Increased muscular triglyceride content and hyperglycemia in Goto-Kakizaki rat are decreased by egg white hydrolysate

We investigated the fat metabolic characteristics in non-obese and diabetic Goto-Kakizaki (GK) rat and the effects of dietary egg white hydrolysate (EWH) on glucose and fat metabolism. Wistar (W) and GK (G) rats were placed into dietary casein (WC and GC) or EWH (WE and GE) group, and fed their respective diet for six weeks. Triglyceride (TG) content and stearoyl-CoA desaturase (SCD) indices in the soleus muscle were higher in the GC group than WC group in parallel with worsening serum glucose metabolic parameters. The glucose metabolic parameters were significantly improved in the GE group. The TG accumulation and SCD indices in the soleus muscle were also significantly lower in the GE group than in the GC group. In conclusion, dietary EWH not only improved glucose metabolism but also reduced both TG accumulation and SCD indices in the soleus muscle of GK rat.     

Pharmacokinetic aspects and in vitro–in vivo correlation potential for lipid-based formulations

Lipid-based formulations have been an attractive choice among novel drug delivery systems for enhancing the solubility and bioavailability of poorly soluble drugs due to their ability to keep the drug in solubilized state in the gastrointestinal tract. These formulations offer multiple advantages such as reduction in food effect and inter-individual variability, ease of preparation, and the possibility of manufacturing using common excipients available in the market. Despite these advantages, very few products are available in the present market, perhaps due to limited knowledge in the in vitro tests (for prediction of in vivo fate) and lack of understanding of the mechanisms behind pharmacokinetic and biopharmaceutical aspects of lipid formulations after oral administration. The current review aims to provide a detailed understanding of the in vivo processing steps involved after oral administration of lipid formulations, their pharmacokinetic aspects and in vitro in vivo correlation (IVIVC) perspectives. Various pharmacokinetic and biopharmaceutical aspects such as formulation dispersion and lipid digestion, bioavailability enhancement mechanisms, impact of excipients on efflux transporters, and lymphatic transport are discussed with examples. In addition, various IVIVC approaches towards predicting in vivo data from in vitro dispersion/precipitation, in vitro lipolysis and ex vivo permeation studies are also discussed in detail with help of case studies.KEY WORDS: Pharmacokinetics, Lipolysis, IVIVC, Efflux transporters, Lymphatic delivery, Food effectAbbreviations: ADME, absorption/distribution/metabolism/elimination; AUC, area under the curve; BCS, biopharmaceutics classification system; BDDCS, biopharmaceutics drug disposition classification system; CACO, human epithelial colorectal adenocarcinoma cells; C_max, maximum plasma concentration; CMC, critical micellar concentration; CYP, cytochrome; DDS, drug delivery systems; FaSSGF, fasted-state simulated gastric fluid; FaSSIF, fasted-state simulated intestinal fluid; FeSSIF, fed-state simulated intestinal fluid; GIT, gastrointestinal tract; IVIVC, in vitro in vivo correlation; LCT, long chain triglyceride; LFCS, lipid formulation classification system; log P, n-octanol/water partition coefficient; MCT, medium chain triglyceride; MDCK, Madin–Darby canine kidney cells; NCE, new chemical entity; P-app, apparent permeability; P-gp, permeability glycoprotein; SCT, short chain triglyceride; SEDDS, self-emulsifying drug delivery system; SIF, simulated intestinal fluid; SMEDDS, self-microemulsifying drug delivery system; SNEDDS, self-nanoemulsifying drug delivery system; Vit E, vitamin E     

泌尿系统结石成分谱及与血清TG、TC及PGE2水平的相关性

目的分析泌尿系统结石成分谱及与血清三酰甘油(TG)、总胆固醇(TC)及前列腺素E2(PGE2)水平的相关性。方法选取2015年5月至2018年12月于该院就诊的肾结石患者1875例为患者组,选取同期于该院体检合格的健康者83例为对照组。在征得受试者同意的前提下,分别于进入研究队列时刻(T0)及治疗后即入选后第90天(T1)对受试者进行血液标本采集(对照组仅采集T0时的血液标本),采用酶联免疫吸附测定(ELISA)检测血清TG、TC及PGE2水平。结果1875例患者中1677例患者的主要结石成分为草酸钙;主要结石成分为磷酸磷灰石的患者为117例;主要结石成分为尿酸的患者55例;主要结石成分为磷酸镁铵的患者23例;主要结石成分为胱氨酸的患者3例。不同结石成分患者24h尿量及尿pH值比较,差异均无统计学意义(P>0.05)。患者组和健康组血清TG、TC及PGE2水平比较,差异均有统计学意义(P<0.05)。患者组T0和T1的血清TG、TC及PGE2水平比较,差异均有统计学意义(P<0.05)。以治疗后水平为基线,血清TG、TC及PGE2水平均存在两两间的正相关(P<0.05)。草酸钙结石患者肾组织标本切片的HE染色显示,肾小管有扩张表现,且多数肾小管中存在草酸钙结晶或结晶团块。结论荆门地区泌尿系统结石成分以草酸钙为主,血清TG、TC及PGE2水平有助于泌尿系统结石的诊断;相比于其他结石成分,草酸钙结石对肾组织损伤更为明显。     

甘油三酯介导途径与冠心病的因果联系：直接还是间接？

胆固醇作为冠心病的独立危险因素已为基础研究及临床研究所证实，而廿油二三酯与冠心病之间的关系却颇具争议．2010年5月发表在《柳叶刀》（Lancet）杂志的一项大规模协同分析研究表明：甘油三酯渊控基因载脂蛋门A5（APOA5）-113IT〉C多态性与甘油三酯浓度、冠心病风险显著相关；甘油三酯介导途径与冠心病问存在凶果联系．然而，该研究采川的盂德尔随机化方法受到了遗传关联研究的限制．不足以全面真实地反映甘油三酯与冠心病的闭果联系。针对这一问题，我们提出了不同的见解，认为甘油三酯与冠心病问的因果联系有待于进一步验汪．外得到了作者的认可。     

A 90-day ad libitum administration toxicity study of oligoglucosamine in F344 rats.

A 90-day ad libitum administration toxicity study of oligoglucosamine (OG) was carried out using F344 rats of both sexes. The animals were divided into four groups of 20 animals each, 10 of each sex, and fed a diet containing 0, 0.04, 0.2 or 1.0 (w/w)% OG. During the administration period, no animals of either sex died or exhibited abnormal signs in the 0.04% OG and 0.2% OG groups. In the 1% OG group, in both sexes, erythema and swelling of the snout and forelimbs and loss of fur in the forelimbs were observed. On macroscopic observation, emaciation, swelling of the snout, auricles and forelimbs and alopecia of the forelimbs were also observed in 2-3 males of the 1% OG group. It was suggested that these topical abnormalities might be due to dermal responses to OG adhering to the skin and fur, which are easily soiled with saliva during grooming. In the animals of the 1% OG group, food consumption decreased, resulting in body weight gain being suppressed. This was found concomitantly with the abnormal findings mentioned above. Thus, feeding difficulties due to the topical lesions on the snout and forelimbs were thought to affect body weight. In hematology, platelet count, lymphocyte count and differential neutrophil count increased in males of the 1% OG group. These changes might be related to the dermal inflammation. Abnormalities in urinalysis and blood chemistry, as well as a small thymus, small spleen, dark spots or areas on the glandular stomach mucosa, pale Harderian glands and small testes in histopathology, were also observed in males in the 1% OG group. Whether or not all these changes were related only to the malnutrition remains to be elucidated. From these results, OG gave rise to no adverse effects in rats up to the dose level of 0.2 (w/w)%. Thus, the no observed adverse effect level was determined to be 0.2 (w/w)% for rats of either sex (124.0mg/kg/day in males, 142.0mg/kg/day in females).     

One-year chronic toxicity of madder color in F344 rats – Induction of preneoplastic/neoplastic lesions in the kidney and liver

To evaluate chronic toxicity of madder color (MC), a natural food colorant extracted from the roots of Rubia tinctorum L., F344 rats were fed diet containing 0%, 0.2%, 1.0% or 5.0% MC for 53 weeks. Hematological changes including anemia and serum biochemical alterations indicating hepatotoxicity were demonstrated at 5.0% in both sexes. Relative weights of the liver were significantly increased from 1.0% in both sexes, and those of the kidney were significantly increased from 1.0% in males and from 0.2% in females. Histopathologically, atypical renal tubule hyperplasias were increased at 1.0% or higher in both sexes in association with increase of cell proliferative activity in the tubules. A renal cell adenoma was observed in a male rat receiving 5.0% MC. In addition, glutathione S-transferase placental form-positive liver cell foci were significantly increased at 5.0% in both sexes. These results indicate that MC has chronic toxicity targeting kidney, liver and blood cells. Moreover, the results strongly suggest that MC may have the carcinogenic potential in the kidney and the liver.     

中链甘油三酯干预对2型糖尿病血脂和血浆游离脂肪酸的影响

目的探讨中链甘油三酯(MCT)干预对2型糖尿病(T2DM)患者体重、血脂和血浆游离脂肪酸的影响。方法以长链甘油三酯(LCT)为对照,将所有T2DM患者分为MCT组、MCT/LCT组和LCT组,在控制总能量和脂肪摄入量的基础上,3组分别连续食用100%MCT油、50%MCT油 50%LCT油和100%LCT油12周。在0、6和12周时检测血浆总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(ApoA1)和载脂蛋白B(ApoB)浓度以及血浆游离脂肪酸浓度。计算体质指数(BMI)、LDL/HDL、ApoA1/ApoB、总游离脂肪酸(TFFA)、长链饱和脂肪酸(LCSFA)和不饱和脂肪酸(USFA)浓度。结果在6和12周时,MCT和MCT/LCT组的体重和BMI均较LCT组低(P<0.05)。在12周时MCT/LCT组的TC水平较LCT组低(P<0.05)。与实验前相比,MCT/LCT组6和12周时的LDL-C水平均显著下降(P<0.05);与6周时相比,MCT组12周时的LDL-C水平显著下降(P<0.05)。12周时LCT组的HDL-C水平较MCT组高(P<0.05)。与MCT组相比,LCT组的LCSFA水平在6周时显著升高(P<0.05)。3组的TFFA和USFA水平差异无显著性。结论在控制总能量和脂肪摄入量的基础上,用MCT取代100%或50%的膳食油脂,患者的BMI和血脂谱得到改善,而血浆游离脂肪酸无明显变化。     

The Effect of MCT Oil Supplement in Very Low Birth Weight Infants, with Evaluation by the 13C-Labeled MCT Breath Test

We studied the efficacy of medium-chain triglyceride (MCT) as an energy source in premature infants. Infants who were given 3 g/kg/day of MCT oil gained body weight better than the control group in spite of a smaller water intake. This is advantageous to premature infants who need water restriction due to patent ductus arteriosus (PDA), bronchopulmo nary dysplasia (BPD), etc. We also proved that MCT oil is rapidly absorbed and digested, by means of the ¹³C-trioctanoin breath test.     

Cholesteryl ester transfer protein facilitates the movement of water-insoluble drugs between lipoproteins: a novel biological function for a well-characterized lipid transfer protein

This review article addresses the recently discovered finding that cholesteryl ester transfer protein (CETP) can facilitate the transfer of water-insoluble drugs between different lipoprotein subclasses. This protein, which is often referred to as lipid transfer protein I (LTP I), is involved in the lipid regulation of lipoproteins. It is responsible for the facilitated transfer of core lipoprotein lipids, cholesteryl ester and triglycerides, and approximately one-third of the coat lipoprotein lipid, phosphatidylcholine, between different plasma lipoproteins. The human body appears to recognize exogenous water-insoluble drugs as lipid-like particles, which suggests that these compounds may interact with lipoproteins just like endogenous plasma lipids, and thus their transfer between lipoproteins may be facilitated by plasma CETP. Patients with a variety of diseases (i.e. diabetes, cancer, AIDS) often exhibit hypo- and/or hypercholesterolemia and triglyceridemia, commonly referred to as dyslipidemias, which result in changes in their plasma lipoprotein-lipid composition and concentration. The interaction of water-insoluble drugs with these dyslipidemic lipoproteins may be responsible for the differences seen in the pharmacokinetics and pharmacodynamics of the drug within different diseased patient populations. It is possible that these differences may be linked to the ability of CETP to transfer these compounds from one lipoprotein to another. This review examines the current understanding of the relationship between CETP activity and the lipoprotein distribution of a number of compounds (e.g. amphotericin B and cyclosporine A). It further suggests that additional research will expand our understanding of the role of CETP to explain other functions in lipophilic drug distribution and metabolism.