bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpha- and Beta-Components of the Popliteal Efferent Lymph Flow Response to Intra-Arterial Catecholamine Infusions in the Sheep
Authors: Thornbury K.D. , McHale N.G. , McGeown J.G.
Published: April 2017

Lymph flow and lymphatic pressure fluctuations were measured in cannulated popliteal efferent lymphatics of the sheep. Five-minute intra-arterial infusions of norepinephrine (0.4 µg/kg/min) produced up to fivefold increases in lymph flow and lymphatic contraction frequency. This effect was blocked by the α-antagonist phentolamine but not by the P-antagonist propranolol. Isoproterenol (0.4 µg/kg/min i.a.) inhibited flow. This effect was antagonized by propranolol. Acetylcholine (0.4 µg/kg/min) had little effect on lymph flow. Since norepinephrine and isoproterenol respectively stimulate and inhibit lymphatic pumping activity in vitro, it is proposed that the effects of these agents on lymph flow and lymphatic contraction frequency in vivo are best explained by direct modulatory actions on the lymphatic smooth muscle pump.
Action of Fenoldopam, a Selective Dopamine (DA1 Receptor Agonist, on Isolated Human Arteries
Authors: Hughes A.D. , Sever P.S.
Published: April 2017

The effects of a DAi dopamine receptor selective agonist, fenoldopam, were examined on human blood vessels. Fenoldopam relaxed precontracted human arteries in vitro from brachial, cerebral, cervical, colic, coronary, lumbar, pulmonary, renal and splenic sites. Fenoldopam failed to relax uterine or external iliac arteries or saphenous vein segments. These effects of fenoldopam were not endothelium dependent, but were antagonised by the selective DAi receptor antagonists, SCH 23390, (+)-butaclamol, and (R)- more than (S)-sulpiride. The effect of fenoldopam may involve cyclic adenosine monophosphate. These studies indicate the presence of DAi receptors on a variety of large isolated human arteries.
Release of Nerve Growth Factor from Cultured Aortic Smooth-Muscle Cells
Authors: Ueyama Takashi , Hamada Masanori , Hano Takuzo , Nishio Ichiro , Masuyama Yoshiaki , Ooshima Akira
Published: April 2017

Conditioned medium from cultured aortic smooth-muscle cells from rat aorta yielded neurite-extending effects on sensory and sympathetic ganglia of chick embryos. These effects were blocked by adding specific antiserum against 2.5S nerve growth factor (NGF), suggesting that NGF might be released from vascular smooth-muscle cells.
Arteriolar Vasomotion: Implications for Tissue Ischemia
Authors: Intaglietta M.
Published: April 2017

Vasomotion, the rhythmical contraction and relaxation of the arterioles, is a natural property of the arteriolar microcirculation. It is observed clinically through related flow variations (flux motion) which are detected by laser Doppler flowmetry. It presents two distinct regimens: slow and fast waves, with frequencies of 1–2 and 10–20 cpm, respectively. Both activities are found in normal tissues, and their rate of incidence as well as their magnitude become significantly enhanced during abnormal conditions associated with low blood pressure and hypoperfusion. The institution of this activity by abnormal tissue conditions suggests that vasomotion is a reaction of the microcirculation aimed at improving microvascular function.
Expression of IL-17 and Its Role in Bone Destruction in Human Middle Ear Cholesteatoma
Authors: Haruyama Takuo , Furukawa Masayuki , Kusunoki Takeshi , Onoda Junko , Ikeda Katsuhisa
Published: April 2017

Purpose: The present study was designed to elucidate the immunoreactivity and protein level of IL-17 in human cholesteatomas. Procedures: The expression and localization of IL-17 and receptor activator of nuclear factor ĸB ligand (RANKL) were examined by immunohistochemistry in tissue specimens collected from 24 patients with cholesteatomas. The cellular sources of IL-17 were assessed by double staining with CD4. The level of IL-17 protein was determined using an enzyme-linked immunosorbent assay. The degree of bone destruction was compared with the IL-17 immunoreactivity. Results: IL-17 immunoreactivity was detected in the inflammatory cells in the granulation tissues and there were increased levels of IL-17 protein. The localization of IL-17 expression coincided with CD4-positive lymphocytes. IL-17 was correlated with the cells positive for RANKL. The degree of bone destruction was dependent on the number of infiltrated IL-17-positive cells. IL-17-driven pathology was observed in the congenital type as compared with the acquired type. Conclusions: The present study suggests that IL-17 is related to the pathogenesis of the disease.
Noninvasive Detection of Coronary Artery Stenoses with Contrast-Enhanced Whole-Heart Coronary Magnetic Resonance Angiography at 3.0 T
Authors: Chen Zhiyong , Duan Qing , Xue Xunjing , Chen Lianglong , Ye Wenbin , Jin Lixin , Sun Bin
Published: April 2017

Purpose: To prospectively evaluate the accuracy of contrast-enhanced whole-heart coronary magnetic resonance angiography (CMRA) at 3.0 T, with the use of sublingual nitroglycerin and abdominal banding, for assessing significant stenosis (≧50% lumen diameter reduction) in patients with suspected coronary disease, using conventional coronary artery angiography as the reference standard. Methods: We prospectively studied 71 consecutive patients with suspected coronary artery disease scheduled for conventional coronary angiography. Contrast-enhanced whole-heart CMRA was performed after sublingual nitroglycerin with an abdominal banding rolled tightly along the side of the ribs. The diagnostic performance of CMRA for the detection of significant lesions was compared with that of quantitative coronary angiography. Results: The acquisition of CMRA was completed in 67 of 71 patients, with an average imaging time of 9.6 ± 3.2 min. The average navigator efficiency was 48%. The sensitivity, specificity as well as positive and negative predictive values of whole-heart CMRA for the detection of significant lesions on a segment-by-segment analysis were 91.4, 85.8, 48.7 and 98.5%, respectively, and in a patient-based analysis 94.6, 86.7, 89.7 and 92.9%, respectively. Conclusions: Contrast-enhanced whole-heart CMRA with 3.0 T optimized by using sublingual nitroglycerin and abdominal banding methods permits reliable detection of significant obstructive coronary artery disease in patients with suspected coronary disease.
Improvement in Cardiac Function following Transplantation of Human Umbilical Cord Matrix-Derived Mesenchymal Cells
Authors: Latifpour Mostafa , Nematollahi-Mahani Seyed Noureddin , Deilamy Massoud , Azimzadeh Behzad Sorour , Eftekhar-Vaghefi Seyed Hasan , Nabipour Fatemeh , Najafipour Hamid , Nakhaee Nouzar , Yaghoubi Mohammad , Eftekhar-Vaghefi Rana , Salehinejad Parvin , Azizi Hossein
Published: April 2017

Objectives: Human umbilical cord mesenchymal cells (hUCM) can be easily obtained and processed in a laboratory. These cells may be considered as a suitable source in the repair of heart failure diseases. We, therefore, examined whether these cells may contribute to heart regeneration following an acute experimental myocardial infarction (MI). Methods: MI-induced animals received 5 × 106 hUCM cells, 5 × 106 5-azacytidine-treated cells (dhUCM), or PBS alone, subepicardially. A group of animals with MI and no other former intervention served as controls. dhUCM cells were assessed for F-actin, myogenin and troponin-I expression. Results: dhUCM cells appeared as binucleated cells with extensive cytoplasmic processes. These differentiated cells were F-actin and myogenin positive. Thirty days after LAD ligation, left ventricular ejection fraction and the percentage of fractional shortening improved significantly in cell-receiving animals. In addition, the amount of scar tissue was significantly reduced in hUCM and dhUCM groups compared to MI group (p < 0.05). These parameters were comparable between hUCM and dhUCM groups. Histopathological evaluations revealed that some engrafted cells adjacent to and remote from the MI area expressed troponin-I, F-actin and connexin43. Conclusion: These findings demonstrated the potential therapeutic use of either differentiated or undifferentiated hUCM cells in treatment of heart failure conditions.
Effect of Erythropoietin on Healing of Corneal Epithelial Defects in Rabbits
Authors: Livny Eitan , Livnat Tami , Yakimov Maxim , Masoud Muhannad , Weinberger Dov , Bahar Irit
Published: April 2017

Background/Aim: Corneal epithelial defects may heal slowly in patients with diabetes, limbal stem cell deficiency, extensive chemical burns or anesthetized corneas. Studies have shown that erythropoietin, a glycoprotein hormone that promotes red blood cell proliferation and inhibits apoptosis of erythroid progenitors, may also exert a cytoprotective, antiapoptotic effect on nonhematopoietic cells. The aim of the study was to examine the effect of erythropoietin on the healing process of corneal epithelial erosions in rabbit eyes. Methods: Fifteen New Zealand albino rabbits were divided into 3 groups following induction of unilateral uniform corneal epithelial erosions. The first group received local treatment with erythropoietin-containing cellulose-based gel 4 times daily; the second group received treatment with cellulose-based gel without erythropoietin 4 times daily, and the third group received no treatment. The healing process was monitored twice daily using cobalt-blue-filtered slit lamp photography and digital images of fluorescein-stained corneas until complete re-epithelization was achieved. Following re-epithelization, corneas were removed for histologic processing. One-way analysis of variance and Mann-Whitney tests were used for statistical analysis. Results: Mean ± SD time to complete re-epithelization was 55 ± 2.19 h in the group treated with erythropoietin-containing cellulose-based gel, 66.5 ± 14.25 h in the group treated with gel only and 62.2 ± 9.09 h in the untreated group (p = 0.16, not significant). There was no significant difference among the groups in the time to complete re-epithelization or the rate of epithelial healing. Histologic corneal evaluation revealed stromal vascularization in 2 of the 6 erythropoietin-treated rabbits and in neither of the control groups. Conclusion: Erythropoietin has no beneficial effect on the rate of healing of corneal epithelial erosions in rabbit eyes, and corneal stroma neovascularization seems to be a significant adverse effect.
A Double Dose of Levocetirizine Leads to Better Control of Histamine-Induced Flare, Wheal and Itch in Healthy Donors
Authors: Tanizaki Hideaki , Nakamizo Satoshi , Nakahigashi Kyoko , Miyachi Yoshiki , Kabashima Kenji
Published: April 2017

Levocetirizine is classified as a nonsedating second-generation antihistamine. This drug is used to treat allergic disorders such as urticaria and pruritus. Thus far, studies have demonstrated an increase in efficacy for refractory urticaria by increasing doses of antihistamines; however, more lines of supportive evidence for these guidelines are required to justify this management strategy. In this study, we found that a double dose of levocetirizine suppressed histamine-induced flare formation more rapidly and sustainably, and wheal and itch more extensively, compared with the conventional dose using both visual and laser Doppler imaging scales in a noninvasive manner. These results suggest that double-dosed levocetirizine treatment suppresses histamine-induced skin symptoms more rapidly, profoundly and sustainably than conventionally dosed levocetirizine treatment.
Dental Caries and Microbiota in Children with Black Stain and Non-discoloured Dental Plaque
Authors: Heinrich-Weltzien R. , Bartsch B. , Eick S.
Published: April 2017

Aim: We aimed to assess caries experience and microbiota in systemically healthy children with black stain (BS) and non-discoloured plaque. Methods: Forty-six children with BS and 47 counterparts with non-discoloured plaque aged 7.9 ± 1.3 years were clinically examined. Dental caries was scored using WHO criteria. Samples of BS and non-discoloured dental plaque were collected from tooth surfaces. The DNA of the samples was extracted and real-time PCR was performed to determine the total number of bacteria and the species Streptococcus mutans, S. sobrinus, Lactobacillus sp., Actinomyces naeslundii, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum. Results: Children with BS had lower DMFT (p = 0.013), lower DT values (p = 0.005) and a tendency to lower caries prevalence (p = 0.061) than children with non-discoloured plaque. Plaque samples of the BS group contained higher numbers of A. naeslundii (p = 0.005) and lower numbers of F. nucleatum (p = 0.001) and Lactobacillus sp. (p = 0.001) compared to the non-discoloured plaque samples of the control group. Comparing the children with BS and non-discoloured plaque, higher counts for A. naeslundii (p = 0.013) were observed in caries-free children with BS while in caries-affected children with BS, lower counts of F. nucleatum (p = 0.007) were found. Counts of Lactobacillus sp. were higher in non-discoloured plaque samples than in BS of caries-free and caries-affected children. Conclusion: Results suggest that the different microbial composition of BS might be associated with the lower caries experience in affected subjects. The role of black-pigmented bacteria associated with periodontitis needs further studies.
Effects of Phosphate Binder Therapy on Vascular Stiffness in Early-Stage Chronic Kidney Disease
Authors: Seifert Michael E. , de las Fuentes Lisa , Rothstein Marcos , Dietzen Dennis J. , Bierhals Andrew J. , Cheng Steven C. , Ross Will , Windus David , Dávila-Román Víctor G. , Hruska Keith A.
Published: April 2017

Background/Aims: Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. Methods: We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. Results: There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3. Conclusion: Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.
Effect of Gallium on Growth of Streptococcus mutans NCTC 10449 and Dental Tissues
Authors: Valappil S.P. , Owens G.J. , Miles E.J. , Farmer N.L. , Cooper L. , Miller G. , Clowes R. , Lynch R.J.M. , Higham S.M.
Published: April 2017

Gallium-doped phosphate-based glasses (Ga-PBG) were assessed for their impact on Streptococcus mutans and dental mineralisation, firstly by disc diffusion assays followed by biofilms grown on nitrocellulose filter membrane (NFM) and constant-depth film fermentor (CDFF). Short-time exposure (10 min) effects of Ga-PBG on S. mutans biofilm were compared with that of 0.2% chlorhexidine. The effects of Ga-PBG on bovine enamel (which was investigated under pH-cycling condition) and dentine were analysed using transverse microradiography (TMR), profilometry and inductively coupled plasma optical-emission spectrometry (ICP-OES). The disc diffusion assays showed inhibition zones of 24.5 ± 0.5 mm for Ga-PBG compared with controls (C-PBG). Ga-PBG showed statistically significant growth inhibition of S. mutans biofilms on NFM (p = 0.001) and CDFF (p < 0.046) compared with hydroxyapatite (HA) and C-PBG. The CDFF assay revealed a maximum of 2.11 log colony-forming unit (CFU) reduction at 48 h, but short-time exposure effects were comparable with that of 0.2% chlorhexidine only on older biofilms (maximum of 0.59 vs. 0.69 log CFU reduction at 120 h). TMR analyses of the enamel revealed non-significant mineral loss (p = 0.37) only in the case of Ga-PBG samples compared with controls including sodium fluoride. ICP-OES analyses indicated transient gallium adsorption into dentine by calcium displacement. The results confirmed that gallium inhibited S. mutans growth and appears to have the potential to protect the enamel surface under conditions representative of the oral environment. Further work is needed to establish whether it has an application in daily oral hygiene procedures to prevent or reduce caries.
Susac Syndrome Treated with Subcutaneous Immunoglobulin
Authors: Kleffner Ilka , Dörr Jan , Duning Thomas , Young Peter , Ringelstein E. Bernd , Schilling Matthias
Published: April 2017

Background: Susac syndrome is a rare disease characterized by the triad of encephalopathy, branch retinal artery occlusion, and sensorineural hearing loss mainly affecting young women. The finding of antibodies against the endothelium in the sera of these patients has supported the hypothesis of an autoimmune endotheliopathy of the brain, inner ear and retina. Because of the rarity of the disease, treatment is based on the knowledge of case reports and small case series. Medical therapy consists of glucocorticoids, immunosuppressants, acetyl salicylic acid, and immunomodulatory agents such as intravenous immunoglobulin. Methods: We present the case histories of 2 young women with Susac syndrome presenting with several episodes of encephalopathy, branch retinal artery occlusions, and hearing loss that were treated with different immunosuppressive drugs, glucocorticoids and intravenous immunoglobulin. In the course of the disease, the treatment was successfully switched to subcutaneous immunoglobulin without any further relapse in both patients. Conclusion: We conclude that the application of subcutaneous immunoglobulin is easy to learn, helps to reduce in-hospital costs and enables a more flexible everyday life. The treatment with subcutaneous immunoglobulin helps to reduce immunosuppressants and appears to prevent relapses.
Long-Term Outcomes of Developmental Exposure to Fluoxetine: A Review of the Animal Literature
Authors: Kiryanova Veronika , McAllister Brendan B. , Dyck Richard H.
Published: April 2017

During and following pregnancy, women are at high risk of experiencing depression, for which fluoxetine (FLX; brand names Prozac, Sarafem, Rapiflux) is the most commonly prescribed treatment. An estimated 1.4-2.1% of pregnant women use this medication, which inhibits the reuptake of serotonin and thereby increases serotonergic activity at the synapse. Serotonin acts as a cue guiding numerous neurodevelopmental processes, and changes in the concentration of serotonin can disrupt normal in utero brain development and organization in humans and other animals, thus providing a mechanism by which maternal intake of FLX might alter neural development and ultimately behaviour. Despite this possibility, long-term alterations of behaviour and the brain have not been well studied in individuals exposed to FLX during pregnancy or soon after birth, perhaps because conducting such studies beyond infancy presents significant challenges. To remedy this problem, many researchers have turned to modelling the effects of developmental FLX exposure in non-human animals, primarily rodents. The body of literature on this topic has expanded considerably over the past several years, yet a comprehensive review is lacking. In order to fill this gap, we have summarized the findings of those studies describing the long-term behavioural and neurophysiological effects of FLX exposure in non-human animals in early development. We also discuss methodological considerations and common shortcomings of research in this area. The precise nature of the long-term effects of developmental FLX exposure remains difficult to specify, as these effects appear to be highly variable and dependent on numerous factors. Overall, however, it is clear that early FLX exposure in non-human animals can alter the development of the brain in ways that are relevant to behaviour in adulthood, decreasing exploration and social interaction, and in some cases altering anxiety- and depression-like behaviours.
Regulation of Inflammation and T Cells by Glycogen Synthase Kinase-3: Links to Mood Disorders
Authors: Beurel Eleonore
Published: April 2017

Accumulative evidence shows a role of the immune system in susceptibility to depression. Proinflammatory cytokines have been shown to be involved in the induction of depressive behavior both in humans and mice, opening a new avenue of therapeutic strategy. Because glycogen synthase kinase-3 (GSK3) was recently identified to be controlling the production of proinflammatory cytokines, and GSK3 has been shown to be implicated in mood disorders for many years, it has been proposed that the proinflammatory action of GSK3 could be responsible for the increased susceptibility to depressive behavior. Moreover, besides regulating cytokines, GSK3 also promotes differentiation of proinflammatory subtypes of Th cells, which are sufficient to induce depressive behavior in mice. Although the clear involvement of the immune system during depressive behavior still needs to be firmly demonstrated, there is growing evidence for the involvement of inflammation in the induction of depressive behavior.
The Risk Factors of Severe Acute Kidney Injury Induced by Cisplatin
Authors: Mizuno Tomohiro , Ishikawa Kazuhiro , Sato Waichi , Koike Takahiro , Kushida Mayu , Miyagawa Yasuhiro , Yamada Kiyofumi , Hirata Sumio , Imai Enyu , Noda Yukihiro
Published: April 2017

Objectives: We reported that the KDIGO (Kidney Disease: Improving Global Outcomes) criteria could stratify the risk of mortality in acute kidney injury (AKI) caused by cisplatin. The purpose of this study was to investigate risk factors of severe cisplatin-induced AKI (CIA). Methods: From January 2006 to December 2012, we identified Japanese cancer patients who were treated with cisplatin as a first-line chemotherapy at Nagoya University Hospital. Serum creatinine levels were used to define CIA. Results: We evaluated 1,721 patients treated with cisplatin. In multivariable analysis, cisplatin dosages/m2 [odds ratio (OR) 1.019] or diagnosis of cancer stage 4 (OR 1.797) were risk factors of moderate CIA. History of diabetes mellitus (OR 3.454), history of cardiovascular disease (OR 3.612) or diagnosis of cancer stage 4 (OR 2.610) were risk factors of severe CIA. Conclusions: Diabetes mellitus, cardiovascular disease and advanced cancer increased the risk of severe CIA. As severe CIA shortens the survival period, we should consider whether the use of cisplatin benefits these patients.
Evolutionary and Developmental Contributions for Understanding the Organization of the Basal Ganglia
Authors: Medina Loreta , Abellán Antonio , Vicario Alba , Desfilis Ester
Published: April 2017

Herein we take advantage of the evolutionary developmental biology approach in order to improve our understanding of both the functional organization and the evolution of the basal ganglia, with a particular focus on the globus pallidus. Therefore, we review data on the expression of developmental regulatory genes (that play key roles in patterning, regional specification and/or morphogenesis), gene function and fate mapping available in different vertebrate species, which are useful to (a) understand the embryonic origin and basic features of each neuron subtype of the basal ganglia (including neurotransmitter/neuropeptide expression and connectivity patterns); (b) identify the same (homologous) subpopulations in different species and the degree of variation or conservation throughout phylogeny, and (c) identify possible mechanisms that may explain the evolution of the basal ganglia. These data show that the globus pallidus of rodents contains two major subpopulations of GABAergic projection neurons: (1) neurons containing parvalbumin and neurotensin-related hexapetide (LANT6), with descending projections to the subthalamus and substantia nigra, which originate from progenitors expressing Nkx2.1, primarily located in the pallidal embryonic domain (medial ganglionic eminence), and (2) neurons containing preproenkephalin (and possibly calbindin), with ascending projections to the striatum, which appear to originate from progenitors expressing Islet1 in the striatal embryonic domain (lateral ganglionic eminence). Based on data on Nkx2.1, Islet1, LANT6 and proenkephalin, it appears that both cell types are also present in the globus pallidus/dorsal pallidum of chicken, frog and lungfish. In chicken, the globus pallidus also contains neurons expressing substance P (SP), perhaps originating in the striatal embryonic domain. In ray-finned and cartilaginous fishes, the pallidum contains at least the Nkx2.1 lineage cell population (likely representing the neurons containing LANT6). Based on the presence of neurons containing enkephalin or SP, it is possible that the pallidum of these animals also includes the Islet1 lineage cell subpopulation, and both neuron subtypes were likely present in the pallidum of the first jawed vertebrates. In contrast, lampreys (jawless fishes) appear to lack the pallidal embryonic domain and the Nkx2.1 lineage cell population that mainly characterize the pallidum in jawed vertebrates. In the absence of data in other jawless fishes, the ancestral condition in vertebrates remains to be elucidated. Perhaps, a major event in telencephalic evolution was the novel expression of Nkx2.1 in the subpallium, which has been related to Hedgehog expression and changes in the regulatory region of Nkx2.1.
Systemic Effects of Ophthalmic Cyclopentolate on Body Weight in Neonatal Mice
Authors: Rozette Nicole A. , Matragoon Suraporn , Sethi Shivani , Goei Stephanie , Manasco Kalen B. , El-Remessy Azza B.
Published: April 2017

Background: Cyclopentolate is standardly used in ophthalmologic examinations of neonates to facilitate screening for retinopathy of prematurity. Reports of systemic effects have raised concerns of an increased risk of feeding intolerance after the examinations. Objectives: The goal of this study was to evaluate systemic concentrations of cyclopentolate after ophthalmic administration, as well as assess changes in weight as an indirect measure of alteration in feeding. Methods: Neonatal mice were randomized into three groups to simulate a neonatal model for ophthalmic medication administration. The cyclopentolate group received a one-time administration of tetracaine, cyclopentolate, and phenylephrine ophthalmologic solutions in accordance with the protocol used at the children's hospital. The placebo group received the same ophthalmic drop administration, except for normal saline in place of cyclopentolate, and the control group received no ophthalmic drops and minimal handling. Daily weights and serum samples to measure systemic concentrations of cyclopentolate post-ophthalmic administration were assessed at baseline and for 7 days following drop administration. Results: Analysis of serum levels demonstrated detectability of systemic cyclopentolate after ophthalmic administration as early as 30 min (86 ng/ml), 1 h (60 ng/ml), and 24 h (6.2 ng/ml). There were also differences in weight gained on following ophthalmic administration observed between the cyclopentolate group and placebo group, with the cyclopentolate group weighing significantly less on days 3 and 7 (p = 0.02). Conclusions: Results indicate cyclopentolate is absorbed systemically and instillation of cyclopentolate decreases weight gain in neonatal mice compared to placebo. These preclinical findings provide rationale for further studies in neonatal patients.
Sex Differences in the Relation of Body Composition to Cardiovascular Parameters and Functions in Korean Adolescents: A School-Based Study
Authors: Song Young-Hwan , Kim Hae Soon , Park Hae Sook , Jung Jo Won , Kim Nam Su , Noh Chung Il , Hong Young Mi
Published: April 2017

Objective: Obesity in adolescence is associated with increased cardiovascular risk. The patterns of obesity and body composition differ between boys and girls. It is uncertain how body composition correlates with the cardiovascular system and whether such correlations differ by sex in adolescents. Methods: Body composition (fat-free mass (FFM), adipose mass, waist circumference (WC)) and cardiovascular parameters and functions were studied in 676 healthy Korean adolescents aged 12-16 years. Partial correlation and path analyses were done. Results: WC correlated with stroke volume (SV) and cardiac output (CO), systolic blood pressure (SBP) and pulse pressure (PP), cardiac diastolic function (ratio of early to late filling velocity (E/A ratio)), and vascular function (pulse wave velocity (PWV)) in boys. Adipose mass was related to SV, CO, SBP, PP, left ventricular mass (LVM), and PWV in girls - and to E/A ratio in both sexes. FFM affected SV, CO, SBP, and PP in both sexes and LVM in boys. Cardiac systolic functions had no relation with any body composition variable in either sex. Conclusion: In adolescence, the interdependence of the cardiovascular system and the body composition differs between sexes. Understanding of those relations is required to control adolescent obesity and prevent adult cardiovascular disease.
Metabolic Syndrome in Overweight and Obese Adolescents: A Comparison of Two Different Diagnostic Criteria
Authors: Tavares Giannini Denise , Caetano Kuschnir Maria Cristina , Szklo Moyses
Published: April 2017

Background: Due to the lack of consensus on its definition, the metabolic syndrome (MS) in children and adolescents is not formally recognized. However, several researchers have changed the adult criteria for pediatric standards in order to assess the prevalence. Objective: The aim of this study was to evaluate the frequency of MS and its components according to two of the currently used definitions in overweight and obese adolescents. Methods: A cross-sectional study with 232 adolescents with excess weight from a public school of the city of Rio de Janeiro. Anthropometric, blood pressure, and biochemical variables were assessed. MS was defined using two different diagnostic criteria: the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) and International Diabetes Federation (IDF). Results: MS was diagnosed in 40.4 and 24.6% of obese adolescents and 9.4 and 1.9% of overweight adolescents according to the NCEP-ATPIII and IDF criteria, respectively. The degree of agreement, assessed by the κ index, from the definitions adopted in this study was 0.48. Conclusion: The results show a significant difference between the two diagnostic criteria. A higher frequency was found when the NCEP-ATPIII was used, which is of concern given the association of MS with diabetes and cardiovascular disease.
Invertebrate Models for Coenzyme Q10 Deficiency
Authors: Fernández-Ayala Daniel J.M. , Jiménez-Gancedo Sandra , Guerra Ignacio , Navas Plácido
Published: April 2017

The human syndrome of coenzyme Q (CoQ) deficiency is a heterogeneous mitochondrial disease characterized by a diminution of CoQ content in cells and tissues that affects all the electron transport processes CoQ is responsible for, like the electron transference in mitochondria for respiration and ATP production and the antioxidant capacity that it exerts in membranes and lipoproteins. Supplementation with external CoQ is the main attempt to address these pathologies, but quite variable results have been obtained ranging from little response to a dramatic recovery. Here, we present the importance of modeling human CoQ deficiencies in animal models to understand the genetics and the pathology of this disease, although the election of an organism is crucial and can sometimes be controversial. Bacteria and yeast harboring mutations that lead to CoQ deficiency are unable to grow if they have to respire but develop without any problems on media with fermentable carbon sources. The complete lack of CoQ in mammals causes embryonic lethality, whereas other mutations produce tissue-specific diseases as in humans. However, working with transgenic mammals is time and cost intensive, with no assurance of obtaining results. Caenorhabditis elegans and Drosophila melanogaster have been used for years as organisms to study embryonic development, biogenesis, degenerative pathologies, and aging because of the genetic facilities and the speed of working with these animal models. In this review, we summarize several attempts to model reliable human CoQ deficiencies in invertebrates, focusing on mutant phenotypes pretty similar to those observed in human patients.
Physiology of Iron Metabolism
Authors: Waldvogel-Abramowski Sophie , Waeber Gérard , Gassner Christoph , Buser Andreas , Frey Beat M. , Favrat Bernard , Tissot Jean-Daniel
Published: April 2017

A revolution occurred during the last decade in the comprehension of the physiology as well as in the physiopathology of iron metabolism. The purpose of this review is to summarize the recent knowledge that has accumulated, allowing a better comprehension of the mechanisms implicated in iron homeostasis. Iron metabolism is very fine tuned. The free molecule is very toxic; therefore, complex regulatory mechanisms have been developed in mammalian to insure adequate intestinal absorption, transportation, utilization, and elimination. ‘Ironomics' certainly will be the future of the understanding of genes as well as of the protein-protein interactions involved in iron metabolism.
Clinical Factors Affecting Symptom Recurrence in Patients with Syncope
Authors: Lee Sung Ho , Kim Bum Soo , Park Seung-Jung , On Young Keun , Huh June , Kim June Soo
Published: April 2017

Purpose: Recurrent syncope leads to poor functional status and psychiatric impairment in patients with syncope. The aim of the study was to prospectively analyze the risk factors attributed to syncope recurrence. Materials and Methods: Between 2009 and 2010, 289 patients with all cause of syncope visited our institution. Syncope recurrences were followed for 1 year by telephone interview every 3 months. Results: We diagnosed 181 (63%) patients with neurally mediated syncope (NMS), 39 (13%) with orthostatic hypotension, 34 (12%) with cardiac syncope, and 35 (12%) with unexplained syncope. During the 1-year follow-up period, 19 (6.6%) patients suffered recurrent syncope. Kaplan-Meier curves showed that recurrent syncope was observed more often in patients with unexplained syncope compared with those with NMS (p < 0.01), and also observed more often in patients with six previous syncopal episodes compared to those with fewer episodes (p = 0.02). Cox regression analysis showed that the recurrence of syncope was significantly associated with more than six previous syncopal episodes (HR 5.38, 95% CI 1.17-24.71, p = 0.03) and that there was a tendency for association between recurrence of syncope and unexplained syncope (HR 6.13, 95% CI 0.96-39.1, p = 0.05). Conclusions: Patients with previous frequent syncopal episodes or unexplained syncope had higher rates of syncope recurrence during the follow up period.
Stent Thrombosis with Biodegradable Polymer Drug-Eluting Stents versus Durable Polymer Sirolimus-Eluting Stents: An Update Meta-Analysis
Authors: Zhu Lin , Lv Yi Ning , Wang Li Yu
Published: April 2017

Objective: Durable polymer sirolimus-eluting stents (DP-SES) are associated with a low risk of stent thrombosis; biodegradable polymer drug-eluting stents (BP-DES) were designed to reduce these risks. However, their benefits are still variable. Method: We undertook a meta-analysis of randomized trials identified by systematic searches of Medline, Embase, and the Cochrane Database. Results: Eleven studies (9,676 patients) with a mean follow-up of 22.6 months were included. Overall, compared with DP-SES, BP-DES significantly lowered the rate of definite or probable stent thrombosis (RR, 0.73; 95% CI, 0.55-0.97; p = 0.03; I2 = 0.0%) due to a decreased risk of very late stent thrombosis (RR, 0.26; 95% CI, 0.11-0.63; p = 0.00; I2 = 0.0%). However, BP-DES were associated with a comparable rate of early and late stent thrombosis. Meanwhile, BP-DES were associated with a broadly equivalent risk of target vessel revascularization (RR, 0.90; 95% CI, 0.78-1.03; p = 0.13; I2 = 0.0%), cardiac death (RR, 0.89; 95% CI, 0.72-1.09; p = 0.24; I2 = 0.0%), myocardial infarction (RR, 1.03; 95% CI, 0.84-1.26; p = 0.79; I2 = 0.0%), and major adverse cardiac events (MACE; RR, 0.91; 95% CI, 0.83-1.0; p = 0.08; I2 = 0.0%). Furthermore, angiographic data showed that in-stent and in-segment late luminal loss were similar between the two groups. Conclusions: Compared with DP-SES, BP-DES were associated with a lower rate of very late stent thrombosis and an equivalent risk of MACE. Larger randomized studies are needed to confirm this finding.
Palliative Treatment of Colorectal Cancer with Secondary Metastasis Resection in Germany - Impact of the Multidisciplinary Treatment Approach on Prognosis and Cost: The Northern Bavaria IVOPAK I Project
Authors: Wein Axel , Emmert Martin , Merkel Susanne , Harich Hanns-Detlev , Siebler Juergen , Thiemann Roland , Lamberti Christof , Göttler Bernhard , Fries Stefan , Kiani Alexander , Schlag Rudolf , Grüner Marcus , Steinbild Simone , Eberl Sonja , Pohl-Dernick Katharina , Dörje Frank , Horbach Thomas , Schöffski Oliver , Neurath Markus F. , Hohenberger Werner
Published: April 2017

Purpose: The aim of this study was to evaluate the quality of care and interdisciplinary cooperation in the palliative treatment of colorectal cancer (CRC), including the associated costs. Patients and Methods: 103 patients were enrolled from 13 institutions to reflect the existing clinical treatment reality and costs of palliative CRC treatment. We present the clinical outcome of the patients and compare the results obtained in the 3 centers with double-figure recruitment numbers (centers A, B, and C). Results: First-line treatment with 5-fluorouracil monotherapy was applied in exceptional cases. The regular treatment method comprised either an irinotecan- (30%) or an oxaliplatin-based regimen (32%). Biological agents were added to the treatment of 33 patients (32%). The median overall survival (OS) of the total patient collective was 25 months. The OS differed significantly in 2 out of the 3 centers, ranging between 27 and 11 months. Secondary metastasis resections were performed in 26% of the total patient collective. The center with the most favorable outcome results also had the lowest costs for palliative treatment and care, including the lowest drug costs. Conclusion: A combined chemotherapy treatment was the rule. Concerning biological agents, a significant lack of their application in first-line treatment and the quality of interdisciplinary cooperation have to be addressed. © 2014 S. Karger AG, Basel
Kidney Dysfunction and Left Ventricular Assist Device Support: A Comprehensive Perioperative Review
Authors: Coffin Samuel T. , Waguespack Dia R. , Haglund Nicholas A. , Maltais Simon , Dwyer Jamie P. , Keebler Mary E.
Published: April 2017

Left ventricular assist devices (LVADs) are used increasingly as a bridge to transplantation or as destination therapy in end-stage heart failure patients who do not respond to optimal medical therapy. Many of these patients have end-organ dysfunction, including advanced kidney dysfunction, before and after LVAD implantation. Kidney dysfunction is a marker of adverse outcomes, such as increased morbidity and mortality. This review discusses kidney dysfunction and associated management strategies during the dynamic perioperative time period of LVAD implantation. Furthermore, we suggest potential future research directions to better understand the complex relationship between renal pathophysiology and mechanical circulatory support.
MiR-376a and Histone Deacetylation 9 Form A Regulatory Circuitry in Hepatocellular Carcinoma
Authors: Zheng Yongxia , Chen Huan , Yin Manxiang , Ye Xiaoqian , Chen Guiqian , Zhou Xinmei , Yin Lei , Zhang Chengwen , Ding Baoyue
Published: April 2017

Background/Aims: Our previous study has demonstrated that down-regulation of miR-376a might contribute to the development of hepatocellular carcinoma (HCC), but the mechanism underlying this down-regulation remains obscure. Methods/Results: histone deacetylase (HDAC) inhibitor increased the level of miR-376a in L02 and Huh7 cells by up-regulating the acetylation level of histone 3 at the Maternally expressed 3 (Meg3) differentially methylated region (DMR). Interestingly, HDAC9, a histone deacetylase responsible for deacetylating lysine 18 of histone 3 (H3K18), was identified as the target of miR-376a. In addition, HDAC9 siRNA increased the expression of miR-376a by up-regulating the global histone H3K18 acetylation level, with Meg3 DMR included. Finally, miR-376a and HDAC9 were inversely correlated in HCC. Conclusion: HDAC9 plays an important role both as effects and targets of miR-376a.
Hyperthyroidism Evokes Myocardial Ceramide Accumulation
Authors: Mikłosz Agnieszka , Łukaszuk Bartłomiej , Chabowski Adrian , Rogowski Filip , Kurek Krzysztof , Żendzian-Piotrowska Małgorzata
Published: April 2017

Background: Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Methods: Male Wistar rats were treated for 10 days with triiodothyronine (T3) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. Results: We have demonstrated that prolonged, in vivo, T3 treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). Conclusions: We conclude that prolonged T3 treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.
Diagnostics and Treatment of Hepatocellular Carcinoma in 2016: Standards and Developments
Authors: Trojan Jörg , Zangos Stephan , Schnitzbauer Andreas A.
Published: April 2017

Background: Hepatocellular carcinoma (HCC) is a frequent complication of liver cirrhosis. Worldwide, HCC is one of the most common cancers, with a rising incidence. Methods: A selective literature search was conducted, taking into account current studies, reviews, meta-analyses, and guidelines. Results: The diagnosis is established either non-invasively by dynamic imaging, showing a typical contrast enhancement and wash-out, or histopathologically. Pathological diagnosis of HCC is recommended for all atypical nodules in patients with cirrhosis and for those in non-cirrhotic patients. Tumor therapy as well as treatment of the underlying chronic liver disease and/or preservation of liver function are important for the management of patients with HCC. Standard stage-adapted treatments are based on the widely applied Barcelona Clinic Liver Cancer staging system including liver resection and transplantation, interventional treatments such as thermal ablation and transarterial therapies, and systemic treatment with the tyrosine kinase inhibitor sorafenib. After failure of sorafenib, anti-angiogenic drugs, MET inhibitors, and immunotherapeutics are currently under advanced clinical investigation. Conclusion: Treatment of HCC is multidisciplinary and therefore requires a close cooperation between various disciplines such as hepatology, visceral surgery, radiology, and oncology to achieve the best outcome depending on the tumor stage and degree of liver function impairment.
Schnelles intrakranielles Ansprechen auf Osimertinib bei einer Patientin mit EGF-Rezeptor T790M-positivem Adenokarzinom der Lunge
Authors: Reichegger Hermann , Jochum Wolfram , Förbs Diana , Hader Claudia , Früh Martin
Published: April 2017

Hintergrund: Osimertinib (AZD9291, Tagrisso) ist ein starker, irreversibler EGFR-Tyrosinkinase-Inhibitor (EGFR-TKI) der dritten Generation. Fallbericht: Unser Bericht zeigt, dass Osimertinib in der Lage ist, bei einem Patienten mit einem Adenokarzinom der Lunge das Wachstum einer bestrahlungs- und operationsrefraktären EGFR T790M-positiven Hirnmetastase aufzuhalten. Schlussfolgerung: Diese Daten belegen, dass bei Patienten mit EGFR-mutiertem nicht-kleinzelligen Lungenkrebs mit erworbener TKI-Resistenz eine erneute Biopsie durchgeführt werden sollte. Übersetzung aus Oncol Res Treat 2016; 39:461-463 (DOI: 10.1159/000446759)
Infrared Thermography in Surgery of Newly Diagnosed Glioblastoma Multiforme: A Technical Case Report
Authors: Naydenov Emanuil , Minkin Krasimir , Penkov Marin , Nachev Sevdalin , Stummer Walter
Published: April 2017

Infrared thermography (IRT) is a real-time non-contact diagnostic tool with a broad potential for neurosurgical applications. Here we describe the intraoperative use of this technique in a single patient with newly diagnosed glioblastoma multiforme (GBM). An 86-year-old female was admitted in the clinic with a 2-month history of slowly progressing left-sided paresis. Neuroimaging studies demonstrated an irregular space-occupying process consistent with a malignant glioma in the right fronto-temporo-insular region. An elective surgical intervention was performed by using 5-aminolevulinic acid fluorescence (BLUE 400, OPMI) and intraoperative IRT brain mapping (LWIR, 1.25 mRad IFOV, 0.05°C NETD). After dura opening, the cerebral surface appeared inconspicuous. However, IRT revealed a significantly colder area (Δt° 1.01°C), well corresponding to the cortical epicenter of the lesion. The underlying tumor was partially excised and the histological result was GBM. Intraoperative IRT seems to be a useful technique for subcortical convexity brain tumor localization. Further studies with a large number of patients are needed to prove the reliability of this method in GBM surgery.