TCA Levels Research Articles

8032 Clinical And Laboratory Characteristics Of Patients With Primary Hyperparathyroidism Followed At A Brazilian University Hospital

Abstract Disclosure: G. Koga: None. D. Amorim: None. L.M. dos Santos: None. D. Calixto: None. M. Ohe: None. J.G. Vieira: None. M. Lazaretti-Castro: None. Primary hyperparathyroidism (PHPT) is an endocrine disorder characterized by hypercalcemia due to hyperfunction of parathyroid glands. Its clinical presentation has been changing, becoming mostly asymptomatic. However, there are few data on developing countries.Objective: to describe clinical and biochemical features of primary hyperparathyroidism in a Brazilian population of a tertiary hospital. Methods: 259 individuals with PHPT are followed in a school-hospital in Sao Paulo in the last 2 years and this preliminary analysis included 161 of them. Clinical and laboratorial data were obtained by reviewing medical records. Data are presented as median [min-max] and statistical differences were considered if p<0.05. Results: 133 (82.6%) were women (3.7:1 female:male ratio) with a median age at diagnosis of 63 years [24-88]. There was higher prevalence of Caucasian (62.7%) then among Afro-descendants and Asians/indigenous: 35.4% and 1.9%, respectively. 99 (61.5%) patients were asymptomatic. Symptoms were observed in 38,5% (nephrolithiasis, fractures, bone pain, hypercalcemic crisis). Target organ involvement was evaluated: 48.4% had osteoporosis, and 47.2% kidney stones. At diagnosis, median total calcium (tCa) was 11.2 mg/dL [10.0-19.1], ionized calcium (iCa) 1.48 mmol/L [1.30-2.48], PTH 277.7 pg/mL [51.4-2374.0] and 25OHD 23.5 ng/mL [5.0-54.2]. Symptomatic patients were diagnosed younger (61 [24-83] vs 64 [31-88]; p=0.036), had higher tCa (11.4 [10.2-19.1] vs 11.2 [10-16]; p=0.049) and greater prevalence of 25OHD<20 ng/mL (50.0 vs 30.4%; p=0.03) than asymptomatic. Patients with severe hypercalcemia (>14 mg/dL) were diagnosed younger than those with non-severe hypercalcemia (52 [41-54] vs 63 [24-88] years; p=0.002). Patients with osteoporosis had older age at diagnosis compared to those without (64.0 [42-86] vs 61.5 [24-88]; p=0.018). Histological data were obtained from 94 individuals out of 104 submitted to surgery: 59.6% had single adenoma, 39.3% hyperplasia or multiple adenomas and 1.1% parathyroid carcinoma. Patients with single adenoma had higher levels of tCa and iCa than those with multiglandular disease (median of 11.4 [10.0-19.1] vs 10.9 [10.3-13.4]; p=0.042 and 1.52 [1.32-2.48] vs 1.43 [1.30-1.59]; p=0.02, respectively). Conclusion: Our preliminary data showed that most of the patients were Caucasian women presenting with asymptomatic disease. Compared with other countries, we still have a greater proportion of symptomatic presentations (38.5%) and multiglandular diseases (39.3%) than the reported in literature. Severe forms were diagnosed earlier, in younger patients and with a single adenoma, suggesting that they may have a different disease from the asymptomatic ones. These aspects demonstrate that there may be ethnic and environmental influences interfering with the presentation of this disease. Presentation: 6/2/2024

Association between serum calcium and prognosis in patients with acute ischemic stroke in ICU: analysis of the MIMIC-IV database

BackgroundWhile serum Ca has proven to be a reliable predictor of mortality across various diseases, its connection with the clinical outcomes of ischemic stroke (IS) remains inconclusive. Our research aimed to explore the relationships between serum total Ca (tCa) and serum ionized Ca (iCa) and mortality among acute IS (AIS) patients.MethodsWe gathered data from 1773 AIS patients in the Medical Information Mart for Intensive Care Database IV, including baseline demographic data, comorbidities, vital signs, laboratory-based data, and scoring systems. Endpoints for the study encompassed 30-d, 90-d, and 365-d all-cause mortalities. Employing restricted cubic spline Cox regression, we explored potential nonlinear relationships between admission serum iCa and tCa levels and mortality. Participants were categorized into four groups based on serum iCa and tCa quartiles. Multivariable Cox regression analysis was then conducted to evaluate the independent association of iCa and tCa quartiles with all-cause mortality.ResultsThe restricted cubic spline revealed a U-shaped association between iCa and 30-d and 90-d mortality (P<0.05), while the relationship between iCa and 365-d mortality was linear (P<0.05). After adjusting for confounders, multivariable Cox analysis demonstrated that the lowest serum iCa level quartile was independently associated with increased risks of 30-d, 90-d, and 365-d mortality. Similarly, the highest serum iCa level quartile was independently associated with increased risks of 30-d and 90-d mortality, but not 365-d mortality. Notably, serum tCa level showed no association with increased risks of 30-d, 90-d, and 365-d mortality.ConclusionsOur findings suggest that serum iCa, rather than tCa, is linked to ischemic stroke prognosis. Both high and low serum iCa levels are associated with poor short-term prognosis, while only low serum iCa is associated with poor long-term prognosis in AIS patients.

Bile acids induce liver fibrosis through the NLRP3 inflammasome pathway and the mechanism of FXR inhibition of NLRP3 activation

BackgroundAltered patterns of bile acids (BAs) are frequently present in liver fibrosis, and BAs function as signaling molecules to initiate inflammatory responses. Therefore, this study was conducted to uncover the notably altered components of BAs and to explore the pathway of altered BA induced inflammation in the development of liver fibrosis.MethodsBile acids were quantified by ultraperformance liquid chromatography coupled to mass spectrometry (UPLC‒MS/MS). Cell Counting Kit-8 assays were used to determine the proliferative capacity of HSCs. Transwell assays and wound healing assays were used to determine the migratory capacity of LX2 cells. Protein expression was evaluated by western blotting.ResultsPlasma bile acid analysis showed higher levels of GCDCA, TCDCA, GCA and TCA in patients with liver fibrosis than in normal controls. The AUC of GCDCA was the highest. Western blotting showed that GCDCA treatment increased the expression of NLRP3-related proteins and collagen1 in vitro and significantly increased LX2 cells proliferation and migration. Furthermore, knockdown of NLRP3 or overexpression of FXR in LX2 cells decreased the expression of the above proteins, and FXR inhibited NLRP3 (ser 295) phosphorylation in vitro and vivo. In vivo, HE, Masson’s trichrome, and Sirius Red staining showed that GCDCA increased collagen fibers in the mouse liver, and the expression of NLRP3-related proteins, collagen 1, and α-SMA in the liver increased significantly. However, the knockout of NLRP3 reversed these patterns.Conclusion(1) Primary conjugated bile acids increased in patients with liver fibrosis; (2) GCDCA induce hepatic fibrosis via the NLRP3 inflammasome pathway; (3) FXR inhibits NLRP3 activity by restraining its phosphorylation; (4) knockdown or knockout of NLRP3 may relieve the onset of hepatic fibrosis.

Clinical Significance of Serum Bile Acid Profiles in Fatty Liver.

This study aims to investigate the alterations in serum bile acid profiles among individuals with fatty liver (including non-alcoholic fatty liver (NAFL) and alcoholic fatty liver (AFL) and evaluate their clinical significance when combined with liver enzyme levels. A cohort of 110 individuals with fatty liver (including non-alcoholic fatty liver 58 individuals and alcoholic fatty liver 52 individuals) was selected from the Department of Gastroenterology at Wenzhou People's Hospital between January 2021 and December 2022, while a control group of 66healthy individuals was recruited from the hospital's health examination center during the same period. Clinical data and blood samples were collected from all participants. Serum bile acid profiles were quantified using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Statistical analysis was conducted in conjunction with liver enzyme indicators. In the NAFL group, GCA, TCA, and TCDCA levels were significantly elevated compared to the control group, with GCA (AUC 0.754, sensitivity 0.707, specificity 0.712), TCA (AUC 0.770, sensitivity 0.724, specificity 0.712), and TCDCA (AUC 0.782, sensitivity 0.810, specificity 0.652) showing strong diagnostic value. In the AFL group, TCDCA, TCA, GCA, TUDCA, and GUDCA were significantly elevated, with AUC values ranging from 0.848 to 0.912. Among these, TUDCA had the highest sensitivity (0.885) and specificity (0.773) for AFL diagnosis. TUDCA (sensitivity 0.615, specificity 0.897) was the key bile acid distinguishing AFL from NAFL, with an optimal cut-off of 36.33 nmol/L. These bile acids show significant diagnostic potential for differentiating NAFL and AFL. The bile acid profiles in both NAFL and AFL patients show changes, which hold potential clinical significance and may serve as serum biomarkers to differentiate NAFL from AFL.

Targeted LC-MS/MS profiling of bile acids reveals primary/secondary bile acid ratio as a novel biomarker for necrotizing enterocolitis.

Bile acids (BAs) are involved in the development of necrotizing enterocolitis (NEC), which mainly occurs in preterm infants. We aim to identify the change of BAs in preterm infants and validate its potential value in the detection of NEC. Targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to measure the plasma BAs in healthy preterm infants and patients with NEC. By analyzing the level of BAs in healthy preterm infants, we found that the plasma concentrations of BAs were related to sex, gestational/postnatal age, birth weight, mode of birth, and feeding type after birth. The plasma levels of TCA, GCA, TCDCA, GCDCA, primary BAs, and total BAs and the primary/secondary BA ratio were decreased, while DCA, UDCA, and secondary BAs were increased in NEC. The primary/secondary BA ratio (cutoff point 62.9) can effectively differentiate NEC from healthy preterm infants, with an AUC of 0.9, a sensitivity of 94.5%, and a specificity of 78.1%. Combining the ratio with high-risk factors of NEC can better distinguish between NEC and control, with an AUC of 0.95. Importantly, significantly lower levels of primary/secondary BA ratio were found in infants with surgical NEC than in nonsurgical NEC cases. The cutoff point of 28.7 identified surgical NEC from nonsurgical NEC with sensitivity and specificity of 76.9% and 100%. Thus, our study identified that the primary/secondary BA ratio in the plasma can differentiate NEC from healthy preterm infants and effectively differentiate the surgical NEC from nonsurgical NEC. Therefore, LC-MS/MS was expected to be a novel measurement platform used to distinguish infants who are most in need of close monitoring or early surgical intervention.

Per- and Poly-fluoroalkyl Substances and Bile Acid Profiles in Pregnant Women.

Alterations in bile acid (BA) profiles are closely associated with adverse outcomes in pregnant women and their offspring and may be one potential pathway underlying the related metabolic effects of per- and poly-fluoroalkyl substances (PFAS) exposure. However, evidence of associations between PFAS exposure and BA profiles in pregnant women is scarce. This study examined the associations of individual PFAS and PFAS mixture with BA profiles of pregnant women. We obtained quantitative data on the plasma concentrations of 13 PFAS and 15 BAs in 645 pregnant women from the Jiashan birth cohort. In Bayesian kernel machine regression models, the PFAS mixture was associated with increased plasma CA, TCA, TCDCA, and GLCA levels but with decreased GCA and LCA concentrations. Furthermore, the PFAS mixture was associated with increased concentrations of total BAs and the secondary/primary BA ratio but with decreased conjugated/unconjugated and glycine/taurine-conjugated BA ratios. PFHxS, PFUdA, PFOS, PFNA, and PFDA were the dominant contributors. The results of the linear regression analysis of individual PFAS were generally similar. Our findings provide the first epidemiological evidence for the associations of a PFAS mixture with BA profiles in pregnant women and may provide explanatory insights into the biological pathways underlying the related metabolic effects of PFAS exposure.

Assessment of some hematological and biochemical parameters in patients with renal failure in Al-najaf province

Chronic renal failure is a condition in which the kidneys gradually lose their ability to function because of the gradual loss of their parenchyma. This study aimed to detect some hematological and biochemical parameters in patients with chronic kidney disease (CKD) attending a hemodialysis center. A cross-sectional study included a review of (89) cases of chronic kidney disease at Al-Hakeem Hospital's dialysis center in Najaf from September 7th to October 16th, 2021. The collected data were analyzed using Office Excel and SPSS-23. Variables were analyzed by frequencies, proportions, and percentages. The current study discovered that males had longer sequences than females, and that patients in rural areas had longer sequences than those in urban areas. In the current study, blood Sug, B. Urea, S. Crea, K, Na, Cl, Ca+2, Alb, and Tpro levels did not differ significantly between males and females with renal failure, whereas HB and TCA levels did. At last, we recommend people conduct an early medical examination for kidney disease, especially those who suffer from symptoms such as low urine output, swelling of the legs, fatigue, tachycardia, and others, to obtain early treatment.

Deoxycholic acid induces gastric intestinal metaplasia by activating STAT3 signaling and disturbing gastric bile acids metabolism and microbiota

ABSTRACT Intestinal metaplasia (IM) is the inevitable precancerous stage to develop intestinal-type gastric cancer (GC). Deoxycholic acid (DCA) is the main bile acid (BA) component of duodenogastric reflux and has shown an increased concentration during the transition from chronic gastritis to IM associated with continued STAT3 activation. However, the mechanisms underlying how DCA facilitates IM in the gastric epithelium need exploration. We evaluated IM and bile reflux in corpus tissues from 161 subjects undergoing GC screening. Cell survival and proliferation, proinflammatory cytokine expression and TGR5/STAT3/KLF5 axis activity were measured in normal human gastric cells, cancer cells, and organoid lines derived from C57BL/6, FVB/N and insulin-gastrin (INS-GAS) mice treated with DCA. The effects of DCA on IM development were determined in INS-GAS mice with long-term DCA supplementation, after which the gastric bacterial and BA metabolic profiles were measured by 16S rRNA gene sequencing and LC-MS. We revealed a BA-triggered TGR5/STAT3/KLF5 pathway in human gastric IM tissues. In gastric epithelial cells, DCA promoted proliferation and apoptotic resistance, upregulated proinflammatory cytokines and IM markers, and facilitated STAT3 phosphorylation, nuclear accumulation and DNA binding to the KLF5 promoter. DCA triggered STAT3 signaling and the downstream IM marker KLF5 in mouse gastric organoids in vitro and in vivo. In INS-GAS mice, DCA promoted the accumulation of serum total BAs and accelerated the stepwise development of gastric IM and dysplasia. DCA induced gastric environmental alterations involving abnormal BA metabolism and microbial dysbiosis, in which the Gemmobacter and Lactobacillus genera were specifically enriched. Lactobacillus genus enrichment was positively correlated with increased levels of GCA, CA, T-α-MCA, TCA and β-MCA in DCA-administrated INS-GAS mice. DCA promotes nuclear STAT3 phosphorylation, which mediates KLF5 upregulation associated with gastric inflammation and IM development. DCA disturbs the gastric microbiome and BA metabolism homeostasis during IM induction.

Association of Vitamin D and Calcium Levels in E-waste Workers and Environmentally Exposed Participants in Southwestern Nigeria

&#x0D; &#x0D; &#x0D; Exposure to e-waste either by occupation or through the environment have been implicated in cancer development. The growing influx of e-waste to Nigeria and inadequate recycling, part salvaging, distribution and disposal of discarded or obsolete electronic devices is creating new sets of environmental and public health challenges. This study investigated the effect of exposure on vitamin D (25(OH) Vit D), total and ionized calcium levels in workers and individuals environmentally exposed to e-waste in Lagos, Benin and Ibadan cities in Southwestern Nigeria. Six hundred and thirty-two participants from three major cities in Nigeria were recruited for this study. They included e-waste workers, environmental e-waste exposed individuals and age matched unexposed individuals. 25(OH) Vit D was determined using ELISA, while total and ionized calcium by colorimetric method. Total calcium (tCa) in e-waste workers was significantly different from environmental exposed groups (p=0.000) while ionized calcium (iCa) was significantly increased for both e-waste exposed groups when compared with the unexposed group. 25(OH)Vit D level was significantly increased in e-waste workers compared with environmental and unexposed populations (p&lt;0.001). Optimal levels of tCa, iCa and vitamin D in the e-waste exposed population may offer some forms of defense against the severity of existing and undiagnosed cancers or reduce the risk of cancer development in the e-waste exposed participants. However, e-waste may unfavourably modulate these expected beneficial roles in the e-waste exposed populations with continued exposure.&#x0D; &#x0D; &#x0D;

Hypocalcemia in COVID-19 is associated with low vitamin D levels and impaired compensatory PTH response.

BackgroundHypocalcemia has been identified as a major distinctive feature of COVID-19, predicting poor clinical outcomes. Among the mechanisms underlying this biochemical finding, high prevalence of vitamin D (VD) deficiency in COVID-19 patients reported so far in several studies was advocated. However, robust data in favor of this hypothesis are still lacking. Therefore, aim of our study was to investigate the role of hypovitaminosis D and parathyroid hormone (PTH) levels in the development of hypocalcemia in COVID-19 patients.MethodsPatients admitted to IRCCS Ospedale San Raffaele for COVID-19 were enrolled in this study, excluding those with comorbidities and therapies influencing calcium and VD metabolism. Serum levels of total calcium (tCa), ionized calcium (Ca2+), 25-OH-VD, and PTH were evaluated at admission. We defined VD deficiency as VD below 20 ng/mL, hypocalcemia as tCa below 2.2 mmol/L or as Ca2+ below 1.18 mmol/L, and hyperparathyroidism as PTH above 65 pg/mL.ResultsA total of 78 patients were included in the study. Median tCa and Ca2+ levels were 2.15 and 1.15 mmol/L, respectively. Total and ionized hypocalcemia were observed in 53 (67.9%) and 55 (70.5%) patients, respectively. VD deficiency was found in 67.9% of patients, but secondary hyperparathyroidism was detected in 20.5% of them, only. tCa levels were significantly lower in patients with VD deficiency and regression analyses showed a positive correlation between VD and tCa.ConclusionsIn conclusion, we confirmed a high prevalence of hypocalcemia in COVID-19 patients and we showed for the first time that it occurred largely in the context of marked hypovitaminosis D not adequately compensated by secondary hyperparathyroidism.

Admission Serum Ionized and Total Calcium as New Predictors of Mortality in Patients with Cardiogenic Shock.

Background Although serum calcium has been proven to be a predictor of mortality in a wide range of diseases, its prognostic value in critically ill patients with cardiogenic shock (CS) remains unknown. This retrospective observational study is aimed at investigating the association of admission calcium with mortality among CS patients. Methods Critically ill patients diagnosed with CS in the Medical Information Mart for Intensive Care-III (MIMIC-III) database were included in our study. The study endpoints included 30-day, 90-day, and 365-day all-cause mortalities. First, admission serum ionized calcium (iCa) and total calcium (tCa) levels were analyzed as continuous variables using restricted cubic spline Cox regression models to evaluate the possible nonlinear relationship between serum calcium and mortality. Second, patients with CS were assigned to four groups according to the quartiles (Q1-Q4) of serum iCa and tCa levels, respectively. In addition, multivariable Cox regression analyses were used to assess the independent association of the quartiles of iCa and tCa with clinical outcomes. Results A total of 921 patients hospitalized with CS were enrolled in this study. A nonlinear relationship between serum calcium levels and 30-day mortality was observed (all P values for nonlinear trend < 0.001). Furthermore, multivariable Cox analysis showed that compared with the reference quartile (Q3: 1.11 ≤ iCa < 1.17 mmol/L), the lowest serum iCa level quartile (Q1: iCa < 1.04 mmol/L) was independently associated with an increased risk of 30-day mortality (Q1 vs. Q3: HR 1.35, 95% CI 1.00-1.83, P = 0.049), 90-day mortality (Q1 vs. Q3: HR 1.36, 95% CI 1.03-1.80, P = 0.030), and 365-day mortality (Q1 vs. Q3: HR 1.28, 95% CI 1.01-1.67, P = 0.046) in patients with CS. Conclusions Lower serum iCa levels on admission were potential predictors of an increased risk of mortality in critically ill patients with CS.

Technological capabilities accumulation and internationalization strategies of Mexican biotech firms: a multi case study from agro-food & pharma industries

ABSTRACT In this paper our aim is to analyze the relationship between technological capabilities accumulation of Mexican biotech firms and their different types of internationalization strategies. Because of the determining effect of firms’ capital investment level, we analyzed three groups of firms: start-ups, small and medium-sized firms (SMEs) and multinational firms (MNEs). We made use of a wide range of information: The First Survey of Biotechnology Development Firms in Mexico, the systematization of 20 case studies, interviews with key persons in the industry and public sources. We confirmed the two hypotheses outlined: (i) TCA process does not follow a linear path in Mexican biotech firms and (ii) firms with lower capital investment levels exhibit a lower level of TCA and less complex internationalization strategies; while firms with higher capital investment levels are associated with higher TCA levels and more complex internationalization strategies. Biotechnology requires high levels of capital investment and these to a large extent determine the development and technological capabilities accumulation. Therefore, we suggest that a capitalization program is much needed to foster Mexican biotech firms’ TCA processes and develop internationalization strategies.

Investigation of olfactory interactions of low levels of five off-flavour causing compounds in a red wine matrix

The qualitative sensory perception of individual and of complex mixtures of five compounds, guaiacol ('burnt note'), o-cresol ('phenolic/tar'), 4-ethylphenol (4-EP, 'leather/barnyard'), 2-iso-butyl-3-methoxypyrazine (IBMP, 'green pepper/herbaceous'), and 2,4,6-trichloroanisole (TCA, 'cork taint/ mouldy') were tested in a partially de-aromatised red wine matrix using descriptive analysis by a trained panel of eleven judges. Compounds were characterised at peri- and sub-threshold concentrations using a partial D-optimal statistical design and response surface methodology. Results indicated that complex mixtures in red wine elicit an olfactory response that could not be predicted from the attributes or descriptors of single compounds. Positive sweet/fruity attributes were more intense in solutions containing fewer off-flavour compounds. Novel findings of this study include that IBMP at sub- and peri-threshold levels shows perceptual interaction with volatile phenols at the same levels, and samples containing combinations of these compounds manifested herbaceous and burnt characteristics. Olfactory interactions of this many off-flavour compounds have not been investigated previously in one study. The findings have direct implications for wines made from cultivars that are known to contain these compounds, and add to the understanding of the behaviour and impact of very low levels (peri- and sub-threshold) of volatile phenols, IBMP, and TCA derived from various sources during winemaking.

Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection

ObjectiveFaecal microbiota transplant (FMT) effectively treats recurrent Clostridioides difficile infection (rCDI), but its mechanisms of action remain poorly defined. Certain bile acids affect C. difficile germination or vegetative growth. We...

Serum Metabolomic Profiling Identifies Key Metabolic Signatures Associated With Pathogenesis of Alcoholic Liver Disease in Humans.

Alcoholic liver disease (ALD) develops in a subset of heavy drinkers (HDs). The goals of our study were to (1) characterize the global serum metabolomic changes in well‐characterized cohorts of controls (Cs), HDs, and those with alcoholic cirrhosis (AC); (2) identify metabolomic signatures as potential diagnostic markers, and (3) determine the trajectory of serum metabolites in response to alcohol abstinence. Serum metabolic profiling was performed in 22 Cs, 147 HDs, and 33 patients with AC using ultraperformance liquid chromatography–tandem mass spectrometry. Hepatic gene expression was conducted in Cs (n = 16) and those with AC (n = 32). We found progressive changes in the quantities of metabolites from heavy drinking to AC. Taurine‐conjugated bile acids (taurocholic acid [TCA], 127‐fold; taurochenodeoxycholic acid [TCDCA], 131‐fold; and tauroursodeoxycholic acid, 56‐fold) showed more striking elevations than glycine‐conjugated forms (glycocholic acid [GCA], 22‐fold; glycochenodeoxycholic acid [GCDCA], 22‐fold; and glycoursodeoxycholic acid [GUDCA], 11‐fold). This was associated with increased liver cytochrome P450, family 7, subfamily B, member 1 and taurine content (more substrates); the latter was due to dysregulation of homocysteine metabolism. Increased levels of GCDCA, TCDCA, GCA, and TCA positively correlated with disease progression from Child‐Pugh A to C and Model for End‐Stage Liver Disease scores, whereas GCDCA, GCA, and GUDCA were better predictors of alcohol abstinence. The levels of glucagon‐like peptide 1 (GLP‐1) and fibroblast growth factor (FGF) 21 but not FGF19 were increased in HDs, and all three were further increased in those with AC. Conclusion: Serum taurine/glycine‐conjugated bile acids could serve as noninvasive markers to predict the severity of AC, whereas GLP‐1 and FGF21 may indicate a progression from heavy drinking to AC.

Myocardial fatty acid uptake through CD36 is indispensable for sufficient bioenergetic metabolism to prevent progression of pressure overload-induced heart failure

The energy metabolism of the failing heart is characterized by reduced fatty acid (FA) oxidation and an increase in glucose utilization. However, little is known about how energy metabolism-function relationship is relevant to pathophysiology of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO), which causes reduction in FA use with an increased reliance on glucose, accelerates the progression from compensated hypertrophy to heart failure. Here, we show the mechanisms by which CD36 deletion accelerates heart failure in response to pressure overload. CD36KO mice exhibited contractile dysfunction and death from heart failure with enhanced cardiac hypertrophy and interstitial fibrosis when they were subjected to transverse aortic constriction (TAC). The pool size in the TCA cycle and levels of high-energy phosphate were significantly reduced in CD36KO-TAC hearts despite an increase in glycolytic flux. De novo synthesis of non-essential amino acids was facilitated in CD36KO-TAC hearts, which could cause a further decline of the pool size. The ingestion of a diet enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts. These findings suggest that myocardial FA uptake through CD36 is indispensable for sufficient ATP production and for preventing an increased glycolytic flux-mediated structural remodeling during pressure overload-induced hypertrophy.

Association of Initial Serum Total Calcium Concentration with Mortality in Critical Illness.

Background Several studies have suggested that serum ionized calcium (iCa) is associated with mortality in critical illness. However, evidence regarding the predictive significance of serum total calcium (tCa) in critical illness remains scarce. The aim of this study was to assess the association of tCa levels with mortality in critical illness. Methods We employed the MIMIC-III v1.3 database. tCa was measured upon ICU admission and its relationship with mortality was determined using smooth curve fitting. The association between admission tCa levels and hospital mortality was determined using logistic regression. Results Inclusion criteria were met by 44,886 critically ill patients. A U-shaped pattern was observed between tCa and hospital mortality. Similar trends were observed for hospital mortality when quintiles were used to group patients according to tCa. In multivariate analysis, adjusted for age and sex, the model indicated that admission tCa levels ⩽7.6mg/dl, 7.7-8.1mg/dl, and ⩾9.0mg/dl were associated with an increase in mortality when compared to the reference level (8.6-9.0mg/dl). However, adjusted for more clinical characteristics, tCa was not associated with hospital mortality. Conclusions The relationship between tCa and hospital mortality followed a ‘‘U” shaped curve. tCa had certain prognostic value in critically ill patients, but it had no independent association with hospital mortality.

Significance of the ionized calcium measurement to assess calcium status in osteopenic/osteoporosis postmenopausal outpatients

Introduction: Evaluation of calcium status is important in the osteoporotic risk assessment. Although guidelines indicate total calcium (tCa) as first-line measurement, directly measured ionized calcium (m-iCa), considered as the gold standard, is more and more often required. Aim of this study is to evaluate the agreement between m-iCa, tCa and iCa calculated from a formula based on total calcium and albumin (c-iCa) in osteopenic/osteoporotic postmenopausal outpatients.Methods: A total of 140 postmenopausal outpatients, 41 osteopenic (OPN) and 99 osteoporotic (OP) were enrolled. Levels of tCa, m-iCa, c-iCa, total protein and albumin, vitamin D (25-OHD), parathyroid hormone 1-84 (PTH), bone alkaline phosphatase, osteocalcin and serum collagen type 1 cross-linked C-telopeptide (CTX) were also measured.Results: There were no statistically significant differences between OPN and OP groups regarding values of tCa, m-iCa, and c-iCa, 25-OHD and PTH. However, OP women had lower levels of CTX (p < 0.05). A significant direct correlation between m-iCa and tCa (r = 0.60, p < 0.001) and c-iCa (r = 0.61, p < 0.001) was found. Women with isolated hyper-m-iCa had similar DEXA parameter levels respect to the other patients. However, one patient with confirmed primary hyperparathyroidism presented hyper-m-iCa versus normal tCa and c-iCa values.Conclusions: The use of tCa could be sufficient to characterize the calcium status in postmenopausal outpatients, but reflexive calcium testing strategy for m-iCa test is necessary to women presenting the low or high extremes of tCa levels, or in women with suspected PHPT.

Can pretreatment serum calcium level predict the efficacy of methotrexate in the treatment of severe plaque psoriasis?

The efficacy of methotrexate (MTX) varies in the treatment of psoriasis. We sought to identify an indicator from routine pretreatment tests to predict MTX efficacy in the treatment of psoriasis. In a retrospective analysis of 77 psoriatic patients, the correlation between MTX efficacy and pretreatment routine test results was analyzed with Spearman correlation. The potential risks were further evaluated with a linear regression model. Receiver operating characteristic analysis was performed to examine the effectiveness of serum total calcium (tCa) to predict the effect of MTX on psoriasis. The highest Youden index was used to determine the cutoff point, with which the positive and negative predictive values were calculated. Synergistic effects of MTX and calcium on keratinocyte growth and psoriasis-like mouse model were also investigated. The pretreatment tCa level exhibited the closest association with MTX efficacy. The relative psoriasis improvement with tCa was 61.07% (95% confidence interval, 42.85-79.29; P < .001) and better improvements were observed in patients with higher tCa (r = 0.588; P < .002). MTX inhibited keratinocyte growth, which was enhanced synergistically by calcium. In a psoriasis-like mouse model, MTX strongly inhibited epidermis proliferation in the high-calcium group. One limitation of our study is the relatively small sample size. Pretreatment tCa level has the highest correlation with MTX efficacy, which might be useful in predicting beneficial treatment results in psoriasis. Larger studies are required to confirm our findings.

THE DEVELOPMENT OF TOTAL COMPLEMENT ACTIVITY ASSAY BASED ON COMPLEMENT-DEPENDENT IMMUNE LIPOSOME LYSIS

Background: The purpose of work was development of a fast and reproduced procedure for measurement of the total complement activity (ТСА) in human or animal blood serum. Materials and methods: Steady at storage liposomes preparations, which surface sensitized 2,4-DNP haptens, and the internal volume contains calceine or sulforhodamine 101 are obtained. Complement-dependent immune lysis of liposomes at presence of the anti-2,4-DNP immunoglobulines and complement preparations from animals are investigated. Results: It is shown that the degree of liposomes immune lysis depends on complement concentration in a wide range that can be used for definition of TCA level. Research of blood sera from patients has revealed correlation (r =0,793) between data received with the help of liposome immunolytic systems, and the data of nephelometric analysis with application of suspension sheep erythrocytes. Conclusion: The method allows to define total complement activity in blood serum in 15 minutes without separation of reaction components. This might be useful for measurement ТСА level at patients with various diseases and realization of scientific researches.