Context: Visfatin was recently reported to be expressed in human adipose tissue and to exert insulin-mimicking effects.
Objective: The objective of this study was to examine whether visfatin is a ...true adipokine and is expressed in isolated fat cells. We also examined whether visfatin is regulated by thiazolidinediones and, thus, can contribute to the ability of these agents to improve insulin sensitivity.
Design: This was an open-labeled drug therapy trial.
Setting: This study was performed at a university hospital.
Patients: Seven newly diagnosed and previously untreated type 2 diabetic patients and six healthy individuals with reduced insulin sensitivity participated in the study.
Intervention: Pioglitazone therapy (30–45 mg/d) was given for 3–4 wk.
Main Outcome Measures: Serum and adipose tissue mRNA levels of visfatin and adiponectin were the main outcome measures.
Results: Visfatin mRNA is expressed in both adipose tissue and isolated adipocytes. Treatment with thiazolidinediones for 3–4 wk did not alter the gene expression or circulating levels of visfatin in either nondiabetic or the diabetic individuals, whereas adiponectin increased significantly.
Conclusion: The present study shows that visfatin is a true adipokine, but it is not regulated by TZD and, thus, is unlikely to contribute to the insulin-sensitizing actions of these drugs.
Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated ...whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45-64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p = 0.002) and CVD mortality (p = 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause (hazards ratio HR 1.51; 95% confidence intervals CI, 1.14-1.99; p = 0.004), CVD (HR 1.56; 95% CI 1.12-2.19; p = 0.009), and CHD (HR 1.68; 95% CI 1.11-2.52; p = 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Objectives
The association of trigeminal neuralgia (TN) with multiple sclerosis (MS) is still widely unaddressed in larger, systematical clinical series. In this study, a cohort of Finnish MS ...patients was assessed regarding the incidence and prevalence of TN, as well as the presence of demyelinating lesions near the trigeminal ganglion, thus searching for a causative role of MS plaques in TN onset.
Materials & Methods
All consecutive patients treated and followed up for MS (ICD‐code G35) in Helsinki University Hospital during 2004‐2017 were identified from the Finnish MS register. A hospital administrative database search was used to identify all patients treated and followed up for TN during the same period. Among the MS patients, head MRI scans available from the diagnostic phase of TN or thereafter were analysed.
Results
We identified a total of 2575 patients with MS and 2008 patients with TN. Both diagnoses could be verified for 55 patients, giving a prevalence of 2.1% for TN in MS. The incidence of TN in MS patients was 149/100 000 person‐years (95% CI 108‐190). In the general outpatient population of our neurological department, the incidence of TN was 9.9/100 000 person‐years (95% CI 9.5‐10.3). A demyelinating lesion in the proximity of the trigeminal ganglia was seen for 63% of the 41 patients with relevant MRI data available.
Conclusions
Incidence of TN among MS patients was 15‐fold higher than in the general neurological outpatient population, thus in favour of a strong association between MS and TN.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Our purpose was to use volumetric MR imaging to compare the extent of atrophy and discriminative ability of the volumes of two temporal lobe structures, the entorhinal cortex and the hippocampus, ...between patients with Alzheimer disease and control subjects.
The study group consisted of 30 patients with probable Alzheimer disease diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria and 32 healthy control subjects. The MR volumes of the entorhinal cortex and the hippocampus were used for the discriminant function and receiver operator characteristic analysis as well as multivariate analysis of variance for repeated measures to compare their discriminative power.
Compared with control subjects, patients with Alzheimer disease had significantly smaller volumes of the entorhinal cortex and the hippocampus on both sides. Both the receiver operator characteristic and the discriminant function analyses using both volumes classified control subjects and Alzheimer patients with a high degree of accuracy (approximately 90%). Significant group x region interaction favoring hippocampal volumetry was determined by multivariate analysis of variance.
The volumetric measurements of both the entorhinal cortex and hippocampus have comparably high discriminative power in diagnosing Alzheimer disease. In clinical practice, hippocampal volumetry may be more feasible, because the method is easier to use and has less variability.
The ability of thymic histopathology to predict the long-term impact of thymectomy in non-thymomatous myasthenia gravis (NTMG) is mainly uncharted. We applied digital pathology to quantitatively ...characterize differences of thymic histology between early-onset (EOMG) and late-onset MG (LOMG) and to investigate the role of thymic changes for thymectomy outcomes in MG. We analyzed 83 thymic H&E slides from thymectomized NTMG patients, of which 69 had EOMG and 14 LOMG, using digital pathology open-access software QuPath. We compared the results to the retrospectively assessed clinical outcome at two years after thymectomy and at the last follow-up visit where complete stable remission and minimal use of medication were primary outcomes. The automated annotation pipeline was an effective and reliable way to analyze thymic H&E samples compared to manual annotation with mean intraclass correlation of 0.80. The ratio of thymic tissue to stroma and fat was increased in EOMG compared to LOMG (p = 8.7e-07), whereas no difference was observed in the ratio of medulla to cortex between these subtypes. AChRAb seropositivity correlated with the number of ectopic germinal centers (eGC; p = 0.00067) but not with other histological areas. Patients with an increased number of eGCs had better post-thymectomy outcomes at two years after thymectomy (p = 0.0035) and at the last follow-up (p = 0.0267). ROC analysis showed that eGC area predicts thymectomy outcome in EOMG with an AUC of 0.79. Digital pathology can thus help in providing a predictive tool to the clinician, the eGC number, to guide the post-thymectomy treatment decisions in EOMG patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine the effects of subcortical ischemic vascular dementia (SIVD) and AD on entorhinal cortex (ERC) and hippocampus.
Thirty-eight cognitively normal subjects, 18 patients with SIVD, and 22 ...patients with AD were included. Volumes of ERC and hippocampus were manually measured based on MRI. Global cerebral changes of cortical gray matter, subcortical gray matter, white matter, sulcal CSF, ventricular CSF (vCSF), and white matter signal hyperintensities (WMSH) were assessed.
Patients with SIVD had 21.7% (p < 0.01) smaller ERC and 18.2% (p < 0.01) smaller hippocampi than cognitively normal subjects and 24.4% (p < 0.01) larger ERC and 11.1% (p < 0.05) larger hippocampi than patients with AD. In addition, patients with SIVD had less cortical gray matter and white matter and more vCSF and WMSH (all p < 0.01) than cognitively normal subjects and more vCSF and WMSH (p < 0.01) than patients with AD. The volumes of ERC and hippocampus were positively correlated to similar extents (p < 0.01) in SIVD and AD. Cortical gray matter loss was positively correlated (p < 0.01) with hippocampal atrophy, but not with ERC atrophy, in SIVD and AD. Hippocampal volume alone could classify 82% of patients with SIVD from cognitively normal subjects and 63% of patients with SIVD from subjects with AD. Adding global cerebral changes to hippocampus substantially improved the classification to 96% between patients with SIVD and cognitively normal subjects and 83% between subjects with SIVD and those with AD, whereas adding ERC change to hippocampus did not significantly improve the discrimination.
The entorhinal cortex and hippocampus are less affected by subcortical ischemic vascular dementia than by AD.
Aims We explored gender differences in the association of high‐sensitivity C‐reactive protein (hs‐CRP), interleukin‐1 receptor antagonist (IL‐1Ra) and adiponectin with the metabolic syndrome (MetS) ...defined by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) criteria.
Methods A population‐based study of 923 middle‐aged subjects in Pieksämäki, East Finland.
Results The prevalence of the MetS according to the IDF and NCEP definitions was 38% and 34% in men (N = 405) and 34% and 27% in women (N = 497), respectively. hs‐CRP and IL‐1Ra levels were higher in subjects with the MetS compared with those without the MetS in both sexes (P < 0.001). The levels of hs‐CRP (P < 0.001) and IL‐1Ra (P = 0.0016 for NCEP criteria, P = 0.0028 for IDF criteria) were significantly higher in women with MetS than in men with MetS. In contrast, in subjects without MetS, no gender differences in the levels of hs‐CRP or IL‐1Ra were found.
Conclusion Women with MetS, defined by the IDF or NCEP criteria, had higher levels of hs‐CRP and IL‐1Ra than did men with MetS. Thus, low‐grade inflammation may contribute to the high risk of cardiovascular disease in women with MetS.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Myosin-Is are molecular motors that link cellular membranes to the actin cytoskeleton, where they play roles in mechano-signal transduction and membrane trafficking. Some myosin-Is are proposed to ...act as force sensors, dynamically modulating their motile properties in response to changes in tension. In this study, we examined force sensing by the widely expressed myosin-I isoform, myo1b, which is alternatively spliced in its light chain binding domain (LCBD), yielding proteins with lever arms of different lengths. We found the actin-detachment kinetics of the splice isoforms to be extraordinarily tension-sensitive, with the magnitude of tension sensitivity to be related to LCBD splicing. Thus, in addition to regulating step-size, motility rates, and myosin activation, the LCBD is a key regulator of force sensing. We also found that myo1b is substantially more tension-sensitive than other myosins with similar length lever arms, indicating that different myosins have different tension-sensitive transitions.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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