GC–MS analysis of the ruminal metabolome response to thiamine supplementation during high grain feeding in dairy cows

Introduction

Thiamine is known to attenuate high-concentrate diet induced subacute ruminal acidosis (SARA) in dairy cows, however, the underlying mechanisms remain unclear.

Objectives

The major objective of this study was to investigate the metabolic mechanisms of thiamine supplementation on high-concentrate diet induced SARA.

Methods

Six multiparous, rumen-fistulated Holstein cows were used in a replicated 3?×?3 Latin square design. The treatments included a control diet (CON; 20% starch, dry matter basis), a SARA-inducing diet (SAID; 33.2% starch, dry matter basis) and SARA-inducing diet supplemented with 180 mg of thiamine/kg of dry matter intake (SAID?+?T). On d21 of each period, ruminal fluid samples were collected at 3 h post feeding, and GC/MS was used to analyze rumen fluid samples.

Results

PCA and OPLS-DA analysis demonstrated that the ruminal metabolite profile were different in three treatments. Compared with CON treatment, SAID feeding significantly decreased rumen pH, acetate, succinic acid, increased propionate, pyruvate, lactate, glycine and biogenic amines including spermidine and putrescine. Thiamine supplementation significantly decreased rumen content of propionate, pyruvate, lactate, glycine and spermidine; increase rumen pH, acetate and some medium-chain fatty acids. The enrichment analysis of different metabolites indicated that thiamine supplementation mainly affected carbohydrates, amino acids, pyruvate and thiamine metabolism compared with SAID treatment.

Conclusions

These findings revealed that thiamine supplementation could attenuate high-concentrate diet induced SARA by increasing pyruvate formate-lyase activity to promote pyruvate to generate acetyl-CoA and inhibit lactate generation. Besides, thiamine reduced biogenic amines to alleviate ruminal epithelial inflammatory response.

     

Modelling the lactate response to short-term all out exercise

Background

The maximum post exercise blood lactate concentration (BLC_max) has been positively correlated with maximal short-term exercise (MSE) performance. However, the moment when BLC_max occurs (TBLC_max) is rather unpredictable and interpretation of BLC response to MSE is therefore difficult.

Methods

We compared a 3- and a 4-parameter model for the analysis of the dynamics of BLC response to MSEs lasting 10 (MSE10) and 30 s (MSE30) in eleven males (24.6 ± 2.3 yrs; 182.4 ± 6.8 cm; 75.1 ± 9.4 kg). The 3-parameter model uses BLC at MSE-start, extra-vascular increase (A) and rate constants of BLC appearance (k₁) and disappearance (k₂). The 4-parameter model includes BLC at MSE termination and amplitudes and rate constants of increase (A₁, y₁) and decrease (A₂, y₂) of post MSE-BLC.

Results

Both models consistently explained 93.69 % or more of the variance of individual BLC responses. Reduction of the number of parameters decreased (p < 0.05) the goodness of the fit in every MSE10 and in 3 MSE30. A (9.1 ± 2.1 vs. 15.3 ± 2.1 mmol l^-1) and A₁ (7.1 ± 1.6 vs. 10.9 ± 2.0 mmol l^-1) were lower (p < 0.05) in MSE10 than in MSE30. k₁ (0.610 ± 0.119 vs. 0.505 ± 0.107 min^-1), k₂ (4.21 10^-2 ± 1.06 10^-2 vs. 2.45 10^-2 ± 1.04 10^-2 min^-1), and A₂ (-563.8 ± 370.8 vs. -1412.6 ± 868.8 mmol l^-1), and y₁ (0.579 ± 0.137 vs. 0.489 ± 0.076 min^-1) were higher (p < 0.05) in MSE10 than in MSE30. No corresponding difference in y₂ (0.41 10^-2 ± 0.82 10^-2 vs. 0.15 10^-2 ± 0.42 10^-2 min^-1) was found.

Conclusion

The 3-parameter model estimates of lactate appearance and disappearance were sensitive to differences in test duration and support an interrelation between BLC level and halftime of lactate elimination previously found. The 4-parameter model results support the 3-parameter model findings about lactate appearance; however, parameter estimates for lactate disappearance were unrealistic in the 4-parameter model. The 3-parameter model provides useful information about the dynamics of the lactate response to MSE.

     

Untargeted and stable isotope-assisted metabolomic analysis of MDA-MB-231 cells under hypoxia

Introduction

Hypoxia commonly occurs in cancers and is highly related with the occurrence, development and metastasis of cancer. Treatment of triple negative breast cancer remains challenge. Knowledge about the metabolic status of triple negative breast cancer cell lines in hypoxia is valuable for the understanding of molecular mechanisms of this tumor subtype to develop effective therapeutics.

Objectives

Comprehensively characterize the metabolic profiles of triple negative breast cancer cell line MDA-MB-231 in normoxia and hypoxia and the pathways involved in metabolic changes in hypoxia.

Methods

Differences in metabolic profiles affected pathways of MDA-MB-231 cells in normoxia and hypoxia were characterized using GC–MS based untargeted and stable isotope assisted metabolomic techniques.

Results

Thirty-three metabolites were significantly changed in hypoxia and nine pathways were involved. Hypoxia increased glycolysis, inhibited TCA cycle, pentose phosphate pathway and pyruvate carboxylation, while increased glutaminolysis in MDA-MB-231 cells.

Conclusion

The current results provide metabolic differences of MDA-MB-231 cells in normoxia and hypoxia conditions as well as the involved metabolic pathways, demonstrating the power of combined use of untargeted and stable isotope-assisted metabolomic methods in comprehensive metabolomic analysis.

     

Lipopolysaccharide (LPS)-induced septic shock causes profound changes in myocardial energy metabolites in pigs

Introduction

Energy deficiency is a cause for myocardial dysfunction during septic shock. In rodents, septic shock decreases the oxidation of long-chain fatty acids and glucose in the myocardium causing energy deficiency. However, the effect of septic shock on myocardial energy metabolites in large animals and human is unknown.

Objectives

Investigate the effects of septic shock on myocardial energy metabolites in domestic pigs.

Methods

Seventeen female pigs divided into control and lipopolysaccharide (LPS)-induced septic shock groups. Myocardial metabolites were analyzed ex vivo by ¹H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. Gene and protein expression analysis were analyzed by real-time PCR and western blot.

Results

Septic shock was associated with an increase in myocardial levels of short- and medium-chain acylcarnitines, lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression. COX-2 and prostaglandin E4 receptor gene expression also increased in the septic myocardium, although the only elevated eicosanoid in the septic animals was thromboxane B2. Myocardial levels of niacin, taurine, glutamate, glutamine, and glutathione were higher, and hypoxanthine levels lower in septic pigs than controls.

Conclusions

In pigs, septic shock induced by LPS caused myocardial changes directed to decrease the oxidation of medium- and short-chain fatty acid without an effect on long-chain fatty acid oxidation. The increase in myocardial levels of lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression suggest that septic shock decreases pyruvate dehydrogenase complex activity and glucose oxidation. Homeostasis of niacin, taurine, glutamate, glutamine, glutathione, hypoxanthine and thromboxane B2 is also affected in the septic myocardium.

     

Uncovering the metabolic response of abalone (<Emphasis Type="Italic">Haliotis midae)</Emphasis> to environmental hypoxia through metabolomics

Introduction

Oxygen is essential for metabolic processes and in the absence thereof alternative metabolic pathways are required for energy production, as seen in marine invertebrates like abalone. Even though hypoxia has been responsible for significant losses to the aquaculture industry, the overall metabolic adaptations of abalone in response to environmental hypoxia are as yet, not fully elucidated.

Objective

To use a multiplatform metabolomics approach to characterize the metabolic changes associated with energy production in abalone (Haliotis midae) when exposed to environmental hypoxia.

Methods

Metabolomics analysis of abalone adductor and foot muscle, left and right gill, hemolymph, and epipodial tissue samples were conducted using a multiplatform approach, which included untargeted NMR spectroscopy, untargeted and targeted LC–MS spectrometry, and untargeted and semi-targeted GC-MS spectrometric analyses.

Results

Increased levels of anaerobic end-products specific to marine animals were found which include alanopine, strombine, tauropine and octopine. These were accompanied by elevated lactate, succinate and arginine, of which the latter is a product of phosphoarginine breakdown in abalone. Primarily amino acid metabolism was affected, with carbohydrate and lipid metabolism assisting with anaerobic energy production to a lesser extent. Different tissues showed varied metabolic responses to hypoxia, with the largest metabolic changes in the adductor muscle.

Conclusions

From this investigation, it becomes evident that abalone have well-developed (yet understudied) metabolic mechanisms for surviving hypoxic periods. Furthermore, metabolomics serves as a powerful tool for investigating the altered metabolic processes in abalone.

     

The association of fecal microbiota and fecal,blood serum and urine metabolites in myalgic encephalomyelitis/chronic fatigue syndrome

Introduction

The human gut microbiota has the ability to modulate host metabolism. Metabolic profiling of the microbiota and the host biofluids may determine associations significant of a host–microbe relationship. Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term disorder of fatigue that is poorly understood, but has been linked to gut problems and altered microbiota.

Objectives

Find changes in fecal microbiota and metabolites in ME/CFS and determine their association with blood serum and urine metabolites.

Methods

A workflow was developed that correlates microbial counts with fecal, blood serum and urine metabolites quantitated by high-throughput ¹H NMR spectroscopy. The study consists of thirty-four females with ME/CFS (34.9?±?1.8 SE years old) and twenty-five non-ME/CFS female (33.0?±?1.6 SE years old).

Results

The workflow was validated using the non-ME/CFS cohort where fecal short chain fatty acids (SCFA) were associated with serum and urine metabolites indicative of host metabolism changes enacted by SCFA. In the ME/CFS cohort a decrease in fecal lactate and an increase in fecal butyrate, isovalerate and valerate were observed along with an increase in Clostridium spp. and a decrease in Bacteroides spp. These differences were consistent with an increase in microbial fermentation of fiber and amino acids to produce SCFA in the gut of ME/CFS patients. Decreased fecal amino acids positively correlated with substrates of gluconeogenesis and purine synthesis in the serum of ME/CFS patients.

Conclusion

Increased production of SCFA by microbial fermentation in the gut of ME/CFS patients may be associated with deleterious effects on the host energy metabolism.

     

A randomised,open-labelstudy of insulin glargine or neutral protamine Hagedorn insulin in Chinese paediatric patients with type 1 diabetes mellitus

Background

We aimed to describe the safety and efficacy of insulin glargine in Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral protamine Hagedorn (NPH) insulin was the reference therapy.

Methods

This open-label, randomised, Phase III study was conducted at 10 sites in China. Children aged ≥6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin aspart was given as bolus insulin. The primary endpoint was absolute change in glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and safety. The study was registered at clinicaltrials.gov (NCT01223131).

Results

In total,196 patients were screened, and 162 were randomised (107 and 55 patients were randomised to insulin glargine and NPH insulin, respectively). The mean?±?SD of absolute change in HbA1c was–0.25?±?1.68% (–2.69?±?18.32 mmol/mol) in the insulin glargine group and –0.54?±?1.67% (–5.55?±?20.32 mmol/mol) in the NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments were generally well tolerated. A numerically lower rate of symptomatic hypoglycaemia per patient year was observed for insulin glargine versus NPH insulin (24.3?±?45.8 versus32.3?±?43.2); severe hypoglycaemia was rare (<2%).

Conclusions

Initiation of insulin glargine can aid Chinese paediatric patients with T1DM to safely reduce their HbA1c levels.

     

Non-invasive nuclear magnetic resonance analysis of male and female embryo metabolites during in vitro embryo culture

Introduction

In the past 20+ years, several studies of bovine embryo production showed how the ratio of male to female embryos changes if embryos are made in vivo or in vitro. It is known that in in vitro systems, the sex ratio is in favor of males when there are high levels of glucose, and favors females when the principal energetic substrate is one other than glucose, like citrate.

Objectives

The aim of this study was to evaluate the embryo metabolism during three important periods of in vitro development: the early development (from day 1 until day 3), the middle of culture (day 3 until day 5), and later development (day 5 until day 7).

Methods

To obtain this information we evaluated the spent medium from each time period by ¹H NMR.

Results

Our results confirm that embryo metabolism is different between sexes. The new information obtained by identifies markers that we can use to predict the embryo sex.

Conclusion

These results open a new, non-invasive method to evaluate sex of the embryos before the transfer. In the first period of embryo culture, valine concentration is good indicator (66.7% accurate), while in the last phase of culture, pyruvate depletion is the best marker (64% accurate) to evaluate the sex of the embryo.

     

Effect of everolimus on the glucose metabolic pathway in mouse skeletal muscle cells (C2C12)

Introduction

Everolimus selectively inhibits mammalian target of rapamycin complex 1 (mTORC1) and exerts an antineoplastic effect. Metabolic disturbance has emerged as a common and unique side effect of everolimus.

Objectives

We used targeted metabolomic analysis to investigate the effects of everolimus on the intracellular glycometabolic pathway.

Methods

Mouse skeletal muscle cells (C2C12) were exposed to everolimus for 48 h, and changes in intracellular metabolites were determined by capillary electrophoresis time-of-flight mass spectrometry. mRNA abundance, protein expression and activity were measured for enzymes involved in glycometabolism and related pathways.

Results

Both extracellular and intracellular glucose levels increased with exposure to everolimus. Most intracellular glycometabolites were decreased by everolimus, including those involved in glycolysis and the pentose phosphate pathway, whereas no changes were observed in the tricarboxylic acid cycle. Everolimus suppressed mRNA expression of enzymes related to glycolysis, downstream of mTOR signaling enzymes and adenosine 5′-monophosphate protein kinases. The activity of key enzymes involved in glycolysis and the pentose phosphate pathway were decreased by everolimus. These results show that everolimus impairs glucose utilization in intracellular metabolism.

Conclusions

The present metabolomic analysis indicates that everolimus impairs glucose metabolism in muscle cells by lowering the activities of glycolysis and the pentose phosphate pathway.

     

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.

     

Triterpenoid-rich loquat leaf extract induces growth inhibition and apoptosis of pancreatic cancer cells through altering key flux ratios of glucose metabolism

Introduction

Loquat leaf extract (LLE) is a mixture rich in terpenoids, and has broad biological activities including the inhibition of cancer cell growth. The exact metabolic mechanism of this growth inhibiting effect is not known.

Objectives

We investigated the cellular metabolic effect of LLE, and ursolic acid (UA) on pancreatic cancer cells using a ¹³C carbon tracing technology.

Methods

MIA PaCa-2 cells were cultured in medium containing [1, 2 ¹³C₂]-glucose in the presence of either LLE (50 µg/ml), UA (50 µM), or metformin (1 mM). The mass isotopomer distribution of glucose, lactate, ribose, glutamate and palmitate in medium was determined. Based on the mass isotopomer distribution in metabolites we were able to determine individual ¹³C enrichment (∑M?×?n) and the minimum fraction of new synthesis?(1-M0) in each metabolite. Several flux ratios of energy metabolic pathways were calculated from the mass isotopomer ratios of these metabolites.

Results

We found that tumor viability was suppressed by LLE and UA in a dose dependent manner, and the tumor-inhibiting effect was associated with the changes in oxidative/non-oxidative pentose (Ox/Non-ox) and pyruvate dehydrogenase/isocitrate dehydrogenase (PDH/ICDH) flux ratios resulting in decreased new syntheses of ribose and fatty acids.

Conclusion

Metabolic homeostasis (balance of fluxes) in cancer cells is maintained through the regulation of metabolic fluxes by oncogenes and tumor-suppressor genes. Treatment of MIA PaCa-2 cells by LLE, UA and metformin likely altered key metabolic flux ratios affecting metabolic homeostasis required for energy and macromolecular production in tumor growth.

     

Safety and efficacy of inspiratory muscle training for preventing adverse outcomes in patients at risk of prolonged hospitalisation

Background

The early institution of inspiratory muscle training on hospitalised patients with no established respiratory deficits could prevent in-hospital adverse outcomes that are directly or indirectly associated to the loss of respiratory muscle mass inherent to a prolonged hospital stay. The objective of the clinical trial is to assess the impact of inspiratory muscle training on hospital inpatient complications.

Methods

This is a double-blind randomised controlled trial. Subjects in the intervention group underwent an inspiratory muscle training loaded with 50% maximum inspiratory pressure twice daily for 4 weeks from study enrolment. Patients were randomly assigned to an inspiratory muscle training group or a sham inspiratory muscle training group. All patients received conventional physiotherapy interventions. Baseline and post-intervention respiratory and peripheral muscle strength, functionality (performance of activities of daily living), length of hospital stay, and death were evaluated. Clinical outcomes were assessed until hospital discharge. This study was approved by the Institutional Hospital Ethics Committee (03/2014).

Results

Thirty-one patients assigned to the inspiratory muscle training group and 34 to the sham inspiratory muscle training group were analysed. Patients in the inspiratory muscle training group had a shorter mean length of hospital stay (35.3?±?2.7 vs. 41.8?±?3.5 days, p?<?0.01) and a lower risk of endotracheal intubation (relative risk (RR)?=?0.36; 95% confidence interval (CI) 0.27–0.97; p?=?0.03) as well as muscle weakness (RR?=?0.36; 95% CI 0.19–0.98; p?=?0.02) and mortality (RR?=?0.23; 95% CI 0.2–0.94; p?=?0.04). The risk of adverse events did not differ significantly between groups.

Conclusion

Inspiratory muscle training was a protective factor against endotracheal intubation, muscle weakness, and mortality.

Trial registration

ClinicalTrials.gov, ID: NCT02459444. Registered on 19 May 2015.

     

Effects of time delay and body temperature on measurements of central venous oxygen saturation,venous-arterial blood carbon dioxide partial pressures difference,venous-arterial blood carbon dioxide partial pressures difference/arterial-venous oxygen difference ratio and lactate

Background

Central venous oxygen saturation (ScvO₂), venous-arterial blood carbon dioxide partial pressures difference (Pv-aCO₂), venous-arterial blood carbon dioxide partial pressures difference/arterial-venous oxygen difference ratio (Pv-aCO₂/Ca-vO₂) and lactate are important parameters employed during shock resuscitation. We designed this study to confirm the effects of time delay and body temperature on measurements of these four parameters.

Methods

Arterial and central venous blood samples were simultaneously drawn by plastic syringes via indwelling intra-arterial and central venous catheters from critically ill patients. Blood gas analyses were performed on both samples and repeated after 10, 20, 30, 40, 50 and 60?min. Patients were divided into a control group and a high temperature group according to whether the body temperature was greater than 38?°C.

Results

A total of 30 critically ill patients were enrolled. There was a trend of increasing values for ScvO₂, Pv-aCO₂, Pv-aCO₂/Ca-vO₂ and lactate over time (P?<?0.001). The ScvO₂ differences were all lower in high temperature group after 10, 20, 30, 40, 50 and 60?min when compared to the corresponding differences in the control group (P?<?0.05). The differences in lactate values were slightly higher in the high temperature group, relative to the control group after 20, 30, 40, 50 and 60?min (P?<?0.05).

Conclusions

Measurements of ScvO₂, Pv-aCO₂, lactate and Pv-aCO₂/Ca-vO₂ were affected by time delay or body temperature. We recommend that arterial and central venous blood gas samples be analyzed quickly within 10?min, especially for patients with body temperature <38?°C.

Trial registration

ChiCTR, ChiCTR1800014484. Registered 16 January 2018.

     

Evaluation of insulin-like growth factor-I in postmenopausal women with breast cancer treated with raloxifene

Background

The objective of this study was to evaluate serum IGF-I levels in postmenopausal women with breast cancer treated primarily with raloxifene.

Methods

Twenty-two postmenopausal patients with operable, stage I or II, estrogen receptor-positive carcinomas participated in this study. Following confirmation of diagnosis, the patients received 60 mg of raloxifene for 28 days prior to definitive surgery. Blood samples were collected for evaluation of serum IGF-I levels prior to initiating medication and following a 28-day treatment course. Student's t-test for paired samples was used in the statistical analysis. Significance was established at p < 0.05.

Results

Mean serum IGF-I levels pre- and post-raloxifene treatment were 143.7 ± 9.7 ng/ml and 94.8 ± 7.6 ng/ml, respectively. This reduction in serum IGF-I levels following treatment with raloxifene was statistically significant (p < 0.001).

Conclusion

Raloxifene significantly reduced serum IGF-I levels in postmenopausal women with breast cancer.

     

In-patient Tolvaptan use in SIADH: care audit,therapy observation and outcome analysis

Background

Indications for use of tolvaptan in SIADH-associated hyponatraemia remain controversial. We audited our local guidelines for Tolvaptan use in this situation to review treatment implications including drug safety, hospital admission episode analysis (episodes of liver toxicity, CNS myelinolysis, sodium-related re-admission rates), morbidity; mortality and underlying aetiologies.

Methods

We report a retrospective case series analysis of on-going treatment outcomes (case-note review) for 31 patients (age 73.3 ± 10.5 years, 55% females) consecutively treated with Tolvaptan as in-patient for confirmed SIADH with persistent S/Na⁺ < 125 mmol/L despite removal of reversible causes and 24-48 h fluid restriction, and include longer-term outcome data (re-treatment/readmissions/mortality) for up to 4 years of follow-up. A minimum of 6 months follow-up data were reviewed unless the patient died before that period.

Results

Short-term outcomes were favourable; 94%-achieved treatment targets after a mean of 3.48 ± 2.46 days. There was statistically significant rise in S/Na⁺ level after Tolvaptan treatment (before treatment: mean sodium 117.8 ± 3.73, 108–121 mmol/L and after treatment: mean sodium 128.7 ± 3.67, 125–135.2 mmol/L, P < .001). Although the target S/Na⁺ level was >125 mmol/L in fact one third (35%) of the patients achieved a S/Na⁺ level of >130 mmol/L by the time of hospital discharge. No patient experienced S/Na⁺ rise >12 mmol/L/24 h, drug-associated liver injury or CNS-myelinolysis. The average length of hospital stay following start of Tolvaptan treatment was 3.2 days. Relapse of hyponatraemia occurred in 26% of the patients, requiring retreatment with Tolvaptan. In all patients where either relapse of hyponatraemia occurred or readmission was necessary, SIADH was associated with malignancy, which was present overall in 60% of the group studied.

Conclusions

This study confirms the safety and efficacy of Tolvaptan in the treatment of SIADH-related significant, symptomatic hyponatraemia when used under specialist guidance and strict monitoring. A sodium level relapsing below the treatment threshold by 1 week after discontinuation is a good indicator of a patient group with re-treatment/longer-term therapy needs, all of whom had underlying malignancy. The criteria set locally in our trust to initiate Tolvaptan use also identifies a group where further investigation for underlying malignancy should be considered.

     

Postprandial endothelial dysfunction in subjects with new-onset type 2 diabetes: an acarbose and nateglinide comparative study

Background

Postprandial hyperglycemia is believed to affect vascular endothelial function. The aim of our study was to compare the effects of acarbose and nateglinide on postprandial endothelial dysfunction.

Methods

We recruited a total of 30 patients with newly diagnosed type 2 diabetes (19 men and 11 women, age 67.8 ± 7.3 years). Patients were randomly assigned to 3 groups receiving either 300 mg/day acarbose, 270 mg/day nateglinide, or no medication. A cookie test (consisting of 75 g carbohydrate, 25 g butter fat, and 7 g protein for a total of 553 kcal) was performed as dietary tolerance testing. During the cookie test, glucose and insulin levels were determined at 0, 30, 60, and 120 min after load. In addition, endothelial function was assessed by % flow-mediated dilation (FMD) of the brachial artery at 0 and 120 min after cookie load.

Results

Postprandial glucose and insulin levels were similar in the 3 groups. Postprandial endothelial dysfunction was similar in the 3 groups before treatment. After 12 weeks of intervention, postprandial FMD was significantly improved in the acarbose group compared with the control group (6.8 ± 1.3% vs 5.2 ± 1.1%, p = 0.0022). Area under the curve (AUC) for insulin response was significantly increased in the nateglinide and control groups; however, no significant change was observed in the acarbose group.

Conclusions

Our results suggest that acarbose improves postprandial endothelial function by improvement of postprandial hyperglycemia, independent of postprandial hyperinsulinemia. Acarbose may thus have more beneficial effects on postprandial endothelial function in patients with type 2 diabetes than nateglinide.

     

High nutrient intake during the early postnatal period accelerates skeletal muscle fiber growth and maturity in intrauterine growth-restricted pigs

Background

Intrauterine growth-restricted (IUGR) neonates impair postnatal skeletal muscle growth. The aim of this study was to investigate whether high nutrient intake (HNI) during the suckling period could improve muscle growth and metabolic status of IUGR pigs.

Methods

Twelve pairs of IUGR and normal birth weight (NBW) pigs (7 days old) were randomly assigned to adequate nutrient intake and HNI formula milk groups. Psoas major (PM) muscle sample was obtained after 21 days of rearing.

Results

IUGR decreased cross-sectional areas (CSA) and myofiber numbers, activity of lactate dehydrogenase (LDH), and mRNA expression of insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R), mammalian target of rapamycin (mTOR), ribosomal protein s6 (RPS6), eukaryotic translation initiation factor 4E (eIF4E), protein expression of phosphorylated mTOR (P-mTOR), and phosphorylated protein kinase B (P-Akt) in the PM muscle of pigs. Irrespective of birth weight, HNI increased muscle weight and CSA, the concentration of RNA, and ratio of RNA to DNA, as well as ratio of LDH to β-hydroxy-acyl-CoA-dehydrogenase in the PM muscle of pigs. Furthermore, HNI increased percentages of MyHC IIb, mRNA expression of IGF-1, IGF-1R, Akt, mTOR, RPS6, and eIF4E, as well as protein expression of P-mTOR, P-Akt, P-RPS6, and P-eIF4E in the PM muscle of pigs.

Conclusion

The present findings suggest that high nutrient intake during the suckling period could improve skeletal muscle growth and maturity, which is associated with increasing the expression of protein deposition-related genes and accelerating the development of glycolytic-type myofiber in pigs.

     

Regional muscle oxygenation differences in vastus lateralis during different modes of incremental exercise

Background

Near infrared spectroscopy (NIRS) is used to assess muscle oxygenation (MO) within skeletal muscle at rest and during aerobic exercise. Previous investigations have used a single probe placement to measure MO during various forms of exercise. However, regional MO differences have been shown to exist within the same muscle which suggests that different areas of the same muscle may have divergent MO. Thus, the aim of this study was to examine whether regional differences in MO exist within the same muscle during different types of incremental (rest, 25, 50, 75, 100 % of maximum) exercise (1 leg knee extension (KE), 2 leg KE, or cycling).

Methods

Nineteen healthy active males (Mean ± SD: Age 27 ± 4 yrs; VO_2max: 55 ± 11 mL/kg/min) performed incremental exercise to fatigue using each mode of exercise. NIRS probes were placed on the distal and proximal portion of right leg vastus lateralis (VL). Results were analyzed with a 3-way mixed model ANOVA (probe × intensity × mode).

Results

Differences in MO exist within the VL for each mode of exercise, however these differences were not consistent for each level of intensity. Comparison of MO revealed that the distal region of VL was significantly lower throughout KE exercise (1 leg KE proximal MO – distal MO = 9.9 %; 2 leg KE proximal MO – distal MO = 13 %). In contrast, the difference in MO between proximal and distal regions of VL was smaller in cycling and was not significantly different at heavy workloads (75 and 100 % of maximum).

Conclusion

MO is different within the same muscle and the pattern of the difference will change depending on the mode and intensity of exercise. Future investigations should limit conclusions on MO to the area under assessment as well as the type and intensity of exercise employed.

     

A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil

Background

Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil.

Methods

A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n?=?50) received Ringer’s lactate 10 mL and Group D received Ringer’s lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively.

Results

Incidence of EA, defined as a score?≥?3 on Aono’s four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score?≥?10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score?≥?13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P?<?0.05). Mean Children and Infants Postoperative Pain Scale (CHIPPS) score was significantly lower in Group D compared to Group C (1.2?±?0.5 vs. 5.2?±?0.6; P?<?0.05). Patients need for fentanyl (18% vs. 4%) or propofol rescue (20% vs. 0) was significantly greater in Group C compared to Group D. No significant differences in other relative aspects after surgery between groups.

Conclusion

Administration of dezocine 0.1 mg/kg decreased the incidence and severity of EA in preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia.

Trial registration

A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

     

Male breast cancer: thirteen years experience of a single center

Background

This retrospective study analysed the epidemiological, clinical, and therapeutic profiles of breast cancer in males.

Methods

We report our experience at the Hospital of the University of Baskent, where 20 cases of male breast cancer were observed and treated between 1995–2008.

Results

Median age at presentation was 66,7 ± 10,9 years. Average follow-up was 63 ± 18,5 months. The main presenting symptom was a mass in 65% of cases (13 patients). Ýnvasive ductal carcinoma was the most frequent pathologic type (70% of cases).

Conclusion

Male breast cancer patients have an incidence of prostate cancer higher than would be predicted in the general population. Cause of men have a higher rate of ER positivity the responses with hormonal agents are good.