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1.
Importance
Psychological and health-restorative benefits of mind-body therapies have been investigated, but their impact on the immune system remain less defined.Objective
To conduct the first comprehensive review of available controlled trial evidence to evaluate the effects of mind-body therapies on the immune system, focusing on markers of inflammation and anti-viral related immune responses.Methods
Data sources included MEDLINE, CINAHL, SPORTDiscus, and PsycINFO through September 1, 2013. Randomized controlled trials published in English evaluating at least four weeks of Tai Chi, Qi Gong, meditation, or Yoga that reported immune outcome measures were selected. Studies were synthesized separately by inflammatory (n = 18), anti-viral related immunity (n = 7), and enumerative (n = 14) outcomes measures. We performed random-effects meta-analyses using standardized mean difference when appropriate.Results
Thirty-four studies published in 39 articles (total 2, 219 participants) met inclusion criteria. For inflammatory measures, after 7 to 16 weeks of mind-body intervention, there was a moderate effect on reduction of C-reactive protein (effect size [ES], 0.58; 95% confidence interval [CI], 0.04 to 1.12), a small but not statistically significant reduction of interleukin-6 (ES, 0.35; 95% CI, −0.04 to 0.75), and negligible effect on tumor necrosis factor-α (ES, 0.21; 95% CI, −0.15 to 0.58). For anti-viral related immune and enumerative measures, there were negligible effects on CD4 counts (ES, 0.15; 95% CI, −0.04 to 0.34) and natural killer cell counts (ES, 0.12, 95% CI −0.21 to 0.45). Some evidence indicated mind-body therapies increase immune responses to vaccination.Conclusions
Mind-body therapies reduce markers of inflammation and influence virus-specific immune responses to vaccination despite minimal evidence suggesting effects on resting anti-viral or enumerative measures. These immunomodulatory effects, albeit incomplete, warrant further methodologically rigorous studies to determine the clinical implications of these findings for inflammatory and infectious disease outcomes. 相似文献2.
Background
Curcumin (CUR) has deserved extensive research due to its anti-inflammatory properties, of interest in human diseases including cancer. However, pleiotropic even paradoxical responses of tumor cells have been reported, and the mechanisms of action of CUR remain uncompletely elucidated.Methodology/Principal Findings
1H-NMR spectroscopy-based metabolomics was applied to get novel insight into responses of MCF7 and MDA-MB-231 breast cancer cells to CUR alone, and MCF7 cells to CUR in cotreatment with docetaxel (DTX). In both cell types, a major target of CUR was glutathione metabolism. Total glutathione (GSx) increased at low dose CUR (≤ 10 mg.l−1–28 µM-) (up to +121% in MCF7 cells, P<0.01, and +138% in MDA-MB-231 cells, P<0.01), but decreased at high dose (≥ 25 mg.l−1 −70 µM-) (−49%, in MCF7 cells, P<0.02, and −56% in MDA-MB-231 cells, P<0.025). At high dose, in both cell types, GSx-related metabolites decreased, including homocystein, creatine and taurine (−60 to −80%, all, P<0.05). Together with glutathione-S-transferase actvity, data established that GSx biosynthesis was upregulated at low dose, and GSx consumption activated at high dose. Another major target, in both cell types, was lipid metabolism involving, at high doses, accumulation of polyunsaturated and total free fatty acids (between ×4.5 and ×11, P<0.025), and decrease of glycerophospho-ethanolamine and -choline (about −60%, P<0.025). Multivariate statistical analyses showed a metabolic transition, even a biphasic behavior of some metabolites including GSx, between low and high doses. In addition, CUR at 10 mg.l−1 in cotreatment with DTX induced modifications in glutathione metabolism, lipid metabolism, and glucose utilization. Some of these changes were biphasic depending on the duration of exposure to CUR.Conclusions/Significance
Metabolomics reveals major metabolic targets of CUR in breast cancer cells, and biphasic responses that challenge the widely accepted beneficial effects of the phytochemical. 相似文献3.
Background
Obesity is considered as a systemic chronic low grade inflammation characterized by increased serum pro-inflammatory proteins and accumulation of macrophages within white adipose tissue (WAT) of obese patients. C5L2, a 7-transmembrane receptor, serves a dual function, binding the lipogenic hormone acylation stimulating protein (ASP), and C5a, involved in innate immunity.Aim
We evaluated the impact of C5L2 on macrophage infiltration in WAT of wildtype (Ctl) and C5L2 knock-out (C5L2−/−) mice over 6, 12 and 24 weeks on a chow diet and moderate diet-induced obesity (DIO) conditions.Results
In Ctl mice, WAT C5L2 and C5a receptor mRNA increased (up to 10-fold) both over time and with DIO. By contrast, in C5L2−/−, there was no change in C5aR in WAT. C5L2−/− mice displayed higher macrophage content in WAT, varying by time, fat depot and diet, associated with altered systemic and WAT cytokine patterns compared to Ctl mice. However, in all cases, the M1 (pro-) vs M2 (anti-inflammatory) macrophage proportion was unchanged but C5L2−/− adipose tissue secretome appeared to be more chemoattractant. Moreover, C5L2−/− mice have increased food intake, increased WAT, and altered WAT lipid gene expression, which is reflected systemically. Furthermore, C5L2−/− mice have altered glucose/insulin metabolism, adiponectin and insulin signalling gene expression in WAT, which could contribute to development of insulin resistance.Conclusion
Disruption of C5L2 increases macrophage presence in WAT, contributing to obesity-associated pathologies, and further supports a dual role of complement in WAT. Understanding this effect of the complement system pathway could contribute to targeting treatment of obesity and its comorbidities. 相似文献4.
Prin Vathesatogkit Piyamitr Sritara Merel Kimman Bunlue Hengprasith Tai E-Shyong Hwee-Lin Wee Mark Woodward 《PloS one》2012,7(11)
Background
The impact of the presence and awareness of individual health states on quality of life (HRQoL) is often documented. However, the impacts of different health states have rarely been compared amongst each other, whilst quality of life data from Asia are relatively sparse. We examined and compared the effects of different health states on quality of life in a Thai population.Methods
In 2008–2009, 5,915 corporate employees were invited to participate in a survey where HRQoL was measured by the Short Form 36 (SF-36) questionnaire. The adjusted mean SF-36 scores were calculated for each self-reported illness, number of chronic conditions, lifestyle factors and awareness of diabetes and hypertension. The effect sizes (ES) were compared using Cohen''s d.Results
The response rate was 82% and 4,683 (79.1%) had complete data available for analysis. Physical and Mental Component Summary (PCS and MCS) scores decreased as the number of chronic conditions increased monotonically (p<0.0001). Diabetes and hypertension negatively influenced PCS (mean score differences −0.6 and −1.5, p<0.001 respectively) but not MCS, whereas awareness of diabetes and hypertension negatively influenced MCS (−2.9 and −1.6, p<0.005 respectively) but not PCS. Arthritis had the largest ES on PCS (−0.37), while awareness of diabetes had the largest ES on MCS (−0.36). CVD moderately affected PCS and MCS (ES −0.34 and −0.27 respectively). Obesity had a negative effect on PCS (ES −0.27). Exercise positively affected PCS and MCS (ES +0.08 and +0.21 (p<0.01) respectively).Conclusion
Health promotion to reduce the prevalence of chronic diseases is important to improve the quality of life in Asian populations. Physical activity is an important part of such programs. Awareness of diseases may have greater impacts on mental health than having the disease itself. This has implications for the evaluation of the cost-benefit of screening and labeling of individuals with pre-disease states. 相似文献5.
Lu Yin Na Wang Sten H. Vermund Bryan E. Shepherd Yuhua Ruan Yiming Shao Han-Zhu Qian 《PloS one》2014,9(9)
Background
Prevention intervention trials have been conducted to reduce risk of sexual transmission among people living with HIV/AIDS (PLWHA), but the findings were inconsistent. We performed a systematic review and meta-analysis to evaluate overall efficacy of prevention interventions on unprotected vaginal or anal intercourse (UVAI) among PLWHA from randomized clinical trials (RCTs).Methods
RCTs of prevention interventions among PLWHA published as of February 2012 were identified by systematically searching thirteen electronic databases. The primary outcome was UVAI. The difference of standardized mean difference (SMD) of UVAI between study arms, defined as effect size (ES), was calculated for each study and then pooled across studies using standard meta-analysis with a random effects model.Results
Lower likelihood of UVAI was observed in the intervention arms compared with the control arms either with any sexual partners (mean ES: −0.22; 95% confidence interval [CI]: −0.32, −0.11) or with HIV-negative or unknown-status sexual partners (mean ES and 95% CI: −0.13 [−0.22, −0.04]). Short-term efficacy of interventions with ≤10 months of follow up was significant in reducing UVAI (1–5 months: −0.27 [−0.45, −0.10]; 6–10 months: −0.18 [−0.30, −0.07]), while long-term efficacy of interventions was weaker and might have been due to chance (11–15 months: −0.13 [−0.34, 0.08]; >15 months: −0.05 [−0.43, 0.32]).Conclusions
Our meta-analyses confirmed the short-term impact of prevention interventions on reducing self-reported UVAI among PLWHA irrespective of the type of sexual partner, but did not support a definite conclusion on long-term effect. It is suggested that booster intervention sessions are needed to maintain a sustainable reduction of unprotected sex among PLWHA in future risk reduction programs. 相似文献6.
Effie Viguiliouk Cyril W. C. Kendall Sonia Blanco Mejia Adrian I. Cozma Vanessa Ha Arash Mirrahimi Viranda H. Jayalath Livia S. A. Augustin Laura Chiavaroli Lawrence A. Leiter Russell J. de Souza David J. A. Jenkins John L. Sievenpiper 《PloS one》2014,9(7)
Background
Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.Objective
To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.Data Sources
MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.Study Selection
Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.Data Extraction and Synthesis
Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I2).Results
Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.Limitations
Majority of trials were of short duration and poor quality.Conclusions
Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.Trial Registration
ClinicalTrials.gov NCT01630980相似文献7.
Hongyan Lu Yu Liu Kapil Dahiya Han-Zhu Qian Wensheng Fan Li Zhang Juntao Ma Yuhua Ruan Yiming Shao Sten H. Vermund Lu Yin 《PloS one》2013,8(8)
Objective
To evaluate the effect of risk reduction interventions on HIV knowledge, attitudes and behaviors among men who have sex with men (MSM) in China.Methods
We performed a systematic review and meta-analysis of HIV risk reduction intervention studies among Chinese MSM. The summary difference of standardized mean differences (SMD) between both study arms or between pre- and post-intervention assessments were defined as the effect size (ES); ES was calculated using standard meta-analysis in random effects models.Results
Thirty-four eligible studies were included in the analysis, including two randomized clinical trials (RCT), six quasi-experimental studies, six pre-and-post intervention studies, and twenty serial cross-sectional intervention studies. These studies showed an increase in consistent condom use with any male sexual partners (mean ES, 0.46; 95% confidence interval [CI], 0.35–0.56), with regular sexual partners (mean ES, 0.41; 95% CI, 0.18–0.63), and casual sexual partners (mean ES, 0.52; 95% CI, 0.24–0.79). The analysis of ten studies that measured the impact on uptake of HIV testing also showed a positive result (mean ES, 0.55; 95% CI, 0.38–0.71). The risk reduction interventions also improved HIV/AIDS-related knowledge (mean ES, 0.77; 95% CI, 0.60–0.94) and attitudes (mean ES, 1.35; 95% CI, 0.91–1.79), but did not reduce prevalence of HIV (mean ES, 0.23; 95% CI, 0.02–0.45) and syphilis infections (mean ES, −0.01; 95% CI, −0.19–0.17). There was significant heterogeneity among these studies.Conclusions
On aggregate, HIV risk reduction interventions were effective in reducing risky behaviors and improving knowledge and attitudes among Chinese MSM, but were not associated with a change in the prevalence of HIV and syphilis. Future studies should use incidence as definitive study outcome. 相似文献8.
9.
Background
The phosphatidylinositol 3-kinase–regulated protein kinase, Akt, plays an important role in the initiation and progression of human cancer. Mammalian cells express three Akt isoforms (Akt1–3), which are encoded by distinct genes. Despite sharing a high degree of amino acid identity, phenotypes observed in knockout mice suggest that Akt isoforms are not functionally redundant. The relative contributions of the different Akt isoforms to oncogenesis, and the effect of their deficiencies on tumor development, are not well understood.Methods
Here we demonstrate that Akt isoforms have non-overlapping and sometimes opposing functions in tumor initiation and progression using a viral oncogene-induced mouse model of lung cancer and Akt isoform-specific knockout mice.Results
Akt1 ablation significantly delays initiation of lung tumor growth, whereas Akt2 deficiency dramatically accelerates tumorigenesis in this mouse model. Ablation of Akt3 had a small, not statistically significant, stimulatory effect on tumor induction and growth by the viral oncogene. Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and Ki67 immunostaining of lung tissue sections revealed that the delayed tumor induction in Akt1−/− mice was due to the inhibitory effects of Akt1 ablation on cell growth and survival. Conversely, the accelerated growth rate of lung tumors in Akt2−/− and Akt3−/− mice was due to increased cell proliferation and reduced tumor cell apoptosis. Investigation of Akt signaling in tumors from Akt knockout mice revealed that the lack of Akt1 interrupted the propagation of signaling in tumors to the critical downstream targets, GSK-3α/β and mTOR.Conclusions
These results demonstrate that the degree of functional redundancy between Akt isoforms in the context of lung tumor initiation is minimal. Given that this mouse model exhibits considerable similarities to human lung cancer, these findings have important implications for the design and use of Akt inhibitors for the treatment of lung cancer. 相似文献10.
Ya-li Li Guang-zhi Wu Gavin S. Dawe Li Zeng Shu-sen Cui Gabriele Loers Thomas Tilling Li Sun Melitta Schachner Zhi-Cheng Xiao 《PloS one》2008,3(12)
Background
Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown.Methodology/Principal Findings
Using a panel of carbohydrate surface markers, we have shown that cell surface sialylation and fucosylation were downregulated in L1−/y neurons versus L1+/y neurons. Consistently, mRNA levels of sialyltransferase ST6Gal1, and fucosyltransferase FUT9 were significantly reduced in L1−/y neurons. Moreover, treatment of L1+/y neurons with L1 antibodies, triggering signal transduction downstream of L1, led to an increase in cell surface sialylation and fucosylation compared to rat IgG-treated cells. ShRNAs for both ST6Gal1 and FUT9 blocked L1 antibody-mediated enhancement of neurite outgrowth, cell survival and migration. A phospholipase Cγ (PLCγ) inhibitor and shRNA, as well as an Erk inhibitor, reduced ST6Gal1 and FUT9 mRNA levels and inhibited effects of L1 on neurite outgrowth and cell survival.Conclusions
Neuronal surface sialylation and fucosylation are regulated via PLCγ by L1, modulating neurite outgrowth, cell survival and migration. 相似文献11.
Robert M. Weiss Donald D. Lund Yi Chu Robert M. Brooks Kathy A. Zimmerman Ramzi El Accaoui Melissa K. Davis Georges P. Hajj M. Bridget Zimmerman Donald D. Heistad 《PloS one》2013,8(6)
Background
There are no rigorously confirmed effective medical therapies for calcific aortic stenosis. Hypercholesterolemic Ldlr −/− Apob 100/100 mice develop calcific aortic stenosis and valvular cardiomyopathy in old age. Osteoprotegerin (OPG) modulates calcification in bone and blood vessels, but its effect on valve calcification and valve function is not known.Objectives
To determine the impact of pharmacologic treatment with OPG upon aortic valve calcification and valve function in aortic stenosis-prone hypercholesterolemic Ldlr −/− Apob 100/100 mice.Methods
Young Ldlr −/− Apob 100/100 mice (age 2 months) were fed a Western diet and received exogenous OPG or vehicle (N = 12 each) 3 times per week, until age 8 months. After echocardiographic evaluation of valve function, the aortic valve was evaluated histologically. Older Ldlr −/− Apob 100/100 mice were fed a Western diet beginning at age 2 months. OPG or vehicle (N = 12 each) was administered from 6 to 12 months of age, followed by echocardiographic evaluation of valve function, followed by histologic evaluation.Results
In Young Ldlr −/− Apob 100/100 mice, OPG significantly attenuated osteogenic transformation in the aortic valve, but did not affect lipid accumulation. In Older Ldlr −/− Apob 100/100 mice, OPG attenuated accumulation of the osteoblast-specific matrix protein osteocalcin by ∼80%, and attenuated aortic valve calcification by ∼ 70%. OPG also attenuated impairment of aortic valve function.Conclusions
OPG attenuates pro-calcific processes in the aortic valve, and protects against impairment of aortic valve function in hypercholesterolemic aortic stenosis-prone Ldlr −/− Apob 100/100 mice. 相似文献12.
Aaron L. Leppin Pavithra R. Bora Jon C. Tilburt Michael R. Gionfriddo Claudia Zeballos-Palacios Megan M. Dulohery Amit Sood Patricia J. Erwin Juan Pablo Brito Kasey R. Boehmer Victor M. Montori 《PloS one》2014,9(10)
Importance
Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders.Objectives
To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases.Data Sources
Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts.Study Selection
Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used.Data Extraction and Synthesis
Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups.Main Outcomes
The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety.Results
We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I2 = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I2 = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I2 = 61%].Conclusions
We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it.Registration Number
PROSPERO #CRD42014007185 相似文献13.
Background
Guanylate Cyclase C (GC-C; Gucy2c) is a transmembrane receptor expressed in intestinal epithelial cells. Activation of GC-C by its secreted ligand guanylin stimulates intestinal fluid secretion. Familial mutations in GC-C cause chronic diarrheal disease or constipation and are associated with intestinal inflammation and infection. Here, we investigated the impact of GC-C activity on mucosal immune responses.Methods
We utilized intraperitoneal injection of lipopolysaccharide to elicit a systemic cytokine challenge and then measured pro-inflammatory gene expression in colonic mucosa. GC-C+/+ and GC-C−/− mice were bred with interleukin (IL)-10 deficient animals and colonic inflammation were assessed. Immune cell influx and cytokine/chemokine expression was measured in the colon of wildtype, IL-10−/−, GC-C+/+IL-10−/− and GC-C−/−IL-10−/− mice. GC-C and guanylin production were examined in the colon of these animals and in a cytokine-treated colon epithelial cell line.Results
Relative to GC-C+/+ animals, intraperitoneal lipopolysaccharide injection into GC-C−/− mice increased proinflammatory gene expression in both whole colon tissue and in partially purified colonocyte isolations. Spontaneous colitis in GC-C−/−IL-10−/− animals was significantly more severe relative to GC-C+/+IL-10−/− mice. Unlike GC-C+/+IL-10−/− controls, colon pathology in GC-C−/−IL-10−/− animals was apparent at an early age and was characterized by severely altered mucosal architecture, crypt abscesses, and hyperplastic subepithelial lesions. F4/80 and myeloperoxidase positive cells as well as proinflammatory gene expression were elevated in GC-C−/−IL-10−/− mucosa relative to control animals. Guanylin was diminished early in colitis in vivo and tumor necrosis factor α suppressed guanylin mRNA and protein in intestinal goblet cell-like HT29-18-N2 cells.Conclusions
The GC-C signaling pathway blunts colonic mucosal inflammation that is initiated by systemic cytokine burst or loss of mucosal immune cell immunosuppression. These data as well as the apparent intestinal inflammation in human GC-C mutant kindred underscore the importance of GC-C in regulating the response to injury and inflammation within the gut. 相似文献14.
éva Borbély Zsófia Hajna Katalin Sándor László Kereskai István Tóth Erika Pintér Péter Nagy János Szolcsányi John Quinn Andreas Zimmer James Stewart Christopher Paige Alexandra Berger Zsuzsanna Helyes 《PloS one》2013,8(4)
Objective
Substance P, encoded by the Tac1 gene, is involved in neurogenic inflammation and hyperalgesia via neurokinin 1 (NK1) receptor activation. Its non-neuronal counterpart, hemokinin-1, which is derived from the Tac4 gene, is also a potent NK1 agonist. Although hemokinin-1 has been described as a tachykinin of distinct origin and function compared to SP, its role in inflammatory and pain processes has not yet been elucidated in such detail. In this study, we analysed the involvement of tachykinins derived from the Tac1 and Tac4 genes, as well as the NK1 receptor in chronic arthritis of the mouse.Methods
Complete Freund’s Adjuvant was injected intraplantarly and into the tail of Tac1−/−, Tac4−/−, Tacr1−/− (NK1 receptor deficient) and Tac1−/−/Tac4−/− mice. Paw volume was measured by plethysmometry and mechanosensitivity using dynamic plantar aesthesiometry over a time period of 21 days. Semiquantitative histopathological scoring and ELISA measurement of IL-1β concentrations of the tibiotarsal joints were performed.Results
Mechanical hyperalgesia was significantly reduced from day 11 in Tac4−/− and Tacr1−/− animals, while paw swelling was not altered in any strain. Inflammatory histopathological alterations (synovial swelling, leukocyte infiltration, cartilage destruction, bone damage) and IL-1β concentration in the joint homogenates were significantly smaller in Tac4−/− and Tac1−/−/Tac4−/− mice.Conclusions
Hemokinin-1, but not substance P increases inflammation and hyperalgesia in the late phase of adjuvant-induced arthritis. While NK1 receptors mediate its antihyperalgesic actions, the involvement of another receptor in histopathological changes and IL-1β production is suggested. 相似文献15.
Fabrice Prunier Gwenola Terrien Yannick Le Corre Ailea L. Y. Apana Lo?c Bière Gilles Kauffenstein Alain Furber Arthur A. B. Bergen Theo G. M. F. Gorgels Olivier Le Saux Georges Leftheriotis Ludovic Martin 《PloS one》2013,8(7)
Background
Pseudoxanthoma elasticum (PXE), caused by mutations in the ABCC6 gene, is a rare multiorgan disease characterized by the mineralization and fragmentation of elastic fibers in connective tissue. Cardiac complications reportedly associated with PXE are mainly based on case reports.Methods
A cohort of 67 PXE patients was prospectively assessed. Patients underwent physical examination, electrocardiogram, transthoracic echocardiography, cardiac magnetic resonance imaging (CMR), treadmill testing, and perfusion myocardial scintigraphy (SPECT). Additionally, the hearts of a PXE mouse models (Abcc6−/−) and wild-type controls (WT) were analyzed.Results
Three patients had a history of proven coronary artery disease. In total, 40 patients underwent exercise treadmill tests, and 28 SPECT. The treadmill tests were all negative. SPECT showed mild perfusion abnormalities in two patients. Mean left ventricular (LV) dimension and function values were within the normal range. LV hypertrophy was found in 7 (10.4%) patients, though the hypertrophy etiology was unknown for 3 of those patients. Echocardiography revealed frequent but insignificant mitral and tricuspid valvulopathies. Mitral valve prolapse was present in 3 patients (4.5%). Two patients exhibited significant aortic stenosis (3.0%). While none of the functional and histological parameters diverged significantly between the Abcc6−/− and WT mice groups at age of 6 and 12 months, the 24-month-old Abcc6−/− mice developed cardiac hypertrophy without contractile dysfunction.Conclusions
Despite sporadic cases, PXE does not appear to be associated with frequent cardiac complications. However, the development of cardiac hypertrophy in the 24-month-old Abcc6−/− mice suggests that old PXE patients might be prone to developing late cardiopathy. 相似文献16.
Lars Knudsen Elena N. Atochina-Vasserman Chang-Jiang Guo Pamela A. Scott Beat Haenni Michael F. Beers Matthias Ochs Andrew J. Gow 《PloS one》2014,9(1)
Rationale
Surfactant protein D (SP-D) has important immuno-modulatory properties. The absence of SP-D results in an inducible NO synthase (iNOS, coded by NOS2 gene) related chronic inflammation, development of emphysema-like pathophysiology and alterations of surfactant homeostasis.Objective
In order to test the hypothesis that SP-D deficiency related abnormalities in pulmonary structure and function are a consequence of iNOS induced inflammation, we generated SP-D and iNOS double knockout mice (DiNOS).Methods
Structural data obtained by design-based stereology to quantify the emphysema-like phenotype and disturbances of the intracellular surfactant were correlated to invasive pulmonary function tests and inflammatory markers including activation markers of alveolar macrophages and compared to SP-D (Sftpd−/−) and iNOS single knockout mice (NOS2−/−) as well as wild type (WT) littermates.Measurements and Results
DiNOS mice had reduced inflammatory cells in BAL and BAL-derived alveolar macrophages showed an increased expression of markers of an alternative activation as well as reduced inflammation. As evidenced by increased alveolar numbers and surface area, emphysematous changes were attenuated in DiNOS while disturbances of the surfactant system remained virtually unchanged. Sftpd−/− demonstrated alterations of intrinsic mechanical properties of lung parenchyma as shown by reduced stiffness and resistance at its static limits, which could be corrected by additional ablation of NOS2 gene in DiNOS.Conclusion
iNOS related inflammation in the absence of SP-D is involved in the emphysematous remodeling leading to a loss of alveoli and associated alterations of elastic properties of lung parenchyma while disturbances of surfactant homeostasis are mediated by different mechanisms. 相似文献17.
Hai-Feng Shu Tao Yang Si-Xun Yu Hai-Dong Huang Ling-Li Jiang Jian-Wen Gu Yong-Qin Kuang 《PloS one》2014,9(7)
Background
Although some trials assessed the effectiveness of aerobic exercise for Parkinson''s disease (PD), the role of aerobic exercise in the management of PD remained controversial.Objective
The purpose of this systematic review is to evaluate the evidence about whether aerobic exercise is effective for PD.Methods
Seven electronic databases, up to December 2013, were searched to identify relevant studies. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. Standardised mean difference (SMD) and 95% confidence intervals (CI) of random-effects model were calculated. And heterogeneity was assessed based on the I2 statistic.Results
18 randomized controlled trials (RCTs) with 901 patients were eligible. The aggregated results suggested that aerobic exercise should show superior effects in improving motor actions (SMD, −0.57; 95% CI −0.94 to −0.19; p = 0.003), balance (SMD, 2.02; 95% CI 0.45 to 3.59; p = 0.01), and gait (SMD, 0.33; 95% CI 0.17 to 0.49; p<0.0001) in patients with PD, but not in quality of life (SMD, 0.11; 95% CI −0.23 to 0.46; p = 0.52). And there was no valid evidence on follow-up effects of aerobic exercise for PD.Conclusion
Aerobic exercise showed immediate beneficial effects in improving motor action, balance, and gait in patients with PD. However, given no evidence on follow-up effects, large-scale RCTs with long follow-up are warrant to confirm the current findings. 相似文献18.
Malcolm A. West Lisa Loughney Daniel Lythgoe Christopher P. Barben Valerie L. Adams William E. Bimson Michael P. W. Grocott Sandy Jack Graham J. Kemp 《PloS one》2014,9(12)
Background
In the United Kingdom, patients with locally advanced rectal cancer routinely receive neoadjuvant chemoradiotherapy. However, the effects of this on physical fitness are unclear. This pilot study is aimed to investigate the effect of neoadjuvant chemoradiotherapy on objectively measured in vivo muscle mitochondrial function and whole-body physical fitness.Methods
We prospectively studied 12 patients with rectal cancer who completed standardized neoadjuvant chemoradiotherapy, recruited from a large tertiary cancer centre, between October 2012 and July 2013. All patients underwent a cardiopulmonary exercise test and a phosphorus magnetic resonance spectroscopy quadriceps muscle exercise-recovery study before and after neoadjuvant chemoradiotherapy. Data were analysed and reported blind to patient identity and clinical course. Primary variables of interest were the two physical fitness measures; oxygen uptake at estimated anaerobic threshold and oxygen uptake at Peak exercise (ml.kg−1.min−1), and the post-exercise phosphocreatine recovery rate constant (min−1), a measure of muscle mitochondrial capacity in vivo.Results
Median age was 67 years (IQR 64–75). Differences (95%CI) in all three primary variables were significantly negative post-NACRT: Oxygen uptake at estimated anaerobic threshold −2.4 ml.kg−1.min−1 (−3.8, −0.9), p = 0.004; Oxygen uptake at Peak −4.0 ml.kg−1.min−1 (−6.8, −1.1), p = 0.011; and post-exercise phosphocreatine recovery rate constant −0.34 min−1 (−0.51, −0.17), p<0.001.Conclusion
The significant decrease in both whole-body physical fitness and in vivo muscle mitochondrial function raises the possibility that muscle mitochondrial mechanisms, no doubt multifactorial, may be important in deterioration of physical fitness following neoadjuvant chemoradiotherapy. This may have implications for targeted interventions to improve physical fitness pre-surgery.Trial Registration
Clinicaltrials.gov registration NCT01859442相似文献19.
Moritz J?rg Schneider Clemens Christian Cyran Konstantin Nikolaou Heidrun Hirner Maximilian F. Reiser Olaf Dietrich 《PloS one》2014,9(9)
Objectives
To evaluate the use of diffusion-weighted MRI (DW-MRI) and volume measurements for early monitoring of antiangiogenic therapy in an experimental tumor model.Materials and Methods
23 athymic nude rats, bearing human colon carcinoma xenografts (HT-29) were examined before and after 6 days of treatment with regorafenib (n = 12) or placebo (n = 11) in a clinical 3-Tesla MRI. For DW-MRI, a single-shot EPI sequence with 9 b-values (10–800 s/mm2) was used. The apparent diffusion coefficient (ADC) was calculated voxelwise and its median value over a region of interest, covering the entire tumor, was defined as the tumor ADC. Tumor volume was determined using T2-weighted images. ADC and volume changes between first and second measurement were evaluated as classifiers by a receiver-operator-characteristic (ROC) analysis individually and combined using Fisher''s linear discriminant analysis (FLDA).Results
All ADCs and volumes are stated as median±standard deviation. Tumor ADC increased significantly in the therapy group (0.76±0.09×10−3 mm2/s to 0.90±0.12×10−3 mm2/s; p<0.001), with significantly higher changes of tumor ADC than in the control group (0.10±0.11×10−3 mm2/s vs. 0.03±0.09×10−3 mm2/s; p = 0.027). Tumor volume increased significantly in both groups (therapy: 347.8±449.1 to 405.3±823.6 mm3; p = 0.034; control: 219.7±79.5 to 443.7±141.5 mm3; p<0.001), however, the therapy group showed significantly reduced tumor growth (33.30±47.30% vs. 96.43±31.66%; p<0.001). Area under the curve and accuracy of the ADC-based ROC analysis were 0.773 and 78.3%; and for the volume change 0.886 and 82.6%. The FLDA approach yielded an AUC of 0.985 and an accuracy of 95.7%.Conclusions
Regorafenib therapy significantly increased tumor ADC after 6 days of treatment and also significantly reduced tumor growth. However, ROC analyses using each parameter individually revealed a lack of accuracy in discriminating between therapy and control group. The combination of both parameters using FLDA substantially improved diagnostic accuracy, thus highlighting the potential of multi-parameter MRI as an imaging biomarker for non-invasive early tumor therapy monitoring. 相似文献20.
Ana Rivas-Caicedo Gloria Soldevila Teresa I. Fortoul Andrés Castell-Rodríguez Leopoldo Flores-Romo Eduardo A. García-Zepeda 《PloS one》2009,4(9)