Neuroprotective Activity of Sitagliptin via Reduction of Neuroinflammation beyond the Incretin Effect: Focus on Alzheimer's Disease.

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Neuroprotective Activity of Sitagliptin via Reduction of Neuroinflammation beyond the Incretin Effect: Focus on Alzheimer's Disease.

Biomed Res Int. 2018;2018:6091014

Authors: Wiciński M, Wódkiewicz E, Słupski M, Walczak M, Socha M, Malinowski B, Pawlak-Osińska K

Abstract
Sitagliptin is a member of a class of drugs that inhibit dipeptidyl peptidase (DPP-4). It increases the levels of the active form of incretins such as GLP-1 (glucagon-like peptide-1) or GIP (gastric inhibitory polypeptide) and by their means positively affects glucose metabolism. It is successfully applied in the treatment of diabetes mellitus type 2. The most recent scientific reports suggest beneficial effect of sitagliptin on diseases in which neuron damage occurs. Result of experimental studies may indicate a reducing influence of sitagliptin on inflammatory response within encephalon area. Sitagliptin decreased the levels of proinflammatory factors: TNF-α (tumor necrosis factor-α), IL-6 (interleukin-6), IL-17 (interleukin-17), and CD-163 (cluster of differentiation 163), and contributed to an increase in levels of anti-inflammatory factors: IL-10 (interleukin-10) and TGF-β (transforming growth factor β). Moreover, sitagliptin demonstrated antioxidative and antiapoptotic properties by modifying glutamate and glutathione levels within the region of hippocampus in mice. It has been observed that sitagliptin decreases accumulation of β-amyloid within encephalon structures in experimental models of Alzheimer's dementia. This effect may be connected with SDF-1α (stromal cell-derived factor 1α) concentration. Administration of sitagliptin caused a significant improvement in MMSE (Mini-Mental State Examination) tests used for assessment of dementias. The paper presents potential mechanisms of sitagliptin activity in conditions connected with neuroinflammation with special emphasis on Alzheimer's disease.

PMID: 30186862 [PubMed - in process]

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An Assay for Systematically Quantifying the Vestibulo-Ocular Reflex to Assess Vestibular Function in Zebrafish Larvae.

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An Assay for Systematically Quantifying the Vestibulo-Ocular Reflex to Assess Vestibular Function in Zebrafish Larvae.

Front Cell Neurosci. 2018;12:257

Authors: Sun P, Zhang Y, Zhao F, Wu JP, Pun SH, Peng C, Du M, Vai MI, Liu D, Chen F

Abstract
Zebrafish (Danio rerio) larvae are widely used to study otic functions because they possess all five typical vertebrate senses including hearing and balance. Powerful genetic tools and the transparent body of the embryo and larva also make zebrafish a unique vertebrate model to study otic development. Due to its small larval size and moisture requirement during experiments, accurately acquiring the vestibulo-ocular reflex (VOR) of zebrafish larva is challenging. In this report, a new VOR testing device has been developed for quantifying linear VOR (LVOR) in zebrafish larva, evoked by the head motion about the earth horizontal axis. The system has a newly designed larva-shaped chamber, by which live fish can be steadily held without anesthesia, and the system is more compact and easier to use than its predecessors. To demonstrate the efficacy of the system, the LVORs in wild-type (WT), dlx3b and dlx4b morphant zebrafish larvae were measured and the results showed that LVOR amplitudes were consistent with the morphological changes of otoliths induced by morpholino oligonucleotides (MO). Our study represents an important advance to obtain VOR and predict the vestibular conditions in zebrafish.

PMID: 30186115 [PubMed]

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Back muscle activity and sagittal spinal alignment during quadruped upper and lower extremity lift in young men with low back pain history

Publication date: Available online 6 September 2018

Source: Gait & Posture

Author(s): Mitsuhiro Masaki, Hiroshige Tateuchi, Yumiko Koyama, Kaoru Sakuma, Naoki Otsuka, Noriaki Ichihashi

ABSTRACT

Background

Quadruped upper and lower extremity lift (QULEL) is performed for selective training of the lumbar multifidus muscle in patients with low back pain (LBP) or individuals with LBP history (LBPH). However, the activities of the back muscles and sagittal spinal alignment during QULEL are not clarified in individuals with LBPH.

Research question

This study aimed to analyze the activities of the back muscles and sagittal spinal alignment during QULEL in young male with LBPH.

Methods

The study comprised 9 asymptomatic young men and 8 young men with LBPH. The activities of the lumbar multifidus, latissimus dorsi and thoracic erector spinae, and lumbar erector spinae muscles were measured using surface electromyography. The flexion angles of the upper and lower thoracic spine, and extension angle of the lumbar spine were measured using a 6-DF electromagnetic motion tracking system. The association with LBPH was investigated using multiple logistic regression analysis with a forward selection method, with the activities of the back muscles, sagittal spinal alignment, age, body height, and body weight as independent variables.

Results

Multiple logistic regression analysis (p = 0.0002) showed that the activity of the latissimus dorsi and thoracic erector spinae muscles in the side on which the lower extremity was lifted and body height were significant and independent determinants of LBPH, but other factors were not.

Significance

The results of this study suggest that the activity of the latissimus dorsi and thoracic erector spinae muscles increases while there are no decrease in activity of the lumbar multifidus muscle and excessive extension of the lumbar spine during QULEL in young men with LBPH.

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The Influence of Crouch Gait on Sagittal Trunk Position and Lower Lumbar Spinal Loading in Children with Cerebral Palsy

Publication date: Available online 6 September 2018

Source: Gait & Posture

Author(s): D Kiernan, R O’Sullivan

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Back muscle activity and sagittal spinal alignment during quadruped upper and lower extremity lift in young men with low back pain history

Publication date: Available online 6 September 2018

Source: Gait & Posture

Author(s): Mitsuhiro Masaki, Hiroshige Tateuchi, Yumiko Koyama, Kaoru Sakuma, Naoki Otsuka, Noriaki Ichihashi

ABSTRACT

Background

Quadruped upper and lower extremity lift (QULEL) is performed for selective training of the lumbar multifidus muscle in patients with low back pain (LBP) or individuals with LBP history (LBPH). However, the activities of the back muscles and sagittal spinal alignment during QULEL are not clarified in individuals with LBPH.

Research question

This study aimed to analyze the activities of the back muscles and sagittal spinal alignment during QULEL in young male with LBPH.

Methods

The study comprised 9 asymptomatic young men and 8 young men with LBPH. The activities of the lumbar multifidus, latissimus dorsi and thoracic erector spinae, and lumbar erector spinae muscles were measured using surface electromyography. The flexion angles of the upper and lower thoracic spine, and extension angle of the lumbar spine were measured using a 6-DF electromagnetic motion tracking system. The association with LBPH was investigated using multiple logistic regression analysis with a forward selection method, with the activities of the back muscles, sagittal spinal alignment, age, body height, and body weight as independent variables.

Results

Multiple logistic regression analysis (p = 0.0002) showed that the activity of the latissimus dorsi and thoracic erector spinae muscles in the side on which the lower extremity was lifted and body height were significant and independent determinants of LBPH, but other factors were not.

Significance

The results of this study suggest that the activity of the latissimus dorsi and thoracic erector spinae muscles increases while there are no decrease in activity of the lumbar multifidus muscle and excessive extension of the lumbar spine during QULEL in young men with LBPH.

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The Influence of Crouch Gait on Sagittal Trunk Position and Lower Lumbar Spinal Loading in Children with Cerebral Palsy

Publication date: Available online 6 September 2018

Source: Gait & Posture

Author(s): D Kiernan, R O’Sullivan

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Hearing and Auditory Processing Abilities in Primary School Children with Learning Difficulties

Objectives: This study aimed to investigate hearing and auditory processing ability in primary school children with learning difficulties (LD). Design: A nonrandomized, cross-sectional single measure research design was used. A total of 486 children, aged 7.7 to 10.8 years and attending years 3 and 4 in six primary schools, were classified as having an LD (n = 67) or being typically developing (TD, n = 419). This classification was based on a Learning Score generated from their school report results and National Assessment Program – Literacy and Numeracy scores. All children attempted a conventional hearing assessment (CHA) involving pure-tone audiometry, tympanometry, acoustic reflexes (AR), and otoacoustic emissions (OAEs). Children returning pure-tone audiometry results within normal limits also attempted an auditory processing assessment (APA) including dichotic digits (DD) and low-pass filtered speech (LPFS) tests. Results: In children with LD, 21/67 (31.4%) failed the CHA, 20/58 (34.5%) failed the APA, and 32/58 (55.2%) failed the overall hearing assessment (OHA) if they failed either or both CHA and APA. In comparison, in TD children, 55/413 (13.3%) failed the CHA, 52/314 (16.6%) failed the APA, and 86/313 (27.5%) failed the OHA. Proportionally, children with LD were 2.4 times more likely than TD children to fail the CHA, 2.1 times more likely to fail the APA, and 2.0 times more likely to fail the OHA. In children who had completed the OHA, multiple linear regressions showed average AR thresholds, DD scores, and LPFS scores explained 13 to 18% of the variance in the Learning Score. Conclusion: The potential for hearing impairment should be investigated in children with LD. These investigations should begin with CHA, and for children returning normal-hearing thresholds, should continue with measures of AR, DD, and LPFS, to ensure these children receive the appropriate auditory support needed to enhance their learning. ACKNOWLEDGMENTS: All authors listed in this article contributed equally to this work. R.C., J.K., and W.J.W. designed the study. R.C. collected data with the patients. All authors discussed the results and implications and commented on the article at all stages. The authors have no conflicts of interest to disclose. Address for correspondence: Seong Min Robyn Choi, Hearing Research Unit for Children, Discipline of Audiology, School of Health and Rehabilitation Sciences, The University of Queensland, St Lucia, QLD 4072, Australia. E-mail: r.choi@uq.edu.au. Received January 4, 2018; accepted July 15, 2018. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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