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1.
Pain is an important and distressing symptom in Parkinson’s disease (PD). Our aim was to determine the prevalence of pain, its various types and characteristics, as well as its impact on depression and quality of life (QoL) in patients with PD. How pain differs in early- and advanced-stage PD and male and female PD patients was of special interest. One hundred PD patients on dopaminergic medications had a neurological examination and participated in a structured interview on pain characteristics and completed standardized questionnaires. A total of 76% of the patients had pain. The following types of pain were present: musculoskeletal pain accounted for 41% of the total pain, dystonic pain for 17%, central neuropathic pain for 22%, radicular pain for 27%, and other pains (non-radicular low back pain, arthritic, and visceral pain) made up 24%. One type of pain affected 29% of all the subjects, two types 35%, three types 10%, and four types of pain were reported by 2%. All types of pain were more prevalent in advanced-stage PD subjects than in early-stage PD subjects, except for arthritic pain (subclassified under”other pain”). The frequency and intensity of actual, average, and worst experienced pain were significantly more severe in advanced-stage subjects. PD subjects with general pain and in advanced stages were more depressed and had poorer QoL. Depression correlated with worst pain in the last 24 hours and with pain periodicity (the worst depression score in patients with constant pain). QoL correlated with average pain in the last 7 days. Pain is a frequent problem in PD patients, and it worsens during the course of the disease.  相似文献   

2.
Summary Human microvascular endothelial cells (HMVEC) from adult adipose tissue were cultured in MCDB 131 medium supplemented with 10% fetal bovine serum. Under these conditions, HMVEC from seven different donors had finite proliferative life spans ranging from 14.5 to 23.5 population doublings (PD), with a mean life span of 19 PD. Addition of 10% conditioned medium from activated human leukocyte cultures (BM Condimed?) extended the life span of HMVEC to 31 to 41 PD, with a mean life span of 37 PD. At the end of lifespan, HMVEC cultures both with and without BM Condimed had very low labeling indices (0 to 5% [3H]thymidine labeled nuclei) and consisted of enlarged cells. However, the morphologies of the two types of HMVEC cultures were very different. Untreated HMVEC were polygonal endothelial cells that formed cobblestonelike monolayers with no cell overlapping. In contrast, BM Condimed-treated HMVEC were more elongated, less regularly shaped cells that were not strictly inhibited from overlapping. When old, these cells accumulated numerous vacuoles. The BM Condimed-treated HMVEC expressed Factor VIII antigen, which confirms their identity as endothelial cells. These cells reverted rapidly to the polygonal morphology of untreated HMVEC when they were removed from BM Condimed. Likewise, their proliferative capacity was not extended further once BM condimed was removed. These results suggest that HMVEC can exist in two distinct morphologic states in which the cells have different finite proliferative life spans. This work was supported by grants AG00947 and AG04811 from the National Institute on Aging, Bethesda, MD.  相似文献   

3.
Biological motion (BM) perception is the compelling ability of the visual system to perceive complex animated movements effortlessly and promptly. A recent study has shown that BM can automatically lengthen perceived temporal duration independent of global configuration. The present study aimed mainly to investigate this temporal dilation effect of BM signals in Parkinson’s disease (PD) patients. We used the temporal dilation effect as an implicit measure of visual processing of BM. In all, 32 PD patients (under off-therapy conditions) and 32 healthy controls (HCs) participated in our study. In each trial, an upright BM sequence and an inverted BM sequence were presented within an interval in the center of the screen. We tested both canonical and scrambled BM sequences; the scrambled ones were generated by disturbing the global configuration of the canonical ones but preserving exactly the same local motion components. Observers were required to make a verbal two-alternative forced choice response to indicate which interval (the first or the second) appeared longer. Statistical analyses were conducted on the points of subjective equality (PSEs). We found that the temporal dilation effect was significantly reduced for PD patients compared with HCs in both canonical and scrambled BM conditions. Moreover, no temporal dilation effects of scrambled BM were shown in both early- and late-stage PD patients, while the temporal dilation effect of canonical BM was relatively preserved in the early stages.  相似文献   

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5.
Circulating endothelial progenitor cells (EPCs) derived from the bone marrow (BM) participate in maintaining endothelial integrity and vascular homeostasis. Reduced EPC number and function result in vascular complications in diabetes. EPCs are a population of cells existing in various differentiation stages, and their cell surface marker profiles change during the process of mobilization and maturation. Hence, a generally accepted marker combination and a standardized protocol for the quantification of EPCs remain to be established. To determine the EPC subsets that are affected by diabetes, we comprehensively analyzed 32 surface marker combinations of mouse peripheral blood (PB), BM, and spleen cells by multicolor flow cytometry. Ten subsets equivalent to previously reported mouse EPCs significantly declined in number in the PB of streptozotocin-induced diabetic mice, and this reduction was reversed by insulin treatment. The PI(-)Lin(-)c-Kit(-)Sca-1(+)Flk-1(-)CD34(-)CD31(+) EPC cluster, which can differentiate into mature endothelial cells in vitro, was the highest population in the PB, BM, and spleen and occurred 61 times more in the spleen than in the PB. The cell number significantly decreased in the BM as well as in the PB but paradoxically increased in the spleen under diabetic conditions. Insulin treatment reversed the decrease of EPC subsets in the BM and PB and reversed their increase in spleen. A similar tendency was observed in some of the major cell populations in db/db mice. To the best of our knowledge, we are the first to report spatial population changes in mouse EPCs by diabetes in the blood and in the BM across the spleen. Diminished circulating EPC supply by diabetes may be ascribed to impaired EPC production in the BM and to decreased EPC mobilization from the spleen, which may contribute to vascular dysfunction in diabetic conditions.  相似文献   

6.
The aim of the study was to investigate how chemo-somatosensory event-related potentials (CSSERPs) and pain ratings are modified by repetitive painful stimulation of the nasal mucosa (58% v/v CO2, 200 msec duration). Twenty-two subjects performed 3 experiments during which trains of stimuli were applied. The interstimulus interval (ISI) between stimuli was constant for each experiment, but varied between experiments (8, 4, and 2 sec). CSSERPs were obtained from positions (Fz, C3, Cz, C4, and Pz). The subjects not only rated the overall perceived intensities but also reported the quality of the stimuli. At an ISI of 8 sec estimates decreased and only stinging sensations were reported. In contrast, at an interval of 2 sec estimates increased being accompanied by the buildup of burning pain. This phenomenon was interpreted in terms of the superposition of first (sharp and stinging pain: Aδ fibers) and second pain (dull and burning pain: C fibers), respectively. However, given the special circumstances of short ISIs CSSERP amplitudes decreased the more the shorter the ISI was. In line with previous investigations it is hypothesised that CSSERPs predominantly reflect nociceptive information transmitted via Aδ fibers.  相似文献   

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8.
Singh KA  Brennan DS 《Gerodontology》2012,29(2):106-110
doi: 10.1111/j.1741‐2358.2010.00412.x Chewing disability in older adults attributable to tooth loss and other oral conditions Background: This study evaluates associations between oral health‐related factors and chewing ability, and quantifies the risk contributed by each factor. Materials and methods: Chewing ability and information on number of teeth, dentures and dental problems over the last 12 months were collected by mailing questionnaires to a random sample of 60‐ to 71‐year‐olds from Adelaide, South Australia. Logistic regression was used to model oral status and oral symptoms as predictors of chewing disability, and to estimate the population‐attributable fraction. Results: A total of 444 persons responded (response rate = 68.8%). Among dentate subjects, 10.3% were chewing‐deficient, with chewing disability more prevalent (p < 0.05) among those with <21 teeth (26.4%), dentures (20.4%), painful aching in the mouth (25.4%), pain in the face (16.7%), broken/chipped teeth (15.6%), sensitive teeth (14.1%), loose teeth (37.1%), and sore gums (18.0%). Adjusted Odds ratios (OR) showed inadequate dentition (OR = 4.20), painful aching in the mouth (OR = 4.88), and presence of loose teeth (OR = 4.70) were associated with chewing disability (p < 0.01), and their population attributable fractions were 18.5%, 15.1% and 7.8% respectively. Conclusions: Loose teeth, number of teeth and pain in the mouth were associated with chewing disability, with an inadequate dentition and pain in the mouth contributing most to chewing disability in this population.  相似文献   

9.
Objective: The purpose of this study was to evaluate the prevalence and severity of periodontitis in men of 65+ years and identify demographic and lifestyle factors associated with its presence. Methods: Participants were recruited from the Osteoporotic Fractures in Men Study, a longitudinal study of risk factors for fractures in older men. Dental measures included clinical attachment loss (CAL), pocket depth (PD), calculus, plaque and bleeding on a random half‐mouth, plus a questionnaire regarding access to care, symptoms and previous diagnosis. Results: 1210 dentate men completed the dental visit. Average age was 75 years, 39% reported some graduate school education, 32% smoked 20 + pack years and 88% reported their overall health as excellent/good. In terms of periodontal health, 38% had sub‐gingival calculus, 53% gingival bleeding, 82% CAL ≥5 mm and 34% PD ≥6 mm. The prevalence of severe periodontitis was 38%. Significant demographic and lifestyle factors associated with severe periodontitis in multivariate analyses included age ≥75 (OR 1.4, 95% CI 1.1–1.7) non‐white race (OR 1.9, 95% CI 1.3–2.8), less than an annual dental visit (OR 1.5, 95% CI 1.1–2.0), and 20 + pack years (OR 2.1, 95% CI 1.6–2.7). Conclusion: A high proportion of healthy older men have evidence of periodontal destruction which could, given the growing ageing population, have a significant impact on the dental profession’s ability to provide preventive and therapeutic care. The population at highest risk of periodontitis in MrOS is older minority men who smoke and do not have annual dental visits.  相似文献   

10.
Blood pressure (BP) and heart rate (HR) rhythms were studied in premature infants (299 profiles ranged 24-106 h at 20--min intervals) and 11-13-year-old children (19 profiles for 48 h at 15-min intervals) to explore ultradian-to-circannual rhythm characteristics in BP and HR in preterm human infant and to elucidate the influence of antenatal betamimetic (BM) exposure on adolescent BP and HR rhythms. A circannual modulation of the 3-h amplitude (A) or MESOR of systolic BP (SBP) and diastolic BP (DBP) was seen mainly in prematures with a positive family history of high BP on the father's (f+) side or with both a patro linous and matro-linous history (f+m+), the circannual modulation of HR ultradian A was statistically significant only in "f- m-" infants. In urine collected at 3 h intervals for 24-h spans from 21 premature infants Na+,K+ and 11-oxycorticosteroids had a significant circadian rhythm. 9 adolescents (BM+), which were exposed in utero to different BM doses, had a significantly higher SBP and DBP MESOR and numerically higher circadian A as compared to 10 controls (BM-); correlation (P less than 0.05) between BM dose and HR circadian A was found. DBP led SBP in 8 or 10 "BM-" but in 4 of 9 "BM+" (acrophase difference 17 min and 3 min correspondingly).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

11.
Morphine is a widely used opioid analgesic, which shows large differences in clinical response in children, even when aiming for equivalent plasma drug concentrations. Age-dependent brain disposition of morphine could contribute to this variability, as developmental increase in blood-brain barrier (BBB) P-glycoprotein (Pgp) expression has been reported. In addition, age-related pharmacodynamics might also explain the variability in effect. To assess the influence of these processes on morphine effectiveness, a multi-compartment brain physiologically based pharmacokinetic/pharmacodynamic (PB-PK/PD) model was developed in R (Version 3.6.2). Active Pgp-mediated morphine transport was measured in MDCKII-Pgp cells grown on transwell filters and translated by an in vitro-in vivo extrapolation approach, which included developmental Pgp expression. Passive BBB permeability of morphine and its active metabolite morphine-6-glucuronide (M6G) and their pharmacodynamic parameters were derived from experiments reported in literature. Model simulations after single dose morphine were compared with measured and published concentrations of morphine and M6G in plasma, brain extracellular fluid (ECF) and cerebrospinal fluid (CSF), as well as published drug responses in children (1 day– 16 years) and adults. Visual predictive checks indicated acceptable overlays between simulated and measured morphine and M6G concentration-time profiles and prediction errors were between 1 and -1. Incorporation of active Pgp-mediated BBB transport into the PB-PK/PD model resulted in a 1.3-fold reduced brain exposure in adults, indicating only a modest contribution on brain disposition. Analgesic effect-time profiles could be described reasonably well for older children and adults, but were largely underpredicted for neonates. In summary, an age-appropriate morphine PB-PK/PD model was developed for the prediction of brain pharmacokinetics and analgesic effects. In the neonatal population, pharmacodynamic characteristics, but not brain drug disposition, appear to be altered compared to adults and older children, which may explain the reported differences in analgesic effect.  相似文献   

12.
Objective: To assess the efficacy of subantimicrobial dose doxycycline (SDD; 20 mg doxycycline twice daily) as an adjunct to scaling and root planing (SRP) in the treatment of moderate‐severe chronic periodontitis (CP) in institutionalised elderly patients aged 65 years or older. Background: Previous studies have shown that SDD is of clinical benefit in the treatment of CP. However, the benefits of SDD in geriatric populations (65+ years) have not been determined. Material and methods: A 9‐month, double‐blind, randomised, placebo‐controlled pilot study was conducted. 24 institutionalised geriatric patients (65 years or older) with evidence of CP manifested by baseline clinical attachment levels (CAL) 5–9 mm, probing depths (PD) 4–9 mm and bleeding on probing (BOP) were recruited. At baseline, patients were treated by a standardised episode of SRP, and randomised to receive either adjunctive SDD or placebo. Full mouth PD and CAL were measured using the manual UNC‐15 periodontal probe at 3, 6, and 9 months post‐baseline to assess the response to treatment. Periodontal sites were stratified by baseline PD value: sites with PD 4–5 mm were considered moderately diseased and sites with PD ≥6 mm severely diseased. Results: The SRP + placebo resulted in PD reductions similar to those reported previously in the literature. At all time‐points and in both moderate and deep sites, SRP + SDD resulted in significantly greater PD reductions relative to baseline than SRP + placebo. At month 9, in moderate sites, mean PD reductions of 1.57 ± 0.11 mm were reported in the adjunctive SDD group, compared with 0.63 ± 0.11 mm in the adjunctive placebo group (p < 0.001). In deep sites at month 9, mean PD reductions of 3.22 ± 0.29 mm were reported in the adjunctive SDD group, compared with 0.98 ± 0.31 mm in the adjunctive placebo group (p < 0.05). Similar improvements were observed for CAL in the SDD group compared with the placebo group. Significantly lower BOP scores were also recorded at month 9 in the SDD group (7.5%) compared with the placebo group (71.2%) (p < 0.01). Conclusion: SDD used as an adjunct to SRP provides significant benefit for elderly patients with CP compared with SRP alone.  相似文献   

13.
Research has demonstrated the need for identifying a novel antimicrobial agent for topical use in the pediatric dental population. The essential oil of Lippia sidoides Cham. (LSO) has been described as having favorable biological properties, and a broad in vitro and in vivo antimicrobial spectrum against bacteria and yeast infections. Our aim was to determine a dose and formulation of LSO, acceptable for clinical testing in a pediatric population with dental caries. Thirty-seven 6-12-year old children were selected to participate in this study, and randomly allocated to receive different concentrations of either a gel (0.8%, 1%, 1.2% and 1.4%) or a mouth rinse (0.6%, 0.8%, 1% and 1.2%) formulation. The highest percentage MS reduction was observed with 0.8% mouth rinse and 1.4% gel. The efficacy of these concentrations was compared with a Thy-Car mixture formulated as a mouth rinse and gel treatments in 11 children. Saliva was collected after a single application of the antimicrobial treatment to establish effectiveness against MS. Both rinse (p < 0.001) and gel (p = 0.02) formulations produced significant MS reduction. Mouth rinse concentrations above 0.8% were associated with a transient intra-oral burning sensation. In conclusion, mouth rinse and gel LSO formulations demonstrated effectiveness against MS and good acceptance among children. We suggest future randomized clinical trials to test its effectiveness against early childhood caries.  相似文献   

14.
Time-dependent variations in clock gene expression have recently been observed in mouse hematopoietic cells, but the activity of these genes in human bone marrow (BM) has so far not been investigated. Since such data can be of considerable clinical interest for monitoring the dynamics in stem/progenitor cells, the authors have studied mRNA expression of the clock genes hPer1 , hPer2, hCry1, hCry2, hBmal1, hRev-erb alpha, and hClock in human hematopoietic CD34-positive (CD34( +)) cells. CD34(+) cells were isolated from the BM samples obtained from 10 healthy men at 6 times over 24 h. In addition, clock gene mRNA expression was analyzed in the whole BM in 3 subjects. Rhythms in serum cortisol, growth hormone, testosterone, and leukocyte counts documented that subjects exhibited standardized circadian patterns. All 7 clock genes were expressed both in CD34(+) cells and the whole BM, with some differences in magnitude between the 2 cell populations. A clear circadian rhythm was shown for hPer1, hPer2, and hCry2 expression in CD34(+) cells and for hPer1 in the whole BM, with maxima from early morning to midday. Similar to mouse hematopoietic cells, h Bmal1 was not oscillating rhythmically. The study demonstrates that clock gene expression in human BM stem/progenitor cells may be developmentally regulated, with strong or weaker circadian profiles as compared to those reported in other mature tissues.  相似文献   

15.
16.
Rac2 is a hematopoietic-specific Rho family GTPase implicated as an important constituent of the NADPH oxidase complex and shares 92% amino acid identity with the ubiquitously expressed Rac1. In bone marrow (BM) neutrophils isolated from rac2(-/-) mice generated by gene targeting, we previously reported that PMA-induced superoxide production was reduced by about 4-fold, which was partially corrected in TNF-alpha-primed BM neutrophils and in peritoneal exudate neutrophils. We investigated receptor-mediated activation of the NADPH oxidase in the current study, finding that superoxide production in rac2(-/-) BM and peritoneal exudate neutrophils was normal in response to opsonized zymosan, reduced to 22% of wild type in response to IgG-coated SRBC, and almost absent in response to fMLP. In wild-type murine BM neutrophils, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and Akt was induced by PMA or fMLP, which was decreased in rac2(-/-) neutrophils for ERK1/2 and p38. Activation of p38 by either opsonized zymosan or IgG-coated SRBC was similar in wild-type and rac2(-/-) cells. Inhibition of ERK1/2 or p38 activation using either PD98059 or SB203580, respectively, had only a modest effect on fMLP-elicited superoxide production and no effect on the PMA-induced response. These data provide genetic evidence supporting an important role for Rac2 in regulating neutrophil NADPH oxidase activation downstream of chemoattractant and Fcgamma receptors. The effect of Rac2 deficiency on superoxide production is probably exerted through multiple pathways, including those independent of mitogen-activated protein kinase activation.  相似文献   

17.
Fifteen bone marrow (BM) and venous blood circadian profiles were obtained from 13 diurnally-active, healthy men sampled every 4-5 h for 24 h. Peripheral blood (PB) was also sampled in subsets of 5 men either for 24 h immediately preceding the BM procedure or 5-6 months afterwards. Cortisol and white and red cell parameters were determined in PB. BM cell cycle distribution was investigated in parallel by flow cytometry for S-phase DNA of total mononuclear cells and subpopulations of erythroid and myeloid precursor cells. On a group basis, significant circadian rhythms were found in PB variables commonly referred to as "marker" rhythms (cortisol, total white cells [WBC], neutrophils [N], lymphocytes [L]), with acrophases less than 2 h apart between the contro l day prior to and during BM sampling. Thus, major, but relatively short-lasting physiological stress, like BM aspirations or blood sampling itself, although repeated several times over 24 h, seemed to have minor influence on these rhythms on days of the BM procedure. When comparing the times of highest or lowest values in PB with times of highest or lowest values in BM, several temporal relationships were found. Among other associations, timing of lowest values in WBC, N and L or highest values in cortisol was significantly predictive of highest values in myeloid cells occurring in the following 12 h, whereas highest values in erythroid cells occurred significantly more often in the 12 h interval beginning 4 h after the time of lowest values in WBC, L and N. The stability in the circadian rhythms of the PB variables suggests that information obtained on one day can be used to guide procedures on the next, such as BM myelotoxic chronotherapy or BM harvesting.  相似文献   

18.
doi: 10.1111/j.1741‐2358.2012.00627.x Salivary tests associated with elderly people’s oral health Introduction: The saliva constitutes essential condition for the individual’s health. Aim: Identify the relation of the salivary flow and saliva pH with medicine use and oral discomfort in elderly. Methods and materials: Cross‐sectional study with 68 elderly living in a long staying institution. Salivary tests were performed based on Bo Krasse’s methodology. For pH, the Universalindikator – Merck tape was used. A questionnaire was applied, organising data through Software SPSS version 17. Pearson’s qui‐square distribution, Fisher’s exact test and t‐test for paired data were used, with significance level of 5% and confidence interval of 95%. Results: Among the 68 elderly (average of 70.4 years, SD ± 7.27), 80% showed normal pH. The rate of salivary flow was as follows: very low, 32.3%; lowered, 41.2%; and normal, 25.5%; 30.9% reported dry mouth; 22.1% problems with taste; 17.6%, dysphagia; and 14.7%, burning mouth. 76.5% used medicines. There was statistical significance between medicine use and dry mouth (p = 0.015). They showed an association between salivary flow and medicine use (p = 0.048), feels dry mouth (0.018) and difficulty to swallow (p = 0.046), and saliva pH without stimulation and feels dry mouth (p = 0.003), difficulty to swallow (p = 0.006) and burning mouth sensation (p = 0.014). Conclusion: Low salivary flow and saliva pH interfere on elderly people’s health and medicine use influences on results.  相似文献   

19.
A fluorescence-based continuous-flow enzyme affinity detection (EAD) setup was used to screen cytochrome P450 BM3 mutants on-line for diversity. The flow-injection screening assay is based on the BM3-mediated O-dealkylation of alkoxyresorufins forming the highly fluorescent product resorufin, and can be used in different configurations, namely injection of ligands, enzymes and substrates. Screening conditions were optimized and the activity of a library of 32 BM3 mutants towards the recently synthesized new probe substrate allyloxyresorufin was measured in flow-injection analysis (FIA) mode and it was shown that large activity differences between the mutants existed. Next, six BM3 mutants containing mutations at different positions in the active site were selected for which on-line enzyme kinetics were determined. Subsequently, for these six BM3 mutants affinity towards a set of 30 xenobiotics was determined in FIA EAD mode. It was demonstrated that significant differences existed for the affinity profiles of the mutants tested and that these differences correlated to alterations in the BM3 mutant-generated metabolic profiles of the drug buspirone. In conclusion, the developed FIA EAD approach is suitable to screen for diversity within BM3 mutants and this alternative screening technology offers new perspectives for rapid and sensitive screening of compound libraries towards BM3 mutants.  相似文献   

20.
In order to assess the applicability of bovine microsatellite markers for population genetic studies in Swiss yak, 131 bovine microsatellite markers were tested on a panel of 10 animals. Efficient amplification was observed for 124 markers (94.6%) with a total of 476 alleles, of which 117 markers (94.3%) were polymorphic. The number of alleles per locus among the polymorphic markers ranged from two to nine. Seven loci (ILSTS005, BMS424B, BMS1825, BMS672, BM1314, ETH123 and BM6017) failed to amplify yak genomic DNA. Two cattle Y-chromosome specific microsatellite markers (INRA126 and BM861) amplified genomic DNA from both male and female yaks. However, two additional markers on cattle Y-chromosome (INRA124 and INRA189) amplified DNA from only males. Of the polymorphic markers, 24 microsatellites proposed by CaDBase for within- and cross-species comparisons and two additional highly polymorphic markers (MHCII and TGLA73) were used to investigate the genetic variability and the population structure of a Swiss yak herd that included 51 additional animals. The polymorphic information content ranged from 0.355 to 0.752, while observed heterozygosity (HO) ranged from 0.348 to 0.823. Furthermore, a set of 13 markers, organized into three multiplex polymerase chain reactions, was evaluated for routine parentage testing. This set provided an exclusion probability in a family of four yaks (both parents and two offspring) of 0.995. These microsatellites serve as useful tools for genetic characterization of the yak, which continues to be an important domestic livestock species.  相似文献   

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