Cushing's syndrome (CS) increases cardiovascular risk (CVR) and adipocytokine imbalance, associated with an increased inflammatory state. Telomere length (TL) shortening is a novel CVR marker, ...associated with inflammation biomarkers. We hypothesized that inflammatory state and higher CVR in CS might be related to TL shortening, as observed in premature aging.
To evaluate relationships between TL, CVR and inflammation markers in CS.
In a cross-sectional study, 77 patients with CS (14 males, 59 pituitary-, 17 adrenal- and 1 ectopic-origin; 21 active disease) and 77 age-, gender-, smoking-matched controls were included. Total white blood cell TL was measured by TRF-Southern technique. Clinical data and blood samples were collected (lipids, adrenal function, glucose). Adiponectin, interleukin-6 (IL6) and C-reactive protein (CRP) were available in a subgroup of patients (n=32). Correlations between TL and clinical features were examined and multiple linear regression analysis was performed to investigate potential predictors of TL.
Dyslipidemic CS had shorter TL than non-dyslipidemic subjects (7328±1274 vs 7957±1137 bp, p<0.05). After adjustment for age and body mass index, cured and active CS dyslipidemic patients had shorter TL than non-dyslipidemic CS (cured: 7187±1309 vs 7868±1104; active: 7203±1262 vs 8615±1056, respectively, p<0.05). Total cholesterol and triglycerides negatively correlated with TL (r-0.279 and -0.259, respectively, p<0.05), as well as CRP and IL6 (r-0.412 and -0.441, respectively, p<0.05). No difference in TL according the presence of other individual CVR factors (hypertension, diabetes mellitus, obesity) were observed in CS or in the control group. Additional TL shortening was observed in dyslipidemic obese patients who were also hypertensive, compared to those with two or less CVR factors (6956±1280 vs 7860±1180, respectively, p<0.001). Age and dyslipidemia were independent negative predictors of TL.
TL is shortened in dyslipidemic CS patients, further worse if hypertension and/or obesity coexist and is negatively correlated with increased inflammation markers. Increased lipids and a "low" grade inflammation may contribute to TL shortening and consequently to premature ageing and increased morbidity in CS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Telomere length analysis in Cushing's syndrome Aulinas, Anna; Ramírez, María-José; Barahona, María-José ...
European journal of endocrinology,
07/2014, Letnik:
171, Številka:
1
Journal Article
Recenzirano
Odprti dostop
IntroductionHypercortisolism in Cushing's syndrome (CS) is associated with increased morbidity and mortality. Hypercortisolism also occurs in chronic depressive disorders and stress, where telomere ...length (TL) is shorter than in controls. We hypothesized that shortening of telomere might occur in CS and contribute to premature aging and morbidity.AimTo investigate TL in CS patients compared with controls.MethodsSeventy-seven CS patients (14 males, 59 pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated longitudinally, during active disease and after remission of hypercortisolism. Leukocyte TL was measured by telomere restriction fragment–Southern technique. Clinical markers were included in a multiple linear regression analysis to investigate potential predictors of TL.ResultsMean TL in CS patients and controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the longitudinal evaluation, TL was shorter in active disease than after remission (7273 vs 7870, P<0.05). Age and dyslipidemia were negative predictors (P<0.05), and total leukocyte count was a positive predictor for TL (P<0.05). As expected, a negative correlation was found between TL and age (CS, R=−0.400 and controls, R=−0.292; P<0.05). No correlation was found between circulating cortisol, duration of exposure to hypercortisolism or biochemical cure and TL.ConclusionEven though in the cross-sectional comparison of CS and controls no difference in TL was found, in the longitudinal evaluation, patients with active CS had shorter TL than after biochemical cure of hypercortisolism. These preliminary results suggest that hypercortisolism might negatively impact telomere maintenance. Larger studies are needed to confirm these findings.
Display omitted
•Cellulose hydrolysis model based on reaction kinetics and mass transfer effects.•Progressive consumption of the cellulose particles.•The hydrolysis is produced on the surface of the ...cellulose particles.•Mass transfer resistance generated by an oligosaccharide layer.
Conventional kinetic models of cellulose hydrolysis in supercritical water do not accurately represent the operation with concentrated suspensions since they neglect the mass transfer effects. This work proposes a kinetic model which is able to reproduce cellulose hydrolysis at high concentrations providing the optimum reaction conditions to obtain nanocellulose particles and oligomers of controlled size. The basic idea of the model, which is applicable to other lignocellulosic materials, is that the hydrolysis of the cellulose particles generates an oligosaccharides layer which creates a mass transfer resistance. Therefore, it considers both the diffusion of the water molecules from the bulk phase to the surfaces of the cellulose particles and the superficial hydrolysis kinetics. Experimental points were obtained working with two different cellulose types (Dp = 75 µm and Dp = 50 µm) at 390 °C and 25 MPa, residence times between 50 ms and 250 ms and initial cellulose suspension concentration from 3% to 7% w/w (1% to 2.3% w/w at the inlet of the reactor). The average deviation between the experimental points and the theoretical values is lower than 10% proving the applicability of the kinetic model. The experimental and theoretical results demonstrated that increasing the total number of cellulose particles, either increasing the initial concentration or decreasing the average particle diameter, reduces the hydrolysis rate.
Primary liver cancer (HCC) is recognized as the fifth most common neoplasm and the second leading cause of cancer death worldwide. Most risk factors are known, and the molecular pathogenesis has been ...widely studied in the past decade; however, the underlying molecular mechanisms remain to be unveiled, as they will facilitate the definition of novel biomarkers and clinical targets for more effective patient management. We utilize the B/D-HPP popular protein strategy. We report a list of popular proteins that have been highly cocited with the expression “liver cancer”. Several enzymes highlight the known metabolic remodeling of liver cancer cells, four of which participate in one-carbon metabolism. This pathway is central to the maintenance of differentiated hepatocytes, as it is considered the connection between intermediate metabolism and epigenetic regulation. We designed a targeted selective reaction monitoring (SRM) method to follow up one-carbon metabolism adaptation in mouse HCC and in regenerating liver following exposure to CCl4. This method allows systematic monitoring of one-carbon metabolism and could prove useful in the follow-up of HCC and of chronically liver-diseased patients (cirrhosis) at risk of HCC. The SRM data are available via ProteomeXchange in PASSEL (PASS01060)
•Thermal treatments on enhanced polyphenol extraction degrades active compounds.•Antioxidant degradation was studied at 80–150°C of grape marc and filtered extract.•Anthocyanins (AC) follow first ...order degradation; total phenol content and ORAC not.•Degradation was 10 times faster in grape marc than in filtered extract.•90% of AC can be preserved in a pretreatment at 150°C, if no longer than 1min.
Bioactive compounds of wine making by-products are of interest in food, cosmetics and pharmaceutical industries. Extraction of antioxidants under mild conditions is time-consuming, giving ground to the development of intensification processes where the operation at high temperature may deteriorate extract quality. This study examined thermal degradation of grape marc and its filtered extract (80, 100 and 150°C). The decrease in anthocyanin content was modelled under non-isothermal conditions by first order kinetics, using the Arrhenius equation. Simulated degradation under isothermal heating showed that the grape marc is more sensitive by one order of magnitude to heat than the filtered extract. This tendency was also confirmed by analyses of the total phenolic content and antioxidant activity. It is suggested that an optimal combination of temperature, treatment time and also raw material environment could be found in process intensification.
Summary
Telomeres, located at the end of linear chromosomes, are essential to maintain genomic stability. Telomere biology has recently emerged as an important player in the fields of ageing and ...disease. To maintain telomere length (TL) and reduce its degradation after mitosis, the telomerase enzyme complex is produced. Genetic, epigenetic, hormonal and environmental factors can regulate telomerase function. These include stress hormones such as cortisol and growth factors. The hypothalamic–pituitary–adrenal (HPA) axis has been evaluated in psychiatric diseases where hypercortisolism and oxidative stress are often present. Some researches have linked TL shortening to increases in stress‐related cortisol, but others have not. The effects of cortisol on the telomere system are complex and may depend on the intensity and duration of exposure. On the other hand, low levels of IGF‐1 are associated with inflammation and ageing‐related diseases (ischaemic heart disease, congestive heart failure). Both IGF‐1 and TL diminish with age and are positively and strongly correlated with each other. It is not clear whether this positive correlation reflects a single association or a cause–effect relationship. Further research will ideally investigate longitudinal changes in telomeres and both these hormonal axes. To our knowledge, TL dysfunction has not been described in either endogenous hypercortisolism (Cushing's syndrome) or acromegaly where excessive amounts of GH and consequently IGF‐1 are produced. This review focuses on the possible relationships between telomere dysfunction and the hypothalamic–pituitary–adrenal (HPA) axis and GH‐IGF‐1 system.
Objective
To analyze the specificity of calcitonin gene–related peptide (CGRP) levels, we measured alpha‐CGRP circulating levels in a large series of patients with a recent diagnosis of inflammatory ...bowel disease (IBD) who were interviewed regarding comorbid headache.
Background
Several studies have found an association between migraine and IBD.
Methods
In this cross‐sectional study performed in an IBD clinic, morning serum alpha‐CGRP levels were measured by enzyme‐linked immunosorbent assay in 96 patients who were recently diagnosed with IBD and compared to those from 50 similar patients with chronic migraine (CM) and 50 healthy controls (HC).
Results
Alpha‐CGRP levels were higher in patients with IBD (median interquartile range 56.9 35.6–73.9 pg/mL) and patients with CM (53.0 36.7–73.9 pg/mL) compared to HC (37.2 30.0–51.8 pg/mL; p = 0.003; p = 0.019, respectively). Regarding IBD diagnostic subtypes, alpha‐CGRP levels for ulcerative colitis (67.2 ± 49.3 pg/mL; 57.0 35.6–73.4 pg/mL) and Crohn's disease (54.9 ± 27.5 pg/mL; 57.7 29.1–76.1 pg/mL) were significantly higher than those of HC (p = 0.013, p = 0.040, respectively). Alpha‐CGRP levels were further different in patients with IBD with migraine (70.9 51.8–88.7 pg/mL) compared to HC (p < 0.001), patients with IBD without headache (57.5 33.3–73.8 pg/mL; p = 0.049), and patients with IBD with tension‐type headache but without migraine (41.7 28.5–66.9 pg/mL; p = 0.004), though alpha‐CGRP levels in patients with IBD without migraine (53.7 32.9–73.5 pg/mL) remained different over HC (p = 0.028).
Conclusion
Together with CM, circulating alpha‐CGRP levels are different in patients with IBD, perhaps reflecting a chronic inflammatory state. IBD is an example of how alpha‐CGRP levels are not a totally specific migraine biomarker. However, alpha‐CGRP levels were further increased in patients with IBD who have a history of migraine, which reinforces its role as a biomarker in migraine patients, always bearing in mind their comorbidities.
Plain Language Summary
Alpha‐calcitonin gene–related peptide (CGRP) levels may be a potential migraine biomarker, but it is unclear if this is the case because changes in CGRP concentrations can also be present in other conditions. We measured morning serum alpha‐CGRP levels in 96 patients with a recent inflammatory bowel disease (IBD) diagnosis, and compared them to 50 matched healthy participants and 50 matched patients with chronic migraine (CM). We found a significant increase in serum alpha‐CGRP levels in both patients with IBD and CM compared to healthy controls, which we think may reflect chronic inflammation found in IBD; these results offer another example that alpha‐CGRP concentrations are not totally specific for migraine.
Display omitted
•Clinacanthus nutans oil extracted by microwaves, supercritical CO2 and Soxhlet.•Total phenols, flavonoids, phytosterol, β-sitosterols and chlorophyll were measured.•Phytocompounds ...were screened by GC–MS and by UPLC–MS for phenolics characterization.•MAE was superior to SFE and Soxhlet in total yield, time and solvent consumption.•50% v/v of ethanol was optimum concentration for polyphenols enrichment.
The composition and bioactivity of natural plant extracts strongly depends on the extraction technique employed. Clinacanthus nutans Lindau (C. nutans) is a well-known medicinal plant in South-East Asia that has been traditionally used for treatment of hepatitis, skin-rashes and snake venom poisoning, and recently has attracted attention for its applications for treatment and prevention of cancer diseases. In previous studies, the extraction of bioactive compounds from C. nutans by conventional Soxhlet solvent extraction has been described, but this method shows limitations in terms of selectivity, extraction yield and toxicity of the solvents employed. In this study, phytochemical compounds were extracted from leaves and stems of C. nutans by microwave-assisted extraction (MAE), pressurized microwave-assisted extraction (PMAE), supercritical carbon dioxide extraction (SFE) and Soxhlet method to investigate the best technique in terms of yield, extraction time and recovery of bioactive compounds: phenols, flavonoids, phytosterols and β-sitosterol. The extracted phytocompounds and phenolics were characterized by gas chromatography mass spectrometry (GC/MS) and ultra performance liquid chromatography (UPLC). The results showed that MAE was the best technique to achieve a high yield and a maximal total polyphenol content (11.30±0.39mg GAE/g DM) and flavonoids content (and 4.66±0.20mg GAE/g DM), whereas SFE was the best method for phytosterols and β-Sitosterol extraction. P-MAE merely enhanced the polyphenol and flavonoids yield to 14.56±0.77mgGAE/g DM and 5.29±0.30mg QE/g DM respectively, without significant variations on the type of compounds obtained. MAE appears as the most efficient technique for the extraction of phytochemical compounds from C. nutans in a short time with a reasonable yield and a good selectivity toward bioactive nutraceutical compounds, with high concentrations of antioxidants, anti-inflammatory and antimicrobial compounds.
Aim
Fetal blood contains higher concentrations of glutamate‐oxaloacetate transaminase (GOT; a blood enzyme able to metabolize glutamate) than maternal blood. The aim of this study was to determine ...the relationship between GOT and glutamate levels in arterial blood samples from umbilical cord in control newborn infants and newborn infants with hypoxic–ischaemic insult and/or symptoms of hypoxia–ischemia after delivery.
Method
A total of 46 newborn infants (28 females, 18 males) were prospectively included in the study. Twenty‐three infants (18 females, five males) were included as control participants and 23 (10 females, 13 males) were included as newborn infants at risk of adverse neurological outcome (defined as umbilical blood with pH <7.1).
Results
Analysis of glutamate concentration and GOT activity in umbilical blood samples showed that newborn infants with pH <7.1 had higher levels of glutamate (142.4μmol/L SD 61.4 vs 62.8μmol/L SD 25.5; p<0.001) and GOT (83.1U/L SD 60.9 vs 34.9U/L SD 18.2; p<0.001) compared to newborn infants without fetal distress. Analysis of Apgar scores and blood pH values (markers of perinatal distress) showed that conditions of severe distress were associated with higher glutamate and GOT levels.
Interpretation
During fetal development, the ability of GOT to metabolize glutamate suggests that this enzyme can act as an endogenous protective mechanism in the control of glutamate homeostasis.
What this paper adds
Correlation of glutamate and glutamate‐oxaloacetate transaminase (GOT) in fetal asphyxia.
GOT in the control of glutamate homeostasis during development.
Potential use of GOT as treatment in fetal asphyxia.
This article is commented on by Johnston pages 9–10 of this issue.
Microwave assisted extraction has been proved to be a useful tool for the recovery of valuable compounds from natural products. However, little is known about the dielectric properties for mixtures ...of natural products and solvents. In this work, a semi-empirical model is proposed to calculate the dielectric properties of these systems. The variables considered were temperature, solvent composition and solid-liquid ratio. Grape pomace was used as the solid matrix and ethanol-water mixtures as the solvent. The experimental dielectric constant and loss factor of these multiphase solid-solvent samples were measured and compared to the proposed model. Loss factor values were taken under special consideration, since they were boosted by the release of ions from the solid (an increase between 9 and 83%). The model proposed here reproduces the dielectric properties of this multiphase media with an average deviation of 8.1% for the dielectric constant and of 24.8% for the loss factor.
•Measurements of multiphase grape pomace ethanol-water mixtures permittivities.•An empirical model is proposed to calculate multiphase system dielectric properties.•Model variables are temperature, solvent composition and solid-liquid ratio.•Grape pomace boosts ionic conductivity by releasing ions into the solvent.•Solvent composition revealed as the most influential variable.
PDF
