bluuebunny/crossref_metadata_2025 huggingface dataset:
Biocompatibility Assessment of Poly(lactic acid) Films after Sterilization with Ethylene Oxide in Histological Study In Vivo with Wistar Rats and Cellular Adhesion of Fibroblasts In Vitro
Authors: Savaris Michele , Braga Gustavo L. , dos Santos Venina , Carvalho Glaucio A. , Falavigna Asdrubal , Machado Denise C. , Viezzer Christian , Brandalise Rosmary N.
Published: April 2017

Biomaterials must meet certain fundamental requirements for their usage in living beings, such as biocompatibility, bifunctionality, and sterilizability, without having chemical and structural changes. The biocompatibility of poly(lactic acid) (PLA) films, shaped by compression, was evaluated after sterilization by ethylene oxide by a histological in vivo test with Wistar rats and cytotoxicity in cell adhesion in vitro. The cytotoxicity test was performed by the reduction of tetrazolium salt (MTT). Thermal and chemical changes in PLA films concerning the proposed sterilization process and characteristics were not observed to evidence polymer degradation due to sterilization. The analysis of the cytotoxicity by the MTT method has shown that the sterilized PLA films are not cytotoxic. The adhesion and proliferation of fibroblasts on PLA films were homogeneously distributed over the evaluation period, showing an elongated appearance with unnumbered cytoplasmic extensions and cell-cell interactions. By examining the biocompatibility in a histological study, a mild tissue inflammation was observed with the presence of fibrosis in the samples that had been exposed for 21 days in the rats’ bodies. PLA films sterilized with ethylene oxide did not exhibit cell adhesion in vitro and toxicity to the surrounding tissue in vivo and they may be used in future in vivo testing, according to histological findings in Wistar rats in the present study.
EEG-Based Computer Aided Diagnosis of Autism Spectrum Disorder Using Wavelet, Entropy, and ANN
Authors: Djemal Ridha , AlSharabi Khalil , Ibrahim Sutrisno , Alsuwailem Abdullah
Published: April 2017

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder with core impairments in the social relationships, communication, imagination, or flexibility of thought and restricted repertoire of activity and interest. In this work, a new computer aided diagnosis (CAD) of autism ‎based on electroencephalography (EEG) signal analysis is investigated. The proposed method is based on discrete wavelet transform (DWT), entropy (En), and artificial neural network (ANN). DWT is used to decompose EEG signals into approximation and details coefficients to obtain EEG subbands. The feature vector is constructed by computing Shannon entropy values from each EEG subband. ANN classifies the corresponding EEG signal into normal or autistic based on the extracted features. The experimental results show the effectiveness of the proposed method for assisting autism diagnosis. A receiver operating characteristic (ROC) curve metric is used to quantify the performance of the proposed method. The proposed method obtained promising results tested using real dataset provided by King Abdulaziz Hospital, Jeddah, Saudi Arabia.
A Squalene-Based Nanomedicine for Oral Treatment of Colon Cancer
Authors: Kotelevets Larissa , Chastre Eric , Caron Joachim , Mougin Julie , Bastian Gerard , Pineau Alain , Walker Francine , Lehy Therese , Desmaële Didier , Couvreur Patrick
Published: April 2017

Nanotechnology offers many possibilities to improve drug treatments, including with regard to drug pharmacology. The current study reports a simple approach to improve cisplatin efficacy in the treatment of colon cancer through the creation of orally administered squalenoylated nanoparticles loaded with cisplatin (SQ-CDDP NP). Cytotoxic effects of SQ-CDDP NP were assessed in human colonic cells and in mouse models of intestinal cancer. In cell culture, SQ-CDDP NP exhibited at least 10-fold greater cytotoxic potency compared with uncomplexed cisplatin, reflecting an enhancement in intracellular accumulation and DNA platination. Mechanistic investigations showed that SQ-CDDP NP stimulated ROS production, expression of heavy metal–inducible and stress-inducible genes, stress kinase cascades, and apoptosis. In ApcMin/+ mice, a model of intestinal tumorigenesis, oral administration of SQ-CDDP NP curtailed spontaneous tumor formation and azoxymethane-induced colon carcinogenesis with no apparent evidence of tissue toxicity. Our results offer preclinical validation of a nanocarrier formulation that can safely improve chemotherapeutic efficacy, address risks of drug resistance, and improve patient compliance by enabling oral administration. Cancer Res; 77(11); 2964–75. ©2017 AACR.
SFK/FAK Signaling Attenuates Osimertinib Efficacy in Both Drug-Sensitive and Drug-Resistant Models of EGFR-Mutant Lung Cancer
Authors: Ichihara Eiki , Westover David , Meador Catherine B. , Yan Yingjun , Bauer Joshua A. , Lu Pengcheng , Ye Fei , Kulick Amanda , de Stanchina Elisa , McEwen Robert , Ladanyi Marc , Cross Darren , Pao William , Lovly Christine M.
Published: April 2017

Mutant-selective EGFR tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR-mutant lung cancer. Specifically, these agents can overcome the effects of the T790M mutation, which mediates resistance to first- and second-generation EGFR TKI, and recent clinical trials have documented their efficacy in patients with EGFR-mutant lung cancer. Despite promising results, therapeutic efficacy is limited by the development of acquired resistance. Here we report that Src family kinases (SFK) and focal adhesion kinase (FAK) sustain AKT and MAPK pathway signaling under continuous EGFR inhibition in osimertinib-sensitive cells. Inhibiting either the MAPK pathway or the AKT pathway enhanced the effects of osimertinib. Combined SFK/FAK inhibition exhibited the most potent effects on growth inhibition, induction of apoptosis, and delay of acquired resistance. SFK family member YES1 was amplified in osimertinib-resistant EGFR-mutant tumor cells, the effects of which were overcome by combined treatment with osimertinib and SFK inhibitors. In conclusion, our data suggest that the concomitant inhibition of both SFK/FAK and EGFR may be a promising therapeutic strategy for EGFR-mutant lung cancer. Cancer Res; 77(11); 2990–3000. ©2017 AACR.
Metabolic Markers and Statistical Prediction of Serous Ovarian Cancer Aggressiveness by Ambient Ionization Mass Spectrometry Imaging
Authors: Sans Marta , Gharpure Kshipra , Tibshirani Robert , Zhang Jialing , Liang Li , Liu Jinsong , Young Jonathan H. , Dood Robert L. , Sood Anil K. , Eberlin Livia S.
Published: April 2017

Ovarian high-grade serous carcinoma (HGSC) results in the highest mortality among gynecological cancers, developing rapidly and aggressively. Dissimilarly, serous borderline ovarian tumors (BOT) can progress into low-grade serous carcinomas and have relatively indolent clinical behavior. The underlying biological differences between HGSC and BOT call for accurate diagnostic methodologies and tailored treatment options, and identification of molecular markers of aggressiveness could provide valuable biochemical insights and improve disease management. Here, we used desorption electrospray ionization (DESI) mass spectrometry (MS) to image and chemically characterize the metabolic profiles of HGSC, BOT, and normal ovarian tissue samples. DESI-MS imaging enabled clear visualization of fine papillary branches in serous BOT and allowed for characterization of spatial features of tumor heterogeneity such as adjacent necrosis and stroma in HGSC. Predictive markers of cancer aggressiveness were identified, including various free fatty acids, metabolites, and complex lipids such as ceramides, glycerophosphoglycerols, cardiolipins, and glycerophosphocholines. Classification models built from a total of 89,826 individual pixels, acquired in positive and negative ion modes from 78 different tissue samples, enabled diagnosis and prediction of HGSC and all tumor samples in comparison with normal tissues, with overall agreements of 96.4% and 96.2%, respectively. HGSC and BOT discrimination was achieved with an overall accuracy of 93.0%. Interestingly, our classification model allowed identification of three BOT samples presenting unusual histologic features that could be associated with the development of low-grade carcinomas. Our results suggest DESI-MS as a powerful approach for rapid serous ovarian cancer diagnosis based on altered metabolic signatures. Cancer Res; 77(11); 2903–13. ©2017 AACR.
TRA2A Promoted Paclitaxel Resistance and Tumor Progression in Triple-Negative Breast Cancers via Regulating Alternative Splicing
Authors: Liu Tieju , Sun Huizhi , Zhu Dongwang , Dong Xueyi , Liu Fang , Liang Xiaohui , Chen Chen , Shao Bing , Wang Meili , Wang Yi , Sun Baocun
Published: April 2017

Treatment of triple-negative breast cancer (TNBC) has been challenging, and paclitaxel resistance is one of the major obstacles to the better prognosis. Deregulation of alternative splicing (AS) may contribute to tumor progression and chemotherapy resistance. Human AS factor TRA2 has two separate gene paralogs encoding TRA2A and TRA2B proteins. TRA2B is associated with cancer cell survival and therapeutic sensitivity. However, the individual role of TRA2A in cancer progression has not been reported. Here we report that TRA2A facilitates proliferation and survival and migration and invasion of TNBC cells. In addition, TRA2A promotes paclitaxel resistance of TNBC by specifically controlling cancer-related splicing, which is independent of other splicing factors. TRA2A overexpression could promote AS of CALU, RSRC2, and PALM during paclitaxel treatment of TNBC cells. The isoform shift of RSRC2 from RSRC2s to RSRC2l leads to a decreased RSRC2 protein expression, which could contribute to TNBC paclitaxel resistance. TRA2A can regulate RSRC2 AS by specifically binding upstream intronic sequence of exon4. Strikingly, TRA2A expression is increased dramatically in patients with TNBC, and has a close relationship with decreased RSRC2 expression; both are associated with poor survival of TNBC. Collectively, our findings suggest that paclitaxel targets the TRA2A–RSRC2 splicing pathway, and deregulated TRA2A and RSRC2 expression may confer paclitaxel resistance. In addition to providing a novel molecular mechanism of cancer-related splicing dysregulation, our study demonstrates that expression of TRA2A in conjunction with RSRC2 may provide valuable molecular biomarker evidence for TNBC clinical treatment decisions and patient outcome. Mol Cancer Ther; 16(7); 1377–88. ©2017 AACR.
The Role of the Selective Serotonin Reuptake Inhibitor Fluoxetine in Temperature Regulation in Ovariectomized Rat Models
Authors: Maswood Navin , Cosmi Scott , Alfinito Peter D. , Leventhal Liza , Deecher Darlene C.
Published: April 2017

Thermoregulation is an integrated network of neuroendocrine, autonomic and somatosensory responses. Thermoregulatory dysfunction occurs during fluctuations or decline of gonadal hormone levels and results in vasomotor symptoms such as hot flushes and/or night-time sweating. The neurotransmitter serotonin (5-HT), has been reported to play a role in thermoregulation via changes in extracellular 5-HT levels and/or activation of various 5-HT receptors. The purpose of this study was to evaluate the role of the selective 5-HT reuptake inhibitor (SSRI), fluoxetine (FLX), on temperature regulation using ovariectomized (OVX) rodent models of thermoregulation. Single, subcutaneous (s.c.) administration of FLX (3, 10, 30 and 60 mg/kg) dose-dependently reduced core body temperature (CBT). FLX at 3 and 10 mg/kg s.c. showed no statistically significant decrease on tail-skin temperature (TST), whereas at higher doses (30 and 60 mg/kg) a significant decrease in TST was noted in the telemetry model. To mimic chronic SSRI treatment, a 5-HT1A antagonist (WAY-100635; 0.3 mg/kg) was administered 20 min prior to FLX (10 mg/kg). This combination showed no significant improvement on temperature dysfunction compared to FLX alone. Similarly, in a morphine-dependent model of temperature dysfunction FLX, was inactive at 10 mg/kg whereas the 30 and 60 mg/kg s.c. dose abated the naloxone-induced increase in TST by 55 and 81%, respectively. In summary, FLX affected CBT at all doses, but alleviated thermoregulatory dysfunction only at higher doses that are non-selective for the 5-HT system.
Gonadotropin-Releasing Hormone Functionally Antagonizes Testosterone Activation of the Human Androgen Receptor in Prostate Cells through Focal Adhesion Complexes Involving Hic-5
Authors: Maudsley Stuart , Davidson Lindsay , Pawson Adam J. , Freestone Sarah H. , López de Maturana Rakel , Thomson Axel A. , Millar Robert P.
Published: April 2017

Gonadotropin-releasing hormone (GnRH) analogs constitute the most widely employed medical treatment for prostatic cancer. The predominant mechanism of action is presumed to be via the inhibition of gonadotropins and resultant decrease in androgen. However, GnRH analogs have also been shown to directly inhibit prostate cancer cells both in vitro and in vivo through antiproliferative cell cycle arrest and stimulation of apoptosis. Since the GnRH receptor has been shown to affect sex steroid hormone receptor function, we considered that part of GnRH analog actions on prostate cells may be mediated through modulation of the human androgen receptor. Using a model HEK293 cell line expressing the GnRH receptor, we demonstrated a novel signalling pathway of the GnRH receptor that induces nuclear translocation of the androgen receptor that renders it transcriptionally inactive. This mechanism involves the calcium-dependent tyrosine kinase Pyk2, the non-receptor tyrosine kinase c-Src and the focal adhesion protein/steroid receptor co-factor, Hic-5. In this setting there is a GnRH-induced association and nuclear translocation of the androgen receptor with Hic-5. GnRH-induced Pyk2 activation opposed the association of Hic-5 with androgen receptor as overexpression of a dominant negative Pyk2 enhanced the GnRH-induced nuclear translocation of a green fluorescent protein-tagged human androgen receptor. GnRH-induced c-Src activation resulted in the phosphorylation of expressed Hic-5 and promoted its association with the human androgen receptor. In contrast to testosterone, GnRH-induced nuclear translocation did not transcriptionally activate the androgen receptor. We then demonstrated that GnRH can also stimulate androgen receptor mobilization in human prostate PC3, BPH-1 and LNCaP cells, and in cultured rat ventral prostate cells through the same mechanism. To determine if GnRH could antagonize androgen effects in normal tissue, we examined the effect of GnRH on rat ventral prostate organ cultures and demonstrated that GnRH can functionally antagonize the actions of testosterone on prostate cell proliferation and tissue growth. This antagonism of testosterone action by GnRH may underlie in part the capacity of GnRH receptor activation to inhibit prostate tumor growth.
Dermopathy and Retinopathy in Diabetes: Is There an Association?
Authors: Abdollahi Ali , Daneshpazhooh Maryam , Amirchaghmaghi Elham , Sheikhi Samira , Eshrati Babak , Bastanhagh Mohammad-Hassan
Published: April 2017

Background/Aims: Diabetic dermopathy is the most common cutaneous marker of diabetes mellitus presenting as single or multiple well-demarcated brown atrophic macules, predominantly on the shins. Although diabetic dermopathy and diabetic retinopathy are both considered by some authors as manifestations of diabetic microangiopathy, only a few studies are published about their possible association. Our purpose was to investigate the association of diabetic dermopathy and diabetic retinopathy. Methods: We conducted a cross-sectional study in an outpatient diabetes clinic during a 6-month period. One-hundred and eighty-one consecutive patients (8 cases of insulin-dependent diabetes mellitus and 173 cases of non-insulin-dependent diabetes mellitus) were examined for the presence of diabetic dermopathy and diabetic retinopathy. Results: Forty-seven (26%) showed diabetic dermopathy and 68 patients (37.6%) suffered from diabetic retinopathy. The frequency of retinopathy in patients with diabetic dermopathy (44%; 30 cases) was significantly greater than in patients without dermopathy (15%; 17 cases; p < 0.0001). Retinopathy showed a statistically significant association with dermopathy [odds ratio (OR): 3.60; 95% confidence interval (CI): 1.53–8.44; p = 0.003] and diabetes duration (OR: 3.36; 95% CI: 1.67–6.77; p = 0.001). Conclusion: Our study further supports that diabetic dermopathy might be used as a telltale sign of diabetic retinopathy, necessitating more intensive ophthalmologic care, especially in long-lasting diabetes.
Population Estimates of Extended Family Structure and Size
Authors: Garceau Anne , Wideroff Louise , McNeel Timothy , Dunn Marsha , Graubard Barry I.
Published: April 2017

Background: Population-based estimates of biological family size can be useful for planning genetic studies, assessing how distributions of relatives affect disease associations with family history and estimating prevalence of potential family support. Methods: Mean family size per person is estimated from a population-based telephone survey (n = 1,019). Results: After multivariate adjustment for demographic variables, older and non-White respondents reported greater mean numbers of total, first- and second-degree relatives. Females reported more total and first-degree relatives, while less educated respondents reported more second-degree relatives. Conclusions: Demographic differences in family size have implications for genetic research. Therefore, periodic collection of family structure data in representative populations would be useful.
Family Physicians’ Beliefs about Genetic Contributions to Racial/Ethnic and Gender Differences in Health and Clinical Decision-Making
Authors: Warshauer-Baker Esther , Bonham Vence L. , Jenkins Jean , Stevens Nancy , Page Zintesia , Odunlami Adebola , McBride Colleen M.
Published: April 2017

Greater attention towards genetics as a contributor to group health differences may lead to inappropriate use of race/ethnicity and gender as genetic heuristics and exacerbate health disparities. As part of a web-based survey, 1,035 family physicians (FPs) rated the contribution of genetics and environment to racial/ethnic and gender differences in health outcomes, and the importance of race/ethnicity and gender in their clinical decision-making. FPs attributed racial/ethnic and gender differences in health outcomes equally to environment and genetics. These beliefs were not associated with rated importance of race/ethnicity or gender in clinical decision-making. FPs appreciate the complexity of genetic and environmental influences on health differences by race/ethnicity and gender.
Neuroendocrine Dysfunction in Sjögren’s Syndrome
Authors: Tzioufas Athanasios G. , Tsonis John , Moutsopoulos Haralampos M.
Published: April 2017

Interactions among the immune, nervous and endocrine systems, which are mediated by hormones, neuropeptides, neurotransmitters, cytokines and their receptors, appear to play an important role in modulating host susceptibility and resistance to inflammatory disease. The neuroendocrine system has two main components: the central and the peripheral. The central compartment is located in the locus ceruleus, the brainstem centers of the autonomic system and the paraventricular nucleus; the peripheral mainly consists of the sympathetic/adrenomedullary system, the hypothalamic-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal (HPG) axis, and the neuroendocrine tissue located in several organs throughout the body. Hormones and neuropeptides may influence the activities of lymphoid organs and cells via endocrine and local autocrine/paracrine pathways or alter the function of different cell types in target organs. Recent studies highlighted alterations of the neuroendocrine system in systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and Sjögren’s syndrome (SS). SS, a prototype autoimmune disorder, has a wide clinical spectrum, extending from organ involvement (autoimmune exocrinopathy) to systemic disease and B cell lymphoma. In SS, several functions of the neuroendocrine system are impaired. First, the HPA axis appears to be disturbed, since significantly lower basal ACTH and cortisol levels were found in patients with SS and were associated with a blunted pituitary and adrenal response to ovine corticotropin-releasing factor compared to normal controls. Second, HPG axis is also involved, since lack of estrogens is associated with human disease and the development of autoimmune exocrinopathy in several experimental models. Finally, exocrine glands are enriched with neuroendocrine-related molecules, adjacent to local autoimmune lesions. Certain clinical manifestations of the disease, including the sicca manifestations, easy fatigue, fibromyalgia and psychological disturbances can be very well explained by mechanisms directly related to disturbances of the neuroendocrine axis. On the other hand, the molecular and biochemical effects of the inflammatory molecules or cell-to-cell interaction, observed during the local or systemic autoimmune injury with cells and mediators of the neuroendocrine system, are largely unexplored.
Brain Alterations in Autoimmune and Pharmacological Models of Diabetes Mellitus: Focus on Hypothalamic-Pituitary-Adrenocortical Axis Disturbances
Authors: Beauquis J. , Homo-Delarche F. , Revsin Y. , De Nicola A.F. , Saravia F.
Published: April 2017

Type 1 diabetes (T1D) is linked to an ‘encephalopathy’ explained by some features common to the aging process, degenerative and functional disorders of the central nervous system. In the present study we describe a manifest hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in two different experimental mouse models of T1D including the pharmacological one induced by streptozotocin and the spontaneous NOD (nonobese diabetic mice). The high expression of hypothalamic hormones like oxytocin and vasopressin were part to this alteration, together with elevated adrenal glucocorticoids and prominent susceptibility to stress. In the hippocampus of diabetic animals a marked astrogliosis, often associated with neural damage, was present. Dentate gyrus neurogenesis was also affected by the disease: proliferation and differentiation measured by bromodeoxyuridine immunodetection were significantly reduced in both experimental models used. Several facts, including changes associated with chronic hyperglycemia, hyperstimulation of the HPA axis, increased levels of circulating glucocorticoids in combination with brain inflammation and low production of new neurons, contribute to emphasize the impact of diabetes on the central nervous system.
γ-Aminobutyric Acid Inhibits Synergistic Interleukin-6 Release but Not Transcriptional Activation in Astrocytoma Cells
Authors: Roach Jr. Joseph D. , Aguinaldo Grant T. , Jonnalagadda Kaumudi , Hughes Jr. Francis M. , Spangelo Bryan L.
Published: April 2017

Objective: A decline in the inhibitory neurotransmitter γ-aminobutyric acid (GABA) may enhance cytokine release in Alzheimer’s disease (AD) resulting in neuroinflammation. We investigated the GABA-mediated suppression of the synergistic release of interleukin (IL)-6 due to interleukin 1-β (IL-1β) and tumor necrosis factor-α (TNF-α). Methods: Rat C6 astrocytoma cells were treated with IL-1β and TNF-α in the absence and presence of GABA. Activation of p38, degradation of IĸB-α and total cellular IL-6 were determined by Western blot analysis. IL-6 release and gene expression were measured by ELISA and RT-PCR, respectively. Results: Although p38 and nuclear factor (NF)-ĸB are essential for the synergistic release of IL-6, GABA did not affect either p38 phosphorylation or IĸB-α degradation. Additionally, GABA suppressed IL-6 release but did not alter cytokine-driven synergistic increases in IL-6 gene expression. Western blot analysis revealed that co-treatments with IL-1β and TNF-α resulted in an increase in intracellular IL-6 that was prevented by GABA. Conclusion: GABA-induced inhibition of IL-6 release appears to coincide with a reduction in cellular IL-6. The GABA-induced suppression of IL-6 release may include inhibition of IL-6 gene translation.
Effect of Bacterial Lipopolysaccharide on the Reproductive Axis of Prepubertal and Peripubertal Female Rats
Authors: Reynoso Roxana , Ponzo Osvaldo , Cardoso Nancy , Szwarcfarb Berta , Carbone Silvia , Moguilevsky Jaime , Scacchi Pablo
Published: April 2017

The immune, endocrine and nervous systems are closely interrelated, which allows the organism to respond to different types of stress such as infection. Chronic infectious and inflammatory conditions are often accompanied by an impaired reproductive function. Leptin, a hormone produced by adipose tissue, exerts a regulatory function on the reproductive axis. It has homology with other proinflammatory cytokines and could be modified by lipopolysaccharide (LPS). Therefore, these studies were designed to investigate the effect of LPS administration on the neuroendocrine mechanisms involved in the regulation of the reproductive axis during sexual maturation. Fifteen- and 30-day-old female rats were injected with a single dose of LPS 250 µg/kg (i.p.) and then nitric oxide synthase (NOS) activity, hypothalamic excitatory/inhibitory amino acids and Gn-RH content, serum LH and leptin concentration were studied. In 15-day-old female rats LPS treatment did not modify hypothalamic inducible (iNOS) and constitutive (cNOS) NOS activity, Gn-RH, glutamate (GLU) and GABA content. Also serum LH and leptin levels were not modified. In 30-day-old rats LPS increased iNOS and cNOS activity (p < 0.001) and hypothalamic Gn-RH content (p < 0.001). At this age hypothalamic GABA content was significantly decreased (p < 0.001) without changes in GLU content, and serum LH (p < 0.001) and leptin (p < 0.0001) decreased significantly. In summary, current studies have demonstrated that LPS administration to 15- and 30-day-old female rats results in a different response of the hypothalamus-pituitary-gonadal axis and of the adipose tissue, demonstrating an ontogenic response of the immune-neuroendocrine system to LPS administration.
In vitro Macrophage Activity: Biphasic Effect of Prolactin and Indirect Evidence of Dopaminergic Modulation
Authors: Carvalho-Freitas Maria I.R. , Rodrigues-Costa Elaine C. , Nasello Antonia G. , Palermo-Neto João , Felicio Luciano F.
Published: April 2017

Objective: Prolactin (PRL), a peptide hormone produced by the pituitary gland, is involved in the interaction between the neuroendocrine and immune system. Since dopamine receptor antagonists increase serum levels of PRL, both PRL and dopamine receptors might be involved in the modulation of macrophage activity, providing means of communication between the nervous and immune systems. This study evaluated the effects of PRL and the dopamine antagonist domperidone (DOMP) on macrophage activity of female rats. Methods: Oxidative burst and phagocytosis of peritoneal macrophages were evaluated by flow cytometry. Samples of peritoneal liquid from female rats were first incubated with PRL (10 and 100 nM) for different periods. The same procedure was repeated to evaluate the effects of DOMP (10 and 100 nM). Results: In vitro incubation of macrophages with 10 nM DOMP decreased oxidative burst, after 30 min, whereas the PMA-induced burst was decreased by DOMP 10 nM after 2 and 4 h. Treatment with PRL (10 and 100 nM) for 30 min decreased oxidative burst and rate of phagocytosis (10 nM). After 2 h of incubation, 10 nM PRL decreased oxidative burst and phagocytosis intensity, but increased the rate of phagocytosis. On the other hand, after 4 h, PRL 10 and 100 nM increased oxidative burst and the rate of phagocytosis, but decreased intensity of phagocytosis. Conclusions: These observations suggest that macrophage functions are regulated by an endogenous dopaminergic tone. Our data also suggest that both PRL and dopamine exert their action by acting directly on the peritoneal macrophage.
The Novel NF-κB Activation Inhibitor Dehydroxymethyl-Epoxyquinomicin Suppresses Anti-Thy1.1-Induced Glomerulonephritis in Rats
Authors: Kosaka Takeo , Miyajima Akira , Kikuchi Eiji , Horiguchi Yutaka , Umezawa Kazuo , Ohigashi Takashi , Nakashima Jun , Asano Tomohiko , Oya Mototsugu
Published: April 2017

Abstract
Background: NF-κB participates in the transcriptional regulation of numerous genes, and many studies have confirmed the activation of NF-κB in inflammatory renal diseases. Therefore, NF-κB is a promising target for the treatment of these diseases. We tested the effects of dehydroxymethyl-epoxyquinomicin (DHMEQ), a novel NF-κB activation inhibitor, on anti-thy1.1 antibody-induced glomerulonephritis (Thy1.1 GN). Methods: Thy1.1 GN was induced in Sprague-Dawley rats (6/group) by intravenous injection of anti-thy 1.1 antibody. The effects of DHMEQ (8 mg/kg/day) on the glomerular disease were evaluated using periodic acid-Schiff and Masson trichrome stains, immunohistochemistry for proliferating cell nuclear antigen, fibronectin and CD45 (leukocyte common antigen) and TUNEL staining. NF-κB activation was analyzed by a fluorescent electrophoretic mobility shift assay. Results: On day 7, DHMEQ treatment resulted in marked inhibition of NF-κB, decreased proteinuria (223.2 ± 42.3 vs. 434.8 ± 16.5 mg/kg/day, p < 0.05), preserved creatinine clearance (1.93 ± 0.38 vs. 1.07 ± 0.29 l/day, p < 0.01), decreased glomerular cell proliferation (15.8 ± 1.2 vs. 31.2 ± 0.8 nuclei/glomerular cross-section) and mesangial matrix deposition, and an increase in glomerular and tubular apoptosis without inducing any obvious adverse effects. Conclusion: DHMEQ inhibited NF-κB and thereby suppressed the inflammatory renal responses in rats with Thy1.1 GN.
Unusual Association of Omphalocele and Wandering Spleen
Authors: Yilmaz Ö. , Genc A. , Ozcan T. , Aygoren R.S. , Taneli C.
Published: April 2017

A wandering spleen is a rare anomaly and its association with omphalocele has been reported in the literature only once. We present a female infant that has a wandering spleen associated with omphalocele. The patient was admitted with the diagnosis of omphalocele. Primary repair was performed and the patient was discharged on the 6th postoperative day. Nine months later, the girl was referred to our emergency unit with complaints about abdominal distention and restlessness. After 2 days of clinical observation, an immobile, firm abdominal mass was palpated. Ultrasonographic evaluation revealed that the mass was the spleen and it was found exactly under the left side of the umbilicus, instead of its original location. During the operation, the spleen was beneath the left side of the umbilicus, with its upper surface completely adhered to the peritoneum, and it was rotated 180° clockwise. Then the spleen was rotated back and placed in its normal anatomic location. At 1 month postoperatively, a radionuclide scan was performed and splenic perfusion was evaluated to be normal. In conclusion, herniations and eventrations of organs through defects on the abdominal wall may either result in restriction of normal rotations of the stomach and the spleen or in inefficient fusion after the rotation has been completed.
Social Factors Influencing Performance of a Foraging Task for Captive Chimpanzees
Authors: Brent Linda , Fisher Stan , Eichberg Jorg W.
Published: April 2017

The performance of captive chimpanzees (Pan troglodytes) during a simulated foraging activity was compared to that reported for the foraging behavior of wild chimpanzees. The ability to find hidden fruit in a large outdoor play area was measured for 34 subjects housed in ten separate groups. Sex differences were apparent, with females searching for and finding significantly more fruit than males did. Chimpanzees of high and medium dominance rank found more fruit than those of low rank. Neither age nor stage of the female sexual cycle exerted an influence. The subjects became more proficient at finding fruit during the second block of trials. The results reflect possible influences of captivity on chimpanzee social behavior.
Karyotype Polymorphism in the Slender Loris (Loris tardigradus)
Authors: Goonan Peter M. , Groves Colin P. , Smith Rosalie D.
Published: April 2017

Three wild-caught Sri Lankan and two captive-bred slender lorises (Loris tardigradus) in Adelaide Zoo, South Australia, were karyotyped from leucocyte cultures. The founder male and one of the founder females were of the grey subspecies L. tardigradus grandis, of which L. tardigradus nordicus is probably a synonym. The other founder female was a small red-brown L. tardigradus tardigradus. All three wild-caught individuals were karyotypically distinct from each other and their offspring showed the expected heterozygosity. The L. tardigradus tardigradus karyotype was no more distinct from the grey subspecies karyotypes than they were from each other. On present evidence, Indian and Sri Lankan lorises appear to be chromosomally distinct.
Leaping Behaviors and the Functional Morphology of Strepsirhine Primate Long Bones
Authors: Terranova Carl J.
Published: April 2017

Recent examinations of the functional morphology underlying strepsirhine primate leaping behaviors have identified several cross-sectional features of long bones that can be associated with interspecific differences in leaping frequency and/or body size. In this study the cross-sectional parameters of strepsirhine fore- and hindlimb long bones are examined relative to body weight, bone length, phylogenetic affiliation, leaping frequency and landing kinematics. Humeral cross-sectional morphology is conservative relative to both phylogenetic and functional groupings. As a result, humeral cross-sectional area should prove useful as a size surrogate in future comparative studies. After the effects of bone length and body weight are controlled, ‘frequent’ leapers have stronger and more rigid femoral and tibial midshafts than do ‘less-frequent’ leapers. Landing style is conflated with leaping frequency and it is difficult to explain morphological variation exclusively by either leaping frequency or landing style. Further behavioral research, especially field study of locomotion, is needed to disentangle the effects of these mechanically important aspects of leaping locomotion.
Haptic Perception in Baboons (Papio papio): Preliminary Evidence for Lateralization in Accuracy and Exploration Time
Authors: Lacreuse Agnès
Published: April 2017

Two baboons performed 2 types of haptic discrimination of three-dimensional object pairs, by using the right and left hands in the same number of trials. One task focused on the discrimination of the objects’ shape, another on the convexity or concavity of the objects. It was found that the left was better than the right hand to discriminate the shape of objects. Regardless of the task, objects were also explored longer with the left than with the right hand. It is suggested that these hand differences are congruent with the hypothesis of an advantage of the right hemisphere in monkeys for haptic perception.
Triangulating Stapling Technique for Anastomosis in Laparoscopy-Assisted Pylorus-Preserving Gastrectomy
Authors: Nunobe Souya , Kiyokawa Takashi , Hatao Fumihiko , Wada Ikuo , Shimizu Nobuyuki , Nomura Sachiyo , Seto Yasuyuki
Published: April 2017

Background/Aims: The anastomosis performed during laparoscopy-assisted pylorus-preserving gastrectomy (PPG) is usually handsewn; however, the technique is sometimes difficult because it is done through a small incision and the level of skill of each operator may vary. The present study describes a triangulating stapling technique used during an anastomosis in laparoscopy-assisted pylorus-preserving gastrectomy. Method: The 80-mm stapler was used 3 times for the triangulating stapling technique. The posterior walls, including the stay sutures, were joined by firing the stapler, and the anterior stomach ends were stapled in an everting fashion using two firings of the stapler. Both the anterior staple lines should overlap in the middle. Patient demographics and the operative data were examined. Results: The triangulating stapling technique was performed during laparoscopy-assisted PPG in 9 patients. The median time for the anastomosis during laparoscopy-assisted PPG using the triangulating stapling technique was 19.0 min (16.0–31.0). Postoperative complications, including gastric stasis and anastomotic failure, were not found in any of the present patients. Conclusion: The triangulating stapling technique using a linear stapler is a safe and reliable technique to perform and can be easily conducted in a short time. We therefore consider it a useful anastomosis method for laparoscopy-assisted pylorus-preserving gastrectomy, even by unskilled surgeons.
Vitreous and Aqueous Penetration of Orally and Topically Administered Moxifloxacin
Authors: Fukuda Masamichi , Shibata Naoko , Osada Hiromi , Yamashiro Yoko , Sasaki Hiroshi
Published: April 2017

Aim: It was the aim of this study to compare the pharmacokinetics of moxifloxacin (MFLX) hydrochloride in rabbits after topical and oral administration. Methods: Three 50-µl applications of MFLX (0.5%) topical ophthalmic solution were instilled into the cul-de-sac of New Zealand white rabbits at 15-min intervals. Aqueous and vitreous samples were collected and analyzed 30–240 min after the final instillation. Assays were performed using high-performance liquid chromatography. MFLX (16 mg/kg of body weight) was administered orally. Drug concentrations in aqueous, vitreous and serum samples, collected at 30–360 min after administration, were determined using high-performance liquid chromatography. Results: After topical administration, the maximum concentrations of MFLX in the aqueous and vitreous samples were 10.2 ± 1.6 µg/ml (30 min; n = 6) and 0.10 ± 0.03 µg/ml (30 min; n = 6), respectively. After oral administration, the maximum concentrations in the aqueous, vitreous and serum samples were 0.9 ± 0.3 µg/ml (120 min; n = 6), 0.7 ± 0.2 µg/ml (240 min; n = 6) and 1.6 ± 0.9 µg/ml (120 min; n = 6), respectively. The percentages of serum MFLX concentration in the aqueous and vitreous samples after oral administration were 55.2 and 41.7%, respectively. Conclusions: The aqueous concentration of MFLX was about 10-fold higher after topical than after oral administration. However, intravitreal MFLX concentrations after oral administration were about 7-fold higher than those after topical administration. The MFLX concentrations in the aqueous humor following oral administration exceeded the minimum inhibitory concentration for 90% of the bacteria involved in ocular infection.
Tooth Size Variation Related to Age in Amboseli Baboons
Authors: Galbany Jordi , Dotras Laia , Alberts Susan C. , Pérez-Pérez Alejandro
Published: April 2017

We measured the molar size from a single population of wild baboons from Amboseli (Kenya), both females (n = 57) and males (n = 50). All the females were of known age; the males represented a mix of known-age individuals (n = 31) and individuals with ages estimated to within 2 years (n = 19). The results showed a significant reduction in the mesiodistal length of teeth in both sexes as a function of age. Overall patterns of age-related change in tooth size did not change whether we included or excluded the individuals of estimated age, but patterns of statistical significance changed as a result of changed sample sizes. Our results demonstrate that tooth length is directly related to age due to interproximal wearing caused by M2 and M3 compression loads. Dental studies in primates, including both fossil and extant species, are mostly based on specimens obtained from osteological collections of varying origins, for which the age at death of each individual in the sample is not known. Researchers should take into account the phenomenon of interproximal attrition leading to reduced tooth size when measuring tooth length for ondontometric purposes.
A Potential Role for Glucose Transporters in the Evolution of Human Brain Size
Authors: Fedrigo Olivier , Pfefferle Adam D. , Babbitt Courtney C. , Haygood Ralph , Wall Christine E. , Wray Gregory A.
Published: April 2017

Differences in cognitive abilities and the relatively large brain are among the most striking differences between humans and their closest primate relatives. The energy trade-off hypothesis predicts that a major shift in energy allocation among tissues occurred during human origins in order to support the remarkable expansion of a metabolically expensive brain. However, the molecular basis of this adaptive scenario is unknown. Two glucose transporters (SLC2A1 and SLC2A4) are promising candidates and present intriguing mutations in humans, resulting, respectively, in microcephaly and disruptions in whole-body glucose homeostasis. We compared SLC2A1 and SLC2A4 expression between humans, chimpanzees and macaques, and found compensatory and biologically significant expression changes on the human lineage within cerebral cortex and skeletal muscle, consistent with mediating an energy trade-off. We also show that these two genes are likely to have undergone adaptation and participated in the development and maintenance of a larger brain in the human lineage by modulating brain and skeletal muscle energy allocation. We found that these two genes show human-specific signatures of positive selection on known regulatory elements within their 5′-untranslated region, suggesting an adaptation of their regulation during human origins. This study represents the first case where adaptive, functional and genetic lines of evidence implicate specific genes in the evolution of human brain size.
Development of an Outpatient Native Kidney Biopsy Service in Low-Risk Patients: A Multidisciplinary Approach
Authors: McMahon Gearoid M. , McGovern Molly E. , Bijol Vanesa , Benson Carol B. , Foley Richard , Munkley Karen , Schnipper Jeffrey , Franz Calvin , Lin Julie
Published: April 2017

Background: In the US, native kidney biopsies are usually inpatient procedures. We developed an outpatient biopsy protocol for low-risk patients and assessed its safety and efficacy. Methods: Patients with an SBP <140 mm Hg and a BMI ≤35 who were not taking anticoagulants, ASA and NSAIDS in the preceding week were included. Biopsies were performed under ultrasound guidance using a 15-gauge needle that changed to a 14-gauge needle during the study. Patients were discharged after 5 h of observation if there were no signs of bleeding. Complications were carefully recorded. Results: Between November 2008 and April 2011, 105 patients underwent outpatient renal biopsies. A 15-gauge needle was used in 43 patients (group A) while a 14-gauge needle was used in 62 (group B). A median of 25 (range 4–64) glomeruli were obtained in group A versus 39 (range 0–107) in group B (p < 0.001). Complications requiring admission for observation occurred in 7 patients (16%) in group A versus 5 patients (8%) in group B (p = 0.22). One patient in group B had bleeding requiring intervention, while all other complications were minor. Nine complications occurred during the observation period, while 3 patients presented >48 h after biopsy. The mean cost per patient for each outpatient biopsy was USD 976 versus USD 5,489 for inpatients. Conclusions: In a selected low-risk population, outpatient renal biopsy is safe with low complication rates and results in significant cost savings relative to elective inpatient biopsies. The use of a 14-gauge biopsy needle resulted in a greater yield of glomeruli without increased complications.
Clinical Study of Therapeutic Ocular Surface Medium for Persistent Epithelial Defect
Authors: Watson S.L. , Geerling G. , Dart J.K.G.
Published: April 2017

Purpose: To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for persistent epithelial defect (PED). Methods: 11 eyes of 10 patients with PED for ≥2 weeks without improvement despite conventional treatment were enrolled in a prospective pilot study of TOSM over 1 month. Results: Healing of the PED occurred in 3 out of the 11 eyes at 1, 2 and 4 weeks, respectively. At week 4, 2 eyes were almost healed (PED area ≤0.5 mm2). In 4 of the remaining 6 eyes, the PED area was reduced. Failure occurred in 1 case with end-stage ocular cicatricial pemphigoid and severe dry eye, and 1 patient withdrew due to a mild allergic reaction. There were no serious or irreversible side effects with TOSM. Conclusions: TOSM is a potential novel physiological therapy for PED that, unlike autologous serum, has the potential to be easily manufactured and widely available.
Gastric Bypass Increases Postprandial Insulin and GLP-1 in Nonobese Minipigs
Authors: Verhaeghe R. , Zerrweck C. , Hubert T. , Tréchot B. , Gmyr V. , D'Herbomez M. , Pigny P. , Pattou F. , Caiazzo R.
Published: April 2017

Background: Gastric bypass in obese patients induces a dramatic increase of postprandial insulin and glucagon-like peptide-1 (GLP-1) secretion, independently of weight loss. We explored postprandial insulin and GLP-1 secretion in nonobese minipigs before and after RYGB. Methods: Lean adult Göttingen minipigs (n = 7) were submitted to an open gastric bypass surgery mimicking the clinical procedure in humans (30-cm3 gastric pouch/150-cm alimentary limb/70-cm biliary limb). All animals were evaluated at baseline and then 10 and 30 days after surgery. At each time point, serum glucose, insulin, GLP-1 and D-xylose levels were measured 3 h after a standardized mixed meal. Results: Weight remained stable during follow-up. Insulin and GLP-1 responses to the test meal were dramatically and similarly increased at 10 days and 1 month after RYGB. Maximal postprandial insulin and GLP-1 levels were 16.3 ± 1.7 mIU/l and 71.7 ± 16.5 pmol/l at baseline, 111.5 ± 38.9 mIU/l and 320.8 ± 84.0 pmol/l at 10 days and 96.6 ± 10.4 mIU/l and 297.3 ± 79.1 pmol/l at 1 month, respectively. D-Xylose absorption remained unchanged before and after surgery. Conclusions: RYGB induced a dramatic increase of postprandial insulin and GLP-1 secretion in nonobese minipigs. This preclinical model could help to understand the underlying metabolic effects of RYGB, focusing on the role of postsurgical anatomical rearrangement, especially duodenojejunal exclusion and ileal brake. This study supports the use of RYGB in diabetic nonobese patients in absence of obesity.
FAF and SufA: Proteins of Finegoldia magna That Modulate the Antibacterial Activity of Histones
Authors: Murphy Elizabeth C. , Mohanty Tirthankar , Frick Inga-Maria
Published: April 2017

Many bacterial pathogens have developed methods to overcome the defences of the host innate immune system. One such defence is the release of antimicrobial peptides (AMPs). Histones have been found to function as AMPs, in addition to their main biological function of packaging and organising DNA into nucleosomes. In this study, the Gram-positive anaerobic coccus Finegoldia magna was found to bind histones by Western blot and immunoprecipitation analysis. F. magna, which is normally a commensal of the skin and mucous membranes, is also known to act as an opportunistic pathogen and has been isolated from various clinical infection sites. It was found to bind to histones extracted from human skin epidermis through its surface and extracellular adhesion protein FAF. Through FAF binding, F. magna was protected from histone bactericidal activity. Furthermore, the histones were found to be degraded by SufA, a subtilisin-like extracellular serine protease of F. magna. Hence, the results of the present study will give more insight into how F. magna persists both as a commensal organism at the basement membrane of the skin and as an opportunistic pathogen during infection.