Easy-to-swallow mooncake using 3D printing: Effect of oil and hydrocolloid addition.

3D printing is a promising technology for food production, capable of producing and developing personalized food products. In recent years, research on the application of 3D printing technology to create easy-to-swallow foods for the elderly with dysphagia has received extensive attention. In this study, we applied dual nozzle 3D printing technology to develop an easy-to-swallow mooncake food using a traditional Chinese food, mooncake, as a model system. We optimized the printing dough ink formulation by setting up soybean oil gradient experiments and Arabic gum gradient experiments, and then we applied the optimized dough ink as the crust of the mooncake to produce easy-to-swallow mooncakes. The experimental results show that the addition of 2.5 g of soybean oil and 0.125 g of Arabic gum could improve the texture of the dough product and reduce its hardness and adhesiveness. The mooncake produced with this crust dough ink was rated in the IDDSI texture level four, which met expectations. Therefore, this work provides insights into the development of easy-to-swallow food products.

Acupuncture and moxibustion combined with cupping for the treatment of post-herpetic neuralgia: A meta-analysis.

BACKGROUND: There are still controversies between the curative effect of acupuncture combined with cupping therapy and western medicine for post-herpetic neuralgia (PHN). Our meta-analysis fully incorporates the research of acupuncture combined with cupping therapy versus Western medicine for PHN, aiming to explore the difference in the efficacy of the 2 therapies, so as to provide guidance for clinical treatment. METHODS: We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, CBM, from establishment of the database to September, 2020. Include studies that are clearly defined as PHN or herpes zoster, and exclude duplicate publications; studies with no full text, incomplete information, or inability to extract data; the definition of exposure is quite different from most literature; animal experiments. RESULTS: The total effective rate (relative ratio [RR] = 1.21, 95% confidence interval [CI]: 1.12-1.31) and the rate of remarkable effect (RR = 1.46, 95% CI: 1.30-1.63) of acupuncture and moxibustion combined with cupping in the treatment of PHN were significantly higher than that of conventional western medicine. The visual analogue scale score of acupuncture and moxibustion combined with cupping for PHN was significantly lower than that of conventional western medicine treatment (WMD = -1.77, 95% CI [-2.79, -0.75]). In addition, acupuncture and moxibustion combined with cupping therapy significantly reduced the occurrence of PHN compared with conventional western medicine treatment after treatment of acute herpes zoster (RR = 0.30, 95% CI: 0.20-0.45). In order to explore the differences in the efficacy and preventive effects of different types of acupuncture and cupping therapy, we have further conducted a subgroup analysis. CONCLUSION: The effect of acupuncture and moxibustion combined with cupping in the treatment of PHN is significantly higher than that of conventional western medicine, and it can significantly prevent the occurrence of PHN. Chinese medicine should be used more widely in the treatment of PHN.

Distinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive Disorders.

OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.

The Application and Functional Progress of γ-Poly-Glutamic Acid in Food: A Mini-Review.

γ-Poly-glutamic acid (γ-PGA) is a naturally occurring homo-polyamide produced by various strains of Bacillus. As a biopolymer substance, γ-PGA possesses a few predominant features containing good water solubility, biocompatibility, degradability and non-toxicity. Based on this, γ-PGA can be used in pharmaceutical, such as drug carrier/deliverer, vaccine adjuvant, and coating material for microencapsulation, etc. Moreover, it has also been applied in a broad range of industrial fields including food, medicine, bioremediation, cosmetics, and agriculture. Especially, γ-PGA is an extremely promising food ingredient. In this mini-review, our aim is to review the function and application progress of γ-PGA in the food industry: e.g., improving taste and flavor, enhancing physical property, and promoting health.

Effects of low doses of UV-B radiation supplementation on tuber quality in purple potato (Solanum tuberosum L.).

UV-B is an important environmental factor that differentially affects plant growth and secondary metabolites. However, our knowledge regarding the physiological and biochemical changes in under-ground plant organs responded to UV-B treatment remains limited. In this study, we investigated potato plant (Solanum tuberosum L.) and tuber responses to short-term supplemental UV-B exposure performed during tuber development. Our results indicated that the supplemental UV-B radiation with relative low dose had no obvious adverse impact on plant growth or tuber production. Nutritional composition analyses of tubers revealed that the contents of starch, soluble sugars, and proteins were significantly increased under lower UV-B radiation relative to controls. Similarly, low dose of UV-B treatment promoted the health-promoting compounds, including anthocyanin, phenols, and flavonoids in tubers. Moreover, higher activities of antioxidant enzymes were significantly induced in tubers in response to lower UV-B radiation. These findings suggest that short-term UV-B radiation supplementation at relative low doses can improve the tuber quality in potato plants.

Transcriptome analysis reveals the protection mechanism of proanthocyanidins for Saccharomyces cerevisiae during wine fermentation.

Grape-derived proanthocyanidins could act as a protector against various environmental stresses for Saccharomyces cerevisiae during wine fermentation, resulting in the increased physiological activity, fermentation efficiency and improved wine quality. In order to explore the possible protection mechanism of proanthocyanidins globally, RNA-seq analysis for wine yeast AWRI R2 cultivated with 0 g/L (group A), 0.1 g/L (group B), 1.0 g/L (group C) proanthocyanidins were applied in this study. Differentially expressed genes were enriched into six metabolic pathways including vitamin B6, thiamine, amino acids, aminoacyl-tRNA, carbohydrate and steroid based on KEGG enrichment analysis. Four key genes (SNZ2, THI6, THI21 and THI80), participated in the biosynthesis of vitamin B6 and thiamine, were up-regulated significantly in proanthocyanidins treated yeast cells and the gene expression levels were verified by RT-qPCR. Yeast cells supplemented with proanthocyanidins performed increased intracellular levels of vitamin B6 and thiamine and higher cell viability compared to the control group. In addition, the composition of intracellular fatty acids showed an obvious alternation in proanthocyanidins-treated yeast cells, in which the UFAs content increased whereas the SFA content decreased. In general, we provided an indirect protection effect of proanthocyanidins on the yeast cells to alleviate environmental stresses during wine fermentation.

Melatonin enhances atherosclerotic plaque stability by inducing prolyl-4-hydroxylase α1 expression.

OBJECTIVE: Melatonin, an endogenous neurohormone secreted predominately by the pineal gland, has a variety of physiological functions. However, its protective role in atherosclerosis is not clear. In this study, we sought to investigate the potential effects of melatonin in modulating atherosclerotic plaque stability in apolipoprotein E knockout (ApoE) mice. METHOD AND RESULTS: Smooth muscle cells were treated with melatonin, which significantly increased mRNA and protein levels of a key intracellular enzyme essential for collagen maturation and secretion, prolyl-4-hydroxylase α1 (P4Hα1). Mechanistically, melatonin increased Akt phosphorylation and transcriptional activation of specificity protein 1 (Sp1), which bound with the P4Hα1 promoter and then induced P4Hα1 expression. Pretreatment with either Akt inhibitor LY294002 or Sp1 inhibitor mithramycin A (MTM) could inhibit melatonin-induced P4Hα1 expression. Finally, atherosclerotic lesions were induced by placing a perivascular collar on the right common carotid artery of ApoE mice, which were received with or without different doses of melatonin or MTM. High-dose melatonin enhanced atherosclerotic plaque stability in ApoE mice in vivo by inducing the expression of P4Hα1, which was reversed by MTM. CONCLUSION: We propose that melatonin supplementation may provide a novel and promising approach to atherosclerosis treatment.

Metabolic profiling of the effects of ginsenoside Re in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is one of the major neurological diseases among the elderly, and there are presently no approved treatments that can slow its progression. It has been reported that ginsenoside Re (G-Re), an active pharmacological component of ginseng, can ameliorate the symptoms of AD, but the underlying mechanisms are not clear. The current study was designed to test the effects of G-Re by investigating the metabolite profiles of AD mice. An AD animal model was induced by intracerebroventricular injection of ß-amyloid in Kunming mice. Model mice were administered G-Re intragastrically (4mg/kg/day as a high dose and 1mg/kg/day as a low dose) for 30days. Cognitive function of the mice was tested using a Morris water maze, and pathological changes in the brain tissue were assessed by immunohistochemistry. Global metabolite profiling using ultra performance liquid chromatography-mass spectrometry was carried out to identify the metabolites that were differentially expressed in the plasma of mice. A total of 10 potential biomarkers were identified in AD mice. The peak intensities of tryptophan, hexadecasphinganine, phytosphingosine, and various lysophosphatidylcholines were lower whereas that of phenylalanine was higher in the AD mice than in the control mice. G-Re treatment (4mg/kg) affected all of these metabolic pathways. This is the first metabonomics study to biochemically profile the plasma metabolic pathways of AD animals affected by G-Re. These outcomes provide reliable evidence that illuminates the biochemical mechanisms of AD and facilitates investigation of the therapeutic benefits of G-Re in AD treatment.

Hierarchical Subcortical Sub-Regional Shape Network Analysis in Alzheimer's Disease.

In this paper, by utilizing surface diffeomorphic deformations, we constructed and analyzed subcortical shape morphometric networks in 210 healthy control (HC) subjects and 175 subjects with Alzheimer's disease (AD), aiming to identify AD-induced abnormalities in the subcortical shape network. We quantitatively analyzed pertinent network attributes of the entire network and each node. Further to this, hierarchical analyses were performed; group comparisons were conducted at the structure level first and then the sub-region level. The bilateral amygdalae, hippocampi, as well as the thalamus were all divided into multiple functionally distinct sub-regions. From the structure level analysis, we found significant HC-vs-AD group differences in the average local efficiency and average global efficiency. In addition, the local nodal efficiencies between the right thalamus and all three of the right hippocampus, right amygdala, and left thalamus, as well as that between the left amygdala and left hippocampus, decreased significantly in AD. According to the sub-regional network analyses, we observed significant AD-induced local efficiency decreases between different sub-regions within the right hippocampus itself and between the subiculum of the right hippocampus and the sub-region of the right thalamus connecting to the temporal lobe, indicating a degradation of circuit between the hippocampus, thalamus, and temporal lobe. Statistical comparisons were performed using 40,000 non-parametric permutation tests, with false discovery rate correction employed for multiple comparison correction.

Xuebijing Injection () increases early survival rate by alleviating pulmonary vasopermeability in rats subjected to severe burns.

OBJECTIVE: To investigate the effects of Xuebijing Injection (, XBJ) on survival rate and pulmonary vasopermeability in a rat model of severe scald injury. METHODS: Rats were divided into two experiments: experiment 1 was monitored for 12 h post-injury for survival analysis after severe burns; in experiment 2, rats were killed for determination of pulmonary vascular permeability and pro-inflflammatory mediators. In both experiments, rats were subject to third-degree 50% total body surface area (TBSA) burns or sham injury followed by XBJ or normal saline (NS) treatment. In addition, rat pulmonary microvascular endothelium cells (PMECs) were pretreated with either XBJ or phosphate buffer saline (PBS), and then subjected to sham serum or scald serum stimulation for 2 or 6 h, followed by transwell examination for the permeability of PMECs. Meanwhile, pro-inflflammatory mediators in PMECs culture supernatant were also investigated. RESULTS: The average survival time in the scald+XBJ group was 582.1±21.2 min, which was signifificantly longer than that in the scald + NS group (345.8±25.4 min, P<0.01). Plasma levels of tumor necrosis factor-alpha (TNF-α), E-selectin, interleukin-6 (IL-6), vascular permeability and water content of lung tissues were signifificantly increased in animals after severe burns (P<0.01). However, administration of XBJ signifificantly decreased these levels in plasma and lung tissue. In in vitro cell experiments, XBJ markedly attenuated permeability in PMECs monolayer and reduced the levels of TNF-α, IL-6 and soluble E-selectin after stimulation with scald serum (P<0.01). CONCLUSIONS: XBJ increases early survival rate by alleviating pulmonary vasopermeability and inhibiting pro-inflflammatory mediators in rats subjected to lethal scald injury. XBJ may be a potent drug in treatment of severe burns.

Intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via Caveolin2/STAT3/GSK-3ß pathway.

BACKGROUND: We recently demonstrated that the heart of late pregnant (LP) rodents is more prone to ischemia/reperfusion (I/R) injury compared to non-pregnant rodents. Lipids, particularly polyunsaturated fatty acids, have received special attention in the field of cardiovascular research. Here, we explored whether Intralipid (ITLD) protects the heart against I/R injury in LP rodents and investigated the mechanisms underlying this protection. METHODS AND RESULTS: In-vivo female LP rat hearts or ex-vivo isolated Langendorff-perfused LP mouse hearts were subjected to ischemia followed by reperfusion with PBS or ITLD (one bolus of 5mg/kg of 20% in in-vivo and 1% in ex-vivo). Myocardial infarct size, mitochondrial calcium retention capacity, genome-wide expression profiling, pharmacological inhibition and co-immunoprecipitation were performed. One bolus of ITLD at reperfusion significantly reduced the in-vivo myocardial infarct size in LP rats (23.3±2% vs. 55.5±3.4% in CTRL, p<0.01). Postischemic administration of ITLD also protected the LP hearts against I/R injury ex-vivo. ITLD significantly increased the threshold for the opening of the mitochondrial permeability transition pore in response to calcium overload (nmol-calcium/mg-mitochondrial protein: 290±17 vs. 167±10 in CTRL, p<0.01) and significantly increased phosphorylation of STAT3 (1.8±0.08 vs. 1±0.16 in CTRL, p<0.05) and GSK-3ß (2.63±0.55 vs. 1±0.0.34 in CTRL, p<0.05). The ITLD-induced cardioprotection was fully abolished by Stattic, a specific inhibitor of STAT3. Transcriptome analysis revealed caveolin 2 (Cav2) was significantly upregulated by ITLD in hearts of LP rats under I/R injury. Co-immunoprecipitation experiments showed that Cav2 interacts with STAT3. CONCLUSIONS: ITLD protects the heart in late pregnancy against I/R injury by inhibiting the mPTP opening through Cav2/STAT3/GSK-3ß pathway.

Calcium Supplementation Abates the Inhibition Effects of Acetic Acid on Saccharomyces cerevisiae.

The toxic level of acetic acid could be released during the pretreatment of lignocellulosic biomass, and an economical method was reported to minimize the acidic stress on the fermentation of Saccharomyces cerevisiae by cation supplementation. A dose-dependent protection of Ca2+ was monitored, and the optimal concentration of Ca2+ was 8 mM under 4.5 g/L acetic acid stress. The activities of catalase and superoxide dismutase of yeast cells supplemented with optimal Ca2+ increased by 18.6 and 27.3 %, respectively, coupling with an obvious decrease of reactive oxygen species content. Cell viability also performed a significant increase from 52.4 % (without Ca2+ addition) to 73.56 % (with 8 mM Ca2+ addition). No significant improvements were found in the bioethanol yields by Ca2+ supplementation; however, the fermentation time was shortened by about 8 h obviously. Our results illustrated that the Ca2+ supplementation could be an economical method to make the bioethanol production more efficient and cost-effective.

The Effect of Proanthocyanidins on Growth and Alcoholic Fermentation of Wine Yeast under Copper Stress.

Proanthocyanidins (PAs) derived from the grape skin, as well as from grape seeds, grape stems, are an important group of polyphenols in wine. The aim of this study was to understand the effect of PAs (0.1, 1.0 g/L) on growth and alcoholic fermentation of 2 strains of Saccharomyces cerevisiae (commercial strain FREDDO and newly selected strain BH8) during copper-stress fermentation, using a simple model fermentation system. Our results showed that both PAs and Cu(2+) could pose significant inhibition effects on the growth of yeast cells, CO2 release, sugar consumption, and ethanol production during the initial phase of the fermentation. Compared to PAs, Cu(2+) performed more obvious inhibition on the yeast growth and fermentation. However, adding 1.0 g/L PAs increased in the vitality and metabolism activity of yeast cells at the mid-exponential phase of fermentation in the mediums with no copper and 0.1 mM Cu(2+) added, shortened the period of wine fermentation, and decreased the copper residues. It indicated that PAs could improve the ability of wine yeast to resist detrimental effects under copper-stress fermentation condition, maintaining cells metabolic activity, and fermentation could be controlled by manipulating PAs supplementation.

Protective effect of linalool against lipopolysaccharide/D-galactosamine-induced liver injury in mice.

Linalool, a natural compound of the essential oils, has been shown to have antinociceptive, antimicrobial, and anti-inflammatory properties. The aim of this study was to investigate the effects of linalool against lipopolysaccharide (LPS)/D-galactosamine (GalN)-induced liver injury in mice. Mice were administered with linalool 1h before receiving LPS (50 µg/kg) and GalN (800 mg/kg). The results demonstrated that linalool had a protective effect on LPS/GalN-induced acute liver injury, as evidenced by the attenuation of hepatic pathological damage, malondialdehyde (MDA) content, MPO activity and serum ALT and AST levels. Linalool alleviated serum and hepatic TNF-α and IL-6 production, as well as hepatic iNOS and COX-2 expression by inhibiting NF-κB activation. Treatment of linalool increased bcl-2 expression and inhibited caspase-3 and caspase-8 expression. In addition, linalool increased Nrf2 and heme oxygenase-1 expression up-regulation by LPS/GalN. In conclusion, our results suggested that linalool was protected against LPS/GalN-induced liver injury through induction of antioxidant defense via Nrf2 activating and reduction inflammatory response via NF-κB inhibition.

Mechanism of proanthocyanidins-induced alcoholic fermentation enhancement in Saccharomyces cerevisiae.

Our previous work revealed proanthocyanidins (PAs) could pose significant enhancement on the activity of H(+)-ATPase and fermentation efficiency after a transient initial inhibition (Li et al in Am J Enol Vitic 62(4):512-518, 2011). The aim of the present work was to understand the possible mechanism for this regulation. At Day 0.5 the gene expression level of PMA1 in AWRI R2 strain supplemented with 1.0 mg/mL PAs was decreased by around 54 % with a 50 % and a 56.5 % increase in the concentration of intracellular ATP and NADH/NAD(+) ratio, respectively, compared to that of control. After the transient adaptation, the gene expression levels of PMA1 and HXT7 in PAs-treated cells were enhanced significantly accompanied by the decrease of ATP contents and NADH/NAD(+) ratio, which resulted in the high level of the activities of rate-limiting enzymes. PAs could pose significant effects on the fermentation via glucose transport, the energy and redox homeostasis as well as the activities of rate-limiting enzymes in glycolysis.

Supramolecular adducts of squaraine and protein for noninvasive tumor imaging and photothermal therapy in vivo.

Extensive efforts have been devoted to the development of near-infrared (NIR) dye-based imaging probes and/or photothermal agents for cancer theranostics in vivo. However, the intrinsic chemical instability and self-aggregation properties of NIR dyes in physiological condition limit their widely applications in the pre-clinic study in living animals. Squaraine dyes are among the most promising NIR fluorophores with high absorption coefficiencies, bright fluorescence and photostability. By introducing dicyanovinyl groups into conventional squaraine (SQ) skeleton. These acceptor-substituted SQ dyes not only show superior NIR fluorescence properties (longer wavelength, higher quantum yield) but also exhibit more chemical robustness. In this work, we demonstrated highly stable and biocompatible supramolecular adducts of SQ and the natural carrier protein, i.e., bovine serum albumin (BSA) (SQ⊂BSA) for tumor targeted imaging and photothermal therapy in vivo. SQ was selectively bound to BSA hydrophobic domain via hydrophobic and hydrogen bonding interactions with up to 80-fold enhanced fluorescence intensity. By covalently conjugating target ligands to BSA, the SQ⊂BSA was capable of targeting tumor sites and allowed for monitoring the time-dependent biodistribution of SQ⊂BSA, which consequently determined the protocol of photothermal therapy in vivo. We envision that this supramolecular strategy for selectively binding functional imaging agents and/or drugs into human serum albumin might potentially utilize in the preclinical and even clinic studies in the future.

Synergetic effect of functional cadmium-tellurium quantum dots conjugated with gambogic acid for HepG2 cell-labeling and proliferation inhibition.

We prepared and studied novel fluorescent nanocomposites based on gambogic acid (GA) and cadmium-tellurium (CdTe) quantum dots (CdTe QDs) modified with cysteamine for purpose of cancer cell labeling and combined treatment. The nanocomposites were denoted as GA-CdTe. Characterization results indicated that the CdTe QDs can readily bind onto cell plasma membranes and then be internalized into cancer cells for real-time labeling and tracing of human liver hepatocellular carcinoma cell line (HepG2) cells. GA-CdTe significantly enhanced drug accumulation in HepG2 cells and inhibited cancer cell proliferation. GA-CdTe nanocomposites also improved the drug action of GA molecules in HepG2 cells and induced the G2/M phase arrest of the cancer cell cycle, promoting cell apoptosis. Given the sensitive, pH-triggered release of GA-CdTe, the side effects of GA anticancer agents on normal cells/tissues in the blood circulation markedly decreased. Efficient drug release and accumulation in target tumor cells were also facilitated. Thus, the fluorescent GA-CdTe offered a new strategy for potential multimode cancer therapy and provided new channels for research into naturally-active compounds extracted from traditional Chinese medicinal plants.

Intralipid, a clinically safe compound, protects the heart against ischemia-reperfusion injury more efficiently than cyclosporine-A.

BACKGROUND: We have recently shown that postischemic administration of intralipid protects the heart against ischemia-reperfusion injury. Here we compared the cardioprotective effects of intralipid with cyclosporine-A, a potent inhibitor of the mitochondrial permeability transition pore opening. METHODS: In vivo rat hearts or isolated Langendorff-perfused mouse hearts were subjected to ischemia followed by reperfusion with intralipid (0.5%, 1% and 2% ex-vivo, and 20% in vivo), cyclosporine-A (0.2 µM, 0.8 µM, and 1.5 µM ex- vivo and 10 mg/kg in vivo), or vehicle. The hemodynamic function, infarct size, calcium retention capacity, mitochondrial superoxide production, and phosphorylation levels of protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß) were measured. The values are mean ± SEM. RESULTS: Administration of intralipid at reperfusion significantly reduced myocardial infarct size compared with cyclosporine-A in vivo (infarct size/area at risk)%: 22.9 ± 2.5% vs. 35.2 ± 3.5%; P = 0.030, n = 7/group). Postischemic administration of intralipid at its optimal dose (1%) was more effective than cyclosporine-A (0.8 µM) in protecting the ex vivo heart against ischemia-reperfusion injury, as the rate pressure product at the end of reperfusion was significantly higher (mmHg · beats/min: 12,740 ± 675 [n = 7] vs. 9,203 ± 10,781 [n = 5], P = 0.024), and the infarct size was markedly smaller (17.3 ± 2.9 [n = 7] vs. 29.2 ± 2.7 [n = 5], P = 0.014). Intralipid was as efficient as cyclosporine-A in inhibiting the mitochondrial permeability transition pore opening (calcium retention capacity = 280 ± 8.2 vs. 260.3 ± 2.9 nmol/mg mitochondria protein in cyclosporine-A, P = 0.454, n = 6) and in reducing cardiac mitochondrial superoxide production. Unlike intralipid, which increased phosphorylation of Akt (6-fold) and GSK-3ß (5-fold), cyclosporine-A had no effect on the activation of these prosurvival kinases. CONCLUSIONS: Although intralipid inhibits the opening of the mitochondrial permeability transition pore as efficiently as cyclosporine-A, intralipid is more effective in reducing the infarct size and improving the cardiac functional recovery.

Fatty-acid oxidation and calcium homeostasis are involved in the rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats.

OBJECTIVES: Lipid emulsion has been shown to be effective in resuscitating bupivacaine-induced cardiac arrest but its mechanism of action is not clear. Here we investigated whether fatty-acid oxidation is required for rescue of bupivacaine-induced cardiotoxicity by lipid emulsion in rats. We also compared the mitochondrial function and calcium threshold for triggering of mitochondrial permeability transition pore opening in bupivacaine-induced cardiac arrest before and after resuscitation with lipid emulsion. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Asystole was achieved with a single dose of bupivacaine (10 mg/kg over 20 secs, intravenously) and 20% lipid emulsion infusion (5 mL/kg bolus, and 0.5 mL/kg/min maintenance), and cardiac massage started immediately. The rats in CVT-4325 (CVT) group were pretreated with a single dose of fatty-acid oxidation inhibitor CVT (0.5, 0.25, 0.125, or 0.0625 mg/kg bolus intravenously) 5 mins prior to inducing asystole by bupivacaine overdose. Heart rate, ejection fraction, fractional shortening, the threshold for opening of mitochondrial permeability transition pore, oxygen consumption, and membrane potential were measured. The values are mean ± SEM. MEASUREMENTS AND MAIN RESULTS: Administration of bupivacaine resulted in asystole. Lipid Emulsion infusion improved the cardiac function gradually as the ejection fraction was fully recovered within 5 mins (ejection fraction=64±4% and fractional shortening=36±3%, n=6) and heart rate increased to 239±9 beats/min (71% recovery, n=6) within 10 mins. Lipid emulsion was only able to rescue rats pretreated with low dose of CVT (0.0625 mg/kg; heart rate~181±11 beats/min at 10 mins, recovery of 56%; ejection fraction=50±1%; fractional shortening=26±0.6% at 5 mins, n=3), but was unable to resuscitate rats pretreated with higher doses of CVT (0.5, 0.25, or 0.125 mg/kg). The calcium-retention capacity in response to Ca²âº overload was significantly higher in cardiac mitochondria isolated from rats resuscitated with 20% lipid emulsion compared to the group that did not receive Lipid Emulsion after bupivacaine overdose (330±42 nmol/mg vs. 180±8.2 nmol/mg of mitochondrial protein, p<.05, n=3 in each group). The mitochondrial oxidative rate and membrane potential were similar in the bupivacaine group before and after resuscitation with lipid emulsion infusion. CONCLUSIONS: Fatty-acid oxidation is required for successful rescue of bupivacaine-induced cardiotoxicity by lipid emulsion. This rescue action is associated with inhibition of mitochondrial permeability transition pore opening.