High Protein Diet that Cause Weight Loss and Lower Blood Glucose Level Have a Serious Impact on the Kidney Functions of Male Diabetic Obese Albino Rats

Background: High protein (HP) diets are increasingly being recommended as one of the management strategies for weight control in overweight and obese individuals. The health benefits of high protein diets are well-established, but the mechanisms of action on body systems responsible for the changes in body weight and glycaemic control are not well-clear. Objective: The present study aimed to examine the effect of HP diets on the kidney functions of diabetic obese albino rats. Material and Methods: Eighty male adult male albino rats were used in this study. The animals were divided into eight equal groups (10 rats for each). Type 2 DM and obesity were induced. At the end of the 12 weeks, samples were collected for biochemical analysis. Results: The high protein diet led to significant decrease in BW, FI, BG, TC, LDL, TG, Lactate dehydrogenase, albumin, urine pH and urine citrate;while serum insulin, HDL, urea, creatinine, total protein, urine volume and urinary excretion of Ca were significantly higher in high protein diet groups. Conclusion: A high protein intake in diabetic obese albino rats for 12 weeks led to changes in the serum and urine levels of markers of renal function which indicated abnormalities in the functions of the kidney.

Idiopathic Reactive Hypoglycemia: Mechanisms of Onset and Remission with High Protein Low Carbohydrate Diet

Objective: Idiopathic reactive hypoglycemia is defined as early postprandial hypoglycemia occurring on ingestion of high carbohydrate containing meal. Remission ensues with high protein low carbohydrate diet. This study assessed roles of insulin and glucagon in its onset and remission. Methods: Plasma glucose, insulin and glucagon were determined after an overnight fast and repeatedly until 180 minutes on ingestion of 3 meals;100 g glucose;100 g pure protein liquid and mixture of 50 g each at 14 days’ interval. Five adults with IRH and 6 age matched healthy volunteers participated. Results: In IRH, glucose ingestion induced prompt rise in glucose (5.1 ± 0.8 to10.5 ± 1.2 mM/L) followed later by hypoglycemia (2.6 ± 0.4 mM/L). Insulin rose from 7 ± 2 to 90 ± 18 mU/L. Glucagon rose initially (10% ± 2%) from elevated basal concentration (373 ± 57 mU/L) followed by later decline (-43% ± 12%). On protein ingestion, glucose declined followed by a restoration to basal level while both insulin and glucagon rose (28 ± 6 mU/L;148% ± 38%, p < 0.01). However, insulin response was lower and glucagon rise was greater when compared to responses on glucose ingestion (p < 0.01). With mixed meal, glucose (8.2 ± 0.6 mM/L), insulin (65 ± 12 mU/L) and glucagon (48% ± 7%) responses were lesser than rises following glucose ingestion (p < 0.05) and hypoglycemia did not occur. Conclusion: In IRH, initial hyperglycemia on glucose ingestion may be exacerbated by paradoxical glucagon rise and hypoglycemia may be induced by increased insulin and declining glucagon responses. Resolution of hypoglycemia with high protein low carbohydrate diet may be attributed to blunting of insulin response and concurrent glucagon rise.

Optimization of Multigrain Premix for High Protein and Dietary Fibre Biscuits Using Response Surface Methodology (RSM)

In order to improve the nutritional quality of biscuits, a multigrain premix (MGP) was developed by using whole barley, sorghum, chickpea, pea and defatted soya flour, each at 20% level. The developed MGP had 26.28% protein, 10.13% insoluble dietary fiber and 7.38% soluble dietary fiber. The experiment was designed to optimise the MGP and wheat flour concentration for the development of multigrain biscuits with high protein, dietary fibre and to maximize the acceptability by the application of central composite rotatable design (CCRD) of Response Surface Methodology (RSM). The levels of incorporation of MGP and wheat flour were taken as variables whereas protein, soluble, insoluble fibers, biscuit dough hardness, breaking strength and overall acceptability (OAA) as responses. The optimum level of MGP and wheat flour obtained using numerical optimization was found to be 40 g and 60 g respectively. The biscuits prepared using these had 16.61% protein, 2.57% soluble fibre, and 6.67% insoluble fibre which is significantly (p ≤ 0.05) higher than control biscuit.

Hmo1:A versatile member of the high mobility group box family of chromosomal architecture proteins

Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.

Relationship of High Sensitivity C-Reactive Protein with Cardiovascular, Diabetic, and Hepatic Biomarkers

Biomarkers are early predictors of various disorders, circulating level of C-reactive protein is a sensitive biomarker of systemic inflammation and may also be associated with the development of diabetic, hepatic, and cardiovascular diseases. In the present study, we aimed to investigate the association between circulating levels of high sensitive C-reactive protein (hs-CRP) and various biomarkers for hepatic, diabetic, and cardiovascular health. The retrospective analysis included 438 individuals who were tested for these panels simultaneously at Vibrant America Clinical Laboratory. The study population included free-living individuals without any preexisting clinical conditions. Among the cardiovascular markers, a positive correlation and significant association was found between high levels of hs-CRP and serum levels of triglycerides (r = 0.0964, p −0.1423, p −0.1216, p < 0.0105) with circulating levels of hs-CRP. Among all the diabetic markers, glucose (r = 0.1547, p < 0.0011) and glycated serum protein (r = 0.1725, p < 0.0003) were positively correlated with circulating hs-CRP. In the hepatic panel, AST, a transaminase that plays a vital role in amino acid metabolism, was found to have a strong positive correlation with hs-CRP (r = 0.2139, p < 0.0001). In conclusion, the results clearly show the association of hs-CRP with diabetic, hepatic, and cardiovascular risk factors indicating its central value as a key marker for several lifestyle-associated disorders.

Optimization of High-Protein Glutinous Rice Flour Production Using Response Surface Method

A response surface method was employed to study the effect of α-amylase concentration, hydrolysis temperature and time on the production of high protein glutinous rice flour(HPGRF). The suspension of glutinous rice flour(15%) that contained 6.52% protein was gelatinized and subsequently hydrolyzed by thermostable α-amylase. The hydrolysis yielded 0.144–0.222 g/g HPGRF with 29.4%–45.4% protein content. Hydrolysis time exerted a significant effect, while enzyme concentration and hydrolysis temperature showed insignificant effect on the protein content and production yield of HPGRF. The result of response surface method showed that the optimum condition for the production of HPGRF that contained at least 36% protein was treating gelatinized 15% glutinous rice flour suspension with 0.90 Kilo Novo α-amylase Unit(KNU)/g α-amylase at 80 oC for 99 min. By carrying out the predicted hydrolysis condition, HPGRF with 35.9% protein and 61.8% carbohydrates was resulted. The process yielded 0.172 g/g HPGRF. HPGRF contained higher amount of essential amino acids compared to glutinous rice flour. HPGRF had higher solubility and lower swelling power, and also showed no pasting peak compared with glutinous rice flour.

Dietary high protein-induced diarrhea and intestinal inflammation by activation of NF-kB signaling in piglets

The present study aimed to investigate whether inflammation-associated responses in piglets are induced by high protein(HP)through activating nuclear factor kappa B(NF-κB)signaling.Sixteen piglets(35 d of age,Duroc×[Landrace×Yorkshire],weaned at d 21,initial BW=9.70±0.11 kg)were allocated to 18%and 26%CP(HP group)at random,comprising 8 replicate pens per treatment.The piglets were slaughtered to collect intestinal tissues when apparent,persistent,and stable diarrhea syndromes happened(on d 12).No significant differences were observed in their growth performance(P>0.05),but reduction by 19.11%,25.31%,23.64%of ADFI,ADG,and G:F,respectively was detected in the HP group.The HP group had greater(P=0.002)diarrhea rates.Furthermore,dietary HP had lower ileal villus height(VH;P=0.048),ratio of villus height to crypt depth(VH/CD ratio;P=0.016),and colonic CD(P=0.034),as well as had the trend(P=0.075)to reduce the ileal villus absorptive area.Moreover,HP diets significantly elevated the goblet cell numbers in the ileal villi(P=0.016)and colonic crypts(P<0.001)and up-regulated(P=0.012)the mRNA expression of mucin2(Muc2)in the ileum.In addition,HP diets increased the myeloperoxidase concentration in the ileum(P=0.002)and colon(P=0.007)of piglets.Dietary HP significantly down-regulated the mRNA expression of tumor necrosis factor-α(TNF-α;P<0.001)in the ileum,induced nitric oxide synthase(iNOS;P=0.040)and interleukin-22(IL-22;P=0.008)in the colon,and inclined to down-regulate interleukin-1β(IL-1β;P=0.076)expression in the colon.The relative protein abundance of Galectin-3(P=0.046)in the colon and the ratio of phosphorylation NF-κB to NF-κB(p-NF=κB/NF-κB ratio)in the ileum of HP piglets were also greater(P=0.038).These results suggest that dietary HP may cause diarrhea in piglets by activating NF-icB signaling induced intestinal inflammation.

Expression and Purification of Arabidopsis High Mobility Group B Protein Gene At2G34450 in Pichia pastoris

[Objective] The aim was to study the expression of Arabidopsis gene A/2G34450 in Pichia pastoris and to obtain recombinant Arabidopsis HMGB protein. [Method] The At2G34450 gene was cloned into yeast expression vector pPIC9K containing AOXl promoter and the sequences of secreting α-signal peptides. Recombinant plasmid was linearized by Sal l and transformed into P. pastoris GSl15 competent cells by electroporation. Positive integrated clones were screened out, and the At2G34450 protein was expressed under the induction of methanol. [Result] The At2G34450 protein was expressed in yeast medium through methanol induction. SDS-PAGE results showed that recombination product was At2G34450 protein. [Conclusion] At2G34450 protein was successfully expressed in the P. pastoris system for the first time, which paves a direct path to further research on the functions of HMGB family members.

The Expression and Functional Analysis of the Gene At2G34450 in High Mobility Group B Proteins from Arabidopsis thaliana

[Objective]To better understand the functions of High Mobility Group B （HMGB） proteins in the transcriptional regulation of plant stress responses.[Method]We cloned the At2G33450 gene encoding At2G34450 protein in Arabidopsis thaliana.Binary vectors carrying the above gene were transformed into Arabidopsis to detect the influences of environmental stimuli to transgenic Arabidopsis.[Result] Under salt or drought stress the transgenic Arabidopsis plants over-expressed At2G33450 displayed retarded germination and subsequent growth compared with wild-type plants.[Conclusion]Our results provide a novel basis for understanding the biological functions of HMGB protein family members that differently affect germination and seedling growth of Arabidopsis plants under various stress conditions.

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure

Background The data on the prognostic values of high sensitivity C-reactive protein （hsCRP） levels in patients with advanced symp-tomatic heart failure （HF） receiving cardiac resynchronization therapy （CRT） are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP （〉3 mg/L） prior to CRT was associated with a significant 2.39-fold increase （P=0.006） in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels （–0.5 ± 4.1 mg/L reduction） compared with non-responders （1.7 ± 6.1 mg/L increase, P=0.018）. Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations （Log-rank P〈0.001）. The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.

High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken the immune activity of Treg cells. It is suggested that effectively inhibiting HMGB1 expression could be a feasible way to treat liver failure by suppressing endotoxemia and enhancing Treg cell activity.

Effect on proliferation and apoptosis of retinoblastoma cell by RNA inhibiting high mobility group protein box-1 expression

AIM： To investigate the effect of high mobility group protein box-1 （HMGB1） siRNA on proliferation and apoptosis of retinoblastoma （Rb） cells.METHODS： The expression of HMGB1 in Rb cells were detected by real-time polymerase chain reaction （RT-PCR） and Western blot. Chemically synthesized HMGB1 siRNA was transfected into Y79 cells. The inhibitory rate was also examined by RT-PCR and Western blot. After HMGB1 siRNA transfection, the cell proliferation was analyzed by MTT, and cell apoptosis was detected by Caspase-3 active detection kit. Cell cycle distribution and apoptosis were detected by flow cytometry. RESULTS： The expression of HMGB1 significantly elevated in Rb cells （P〈0.01）. After transfected by siRNA, the HMGB1 protein level of Y79 cells was significantly reduced （P〈0.01）. After siRNA interference HMGB1, the proportion of proliferating cells reduced, and the proportion of quiescent cells increased （P〈0.05）. In addition, apoptosis rate of Y79 cells increased from 2.03% to 9.10% after interfering with HMGB1 siRNA （P〈0.05）.CONCLUSION： Specific HMGB1 siRNA can inhibit the expression of HMGB1. The effect may be attributed to inhibit the proliferation and promote cell apoptosis.

Correlation of Enhancement Degree on Contrast-enhanced Ultrasound with Histopathology of Carotid Plaques and Serum High Sensitive C-Reactive Protein Levels in Patients Undergoing Carotid Endarterectomy

This study was undertaken to investigate the correlation of the enhancement degree on contrast-enhanced ultrasound(CEUS) with the histopathology of carotid plaques and the serum high sensitive C-reactive protein(hs-CRP) levels in patients undergoing carotid endarterectomy(CEA). Carotid CEUS was performed preoperatively in 115 patients who would undergo CEA, and the enhancement degree of the carotid plaques was evaluated by both the visual semiquantitative analysis and the quantitative time-intensity curve analysis. Serum hs-CRP levels were detected using the particle-enhanced immunoturbidimetric assay also before the operation. Additionally, the carotid plaque samples were subjected to histopathological examination postoperatively. The density of neovessels and the number of macrophages in the plaques were assessed by immunohistochemistry. The results showed that among the 115 patients, grade 0 plaque contrast enhancement was noted in 35 patients, grade 1 in 48 patients and grade 2 in 32 patients. The degree of plaque enhancement, the density of neovessels, the number of macrophages, and the hs-CRP levels were highest in the grade 2 patients. Correlation analysis showed that the enhancement degree of the carotid plaques was closely related to the immunohistochemical parameters of the plaques and the serum hs-CRP levels. It was suggested that the carotid plaque enhancement on CEUS can be used to evaluate the vulnerability of carotid plaques.

The prognostic role of high-sensitivity C-reactive protein in patients with acute myocardial infarction

1 Introduction Inflammation is one of the main mechanisms in the pathogenesis of atherosclerosis,and the interest to the evaluation of inflammatory biomarkers in coronary artery disease(CAD)has been increasing over the last decade.[1,2]Destabilization of chronic artery plaques,which leads to acute coronary syndromes,has been associated with inflammatory status.[1,3]。

Relationship between high sensitivity C-reactive protein and angiographic severity of coronary artery disease

Background Coronary artery disease(CAD)remains a leading cause of morbidity and mortality.Cytokines play a potential role in atherosclerosis pathogenesis and progression.We investigated the association between high sensitive C-reactive protein(hs CRP)and severity of CAD.Methods CAD patients were stratified according to hs CRP cut-off value into high levels hs CRP group(≥8.4 mg/L)and low levels hs CRP group(<8.4 mg/L).Severity of CAD was assessed according to artery stenosis degree and the number of vessel involved.Statistical analysis was performed using Statistical Package for the Social Sciences(SPSS,version 23.0).Results The mean age was 60.3±11.0 years.The level of hs CRP was increased and ranged from 0.2 to 1020.0 mg/L.Biochemical risk factors and severity of CAD didn’t show significant differences between the two groups.In multivariate linear analysis,cardiac troponin I(c Tn I)and serum amyloid A(SAA)were predictors of hs CRP.As shown in receiver operating characteristic(ROC)curve analysis performed in patients with ST-segment elevation myocardial infarction(STEMI)and compared to myonecrosis biomarkers,hs CRP(area under the curve(AUC):0.905;95%CI:0.844-0.966;P<0.001)could be a powerful predictor marker in evaluating the infarct size after myocardial infarction but not better than c Tn I.Conclusions Hs CRP levels were not associated with the severity of CAD but could be useful in the evaluation of myocardial necrosis in patients with STEMI.

Novel insights for high mobility group box 1 proteinmediated cellular immune response in sepsis:A systemic review

High mobility group box 1 protein （HMGB1） is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. This systemic review is mainly based on our own work and other related reports HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells （Tregs）, dendritic cells （DCs）, macrophages, and natural killer cells （NK cells）. Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products （RAGE）, Toll-like receptor （TLR）2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors （e.g., ethyl pyruvate） and antagonists （e.g., A box）, can protect against sepsis lethality and give a wider window for the treatment opportunity. HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications.

Inflammatory response and immune regulation of high mobility group box-1 protein in treatment of sepsis

Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein （HMGB1）, are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGBl-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGBl-targeted Chinese herbal therapies in sepsis.

High mobility group box 1 protein(HMGB1)as an immune-modulating factor for polarization of human T lymphocytes

Objective This study was performed to investigate the effect of high mobility group box-1 protein(HMGB1)on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunction.Methods Fresh blood was obtained from healthy adult volunteers and peripheral blood mononuclear cells(PBMCs)were isolated,then rhHMGB1 was added to PBMCs.Four-color flow cytometric(FCM)analysis was used for the measurement of intracellular cytokine including interleukin IL-4 and interferon IFN-?ELISA kits were employed for the determination of IL-2 and sIL-2R protein levels in cell culture supernatants.Results(1)Different stimulating time and dosage of rhHMGB1 did not alter the number of IFN-αpositive cells(Th1).rhHMGB1 stimulation provoked a dose-dependent and time-dependent increase in Th2 subset and decrease in ratio of Th1 to Th2.(2)Compared with the untreated cells,when the cells were coincubated with rhHMGB1(10-100ng/ml)for 12 hrs,protein release of IL-2 and sIL-2R were significantly up-regulated.At 48 hrs,in contrast,protein production was relatively lower in cells after exposure to 100-1000 ng/ml rhHMGB1.Conclusions These findings demonstrated that HMGB1 has a dual influence on immune functions of human T lymphocytes.

Apoptosis induced by a low-carbohydrate and high-protein diet in rat livers

AIM: To determine whether high-protein, high-fat, and low-carbohydrate diets can cause lesions in rat livers.METHODS: We randomly divided 20 female Wistar rats into a control diet group and an experimental diet group. Animals in the control group received an AIN-93 M diet, and animals in the experimental group received an Atkins-based diet(59.46% protein, 31.77% fat, and 8.77% carbohydrate). After 8 wk, the rats were anesthetized and exsanguinated for transaminases analysis, and their livers were removed for flow cytometry, immunohistochemistry, and light microscopy studies. We expressed the data as mean ± standard deviation(sd) assuming unpaired and parametric data; we analyzed differences using the student's t-test. statistical significance was set at P < 0.05.RESULTS: We found that plasma alanine aminotransferase and aspartate aminotransferase levels were significantly higher in the experimental group than in the control group. According to flow cytometry, the percentages of nonviable cells were 11.67% ± 1.12% for early apoptosis, 12.07% ± 1.11% for late apoptosis, and 7.11% ± 0.44% for non-apoptotic death in the experimental diet group and 3.73% ± 0.50% for early apoptosis, 5.67% ± 0.72% for late apoptosis, and 3.82% ± 0.28% for non-apoptotic death in the control diet group. The mean percentage of early apoptosis was higher in the experimental diet group than in the control diet group. Immunohistochemistry for autophagy was negative in both groups. sinusoidal dilation around the central vein and small hepatocytes was only observed in the experimental diet group, and fibrosis was not identified by hematoxylin-eosin or Trichrome Masson staining in either group.CONCLUSION: Eight weeks of an experimental diet resulted in cellular and histopathological lesions in rat livers. Apoptosis was our principal finding; elevated plasma transaminases demonstrate hepatic lesions.

EFFECTS OF SIMVASTAIN COMBINED WITH OMEGA-3 FATTY ACIDS ON HIGH SENSITIVE C-REACTIVE PROTEIN, LIPIDEMIA, ANDFIBRINOLYSIS IN PATIENTS WITH MIXED DYSLIPIDEMIA

Objective To evaluate the effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein(HsCRP), lipidemia, and fibrinolysis in coronary heart disease (CHD) and CHD risk equivalent patients with mixed dyslipi-demia. Methods A randomized, double-blind placebo controlled and parallel group trial was conducted. Patients with CHD and CHD risk equivalents with mixed dyslipidemia were treated with 10 or 20 mg simvastatin for 6-12 weeks. Following with the treatment of patients whose low-density lipoprotein cholesterol (LDL-ch) reaching goal level (< 100 mg/dL) or close to the goal (< 130 mg/dL), while triglyceride (TG) ≥200 mg/dL and < 500 mg/dL, was combined with omega-3 fatty acids (3 g/d) or a placebo for 2 months. The effects of the treatment on HsCRP, total cholesterol (TC), LDL-ch, high-density lipoprotein cholesterol (HDL-ch), TG, lipoprotein (a) [LP (a)], apolipoprotein A1 (apoA1), apolipoprotein B (apoB), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) were investigated. Forty patients finished the study with each group consisting of twenty patients. Results (1) There were significant reductions of HsCRP, TG, TC, and TC/HDL-ch, which decreased by 2.16 ±2.77 mg/L (38.5%), 94.0 ±65.4 mg/dL (31.1%), 13.3 ±22.3 mg/dL (6.3%), 0.78 ±1.60 respectively in the omega-3 fatty acids group (P< 0.01, < 0.001, < 0.05, < 0.05) compared to the baseline. HsCRP and triglyceride reduction were more significant in omega-3 fatty acids group compared to the placebo group (P=0.021 and 0.011 respectively). (2) In the omega-3 fatty acids group, the values and percentage of TG reduction had a significantly positive relation with HsCRP reduction (r=0.51 and 0.45, P=0.021 and 0.047 respectively). Conclusion In CHD and CHD risk equivalent patients with mixed dyslipidemia, dyslipidemia’s therapeutic effect using simvastatin and omega-3 fatty acids may result from not only the combination of lipid adjustment, but also enhancement of their own nonlipid influences.