bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroprotective and anti‐apoptotic effects of liraglutide on SH‐SY5Y cells exposed to methylglyoxal stress
Authors: Sharma Mohit K. , Jalewa Jaishree , Hölscher Christian 
Published: October 2013

AbstractGlucagon‐like peptide 1 (GLP‐1) is a growth factor that has demonstrated neuroprotective properties in a range of studies. In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP‐1 analogue liraglutide in human neuroblastoma cell line SH‐SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dose‐dependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro‐survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro‐apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP‐1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor‐related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza®). It is also tested in clinical trials in patients with Alzheimer disease.
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We investigated the neuroprotective properties of the GLP‐1 analogue liraglutide in SH‐SY5Y cells during methyl glyoxal stress. Cell survival was enhanced, while cytotoxicity and apoptosis was reduced. Expression of the pro‐survival Mcl1 signaling protein, activation of Akt, MEK1/2 and the transcription factor p90RSK was increased. Pro‐apoptotic Bax and Bik expression was reduced, and the influx of calcium into the cell was normalised. The results demonstrate a range of growth factor related cytoprotective processes induced by the drug liraglutide.
Aβ40 modulates GABAA receptor α6 subunit expression and rat cerebellar granule neuron maturation through the ERK/mTOR pathway
Authors: Zhan Xiao‐Qin , Yao Jin‐Jing , Liu Dong‐Dong , Ma Qianqian , Mei Yan‐Ai 
Published: October 2013

AbstractIn addition to their neurotoxic role in Alzheimer's disease (AD), β‐amyloid peptides (Aβs) are also known to play physiological roles. Here, we show that recombinant Aβ40 significantly increased the outward current of the GABAA receptor containing (GABAAα6) in rat cerebellar granule neurons (CGNs). The Aβ40‐mediated increase in GABAAα6 current was mediated by an increase in GABAAα6 protein expression at the translational rather than the transcriptional level. The exposure of CGNs to Aβ40 markedly induced the phosphorylation of ERK (pERK) and mammalian target of rapamycin (pmTOR). The increase in GABAAα6 current and expression was attenuated by specific inhibitors of ERK or mTOR, suggesting that the ERK and mTOR signaling pathways are required for the effect of Aβ40 on GABAAα6 current and expression in CGNs. A pharmacological blockade of the p75 neurotrophin receptor (p75NTR), but not the insulin or α7‐nAChR receptors, abrogated the effect of Aβ40 on GABAAα6 protein expression and current. Furthermore, the expression of GABAAα6 was lower in CGNs from APP−/− mice than in CGNs from wild‐type mice. Moreover, the internal granule layer (IGL) in APP−/− mice was thinner than the IGL in wild‐type mice. The injection of Aβ40 into the cerebellum reversed this effect, and the application of p75NTR blocking antibody abolished the effects of Aβ40 on cerebellum morphology in APP−/− mice. Our results suggest that low concentrations of Aβ40 play a role in regulating CGN maturation through p75NTR.
imageIn addition to its neurotoxic role in Alzheimer's disease, Aβ is known to play important physiological roles. Whether Aβ improves neuronal development and maturation remains elusive. Our results demonstrate that low concentrations of Aβ40 significantly increase the GABAA receptor α6 subunit expression and associated current in cerebellar granule neurons (CGNs) via the p75NTR and MEK/ERK pathway. Aβ also increases the thickness of the internal granule layer in APP−/− mice cerebellum. Our data provide new evidence for the role of Aβ40 in regulating the maturation of CGNs.
Inflammation induces multinucleation of Microglia via PKC inhibition of cytokinesis, generating highly phagocytic multinucleated giant cells
Authors: Hornik Tamara C. , Neniskyte Urte , Brown Guy C. 
Published: October 2013

AbstractMicroglia are brain macrophages, which can undergo multinucleation to give rise to multinucleated giant cells that accumulate with ageing and some brain pathologies. However, the origin, regulation and function of multinucleate microglia remain unclear. We found that inflammatory stimuli, including lipopolysaccharide, amyloid β, α‐synuclein, tumour necrosis factor‐α and interferon γ, but not interleukin‐4, induced multinucleation of cultured microglia: primary rat cortical microglia and the murine microglial cell line BV‐2. Inflammation‐induced multinucleation was prevented by a protein kinase C (PKC) inhibitor Gö6976 (100 nM) and replicated by a PKC activator phorbol myristate acetate (160 nM). Multinucleation was reversible and not because of cell fusion or phagocytosis, but rather failure of cytokinesis. Time‐lapse imaging revealed that some dividing cells failed to abscise, even after formation of long cytoplasmic bridges, followed by retraction of bridge and reversal of cleavage furrow to form multinucleate cells. Multinucleate microglia were larger and 2–4 fold more likely to phagocytose large beads and both dead and live PC12 cells. We conclude that multinucleate microglia are reversibly generated by inflammation via PKC inhibition of cytokinesis, and may have specialized functions/dysfunctions including the phagocytosis of other cells.
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Inflammation resulted in the accumulation of multiple nuclei per cell in cultured microglia. This multinucleation was reversible and due to a PKC‐dependent block of the last step of cell division. Multinucleate microglia were larger and had a greater capacity to phagocytose other cells, suggesting they might remove neurons in the brain.
Neurobiological consequences of acute footshock stress: effects on tyrosine hydroxylase phosphorylation and activation in the rat brain and adrenal medulla
Authors: Ong Lin Kooi , Guan Liying , Damanhuri Hanafi , Goodchild Ann K. , Bobrovskaya Larisa , Dickson Phillip W. , Dunkley Peter R. 
Published: October 2013

AbstractStress activates selected neuronal systems in the brain and this leads to activation of a range of effector systems. Our aim was to investigate some of the relationships between these systems under basal conditions and over a 40‐min period in response to footshock stress. Specifically, we investigated catecholaminergic neurons in the locus coeruleus (LC), ventral tegmental area and medial prefrontal cortex (mPFC) in the brain, by measuring tyrosine hydroxylase (TH) protein, TH phosphorylation and TH activation. We also measured the effector responses by measuring plasma adrenocorticotrophic hormone, corticosterone, glucose and body temperature as well as activation of adrenal medulla protein kinases, TH protein, TH phosphorylation and TH activation. The LC, ventral tegmental area and adrenal medulla all had higher basal levels of Ser19 phosphorylation and lower basal levels of Ser31 phosphorylation than the mPFC, presumably because of their cell body versus nerve terminal location, while the adrenal medulla had the highest basal levels of Ser40 phosphorylation. Ser31 phosphorylation was increased in the LC at 20 and 40 min and in the mPFC at 40 min; TH activity was increased at 40 min in both tissues. There were significant increases in body temperature between 10 and 40 min, as well as increases in plasma adrenocorticotropic hormone at 20 min and corticosterone and glucose at 20 and 40 min. The adrenal medulla extracellular signal‐regulated kinase 2 was increased between 10 and 40 min and Ser31 phosphorylation was increased at 20 min and 40 min. Protein kinase A and Ser40 phosphorylation were increased only at 40 min. TH activity was increased between 20 and 40 min. TH protein and Ser19 phosphorylation levels were not altered in any of the brain regions or adrenal medulla over the first 40 min. These findings indicate that acute footshock stress leads to activation of TH in the LC, pre‐synaptic terminals in the mPFC and adrenal medullary chromaffin cells, as well as changes in activity of the hypothalamic‐pituitary‐adrenal axis.imageWe measured the basal levels of tyrosine hydroxylase phosphorylation and determined the effects of footshock stress over a 40 minute period. Footshock leads to changes in the activity of neurons in the locus coeruleus (LC) and presynaptic terminals in the medial prefrontal cortex (mPFC), as well as changes in activity of the hypothalamic‐pituitary‐adrenal (HPA) axis and adrenal medullary (AM) chromaffin cells.
Phosphoproteomic evaluation of pharmacological inhibition of leucine‐rich repeat kinase 2 reveals significant off‐target effects of LRRK‐2‐IN‐1
Authors: Luerman Gregory C. , Nguyen Chuong , Samaroo Harry , Loos Paula , Xi Hualin , Hurtado‐Lorenzo Andres , Needle Elie , Stephen Noell G. , Galatsis Paul , Dunlop John , Geoghegan Kieran F. , Hirst Warren D. 
Published: October 2013

AbstractGenetic mutations in leucine‐rich repeat kinase 2 (LRRK2) have been linked to autosomal dominant Parkinson's disease. The most prevalent mutation, G2019S, results in enhanced LRRK2 kinase activity that potentially contributes to the etiology of Parkinson's disease. Consequently, disease progression is potentially mediated by poorly characterized phosphorylation‐dependent LRRK2 substrate pathways. To address this gap in knowledge, we transduced SH‐SY5Y neuroblastoma cells with LRRK2 G2019S via adenovirus, then determined quantitative changes in the phosphoproteome upon LRRK2 kinase inhibition (LRRK2‐IN‐1 treatment) using stable isotope labeling of amino acids in culture combined with phosphopeptide enrichment and LC‐MS/MS analysis. We identified 776 phosphorylation sites that were increased or decreased at least 50% in response to LRRK2‐IN‐1 treatment, including sites on proteins previously known to associate with LRRK2. Bioinformatic analysis of those phosphoproteins suggested a potential role for LRRK2 kinase activity in regulating pro‐inflammatory responses and neurite morphology, among other pathways. In follow‐up experiments, LRRK2‐IN‐1 inhibited lipopolysaccharide‐induced tumor necrosis factor alpha (TNFα) and C‐X‐C motif chemokine 10 (CXCL10) levels in astrocytes and also enhanced multiple neurite characteristics in primary neuronal cultures. However, LRRK2‐IN‐1 had almost identical effects in primary glial and neuronal cultures from LRRK2 knockout mice. These data suggest LRRK2‐IN‐1 may inhibit pathways of perceived LRRK2 pathophysiological function independently of LRRK2 highlighting the need to use multiple pharmacological tools and genetic approaches in studies determining LRRK2 function.
imageGenetic mutations in leucine‐rich repeat kinase 2 (LRRK2) have been linked to Parkinson's disease, potentially contributing to the pathogenesis through increased kinase activity acting via phosphorylation‐dependent LRRK2 substrate pathways. To determine the potential pathways, we performed SILAC combined with phosphopeptide enrichment and LC‐MS/MS analysis +/‐ LRRK2 inhibitor. Bioinformatic analysis of those phosphoproteins suggested a potential role for LRRK2 kinase activity in regulating pro‐inflammatory responses and neurite morphology, among other pathways.
The dermal arteries of the human thumb pad
Authors: Geyer S. H. , Nöhammer M. M. , Tinhofer I. E. , Weninger W. J. 
Published: October 2013

AbstractThe arteries of the skin have been postulated to form a profound plexus at the dermal/hypodermal junction and a superficial plexus in the papillary dermis. Our article aims to rebut this concept and to provide an alternative description of the arrangement of the dermal arteries. Employing a novel technique, we produced digital volume data (volume size: 2739 × 2054 × 3000 μm3; voxel size: 1.07 × 1.07 × 2 μm3) from biopsies of the skin of the thumb pads of 15 body donors. Utilizing these data, we analysed the arrangement of the dermal arteries with the aid of virtual re‐sectioning tools, and, in three specimens, with high‐quality three‐dimensional (3D) surface models. In all specimens we observed a tree‐like ramification of discrete dermal arteries. The terminal branches of the arterial trees gave rise to the ascending segments of the capillary loops of the dermal papillae. None of the specimens showed a superficial arterial plexus. This suggests that the skin of the human thumb pad can be split in discrete ‘arterial units’. Each unit represents the zone of the papillary dermis and epidermal/dermal junction, to which blood is supplied exclusively by the branches of a single dermal artery. The concept of dermal arterial units is in contrast to all existing descriptions of the architecture of the dermal arteries. However, whether it can be transferred to the skin of other body parts, remains to be tested. Likewise, the consequences of arterial units for understanding the mechanisms of wound healing and the appearance and genesis of skin diseases remain to be examined.
Effects of glycolic acid chemical peeling on facial pigment deposition: Evaluation using novel computer analysis of digital‐camera‐captured images
Authors: Kakudo Natsuko , Kushida Satoshi , Suzuki Kenji , Kusumoto Kenji 
Published: October 2013

SummaryBackgroundChemical peeling is becoming increasingly popular for skin rejuvenation in dermatological cosmetic medicine. However, the improvements seen with chemical peeling are often very minor, and it is difficult to conduct a quantitative assessment of pre‐ and post‐treatment appearance.AimsWe report the pre‐ and postpeeling effects for facial pigment deposition using a novel computer analysis method for digital‐camera‐captured images.Patients/MethodsGlycolic acid chemical peeling was performed a total of 5 times at 2‐week intervals in 23 healthy women. We conducted a computer image analysis by utilizing Robo Skin Analyzer CS 50 and Clinical Suite 2.1 and then reviewed each parameter for the area of facial pigment deposition pre‐ and post‐treatment. Parameters were pigmentation size and four pigmentation categories: little pigmentation and three levels of marked pigmentation (Lv1, 2, and 3) based on detection threshold. Each parameter was measured, and the total area of facial pigmentation was calculated.ResultsThe total area of little pigmentation and marked pigmentation (Lv1) was significantly reduced. On the other hand, a significant difference was not observed for the total area of marked pigmentation Lv2 and Lv3.ConclusionThis suggests that glycolic acid chemical peeling has an effect on small facial pigment disposition or has an effect on light pigment deposition. As the Robo Skin Analyzer is useful for objectively quantifying and analyzing minor changes in facial skin, it is considered to be an effective tool for accumulating treatment evidence in the cosmetic and esthetic skin field.
Registered nurses' reflections on discussing sexuality with patients: responsibilities, doubts and fears
Authors: Saunamäki Nina , Engström Maria 
Published: October 2013

Aims and objectivesTo describe registered nurses' reflections on discussing sexuality with patients.BackgroundIt is known that many diseases and treatments have a negative impact on sexual health. Despite these facts, registered nurses typically do not address sexual issues with patients.DesignA descriptive design and a qualitative approach were used.MethodsInterviews were conducted in 2010 with 10 registered nurses. The data were analysed using qualitative content analysis.ResultsThe themes ‘Doing the right thing and doing good’, ‘Could've, would've, should've: a nurse's conflicting feelings’ and ‘I just don't talk about it: sexuality as a nontopic’ confirmed the notion that discussing sexuality in nursing care is still challenging and difficult for nurses, but also revealed that nurses who do talk to patients about sexual issues do so based on their strong sense of wanting to help. They felt a responsibility because of their knowledge in the area, but the topic also brought out conflicting feelings such as fear and embarrassment. Lack of time, support and places to talk to patients in private as well as prejudice were contributing factors to their not addressing sexuality. Some nurses also felt that sexuality was someone else's responsibility and a taboo subject.ConclusionsPatients' sexuality is still surrounded by silence. But factors exist that can facilitate discussion of sexuality. Nurses have a key role in detecting ill‐health. This study suggests that when nurses use their knowledge and go beyond their comfort zone and address sexuality, they can identify patients' sexual problems.Relevance to clinical practiceNurses need to understand how their knowledge can help patients who are experiencing sexual problems; they also need support from the workplace and to have access to routines that reinforce the notion that sexuality is a topic worth discussing.
Administration of oral and vaginal prebiotic lactoferrin for a woman with a refractory vaginitis recurring preterm delivery: Appearance of lactobacillus in vaginal flora followed by term delivery
Authors: Otsuki Katsufumi , Tokunaka Mayumi , Oba Tomohiro , Nakamura Masamitsu , Shirato Nahoko , Okai Takashi 
Published: October 2013

AbstractLactoferrin (LF) is one of the prebiotics present in the human body. A 38‐year‐old multiparous woman with poor obstetrical histories, three consecutive preterm premature rupture of membrane at the 19th, 23rd and 25th week of pregnancy, was referred to our hospital. She was diagnosed as having refractory vaginitis. Although estriol vaginal tablets were used for 4 months, the vaginitis was not cured. We administrated vaginal tablets and oral agents of prebiotic LF, resulting in a Lactobacillus predominant vaginal flora. When she was pregnant, she continued to use the LF, and the Lactobacillus in the vaginal flora was continuously observed during pregnancy. An elective cesarean section was performed at the 38th week of pregnancy. When the administration of LF was discontinued after the delivery, Lactobacillus in the vaginal flora was disappeared.
Uterine artery pseudoaneurysm hidden behind septic abortion: Pseudoaneurysm without preceding procedure
Authors: Matsubara Shigeki , Nakata Manabu , Baba Yosuke , Suzuki Haruna , Nakamura Hiroyasu , Suzuki Mitsuaki 
Published: October 2013

AbstractUterine artery pseudoaneurysm (UAP) can occur after cesarean section or traumatic delivery, usually manifesting as postpartum hemorrhage. Here we report a patient with UAP possibly caused by septic abortion. She had high fever and bleeding with positive urine pregnancy test. We diagnosed this condition as septic abortion. Ultrasound revealed an intrauterine echogenic mass and color Doppler revealed swirling blood flow within the mass. Contrast‐enhanced computed tomography showed a heterogeneously enhanced intrauterine mass. Selective internal iliac artery angiography revealed contrast medium within the mass immediately after medium injection. Bilateral uterine artery embolization was performed, after which medium no longer accumulated in the uterus, and hemostasis was achieved, confirming the diagnosis as UAP. Antibiotic treatment ameliorated the infection and the uterine content was expelled and absorbed. UAP can occur even without preceding procedures and may manifest abortive, and not postpartum, hemorrhage. UAP may be hidden behind septic abortion.
Use of periurethral injections of polyacrylamide hydrogel for treating post‐vesicovaginal fistula closure urinary stress incontinence
Authors: Krause Hannah G. , Lussy Justin P. , Goh Judith T. W. 
Published: October 2013

AbstractAimsFollowing successful closure of obstetric genitourinary fistula, stress urinary incontinence (SUI) is a common and challenging problem. Despite many decades of various treatment options, the effective management of post‐fistula SUI remains unresolved. This study aims to assess the feasibility of periurethral injections of polyacrylamide hydrogel, commonly used for urinary stress incontinence in non‐fistula women, in women with post‐fistula closure SUI.Material and MethodsWomen with urinary incontinence following successful fistula closure were assessed to exclude detrusor overactivity and urinary residual volumes of more than 100 mL. The urethrovesical junction was identified and polyacrylamide hydrogel was injected through the periurethral skin and vaginal epithelium at three sites.ResultsFour women with post‐fistula SUI were treated with polyacrylamide hydrogel injections. Three of the four women were dry post‐operatively and remained continent at discharge.ConclusionIn the short‐term, periurethral injections of polyacrylamide hydrogel appears to be a promising method to treat post‐obstetric fistula urinary stress incontinence.
Melatonin and female reproduction
Authors: Tamura Hiroshi , Takasaki Akihisa , Taketani Toshiaki , Tanabe Manabu , Lee Lifa , Tamura Isao , Maekawa Ryo , Aasada Hiromi , Yamagata Yoshiaki , Sugino Norihiro 
Published: October 2013

AbstractMelatonin (N‐acetyl‐5‐methoxytryptamine) is secreted during the dark hours at night by the pineal gland. After entering the circulation, melatonin acts as an endocrine factor and a chemical messenger of light and darkness. It regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It also affects the brain, immune, gastrointestinal, cardiovascular, renal, bone and endocrine functions and acts as an oncostatic and anti‐aging molecule. Many of melatonin's actions are mediated through interactions with specific membrane‐bound receptors expressed not only in the central nervous system, but also in peripheral tissues. Melatonin also acts through non‐receptor‐mediated mechanisms, for example serving as a scavenger for reactive oxygen species and reactive nitrogen species. At both physiological and pharmacological concentrations, melatonin attenuates and counteracts oxidative stress and regulates cellular metabolism. Growing scientific evidence of reproductive physiology supports the role of melatonin in human reproduction. This review was conducted to investigate the effects of melatonin on female reproduction and to summarize our findings in this field.
Anorectal abscess during pregnancy
Authors: Koyama Shinsuke , Hirota Masaki , Kobayashi Masaki , Tanaka Yusuke , Kubota Satoshi , Nakamura Ryo , Isobe Masanori , Shiki Yasuhiko 
Published: October 2013

AbstractAnorectal symptoms and complaints caused by hemorrhoids or anal fissures are common during pregnancy. It is known that one‐third of pregnant women complain of anal pain in the third trimester. Anal pain may be caused by a wide spectrum of conditions, but if it begins gradually and becomes excruciating within a few days it may indicate anorectal abscess. We experienced a case of anorectal abscess during pregnancy which was diagnosed by magnetic resonance imaging and treated by incision and seton drainage at 36 weeks of gestation, followed by a normal spontaneous delivery at 38 weeks of gestation. To our knowledge, this is the first case report of anorectal abscess during pregnancy in the English‐language published work. The clinical course of our case and clinical considerations of anorectal abscesses are discussed.