bluuebunny/crossref_metadata_2025 huggingface dataset:
Allometric scaling models: history, use, and misuse in translating resveratrol from basic science to human clinical applications
Authors: Smoliga James M. , Blanchard Otis L.
Published: December 2019

Background: Determination of the first-in-human and pharmacologically active dosage for drugs and nutraceutical compounds is a critical step in study design and product development.  Allometric scaling is a form of mathematic modeling commonly used to convert dosages between species.  While allometric scaling allows for quick and straightforward conversions between species, it is often misunderstood and misused in translational clinical applications.  This is readily demonstrated in the case of resveratrol – a polyphenol which is found in red wine.  In the past decade, a considerable amount of research has emerged regarding the health benefits of the resveratrol supplementation.  Although data from rodent models suggests that resveratrol can have major effects on cardiometabolic and neurologic health, human clinical trials have had mixed results.  While some human clinical trials have yielded encouraging results, a few noteworthy trials have reported that seemingly appropriate allometry-derived dosages of resveratrol did not provide the expected health benefits reported in animal models.Here, we discuss the history of various models within allometry, including their advantages, disadvantages, and nuances from a clinical perspective.  This historical information will provide some insight into why dosages recommended from allometric scaling are appropriate in some circumstances and inappropriate in others.  We will then demonstrate how allometric models have been utilized to translate dosages of resveratrol from rodent models into the dosages recommended for human clinical trials.  Pharmacokinetic data from various human clinical trials will be summarized and compared to data predicted from allometric models.  Data from selected human clinical trials will then synthesized to demonstrate the dosage-dependent effects of resveratrol, and provide further insight into the appropriate use of allometric models for selecting resveratrol dosage.  Together, this information will promote a greater understanding of the role of allometric scaling in dose selection and provide an explanation for some of the apparent inconsistencies in translational research regarding resveratrol.Keywords: allometric scaling, dose conversion, bioavailability, pharmacokinetics, resveratrol
Antioxidant activity and phenolic contents of Ajwa date and their effect on lipo-protein profile
Authors: Khalid Sumaira , Ahmad Dr. Asif , Kaleem Muhammad
Published: December 2019

Background: Date pits although being rich in phenolic and antioxidant content are neglected part and treated as waste product. Ethanobotanical records indicates potential of ajwa dates pits and flesh having phenolics, antioxidants and some other nutrients.Objective: The study was planned to extract the phenolic contents and antioxidant activity of ajwa date flesh and pits in comparison to local date varieties, in three different solvents with three different concentrations and to observe their effect on high lipo-protein profile of albino mice.Materials and Methods: Three solvents viz. Methanol, Ethanol and Acetone was used at concentration of 70%, 80% and 90% to make nutraceutical extracts. These extracts were characterized for numerous nutritional parameters.  Correlation of flavonoid with phenolic, DPPH, and ABTS and other parameters were studied. The above extracted ajwa flesh and pits extracts were then administrated to high cholesterol induced albino mice under three different treatments (10%, 20% and 30%) in four different groups where one group was studied as control.Results: Pits appeared as significantly richest source for total phenols, total flavonoid contents. Such extracts from pits were high in DPPH and ABTS activity as compared to flesh in all date cultivars being highest in ajwa pits (3932.3 mg GAE/100g, 2956.2 mg QEC/100g, 96.3% and 86.2% respectively). In comparative analysis of solvents, 80% ethanol extracted highest antioxidant activity for both DPPH and ABTS assay in all date varieties and their parts. Behavior of solvent for polyphenols (Total phenols and total flavonoids) extraction was highly variable so that a single solvent cannot be recommended for extraction. Highly significant correlation of flavonoids with DPPH was observed in pits part. Phenolic contents positively correlated with flavonoids, DPPH and ABTS. DPPH and ABTS also revealed strongly positive increasing correlation. In PCA analysis phenolic contents, flavonoid contents and antioxidant activity showed a closeness in case of pits while showed weak relation in flesh parts.  Furthermore, results also depicted that 30% extracts of ajwa pits have higher effect on percent reduction of total protein, total triglycerides, total cholesterol and LDL-C levels while also significantly increased the percent HDL-C levels in treated albino miceConclusion: The work identifies variability among flesh and pits of ajwa date and local date varieties for their polyphenols contents and antioxidant activity and their health beneficial effect against high Lipo-protein profile that can be used as an active ingredient against different maladies in food products and supplements. Key words: Ajwa, Phenolics, antioxidants, PCA
Anti-atherosclerotic effects of tomatoes
Authors: Yanai Hidekatsu
Published: December 2019

Background: Tomatoes are rich in lycopene which is responsible for the red color seen in tomatoes. Several reports have suggested the role of lycopene in the prevention of cardiovascular diseases. Here, we systematically reviewed the interventional studies using tomatoes or tomato products, to understand anti-atherosclerotic effects of tomato as a functional food. We found that relatively great number of interventional studies reported anti-atherosclerotic effects of tomatoes such as anti-obesity effect, hypotensive effect, improvement of lipid/glucose metabolism and endothelial function, anti-oxidative and anti-inflammatory effect, and also anti-platelet effect, though, which were denied by some studies. Furthermore, we discovered that the cooking methods significantly affect anti-atherosclerotic effects of tomatoes.Keywords: anti-oxidative effect, atherosclerosis, body weight, tomatoes, serum lipids
Aegeline vs Statin in the treatment of Hypercholesterolemia: A comprehensive study in rat model of liver steatosis
Authors: Singh A. , Gowtham S. , Chakrapani L.N. , Ashokkumar S. , Kumar S.N. Kishore , Prema V. , Bhavani R. Divya , Mohan T. , Sathyamoorthy Y.K.
Published: December 2019

Background: Aegeline (AG) is a natural hydroxyamide which has not been explored in depth for its potential applications in food, pharmaceutical, and cosmetic industries. Accordingly, in this study, the property of AG as antioxidant, anti-hypercholesterolemic, and an anti-aging component was explored. The hepatoprotective effect of AG on hypercholesterolemic rats was investigated for health care benefits as a hypocholesterolemic drug vs Atorvastatin (AV) for the first time.Objective: The objective was to delineate the mechanism of action of AG in impeding high cholesterol diet (HCD) induced hepatic steatosis in a rat model with special reference to antioxidant status and expression of Nuclear Factor Kappa B (NF-κB) mediated cell adhesion molecules.Methods: Thirty-six Wistar rats were divided into six groups. The pathology group rats were fed with HCD for 16 weeks and treatment groups rats were fed with HCD for 12 weeks and further supplemented with AG/AV for another 4 weeks. In vivo and in vitro experiments were carried out to find out the relative markers of the pathological condition likely Malondialdehyde (MDA), Oxidized LDL (Ox-LDL), and CRP levels were determined. Standard biochemical parameters were carried out. The expression profile by Western blot analysis was performed to assess the levels of NF-κB, Interleukin 6(IL6) and vascular cell adhesion molecule1 (VCAM1), in the hepatic tissues of various experimental groups. Additionally, histopathological examination of liver tissue sections was carried out.Results: AG administration effectively decreased the oxidative stress induced by HCD as evidenced by MDA levels. Furthermore, the lowered levels of Ox-LDL and CRP in AG administered rats deem it to be a potent anti-inflammatory agent. Compared to AV, AG had a pronounced effect in down-regulating the expression of cell adhesion molecules.Conclusion: Thus, this study validates AG to be an effective stratagem in bringing down the oxidative stress induced by HCD and can be deemed as an anti-hypercholesterolemic and anti-steatotic agent.Keywords: Aegeline, Atorvastatin, liver, hypercholesterolemia, aging
Effects of 4-week continuous ingestion of champignon extract on bowel movements and intestinal putrefaction products: a randomized, placebo-controlled, double-blinded, parallel-group comparative trial
Authors: Nishihira Jun , Nishimura Mie , Tanaka Aiko , Kagami-katsuyma Hiroyo , Yamaguchi Akihiro , Taira Toshio
Published: December 2019

Background: The aim of this study was to analyze the putrefaction products in the feces of subjects from a previous study (age range 50–79 years) which assessed the improvement of breath, body, and fecal odor after ingesting champignon extract.Methods: The study was designed as a randomized, placebo-controlled, double-blinded, and parallel-group comparative trial. Subjects were divided into four groups, including the placebo (n=20), champignon extract at 50 mg/day (n=20), champignon extract at 500 mg/day (n=20), and champignon extract at 1000 mg/day (n=20) for 4 weeks.Results: The results revealed significant reduction in ammonia and p-cresol levels (both of which are intestinal putrefaction products) among subjects who ingested 50, 500, and 1000 mg of champignon extract per day compared with subjects in the placebo group. Additionally, a significant difference was observed in indole levels in the group that consumed 500 mg/day of the extract compared to the placebo group.Conclusions: The re-analysis of bowel movement in each test group revealed that the extract improved the number of days with bowel movement, number of bowel movements, and stool volume, which suggests the intestinal environment was improved.Clinical trial registration: UMIN000014256Keywords: ammonia, champignon, fecal odor, p-cresol, putrefaction
Leptin, hs-CRP and HOMA-IR in patients with type 2 diabetes: The role of different levels of vitamin D deficiency
Authors: Salehi‍ Salome Sadat , Rabizadeh Soghra , Karimpour Sahar Karimpour Reyhan Reyhan , Mouodi Marjan , Nakhjavani Manouchehr , Esteghamati Alireza , Mirmiranpour Hossein
Published: December 2019

Background: To evaluate the effects of different levels of vitamin D deficiency on blood glucose, leptin, and high sensitivity C-reactive protein (hs-CRP), insulin resistance and their associations.Methods: We quantified serum vitamin D level, hs-CRP, leptin, and fasting  blood  sugar (FBS)  levels in 25 type-2 diabetic patients with very low serum levels of 25-hydroxy vitamin D (deficient), ≤15 ng/ml; and 25 age, sex, and body mass index (BMI)-matched  type-2 diabetic patients with low serum levels of 25-hydroxy vitamin D (insufficient), 16 to 30 ng/ml. Homeostasis model assessment of insulin resistance (HOMA-IR) was  calculated  by  a  formula based  upon  values  of  FBS and insulin concentrations.Results: The mean value of vitamin D levels was 7.67±3.10 in vitamin D deficient group and 23.20±9.97 in vitamin D insufficient group. Patients with vitamin D deficiency had significantly higher FBS, postprandial glucose (PPG) and hemoglobin A1C (HbA1C) as compared to vitamin D insufficient group (p<0.01). We studied correlations of hs-CRP, HOMA-IR, and leptin in both vitamin D insufficient and deficient groups. There were significant positive correlations between leptin with hs-CRP (r = 0.58, p<0.01) and with HOMA-IR (r = 0.49, p<0.05) in vitamin D deficient group; Which these correlations remained significant after multiple adjustment for age, sex, BMI, systolic and diastolic blood pressure.Conclusion: In conclusion vitamin D deficient diabetic patients had elevated FBS, PPG and HbA1C compared with insufficient ones. The results also could possibly point the effect of vitamin D deficiency level on leptin associations with hs-CRP and insulin resistance.Keywords: Vitamin D deficiency, type 2 diabetes, leptin, C reactive protein, homeostasis model assessment of insulin resistance
Effects of six weeks consumption of coconut milk oil on vascular functions and fasting blood glucose and lipid profile in middle-aged male rats
Authors: Naphatthalung Jomkarn , Chairuk Pilaipan , Kanokwiroon Kanyanatt , Radenahmad Nisaudah , Jansakul Chaweewan
Published: December 2019

Background: Coconut milk consumption in middle-aged male rats can cause increased blood vessel endothelial nitric oxide synthase (eNOS) and cystathionine-γ-lyase (CSE) protein expression, and decreased fasting blood glucose.Objective: The present study aimed to investigate whether coconut milk oil (CO), the major constituents of the coconut milk, was responsible for those effects.Methods: CO was isolated from dried fresh coconut milk and gavaged (1 and 3 ml/kg) to middle-aged male rats for 6 weeks. Blood biochemistry, lipid profile and vascular functions were investigated.Results: In comparison to a distilled water control group, no differences were observed in any of the parameters studied in the group fed 1 ml/kg of CO except for an increase in retroperitoneal fat accumulation. Feeding 3 ml/kg of CO caused decreased fasting blood glucose, plasma alkaline phosphatase and blood urea nitrogen and liver cell lipid accumulation, but increased retroperitoneal fat tissue. It also caused decreased maximal contractile response of endothelium-intact thoracic aortic rings to phenylephrine although the effect disappeared in the presence of N-nitro-L-arginine (L-NA) or removal of the endothelium. DL-propargylglycine together with L-NA caused a higher contraction to phenylephrine in the CO-treated groups than in the control group. It also caused an increase in vasodilatation to acetylcholine, but not to glyceryl trinitrate, of the phenylephrine pre-contracted aortic rings. CO treatment caused increased vascular wall eNOS and CSE protein expression.Conclusion: CO at a dose of 3 ml/kg causes some decrease in cardiovascular risk factors in middle-aged male rats, although the amount of CO consumption should be limited as it caused an increase in retroperitoneal fat.
Batch corn thresher
Authors: Pogosyan V. M
Published: December 2019

Nowadays for the threshing of individual corn cobs at the selection stage there are no commercially available threshing devices of Russian production. Therefore, Russian scientists began to actively develop selective corn threshers, in particular, in the Krasnodar Research Institute of Agriculture named after P. Lukyanenko a batch corn thresher was developed. On the basis of research carried out in the Kuban State Agrarian University, a scheme of a single-corn maize thresher providing a higher quality of maize threshing in comparison with existing structures is proposed. Therefore, the goal of our study is to improve the quality of threshing cobs of corn selection material. The relationship of the geometric parameters of the proposed device and their influence on the technological process of cobs threshing were analyzed. As a result, the conclusion was made that each cob, depending on its diameter, is threshed by one of the elementary threshing devices, i.e., the correspondence of the gaps of the threshing gap with the diameter of the cobs is achieved automatically. There is no need to adjust the gaps of the threshing gap. Thus, the parameters of the process of threshing the сobs of the corn selection material are optimized and the quality of the threshing is improved.
Listing's plane and the 3D-VOR in microgravity – The role of the otolith afferences
Authors: Clarke Andrew H. , Just K. , Krzok W. , Schönfeld U.
Published: December 2019

The study addresses the question as to what extent the otolith-mediated gravity vector maintains the stability of the coordinate frames of the vestibulo-ocular reflex and the oculomotor system, described by Listing's Plane. Under normal 1 G conditions it has been demonstrated in the monkey that Listing's Plane (LP) and the 3D vestibulo-ocular response (3D-VOR) are close to collinear [10]. In the present study the coordinate frames of the oculomotor system and the three-dimensional vestibulo-ocular reflex (3D-VOR) system were measured under one-g gravity conditions and during a period of prolonged microgravity, on-board the International Space Station (ISS). To this end, the coordinate frame of the oculomotor system is described in Listing's coordinates and that of the 3D-VOR system by the minimal gain vector. The findings demonstrate that under Earthbound, one-g conditions the two coordinate frames diverge by approximately 20° in the human. In the absence of the gravity vector the radical loss in the otolith-mediated contribution to the dynamic VOR leads to a reduction of the torsional VOR component and in turn to a forward tilt of the oculomotor coordinate frame, described by the minimal gain vector. In contrast, the torsional component of LP during horizontal and vertical saccades was found to increase, resulting in a backward tilt of LP. Together with the backward tilt of LP a small but consistent change in LP vergence was observed. The thickness of LP did not appear to change in the absence of gravity. The changes in coordinate frame orientation persisted over the six-month periods spent in zero gravity. The postflight measurements demonstrate that re-adaptation to preflight values proceeds over several days to weeks. The findings demonstrate that the gravity vector represents a common reference for vestibular and oculomotor responses. They also support the idea that the gravity vector provides a central reference for the entire sensorimotor complex.
Two-dimensional analysis of head-shaking nystagmus in patients with Meniere's disease
Authors: Kim C.-H. , Shin J.E. , Kim T.S. , Shim B.S. , Park H.J.
Published: December 2019

The HSN test is a simple examination that can be easily performed by clinicians, however only a few studies have analyzed the 2-dimensional characteristics of HSN in patients with MD. The objective of the study was to characterize different types of 2-dimensional head-shaking nystagmus (HSN) in patients with Meniere's disease (MD). Sixty-five patients with definite MD were enrolled. HSN was considered pathologic, if slow-phase velocity (SPV) was ⩾ 4°/s and was classified as paretic or recovery according to the direction, and as monophasic or biphasic according to the presence of direction change. HSN was categorized as pure horizontal, mixed or pure vertical. When vertical SPV was larger than horizontal SPV, HSN was categorized as perverted. Forty-four patients (68%) had pathologic HSN and 28 patients (43%) had pathologic canal paresis. Monophasic-paretic HSN was the most common and followed by biphasic-paretic HSN, monophasic-recovery HSN and biphasic-recovery HSN. Delayed-peak monophasic-paretic HSN, which was not observed in vestibular neuritis, was found in 6 patients with MD. Thirty-three patients (51%) had a vertical component, which was monophasic and downbeat in 32 (97%). Every pathologic HSN in horizontal plane had higher SPV in horizontal plane than that of vertical plane. Perverted HSN was found in 4 patients, of whom 3 had pure vertical and one had mixed type HSN. Our data showed that HSN is a sensitive detector of vestibular dysfunction. HSN showed diverse types with a new type of delayed-peak HSN. Vertical components of HSN were observed in about half, but they were negligible compared to horizontal components. Weak perverted HSN (vertical SPV ⩽ 4°/s) could be found in patients with MD.
Dynamic visual acuity (DVA) during locomotion for targets at near and far distances: Effects of aging, walking speed and head-trunk coupling
Authors: Deshpande Nandini , Tourtillott Brandon M. , Peters Brian T. , Bloomberg Jacob J.
Published: December 2019

This study examined effects of aging, head-trunk coupling (HTcoupling) and walking speed on dynamic visual acuity (DVA) at near and far viewing distances. Ten healthy participants were recruited in 3 groups; young: 20–33 years, Older1: 65–74 years, Older2: 75–85 years. The binocular DVA was measured while walking on a treadmill at 0.75 and 1.5 m/s speeds. The optotype display was placed at 0.5 m for NearDVA and at 3.0 m for FarDVA. On randomly selected trials, HTcoupling was achieved by using a collar. A mix-factor ANOVA (age-group x HTcoupling x speed) was performed separately for the Near and FarDVA. NearDVA declined with HTcoupling (p=0.021). Additionally, NearDVA worsened at the faster speed (p< 0.001). At 1.5 m/s speed the differences between Young and Older2 groups were significant (p=0.012) and those between Older1 and Older2 were marginal (p=0.085). FarDVA declined at the faster speed (p< 0.001) with no effect of HTcoupling or age-group. NearDVA is more sensitive to normal aging process. These age-related deficits become more apparent at higher walking speeds. Effect of HTcoupling on NearDVA suggests a possible additive effect of insufficient dampening of the vertical movement of the overall head-trunk complex and inability of the linear vestibulo-ocular reflex to compensate for the consequent high discrepancy.
Impact of oral vitamin C on histamine levels and seasickness
Authors: Jarisch R. , Weyer D. , Ehlert E. , Koch C.H. , Pinkowski E. , Jung P. , Kähler W. , Girgensohn R. , Kowalski J. , Weisser B. , Koch A.
Published: December 2019

Background: Seasickness is a risk aboard a ship. Histamine is postulated as a causative agent, inversely related to the intake of vitamin C. Persons with mastocytosis experienced improvement of nausea after the intake of vitamin C. Objective: To determine whether vitamin C suppresses nausea in 70 volunteers who spent 20 minutes in a life raft, exposed to one-meter-high waves in an indoor pool. Method: Double-blind placebo-controlled crossover study. Two grams of vitamin C or placebo was taken one hour before exposure. Blood samples were taken one hour before and after exposure to determine histamine, diamine oxidase, tryptase, and vitamin C levels. Symptom scores were noted on a visual analog scale. On the second day the test persons were asked which day they had felt better. Results: Seven persons without symptoms were excluded from the analysis. Test persons had less severe symptoms after the intake of vitamin C (p< 0.01). Scores on the visual analog scale were in favor of vitamin C, but the difference was not significant. Twenty-three of 63 persons wished to leave the raft earlier: 17 after the intake of placebo and 6 after the intake of vitamin C (p< 0.03). Women (p< 0.02) and men below 27 years of age (p< 0.02) had less pronounced symptoms after the intake of vitamin C. Histamine (p< 0.01) and DAO levels were increased after the intake of vitamin C (p< 0.001) and after placebo (n.s.). The fact that the second test day was rated less stressful by most volunteers is indicative of habituation. Conclusions: Some of the data show that vitamin C is effective in suppressing symptoms of seasickness, particularly in women and men younger than 27 years of age, and is devoid of side effects. Histamine levels were initially increased after the test persons had been exposed to waves.
The dynamic representation of gravity is suspended when the idiotropic vector is misaligned with gravity
Authors: De Sá Teixeira Nuno Alexandre , Hecht Heiko
Published: December 2019

Background: When people are asked to indicate the vanishing location of a moving target, errors in the direction of motion (representational momentum) and in the direction of gravity (representational gravity) are usually found. These errors possess a temporal course wherein the memory for the location of the target drifts downwards with increasing temporal intervals between target's disappearance and participant's responses (representational trajectory). Objective: To assess if representational trajectory is a body-referenced or a world-referenced phenomenon. Methods: A behavioral localization method was employed with retention times between 0 and 1400 ms systematically imposed after the target's disappearance. The target could move horizontally (rightwards or leftwards) or vertically (upwards or downwards). Body posture was varied in a counterbalanced order between sitting upright and lying on the side (left lateral decubitus position). Results: In the upright task, the memory for target location drifted downwards with time in the direction of gravity. This time course did not emerge for the decubitus task, where idiotropic dominance was found. Conclusions: The dynamic visual representation of gravity is neither purely body-referenced nor world-referenced. It seems to be modulated instead by the relationship between the idiotropic vector and physical gravity.
Ethanol consumption impairs vestibulo-ocular reflex function measured by the video head impulse test and dynamic visual acuity
Authors: Roth Thomas N. , Weber Konrad P. , Wettstein Vincent G. , Marks Guy B. , Rosengren Sally M. , Hegemann Stefan C.A.
Published: December 2019

Ethanol affects many parts of the nervous system, from the periphery to higher cognitive functions. Due to the established effects of ethanol on vestibular and oculomotor function, we wished to examine its effect on two new tests of the vestibulo-ocular reflex (VOR): the video head impulse test (vHIT) and dynamic visual acuity (DVA). We tested eight healthy subjects with no history of vestibular disease after consumption of standardized drinks of 40% ethanol. We used a repeated measures design to track vestibular function over multiple rounds of ethanol consumption up to a maximum breath alcohol concentration (BrAC) of 1.38 per mil. All tests were normal at baseline. VOR gain measured by vHIT decreased by 25% at the highest BrAC level tested in each subject. Catch-up saccades were negligible at baseline and increased in number and size with increasing ethanol consumption (from 0.13° to 1.43° cumulative amplitude per trial). DVA scores increased by 86% indicating a deterioration of acuity, while static visual acuity (SVA) remained unchanged. Ethanol consumption systematically impaired the VOR evoked by high-acceleration head impulses and led to a functional loss of visual acuity during head movement.
Behavior of the human translational vestibulo-ocular reflex during simultaneous head translation and rotation
Authors: Schneider Rosalyn , Liao Ke , Walker Mark F. , Bronstein Adolfo , Leigh R. John
Published: December 2019

Background: During head translations, vestibular eye movements are ∼ 60% of those required to hold the line of sight on target but, during translation of the orbits due to head rotation about an eccentric axis, the eyes are held %eye on target. Objective: To resolve this paradoxical behavior of vestibulo-ocular reflexes. Methods: Subjects sat on a moving platform viewing a near target and were: (1) rotated en bloc in yaw about a vertical axis centered on the head at 1 Hz; (2) rotated with their head displaced ∼ 10 cm anterior (eccentric rotation) at 1 Hz; (3) translated along the inter-aural axis at 1.9 Hz; (4) rotated with the head centered at 1 Hz while they were translated along the inter-aural axis at 1.9 Hz. We calculated compensation ratio (CR): Eye velocity/eye velocity geometrically required to hold the eye on target. Results: During yaw, mean CR was 0.88 and during eccentric rotation CR was 0.93. During translation at 1.9 Hz, CR was 0.65. During combined rotation at 1.0 Hz and translation at 1.9 Hz, CR was 0.81 for head rotations and 0.74 for head translations. Conclusions: Translations of the orbits due to head rotation are better compensated for than translations of the orbits due to head translation. These different behaviors may be determined by context, the important difference being whether the subject is moving through the environment.
Amplitude and frequency prediction in the translational vestibulo-ocular reflex
Authors: Schneider Rosalyn , Walker Mark F.
Published: December 2019

The goal of this study was to assess the effect of amplitude and frequency predictability on the performance of the translational vestibulo-ocular reflex (tVOR). Eye movements were recorded in 5 subjects during continuous vertical translation that consisted of a series of segments with: 1) 3 amplitudes at constant frequency (2 Hz) or 2) 3 different frequencies (1.6, 2, 2.5 Hz). Stimulus changes were presented in a pseudo-random order. We found that there was little change in the tVOR immediately after an unexpected stimulus change, as if eye velocity were being driven more by an expectation based on previous steady-state motion than by current head translation. For amplitude transitions, only about 30% of the eventual response change was seen in the first half cycle. Similarly, a sudden change in translation frequency did not appear in eye velocity for 70 ms, compared to a 8 ms lag during similar yaw rotation. Finally, after a sudden large decrease in frequency, the eyes continued to track at the original higher frequency, resulting initially in an anti-compensatory tVOR acceleration. Our results elucidate further the complexity of the tVOR and show that motion prediction based on prior experience plays an important role in its response.
Applications of neuromodulation to explore vestibular cortical processing; new insights into the effects of direct current cortical modulation upon pursuit, VOR and VOR suppression
Authors: Ahmad H. , Arshad Q. , Siddiqui S. , Nigmatullina Y. , Patel M. , Bronstein A.M. , Roberts R.E.
Published: December 2019

Functional imaging, lesion studies and behavioural observations suggest that vestibular processing is lateralised to the non-dominant hemisphere. Moreover, disruption of interhemispheric balance via inhibition of left parietal cortex using transcranial direct current stimulation (tDCS) has been associated with an asymmetric suppression of the vestibulo-ocular reflex (VOR). However, the mechanism by which the VOR was modulated remains unknown. In this paper we review the literature on non-invasive brain stimulation techniques which have been used to probe vestibular function over the last decade. In addition, we investigate the mechanisms whereby tDCS may modulate VOR, e.g. by acting upon pursuit, VOR suppression mechanisms or direct VOR modulation. We applied bi-hemispheric parietal tDCS in 11 healthy subjects and only observed significant effects on VOR gain (tdcs * condition p=0.041) – namely a trend for VOR gain increase with right anodal/left cathodal stimulation, and a decrease with right cathodal/left anodal stimulation. Hence, we suggest that the modulation of the VOR observed both here and in previous reports, is directly caused by top-down cortical control of the VOR as a result of disruption to interhemispheric balance, likely parietal.
Gaze stabilization in chronic vestibular-loss and in cerebellar ataxia: Interactions of feedforward and sensory feedback mechanisms
Authors: Sağlam M. , Lehnen N.
Published: December 2019

During gaze shifts, humans can use visual, vestibular, and proprioceptive feedback, as well as feedforward mechanisms, for stabilization against active and passive head movements. The contributions of feedforward and sensory feedback control, and the role of the cerebellum, are still under debate. To quantify these contributions, we increased the head moment of inertia in three groups (ten healthy, five chronic vestibular-loss and nine cerebellar-ataxia patients) while they performed large gaze shifts to flashed targets in darkness. This induces undesired head oscillations. Consequently, both active (desired) and passive (undesired) head movements had to be compensated for to stabilize gaze. All groups compensated for active and passive head movements, vestibular-loss patients less than the other groups (P < 0.001, passive/active compensatory gains: vestibular-loss 0.23 ± 0.09/0.43 ± 0.12, healthy 0.80 ± 0.17/0.83 ± 0.15, cerebellar-ataxia 0.68 ± 0.17/0.77 ± 0.30, mean ± SD). The compensation gain ratio against passive and active movements was smaller than one in vestibular-loss patients (0.54 ± 0.10, P=0.001). Healthy and cerebellar-ataxia patients did not differ in active and passive compensation. In summary, vestibular-loss patients can better stabilize gaze against active than against passive head movements. Therefore, feedforward mechanisms substantially contribute to gaze stabilization. Proprioception alone is not sufficient (gain 0.2). Stabilization against active and passive head movements was not impaired in our cerebellar ataxia patients.
Isolated axial lateropulsion with ipsilesional subjective visual vertical tilt in caudal lateral medullary infarction
Authors: Kim Jun-Hyun , Kim Saeromi , Lee Dong Hyun , Lee Tae-Kyeong , Sung Ki-Bum
Published: December 2019

The isolated body lateropulsion has been well recognized in caudal lateral medullary infarction and postulated to result from the involvement of ipsilateral dorsal spinocerebellar tract which is known to convey proprioception of trunk and legs. However, there has been no case accompanied by the tilt of the subjective visual vertical in caudal lateral medullary infarction. Recently, it has been suggested that a lesion in the ipsilateral graviceptive vestibulothalamic pathway can lead to alteration of subjective visual vertical without ocular tilt reaction in various brainstem lesions. Here we describe two cases of caudal lateral medullary infarction with ipsilesional body lateropulsion and subjective visual vertical tilt but without limb ataxia or ocular tilt reaction. It could be hypothesized that the ascending graviceptive information from the spinal cord may run adjacent to the dorsal spinocerebellar tract or perception of the visual vertical can be influenced by ascending spinal proprioception.
Evidence Suggesting Individual Ocular Motor Control of Each Eye (Muscle)
Authors: Dell'Osso L.F.
Published: December 2019

Current models of the ocular motor system are usually presented in their most reduced form, are unilateral in architecture, and precise yoking is presumed. Although this simplifies the models, it does not accurately simulate the actual neuroanatomy and limits the models to simple, stereotyped responses. Studies of normal humans and monkeys have demonstrated striking disconjugacies in normal responses. Normal saccades may be disconjugate, or 1 eye may exhibit a dynamic overshoot. Asymmetric vergence can result in disconjugate saccades, unequal magnification spectacles cause differential saccadic gain adjustment, and saccades to unequal disparities also cause unequal saccades in the 2 eyes. In strabismus, deviated eyes typically do not mimic the movements of the fixating eye nor do their latent or congenital nystagmus waveforms duplicate those of the fixating eye. In spasmus nutans, each eye oscillates independently of the other. In achiasmatic dogs, uni-ocular saccades and uni-ocular nystagmus waveforms are seen; the same may be true in human achiasma. These data from both normals and those with abnormalities suggest that current models for ocular motor control are inadequate representations of the actual system. The inability of unilateral, yoked control (or even bilateral, yoked control) system models to duplicate the ocular motor responses of binocular mammals suggests that their ocular motor systems evolved from the bilateral, independent control systems seen in chameleons. One need only postulate a yoking overlay superimposed on two independent control systems to achieve conjugacy (bilateral, yoked, independent control) of the eyes. Abnormalities producing grossly disconjugate eye movements may then be simulated using the independent control of each eye released by a deficiency in the yoking overlay. Independent control of each eye coupled with the essential bilateral brain stem architecture implies that each individual muscle is driven by independent populations of neurons (burst cells, neural integrator cells, etc.). The agonist muscles of each eye are usually coordinated (yoked) but may function independently if the task dictates or if binocularity did not develop. Models based on the above architecture would be robust and could duplicate the many responses (both normal and abnormal) possible from the neurophysiological system.
Morphometric Studies of Type I And Type II Hair Cells in the Gerbil's Posterior Semicircular Canal Crista1
Authors: Kevetter G.A. , Correia M.J. , Martinez P.R.
Published: December 2019

The existence of separate subtypes of type I vestibular hair cells according to morphological criteria in situ was investigated. Gerbils were anesthetized and perfused with mixed aldehydes. The crista ampullaris of the posterior canal was dissected, fixed in osmium, dehydrated, and embedded in epon. Five-micron sections were cut orthogonal to the long axis of each crista. Measurements were made on camera lucida drawings of individual cells located in the apical, middle, and basal 1/3 of the crista. Measurements for each hair cell included the circumference, greatest width of the body, length, width of the apical surface (cuticular plate region, P), width at narrowest portion of the neck (NW), neck width to plate ratio (NPR), length at a point 2 times NW from the apical surface (L2N). Type I hair cells were subgrouped into three classes (long -l, intermediate -i, and short -s) based on a subjective determination of neck length. Statistical comparisons were made between type I (n=612) and type II (n=74) hair cells and the type I subtypes (l, i, s). Statistically significant differences were found between type I and II hair cells for NPR, width, and length, but not perimeter. Thus, as in pigeons, NPR distinguishes type I and type II hair cells in the gerbil crista. While type I hair cells are wider and longer than type IIs, the circumference is the same, due to the restricted neck in type I hair cells. The L2N statistic separates three subtypes of type I hair cells. Finally, for type I hair cells, a statistically significant difference existed between the L2N statistic and each subregion of the crista.
Dynamics of Directional Plasticity in the Human Vertical Vestibulo-Ocular Reflex1
Authors: Peng G.C.Y. , Baker J.F. , Peterson B.W.
Published: December 2019

Directional plasticity of the human vestibulo-ocular reflex (VOR) was studied in 10 subjects. The adaptation paradigm coupled 0.25 Hz, 19°/s vertical pitch vestibular rotations with 28°/s horizontal optokinetic oscillations. Electro-oculographic recordings in the dark were taken at 0.05, 0.1, 0.25, 0.5, and 1 Hz pitch rotations before and after training and at 15-minute intervals during 0.25 Hz adaptation. Peak head velocity was kept at 19°/sec for frequencies above 0.1 Hz, while constant amplitude was maintained at ±24° for 0.05 and 0.1 Hz. In all subjects, directional training produced slow phase horizontal VOR eye movements that were not present during vertical rotations before adaptation. During the 2-hour training period, the cross-axis VOR gain at 0.25 Hz increased up to 0.16. Adaptive VOR gain was highest at the lowest frequency and reached a tuned peak at the 0.25 Hz training frequency. Cross-axis VOR phase remained around 0° at higher frequencies and lagged at lower frequencies. In all subjects, the cross-axis VOR gain was diminished when subjects were exposed to 0.25 Hz pitch rotations paired with a stationary visual field. The dynamics of the vertical VOR remained constant throughout the experiment. These results are further evidence that the frequency response characteristics of adaptive cross-axis VOR gain are similar in humans and cats, while phase behavior is less complex in humans. The high adaptive gain at low frequencies implicates otolith contributions during cross-axis adaptation.
Dizziness of Suspected Cervical Origin Distinguished by Posturographic Assessment of Human Postural Dynamics1
Authors: Karlberg Mikael , Johansson Rolf , Magnusson Måns , Fransson Per-Anders
Published: December 2019

Useful clinical tests are lacking for the controversial entity “cervical vertigo”. In earlier studies patients assumed to suffer from cervical vertigo or dizziness manifested disturbed postural control as compared to healthy subjects, but were hard to distinguish from patients with other balance disorders. Using posturography in which stance was perturbed by a vibratory stimulus applied towards the calf muscles, we studied 16 consecutive patients with recent onset of neck pain and concomitant complaints of vertigo or dizziness, but normal findings at otoneurological examination and electronystagmography; 18 patients with recent vestibular neuritis; and 17 healthy subjects. We performed system identification of a model of the control of upright human stance, using the vibratory stimulus as input and the recorded body sway as output. According to values for the three normalized parameters of the transfer function of the model (ie, swiftness, stiffness, and damping), cervical vertigo patients were distinguished both from healthy subjects (P < 0.001), and from vestibular neuritis patients (P < 0.001). It was also possible to distinguish the vestibular neuritis group from the group of healthy subjects (P < 0.01). The results show disturbed postural control in patients with cervical vertigo to differ from that in patients with recent vestibular neuritis, and indicate posturographic assessment of human posture dynamics to be a possible future tool for use in diagnosing cervical vertigo.
Fentazin Anesthesia for Labyrinthine Surgery in Guinea Pigs
Authors: Sansom Andrew J. , Smith Paul F. , Darlington Cynthia L.
Published: December 2019

We describe the use of fentazin anesthesia (0.4 mg/ml fentanyl citrate, 58.3 mg/mL xylazine HCl, and 3.2 mg/mL azaperone, Parnell, New Zealand) for labyrinthine surgery in guinea pigs. Fentazin provides stable surgical anesthesia for approximately 1 hour, rapid recovery from anesthesia following the surgery, and has significant analgesic and anxiolytic properties. Its advantages in comparison to other anesthetics (for example, ketamine HCl) are discussed.
Acetylcholinesterase Activity Changes in Medial Vestibular Complex After Hemilabyrinthectomy in the Rat
Authors: Torte-Hoba M.P. , Courjon J.H. , Leroy M.H. , Boyer N. , Dominey P. , Farhat F. , Rebert A.
Published: December 2019

Acetylcholinesterase (AchE) activity was studied in pigmented rats 6 h to 1 y after hemilabyrinthectomy. A strong reduction of this activity was localized in the rostrocaudal extent of both he prepositus hypoglossi nucleus and the medial vestibular nucleus (that is, medial vestibular complex: VCm) ipsilateral to the lesion 6 h after the lesion. This deficit persisted within some areas dispersed throughout this complex 3 w and 1 y postoperatively. This result supports the hypothesis that the asymmetry of AchE activity in VCm could be necessary for vestibular compensation and provides an additional model for functional plasticity in the central nervous system.
Short Latency Vestibular Evoked Potentials in the Chicken Embryo1
Authors: Jones Sherri M. , Jones Timothy A.
Published: December 2019

Electrophysiological responses to pulsed linear acceleration stimuli were recorded in chicken embryos incubated for 19 or 20 days (E19/E20). Responses occurred within the first 16 ms following the stimulus onset. The evoked potentials disappeared following bilateral labyrinthectomy, but persisted following cochlear destruction alone, thus demonstrating that the responses were vestibular. Approximately 8 to 10 response peaks could be identified. The first 4 positive and corresponding negative components (early peaks with latencies < 6.0 ms) were scored and latencies and amplitudes quantified. Vestibular response latencies were significantly longer (P < 0.01) and amplitudes significantly smaller (P < 0.001) than those observed in 2-week-old birds. Mean response threshold for anesthetized embryos was −15.9dBre 1.0 g/ms, which was significantly higher (P < 0.03) than those observed in 2-week-old birds (−23.0dBre 1.0 g/ms). Latency/intensity functions (that is, slopes) were not significantly different between embryos and 2-week-old animals, but amplitude/intensity functions for embryos were significantly shallower than those for 2-week-old birds (P < 0.001). We presume that these differences reflect the refinement of sensory function that occurs following 19 to 20 days of incubation. The recording of vestibular evoked potentials provides an objective, direct and noninvasive measure of peripheral vestibular function in the embryo and, as such, the method shows promise as an investigative tool. The results of the present study form the definitive basis for using vestibular evoked potentials in the detailed study of avian vestibular ontogeny and factors that may influence it.
Effects Of Caloric Vestibular Stimulation on Parietal and Temporal Blood Flow in Human Brain: A Consecutive Technetium-99m-HMPAO SPECT Study
Authors: Takeda N. , Hashikawa K. , Moriwaki H. , Oku N. , Koizuka I. , Kitahara T. , Taya N. , Kubo T. , Nishimura T.
Published: December 2019

The effects of caloric vestibular stimulation on regional cerebral blood flow (rCBF) of the parietal and temporal cortex were examined in 10 healthy volunteers. The consecutive 99mTe-hexa-methyl-propyleneamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) method with region of interest analysis was used. Changes in rCBF induced by caloric stimulation with cold air (25°C) were evaluated in comparison with those induced by control stimulation with air at body temperature (37°C). Caloric stimulation with cold air induced vertigo in 4 subjects, dizziness in 2, and no sensation of self-motion in the remaining 4 subjects, whereas, control stimulation did not induce the sensation of self-motion in any subject. Although both parietal and temporal rCBF were slightly decreased during caloric stimulation, a correlation could be established between the magnitude of left-right differences in change of parietal rCBF and the degree of self-motion perception induced by cold-air caloric stimulation, as compared to control stimulation. Left-right differences in change of parietal rCBF in subjects with vertigo during caloric stimulation were significantly higher than those in subjects without any sensation of self-motion. In contrast, there was no correlation between the magnitude of left-right difference in change of parietal rCBF and maximum slow phase eye velocity induced by caloric stimulation. These findings suggest that the parietal lobe is involved in the perception of vertigo due to vestibular stimulation, but not in the vestibulo-ocular reflex.
The Vestibulo-Ocular Reflex and Seasickness Susceptibility
Authors: Gordon C.R. , Spitzer O. , Doweck I. , Shupak A. , Gadoth N.
Published: December 2019

VOR parameters were compared in subjects at the extremes of the seasickness susceptibility scale. Thirty-nine subjects highly susceptible to seasickness and 30 nonsusceptible subjects participated in the study. The VOR was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08, and 0.16 Hz. In subjects susceptible to seasickness, VOR gain was significantly higher at 0.02 and 0.04 Hz, and phase lead was significantly lower at 0.01, 0.02, 0.04, and 0.08 Hz, than in nonsusceptible subjects. Our findings are in agreement with the notion that the vestibular response will be more intense in subjects susceptible to motion sickness. The present results support the contention that a natural insusceptibility, or increased resistance to seasickness produced by adaptive responses to repeated sea exposures, may be reflected by lower VOR gain and higher phase lead.