共查询到20条相似文献,搜索用时 15 毫秒
1.
Youngwoo Bryan Yoon Je-Yeon Yun Wi Hoon Jung Kang Ik K. Cho Sung Nyun Kim Tae Young Lee Hye Yoon Park Jun Soo Kwon 《PloS one》2015,10(8)
Background
The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered.Methods
To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls.Results
Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03).Conclusions
These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis. 相似文献2.
Objectives
Avoidant personality disorder (AvPD) and social phobia (SP) are common disorders both in the community and in clinical settings. Whether the two disorders represent different severity levels of social anxiety disorder is currently in dispute. The relationship between AvPD and SP is probably more complex than previously assumed. Several environmental, temperamental, and constitutional factors may play a role in the etiology of AvPD and SP. Better knowledge about childhood experiences may shed light on similarities and differences between the two disorders. The aim of this study was to compare self-reported childhood experiences in AvPD and SP patients.Design
This is a cross-sectional multi-site study of 91 adult patients with AvPD and/ or SP. We compared patients with AvPD with and without SP (AvPD group) to patients with SP without AvPD (SP group).Methods
The patients were examined using structured diagnostic interviews and self-report measures, including Child Trauma Questionnaire, Parental Bonding Instrument, and Adult Temperament Questionnaire.Results
Both AvPD and SP were associated with negative childhood experiences. AvPD patients reported more severe childhood neglect than patients with SP, most pronounced for physical neglect. The difference between the disorders in neglect remained significant after controlling for temperamental factors and concurrent abuse.Conclusions
The study indicates that childhood neglect is a risk factor for AvPD and may be one contributing factor to phenomenological differences between AvPD and SP. 相似文献3.
Objective
Evidence suggests that substance P (SP) is involved in chronic joint inflammation, such as the pathogenesis of rheumatoid arthritis and osteoarthritis. The goal of the research was to evaluate the correlation between chronic pain and changes in the SP level in patients with chronic inflammation of the connective tissue.Methods
Patients with osteoarthritis and rheumatoid arthritis were enrolled in this study. The relationship between chronic pain intensity and the serum SP concentration was evaluated in these groups of patients with osteoarthritis and rheumatoid arthritis.Results
The results showed a positive correlation between the serum SP concentrations and chronic pain intensity.Conclusions
1. The SP serum concentration was significantly different between the groups of patients with OA and RA. 2. There was a positive correlation between the serum SP concentration and chronic pain intensity in OA and RA patients. 相似文献4.
Objective
There is a limited information about the role of Substance P (SP) in acute pain nociception following surgical stimulation in patients with a chronic inflammatory state not to mention the link between this neuropeptide level changes and intensity of pain. The goal of the research was to find the correlation between SP level changes and acute pain intensity in patients with rheumatoid arthritis undergoing elective orthopedic surgery.Material and Methods
Patients with rheumatoid arthritis (RA) were enrolled in the study. The correlation between acute pain intensity and concentration of SP in serum as well as in drainage fluid from postoperative wound was assessed in patients with RA who underwent Total Knee Replacement (TKA) under spinal anesthesia.Results
In patients with RA a correlation between intensity of acute pain and serum SP was found postoperatively, whereas there was no correlation between intensity of acute pain and concentration of SP in drainage fluid.Conclusions
1. The correlation between acute pain intensity and SP serum concentration was found postoperatively in patients with RA. 2. The correlation between acute pain intensity and SP concentration in drainage fluid was not found postoperatively in patients with RA. 相似文献5.
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Background
Recent studies have linked certain single nucleotide polymorphisms in the leucine-rich repeat kinase 2 (LRRK2) gene with Parkinson’s disease (PD). Among the mutations, LRRK2 c.4883G>C (R1628P) variant was identified to have a significant association with the risk of PD in ethnic Han-Chinese populations. But the molecular pathological mechanisms of R1628P mutation in PD is still unknown.Principle Findings
Unlike other LRRK2 mutants in the Roc-COR-Kinase domain, the R1628P mutation didn’t alter the LRRK2 kinase activity and promote neuronal death directly. LRRK2 R1628P mutation increased the binding affinity of LRRK2 with Cyclin-dependent kinase 5 (Cdk5). Interestingly, R1628P mutation turned its adjacent amino acid residue S1627 on LRRK2 protein to a novel phosphorylation site of Cdk5, which could be defined as a typical type II (+) phosphorylation-related single nucleotide polymorphism. Importantly, we showed that the phosphorylation of S1627 by Cdk5 could activate the LRRK2 kinase, and neurons ectopically expressing R1628P displayed a higher sensitivity to 1-methyl-4-phenylpyridinium, a bioactive metabolite of environmental toxin MPTP, in a Cdk5-dependent manner.Conclusion
Our data indicate that Parkinson-related LRRK2 mutation R1628P leads to Cdk5 phosphorylation of LRRK2 at S1627, which would upregulate the kinase activity of LRRK2 and consequently cause neuronal death. 相似文献7.
Jana Schwieger Athanasia Warnecke Thomas Lenarz Karl-Heinz Esser Verena Scheper 《PloS one》2015,10(8)
Objectives
The functionality of cochlear implants (CI) depends, among others, on the number and excitability of surviving spiral ganglion neurons (SGN). The spatial separation between the SGN, located in the bony axis of the inner ear, and the CI, which is inserted in the scala tympani, results in suboptimal performance of CI patients and may be decreased by attracting the SGN neurites towards the electrode contacts. Neurotrophic factors (NTFs) can support neuronal survival and neurite outgrowth.Methods
Since brain-derived neurotrophic factor (BDNF) is well known for its neuroprotective effect and ciliary neurotrophic factor (CNTF) increases neurite outgrowth, we evaluated if the combination of BDNF and CNTF leads to an enhanced neuronal survival with extended neurite outgrowth. Both NTFs were added in effective high concentrations (BDNF 50ng/ml, CNTF 100ng/ml), alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours.Results
The neuronal survival and neurite outgrowth were significantly higher in SGN treated with the combination of the two NTFs compared to treatment with each factor alone. Additionally, with respect to the morphology, the combination of BDNF and CNTF leads to a significantly higher number of bipolar neurons and a decreased number of neurons without neurites in culture.Conclusion
The combination of BDNF and CNTF shows a great potential to increase the neuronal survival and the number of bipolar neurons in vitro and to regenerate retracted nerve fibers. 相似文献8.
Susana Garcia-Recio Eva M. Pastor-Arroyo Mercedes Marín-Aguilera Vanessa Almendro Pedro Gascón 《PloS one》2015,10(6)
Background
Substance P (SP) is a pleiotropic cytokine/neuropeptide that enhances breast cancer (BC) aggressiveness by transactivating tyrosine kinase receptors like EGFR and HER2. We previously showed that SP and its cognate receptor NK-1 (SP/NK1-R) signaling modulates the basal phosphorylation of HER2 and EGFR in BC, increasing aggressiveness and drug resistance. In order to elucidate the mechanisms responsible for NK-1R-mediated HER2 and EGFR transactivation, we investigated the involvement of c-Src (a ligand-independent mediator) and of metalloproteinases (ligand-dependent mediators) in HER2/EGFR activation.Results and Discussion
Overexpression of NK-1R in MDA-MB-231 and its chemical inhibition in SK-BR-3, BT-474 and MDA-MB-468 BC cells significantly modulated c-Src activation, suggesting that this protein is a mediator of NK-1R signaling. In addition, the c-Src inhibitor 4-(4’-phenoxyanilino)-6,7-dimethoxyquinazoline prevented SP-induced activation of HER2. On the other hand, SP-dependent phosphorylation of HER2 and EGFR decreased substantially in the presence of the MMP inhibitor 1–10, phenanthroline monohydrate, and the dual inhibition of both c-Src and MMP almost abolished the activation of HER2 and EGFR. Moreover, the use of these inhibitors demonstrated that this Src and MMP-dependent signaling is important to the cell viability and migration capacity of HER2+ and EGFR+ cell lines.Conclusion
Our results indicate that the transactivation of HER2 and EGFR by the pro-inflammatory cytokine/neuropeptide SP in BC cells is a c-Src and MMP-dependent process. 相似文献9.
Ying-Zheng Zhao Rong-Rong Jin Wei Yang Qi Xiang Wen-Ze Yu Qian Lin Fu-Rong Tian Kai-Li Mao Chuan-Zhu Lv Yi-Xiáng J. Wáng Cui-Tao Lu 《PloS one》2016,11(2)
Purpose
Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats.Methods
The SP-loaded gelatin nanoparticles (SP-GNP) were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM). The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH), phosphorylated c-Jun protein (p-c-Jun) and Caspase-3 (Cas-3) expressed in substantia nigra (SN) region of hemiparkinsonian rats.Results
PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration.Conclusions
With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis. 相似文献10.
Background
Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects.Methods
Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise.Results
In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured.Conclusion
EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets. 相似文献11.
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Jolanta Zanelli Kevin Morgan Paola Dazzan Craig Morgan Manuela Russo Izabela Pilecka Paul Fearon Arsime Demjaha Gill A. Doody Peter B. Jones Robin M. Murray Abraham Reichenberg 《PloS one》2013,8(10)
Background
Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance.Methods
Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared.Results
There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences.Conclusions
Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients. 相似文献14.
Heather C. Whalley Rali Dimitrova Emma Sprooten Maria R. Dauvermann Liana Romaniuk Barbara Duff Andrew R. Watson Bill Moorhead Mark Bastin Scott I. Semple Stephen Giles Jeremy Hall Pippa Thomson Neil Roberts Zoe A. Hughes Nick J. Brandon John Dunlop Brandon Whitcher Douglas H. R. Blackwood Andrew M. McIntosh Stephen M. Lawrie 《PloS one》2015,10(6)
Objective
Individuals carrying rare, but biologically informative genetic variants provide a unique opportunity to model major mental illness and inform understanding of disease mechanisms. The rarity of such variations means that their study involves small group numbers, however they are amongst the strongest known genetic risk factors for major mental illness and are likely to have large neural effects. DISC1 (Disrupted in Schizophrenia 1) is a gene containing one such risk variant, identified in a single Scottish family through its disruption by a balanced translocation of chromosomes 1 and 11; t(1;11) (q42.1;q14.3).Method
Within the original pedigree, we examined the effects of the t(1;11) translocation on white matter integrity, measured by fractional anisotropy (FA). This included family members with (n = 7) and without (n = 13) the translocation, along with a clinical control sample of patients with psychosis (n = 34), and a group of healthy controls (n = 33).Results
We report decreased white matter integrity in five clusters in the genu of the corpus callosum, the right inferior fronto-occipital fasciculus, acoustic radiation and fornix. Analysis of the mixed psychosis group also demonstrated decreased white matter integrity in the above regions. FA values within the corpus callosum correlated significantly with positive psychotic symptom severity.Conclusions
We demonstrate that the t(1;11) translocation is associated with reduced white matter integrity in frontal commissural and association fibre tracts. These findings overlap with those shown in affected patients with psychosis and in DISC1 animal models and highlight the value of rare but biologically informative mutations in modeling psychosis. 相似文献15.
Isabelle Girerd-Genessay Dominique Baratin Tristan Ferry Christian Chidiac Vincent Ronin Philippe Vanhems 《PloS one》2016,11(1)
Introduction
Increased human immunodeficiency virus (HIV) virulence at infection has been suggested by a meta-analysis based on viral load and CD4 T lymphocytes (CD4) count during acute infection. This result was obtained after secondary analyses of large databases, facilitating the detection of differences. Similar finding in cohorts of more modest sample size would indicate that the effect could be more substantial.Methods
Change from initial CD4 count and HIV viral load after acute HIV infection by calendar year was explored in patients treated at Lyon University hospitals. All patients admitted to our hospitals with acute HIV infection between 1996 and 2013 were included in our study. Initial CD4 count and viral load before the start of anti-retroviral treatment were analyzed. Trends over time were assessed in linear models.Results
Initial CD4 count remained similar over time. However, in 2006–2013, initial viral load rose significantly (+1.12 log10/ml/year, p = 0.01).Conclusion
Our data, obtained from a single hospital cohort, confirmed findings from a large meta-analysis, showed increased initial viremia at acute HIV infection since 2006 and suggesting potentially higher HIV virulence in recent years. 相似文献16.
Ju-Young Shin Nam-Kyong Choi Joongyub Lee Jong-Mi Seong Mi-Ju Park Shin Haeng Lee Byung-Joo Park 《PloS one》2015,10(3)
Objective
Strong concerns have been raised about whether the risk of ischemic stroke differs between conventional antipsychotics (CAPs) and atypical antipsychotics (AAPs). This study compared the risk of ischemic stroke in elderly patients taking CAPs and AAPs.Method
We conducted a retrospective cohort study of 71,584 elderly patients who were newly prescribed the CAPs (haloperidol or chlorpromazine) and those prescribed the AAPs (risperidone, quetiapine, or olanzapine). We used the National Claims Database from the Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2009. Incident cases for ischemic stroke (ICD-10, I63) were identified. The hazard ratios (HR) for AAPs, CAPs, and for each antipsychotic were calculated using multivariable Cox regression models, with risperidone as a reference.Results
Among a total of 71,584 patients, 24,668 patients were on risperidone, 15,860 patients on quetiapine, 3,888 patients on olanzapine, 19,564 patients on haloperidol, and 7,604 patients on chlorpromazine. A substantially higher risk was observed with chlorpromazine (HR = 3.47, 95% CI, 1.97–5.38), which was followed by haloperidol (HR = 2.43, 95% CI, 1.18–3.14), quetiapine (HR = 1.23, 95% CI, 0.78–2.12), and olanzapine (HR = 1.12, 95% CI, 0.59–2.75). Patients who were prescribed chlorpromazine for longer than 150 days showed a higher risk (HR = 3.60, 95% CI, 1.83–6.02) than those who took it for a shorter period of time.Conclusions
A much greater risk of ischemic stroke was observed in patients who used chlorpromazine and haloperidol compared to risperidone. The evidence suggested that there is a strong need to exercise caution while prescribing these agents to the elderly in light of severe adverse events with atypical antipsychotics. 相似文献17.
Gregor E. Berger Stefan Smesny Miriam R. Sch?fer Berko Milleit Kerstin Langbein Uta-Christina Hipler Christine Milleit Claudia M. Klier Monika Schl?gelhofer Magdalena Holub Ingrid Holzer Michael Berk Patrick D. McGorry Heinrich Sauer G. Paul Amminger 《PloS one》2016,11(2)
Background
Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders.Methods
We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics.Results
Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling.Conclusions
Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a “pro-inflammatory state”, whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated. 相似文献18.
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Inês P. Perpétuo Rita Raposeiro Joana Caetano-Lopes Elsa Vieira-Sousa Raquel Campanilho-Marques Cristina Ponte Helena Canh?o Mari Ainola Jo?o E. Fonseca 《PloS one》2015,10(12)
Introduction
Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients.Methods
13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed.Results
RANKL+ circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline.Conclusion
In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli. 相似文献20.
Shunsuke Fujita Soichiro Ushio Nana Ozawa Ken Masuguchi Takehiro Kawashiri Ryozo Oishi Nobuaki Egashira 《PloS one》2015,10(11)