Cardiovascular System ; drug effects ; Humans ; Trans Fatty Acids ; adverse effects

OBJECTIVETo establish nonalcoholic fatty liver disease (NAFLD) model induced by free fatty acid (FFA) and iron, and to explore the synergistic effect of FFA and Fe(2+) on the pathogenesis of NAFLD and mechanisms.

METHODSHuman liver carcinoma cell HepG2 was respectively treated with 0.250, 0.500, 1.000 mmol/L oleic acid, 0.500 mmol/L oleic acid+0.125 mmol/L Fe(2+), 0.500 mmol/L oleic acid+0.250 mmol/L Fe(2+), and 0.500 mmol/L oleic acid+0.500 mmol/L Fe(2+). Human liver carcinoma cell HepG2 was normally cultured in the control group. Lipid accumulation of cells were observed by oil red O staining and the determination of the triglyceride (TG) contents by GPO-PAP, then the expression of key genes involved in fatty acid β-oxidation (fatty acyl CoA synthetase-1 (ACSL-1), carnitine acyl transferase 1 (CPT-1a), fatty acid synthetase (FAS)) was determined using RT-PCR. The differences of TG content and ACSL-1, CPT-1a, FAS, mRNA relative value were analyzed among different groups.

RESULTSThe results of oil red O staining indicated that the contents of lipid droplets were obviously elevated with the increase of Fe(2+) concentration in human liver carcinoma cell HepG2 treated with 0.500 mmol/L oleic acid and different concentrations of Fe(2+). The TG contents of HepG2 cell in control group, 0.250, 0.500, 1.000 mmol/L oleic acid groups, 0.500 mmol/L oleic acid+0.125 mmol/L Fe(2+) group, 0.500 mmol/L oleic acid+0.250 mmol/L Fe(2+) group, 0.500 mmol/L oleic acid+0.500 mmol/L Fe(2+) group respectively were (90.0 ± 1.6), (131.7 ± 5.4), (153.7 ± 3.0), (254.1 ± 4.0), (164.5 ± 6.0), (180.1 ± 7.7), (235.6 ± 4.5) nmol/mg (F = 396.00, P < 0.05). The expression levels of ACSL-1 mRNA in 0.500 mmol/L oleic acid group, 0.500 mmol/L oleic acid+0.125 mmol/L Fe(2+) group, 0.500 mmol/L oleic acid +0.250 mmol/L Fe(2+) group, 0.500 mmol/L oleic acid +0.500 mmol/L Fe(2+) group respectively were (0.94 ± 0.02), (0.89 ± 0.04), (0.85 ± 0.02), (0.74 ± 0.04) (F = 50.00, P < 0.05); the mRNA levels of CPT-1a were (0.89 ± 0.03), (0.79 ± 0.05), (0.67 ± 0.04), (0.51 ± 0.05) (F = 79.00, P < 0.05); the mRNA levels of FAS were (1.31 ± 0.05) , (1.44 ± 0.03), (1.51 ± 0.05), (1.56 ± 0.06 ) (F = 79.70, P < 0.05).

CONCLUSIONThe NAFLD liver cell model could be established by oleic acid and Fe(2+) in HepG2 cells. FFA and iron might be involved in the pathogenesis of NAFLD through the intervention of fatty acid β-oxidation.

Carnitine O-Palmitoyltransferase ; Coenzyme A Ligases ; Fatty Acid Synthase, Type I ; Fatty Acids ; Fatty Acids, Nonesterified ; adverse effects ; Hep G2 Cells ; Humans ; Iron ; adverse effects ; Non-alcoholic Fatty Liver Disease ; chemically induced ; Oleic Acid ; RNA, Messenger ; Triglycerides

OBJECTIVE: To investigate the changes of tetraspanin 8 (TSPAN8) expression levels and its role in lipid metabolism during the development of non-alcoholic fatty liver disease (NAFLD). METHODS: Thirty male C57BL/6J mice were randomly divided into normal diet group and high-fat diet (HFD) group (n=15), and after feeding for 1, 3, and 6 months, the expression levels of TSPAN8 in the liver tissues of the mice were detected with Western blotting. In a HepG2 cell model of NAFLD induced by free fatty acids (FFA), the effect of TSPAN8 overexpression on lipid accumulation was examined using Oil Red O staining and an automated biochemical analyzer, and the mRNA expressions of the key genes involved in lipid metabolism were detected using qRT-PCR. RESULTS: Western blotting showed that compared with that in mice with normal feeding, the expression of TSPAN8 was significantly decreased in the liver tissues of mice with HFD feeding for 3 and 6 months (P < 0.05). In HepG2 cells, treatment with FFA significantly decreased the expression of TSPAN8 at both the mRNA and protein levels (P < 0.01). TSPAN8 overexpression in FFA-treated cells showed significantly lowered intracellular triglyceride levels (P < 0.001) and obviously reduced mRNA expression of fatty acid transport protein 5 (FATP5) (P < 0.01). The expression of FATP5 was significantly increased in FFA-treated cells as compared with the control cells (P < 0.001). CONCLUSION TSPAN8 is involved in lipid metabolism in NAFLD, and overexpression of TSPAN8 may inhibit cellular lipid deposition by reducing the expression of FATP5.
Animals ; Diet, High-Fat/adverse effects* ; Fatty Acids, Nonesterified ; Lipid Metabolism ; Liver/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/metabolism* ; RNA, Messenger/metabolism*

BACKGROUND: The association between meat, fish, or fatty acid intake and acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) has been investigated in a few studies, and the results were inconsistent. In addition, most studies are mainly based on the United States and European countries, in which the dietary patterns differ from that in Asia. Therefore, the risk of AML/MDS from meat, fish, or fatty acid intake in Asia requires further exploration. The aim of this study was to investigate the association between AML/MDS incidence and meat, fish, or fatty acid intake using the Japan Public Health Center-based prospective study. METHODS: The present study included 93,366 participants who were eligible for analysis and followed up from the 5-year survey date until December 2012. We estimated the impact of their intake on AML/MDS incidence using a Cox proportional hazards model. RESULTS: The study participants were followed up for 1,345,002 person-years. During the follow-up period, we identified 67 AML and 49 MDS cases. An increased intake of processed red meat was significantly associated with the incidence of AML/MDS, with a hazard ratio of 1.63 (95% confidence interval, 1.03-2.57) for the highest versus lowest tertile and a P_trend of 0.04. Meanwhile, the intake of other foods and fatty acids was not associated with AML/MDS. CONCLUSION In this Japanese population, processed red meat was associated with an increased incidence of AML/MDS.
Animals ; Japan/epidemiology* ; Prospective Studies ; Incidence ; Public Health ; Meat/adverse effects* ; Fatty Acids/adverse effects* ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes/epidemiology*

Boronic Acids ; adverse effects ; Bortezomib ; Fatty Acids, Omega-3 ; administration & dosage ; therapeutic use ; Fish Oils ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Peripheral Nervous System Diseases ; chemically induced ; drug therapy ; Pyrazines ; adverse effects

OBJECTIVETo investigate the effect of n-3 polyunsaturated fatty acids (n-3PUFAs) on gut microbiota and endotoxin levels in portal vein of rats fed with a high-fat diet (HFD).

METHODSThirty-six male Sprague-Dawley rats were randomly divided into four groups and fed with normal control diet (CD), HFD, CD supplemented with n-3PUFAs, and HFD supplemented with n-3PUFAs, respectively. Fresh fecal samples were collected to analyze the gut microbiota 10 weeks after feeding. DNA was exacted from the fresh fecal samples. Quantitative PCR was used to detect the composition of the gut microbiota. The endotoxin levels were detected through modified azo chromogenic substrate limulus amebocyte lysate assay.

RESULTSThe differences in body weight before breeding in each group were not statistically significant among these four groups (P=0.613). The increase in the body weight was significantly larger in the HFD group than in the CD group (P=0.0002), CD+n-3PUFAs group (P=0.0001), and HFD+n-3PUFAs group (P=0.022). There were significantly more firmicutes (P=0.002) and enterobacteriales (P=0.022) and significantly less bacteroidetes (P=0.026) and bifidobactera (P=0.034) in the gut of rats from HFD group than those from the CD group. There were significantly more bacteroidetes in the fecal samples of the rats from the CD+n-3PUFAs group compared to those from the CD group (P=0.043). There were significantly more firmicutes (P=0.044)and enterobacteriales (P=0.012) and less bacteroidetes (P=0.042) in the fecal samples of the rats from HFD group compared to those from the HFD+n-3PUFAs group. The endotoxin in plasma form portal vein of rats in HFD group were significantly higher than in CD group (P=0.007) and HFD+n-3PUFAs group (P=0.042) but showed no significant difference between CD+n-3PUFAs and CD group (P=0.210).

CONCLUSIONSHFD can increase body weight and change gut microbiota. Supplementation of n-3PUFAs can partially counteract such gut dysbiosis, lower endotoxin level in portal vein blood, and improve the body weight.

Animals ; Body Weight ; Diet, High-Fat ; adverse effects ; Endotoxins ; blood ; Fatty Acids, Omega-3 ; pharmacology ; Intestines ; microbiology ; Male ; Microbiota ; drug effects ; Portal Vein ; Rats ; Rats, Sprague-Dawley

We present here a case of acrodermatitis enteropathica-like eruption associated with essential free fatty acid and protein deficiencies as well as borderline zinc deficiency that occurred after Whipple's operation in a 31-yr-old woman. Her eruptions were improved not by zinc supplements alone, but her condition was improved by total parenteral nutrition including amino acids, albumin, lipid and zinc. Although we could not exactly decide which of the nutrients contributed the most to her manifestations, we inferred that all three elements in concert caused her dermatoses. This case shows that even though the patient's skin manifestations and laboratory results are suggestive of acrodermatitis enteropathica, the physicians should keep in mind the possibility that this disease can be associated with other nutritional deficiencies such as free fatty acid or protein deficiency.
Acrodermatitis/*diagnosis/*etiology ; Adult ; Fatty Acids, Essential/deficiency ; Female ; Humans ; Malnutrition/*diagnosis/*etiology ; Pancreatectomy/*adverse effects ; Protein-Losing Enteropathies/diagnosis/etiology ; Skin Diseases/*diagnosis/*etiology ; Zinc/deficiency

Although intravenous lipid emulsion (LE) is used mainly for parenteral nutrition, recently it has been used to treat patients with cardiopulmonary resuscitation (CPR)-resistant cardiovascular collapse induced by a toxic dose of local anesthetics or other drugs. Intravenous LE resolves symptoms of local anesthetic systemic toxicity, including convulsion, myoclonus, loss of consciousness, cardiac arrest, supraventricular tachycardia, and ventricular fibrillation. The main underlying mechanisms suggested to be responsible for LE-induced reversal of cardiac arrest due to drug toxicity are the lipid sink effect and the metabolic effect. The lipid sink theory posits that LE extracts a lipid-soluble toxic drug from the tissue. When a patient with cardiovascular collapse induced by a local anesthetic or another lipid-soluble drug is unresponsive to supportive treatments, including CPR and vasopressor therapy, LE administration can be considered. The suggested dosing regimen is as follows: 1) an initial intravenous bolus administration of 20% LE (1.5 mL/kg) is followed by a continuous infusion of 20% LE (0.25 mL/kg/min); and 2) when hemodynamic functions are unstable after the initial LE infusion, an intravenous administration of 20% LE (1.5 mL/kg) is repeated and followed by an increased continuous infusion of 20% LE (0.5 mL/kg/min). Further research is warranted regarding other possible mechanisms of LE's effect, the timing of LE administration, and the effect of various fatty acids on the LE-mediated reversal of cardiac arrest. This article reviews case reports and experimental evidence concerning the LE-mediated reversal of intractable cardiac arrest induced by drug toxicity, the underlying mechanism, and the dosing regimen.
Administration, Intravenous ; Anesthetics, Local* ; Cardiopulmonary Resuscitation ; Drug-Related Side Effects and Adverse Reactions ; Fatty Acids ; Heart Arrest ; Hemodynamics ; Humans ; Myoclonus ; Parenteral Nutrition ; Seizures ; Tachycardia, Supraventricular ; Unconsciousness ; Ventricular Fibrillation

The method has been developed to accurately identify the magnitude of health risks and provide scientific evidence for implementation of risk management in food safety. It combines two parameters including consequence and likelihood of adverse effects based on risk matrix. Score definitions and classification for the consequence and the likelihood of adverse effects are proposed. The risk score identifies the intersection of consequence and likelihood in risk matrix represents its health risk level with different colors: 'low', 'medium', 'high'. Its use in an actual case is shown.
Consumer Product Safety ; Food ; classification ; Food Analysis ; methods ; statistics & numerical data ; Humans ; Likelihood Functions ; Risk Assessment ; Trans Fatty Acids ; adverse effects ; analysis

OBJECTIVETo study the hormonal and metabolic responses of fetal lamb during cardiopulmonary bypass.

METHODSSix pregnant ewes underwent fetal cardiopulmonary bypasses with artificial oxygenators and roller pumps for 30 minutes, which maintained the blood gas value at the fetal physiological level. The fetal blood pressure, heart rate, pH value and blood lactate levels were monitored. The levels of catecholamine, cortisol and insulin were measured pre-bypass and then again 30 minutes later. The blood glucose and free fatty acid levels were monitored continuously during the bypass. Fetal hepatic PAS staining was also carried out.

RESULTSThere were no changes before and during the bypass in fetal blood pressure, heart rate and blood gas. However, pH values decreased and blood lactate levels increased (P < 0.05). The fetal catecholamine and cortisol levels increased significantly (P < 0.01), while the levels of insulin did not change. The blood glucose and free fatty acid levels increased at the beginning of the bypass (P < 0.01), and then gradually slowed down during the bypass. The fetal hepatic PAS staining showed that hepatic glycogen was consumed in large amounts. After 30 minutes of bypass, the fetal lamb would not survive more than 1 hour.

CONCLUSIONThe fetal lamb has a strong negative reaction to cardiopulmonary bypass.

Animals ; Blood Gas Analysis ; Blood Glucose ; analysis ; Cardiopulmonary Bypass ; adverse effects ; Catecholamines ; blood ; Fatty Acids, Nonesterified ; blood ; Fetus ; physiology ; Hemodynamics ; physiology ; Hydrocortisone ; blood ; Lactates ; blood ; Sheep