scholarly journals Apolipoprotein CIII and Angiopoietin-like Protein 8 are Elevated in Lipodystrophy and Decrease after Metreleptin

2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Marissa Lightbourne ◽  
Anna Wolska ◽  
Brent S Abel ◽  
Kristina I Rother ◽  
Mary Walter ◽  
...  

Abstract Context Lipodystrophy syndromes cause hypertriglyceridemia that improves with leptin treatment using metreleptin. Mechanisms causing hypertriglyceridemia and improvements after metreleptin are incompletely understood. Objective Determine relationship of circulating lipoprotein lipase (LPL) modulators with hypertriglyceridemia in healthy controls and in patients with lipodystrophy before and after metreleptin. Methods Cross-sectional comparison of patients with lipodystrophy (generalized lipodystrophy n = 3; partial lipodystrophy n = 11) vs age/sex-matched healthy controls (n = 28), and longitudinal analyses in patients before and after 2 weeks and 6 months of metreleptin. The study was carried out at the National Institutes of Health, Bethesda, Maryland. Outcomes were LPL stimulators apolipoprotein (apo) C-II and apoA-V and inhibitors apoC-III and angiopoietin-like proteins (ANGPTLs) 3, 4, and 8; ex vivo activation of LPL by plasma. Results Patients with lipodystrophy were hypertriglyceridemic and had higher levels of all LPL stimulators and inhibitors vs controls except for ANGPTL4, with >300-fold higher ANGPTL8, 4-fold higher apoC-III, 3.5-fold higher apoC-II, 1.9-fold higher apoA-V, 1.6-fold higher ANGPTL3 (P < .05 for all). At baseline, all LPL modulators except ANGPLT4 positively correlated with triglycerides. Metreleptin decreased apoC-II and apoC-III after 2 weeks and 6 months, and decreased ANGPTL8 after 6 months (P < 0.05 for all). Plasma from patients with lipodystrophy caused higher ex vivo LPL activation vs hypertriglyceridemic control plasma (P < .0001), which did not change after metreleptin. Conclusion Elevations in LPL inhibitors apoC-III and ANGPTL8 may contribute to hypertriglyceridemia in lipodystrophy, and may mediate reductions in circulating and hepatic triglycerides after metreleptin. These therefore are strong candidates for therapies to lower triglycerides in these patients.

2021 ◽  
pp. tobaccocontrol-2020-056160
Author(s):  
Yanhui Liao ◽  
Jinsong Tang ◽  
Ann McNeill ◽  
Brian C Kelly ◽  
Joanna E Cohen

BackgroundSharing and gifting cigarettes are common in China. These social practices promote cigarette consumption, and consequently may reduce quit rates in China. This study investigated sharing and gifting cigarettes, and the relationship of observing pictorial health warnings to attitudes towards sharing and gifting cigarettes in China.MethodsWe conducted an online nationwide cross-sectional study of 9818 adults in China. Experiences of sharing and gifting cigarettes, and attitudes towards sharing and gifting cigarettes before and after viewing text and pictorial health warnings on the packages were assessed, and compared between smokers and non-smokers.ResultsMost current smokers reported experiences of sharing (97%) and gifting (around 90%) cigarettes. Less than half of non-smokers reported sharing cigarettes and receiving gifted cigarettes, but over half (61.4%) gave cigarettes as a gift to others. More than half of non-smokers but less than 10% of smokers disagreed with sharing and gifting cigarettes. After observing both text and pictorial health warnings on the packages, disagreement with sharing and gifting cigarettes increased by more than 10 percentage points among both smokers and non-smokers.ConclusionHaving pictorial health warnings on cigarette packages may reduce sharing and gifting cigarettes in China.


2021 ◽  
Vol 8 (4) ◽  
pp. e1004
Author(s):  
May F. Mrad ◽  
Esber S. Saba ◽  
Layane Nakib ◽  
Samia J. Khoury

ObjectiveTo investigate in a cross-sectional study the effect of serum-derived exosomes on primary human blood monocyte-derived macrophages (MDMs) comparing exosomes from healthy donors vs patients with relapsing-remitting multiple sclerosis in remission and in relapse and to assess whether the response correlates with exosomal Epstein-Barr virus (EBV) protein expression.MethodsA total of 45 serum-derived exosome preparations were isolated from patients and healthy controls and verified for the expression of exosomal and EBV markers. MDMs were differentiated from monocytes for 7 days and incubated for 24 hours with exosomes, and then, cell supernatants were collected for cytokine measurement by cytometric bead array. Cells were immunophenotyped before and after differentiation.ResultsSerum-derived exosomes of patients with multiple sclerosis (MS) expressed higher levels of EBV proteins than healthy controls. Of interest, expression of EBV nuclear antigen EBNA1 and latent membrane proteins LMP1 and 2A was higher on exosomes derived from patients with active RRMS compared with healthy controls and stable patients. After data normalization, we observed that incubation with EBV(+) exosomes induced CXCL10 and CCL2 secretion by MDMs. MDMs differentiated from patients with active disease were better secretors of CXCL10 and other interferon-γ–inducible chemokines, including CCL2 and CXCL9, than MDMs from healthy and stable MS groups. MDMs from active patients had a higher frequency of a CD14(++) subset that correlated with the secreted CXCL10.ConclusionExosomes expressing EBV proteins correlate with disease activity and induce an inflammatory response in MDMs that is compounded by the origin of the responder cells.


2019 ◽  
Vol 22 (2) ◽  
pp. 256-262
Author(s):  
Maureen Groer ◽  
Adetola Louis-Jacques ◽  
Laura Szalacha ◽  
Laura Redwine ◽  
Roberta Dracxler ◽  
...  

Background: The postpartum period can be a vulnerable time during which many women are prone to mood disturbances. Since telomere length (TL) is known to be associated with dysphoric moods, inflammation, and stress in many populations, this study’s objective was to assess the relationships among TL, dysphoric moods, stress, and inflammation during the postpartum period. Method: This cross-sectional pilot study is a secondary analysis of data collected in a larger parent study of anti-thyroid peroxidase (TPO) enzyme antibody positive versus negative women. The parent study followed selected mothers every month for 6 postpartum months. From this parent study, a random sample of preserved peripheral blood mononuclear cells from 97 participants collected at 2–4 months postpartum were measured for TL. Data were available on the production of interleukin-6 (IL-6), an inflammatory cytokine, in stimulated ex vivo cultures for 59 of these women. Dysphoric moods and stress were measured. Pearson correlations and linear regressions were performed, controlling for postpartum thyroiditis status and age. Results: There were no statistically significant relationships between TL and demographic factors, stress, depression, or TPO status. There were significant negative correlations between TL and anxiety and a trend for a relationship between TL and IL-6 levels. IL-6 levels were significantly, positively associated with negative moods. Conclusions: Higher anxiety scores and inflammation were associated with shorter TL. Inflammation was related to anxiety and other dysphoric moods and was marginally associated with shorter TLs.


2020 ◽  
Vol 63 (1) ◽  
Author(s):  
New Fei Ho ◽  
Benjamin J. H. Lee ◽  
Jordon X. J. Tng ◽  
Max Z. Y. Lam ◽  
Guoyang Chen ◽  
...  

Abstract Background. Earlier studies examining structural brain abnormalities associated with cognitively derived subgroups were mainly cross-sectional in design and had mixed findings. Thus, we obtained cross-sectional and longitudinal data to characterize the extent and trajectory of brain structure abnormalities underlying distinct cognitive subtypes (“preserved,” “deteriorated,” and “compromised”) seen in psychotic spectrum disorders. Methods. Data from 364 subjects (225 patients with psychotic conditions and 139 healthy controls) were first used to determine the relationship of cognitive subtypes with cross-sectional measures of subcortical volume and cortical thickness. To probe neurodevelopmental abnormalities, brain structure laterality was examined. To examine whether neuroprogressive abnormalities persist, longitudinal brain structural changes over 5 years were examined within a subset of 101 subjects. Subsequent discriminant analysis using the identified brain measures was performed on an independent subject group. Results. Cross-sectional comparisons showed that cortical thinning and limbic volume reductions were most widespread in “deteriorated” cognitive subtype. Laterality comparisons showed more rightward amygdala lateralization in “compromised” than “preserved” subtype. Longitudinal comparisons revealed progressive hippocampal shrinkage in “deteriorated” compared with healthy controls and “preserved” subtype, which correlated with worse negative symptoms, cognitive and psychosocial functioning. Post-hoc discrimination analysis on an independent group of 52 subjects using the identified brain structures found an overall accuracy of 71% for classification of cognitive subtypes. Conclusion. These findings point toward distinct extent and trajectory of corticolimbic abnormalities associated with cognitive subtypes in psychosis, which can allow further understanding of the biological course of cognitive functioning over illness course and with treatment.


2018 ◽  
Vol 10 (1) ◽  
pp. 9-14
Author(s):  
Wiwik Trapsilowati ◽  
Aryani Pujiyanti ◽  
Wigati Wigati

There has been increased of malaria cases in Purworejo District, especially in Sendangsari Village, Bener District in 2015. The one influence factors of malaria transmission was behavior, it consist of knowledge, attitude and practice domains. The aims this study was described of the knowledge, attitudes and practices of the community and conduct interventions related to survey results. The research method were cross-sectional to collect data of the knowledge, attitudes and practices and one group pretest posttest design to measure the intervention. The number of samples obtained as many as 90 respondents. The results showed that there was a significant relationship between education and knowledge, as well as knowledge with attitude (p < 0.05). While variables relationship of knowledge with practice/action and attitude with practice/action showed an insignificant (p > 0,05). The result of the intervention by direct information showed that knowledge of the respondents between before and after intervention has increased significantly (p < 0,05). Based on these results, it was necessary to encourage local community leaders, both formal and non-formal, for cooperate with the community to protecting themselves and their environment so as not to be potential transmission of malaria


2021 ◽  
Vol 12 (1) ◽  
pp. 588-593
Author(s):  
Ranjit S. Ambad ◽  
Sonal Muley ◽  
Lata Kanyal Butola ◽  
Ajinkya S. Ghogare

Mental disorders were associated with a wide range of chronic illnesses, disability, and even mortality, particularly among elderly people. Depression will be the second cause of disease. Anxiety is an emotional state of antipathy in which the sense of fear is disproportionate to the magnitude of the risk. Enzymatic antioxidants like SOD, GPx, and non-enzymatic antioxidants such as vitamin C, E act as free scavengers, thereby reducing oxidative stress and resulting in cell injury. Thus, we aimed to study SOD, GPx, Vitamin C, and Vitamin E, 1. To study levels of SOD, GPx, Vitamin C, and Vitamin E in psychiatric disorders.2. To study the levels of Vit-C and E before and after vitamin supplementations. To correlate the levels of SOD, GPx, Vitamin C, and Vitamin E between psychiatric patients and healthy controls (age-matched) attending AVBRH Wardha and SMHRC Nagpur. This cross-sectional examination was completed on 50 psychiatric patients and 50 healthy controls and the levels of SOD, GPx, Vitamin C, and Vitamin E are measured before and after giving supplements. In Psychiatric patients, Superoxide dismutase (SOD) levels were 135.26±24.68, Glutathione Peroxidase levels were 1.591±3.35, Vitamin C levels were 0.32±0.11 and Vitamin E levels were 4.302±1.54, which is lower than the normal range. The present study concludes that antioxidant plays a major role to fight against oxidative stress. So proper antioxidant should be taken.


Author(s):  
Rasimcan Meral ◽  
Noemi Malandrino ◽  
Mary Walter ◽  
Adam H Neidert ◽  
Ranganath Muniyappa ◽  
...  

Abstract Context Leptin replacement with metreleptin improves glycemia and hypertriglyceridemia in severely hypoleptinemic patients with Generalized Lipodystrophy (GLD), but its effects are variable in partially leptin-deficient patients with Partial Lipodystrophy (PLD). Objective Compare three leptin assays (Study I); identify diagnostic performance of leptin assays to detect responders to metreleptin for each assay (Study II). Design Study I: cross-sectional analysis of average bias between leptin assays. Study II: retrospective analysis of diagnostic accuracy of potential leptin cut-points to detect clinical responders to metreleptin. Setting National Institutes of Health (NIH); University of Michigan. Participants and Interventions Study I: Metreleptin-naïve patients with lipodystrophy (GLD, n=33, PLD, n=67) and healthy volunteers (n=239). Study II: GLD (n=66) and PLD (n=84) patients treated with metreleptin for 12 months. Outcome Measures Leptin concentrations by Millipore RIA; Millipore ELISA (MELISA); R&D systems ELISA, (RDELISA). Response to metreleptin therapy was defined as either reduction ≥1.0% in A1c or ≥30% in serum triglycerides. Results RDELISA measured 3.0±9.5 ng/mL higher than RIA; MELISA measured 11.0±17.8 and 14.0±19.2 less than RIA and RDELISA, respectively. Leptin by RIA, MELISA, and RDELISA modestly predicted metreleptin response in GLD+PLD (ROC AUC 0.74, 0.69, and 0.71, respectively; p&lt;0.01 for all) with lower predictive power in PLD (ROC AUC 0.63, 0.61 and 0.65, respectively; p&gt;0.05 for all). The only reproducible cut-point identified on sensitivity analyses was RIA leptin 7.2 ng/mL (sensitivity 56%; specificity 78%). Conclusions Three common leptin assays are not interchangeable, and a reliable cut-point to select responders to metreleptin was not identified.


2021 ◽  
Author(s):  
Laura Cappelli ◽  
Clifton O. Bingham III ◽  
Patrick M. Forde ◽  
Valsamo Anagnostou ◽  
Julie Brahmer ◽  
...  

Abstract Background Patients with inflammatory arthritis (IA) associated with immune checkpoint inhibitor (ICI) treatment for cancer are typically seronegative for anti-CCP antibodies and rheumatoid factor, but little is known about the presence of other autoantibodies described in early inflammatory arthritis in this patient population. We investigated the prevalence and characteristics of anti-RA33 antibodies in patients with ICI-induced IA. Methods Anti-RA33 ELISAs were performed on sera from four groups of patients: 79 with ICI-induced IA, 52 with rheumatoid arthritis (RA), 35 treated with ICIs without IA during follow-up, and 50 healthy controls. Anti-RA33 positivity and titer, clinical and demographic data were compared across groups. Results Anti-RA33 antibodies were found in 9/79 (11.4%) patients with ICI-induced IA but in 0/35 patients treated with ICIs who did not develop IA (0%; p=0.04). Of the 9 patients positive for anti-RA33, two had sera available from before ICI treatment; anti-RA33 antibodies were present in both pre-ICI treatment. In RA patients, 7.7% were positive for anti-RA33 antibodies as were 2% of healthy controls. In ICI-induced IA, anti-RA33 antibodies were associated with anti-CCP antibodies (p=0.001). We found no statistically significant differences in other clinical characteristics in those with and without anti-RA33 antibodies, but we observed trends toward anti-RA33 antibodies being more common in women and those receiving prior radiation therapy. Conclusions Anti-RA33 antibodies are present in a subset of patients with ICI-induced IA and may be a biomarker for developing IA. Additional studies evaluating serial samples before and after ICI treatment will further establish the temporal relationship of these antibodies to IA development.


2011 ◽  
Vol 164 (5) ◽  
pp. 833-838 ◽  
Author(s):  
Maurizio Bevilacqua ◽  
Marco Invernizzi ◽  
Velella Righini ◽  
Stefano Carda ◽  
Carlo Cisari

ContextIn healthy subjects and in patients with primary hyperparathyroidism (PH), the administration of a low dose of 25(OH)D (25 μg/day) increases the serum levels of both 25(OH)D and 1,25(OH)2D. It is unknown whether this relationship is present in patients affected by familial benign hypocalciuric hypercalcemia (FBH).ObjectiveTo evaluate the different vitamin D substrate–product relationship after oral vitamin D supplementation in familial benign hypercalcemia, PH, and healthy controls.DesignWe evaluated the main physiological regulators of 1α-hydroxylase and the substrate–product relationship of 25(OH)D and 1,25(OH)2D in 20 patients with PH, 25 with FBH, and 122 healthy sex- and age-matched controls before and after administration of 25(OH)D for 2 weeks.Results25(OH)D increased significantly in all subjects, whereas 1,25(OH)2D serum levels increased significantly in PH patients and healthy controls but not in patients with FBH. Therefore, a significant positive substrate–product relationship of 25(OH)D–1,25(OH)2D was found in PH and healthy controls, but not in FBH. Monomeric calcitonin (hCT-M) was significantly lower at baseline and after 25(OH)D supplementation in the FBH group compared with the other two groups.ConclusionsThe lack of 1,25(OH)2D increase in FBH may be due to a direct inhibitory effect on 1α-hydroxylase of hypercalcemiaper se, increased metabolic clearance of 1,25(OH)2D, or a decreased stimulus of 1α-hydroxylase related to persistently low levels of hCT.


Author(s):  
Kathleen B. Reuter

The reaction rate and efficiency of piperazine to 1,4-diazabicyclo-octane (DABCO) depends on the Si/Al ratio of the MFI topology catalysts. The Al was shown to be the active site, however, in the Si/Al range of 30-200 the reaction rate increases as the Si/Al ratio increases. The objective of this work was to determine the location and concentration of Al to explain this inverse relationship of Al content with reaction rate.Two silicalite catalysts in the form of 1/16 inch SiO2/Al2O3 bonded extrudates were examined: catalyst A with a Si/Al of 83; and catalyst B, the acid/phosphate Al extracted form of catalyst A, with a Si/Al of 175. Five extrudates from each catalyst were fractured in the transverse direction and particles were obtained from the fracture surfaces near the center of the extrudate diameter. Particles were also obtained from the outside surfaces of five extrudates.


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