MSA Groups Research Articles

Exploratory Analysis of the Association Between Plasma Ceramide Alterations and Cognitive Dysfunction in Parkinson's Disease.

Prior research has underscored the importance of sphingolipid metabolism in Parkinson's disease (PD) pathogenesis. Our objective was to explore the associations between plasma ceramide levels and PD patients with cognitive dysfunction (PD-CD). We enrolled two study populations from Eastern China and the Parkinson's Progression Markers Initiative (PPMI), comprising 290 (100 HCs, 160 PDs, and 30 MSAs) and 429 (125 HCs and 304 PDs) participants, respectively. The plasma levels of ceramides (Cer 16:0, Cer 18:0, Cer 24:0, and Cer 24:1) were tested via HPLC-MS/MS analysis. Compared with those in the HC group, the plasma levels of Cer 18:0, Cer 24:1, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were higher in both the PD and MSA groups. Significant differences in the plasma levels of Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were observed among the PD-NC (PD with normal cognition), PD-MCI (PD with mild cognitive impairment), and PDD (PD dementia) groups, with the PDD group exhibiting the highest levels. PD patients with higher baseline levels of plasma ceramides (specifically, Cer 18:0, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0) demonstrated accelerated cognitive decline compared with individuals who had lower baseline plasma ceramide levels during the 5-year follow-up period. A biomarker panel including Cer 18:0/Cer 24:0 and Cer 24:1/Cer 24:0 could effectively differentiate PD-CD from PD-NC with notable diagnostic accuracy. Our results indicate that plasma ceramide levels could potentially be used as diagnostic biomarkers for PD-CD.

Comparison of Genotoxicity and Pulmonary Toxicity Study of Modified SiO2 Nanomaterials

Surface-modified nano-SiO2 is a common additive in many products. However, the safety of nano-SiO2 products under various modifications is still unclear. In this study, we investigated the genotoxicity and acute pulmonary toxicity of nano-SiO2 with or without modification. The samples used in this study included: sample A (SA, 55.16 nm, 411.3 mg/mL), modified sample A (mSA, 82.29 nm, 37.7 mg/mL), sample B (SB, 22 nm, 358.0 mg/mL), and modified sample B (mSB, 86.64 nm, 37.7 mg/mL). In the genotoxicity study, we conducted an Ames test, chromosomal aberration test (CA), and a micronucleus (MN) test. The SA, mSA, and mSB groups showed negative results in all these genotoxicity tests. Only SB showed a weakly positive reaction in these assays, but the genotoxicity could be reversed after S9 metabolism or modification. In the acute pulmonary toxicity test, the rats were given an intratracheal instillation (IT) (0.5 mL/kg) of diluted samples and sacrificed after 1 or 14 days. The mortality rate, number of leukocytes and cytokines of TNF-α in the bronchoalveolar lavage fluid (BALF), and the pathology in the lungs were determined. The results revealed that mSA posed acute toxicity in rats. After modification, the pulmonary toxicity was increased in mSA but decreased in mSB on Day 1, and no significant difference was observed on Day 14. In conclusion, there was no observed genotoxicity in either SA or SB, while mSA posed acute inhalation toxicity to rats that decreased in mSB after modification. This indicates that the decrease in pH level in SA and decrease in the solid content in SB are considered after the trifluorosilane surface-modified amorphous nano-silica.

Analysis of brain‐derived blood exosomes for diagnostics of synucleinopathies

AbstractBackgroundSynucleinopathies are diseases characterized by aggregation and deposition of α‐synuclein in different brain cells. Diagnosis of these neurological disorders is challenging due to overlapping complex clinical symptoms. Developing reliable biomarkers that can distinguish among the synucleinopathies is an urgent public health need. Recently, α‐synuclein was shown to transfer via exosomes between different brain cells suggesting that measuring α‐synuclein in brain‐derived exosomes could serve as a potential biomarker for synucleinopathies.MethodIn this study, we used antibody‐coated magnetic beads to immunochemically isolate specific exosomes released by neurons or oligodendrocytes from serum/plasma of healthy individuals and patients with Parkinson’s disease and Multiple System Atrophy and measured biomarker concentration in them by a sensitive electro‐chemiluminescence ELISA. Oligodendroglial and neuronal exosomes were isolated from serum of 101 patients with MSA, 104 patients with PD and 100 healthy controls.ResultSignificantly higher concentrations of α‐synuclein were found in both neuronal and oligodendroglial exosomes from patients than in controls. The absolute values of α‐synuclein in neuronal and oligodendroglial exosomes provided moderate separation between the MSA and PD groups, yet the ratio between the two cell types allowed separating the two disease groups with 90.0% sensitivity and 90.0% specificity.Conclusionα‐Synuclein in brain‐derived blood exosomes provides a sensitive biomarker for distinguishing patients with MSA from healthy controls and from patients with PD using a blood test and suggest that the method can be expanded further for other neurodegenerative diseases.

Prefrontal cortex hypoactivity distinguishes severe from mild-to-moderate social anxiety as revealed by a palm-sized near-infrared spectroscopy system.

The purpose of this study was to compare prefrontal cortex (PFC) activity among subjects with differing social anxiety (SA) severity levels to identify a possible biomarker for severe SA. Further, SA is generally under-diagnosed, so we examined if such measurements could be acquired conveniently, non-invasively, and at low cost using a portable near-infrared spectroscopy (NIRS) system. We classified 96 participants into three groups based on Liebowitz Social Anxiety Scale (LSAS) total score: Low SA (LSA, n = 40), Moderate SA (MSA, n = 39), and High SA (HSA, n = 17). We compared the prefrontal hemodynamic responses among LSAS severity groups during a verbal fluency task using a palm-sized NIRS system. The HSA group exhibited a significantly lower hemodynamic response in the left PFC compared to LSA and MSA groups, whereas there was no significant difference between LSA and MSA groups. There was also no significant difference in the right PFC hemodynamic response among groups. Differences in the severity of SA symptoms may be related to the left PFC function. Low PFC activity during specific cognitive tasks may provide a biomarker for distinguishing severe from mild/moderate SA symptoms to guide subsequent therapeutic decisions.

Elevated serum growth differentiation factor 15 in multiple system atrophy patients: A case control study.

BACKGROUNDMultiple system atrophy (MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15 (GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIMTo determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease (PD) patients and healthy controls.METHODSA case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTSSerum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls (P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels (P = 0.043 and 0.000; respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients (cutoff: 470.42 pg/mL, sensitivity: 85.7%, specificity: 88.0%; cutoff: 1075.91 pg/mL, sensitivity: 51.0%, specificity: 96.0%; respectively).CONCLUSIONSerum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

Robotic-assisted approaches to GERD following sleeve gastrectomy.

Sleeve gastrectomy (SG) is the most common bariatric operation in the United States but increases the incidence of gastroesophageal reflux disease (GERD). The aim of our study was to describe our experience with robotic-assisted management of intractable GERD after SG. A systematic review of a prospectively maintained database was performed of consecutive patients undergoing robotic-assisted magnetic sphincter augmentation placement after sleeve gastrectomy (MSA-S group) or conversion to Roux-en-Y gastric bypass (RYGB group) for GERD from 2015 to 2019 at our tertiary- care bariatric center. These were compared to a consecutive group of patients undergoing robotic-assisted magnetic sphincter augmentation placement (MSA group) for GERD without a history of bariatric surgery from 2016 to 2019. The primary outcome was perioperative morbidity. Secondary outcomes were operative time (OT), 90-day re-intervention rate, length of stay, symptom resolution and weight change. There were 51 patients included in this study; 18 patients in the MSA group, 13 patients in the MSA-S group, and 20 patients in the RYGB group. There was no significant difference in age, gender, ASA score, preoperative endoscopic findings, or DeMeester scores (P > 0.05). BMI was significantly higher in patients undergoing RYGB compared to MSA or MSA-S (P < 0.0001). There were significant differences in OT between the MSA and RYGB groups (P < 0.0001) and MSA-S and RYGB groups (P = 0.009), but not MSA group to MSA-S group (P = 0.51). There was no significant difference in intraoperative and postoperative morbidity (P = 1.0 and P = 0.60, respectively). 30-day morbidity: 5.6% (MSA), 15.4% (MSA-S) and 15% (RYGB). There was no difference on PPI discontinuation among groups, with more than 80% success rate in all. The use of the robotic platform in the different approaches available for treatment of GERD after SG appears to be a feasible option with low morbidity and high success rate. Further data is needed to support our findings.

The discriminative capacity of CSF β-amyloid 42 and Tau in neurodegenerative diseases in the Chinese population

IntroductionIn the past few years, the β-amyloid 42 peptide and tau protein in cerebrospinal fluid (CSF) have become primary diagnostic biomarkers in differentiating Alzheimer's disease (AD) and cognitive normal controls. As we know, several neurodegenerative diseases have been reported to overlap with AD in neuropathology and clinical symptoms. To examine the discriminative utility of these biomarkers in AD and other neurodegenerative diseases, we measured them in a cohort of Chinese population. MethodsWe measured CSF Aβ42, t-tau and p-tau181 by ELISA tests and calculated the ratios of t-tau/Aβ42 and p-tau181/Aβ42 in 240 Chinese Han patients with AD (n = 82), frontotemporal dementia (FTD, n = 20), Huntington's disease (HD, n = 27), multiple system atrophy (MSA, n = 24), spinocerebellar ataxia type-3 (SCA3, n = 27), amyotrophic lateral sclerosis (ALS, n = 36) and controls (n = 24). ResultsAs expected, all biomarkers showed high discriminative capacity between AD and non-AD groups (p < .05) except for the elevated CSF t-tau in FTD (p > .05). Comparing with the controls, tau related biomarkers significantly elevated in the FTD (p < .001) and MSA (p < .05) groups. Surprisingly, comparing with controls, we found that CSF Aβ42 increased remarkably in the SCA3 (p < .05), HD and ALS groups (p < .001), achieving a high specificity, respectively. ConclusionTo our best knowledge, this is the first comprehensive study in the Han Chinese population that confirmed the discriminative utility of CSF Aβ42 and tau biomarkers between AD and other neurodegenerative diseases.

Clinical correlates of decreased plasma coenzyme Q10 levels in patients with multiple system atrophy

IntroductionMultiple system atrophy (MSA) is a progressive neurodegenerative disease. Recent studies revealed decreased coenzyme Q10 (COQ10) levels in the cerebellum and blood samples of MSA patients. But few studies focused on the associations of COQ10 with the clinical symptoms of MSA. In this study, we aimed to quantify plasma COQ10 and characterize its association with clinical features. MethodsWe recruited 40 patients with MSA, 30 patients with Parkinson's disease (PD), and 30 healthy participants. Plasma COQ10 was quantified by UPLC-MS. The basic demographic data, motor symptoms, and non-motor symptoms were also assessed. ResultsPlasma COQ10 levels were significantly different in MSA, PD, and controls (P = 0.001). Post-hoc analysis revealed plasma COQ10 levels in MSA patients were lower than that in controls after adjusting for age, gender, and total cholesterol (P = 0.001). COQ10 levels differentiated MSA patients from controls with modest accuracy (P = 0.001). A sensitivity of 40% and a specificity of 97.5% was calculated with the receiver operating characteristic curve. However, COQ 10 levels did not discriminate between the MSA and PD groups (P = 0.07). Plasma COQ10 levels were correlated with the severity of motor symptoms only in MSA-C patients (b = −0.025, P = 0.009). ConclusionThe association between decreased COQ10 levels and the severity of motor symptoms in MSA-C patients promotes further research. Plasma COQ10 levels alone may not be a reliable MSA diagnostic biomarker, and cannot be considered a useful biomarker in the differential diagnosis of MSA vs PD.

3-Hz postural tremor in multiple system atrophy cerebellar type (MSA-C)-a static posturography study.

The objective of the study is to evaluate postural dysfunction of multiple system atrophy-parkinsonian type (MSA-P) and cerebellar type (MSA-C) by static posturography exam. A total of 29 MSA-P patients, 40 MSA-C patients, and 23 healthy controls (HC) were recruited and engaged in a sensory organization test (SOT). The amplitude of the postural sway was measured and transformed into energy value by Fourier analyzer. SOT scores, frequency of fallsand typical 3-Hz postural tremors during the four stance tasks, and energy value in three different frequency bands were recorded and compared. Compared with HC, SOT scores were significantly lower in MSA groups (P<0.01). Compared with MSA-P, the vestibular scores were further reduced in MSA-C patients (P<0.05). Falls were more frequent in MSA groups, especially in SOT4 task (foam surface with eyes closed) or in MSA-C group (P<0.05). Typical 3-Hz postural tremor was observed in 97.5% MSA-C patients, in 24.1% MSA-P patients but in none of the HC (P<0.05). Compared with HC, much more energy was consumed in every task, every direction, and nearly every frequency band in MSA groups. Energy value of MSA-C group was significantly higher than that of MSA-P, especially in higher frequency band (2~20Hz) or in more difficult stance tasks (SOT 3~4, foam surface with eyes open or closed) (P<0.05). Both MSA-P and MSA-C were characterized by severe static postural dysfunction. However, typical 3-Hz postural tremor was predominant in MSA-C and was very useful in the differential diagnosis between MSA-P and MSA-C.

Changes in cortisol and glucose concentrations in rabbits transported to the slaughterhouse

The effect of transport on Cortisol and Glucose serum concentrations were assessed in rabbits during summer and winter. Animals were divided into high (HSA, 307cm2/rabbit), medium (MSA, 373cm2/rabbit) and low space allowance (LSA, 475cm2/rabbit) transport groups, and rabbits slaughtered directly in the farm were used as control group (C). During summer, cortisol and glucose concentrations were significantly higher in HSA (high space allowance), MSA and LSA than in C rabbits (P < 0.01). LSA cortisol concentrations were significantly lower than MSA and HSA samples and MSA rabbits’ glycaemia was significantly higher (P < 0.01) compared with HSA animals. During winter, cortisol concentrations in group C were significantly lower than in MSA and HSA groups. Glycaemia in group C was lower than in LSA (P < 0.01) and HSA (P < 0.02) groups. Cortisol and glucose levels in summer were significantly higher than in winter. Our data clearly show that some stress-related physiological parameters are significantly modified by transport, in particular in the case of overcrowded transport crates.

Energy expenditure during everyday activities – a study comparing people with varying mobility limitations due to multiple sclerosis and healthy controls

Purpose: To investigate energy expenditure of people with multiple sclerosis (MS) during everyday activities. Methods: Fifteen healthy controls, 19 people with MS who used at most a stick to walk outdoors (MS-A), and 11 people with MS who used bilateral support for gait (MS-B) completed scripted everyday activities. A portable indirect calorimetry unit calculated energy expenditure. Steps were counted from video. Results: There was no significant difference in kcal between the three groups (ANOVA: F(2, 42) = 2.877, p = 0.067). There was a significant difference in steps: F(2, 42) = 17.93, p < 0.001. (Controls–MS-A 470.5, 95% CI 85.2, 855.7, Control–MS-B 1091.3, 95% CI 648.5, 1534.1, MS-A–MS-B 620.8, 95% CI 198.2, 1043.4.) Energy cost of movement was estimated by dividing kcal by steps. The Kruskal–Wallis analysis found significant difference for total (x2 = 11.726, df2, p = 0.003), Walking (x2 = 9.01, p = 0.011), Stairs (x2 = 16.436, 2, p < 0.001). Post-hoc analysis revealed significant differences between MS-B group and control and MS-A groups. Conclusions: People with MS do not use more energy than healthy controls during everyday activities at a self-selected pace. People with MS take significantly fewer steps during activities of daily living's. People who use bilateral support for gait have greater energy cost per step for walking and stairs activities.Implications for RehabilitationThis study found that the energy cost of movement is greater for people with MS with significant disability.Energy expenditure is an important consideration when prescribing physical activity and structured exercise for people with disability.It may be more appropriate to have energy, rather than movement, targets when prescribing physical activity for this population.

Different Impacts of Metabolic Syndrome Components on Insulin Resistance in Type 2 Diabetes

Objective. To examine the different impacts of MS components on insulin resistance in type 2 diabetes. Methods. A number of subjects (144) who met the criteria of (1) age between 30 and 75 years, (2) had type 2 diabetes for more than one year, and (3) taking gliclazide and metformin for more than 6 months were enrolled. All subjects were assigned to one of the four HOMA index categories. The HOMA index quartile 4 denotes the highest insulin resistance. The main outcome evaluated is the odds ratios (ORs) of different MS components on HOMA index quartile 4. The characteristics in HOMA index quartiles and groups of nonmetabolic syndrome (NMS; number of components < 2), metabolic syndrome A (MSA; number of components = 2), and metabolic syndrome B (MSB; number of components > 2) were also evaluated. Results. The results showed that both MSA and MSB groups had higher ORs (5.9 and 13.8 times, resp.) than the NMS group; and that subjects with large waist circumference (LWC) and high triglyceride (HTG) level have higher ORs (6.1 and 2.6 times, resp.) in developing higher insulin resistance than normal control subjects. Conclusion. Type 2 diabetic patients with greater number of MS components have higher ORs in developing increased insulin resistance.

Comparative Validity of Accelerometer-Based Measures of Physical Activity for People With Multiple Sclerosis

Coote S, O'Dwyer C. Comparative validity of accelerometer-based measures of physical activity for people with multiple sclerosis. ObjectiveTo estimate the criterion validity of accelerometer-based devices as measures of steps and energy expenditure in healthy controls and people with multiple sclerosis (MS) with varying disability levels during everyday activities. DesignCross-sectional study. SettingUniversity research room. ParticipantsPeople with MS who used at most a stick to walk outdoors (MS-A; n=19), people with MS who used bilateral support for gait (MS-B; n=11), and healthy controls (n=15). InterventionsParticipants completed 85 minutes of 9 scripted everyday activities. Main Outcome MeasuresEstimates of metabolic equivalent thresholds (METs) and kilocalories from a portable metabolic system, and steps counted from video of the activities. Step and MET estimates from an integrative accelerometer and from a uniaxial accelerometer, and kilocalorie estimates from the integrative accelerometer. ResultsThe uniaxial accelerometer had >30% error for steps for all groups. MET estimates had an intraclass correlation coefficient (ICC) <0.2 for all groups. For the integrative accelerometer, step estimates for controls had an ICC of .69 and <1% error. The step estimates for MS-A and MS-B groups had >20% error. The MET estimates had an ICC of .50 to .65 and 6% to 15% error. Kilocalorie estimates had 2.9% error for controls, 8.16% for MS-A, and 2.56% for MS-B groups. ICCs were all >.67, and mean differences from criterion were <20kcal. ConclusionsThe agreement between steps and MET estimates from both devices and the criterion was poor, particularly for people with MS. Only the step and MET estimates for the control group for the integrative accelerometer were not significantly different from the criterion. Kilocalorie estimates from the integrative accelerometer using the proprietary algorithms of the device provide the most valid estimate of physical activity during activities of daily living for people with a range of walking disabilities resulting from MS.

Improving Learning during Pediatric Lectures with Multiple Choice Questions

To evaluate the role of multiple choice questions (MCQs) administered at the conclusion of the lecture in improving medical student learning. This prospective interventional study was conducted in a Medical College. In ten randomly chosen pediatric lectures delivered to prefinal year medical students, MCQs were administered at the conclusion of the lecture and the answers were discussed with the students. After the series of lectures, students were evaluated by hundred 'single best response' MCQs with half from the lectures with MCQs self-assessment (MSA group) and the rest were from the other set of lectures (WMSA group). Scores from both groups were compared using paired 't' test. When the scores from MSA and WMSA groups were compared for the study population, no significant difference was noted. A significant difference (p = 0.003) was found between the groups, when the mean (± SD) scores of the men (25.2 ± 4.8 in the MSA group and 28.6 ± 7.3 in the WMSA group) were compared. No difference was seen among women, whose mean (± SD) scores in the MSA and the WMSA group were 26.6 ± 6.9 and 26.3 ± 6.9 respectively. When the scores of the first half of the session was analyzed, there was significant difference between the two groups among men (p = 0.0001) implying that lectures with MCQs self-assessment improved the long-term retention. MCQs' based self-assessment at the conclusion of the lecture does not improve the learning among prefinal year medical students. However, this study has shown the usefulness of MCQs based self-assessment among male medical students.

Gene expression changes in the nucleus accumbens of alcohol-preferring rats following chronic ethanol consumption

The objective of this study was to determine the effects of binge-like alcohol drinking on gene expression changes in the nucleus accumbens (ACB) of alcohol-preferring (P) rats. Adult male P rats were given ethanol under multiple scheduled access (MSA; three 1-h dark cycle sessions/day) conditions for 8 weeks. For comparison purposes, a second ethanol drinking group was given continuous/daily alcohol access (CA; 24 h/day). A third group was ethanol-naïve (W group). Average ethanol intakes for the CA and MSA groups were approximately 9.5 and 6.5 g/kg/day, respectively. Fifteen hours after the last drinking episode, rats were euthanized, the brains extracted, and the ACB dissected. RNA was extracted and purified for microarray analysis. The only significant differences were between the CA and W groups ( p < 0.01; Storey false discovery rate = 0.15); there were 374 differences in named genes between these 2 groups. There were 20 significant Gene Ontology (GO) categories, which included negative regulation of protein kinase activity, anti-apoptosis, and regulation of G-protein coupled receptor signaling. Ingenuity® analysis indicated a network of transcription factors, involving oncogenes ( Fos, Jun, Junb had higher expression in the ACB of the CA group), suggesting increased neuronal activity. There were 43 genes located within rat QTLs for alcohol consumption and preference; 4 of these genes ( Tgfa, Hspa5, Mtus1 and Creb3l2) are involved in anti-apoptosis and increased transcription, suggesting that they may be contributing to cellular protection and maintaining high alcohol intakes. Overall, these findings suggest that chronic CA drinking results in genomic changes that can be observed during the early acute phase of ethanol withdrawal. Conversely, chronic MSA drinking, with its associated protracted withdrawal periods, results in genomic changes that may be masked by tight regulation of these genes following repeated experiences of ethanol withdrawal.

A Late Stone Age sequence from West Ethiopia: the sites of K'aaba and Bel K'urk'uma (Assosa, Benishangul-Gumuz Regional State)

In this paper, the results of the test excavations in two rock shelters in the Central Ethiopian escarpment near the Sudanese border are presented. A continuous sequence of quartz lithic industry, from the lowest levels of K’aaba (with an archaic MSA-like industry of side-scrapers, Levallois- discoid cores and unifacial points) to the upper levels of Bel K’urk’umu (with a LSA industry, characterised by elongated flakes and end-scrapers, that still displays many archaic features such as centripetal flakes and cores) may be inferred. The escarpment’s mountainous and forested areas may have acted as a refuge zone from the end of the Pleistocene, when hyper-arid conditions deterred human occupation of the Sudanese plains nearby, and may also have been a cause for the cultural archaism of the late MSA groups, a case similar to others recorded in the African continent (South Africa, Zimbabwe, Nile Valley). The arrival of Sudanese pottery in the mid-Holocene period may be explained by the onset of arid conditions that drove “aqualithic” groups and early herders towards more humid areas. The conservative character of the late prehistoric cultural sequence derived from both sites is consistent with the resilient traditional nature of the Nilo- Saharan groups that currently settle the Ethio-Sudanese borderlands.

Protein expression changes in the nucleus accumbens and amygdala of inbred alcohol-preferring rats given either continuous or scheduled access to ethanol

Chronic ethanol (EtOH) drinking produces neuronal alterations within the limbic system. To investigate changes in protein expression levels associated with EtOH drinking, inbred alcohol-preferring (iP) rats were given one of three EtOH access conditions in their home-cages: continuous ethanol (CE: 24 h/day, 7 days/week access to EtOH), multiple scheduled access (MSA: four 1-h sessions during the dark cycle/day, 5 days/week) to EtOH, or remained EtOH-naïve. Both MSA and CE groups consumed between 6 and 6.5 g of EtOH/kg/day after the 3rd week of access. On the first day of EtOH access for the seventh week, access was terminated at the end of the fourth MSA session for MSA rats and the corresponding time point (2300 h) for CE rats. Ten h later, the rats were decapitated, brains extracted, the nucleus accumbens (NAcc) and amygdala (AMYG) microdissected, and protein isolated for 2-dimensional gel electrophoretic analyses. In the NAcc, MSA altered expression levels for 12 of the 14 identified proteins, compared with controls, with six of these proteins altered by CE access, as well. In the AMYG, CE access changed expression levels for 22 of the 27 identified proteins, compared with controls, with 8 of these proteins altered by MSA, as well. The proteins could be grouped into functional categories of chaperones, cytoskeleton, intracellular communication, membrane transport, metabolism, energy production, or neurotransmission. Overall, it appears that EtOH drinking and the conditions under which EtOH is consumed, differentially affect protein expression levels between the NAcc and AMYG. This may reflect differences in neuroanatomical and/or functional characteristics associated with EtOH self-administration and possibly withdrawal, between these two brain structures.

THE RELATIONSHIP BETWEEN LOCOMOTOR DISABILITY, AUTONOMIC DYSFUNCTION, AND THE INTEGRITY OF THE STRIATAL DOPAMINERGIC SYSTEM IN PATIENTS WITH MULTIPLE SYSTEM ATROPHY, PURE AUTONOMIC FAILURE, AND PARKINSON'S DISEASE, STUDIED WITH PET

18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present.

Underfeeding versus overfeeding

Coote S, O'Dwyer C. Comparative validity of accelerometer-based measures of physical activity for people with multiple sclerosis.To estimate the criterion validity of accelerometer-based devices as measures of steps and energy expenditure in healthy controls and people with multiple sclerosis (MS) with varying disability levels during everyday activities.Cross-sectional study.University research room.People with MS who used at most a stick to walk outdoors (MS-A; n=19), people with MS who used bilateral support for gait (MS-B; n=11), and healthy controls (n=15).Participants completed 85 minutes of 9 scripted everyday activities.Estimates of metabolic equivalent thresholds (METs) and kilocalories from a portable metabolic system, and steps counted from video of the activities. Step and MET estimates from an integrative accelerometer and from a uniaxial accelerometer, and kilocalorie estimates from the integrative accelerometer.The uniaxial accelerometer had >30% error for steps for all groups. MET estimates had an intraclass correlation coefficient (ICC) <0.2 for all groups. For the integrative accelerometer, step estimates for controls had an ICC of .69 and <1% error. The step estimates for MS-A and MS-B groups had >20% error. The MET estimates had an ICC of .50 to .65 and 6% to 15% error. Kilocalorie estimates had 2.9% error for controls, 8.16% for MS-A, and 2.56% for MS-B groups. ICCs were all >.67, and mean differences from criterion were <20kcal.The agreement between steps and MET estimates from both devices and the criterion was poor, particularly for people with MS. Only the step and MET estimates for the control group for the integrative accelerometer were not significantly different from the criterion. Kilocalorie estimates from the integrative accelerometer using the proprietary algorithms of the device provide the most valid estimate of physical activity during activities of daily living for people with a range of walking disabilities resulting from MS.