tbuckley/cabot-search huggingface dataset:
Dietary Intake and Cell Membrane Levels of Long-Chain n-3 Polyunsaturated Fatty Acids and the Risk of Primary Cardiac Arrest
Authors: D S Siscovick, T E Raghunathan, I King, S Weinmann, K G Wicklund, J Albright, V Bovbjerg, P Arbogast, H Smith, L H Kushi
Journal: JAMA (1995)

<h3>Objective.</h3> —To assess whether the dietary intake of long-chain n-3 polyunsaturated fatty acids from seafood, assessed both directly and indirectly through a biomarker, is associated with a reduced risk of primary cardiac arrest. <h3>Design.</h3> —Population-based case-control study. <h3>Setting.</h3> —Seattle and suburban King County, Washington. <h3>Participants</h3> —A total of 334 case patients with primary cardiac arrest, aged 25 to 74 years, attended by paramedics during 1988 to 1994 and 493 population-based control cases and controls, matched for age and sex, randomly identified from the community. All cases and controls were free of prior clinical heart disease, major comorbidity, and use of fish oil supplements. <h3>Measures of Exposure.</h3> —Spouses of case patients and control subjects were interviewed to quantify dietary n-3 polyunsaturated fatty acid intake from seafood during the prior month and other clinical characteristics. Blood specimens from 82 cases (collected in the field) and 108 controls were analyzed to determine red blood cell membrane fatty acid composition, a biomarker of dietary n-3 polyunsaturated fatty acid intake. <h3>Results.</h3> —Compared with no dietary intake of eicosapentaenoic acid (C<sub>20:5n-3</sub>) and docosahexaenoic acid (C<sub>22:6n-3</sub>), an intake of 5.5 g of n-3 fatty acids per month (the mean of the third quartile and the equivalent of one fatty fish meal per week) was associated with a 50% reduction in the risk of primary cardiac arrest (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.4 to 0.8), after adjustment for potential confounding factors. Compared with a red blood cell membrane n-3 polyunsaturated fatty acid level of 3.3% of total fatty acids (the mean of the lowest quartile), a red blood cell n-3 polyunsaturated fatty acid level of 5.0% of total fatty acids (the mean of the third quartile) was associated with a 70% reduction in the risk of primary cardiac arrest (OR, 0.3; 95% CI, 0.2 to 0.6). <h3>Conclusion.</h3> —Dietary intake of n-3 polyunsaturated fatty acids from seafood is associated with a reduced risk of primary cardiac arrest. (<i>JAMA</i>. 1995;274:1363-1367)
Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data
Authors: Brian Shine, Rebecca F McKnight, Laurence Leaver, John R Geddes
Journal: The Lancet (2015)

Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use.In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates.Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76-2·12; p<0·0001), hypothyroidism (2·31, 2·05-2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21-1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96-1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88-1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes.Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring.None.
Increased Superoxide and Endothelial NO Synthase Uncoupling in Blood Vessels of Bmal1-Knockout Mice
Authors: Ciprian B. Anea, Bo Cheng, Shruti Sharma, Sanjiv Kumar, R. William Caldwell, Lin Yao, M. Irfan Ali, Ana M. Merloiu, David W. Stepp, Stephen M. Black, David J.R. Fulton, R. Daniel Rudic
Journal: Circulation Research (2012)

Rationale: Disruption of the circadian clock in mice produces vascular dysfunction as evidenced by impairments in endothelium-dependent signaling, vasomotion, and blood vessel remodeling. Although the altered function of endothelial NO synthase and the overproduction of reactive oxygen species are central to dysfunction of the endothelium, to date, the impact of the circadian clock on endothelial NO synthase coupling and vascular reactive oxygen species production is not known. Objective: The goals of the present study were to determine whether deletion of a critical component of the circadian clock, Bmal1, can influence endothelial NO synthase coupling and reactive oxygen species levels in arteries from Bmal1-knockout (KO) mice. Methods and Results: Endothelial function was reduced in aortae from Bmal1-KO mice and improved by scavenging reactive oxygen species with polyethylene glycol-superoxide dismutase and nonselectively inhibiting cyclooxygenase isoforms with indomethacin. Aortae from Bmal1-KO mice exhibited enhanced superoxide levels as determined by electron paramagnetic resonance spectroscopy and dihydroethidium fluorescence, an elevation that was abrogated by administration of nitro- l -arginine methyl ester. High-performance liquid chromatography analysis revealed a reduction in tetrahydrobiopterin and an increase in dihydrobiopterin levels in the lung and aorta of Bmal1-KO mice, whereas supplementation with tetrahydrobiopterin improved endothelial function in the circadian clock KO mice. Furthermore, levels of tetrahydrobiopterin, dihydrobiopterin, and the key enzymes that regulate biopterin bioavailability, GTP cyclohydrolase and dihydrofolate reductase exhibited a circadian expression pattern. Conclusions: Having an established influence in the metabolic control of glucose and lipids, herein, we describe a novel role for the circadian clock in metabolism of biopterins, with a significant impact in the vasculature, to regulate coupling of endothelial NO synthase, production of superoxide, and maintenance of endothelial function.
Gadolinium-coordinated elastic nanogels for in vivo tumor targeting and imaging
Authors: Chang-Keun Lim, Ajay Singh, Jeongyun Heo, Daehong Kim, Kyung Eun Lee, Hyesung Jeon, Joonseok Koh, Ick-Chan Kwon, Sehoon Kim
Journal: Biomaterials (2013)
Desmin modifications associate with amyloid-like oligomers deposition in heart failure
Authors: Giulio Agnetti, Victoria L. Halperin, Jonathan A. Kirk, Khalid Chakir, Yurong Guo, Linda Lund, Francesco Nicolini, Tiziano Gherli, Carlo Guarnieri, Claudio M. Caldarera, Gordon F. Tomaselli, David A. Kass, Jennifer E. Van Eyk
Journal: Cardiovascular Research (2014)

The ultimate cause of heart failure (HF) is not known to date. The cytoskeletal protein desmin is differentially modified and forms amyloid-like oligomers in HF. We postulated that desmin post-translational modifications (PTMs) could drive aberrant desmin aggregation in HF. Therefore, we identified these PTMs and investigated their impact on desmin amyloidogenicity in human and experimental HF. We detected increased levels of selectively phosphorylated and cleaved desmin in a canine pacing model of dyssynchronous HF (DHF) compared with either controls or animals treated with cardiac resynchronization therapy (CRT). This unique animal model combines clinically relevant features with the possibility of a partly rescued phenotype. We confirmed analogous changes in desmin modifications in human HF and identified two phosphorylation sites within a glycogen synthase kinase 3 (GSK3) consensus sequence. Desmin-positive oligomers were also increased in DHF hearts compared with controls. Their amyloid properties were decreased by treatment with CRT or an anti-amyloid small molecule. Finally, we confirmed GSK3's involvement with desmin phosphorylation using an in vitro model. Based on these findings, we postulate a new mechanism of cardiac toxicity based on the PTM-driven accumulation of desmin amyloid-like oligomers. Phosphorylation and cleavage as well as oligomers formation are reduced by treatment (CRT) indicating a relationship between the three. Finally, the decrease of desmin amyloid-like oligomers with CRT or small molecules points both to a general mechanism of HF based on desmin toxicity that is independent of protein mutations and to novel potential therapies.
Why stress is BAD for cancer patients
Authors: Archana S. Nagaraja, Guillermo N. Armaiz-Pena, Susan K. Lutgendorf, Anil K. Sood
Journal: Journal of Clinical Investigation (2013)

Behavioral stress is known to promote tumor progression in experimental models, but the role of behavioral stress in cancer initiation is less clear. In this issue, Hassan et al. focus on the signaling and biological effects induced by stress hormones that lead to tumor cell evasion from apoptosis, resulting in prostate cancer progression.
The anti-inflammatory drug sodium salicylate inhibits nitric oxide formation induced by interleukin-1β at a translational step, but not at a transcriptional step, in hepatocytes
Authors: K Sakitani
Journal: Hepatology (1997)

Recent evidence suggests that nitric oxide (NO) mediates cellular injury under the pathological conditions such as endotoxemia in the liver of rats. Regulation of NO production is crucial for improving the hepatic dysfunction. We have previously reported that, in cultured rat hepatocytes, a single cytokine interleukin-1β (IL-1β) stimulated a release of nitrite, an oxidation product of NO, into culture medium dose- and time-dependently. The objective of this study was to investigate an ability of the anti-inflammatory drug NaSA to affect the production of NO in hepatocytes. IL-1β increased levels of inducible NO synthase (iNOS) messenger RNA (mRNA) with a maximal effect at 8 hours in primary cultures of rat hepatocytes. Nuclear factor-κB (NF-κB), that is an important nuclear factor protein in iNOS gene transcription in response to inflammatory mediators, also appeared in the nuclear fraction of hepatocytes 1 hour after addition of IL-1β. Sodium salicylate markedly inhibited the NO formation induced by IL-1β, but did not affect NF-κB activation and iNOS mRNA induction. Western blot analysis revealed that sodium salicylate (NaSA) blocked a step of iNOS protein synthesis. These findings indicate that NaSA may reduce hepatic injury by preventing the induction of NO formation in response to IL-1β at the posttranscriptional step.
Targeting Truncated Retinoid X Receptor-α by CF31 Induces TNF-α–Dependent Apoptosis
Authors: Guang-Hui Wang, Fu-Quan Jiang, Ying-Hui Duan, Zhi-Ping Zeng, Fan Chen, Yi Dai, Jie-Bo Chen, Jin-Xing Liu, Jie Liu, Hu Zhou, Hai-Feng Chen, Jin-Zhang Zeng, Ying Su, Xin-Sheng Yao, Xiao-Kun Zhang
Journal: Cancer Research (2012)

A truncated version of retinoid X receptor-α, tRXR-α, promotes cancer cell survival by activating the phosphoinositide 3-kinase (PI3K)/AKT pathway. However, targeting the tRXR-α-mediated survival pathway for cancer treatment remains to be explored. We report here our identification of a new natural product molecule, CF31, a xanthone isolated from Cratoxylum formosum ssp. pruniflorum, and the biologic evaluation of its regulation of the tRXR-α-mediated PI3K/AKT pathway. CF31 binds RXR-α and its binding results in inhibition of RXR-α transactivation. Through RXR-α mutational analysis and computational studies, we show that Arg316 of RXR-α, known to form salt bridges with certain RXR-α ligands, such as 9-cis-retinoic acid (9-cis-RA), is not required for the antagonist effect of CF31, showing a distinct binding mode. Evaluation of several CF31 analogs suggests that the antagonist effect is mainly attributed to an interference with Leu451 of helix H12 in RXR-α. CF31 is a potent inhibitor of AKT activation in various cancer cell lines. When combined with TNF-α, it suppresses TNF-α activation of AKT by inhibiting TNF-α-induced tRXR-α interaction with the p85α regulatory subunit of PI3K. CF31 inhibition of TNF-α activation of AKT also results in TNF-α-dependent activation of caspase-8 and apoptosis. Together, our results show that CF31 is an effective converter of TNF-α signaling from survival to death by targeting tRXR-α in a unique mode and suggest that identification of a natural product that targets an RXR-mediated cell survival pathway that regulates PI3K/AKT may offer a new therapeutic strategy to kill cancer cells.
The likelihood of low bone mineral density (BMD) in male patients with chronic obstructive pulmonary disease (COPD) in age 40-70 years
Authors: Sviatlana Lemiasheuskaya, Natalia Vasileva
Journal: European Respiratory Journal (2012)

Aim and objectives: to study the likelihood of low BMD in male pts with COPD in age 40-70 yrs.

Material and Methods: We examined (retrospective study) 92 COPD male pts aged 40 – 70 years. All the findings were compared in 34 normal age-, sex- and BMI-matched control subjects. BMD was measured in spine (L1-L4) and femoral necks using DEXA.

Results: Osteopenia and osteoporosis were diagnosed in 46 % and 22 % cases in COPD pts group respectively. The index of odds ratio (OR) was 4.14 with the confidence interval (CL) (95%CI, 3.12-5.51) in pts with the presence of exacerbations in the year 3 and more. Exacerbations occurring with the increase of leukocytes increase the probability of reducing BMD (OR, 3.54; 95% CI, 2.74-4.58). The likelihood of low BMD significantly increase in pts with disease duration 10 yrs or more (OR, 7.34; 95% CI, 5.41-9.95); work with hazardous occupational factors – OR, 2.30 (95% CI, 1.63-3.24); smoking – OR, 5.25 (95% CI, 3.20-8.35); the presence of emphysema in the X-ray – OR, 3.11 (95% CI, 2.37-4.06). Age 57 years and over - increases 5.25 times (95% CI, 3.90-7.07). The likelihood of lower BMD in the 2nd stages is 2.18 (95% CI, 1.36-3.50) and in the 3rd stage is greatly increase – OR, 10.91 (95% CI, 6.98-17.05). The hypoxia (SO2%) significantly increases the risk of secondary reduction of BMD - OR 15, (95% CI 10.05-22.38).

Conclusion: Factors that increase the likelihood of reducing the BMD are the frequency and type of exacerbations, age, duration and severity of disease, the presence of occupational factors, emphysema and hypoxia.
B-Afferents: A fundamental division of the nervous system mediating homeostasis?
Authors: James C. Prechtl, Terry L. Powley
Journal: Behavioral and Brain Sciences (1990)

Abstract The peripheral nervous system (PNS) has classically been separated into a somatic division composed of both afferent and efferent pathways and an autonomic division containing only efferents. J. N. Langley, who codified this asymmetrical plan at the beginning of the twentieth century, considered different afferents, including visceral ones, as candidates for inclusion in his concept of the “autonomic nervous system” (ANS), but he finally excluded all candidates for lack of any distinguishing histological markers. Langley's classification has been enormously influential in shaping modern ideas about both the structure and the function of the PNS. We survey recent information about the PNS and argue that many of the sensory neurons designated as “visceral” and “somatic” are in fact part of a histologically distinct group of afferents concerned primarily autonomic function. These afferents have traditionally been known as “small dark” neurons or B-neurons. In this target article we outline an association between autonomic and B-neurons based on ontogeny, cell phenotype, and functional relations, grouping them together as part of a common reflex system involved in homeostasis. This more parsimonious classification of the PNS, made possible by the identification of a group of afferents associated primarily with the ANS, avoids a number of confusions produced by the classical orientation. It may also have practical implications for an understanding of nociception, homeostatic reflexes, and the evolution of the nervous system.
CPR Techniques That Combine Chest and Abdominal Compression and Decompression
Authors: Charles F. Babbs
Journal: Circulation (1999)

This study was done to elucidate mechanisms by which newer cardiopulmonary resuscitation (CPR) techniques, including interposed abdominal compression (IAC), active compression-decompression (ACD), and Lifestick CPR, augment systemic perfusion pressure and forward flow and to compare the 3 techniques in the same test system.Mathematical models describing hemodynamics of the adult human circulation during cardiac arrest and CPR were created and exercised by use of spreadsheet software. Assumptions of the models are limited to normal human anatomy and physiology, the definition of compliance (volume change/pressure change), and Ohm's law (flow=pressure/resistance). Standard CPR generates 1.3 L/min forward and 25 mm Hg systemic perfusion pressure. In otherwise identical models, IAC-CPR generates 2.4 L/min and 45 mm Hg; ACD-CPR, 1.6 L/min and 30 mm Hg; and Lifestick CPR, which combines IAC and ACD, 3.1 L/min and 58 mm Hg. Augmented CPR techniques work by enhanced priming of either chest or abdominal pump mechanisms.Adjunctive maneuvers, combined with conventional chest compression, can produce substantial hemodynamic benefit in CPR by credible physiological mechanisms.
The Athlete’s Heart
Authors: Babette M. Pluim, Aeilko H. Zwinderman, Arnoud van der Laarse, Ernst E. van der Wall
Journal: Circulation (2000)

Background —It has been postulated that depending on the type of exercise performed, 2 different morphological forms of athlete’s heart may be distinguished: a strength-trained heart and an endurance-trained heart. Individual studies have not tested this hypothesis satisfactorily. Methods and Results —The hypothesis of divergent cardiac adaptations in endurance-trained and strength-trained athletes was tested by applying meta-analytical techniques with the assumption of a random study effects model incorporating all published echocardiographic data on structure and function of male athletes engaged in purely dynamic (running) or static (weight lifting, power lifting, bodybuilding, throwing, wrestling) sports and combined dynamic and static sports (cycling and rowing). The analysis encompassed 59 studies and 1451 athletes. The overall mean relative left ventricular wall thickness of control subjects (0.36 mm) was significantly smaller than that of endurance-trained athletes (0.39 mm, P =0.001), combined endurance- and strength-trained athletes (0.40 mm, P =0.001), or strength-trained athletes (0.44 mm, P &lt;0.001). There was a significant difference between the 3 groups of athletes and control subjects with respect to left ventricular internal diameter ( P &lt;0.001), posterior wall thickness ( P &lt;0.001), and interventricular septum thickness ( P &lt;0.001). In addition, endurance-trained athletes and strength-trained athletes differed significantly with respect to mean relative wall thickness (0.39 versus 0.44, P =0.006) and interventricular septum thickness (10.5 versus 11.8 mm, P =0.005) and showed a trend toward a difference with respect to posterior wall thickness (10.3 versus 11.0 mm, P =0.078) and left ventricular internal diameter (53.7 versus 52.1 mm, P =0.055). With respect to cardiac function, there were no significant differences between athletes and control subjects in left ventricular ejection fraction, fractional shortening, and E/A ratio. Conclusions —Results of this meta-analysis regarding athlete’s heart confirm the hypothesis of divergent cardiac adaptations in dynamic and static sports. Overall, athlete’s heart demonstrated normal systolic and diastolic cardiac functions.
Methylisothiazolinones elicit increased production of both T helper (Th)1- and Th2-like cytokines by peripheral blood mononuclear cells from contact allergic individuals
Authors: K. Masjedi, N. Ahlborg, B. Gruvberger, M. Bruze, A.-T. Karlberg
Journal: British Journal of Dermatology (2003)

Journal Article Methylisothiazolinones elicit increased production of both T helper (Th)1‐ and Th2‐like cytokines by peripheral blood mononuclear cells from contact allergic individuals K. Masjedi, K. Masjedi Department of Medicine, Unit of Clinical Allergy Research, Karolinska Institutet and Hospital, Stockholm, Sweden, Department of Immunology, Stockholm University, Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar N. Ahlborg, N. Ahlborg Department of Medicine, Unit of Clinical Allergy Research, Karolinska Institutet and Hospital, Stockholm, Sweden, Department of Immunology, Stockholm University, Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar B. Gruvberger, B. Gruvberger Department of Occupational and Environmental Dermatology, University Hospital, Malmö, Sweden Search for other works by this author on: Oxford Academic Google Scholar M. Bruze, M. Bruze Department of Occupational and Environmental Dermatology, University Hospital, Malmö, Sweden Search for other works by this author on: Oxford Academic Google Scholar A.‐T. Karlberg A.‐T. Karlberg Department of Chemistry, Dermatochemistry and Skin Allergy, Göteborg University, SE‐412 96 Göteborg, Sweden Professor Ann‐Therese Karlberg. E‐mail: karlberg@chem.gu.se Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 6, 1 December 2003, Pages 1172–1182, https://doi.org/10.1111/j.1365-2133.2003.05750.x Published: 01 December 2003 Article history Accepted: 26 June 2003 Published: 01 December 2003