Glucagon-like peptides 1 and 2 and vasoactive intestinal peptide are neuroprotective on cultured and mast cell co-cultured rat myenteric neurons

<p>Abstract</p> <p>Background</p> <p>Neuropathy is believed to be a common feature of functional and inflammatory intestinal diseases. Vasoactive intestinal peptide (VIP) is an acknowledged neuroprotective agent in peripheral, including enteric, and central neurons. The proglucagon-like hormones glucagon-like peptide 1 and 2 (GLP1 and GLP2) belong to the secretin/glucagon/VIP superfamily of peptides and GLP1 and GLP2 receptors are expressed in enteric neurons. Possible neuroprotective effects of these peptides were investigated in the present study.</p> <p>Methods</p> <p>GLP1, GLP2 and VIP were added to cultured myenteric neurons from rat small intestine or to co-cultures of myenteric neurons and rat peritoneal mast cells. Receptor selectivity was tested by the simultaneous presence of a GLP1 receptor antagonist (exendin (9-39) amide) or a VIP receptor antagonist (hybrid of neurotensin 6-11 and VIP 7-28). Neuronal survival was examined using immunocytochemistry and cell counting.</p> <p>Results</p> <p>GLP1, GLP2 and VIP significantly and concentration-dependently enhanced neuronal survival. In addition the peptides efficiently counteracted mast cell-induced neuronal cell death in a concentration-dependent manner. Exendin(9-39)amide reversed GLP1-induced neuroprotection while GLP2- and VIP-induced enhanced neuronal survival were unaffected. The VIP receptor antagonist reversed GLP1- and VIP-induced neuroprotection while the GLP2-induced effect on neuronal survival was unaffected.</p> <p>Conclusions</p> <p>By activating separate receptors VIP, GLP1 and GLP2 elicit neuroprotective effects on rat myenteric neurons cultured with or without mast cells. This implies a powerful therapeutic potential of these peptides in enteric neuropathies with a broad spectrum of applications from autoimmunity to functional disorders.</p

The feasibility and outcome of a community-based primary prevention program for cardiovascular disease in the 21st century

Objective There is no evidence that systematic screening and risk factor modification in an unselected, asymptomatic population will reduce cardiovascular disease (CVD) mortality. This study aimed to evaluate the effectiveness of a primary care CVD prevention program on mortality during a 13-year follow-up. Design A risk factor survey was sent, followed by a nurse-led lifestyle counselling to respondents with at least one CVD risk factor, and a general practitioner's (GP) appointment for high-risk persons. Screening and interventions were performed during 2005-2006. Setting A public health care centre in the town of Harjavalta, Finland. Subjects All home-dwelling 45-70-year old inhabitants without manifested CVD or diabetes. Main outcome measures All-cause and CVD mortality. Results Altogether 74% (2121/2856) inhabitants responded to the invitation. The intervention was received by 1465 individuals (52% of the invited population): 398 risk persons had an appointment with a nurse, followed by an appointment with a GP for 1067 high-risk persons. During the follow-up, 370 persons died. Mortality among the non-respondents was twofold compared to the participants'. In subjects who received the intervention, the age- and gender-adjusted hazard ratio for all-cause mortality was 0.44 (95% CI: 0.36 to 0.54) compared to the subjects who did not receive the intervention. Conclusions Reducing mortality is possible in a primary care setting by raising health awareness in the community with screening, by targeted lifestyle counselling and evidence-based preventive medication for persons at high risk for CVD. Subjects not willing to participate in health surveys have the worst prognosis.Peer reviewe

Maternal Smoking and Hospital Treatment During Pregnancy

IntroductionPrevious research suggests that young maternal age, smoking, hospitalization during a previous pregnancy, and poor self-rated health could be risk factors for prenatal hospitalization.MethodsThe objective of this retrospective observational register study was to investigate if maternal smoking during pregnancy is associated with mother’s need for hospital treatment during pregnancy. The study population consists of all singleton pregnancies (n = 961 127) in 1999–2015 in Finland. Information on maternal smoking was received from the Medical Birth Register in three classes: nonsmoker, quit smoking in the first trimester, and continued smoking throughout the pregnancy. These data were linked with the Hospital Discharge Register data and analyzed according to ICD-10 chapters.Results10.7% of women continued to smoke after the first trimester. After adjusting for confounding factors women in both smoking groups had more hospital treatment compared with nonsmokers. Especially outpatient treatment was more common among mothers who continued to smoke compared to those who quit smoking in the first trimester in several ICD-10 chapters. Compared to non-smokers, aOR for mental and behavioral disorders (F00–F99) was 2.14 (95% confidence interval 2.00–2.30) in the quit smoking group and 3.88 (3.71–4.06) in the continued smoking group. Similarly, aOR for respiratory diseases (J00–J99) was 1.26 (1.15–1.39) and 1.61 (1.52–1.71), respectively and aOR for genitourinary diseases (N00–N99) was 1.10 (1.03–1.17) and 1.29 (1.23–1.35), respectively. Some similar findings were made also in inpatient care. Some similar findings were made also in inpatient care.ConclusionsWomen who smoke during pregnancy seem to require more hospital care for various reasons. These findings emphasize the importance of actions for smoking cessation during pregnancy and women should be encouraged to quit as early as possible.ImplicationsMaternal smoking during pregnancy is associated with greater rates of both outpatient and inpatient hospital care during pregnancy. Women who quit smoking had a similar risk for hospital care during pregnancy with nonsmokers in certain diagnosis chapters, which is very motivational and could be used as an informational tool in prenatal clinics to encourage smoking cessation as it is never too late to quit smoking during pregnancy.</div

Proteomic correlates of cortical thickness in cognitively normal individuals with normal and abnormal cerebrospinal fluid beta-amyloid1-42

Cortical atrophy is an early feature of Alzheimer´s disease (AD). The biological processes associated with variability in cortical thickness remain largely unknown. We studied 220 cerebrospinal fluid (CSF) proteins to evaluate biological pathways associated with cortical thickness in 34 brain regions in 79 cognitively normal older individuals with normal (>192 ng/L, n = 47), and abnormal (≤192 ng/L, n = 32) CSF beta-amyloid1-42 (Aβ42). Interactions for Aβ42 status were tested. Panther GeneOntology and Cytoscape ClueGO analyses were used to evaluate biological processes associated with regional cortical thickness. 170 (77.3 %) proteins related with cortical thickness in at least 1 brain region across the total group, and 171 (77.7 %) proteins showed Aβ42 specific associations. Higher levels of proteins related to axonal and synaptic integrity, amyloid accumulation, and inflammation were associated with thinner cortex in lateral temporal regions, the rostral anterior cingulum, the lateral occipital cortex and the pars opercularis only in the abnormal Aβ42 group. Alterations in CSF proteomics are associated with a regional cortical atrophy in the earliest stages of AD.</p

Decreased symptoms of depression after mindfulness-based stress reduction: potential moderating effects of religiosity, spirituality, trait mindfulness, sex, and age

Objective: mindfulness-based stress reduction (MBSR) is a secular meditation training program that reduces depressive symptoms. Little is known, however, about the degree to which a participant's spiritual and religious background, or other demographic characteristics associated with risk for depression, may affect the effectiveness of MBSR. Therefore, this study tested whether individual differences in religiosity, spirituality, motivation for spiritual growth, trait mindfulness, sex, and age affect MBSR effectiveness.Methods: as part of an open trial, multiple regression was used to analyze variation in depressive symptom outcomes among 322 adults who enrolled in an 8-week, community-based MBSR program.Results: as hypothesized, depressive symptom severity decreased significantly in the full study sample (d=0.57; p&lt;0.01). After adjustment for baseline symptom severity, moderation analyses revealed no significant differences in the change in depressive symptoms following MBSR as a function of spirituality, religiosity, trait mindfulness, or demographic variables. Paired t tests found consistent, statistically significant (p&lt;0.01) reductions in depressive symptoms across all subgroups by religious affiliation, intention for spiritual growth, sex, and baseline symptom severity. After adjustment for baseline symptom scores, age, sex, and religious affiliation, a significant proportion of variance in post-MBSR depressive symptoms was uniquely explained by changes in both spirituality (?=?0.15; p=0.006) and mindfulness (?=?0.17; p&lt;0.001).Conclusions: these findings suggest that MBSR, a secular meditation training program, is associated with improved depressive symptoms regardless of affiliation with a religion, sense of spirituality, trait level of mindfulness before MBSR training, sex, or age. Increases in both mindfulness and daily spiritual experiences uniquely explained improvement in depressive symptom

Insuliiniresistenssi, aivot ja muistisairausriski

Tyypin 2 diabetes ja siihen liittyvä insuliiniresistenssi ovat muistisairauden riskitekijöitä. Insuliiniresistenssi ennustaa tiedonkäsittelytoimintojen heikentymistä jo henkilöillä, joille ei vielä ole kehittynyt diabetesta. Insuliinilla on useita tärkeitä säätelytehtäviä keskushermostossa. Se vaikuttaa esimerkiksi synapsien toimintaan ja niiden pitkäkestoiseen vahvistumiseen. Insuliiniresistenssiin liittyvään hyperinsulinemiaan on puolestaan yhdistetty paradoksaalisesti keskushermoston pienentynyt insuliinipitoisuus. Alzheimerin tautia sairastavilla insuliinin vaste keskushermostossa on heikentynyt. Insuliinilla ja Alzheimerin taudille tyypillisellä beeta-amyloidilla on aivoissa yhteinen hajottajaentsyymi. Muutokset tämän entsyymin toiminnassa ja määrässä voivat vaikuttaa beeta-amyloidin kertymään aivoissa. Insuliiniresistenssi voi altistaa kognition heikentymiselle myös aivojen pienten suonten muutosten kautta. Insuliiniresistenssi voi siis vaikuttaa tiedonkäsittelytoimintoihin ja Alzheimerin taudin neuropatologiaan useita eri reittejä.</p

Evaluation of methods to estimate production, biomass and turnover of ectomycorrhizal mycelium in forests soils : A review

Peer reviewedPublisher PD

APOE ε4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta-amyloid in cognitively unimpaired elderly

BACKGROUND: Neuroinflammation, characterized by increased reactivity of microglia and astrocytes in the brain, is known to be present at various stages of the Alzheimer's disease (AD) continuum. However, its presence and relationship with amyloid pathology in cognitively normal at-risk individuals is less clear. Here, we used positron emission tomography (PET) and blood biomarker measurements to examine differences in neuroinflammation and beta-amyloid (Aβ) and their association in cognitively unimpaired homozygotes, heterozygotes, or non-carriers of the APOE ε4 allele, the strongest genetic risk for sporadic AD. METHODS: Sixty 60-75-year-old APOE ε4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) were recruited in collaboration with the local Auria biobank. The participants underwent 11C-PK11195 PET (targeting 18-kDa translocator protein, TSPO), 11C-PiB PET (targeting Aβ), brain MRI, and neuropsychological testing including a preclinical cognitive composite (APCC). 11C-PK11195 distribution volume ratios and 11C-PiB standardized uptake value ratios (SUVRs) were calculated for regions typical for early Aβ accumulation in AD. Blood samples were drawn for measuring plasma glial fibrillary acidic protein (GFAP) and plasma Aβ1-42/1.40. RESULTS: In our cognitively unimpaired sample, cortical 11C-PiB-binding increased according to APOE ε4 gene dose (median composite SUVR 1.47 (range 1.38-1.66) in non-carriers, 1.55 (1.43-2.02) in heterozygotes, and 2.13 (1.61-2.83) in homozygotes, P = 0.002). In contrast, cortical composite 11C-PK11195-binding did not differ between the APOE ε4 gene doses (P = 0.27) or between Aβ-positive and Aβ-negative individuals (P = 0.81) and associated with higher Aβ burden only in APOE ε4 homozygotes (Rho = 0.47, P = 0.043). Plasma GFAP concentration correlated with cortical 11C-PiB (Rho = 0.35, P = 0.040), but not 11C-PK11195-binding (Rho = 0.13, P = 0.47) in Aβ-positive individuals. In the total cognitively unimpaired population, both higher composite 11C-PK11195-binding and plasma GFAP were associated with lower hippocampal volume, whereas elevated 11C-PiB-binding was associated with lower APCC scores. CONCLUSIONS: Only Aβ burden measured by PET, but not markers of neuroinflammation, differed among cognitively unimpaired elderly with different APOE ε4 gene dose. However, APOE ε4 gene dose seemed to modulate the association between neuroinflammation and Aβ

Association of Early Beta-amyloid Accumulation and Neuroinflammation Measured with [11C]PBR28 in Elderly Individuals Without Dementia

OBJECTIVE: To examine whether early β-amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia. METHODS: We examined 54 volunteers (mean age 70.0, 56% women, 51% APOE ε4 carriers) with a TSPO-tracer [11C]PBR28 to assess neuroinflammation and with [11C]Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation. [11C]PBR28 and [11C]PiB standardized uptake value ratios (SUVRs) were quantified in six regions of interests by using the cerebellar cortex as a pseudo-reference/reference region, respectively. Fasting venous glucose, insulin, and high sensitivity C-reactive protein (hs-CRP) values were determined. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. A subset of individuals (n=11) underwent CSF sampling, and Aβ40, Aβ42, total-tau, phospho-tau, soluble TREM2 and YKL-40 levels were measured. RESULTS: Among the whole study group, no significant association was found between [11C]PiB and [11C]PBR28 SUVR composite scores (slope 0.02, p=0.30). However, higher [11C]PiB binding was associated with higher [11C]PBR28 binding among amyloid negative ([11C]PiB composite score ≤1.5) (TSPO-genotype, age and sex adjusted slope 0.26, p=0.008) but not among amyloid positive participants (slope: -0.004, p=0.88). Higher CSF sTREM2 (rs 0.72, p=0.01) and YKL-40 (rs=0.63, p=0.04) concentrations were associated with a higher [11C]PBR28 composite score. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher [11C]PBR28 binding in brain regions where Aβ accumulation is first detected in Alzheimer's disease (AD). CONCLUSIONS: While there was no association between amyloid and neuroinflammation in the overall study group, neuroinflammation was associated with amyloid among the subgroup at early stages of amyloid pathology