Objective
Hepcidin is regulated by anemia and inflammation. It is primarily expressed in the liver but studies have reported its expression in adipose tissue. The relationship between BMI and serum ...hepcidin and the relationship between liver histology and serum hepcidin in the morbidly obese was investigated.
Methods
Serum and liver tissue from patients undergoing bariatric surgery (bariatric cohort, n = 105) and serum from healthy blood donors (n = 60) were used to conduct this study. Serum hepcidin was measured using sandwich ELISA, highly specific for hepcidin‐25. Serum ferritin, IL‐6, IL‐1β and liver function biochemistries were also measured.
Results
After controlling for covariates, BMI ≥ 35 kg/m2 was significantly associated with higher serum hepcidin level compared to individuals with lower BMI groups (17.7 ± 11.5 vs. 3.3 ± 4.7 ng/ml, P = 0.002). The presence of NAFLD was not associated with higher serum levels of hepcidin (multivariate P = 0.37). There was no association between serum hepcidin levels and liver histology (presence of steatohepatitis, advanced fibrosis, or NAFLD activity score) in the bariatric cohort.
Conclusions
Obesity, but not the presence of NAFLD was associated with serum hepcidin levels. There was no association between serum hepcidin and liver histology in the morbidly obese undergoing bariatric surgery.
Background
Red blood cell (RBC) transfusion is a lifesaving therapy, the logistic implementation of which requires RBC storage. However, stored RBCs exhibit substantial donor variability in multiple ...characteristics, including hemolysis in vitro and RBC recovery in vivo. The basis of donor variability is poorly understood.
Study Design and Methods
We applied a murine model of RBC storage and transfusion to test the hypothesis that genetically distinct inbred strains of mice would demonstrate strain‐specific differences in RBC storage. In vivo recoveries were determined by monitoring transfused RBCs over 24 hours. Timed aliquots of stored RBCs were subjected to tandem chromatography/mass spectrometry analysis to elucidate metabolic changes in the RBCs during storage.
Results
Using independent inbred mouse strains as donors, we found substantial strain‐specific differences in posttransfusion RBC recovery in vivo after standardized refrigerated storage in vitro. Poor posttransfusion RBC recovery correlated with reproducible metabolic variations in the stored RBC units, including increased lipid peroxidation, decreased levels of multiple natural antioxidants, and accumulation of cytidine. Strain‐dependent differences were also observed in eicosanoid generation (i.e., prostaglandins and leukotrienes).
Conclusion
These findings provide the first evidence of strain‐specific metabolomic differences after refrigerated storage of murine RBCs. They also provide the first definitive biochemical evidence for strain‐specific variation of eicosanoid generation during RBC storage. The molecules described that correlate with RBC storage quality, and their associated biochemical pathways, suggest multiple causal hypotheses that can be tested regarding predicting the quality of RBC units before transfusion and developing methods of improved RBC storage.
The PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis NASH) trial demonstrated that pioglitazone and vitamin E improved ...liver histology to varying degrees, but the mechanisms are unknown. We conducted a study to examine the changes in adipose tissue insulin resistance (Adipo‐IR) during the PIVENS trial and its relationship to histological endpoints. Adipo‐IR (fasting nonesterified fatty acids NEFAs × fasting insulin) was calculated at baseline and after 16 and 96 weeks of therapy. Compared to placebo, the baseline Adipo‐IR was not different in either the vitamin E group (P = 0.34) or the pioglitazone group (P = 0.29). Baseline Adipo‐IR was significantly associated with fibrosis score (P = 0.02), but not with other histological features or nonalcoholic fatty liver disease (NAFLD) activity score (NAS). After 16 weeks, compared to placebo, the pioglitazone group had a significant reduction in Adipo‐IR (−15.7 versus −1.91; P = 0.02), but this effect did not persist at 96 weeks (−3.25 versus −4.28; P = 0.31). Compared to placebo, Adipo‐IR in the vitamin E group did not change significantly either after 16 weeks (P = 0.70) or after 96 weeks (P = 0.85). Change in Adipo‐IR at week 16 was not associated with changes in any histological parameters at week 96, but improvement in Adipo‐IR at week 96 was significantly associated with improvement in ballooning (P = 0.03), fibrosis (P = 0.004), and NAS (P = 0.01). Conclusion: Vitamin E improved liver histology independent of changes in Adipo‐IR, and pioglitazone treatment acutely improved Adipo‐IR, but this was not sustained. Changes in Adipo‐IR were associated with changes in liver histology, including fibrosis. (HEPATOLOGY 2012)
Shared use agreements (SUA) could increase opportunities for physical activity (PA) in under-resourced, urban areas. Despite recent investments in SUAs, the extent to which they reach communities in ...need and the level of community awareness and use of SUAs remains unclear. This cross-sectional study examined: 1) the distribution of SUAs in Los Angeles (LA) during the 2015–2016 academic year, 2) the characteristics of communities where SUAs were located, and 3) the extent to which community members were aware of and using available facilities. Assessment methods included: 1) abstraction of school administrative data reflecting the geographic distribution and scope of SUAs in LA, 2) collation of community-level Census and local planning data to describe demographic characteristics and per capita park acreage of communities where SUAs were located, and 3) collection of data via an Internet panel survey of LA adults (n = 371) examining awareness and use of SUA facilities. Under 3% of schools had a SUA in place during the study period. Compared to other areas of the city, areas within one mile of SUAs had more Hispanic/Latino, low-income, and lower educational status residents. Among survey respondents, 25.6% of those living within one mile of a SUA reported having access to school facilities; 48.6% of those reporting access reported using them. Although potentially targeted in high-needs areas, community members may not be aware of or utilizing SUA facilities. Additional efforts are needed to both expand access to school-based PA resources and attract community users.
•Under 3% of schools in Los Angeles had a shared use agreement in place.•Shared use sites were more concentrated in lower socioeconomic areas.•Only 25.6% of those living near a shared use site were aware of the facility.•Additional resources and activities may be required to attract community users.
To evaluate the effects of surgical weight loss on hepatic lipid peroxidation levels and cytochrome P-450 protein expression in patients with nonalcoholic fatty liver disease (NAFLD).
NAFLD and ...nonalcoholic steatohepatitis (NASH) affect hepatic cytochrome P-450 (CYP) protein expression and activity, and CYP2E1 may play a role in the pathogenesis of NAFLD and NASH through induction of oxidative stress and lipid peroxidation. NAFLD and NASH are associated with increased systemic lipid peroxidation levels and elevated hepatic CYP2E1 activity, but hepatic CYP3A4/5 activity is decreased.
Liver biopsies from 20 patients with NAFLD who underwent bariatric surgery were obtained intraoperatively and at 15 +/- 7 months following surgery. Hepatic malondialdehyde (MDA) levels (a marker of lipid peroxidation), CYP2E1 and CYP3A4/5 protein expression, and steatosis, as a percent of total area, were measured by immunohistochemistry followed by digital image quantitation.
Following weight loss, as reflected by reduced BMI (54 +/- 9 vs. 37 +/- 9 kg/m2; P < 0.001), features of the metabolic syndrome, grade and stage of liver disease, and liver histology were all significantly improved (P < 0.01). Hepatic MDA staining (35 +/- 18% vs. 23 +/- 14%; P = 0.02), CYP2E1 protein content (68 +/- 9% vs. 56 +/- 11%; P < 0.001), and steatosis (17 +/- 7% vs. 2 +/- 3%; P < 0.001) were significantly reduced following weight loss. CYP3A4/5 protein content was unchanged (57 +/- 13% vs. 55 +/- 13%; P = 0.433). The reduction in lipid peroxidation was independently associated with changes in CYP2E1 protein expression after bariatric surgery (r = 0.477; P = 0.033).
Elevations in hepatic lipid peroxidation and CYP2E1 expression that are seen in NAFLD improve significantly with weight loss induced by bariatric surgery.
Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are widely used
laboratory markers of systemic inflammation.
A thorough understanding of the similarities and differences between ...these two serological
markers, including factors that affect measurements, is necessary for the proper utilization
and interpretation of ESR and CRP.
This review summarizes the current published literature (searched on MEDLINE
through February 2016) surrounding the history and utilization of ESR and CRP, and examines
factors that affect ESR and CRP measurements and discordance amongst these two inflammatory
markers.
As ESR and CRP lack sensitivity or specificity, these tests should be used only in combination
with clinical history and physical exam for diagnosis and monitoring of pathological conditions.
The clinical application of these tests in diagnosis is best applied to conditions in which
there is high or low clinical probability of disease. Importantly, discrepancies between ESR and
CRP measurements commonly have been reported in both inpatient and outpatient settings and
this problem may be particularly prevalent in chronic inflammatory diseases. Numerous physiological
factors, including noninfectious conditions and resolution of inflammation can contribute
to abnormally high ESR/low CRP readings or vice versa.
Although discordance may be encountered in certain settings, proper utilization of
ESR and CRP measurements continues to play an important role in clinical management of many
inflammatory and other conditions.
Background:
Although immobility is a common risk factor for venous thromboembolism (VTE) in medical inpatients, lack of a consistent definition of this term may limit accurate assessment of VTE risk ...for thromboprophylaxis.
Objective:
To examine various definitions of immobility used in recent pharmacological thromboprophylaxis clinical trials.
Data Sources:
PubMed and relevant references from articles/reviews from 2008 to 2016 were searched. Randomized controlled trials (RCTs) and other clinical studies involving adult hospitalized medical patients in acute care hospital settings that used the term immobility were selected. Two investigators independently abstracted data in duplicate, and accuracy was checked by a third investigator.
Results:
Twenty-one clinical studies were included. There was heterogeneity among individual VTE risk factors, with respect to the definition of immobility in medical inpatients in these trials. Thirteen studies utilized objective criteria to define “immobility” including duration (12 studies) and distance or time walked (6 studies). In contrast, 7 studies focused principally on subjective definitions (ie, describing the nature of immobility rather than specifying its quantitative measurement). Three RCTs vaguely defined the level of patient’s immobility after hospitalization.
Conclusion:
Despite the well-known effectiveness of pharmacological thromboprophylaxis for the prevention of VTE in acutely ill medical patients, there is no current consensus on how to define immobility. The heterogeneous nature of definitions of immobility has led to uncertainty about the importance of immobility in VTE risk assessment models. Although clinical studies have incorporated varying definitions of immobility into their inclusion criteria, immobility as a specific VTE risk factor has not been clearly defined.
BACKGROUND
Transfusion of platelets (PLTs) is a common therapy in a number of clinical settings. However, it is well understood that there is substantial donor‐to‐donor variation in how well PLTs ...store and thus the quality of the products that are transfused. The basis of such variation is poorly understood, and there are limited metrics by which units of PLTs can be assessed for their posttransfusion performance. It has repeatedly been demonstrated that myriad biologic changes take place during PLT storage; however, which of the changes correlate with quality of the stored PLTs and/or are mechanistically involved in PLT function remains undetermined.
STUDY DESIGN AND METHODS
The current study tested stored PLTs from 21 normal subjects, combining high‐resolution metabolomics of stored PLTs with in vivo PLT recoveries and survivals. Both individual analytes and metabolic pathways that correlate with posttransfusion PLT viability were identified.
RESULTS
Caffeine metabolites were associated with poor PLT recovery; caffeine metabolism was not ongoing in the PLT bag and remained at prestorage levels. Acylcarnitines, particular fatty acid metabolites, and oxidized fatty acids were associated with poor PLT survivals. Of the myriad metabolic changes during PLT storage, these are the first reported metabolic findings to begin distinguishing which changes are of functional importance regarding posttransfusion PLT performance.
CONCLUSIONS
Together, these findings provide novel mechanistic insights into the functional biology of the PLT storage lesion as well as identifying potential targets for modifying donor environment (e.g., caffeine consumption) and also metrics of quality assessment for stored human PLTs.
Colorectal Cancer Screening Bray, Christopher; Bell, Lauren N; Liang, Hong ...
Wisconsin medical journal (Madison, Wis.),
02/2017, Letnik:
116, Številka:
1
Journal Article
Recenzirano
Colorectal cancer (CRC) continues to be one of the most commonly diagnosed cancers and contributes significantly to many cancer-related deaths despite sustained progress in diagnostic and treatment ...options. Many forms of CRC can be prevented through early and routine screening, when precancerous lesions may be detected and removed before they undergo malignant transformation or metastasis. Despite widespread efforts to improve CRC screening rates, at least 40% of age-eligible adults do not adhere to screening guidelines. A new generation of noninvasive, molecular-based diagnostic tests with high sensitivities and specificities has the potential to improve screening rates through optimal risk stratification of patients who may benefit from more invasive screening techniques. This review presents various guidelines and methods that are currently available for CRC screening, summarizes the rationale behind utilization of novel molecular-based diagnostic tests for CRC screening and prevention, and discusses appropriate screening techniques and intervals in populations of varying risk.
Metabolic syndrome (MetS) doubles the risk of adverse cardiovascular events. Glucagon-like peptide 1 (GLP-1) receptor agonists induce weight loss, increase insulin secretion, and improve glucose ...tolerance. Studies in healthy animals suggest cardioprotective properties of GLP-1 receptor agonists, perhaps partially mediated by improved sarco-endoplasmic reticulum Ca(2+) ATPase (SERCA) activity. We examined the acute effect of GLP-1 receptor agonists on coronary smooth muscle cells (CSM) enzymatically isolated from lean, healthy Ossabaw miniature swine. Intracellular Ca(2+) handling was interrogated with fura-2. The GLP-1 receptor agonist exenatide activated SERCA but did not alter other Ca(2+) transporters. Further, we tested the hypothesis that chronic, in vivo treatment with GLP-1 receptor agonist AC3174 would attenuate coronary artery disease (CAD) in swine with MetS. MetS was induced in 20 swine by 6 months' feeding of a hypercaloric, atherogenic diet. Swine were then randomized (n = 10/group) into placebo or AC3174 treatment groups and continued the diet for an additional 6 months. AC3174 treatment attenuated weight gain, increased insulin secretion, and improved glucose tolerance. Intravascular ultrasound and histology showed no effect of AC3174 on CAD. MetS abolished SERCA activation by GLP-1 receptor agonists. We conclude that MetS confers vascular resistance to GLP-1 receptor agonists, partially through impaired cellular signaling steps involving SERCA.
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