ischaemic brain injury. Several critical areas hold the key to overcoming the translational roadblock: (1) vascular occlusion: current recanalization strategies have limited effectiveness and may have serious side effects; (2) complexity of stroke pathobiology: therapy must acknowledge the ‘Janus-faced’ nature of many stroke targets and must identify endogenous neuroprotective and repair mechanisms; (3) inflammation and brain-immune-system interaction: inflammation contributes to lesion expansion, but is also instrumental in lesion containment and repair; stroke outcome is modulated by the interaction of the injured brain with the immune system; (4) regeneration: the potential of the brain for reorganization, plasticity and repair after injury is much greater than previously thought; (5) confounding factors, long-term outcome and predictive modelling. These 5 areas are linked on all levels and therefore need to be tackled by an integrative approach and innovative therapeutic strategies.
β-Lactam Activity against Penicillin-Resistant Streptococcus pneumoniae Strains Exhibiting Higher Amoxicillin versus Penicillin Minimum Inhibitory Concentration Values: An in vitro Pharmacodynamic Simulation
Authors: Sevillano D. , Aguilar L. , Alou L. , Giménez M.J. , González N. , Echeverría O. , Torrico M. , Valdes L. , Coronel P. , Prieto J.
Published: February 2008

Background: Activity of simulated serum concentrations after oral therapy with 400 mg cefditoren pivoxil b.i.d., 500 mg cefuroxime axetil b.i.d. and 875/125 mg amoxicillin/clavulanic acid b.i.d. and t.i.d. regimens was explored over 24 h against Streptococcus pneumoniae.Methods: Computerized pharmacodynamic simulations were performed against strains with penicillin/amoxicillin/cefuroxime/cefditoren minimum inhibitory concentrations (MICs, µg/ml) and serotypes: strain 1 (0.25/0.12/1/0.12; serotype 6A), strain 2 (2/4/ 2/0.25; serotype 6B), strain 3 (4/16/4/0.5; serotype 14), and strain 4 (4/16/8/1; serotype 14). Results: Bactericidal activity (≧3 log10 reduction) at 12 and 24 h was obtained against all strains with cefditoren, against strains 1 and 2 with cefuroxime and amoxicillin/clavulanic acid t.i.d., but only against strain 1 with amoxicillin/clavulanic acid b.i.d.. Bactericidal activity at 24 h was related to T > MIC of >30% dosing interval, 1.7–2.0 log10 reductions with T > MIC of 20–30%, and <1 log10 reduction or regrowth with T > MIC of 0%. Conclusions: It is difficult to achieve pharmacodynamic coverage and bactericidal activity by physiological concentrations of oral β-lactams against penicillin-resistant pneumococcal strains exhibiting higher amoxicillin versus penicillin MICs. Cefditoren may offer alternatives.
Carbapenem-Hydrolyzing Oxacillinase, OXA-48, Persists in Klebsiella pneumoniae in Istanbul, Turkey
Authors: Aktaş Zerrin , Kayacan Çiğdem Bal , Schneider Ines , Can Barış , Midilli Kenan , Bauernfeind Adolf
Published: February 2008

Background: Two OXA-48-producing Klebsiella pneumoniae isolates(KP-4936 and KP-154488) were analyzed. Method: Minimum inhibitory concentrations were determined using agar dilution and E-test, β-lactamase production by phenotypic tests (E-test MBL and ESBL, isoelectric focusing, and bioassay) and molecular methods (PCR, RAPD-PCR, sequencing, plasmid analysis, and conjugation). Results: Isolateswere resistant to all β-lactams, including carbapenems. PCR and sequencing identifiedblaOXA-48in bothisolates and the transconjugant. KP-4936 harbored blaTEM-1 (pI 5.4) and blaCTX-M-15 genes (pI 8.6), while KP-154488 was positive for blaTEM-1 (pI 5.4), blaCTX-M-15 (pI 8.9), and blaSHV2a (pI 7.6), in addition. The enzyme with a pI of 7.2 hydrolyzed imipenem according to a bioassay result. Plasmids (70 and 140 kb) from KP-4936 were transferred by conjugation. RAPD-PCR found no clonal relationship between the two strains. Conclusion: Carbapenem resistance may spread among Enterobacteriaceaevia the transferable enzyme OXA-48.
CNGA2 Channels Mediate Adenosine-Induced Ca2+Influx in Vascular Endothelial Cells
Authors: Cheng Kwong-Tai , Leung Yuk-Ki , Shen Bing , Kwok Yuk-Chi , Wong Ching-On , Kwan Hiu-Yee , Man Yu-Bun , Ma Xin , Huang Yu , Yao Xiaoqiang
Published: February 2008

Objectives—Adenosine is a cAMP-elevating vasodilator that induces both endothelium-dependent and -independent vasorelaxation. An increase in cytosolic Ca2+([Ca2+]i) is a crucial early signal in the endothelium-dependent relaxation elicited by adenosine. This study explored the molecular identity of channels that mediate adenosine-induced Ca2+influx in vascular endothelial cells.

Methods and Results—Adenosine-induced Ca2+influx was markedly reduced by L-cis-diltiazem and LY-83583, two selective inhibitors for cyclic nucleotide-gated (CNG) channels, in H5V endothelial cells and primary cultured bovine aortic endothelial cells (BAECs). The Ca2+influx was also inhibited by 2 adenylyl cyclase inhibitors MDL-12330A and SQ-22536, and by 2 A2Breceptor inhibitors MRS-1754 and 8-SPT, but not by an A2Areceptor inhibitor SCH-58261 or a guanylyl cyclase inhibitor ODQ. Patch clamp experiments recorded an adenosine-induced current that could be inhibited by L-cis-diltiazem and LY-83583. A CNGA2-specific siRNA markedly decreased the Ca2+influx and the cation current in H5V cells. Furthermore, L-cis-diltiazem inhibited the endothelial Ca2+influx in mouse aortic strips, and it also reduced 5-N-ethylcarboxamidoadenosine (NECA, an A2adenosine receptor agonist)-induced vasorelaxation.

Conclusion—CNGA2 channels play a key role in adenosine-induced endothelial Ca2+influx and vasorelaxation. It is likely that adenosine acts through A2Breceptors and adenylyl cyclases to stimulate CNGA2.
Sequential Activation of Matrix Metalloproteinase 9 and Transforming Growth Factor β in Arterial Elastocalcinosis
Authors: Bouvet Céline , Moreau Simon , Blanchette Joannie , de Blois Denis , Moreau Pierre
Published: February 2008

Objective—

Isolated systolic hypertension is associated with increased elastase activity, vascular calcification, and vascular stiffness. We sought to determine the importance of elastase activity and matrix degradation in the development of elastocalcinosis.

Methods and Results—

Elastocalcinosis was induced in vivo and ex vivo using warfarin. Hemodynamic parameters, calcium deposition, elastin degradation, transforming growth factor (TGF)-β signaling, and elastase activity were evaluated at different time points in the in vivo model. Metalloproteinases, serine proteases, and cysteine proteases were blocked to measure their relative implication in elastin degradation. Gradual elastocalcinosis was obtained, and paralleled the elastin degradation pattern. Matrix metalloproteinase (MMP)-9 activity was increased at 5 days of warfarin treatment, whereas TGF-β signaling was increased at 7 days. Calcification was significantly elevated after 21 days. Blocking metalloproteinases activation with doxycycline and TGF-β signaling with SB-431542 were able to prevent calcification.

Conclusions—

Early MMP-9 activation precedes the increase of TGF-β signaling, and overt vascular elastocalcinosis and stiffness. Modulation of matrix degradation could represent a novel therapeutic avenue to prevent the gradual age-related stiffening of large arteries, leading to isolated systolic hypertension.
Intramural Delivery of Rapamycin With α
v
β
3
-Targeted Paramagnetic Nanoparticles Inhibits Stenosis After Balloon Injury
Authors: Cyrus Tillmann , Zhang Huiying , Allen John S. , Williams Todd A. , Hu Grace , Caruthers Shelton D. , Wickline Samuel A. , Lanza Gregory M.
Published: February 2008

Background—

Drug eluting stents prevent vascular restenosis but can delay endothelial healing. A rabbit femoral artery model of stenosis formation after vascular injury was used to study the effect of intramural delivery of α
v
β
3
-integrin-targeted rapamycin nanoparticles on vascular stenosis and endothelial healing responses.

Methods and Results—

Femoral arteries of 48 atherosclerotic rabbits underwent balloon stretch injury and were locally treated with either (1) α
v
β
3
-targeted rapamycin nanoparticles, (2) α
v
β
3
-targeted nanoparticles without rapamycin, (3) nontargeted rapamycin nanoparticles, or (4) saline. Intramural binding of integrin-targeted paramagnetic nanoparticles was confirmed with MR molecular imaging (1.5 T). MR angiograms were indistinguishable between targeted and control arteries at baseline, but 2 weeks later they showed qualitatively less luminal plaque in the targeted rapamycin treated segments compared with contralateral control vessels. In a first cohort of 19 animals (38 vessel segments), microscopic morphometric analysis of the rapamycin-treated segments revealed a 52% decrease in the neointima/media ratio (
P
<0.05) compared to control. No differences (
P
>0.05) were observed among balloon injured vessel segments treated with α
v
β
3
-targeted nanoparticles without rapamycin, nontargeted nanoparticles with rapamycin, or saline. In a second cohort of 29 animals, endothelial healing followed a parallel pattern over 4 weeks in the vessels treated with α
v
β
3
-targeted rapamycin nanoparticles and the 3 control groups.

Conclusions—

Local intramural delivery of α
v
β
3
-targeted rapamycin nanoparticles inhibited stenosis without delaying endothelial healing after balloon injury.
Asymmetric Dimethylarginine Independently Predicts Fatal and Nonfatal Myocardial Infarction and Stroke in Women
Authors: Leong Tora , Zylberstein Dimitri , Graham Ian , Lissner Lauren , Ward Deirdre , Fogarty Jane , Bengtsson Calle , Björkelund Cecilia , Thelle Dag
Published: February 2008

Objective—

Asymmetrical dimethylarginine (ADMA) reduces nitric oxide by inhibiting nitric oxide synthase is associated with cardiovascular disease (CVD). Our study examined the association of ADMA with CVD prospectively in a healthy population-based cohort of women.

Methods and Results—

We measured baseline ADMA of 880 women in the Population Study of Women in Gothenburg using high-performance liquid chromatography. After adjustment for traditional risk factors, creatinine clearance, and homocysteine using Cox models, the HR (95% CI in parentheses) of CVD end points at 24 years for a 0.15 μmol/L (1 SD) increase in ADMA were: all-cause mortality 1.12 (0.96, 1.32), fatal CVD 1.30 (1.04, 1.62), total CVD events 1.29 (1.09, 1.53). The top quintile (ADMA ≥0.71 μmol/L) compared with the bottom four-fifths, conferred a cumulative risk 22 versus 14%, relative risk 1.75 (95% CI 1.18, 2.59) and population attributable risk 12.7% of total CVD events, and further identified individuals who are at higher than expected risk based on the SCORE and Framingham systems.

Conclusions—

A 0.15 μmol/L increase in baseline ADMA levels is associated with approximately 30% increase in incident cardiovascular risk at 24 years in women after adjustment. ADMA levels ≥0.71 μmol/L enhances CVD risk assessment in women.