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1.
Huntington's disease is a movement disorder originated from malfunctioning of Basal Ganglia (BG). There are some models for this disease, most of them being conceptual. So, it seems that considering all physiological information and structural specifications to develop a holistic model is needed. We introduce a computational model based on experimental and physiological findings. Parts of the brain known to be involved in Huntington's disease are all considered in our model and most features of the movement disorders have been appeared in the model. This mathematical model has considered the involved parts of the brain in a fairly accurate way, explaining the behavior and mechanism of the disease according to the physiological information. Our model has several advantages. It is able to simulate the normal and Huntington's disease stride time intervals. It shows how the present treatment, i.e. diazepam, is able to ameliorate the gait disorder. In this research we assessed the effects of changing some neurotransmitter levels in order to propose new treatments. Although we showed that gamma amino butyric acid (GABA) blockers reduce Huntington's disease movement disorder, but we discussed that it is unfair to use this route for treatment. We evaluated our model response to increment of GABA, alone and observed that the gait disorder was strengthened. Our novel idea in this regard is resuscitation of BG loop in order to maintain its major physiological functions, and at the same time raising the threshold in order to weaken the internal disturbances. Our last idea about BG treatment is to decrease glutamate. Our model was able to show the effectiveness of this treatment on Huntington's disease disturbances. We propose that experimental studies should be designed in which these two novel methods of treatment will be evaluated. This validation would implement a milestone in treatment of such a debilitating disease at Huntington.  相似文献   

2.
Hausdorff, Jeffrey M., Susan L. Mitchell, RenéeFirtion, C. K. Peng, Merit E. Cudkowicz, Jeanne Y. Wei, and Ary L. Goldberger. Altered fractal dynamics of gait: reducedstride-interval correlations with aging and Huntington's disease.J. Appl. Physiol. 82(1): 262-269, 1997.Fluctuationsin the duration of the gait cycle (the stride interval) display fractaldynamics and long-range correlations in healthy young adults. Wehypothesized that these stride-interval correlations would be alteredby changes in neurological function associated with aging and certaindisease states. To test this hypothesis, we compared thestride-interval time series of 1) healthy elderly subjects andyoung controls and of 2) subjects with Huntington's diseaseand healthy controls. Using detrended fluctuation analysis, we computed, a measure of the degree to which one stride interval is correlatedwith previous and subsequent intervals over different timescales. The scaling exponent  was significantly lower in elderlysubjects compared with young subjects (elderly: 0.68 ± 0.14; young:0.87 ± 0.15; P < 0.003). The scaling exponent  wasalso smaller in the subjects with Huntington's disease compared withdisease-free controls (Huntington's disease: 0.60 ± 0.24;controls: 0.88 ± 0.17; P < 0.005). Moreover,  was linearly related to degree of functional impairment in subjects withHuntington's disease (r = 0.78, P < 0.0005).These findings demonstrate that stride-interval fluctuations are morerandom (i.e., less correlated) in elderly subjects and in subjects with Huntington's disease. Abnormal alterations in the fractal properties of gait dynamics are apparently associated with changes in central nervous system control.

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3.
Rats with implanted telemetry transponders were blood sampled by jugular puncture, periorbital puncture or tail vein puncture, or sampled by jugular puncture in carbon dioxide (CO2), isoflurane or without anaesthesia in a crossover design. Heart rate, blood pressure and body temperature were registered for three days after sampling. Initially blood pressure increased, but shortly after sampling it decreased, which led to increased heart rate. Sampling induced rapid fluctuations in body temperature, and an increase in body temperature. Generally, rats recovered from sampling within 2-3 h, except for rats sampled from the tail vein, which showed fluctuations in body temperature in excess of 30 h after sampling. Increases in heart rate and blood pressure within the first hours after sampling indicated that periorbital puncture was the method that had the largest acute impact on the rats and that it might take an extra hour to recover from it. CO2 anaesthesia seemed unable to prevent the increase in blood pressure and the fluctuations in body temperature induced by blood sampling, and up to 10 h after sampling, the rats were still affected by CO2 anaesthesia. Rats anaesthetized with isoflurane showed lower increases in blood pressure after, and fewer fluctuations in body temperature during sampling, and the post-anaesthetic effects of isoflurane, if any, seemed to disappear immediately after sampling. It is, therefore, concluded that blood sampling in rats by jugular puncture seems to be the method from which rats most rapidly recover when compared with periorbital puncture and tail vein puncture, and that for anaesthesia, isoflurane is recommended in preference to CO2.  相似文献   

4.
Biomechanical investigation into locomotor pathology in commercial pigs is lacking despite this being a major concern for the industry. Different floor types are used in modern, intensive pig production systems at different stages of the pigs’ production cycle. The general perception holds that slatted and/or hard solid concrete surfaces are inferior to soft straw-covered floors regarding healthy musculoskeletal development. Previous studies have compared pigs housed on different floor types using clinical, subjective assessment of leg weakness and lameness. However, reliability studies generally report a low repeatability of clinical lameness scoring. The objective of this study was to quantitatively assess the long-term effect of pen floors, reflected in the biomechanical gait characteristics and associated welfare of the pigs. A cohort of 24 pigs housed on one of three different floor types was followed from 37 to 90 kg average liveweight, with gait analysis (motion capture) starting at 63 kg. The three floor types were fully slatted concrete, partly slatted concrete and deep straw-bedded surfaces, all located within the same building. Pigs underwent five repeated camera-based motion captures, 7 to 10 days apart, during which 3D coordinate data of reflective skin markers attached to leg anatomical landmarks were collected. Pigs walked on the same solid concrete walkway during captures. One-way ANOVA and repeated measures ANOVA were used to analyse the gait data. Results revealed changes over time in the spatiotemporal gait pattern which were similar in magnitude and direction for the pigs from different floor types. Significant increases in elbow joint flexion with age were observed in all pigs (P⩽0.050; +6°). There were few differences between floor groups, except for the step-to-stride ratio in the hind legs being more irregular in pigs housed on partly slatted floors (P=0.012; 3.6 times higher s.d.) compared with those on 5 to 10 cm straw-bedding in all pen areas. As the level of clinical problems was generally low in this cohort, it may be that floors elicit problems only when there is a primary predisposing factor increasing weakness in susceptible tissues.  相似文献   

5.
Summary The available information on the world distribution of Huntington's disease (HD) from population surveys and death rate analysis is summarised and discussed in the light of genetic studies. It is concluded that most European populations, both Northern and Southern, show a relatively high prevalence (4–8 per 100,000), and that the disorder may also be frequent in India and parts of central Asia. HD is notably rare in Finland and in Japan, but data for Eastern Asia and Africa are inadequate. The disorder may have been underestimated in the American black population. Populations derived from recent European imigration show frequencies and origins of HD comparable to those expected from their own origins and expansion; there is no evidence to suggest that the HD gene has spread disproportionally and its selective effect may be close to neutral. Multiple separate introductions of the gene have been the rule in large populations. Several major foci of HD exist as the result of rapid population expansion. It is likely that a number of separate mutations for HD will be shown to be responsible for the disease, but that the high frequency of HD in European populations will prove to be the result of one or a very small number of mutations, probably of great antiquity.  相似文献   

6.
Increased femoral antetorsion leads to several gait deviations, and amongst others, an increased knee flexion was reported in mid and terminal stance. Therefore, the purpose of this retrospective study was to identify gait deviations caused by increased femoral antetorsion and to perform subgroup analyses based on sagittal knee kinematics. Patients with isolated, CT confirmed increased femoral antetorsion (n = 42) and age-matched typically developing children (TDC, n = 17) were included in this study. Patients were referred to gait analysis because of gait abnormalities going along with an increased femoral antetorsion ≥30°. Kinematic and kinetic data were recorded during 3D gait analysis and three valid gait cycles were analyzed. Principal component (PC) analysis was used to achieve data transformation. A linear mixed model was used to estimate the group effect of PC-scores of retained PCs explaining 90% of the cumulative variance. Group effects of PC-scores revealed that patients walked with more flexed hips and greater anterior pelvic tilt throughout the gait cycle. Knee flexion was increased in patients during mid and terminal stance. Increased frontal plane knee and hip joint moments were found for patients compared to TDC. Furthermore, dividing patients into two subgroups based on their sagittal knee kinematics showed that kinematic gait deviations were more pronounced in patients with higher femoral antetorsion, while deviations in joint moments were more pronounced in patients with lower femoral antetorsion. Increased femoral antetorsion showed alterations in all lower limb joints and may be not only a cosmetic problem. Therefore, 3D gait analysis should be used for clinical management and operative treatment should be considered depending on severity of gait deviations.  相似文献   

7.
Optical coherence tomography (OCT) derived retinal measures, particularly peri-papillary retinal nerve fiber layer (RNFL) thickness, have been proposed as outcome measures in remyelinating and neuroprotective trials in multiple sclerosis (MS). With increasing utilization of multiple centers to improve power, elucidation of the impact of different OCT technologies is crucial to the design and interpretation of such studies. In this study, we assessed relation and agreement between RNFL thickness and total macular volume (in MS and healthy controls) derived from three commonly used OCT devices: Stratus time-domain OCT, and Cirrus HD-OCT and Spectralis, two spectral-domain (SD) OCT devices. OCT was performed on both Cirrus HD-OCT and Stratus in 229 participants and on both Cirrus HD-OCT and Spectralis in a separate cohort of 102 participants. Pearson correlation and Bland-Altman analyses were used to assess correlation and agreement between devices. All OCT retinal measures correlated highly between devices. The mean RNFL thickness was 7.4 μm lower on Cirrus HD-OCT than Stratus, indicating overall poor agreement for this measurement between these machines. Further, the limits of agreement (LOA) between Cirrus HD-OCT and Stratus were wide (-4.1 to 18.9 μm), indicating poor agreement at an individual subject level. The mean RNFL thickness was 1.94 μm (LOA: -5.74 to 9.62 μm) higher on Spectralis compared to Cirrus HD-OCT, indicating excellent agreement for this measurement across this cohort. Although these data indicate that these three devices agree poorly at an individual subject level (evidenced by wide LOA in both study cohorts) precluding their co-utilization in everyday practice, the small difference for mean measurements between Cirrus HD-OCT and Spectralis indicate pooled results from these two SD-devices could be used as outcome measures in clinical trials, provided patients are scanned on the same machine throughout the trial, similar to the utilization of multiple different MRI platforms in MS clinical trials.  相似文献   

8.
Summary The results of an epidemiological survey on Huntington's disease in the Lazio Region, Central Italy, and of linkage studies in a subset of families are reported. From a total of 99 ascertained families and 491 patients, a prevalence of 25.6 × 10–6 was obtained, with distributions of age at onset and age at death similar to those described in the literature. No relationship with the sex of the transmitting parent was observed. Analysis of 10 chromosome 4 restriction fragment length polymorphisms in 11 families showed consistent linkage between the genetic loci D4S10, D4S43 and D4S95, and the disease. A recombination rate of 0.08 for D4S10 markers was obtained in this sample. Allelic frequencies of DNA markers in the general population are also reported.  相似文献   

9.
The new scientific knowledge about the behaviour of the newborn and their interactions as a developing factor, as well as the new neurosciences findings about the initial brain formation, gave us several elements for a new vision and reflection about the perinatal routines in hospitals. This study raises questions about the first experiences of the rooming in newborns during the specific act of bath, as the only determining factor in altering both behaviour and physiology. Through the monitoring of the heart rate frequency and observing the changes in the states of consciousness level, this article shows how the type of bath that the newborn is subjected to influences his/her organisation. The study showed significant results in the parameters observed during the electric shower bath, leading to unbalance of the subsystems where the individuals organise themselves; such findings made us classify this procedure as very stressing to the baby. To the contrary the bath in the "Tummy Tub" presented insignificant changes, showing a relaxed baby with normal bath behaviours and physiological status; thus this procedure appears to contribute to an energetic and interactive balance of the baby's various systems. The aggressive approach (electric shower) does not allow the newborn auto-regulation to occur and to get proper stimulation and learn basic interactive responses which would facilitate his /her healthy early infancy development.  相似文献   

10.
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12.

Background and aims

Sufficient soil phosphorus (P) is important for achieving optimal crop production, but excessive soil P levels may create a risk of P losses and associated eutrophication of surface waters. The aim of this study was to determine critical soil P levels for achieving optimal crop yields and minimal P losses in common soil types and dominant cropping systems in China.

Methods

Four long-term experiment sites were selected in China. The critical level of soil Olsen-P for crop yield was determined using the linear-plateau model. The relationships between the soil total P, Olsen-P and CaCl2-P were evaluated using two-segment linear model to determine the soil P fertility rate and leaching change-point.

Results

The critical levels of soil Olsen-P for optimal crop yield ranged from 10.9 mg kg?1 to 21.4 mg kg?1, above which crop yield response less to the increasing of soil Olsen-P. The P leaching change-points of Olsen-P ranged from 39.9 mg kg?1 to 90.2 mg kg?1, above which soil CaCl2-P greatly increasing with increasing soil Olsen-P. Similar change-point was found between soil total P and Olsen-P. Overall, the change-point ranged from 4.6 mg kg?1 to 71.8 mg kg?1 among all the four sites. These change-points were highly affected by crop specie, soil type, pH and soil organic matter content.

Conclusions

The three response curves could be used to access the soil Olsen-P status for crop yield, soil P fertility rate and soil P leaching risk for a sustainable soil P management in field.  相似文献   

13.

Background  

Joint lesions occur widespread in the Danish sow population and they are the most frequent cause for euthanasia. Clinically, it is generally impossible to differentiate between various types of non-inflammatory joint lesions. Consequently, it is often necessary to perform a post mortem examination in order to diagnose these lesions. A study was performed in order to examine the relation of abnormal gait and posture in sows with specific joint lesions, and thereby obtaining a clinical diagnostic tool, to be used by farmers and veterinarians for the evaluation of sows with joint problems.  相似文献   

14.
15.
Bone morphology and density changes are commonly observed following joint replacement, may contribute to the risks of implant loosening and periprosthetic fracture and reduce the available bone stock for revision surgery. This study was presented in the ‘Bone and Cartilage Mechanobiology across the scales’ WCCM symposium to review the development of remodelling prediction methods and to demonstrate simulation of adaptive bone remodelling around hip replacement femoral components, incorporating intrinsic (prosthesis) and extrinsic (activity and loading) factors. An iterative bone remodelling process was applied to finite element models of a femur implanted with a cementless total hip replacement (THR) and a hip resurfacing implant. Previously developed for a cemented THR implant, this modified process enabled the influence of pre- to post-operative changes in patient activity and joint loading to be evaluated. A control algorithm used identical pre- and post-operative conditions, and the predicted extents and temporal trends of remodelling were measured by generating virtual X-rays and DXA scans. The modified process improved qualitative and quantitative remodelling predictions for both the cementless THR and resurfacing implants, but demonstrated the sensitivity to DXA scan region definition and appropriate implant–bone position and sizing. Predicted remodelling in the intact femur in response to changed activity and loading demonstrated that in this simplified model, although the influence of the extrinsic effects were important, the mechanics of implantation were dominant. This study supports the application of predictive bone remodelling as one element in the range of physical and computational studies, which should be conducted in the preclinical evaluation of new prostheses.  相似文献   

16.
Eight men, 4 with tardive dyskinesia and 4 with Huntington's disease, were treated with oral doses of choline chloride up to 20 g daily for three to eight weeks. Prior to treatment, 7 of the 8 patients were tested with a graded dose of 3 mg of physostigmine salicylate, a cholinesterase inhibitor. Six of these 7 patients had a favorable acute response to physostigmine. The same six patients had a favorable response to chronic treatment with choline chloride. Relapses following a switch from active treatment to placebo were delayed, but this could not be explained on the basis of the rate of choline disappearance from plasma. Re-treatment with choline chloride reversed relapse in most instances. Choline chloride may ameliorate these movement disorders by increasing central cholinergic activity, but other mechanisms are possible. Its practical importance as a treatment needs further elucidation.  相似文献   

17.
Huntington''s disease (HD) is an inherited, neurodegenerative disorder caused by a single-gene mutation: a CAG expansion in the huntingtin (HTT) gene that results in production of a mutated protein, mutant HTT, with a polyglutamine tail (polyQ-HTT). Although the molecular pathways of polyQ-HTT toxicity are not fully understood, because protein misfolding and aggregation are central features of HD, it has long been suspected that cellular housekeeping processes such as autophagy might be important to disease pathology. Indeed, multiple lines of research have identified abnormal autophagy in HD, characterized generally by increased autophagic induction and inefficient clearance of substrates. To date, the origin of autophagic dysfunction in HD remains unclear and the search for actors involved continues. To that end, recent studies have suggested a bidirectional relationship between autophagy and primary cilia, signaling organelles of most mammalian cells. Interestingly, primary cilia structure is defective in HD, suggesting a potential link between autophagic dysfunction, primary cilia and HD pathogenesis. In addition, because polyQ-HTT also accumulates in primary cilia, the possibility exists that primary cilia might play additional roles in HD: perhaps by disrupting signaling pathways or acting as a reservoir for secretion and propagation of toxic, misfolded polyQ-HTT fragments. Here, we review recent research suggesting potential links between autophagy, primary cilia and HD and speculate on possible pathogenic mechanisms and future directions for the field.  相似文献   

18.
The goal of this study was to compare the ability of donor naive and alloantigen-primed effector memory T cells to induce graft-vs-host disease after bone marrow transplantation in MHC-mismatched irradiated host mice. Purified CD4(+) naive (CD62L(high)CD44(low)) T cells and CD4(+) effector memory (CD62L(low)CD44(high)) T cells obtained from unprimed donors and donors primed to host alloantigens, respectively, were injected into host mice, and the rapidity, severity, and pattern of tissue injury of graft-vs-host disease was assessed. Unexpectedly, the naive T cells induced a more acute and severe colitis than the primed memory cells. Whereas the naive T cells expressing CD62L and CCR7 lymph node homing receptors vigorously expanded in mesenteric lymph nodes and colon by day 6 after transplantation, the primed memory T cells without these receptors had 20- to 100-fold lower accumulation at this early time point. These differences were reflected in the significantly more rapid decline in survival and weight loss induced by naive T cells. The primed memory T cells had a greater capacity to induce chronic colitis and liver injury and secrete IL-2 and IFN-gamma in response to alloantigenic stimulation compared with memory T cells from unprimed donors. Nevertheless, the expected increase in potency as compared with naive T cells was not observed due to differences in the pattern and kinetics of tissue injury.  相似文献   

19.
S J Enna 《Life sciences》1977,20(2):205-211
Reverse triiodothyronine (rT3) which is apparently a product of 5-monodeiodination of thyroxine (T4) at the periphery, was measured in 199 chickens of various strains. rT3 was virtually absent in young birds (less than 1 week to 8 weeks of age) in marked contrast to the elevated rT3 levels found in human and other mammalian neonates. At one to two years of age there was a significant increase in the number of birds with detectable rT3. However, rT3 concentrations were low and often close to the detection limits of the assay in contrast to significant rT3 levels found in mammals (man, monkey, sheep, rat and dog). An apparent sex difference in relation to rT3 formation was noted; 46.4% of 97 females and 9.3% of 54 males showed detectable rT3 levels. The observations described suggest a species difference in regard to peripheral T4 monodeiodination between birds and mammals.  相似文献   

20.
The trinucleotide repeat disorders comprise an ever expanding list of diseases, all of which are caused by an unstable expanded trinucleotide repeat tract. Huntington's disease (HD) is a member of this family of diseases and more specifically, is a Type II trinucleotide repeat disorder. This means that the mutation in HD is an unstable expanded polyglutamine repeat tract, which is expressed at protein level. There is no cure or beneficial treatment for this fatal neurodegenerative disorder, and patients suffer from progressive motor, cognitive and psychiatric dysfunction. Recent years has seen the development of many genetic models of HD, which allow study of the early phases of disease process, at several different levels of cell function. In addition, these models are being used to investigate the potential of a variety of therapeutic agents for clinical use. Here we review these findings, and their implication for HD pathogenesis.  相似文献   

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