Association of 24 h–systolic blood pressure variability and cardiovascular disease in patients with obstructive sleep apnea

Background

To evaluate association of 24 h–systolic blood pressure (SBP) variability and obstructive sleep apnea (OSA) as defined by the apnea-hypopnea index ≥5/h; and association of 24 h–SBP variability and prevalent cardiovascular disease (CVD) in OSA patients.

Methods

Participants underwent polysomongraphy to evaluate the presence of OSA, and 24 h–ambulatory blood pressure monitoring was applied to evaluate 24 h–SBP variability as indexed by weighted 24 h–standard deviation (SD) of SBP. Between-group differences were evaluated in participants with and without OSA. Participants with OSA were divided into high and low 24 h–SBP variability groups and between-group differences were evaluated.

Results

Mean age of 384 participants was 50 years old and 42.2% had OSA. Mean 24 h–systolic/diastolic BP were 130/78 mmHg, with mean weighted 24 h–SD of systolic/diastolic BP were 12.9/7.3 mmHg. Compared to those without OSA, OSA participants had higher clinic-, 24 h-, daytime- and nighttime-SBP, and weighted 24 h, daytime- and nighttime-SD of SBP. Age, prevalent CVD and OSA, usage of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker and diuretic were significantly associated with 24 h–SBP variability. In OSA patients, compared to those with low variability, participants with high variability had higher weighted 24 h, daytime- and nighttime-SD of SBP. After adjusted for covariates including clinic-SBP and 24 h–SBP, per 1-SD increment weighted 24 h–SD of SBP was associated with 21% increased prevalent CVD.

Conclusions

Patients with newly-diagnosed OSA have higher 24 h–SBP variability compared to those without OSA; in OSA patients, increased 24 h–SBP variability is associated with increased prevalence of CVD.

     

Foot insensitivity is associated with renal function decline in patients with type 2 diabetes: a cohort study

Background

Identifying patients with diabetes at increased risk of chronic kidney disease (CKD) is essential to prevent/slow the progression to end-stage renal disease (ESRD). CKD and diabetic peripheral neuropathy (DPN) share common mechanisms. Hence, we aimed to examine the relationship between foot insensitivity and CKD in patients with Type 2 diabetes.

Methods

A prospective observational cohort study in adults with Type 2 diabetes. Patients with ESRD were excluded. Foot insensitivity was assessed using the 10-g monofilament test. Renal function was assessed using estimated glomerular filtration rate (eGFR) based on the MDRD equation. Albuminuria was defined as the presence of urinary albumin/creatinine ratio (ACR) >3.4 mg/mmol.

Results

Two hundred and twenty eight patients were recruited and followed-up for 2.5 years. One hundred and ninety patients (83.4%) had eGFR?≥?60 ml/min/1.73 m². Seventy six (33.3%) patients had foot insensitivity (i.e. abnormal monofilament test). Patients with foot insensitivity had lower eGFR and higher prevalence of albuminuria compared to patients with normal monofilament test. After adjustment for age, gender, ethnicity, diabetes duration, HbA1c, body mass index, insulin treatment, number of anti-hypertensives, history of peripheral vascular disease, and baseline eGFR (R² 0.87), baseline foot insensitivity was associated with study-end eGFR (B?=??3.551, p?=?0.036).

Conclusions

Patients with Type 2 diabetes and foot insensitivity are at increased risk of eGFR decline. Identifying these patients offers an opportunity to intensify metabolic and blood pressure control to prevent/retard the development of CKD. Future studies of larger sample size and longer follow up from multiple centres are needed to assess the diagnostic performance of our findings in predicting CKD development, and to compare the performance of the monofilament test with albuminuria.

     

Corneal Collagen Cross-Linking for the Management of Mycotic Keratitis

Purpose

To evaluate the efficiency of corneal collagen cross-linking (CXL) in addition to topical voriconazole in cases with mycotic keratitis.

Design

Retrospective case series in a tertiary university hospital.

Participants

CXL was performed on 13 patients with mycotic keratitis who presented poor or no response to topical voriconazole treatment.

Methods

The clinical features, symptoms, treatment results and complications were recorded retrospectively. The corneal infection was graded according to the depth of infection into the stroma (from grade 1 to grade 3). The visual analogue scale was used to calculate the pain score before and 2 days after surgery.

Main Outcome Measures

Grade of the corneal infection.

Results

Mean age of 13 patients (6 female and 7 male) was 42.4 ± 17.7 years (20–74 years). Fungus was demonstrated in culture (eight patients) or cytological examination (five patients). Seven of the 13 patients (54%) were healed with topical voriconazole and CXL adjuvant treatment in 26 ± 10 days (15–40 days). The remaining six patients did not respond to CXL treatment; they initially presented with higher grade ulcers. Pre- and post-operative pain score values were 8 ± 0.8 and 3.5 ± 1, respectively (p < 0.05).

Conclusions

The current study suggests that adjunctive CXL treatment is effective in patients with small and superficial mycotic ulcers. These observations require further research by large randomized clinical trials.

     

Salivary metabolic profile of children and adolescents after hemodialysis

Introduction

The application of metabolomic analysis in the pediatric nephrology field may offer an innovative approach to profile analysis of renal diseases.

Objective

We aimed to analyze the salivary the major metabolites in the saliva of children and adolescents with chronic kidney disease (CKD) before and after hemodialysis.

Method

Thirty-six children diagnosed with CKD and forty healthy children were recruited for the study. ¹H-NMR spectra were analyzed using multivariate and univariate approaches.

Results

The CKD and the healthy control groups presented with similar numbers of dental caries (p?>?0.05) as determined by the number of decayed, missing, or filled deciduous teeth (0.87?±?2.2 and 0.67?±?2.1, respectively) or permanent teeth (0.79?±?1.30 and 0.90?±?1.7, respectively). The amount of dental calculus was significantly higher in the CKD group than in the healthy control group (p?<?0.001). Multivariate analyses using PLS-DA and O-PLS-DA demonstrated differences in the salivary metabolome of CKD patients before and after hemodialysis, as well as between post-dialysis CKD patients and healthy controls, suggesting that HD was not able to recover oral homeostasis. PLS-DA and OPLS-DA models showed satisfactory accuracy (ACC?=?0.72) and prediction (0.64). On multivariate and univariate analyses, urea, acetate, ethanol, and fatty acid were significantly decreased in CKD saliva after hemodialysis. By contrast, saliva from the healthy controls had significantly higher levels of acetate and propionate and lower levels of ethanol, lactate, butyrate, phenylalanine, and creatinine than saliva from post-dialysis CKD patients.

Conclusion

Our results demonstrate that hemodialysis alters the expression of salivary metabolites; however, this alteration does not reestablish the healthy salivary metabolome, as the salivary metabolomic profile of healthy children is significantly different from that of children and adolescents with CKD, both before and after hemodialysis. The unique salivary characteristics of children with CKD may influence their oral health status.

     

Novel plasma biomarker of atenolol-induced hyperglycemia identified through a metabolomics-genomics integrative approach

Introduction

While atenolol is an effective antihypertensive agent, its use is also associated with adverse events including hyperglycemia and incident diabetes that may offset the benefits of blood pressure lowering. By combining metabolomic and genomic data acquired from hypertensive individuals treated with atenolol, it may be possible to better understand the pathways that most impact the development of an adverse glycemic state.

Objective

To identify biomarkers that can help predict susceptibility to blood glucose excursions during exposure to atenolol.

Methods

Plasma samples acquired from 234 Caucasian participants treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses trial were analyzed by gas chromatography Time-Of-Flight Mass Spectroscopy. Metabolomics and genomics data were integrated by first correlating participant’s metabolomic profiles to change in glucose after treatment with atenolol, and then incorporating genotype information from genes involved in metabolite pathways associated with glucose response.

Results

Our findings indicate that the baseline level of β-alanine was associated with glucose change after treatment with atenolol (Q = 0.007, β = 2.97 mg/dL). Analysis of genomic data revealed that carriers of the G allele for SNP rs2669429 in gene DPYS, which codes for dihydropyrimidinase, an enzyme involved in β-alanine formation, had significantly higher glucose levels after treatment with atenolol when compared with non-carriers (Q = 0.05, β = 2.76 mg/dL). This finding was replicated in participants who received atenolol as an add-on therapy (P = 0.04, β = 1.86 mg/dL).

Conclusion

These results suggest that β-alanine and rs2669429 may be predictors of atenolol-induced hyperglycemia in Caucasian individuals and further investigation is warranted.

     

Altered plasma acylcarnitine and amino acid profiles in type 2 diabetic kidney disease

Introduction

Dysregulation of acylcarnitines (AcylCNs) and amino acids metabolism have implicated in abnormality of fatty acid oxidation in type 2 diabetes (T2D). However, it is not well known whether altered plasma AcylCN, and amino acid profiles are associated with albuminuria or diabetic nephropathy (DN) in T2D.

Objective

The aim of this study was to elucidate alterations in plasma levels of AcylCNs and amino acids with respect to the T2D patients with various stages of albuminuria.

Methods

We recruited 52 healthy subjects as control, and 156 T2D patients which were divided into 52 normoalbuminuria, 52 microalbuminuria, and 52 macroalbuminuria. Plasma 37 AcylCNs and 12 amino acids were analyzed by tandem mass spectrometry.

Results

We found that T2D with normoalbuminuria and microalbuminuria had lower shot-, medium-, and long-chain AcylCNs, whereas T2D with macroalbuminuria had higher short-and medium-chain AcylCNs and lower long-chain AcylCNs than healthy subjects. Moreover, estimated glomerular filtration rate (eGFR) was a negative, independent and significant predictor of albumin to creatinine ratio (ACR) levels (β = ?0.376, P < 0.001), whereas plasma Low-density lipoprotein cholesterol (LDL-C) was significantly and positively associated with ACR levels (β = 0.169, P = 0.049). Furthermore, multivariate ordinal logistic regression analysis revealed that isobutyrylcarnitine (C4) was a positive, independent, and significant predictor of ACR levels with higher odds of having T2D patients with progression normoalbuminuria to microalbuminuria [OR = 9.93, 95 % CI (3.51–28.05), P < 0.001].

Conclusions

The findings suggest that plasma C4 may serve as a potential biomarker for the early stages of DN.

     

Does centrifugation matter? Centrifugal force and spinning time alter the plasma metabolome

Background

Centrifugation is an indispensable procedure for plasma sample preparation, but applied conditions can vary between labs.

Aim

Determine whether routinely used plasma centrifugation protocols (1500×g 10 min; 3000×g 5 min) influence non-targeted metabolomic analyses.

Methods

Nuclear magnetic resonance spectroscopy (NMR) and High Resolution Mass Spectrometry (HRMS) data were evaluated with sparse partial least squares discriminant analyses and compared with cell count measurements.

Results

Besides significant differences in platelet count, we identified substantial alterations in NMR and HRMS data related to the different centrifugation protocols.

Conclusion

Already minor differences in plasma centrifugation can significantly influence metabolomic patterns and potentially bias metabolomics studies.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

R-wave synchronised atrial pacing in pediatric patients with postoperative junctional ectopic tachycardia: the atrioventricular interval investigated by computational analysis and clinical evaluation

Background

R-wave synchronised atrial pacing is an effective temporary pacing therapy in infants with postoperative junctional ectopic tachycardia. In the technique currently used, adverse short or long intervals between atrial pacing and ventricular sensing (AP–VS) may be observed during routine clinical practice.

Objectives

The aim of the study was to analyse outcomes of R-wave synchronised atrial pacing and the relationship between maximum tracking rates and AP–VS intervals.

Methods

Calculated AP–VS intervals were compared with those predicted by experienced pediatric cardiologist.

Results

A maximum tracking rate (MTR) set 10 bpm higher than the heart rate (HR) may result in undesirable short AP–VS intervals (minimum 83 ms). A MTR set 20 bpm above the HR is the hemodynamically better choice (minimum 96 ms). Effects of either setting on the AP–VS interval could not be predicted by experienced observers. In our newly proposed technique the AP–VS interval approaches 95 ms for HR > 210 bpm and 130 ms for HR < 130 bpm. The progression is linear and decreases strictly (? 0.4 ms/bpm) between the two extreme levels.

Conclusions

Adjusting the AP–VS interval in the currently used technique is complex and may imply unfavorable pacemaker settings. A new pacemaker design is advisable to allow direct control of the AP–VS interval.

     

Plasma glutamine and glutamic acid are potential biomarkers for predicting diabetic retinopathy

Introduction

Diabetic patients with a long disease duration usually accompanied complication such as diabetic retinopathy, but in some patients had no complication.

Objectives

We analyzed differences in plasma metabolites according to the presence or absence of diabetic retinopathy (DR) in type 2 diabetic (T2D) patients with disease duration?≥?15 years.

Methods

A cohort of 183 T2D patients was established. Their biospecimens and clinical information were collected in accordance with the guidelines of the National Biobank of Korea, and the Korean Diabetes Association. DR phenotypes of the subjects were verified by ophthalmologic specialists. Plasma metabolites were analyzed using gas chromatography time-of-flight mass spectrometry and ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry. And these results were analyzed using multivariate statistics.

Results

For metabolomic study, propensity score matched case and control subjects were chosen. Mean age of the subjects was 66.4 years and mean T2D duration was 22.2 years. Metabolomic identification revealed various carbohydrates, amino acids, and organic compounds that distinguished between age- and sex-matched non-diabetic controls and T2D subjects. Among these, glutamine and glutamic acid were suggested as the most distinctive metabolites for the presence of DR. Receiver operating characteristics curves showed an excellent diagnostic value of combined (AUC?=?0.739) and the ratio (AUC?=?0.742) of glutamine and glutamic acid for DR. And these results were consistent in validation analyses.

Conclusion

Our results imply that plasma glutamine, glutamic acid, and their ratio may be valuable as novel biomarkers for anticipating DR in T2D subjects.

     

Urine metabolites are associated with glomerular lesions in type 2 diabetes

Introduction

Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives

We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods

Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A_1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results

Participants (n?=?62, mean age 45?±?10 years) had mean?±?standard deviation glomerular filtration rate of 137?±?50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r?=?0.29, P?=?0.030 and r?=?0.50, P?<?0.001) and total filtration surface per glomerulus (partial r?=?0.32, P?=?0.019 and r?=?0.43, P?=?0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r?=?0.32, P?=?0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P?=?0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P?=?0.022).

Conclusions

Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.

     

Minimal variation of the plasma lipidome after delayed processing of neonatal cord blood

Background

Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.

Method

Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.

Results

Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.

Conclusion

Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.

     

Dexamethasone downregulates SIRT1 and IL6 and upregulates EDN1 genes in stem cells derived from gingivae via the AGE/RAGE pathway

Objectives

To evaluate the effects of dexamethasone on the aging of mesenchymal stem cells from human gingiva using next-generation sequencing.

Results

Four mRNAs were upregulated and 12 were downregulated when the results of dexamethasone at 24 h were compared with the control at 24 h. Expressions of SIRT1 and IL6 were decreased in dexamethasone at 24 h but expression of EDN1 was increased.

Conclusions

Application of dexamethasone reduced the expression of SIRT1 and IL6 but enhanced the expression of EDN1 of stem cells.

     

The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative <Emphasis Type="Italic">FBN1</Emphasis> mutations

Background

Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation.

Methods

In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up.

Results

Changes in biventricular dimensions were assessed in 163 Marfan patients (48?% female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. ?8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. ?18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. ?8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. ?7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28).

Conclusion

Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.

     

Presence of arachidonoyl-carnitine is associated with adverse cardiometabolic responses in hypertensive patients treated with atenolol

Introduction

Atenolol, a commonly prescribed β blocker for hypertension, is also associated with adverse cardiometabolic effects such as hyperglycemia and dyslipidemia. Knowledge of the mechanistic underpinnings of these adverse effects of atenolol is incomplete.

Objective

We sought to identify biomarkers associated with risk for these untoward effects of atenolol. We measured baseline blood serum levels of acylcarnitines (ACs) that are involved in a host of different metabolic pathways, to establish associations with adverse cardiometabolic responses after atenolol treatment.

Methods

Serum samples from Caucasian hypertensive patients (n = 224) who were treated with atenolol in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study were interrogated using a quantitative LC/MS assay for a large number of unique ACs in serum. For the 23 ACs that were detected in serum from ≥80 % of all patients, we conducted linear regression for changes in cardiometabolic factors with baseline AC levels, baseline cardiometabolic factors, age, sex, and BMI as covariates. For the 5 ACs that were detected in serum from 20 to 79 % of the patients, we similarly modeled changes in cardiometabolic factors, but with specifying the AC as present/absent in the regression.

Results

Among the 28 ACs, the presence (vs. absence) of arachidonoyl-carnitine (C20:4) was significantly associated with increased glucose (p = 0.0002), and was nominally associated with decreased plasma HDL-C (p = 0.017) and with less blood pressure (BP) lowering (p = 0.006 for systolic BP, p = 0.002 for diastolic BP), after adjustment.

Conclusion

Serum level of C20:4 is a promising biomarker to predict adverse cardiometabolic responses including glucose and poor antihypertensive response to atenolol.

     

Retinal capillary rarefaction in patients with untreated mild-moderate hypertension

Background

Microvascular rarefaction influences peripheral vascular resistance, perfusion and metabolism by affecting blood pressure and flow pattern. In hypertension microvascular rarefaction has been described in experimental animal studies as well as in capillaroscopy of skin and biopsies of muscle tissue in patients. Retinal circulation mirrors cerebral microcirculation and allows non-invasive investigations. We compared capillary rarefaction of retinal vessels in hypertensive versus normotensive subjects.

Methods

In this study retinal capillary rarefaction in 70 patients with long time (more than 67 month of disease duration) and 64 patients with short time hypertension stage 1 or 2 has been compared to 55 healthy control subjects, who participated in clinical trials in our Clinical Research Center (www.clinicaltrials.gov: NCT01318395, NCT00627952, NCT00152698, NCT01319344). Retinal vascular parameters have been measured non-invasively and in vivo in perfusion image by scanning laser Doppler flowmetry (Heidelberg Engineering, Germany). Capillary rarefaction was assessed by capillary area (CapA) (in pixel-number) and intercapillary distance (ICD) (in μm). Additionally retinal capillary flow (RCF) was measured.

Results

ICD was greater in the long time hypertensive group compared to healthy individuals (24.2?±?6.3 μm vs 20.1?±?4.2 μm, p?=?0.001) and compared to short time hypertensive patients (22.2?±?5.2 μm, p?=?0.020). Long time hypertensive patients showed less CapA compared to healthy people (1462?±?690 vs 1821?±?652, p?=?0.005). Accordingly, RCF was significantly lower in the long time hypertensive group compared to the healthy control group (282?±?70 AU vs 314?±?60 AU, p?=?0.032). Our data indicate a lower level of retinal capillary density in hypertensive patients, especially in those with long time hypertension.

Conclusion

Patients with hypertension stage 1 or 2 showed retinal capillary rarefaction in comparison to healthy normotensive subjects. Retinal capillary rarefaction was intensified with duration of disease.

     

Transient expression of recombinant tissue plasminogen activator (rt-PA) gene in cucurbit plants using viral vector

Objective

To use a transient expression system to express a truncated human tissue plasminogen activator (K2S) gene in cucurbit plants.

Results

The recombinant tissue plasminogen activator protein (K2S form) was expressed in active form in cucurbit plants. Its molecular weight was 43 kDa. The plant-derived rt-PA was determined using goat anti-rabbit antibody by western blotting. Among the infected lines, the highest expression of rt-PA was 62 ng/100 mg per leaf tissue as measured by ELISA. The enzymatic activity of the plant-derived rt-PA was 0.8 IU/ml.

Conclusions

The K25 form of rt-PA was expressed for the first time using the viral expression system. Plant-derived rt-PA showed similar potency to commercially-available PA.

     

Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits

Background

There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits.

Methods

A total of 30 rabbits were randomized into control group (CON, n?=?10), alloxan-induced diabetic group (DM, n?=?10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n?=?10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-β1, NF-κB p65 and mitochondrial biogenesis related proteins were determined by Western blotting.

Results

DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e′ ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (??dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1α/NRF1/Tfam signaling pathway.

Conclusions

The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis.

     

Metabolomics profiling of concussion in adolescent male hockey players: a novel diagnostic method

Introduction

Concussions are a major health concern as they cause significant acute symptoms and in some athletes, long-term neurologic dysfunction. Diagnosis of concussion can be difficult, as are the decisions to stop play.

Objective

To determine if concussions in adolescent male hockey players could be diagnosed using plasma metabolomics profiling.

Methods

Plasma was obtained from 12 concussed and 17 non-concussed athletes, and assayed for 174 metabolites with proton nuclear magnetic resonance and direct injection liquid chromatography tandem mass spectrometry. Data were analysed with multivariate statistical analysis and machine learning.

Results

The estimated time from concussion occurrence to blood draw at the first clinic visit was 2.3 ± 0.7 days. Using principal component analysis, the leading 10 components, each containing 9 metabolites, were shown to account for 82 % of the variance between cohorts, and relied heavily on changes in glycerophospholipids. Cross-validation of the classifier using a leave-one out approach demonstrated a 92 % accuracy rate in diagnosing a concussion (P < 0.0001). The number of metabolites required to achieve the 92 % diagnostic accuracy was minimized from 174 to as few as 17 metabolites. Receiver operating characteristic analyses generated an area under the curve of 0.91, indicating excellent concussion diagnostic potential.

Conclusion

Metabolomics profiling, together with multivariate statistical analysis and machine learning, identified concussed athletes with >90 % certainty. Metabolomics profiling represents a novel diagnostic method for concussion, and may be amenable to point-of-care testing.

     

Application of residual polysaccharide-degrading enzymes in dried shiitake mushrooms as an enzyme preparation in food processing

Objective

To examine the activities of residual enzymes in dried shiitake mushrooms, which are a traditional foodstuff in Japanese cuisine, for possible applications in food processing.

Results

Polysaccharide-degrading enzymes remained intact in dried shiitake mushrooms and the activities of amylase, β-glucosidase and pectinase were high. A potato digestion was tested using dried shiitake powder. The enzymes reacted with potato tuber specimens to solubilize sugars even under a heterogeneous solid-state condition and that their reaction modes were different at 38 and 50 °C.

Conclusion

Dried shiitake mushrooms have a potential use in food processing as an enzyme preparation.