A comparison of systemic and local dexamethasone administration: from perilymph/cochlea concentration to cochlear distribution

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): Yixu Wang, Lin Han, Tongxiang Diao, Yuanyuan Jing, Lin Wang, Hongwei Zheng, Xin Ma, Jingcui Qi, Lisheng Yu

Abstract

Different types of inner ear diseases can damage different cochlear subsites by different mechanisms. Steroids administered by different methods are commonly used for treating inner ear diseases. There is reason to believe that dexamethasone (Dex) may reach cochlear subsite targets via different pathways after administration by different methods: Intratympanic (IT), postaural (PA), and intraperitoneal (IP). The purpose of this study was to explore the cochlear concentration and distribution of Dex after administration by different methods. High-performance liquid chromatography-mass spectrometry and immunofluorescence technology were employed to measure and compare the Dex concentration in the perilymph and cochlear tissue and the cochlear distribution of Dex. IT administration resulted in higher Dex concentrations in the perilymph and cochlear tissues than those with the other administration methods. Intratympanic and postaural administration could result in higher Dex concentrations in the organ of Corti than systemic administration, but systemic administration could result in higher Dex concentrations in the stria vascularis than the other administration methods. A decreasing basal-apical gradient of Dex uptake was present in the cochlea after IT but not IP or PA administration. These results indicate that different administration methods result in different Dex distributions, which can be attributed to features of the cochlear vascular system and intracochlear diffusion. Our results provide clinicians with an experimental basis for the use of different steroid injection routes to optimize the effects on inner ear diseases with different target organs.

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Rapamycin but not Acarbose Decreases Age-Related Loss of Outer Hair Cells in the Mouse Cochlea

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): R.A. Altschuler, A. Kanicki, C. Martin, D.C. Kohrman, R.A. Miller

Abstract

Adding rapamycin or acarbose to diet at 9-10 months of age has been shown to significantly increase life span in both male and female UM-HET3 mice. The current study examined cochleae of male and female UM-HET3 mice at 22 months of age to determine if either treatment also influenced age-related loss of cochlear hair cells. A large loss of cochlear outer hair cells was observed at 22 months of age in untreated mice in both apical and basal halves of the cochlear spiral. Addition of acarbose to diet had no significant effect on the amount of outer hair cell loss at 22 months of age or in its pattern, with large loss in both apical and basal halves. The addition of rapamycin to diet, however, significantly reduced outer hair cell loss in the basal half of the cochlea at 22 months of age when compared to untreated mice. There was no significant difference between male and female mice in any of the conditions. Age-related outer hair cell loss in the apical cochlea precedes outer hair cell loss in the base in many mouse strains. The results of the present study suggest that rapamycin but not acarbose treatment can delay age-related loss of outer hair cells at doses at which each drug increases life span.

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A comparison of systemic and local dexamethasone administration: from perilymph/cochlea concentration to cochlear distribution

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): Yixu Wang, Lin Han, Tongxiang Diao, Yuanyuan Jing, Lin Wang, Hongwei Zheng, Xin Ma, Jingcui Qi, Lisheng Yu

Abstract

Different types of inner ear diseases can damage different cochlear subsites by different mechanisms. Steroids administered by different methods are commonly used for treating inner ear diseases. There is reason to believe that dexamethasone (Dex) may reach cochlear subsite targets via different pathways after administration by different methods: Intratympanic (IT), postaural (PA), and intraperitoneal (IP). The purpose of this study was to explore the cochlear concentration and distribution of Dex after administration by different methods. High-performance liquid chromatography-mass spectrometry and immunofluorescence technology were employed to measure and compare the Dex concentration in the perilymph and cochlear tissue and the cochlear distribution of Dex. IT administration resulted in higher Dex concentrations in the perilymph and cochlear tissues than those with the other administration methods. Intratympanic and postaural administration could result in higher Dex concentrations in the organ of Corti than systemic administration, but systemic administration could result in higher Dex concentrations in the stria vascularis than the other administration methods. A decreasing basal-apical gradient of Dex uptake was present in the cochlea after IT but not IP or PA administration. These results indicate that different administration methods result in different Dex distributions, which can be attributed to features of the cochlear vascular system and intracochlear diffusion. Our results provide clinicians with an experimental basis for the use of different steroid injection routes to optimize the effects on inner ear diseases with different target organs.

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Rapamycin but not Acarbose Decreases Age-Related Loss of Outer Hair Cells in the Mouse Cochlea

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): R.A. Altschuler, A. Kanicki, C. Martin, D.C. Kohrman, R.A. Miller

Abstract

Adding rapamycin or acarbose to diet at 9-10 months of age has been shown to significantly increase life span in both male and female UM-HET3 mice. The current study examined cochleae of male and female UM-HET3 mice at 22 months of age to determine if either treatment also influenced age-related loss of cochlear hair cells. A large loss of cochlear outer hair cells was observed at 22 months of age in untreated mice in both apical and basal halves of the cochlear spiral. Addition of acarbose to diet had no significant effect on the amount of outer hair cell loss at 22 months of age or in its pattern, with large loss in both apical and basal halves. The addition of rapamycin to diet, however, significantly reduced outer hair cell loss in the basal half of the cochlea at 22 months of age when compared to untreated mice. There was no significant difference between male and female mice in any of the conditions. Age-related outer hair cell loss in the apical cochlea precedes outer hair cell loss in the base in many mouse strains. The results of the present study suggest that rapamycin but not acarbose treatment can delay age-related loss of outer hair cells at doses at which each drug increases life span.

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Diagnosing Middle Ear Pathology in 6- to 9-Month-Old Infants Using Wideband Absorbance: A Risk Prediction Model

Purpose

The aim of this study was to develop a risk prediction model for detecting middle ear pathology in 6- to 9-month-old infants using wideband absorbance measures.

Method

Two hundred forty-nine infants aged 23–39 weeks (Mdn = 28 weeks) participated in the study. Distortion product otoacoustic emissions and high-frequency tympanometry were tested in both ears of each infant to assess middle ear function. Wideband absorbance was measured at ambient pressure in each participant from 226 to 8000 Hz. Absorbance results from 1 ear of each infant were used to predict middle ear dysfunction, using logistic regression. To develop a model likely to generalize to new infants, the number of variables was reduced using principal component analysis, and a penalty was applied when fitting the model. The model was validated using the opposite ears and with bootstrap resampling. Model performance was evaluated through measures of discrimination and calibration. Discrimination was assessed with the area under the receiver operating characteristic curve (AUC); and calibration, with calibration curves, which plotted actual against predicted probabilities.

Results

AUC of the fitted model was 0.887. The model validated adequately when applied to the opposite ears (AUC = 0.852) and with bootstrap resampling (AUC = 0.874). Calibration was satisfactory, with high agreement between predictions and observed results.

Conclusions

The risk prediction model had accurate discrimination and satisfactory calibration. Validation results indicate that it may generalize well to new infants. The model could potentially be used in diagnostic and screening settings. In the context of screening, probabilities provide an intuitive and flexible mechanism for setting the referral threshold that is sensitive to the costs associated with true and false-positive outcomes. In a diagnostic setting, predictions could be used to supplement visual inspection of absorbance for individualized diagnoses. Further research assessing the performance and impact of the model in these contexts is warranted.

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Facing the Challenges of Primary Progressive Aphasia: The Spousal Perspective

Purpose

Primary progressive aphasia (PPA) is a cognitive–neurodegenerative disorder. Little is known about the personal impact PPA has on those living with this condition, particularly from a spousal perspective. The aim of this qualitative study was to gain an understanding of the personal experiences of spouses living with a partner diagnosed with variant forms of PPA

Method

Thirteen spouses whose partners were diagnosed with PPA participated in 1:1 semistructured, in-depth interviews to explore their lived experiences of this illness. Using a constructivist grounded theory approach, analysis moved through a process of data-driven open and focused coding for the identification of emergent categories, themes, and subthemes that captured the challenges faced by spouses while supporting their partners.

Results

A constructivist grounded theory analysis of the interview data revealed an overarching theme of “facing the challenges of PPA” that captured the experience spouses encountered when living with a partner diagnosed with PPA. Four interdependent and overlapping themes that sat within this overarching theme included acknowledging disconnect in the spousal relationship, living the decline, readjusting sense of self, and getting on with living. Each of these core themes revealed how spouses dealt with the ongoing and evolving challenges of PPA, particularly concerning changing relational dynamics with their partner and adjusting their own self-conceptualization.

Conclusions

Greater understanding of the spousal experiences of PPA is crucial to the development of intervention to help sustain spouses' emotional and relational connections with their partner.

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Information Content and Efficiency in the Spoken Discourse of Individuals With Parkinson's Disease

Purpose

This study compared the information content and information efficiency of spoken language in individuals with Parkinson's disease (PD) to a healthy comparator group.

Method

Nineteen participants with PD and 19 healthy older adults completed the prospective, cross-sectional study. In the primary analysis, 2 language samples elicited by standardized protocols were analyzed for group differences using standard discourse informativeness measures including main events (MEs; Wright, Capilouto, Wagovich, Cranfill, & Davis, 2005) analyzed as %MEs and correct information units (CIUs; Nicholas & Brookshire, 1993) analyzed as %CIUs and CIUs/min. In exploratory analyses, the following were examined: (a) associations among conceptual (%MEs) and lexical (%CIUs and CIUs/min) measures and (b) associations among informativeness measures and age, education, disease severity/duration, global cognition, speech intelligibility, and a verb confrontation naming measure.

Results

In the primary analysis, the PD group differed significantly from the control group on conceptual (%MEs) and lexical measures of content (%CIUs) and efficiency (CIUs/min). In exploratory analyses, for the control group %MEs were significantly correlated with CIUs/min. Significant associations among conceptual and lexical measures of informativeness were not found in the PD group. For controls, there were no significant correlations between informativeness measures and any of the demographic or speech/cognitive/language variables. In the PD group, there was a significant and positive association between CIUs/min and Dementia Rating Scale–Second Edition scores (Mattis, 2001). A significant but negative correlation was found between CIUs/min and motor severity scores. However, %MEs and verb naming were significantly and positively correlated.

Conclusions

Individuals with PD without dementia demonstrated reduced discourse informativeness that reflects disruptions to both conceptual and lexical discourse processes. In exploratory analyses, reduced efficiency of information content was associated with global cognition and motor severity. Clinical and research implications are discussed within a Cognitivist framework of discourse production (Sheratt, 2007).

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Diagnosing Middle Ear Pathology in 6- to 9-Month-Old Infants Using Wideband Absorbance: A Risk Prediction Model

Purpose

The aim of this study was to develop a risk prediction model for detecting middle ear pathology in 6- to 9-month-old infants using wideband absorbance measures.

Method

Two hundred forty-nine infants aged 23–39 weeks (Mdn = 28 weeks) participated in the study. Distortion product otoacoustic emissions and high-frequency tympanometry were tested in both ears of each infant to assess middle ear function. Wideband absorbance was measured at ambient pressure in each participant from 226 to 8000 Hz. Absorbance results from 1 ear of each infant were used to predict middle ear dysfunction, using logistic regression. To develop a model likely to generalize to new infants, the number of variables was reduced using principal component analysis, and a penalty was applied when fitting the model. The model was validated using the opposite ears and with bootstrap resampling. Model performance was evaluated through measures of discrimination and calibration. Discrimination was assessed with the area under the receiver operating characteristic curve (AUC); and calibration, with calibration curves, which plotted actual against predicted probabilities.

Results

AUC of the fitted model was 0.887. The model validated adequately when applied to the opposite ears (AUC = 0.852) and with bootstrap resampling (AUC = 0.874). Calibration was satisfactory, with high agreement between predictions and observed results.

Conclusions

The risk prediction model had accurate discrimination and satisfactory calibration. Validation results indicate that it may generalize well to new infants. The model could potentially be used in diagnostic and screening settings. In the context of screening, probabilities provide an intuitive and flexible mechanism for setting the referral threshold that is sensitive to the costs associated with true and false-positive outcomes. In a diagnostic setting, predictions could be used to supplement visual inspection of absorbance for individualized diagnoses. Further research assessing the performance and impact of the model in these contexts is warranted.

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Facing the Challenges of Primary Progressive Aphasia: The Spousal Perspective

Purpose

Primary progressive aphasia (PPA) is a cognitive–neurodegenerative disorder. Little is known about the personal impact PPA has on those living with this condition, particularly from a spousal perspective. The aim of this qualitative study was to gain an understanding of the personal experiences of spouses living with a partner diagnosed with variant forms of PPA

Method

Thirteen spouses whose partners were diagnosed with PPA participated in 1:1 semistructured, in-depth interviews to explore their lived experiences of this illness. Using a constructivist grounded theory approach, analysis moved through a process of data-driven open and focused coding for the identification of emergent categories, themes, and subthemes that captured the challenges faced by spouses while supporting their partners.

Results

A constructivist grounded theory analysis of the interview data revealed an overarching theme of “facing the challenges of PPA” that captured the experience spouses encountered when living with a partner diagnosed with PPA. Four interdependent and overlapping themes that sat within this overarching theme included acknowledging disconnect in the spousal relationship, living the decline, readjusting sense of self, and getting on with living. Each of these core themes revealed how spouses dealt with the ongoing and evolving challenges of PPA, particularly concerning changing relational dynamics with their partner and adjusting their own self-conceptualization.

Conclusions

Greater understanding of the spousal experiences of PPA is crucial to the development of intervention to help sustain spouses' emotional and relational connections with their partner.

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Information Content and Efficiency in the Spoken Discourse of Individuals With Parkinson's Disease

Purpose

This study compared the information content and information efficiency of spoken language in individuals with Parkinson's disease (PD) to a healthy comparator group.

Method

Nineteen participants with PD and 19 healthy older adults completed the prospective, cross-sectional study. In the primary analysis, 2 language samples elicited by standardized protocols were analyzed for group differences using standard discourse informativeness measures including main events (MEs; Wright, Capilouto, Wagovich, Cranfill, & Davis, 2005) analyzed as %MEs and correct information units (CIUs; Nicholas & Brookshire, 1993) analyzed as %CIUs and CIUs/min. In exploratory analyses, the following were examined: (a) associations among conceptual (%MEs) and lexical (%CIUs and CIUs/min) measures and (b) associations among informativeness measures and age, education, disease severity/duration, global cognition, speech intelligibility, and a verb confrontation naming measure.

Results

In the primary analysis, the PD group differed significantly from the control group on conceptual (%MEs) and lexical measures of content (%CIUs) and efficiency (CIUs/min). In exploratory analyses, for the control group %MEs were significantly correlated with CIUs/min. Significant associations among conceptual and lexical measures of informativeness were not found in the PD group. For controls, there were no significant correlations between informativeness measures and any of the demographic or speech/cognitive/language variables. In the PD group, there was a significant and positive association between CIUs/min and Dementia Rating Scale–Second Edition scores (Mattis, 2001). A significant but negative correlation was found between CIUs/min and motor severity scores. However, %MEs and verb naming were significantly and positively correlated.

Conclusions

Individuals with PD without dementia demonstrated reduced discourse informativeness that reflects disruptions to both conceptual and lexical discourse processes. In exploratory analyses, reduced efficiency of information content was associated with global cognition and motor severity. Clinical and research implications are discussed within a Cognitivist framework of discourse production (Sheratt, 2007).

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Variability in Interpreting “Educational Performance” for Children With Speech Sound Disorders

Purpose

Speech sound disorders (SSDs) can have a negative impact on literacy development, social–emotional well-being, and participation across the life span. Despite this, many public schools do not provide appropriate or timely services to this population of children. In large part, this is a result of variation in how state and local agencies interpret “educational performance” as outlined within the Individuals With Disabilities Education Act. The purpose of this study was to explore which educational performance factors speech-language pathologists (SLPs) consider when determining eligibility for children with SSDs.

Method

This study surveyed public school SLPs to investigate how educational performance is interpreted for children with SSDs. Data from 575 SLPs across the United States are included.

Results

Results supported variability in interpretation of educational performance within a nationwide sample of SLPs. Specifically, SLPs appear to consider educational performance as multidimensional. We also found within-state and between-states variability, indicating ambiguity in interpreting federal mandates. Finally, caseload size and number of years of experience were significantly related to which educational performance factors SLPs chose.

Conclusion

There is significant variability across the United States with respect to factors considered part of educational performance for children with SSD. This variability reflects the general quality and specificity of guidelines and/or special education code published by individual states. Clinical and legislative recommendations are included.

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Variability in Interpreting “Educational Performance” for Children With Speech Sound Disorders

Purpose

Speech sound disorders (SSDs) can have a negative impact on literacy development, social–emotional well-being, and participation across the life span. Despite this, many public schools do not provide appropriate or timely services to this population of children. In large part, this is a result of variation in how state and local agencies interpret “educational performance” as outlined within the Individuals With Disabilities Education Act. The purpose of this study was to explore which educational performance factors speech-language pathologists (SLPs) consider when determining eligibility for children with SSDs.

Method

This study surveyed public school SLPs to investigate how educational performance is interpreted for children with SSDs. Data from 575 SLPs across the United States are included.

Results

Results supported variability in interpretation of educational performance within a nationwide sample of SLPs. Specifically, SLPs appear to consider educational performance as multidimensional. We also found within-state and between-states variability, indicating ambiguity in interpreting federal mandates. Finally, caseload size and number of years of experience were significantly related to which educational performance factors SLPs chose.

Conclusion

There is significant variability across the United States with respect to factors considered part of educational performance for children with SSD. This variability reflects the general quality and specificity of guidelines and/or special education code published by individual states. Clinical and legislative recommendations are included.

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A comparison of systemic and local dexamethasone administration: from perilymph/cochlea concentration to cochlear distribution

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): Yixu Wang, Lin Han, Tongxiang Diao, Yuanyuan Jing, Lin Wang, Hongwei Zheng, Xin Ma, Jingcui Qi, Lisheng Yu

Abstract

Different types of inner ear diseases can damage different cochlear subsites by different mechanisms. Steroids administered by different methods are commonly used for treating inner ear diseases. There is reason to believe that dexamethasone (Dex) may reach cochlear subsite targets via different pathways after administration by different methods: Intratympanic (IT), postaural (PA), and intraperitoneal (IP). The purpose of this study was to explore the cochlear concentration and distribution of Dex after administration by different methods. High-performance liquid chromatography-mass spectrometry and immunofluorescence technology were employed to measure and compare the Dex concentration in the perilymph and cochlear tissue and the cochlear distribution of Dex. IT administration resulted in higher Dex concentrations in the perilymph and cochlear tissues than those with the other administration methods. Intratympanic and postaural administration could result in higher Dex concentrations in the organ of Corti than systemic administration, but systemic administration could result in higher Dex concentrations in the stria vascularis than the other administration methods. A decreasing basal-apical gradient of Dex uptake was present in the cochlea after IT but not IP or PA administration. These results indicate that different administration methods result in different Dex distributions, which can be attributed to features of the cochlear vascular system and intracochlear diffusion. Our results provide clinicians with an experimental basis for the use of different steroid injection routes to optimize the effects on inner ear diseases with different target organs.

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Rapamycin but not Acarbose Decreases Age-Related Loss of Outer Hair Cells in the Mouse Cochlea

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): R.A. Altschuler, A. Kanicki, C. Martin, D.C. Kohrman, R.A. Miller

Abstract

Adding rapamycin or acarbose to diet at 9-10 months of age has been shown to significantly increase life span in both male and female UM-HET3 mice. The current study examined cochleae of male and female UM-HET3 mice at 22 months of age to determine if either treatment also influenced age-related loss of cochlear hair cells. A large loss of cochlear outer hair cells was observed at 22 months of age in untreated mice in both apical and basal halves of the cochlear spiral. Addition of acarbose to diet had no significant effect on the amount of outer hair cell loss at 22 months of age or in its pattern, with large loss in both apical and basal halves. The addition of rapamycin to diet, however, significantly reduced outer hair cell loss in the basal half of the cochlea at 22 months of age when compared to untreated mice. There was no significant difference between male and female mice in any of the conditions. Age-related outer hair cell loss in the apical cochlea precedes outer hair cell loss in the base in many mouse strains. The results of the present study suggest that rapamycin but not acarbose treatment can delay age-related loss of outer hair cells at doses at which each drug increases life span.

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A comparison of systemic and local dexamethasone administration: from perilymph/cochlea concentration to cochlear distribution

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): Yixu Wang, Lin Han, Tongxiang Diao, Yuanyuan Jing, Lin Wang, Hongwei Zheng, Xin Ma, Jingcui Qi, Lisheng Yu

Abstract

Different types of inner ear diseases can damage different cochlear subsites by different mechanisms. Steroids administered by different methods are commonly used for treating inner ear diseases. There is reason to believe that dexamethasone (Dex) may reach cochlear subsite targets via different pathways after administration by different methods: Intratympanic (IT), postaural (PA), and intraperitoneal (IP). The purpose of this study was to explore the cochlear concentration and distribution of Dex after administration by different methods. High-performance liquid chromatography-mass spectrometry and immunofluorescence technology were employed to measure and compare the Dex concentration in the perilymph and cochlear tissue and the cochlear distribution of Dex. IT administration resulted in higher Dex concentrations in the perilymph and cochlear tissues than those with the other administration methods. Intratympanic and postaural administration could result in higher Dex concentrations in the organ of Corti than systemic administration, but systemic administration could result in higher Dex concentrations in the stria vascularis than the other administration methods. A decreasing basal-apical gradient of Dex uptake was present in the cochlea after IT but not IP or PA administration. These results indicate that different administration methods result in different Dex distributions, which can be attributed to features of the cochlear vascular system and intracochlear diffusion. Our results provide clinicians with an experimental basis for the use of different steroid injection routes to optimize the effects on inner ear diseases with different target organs.

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Rapamycin but not Acarbose Decreases Age-Related Loss of Outer Hair Cells in the Mouse Cochlea

Publication date: Available online 7 September 2018

Source: Hearing Research

Author(s): R.A. Altschuler, A. Kanicki, C. Martin, D.C. Kohrman, R.A. Miller

Abstract

Adding rapamycin or acarbose to diet at 9-10 months of age has been shown to significantly increase life span in both male and female UM-HET3 mice. The current study examined cochleae of male and female UM-HET3 mice at 22 months of age to determine if either treatment also influenced age-related loss of cochlear hair cells. A large loss of cochlear outer hair cells was observed at 22 months of age in untreated mice in both apical and basal halves of the cochlear spiral. Addition of acarbose to diet had no significant effect on the amount of outer hair cell loss at 22 months of age or in its pattern, with large loss in both apical and basal halves. The addition of rapamycin to diet, however, significantly reduced outer hair cell loss in the basal half of the cochlea at 22 months of age when compared to untreated mice. There was no significant difference between male and female mice in any of the conditions. Age-related outer hair cell loss in the apical cochlea precedes outer hair cell loss in the base in many mouse strains. The results of the present study suggest that rapamycin but not acarbose treatment can delay age-related loss of outer hair cells at doses at which each drug increases life span.

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

Related Articles

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.

Related Articles

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

Related Articles

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.

Related Articles

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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