Inclusion of lignocaine base into a polar lipid formulation--in vitro release, duration of peripheral nerve block and arterial blood concentrations in the rat

BACKGROUND: Slow-release formulations of local anaesthetics may produce nerve blocks of long duration. The present study aimed at investigating the in vitro and in vivo properties of a polar lipid formulation for slow release of lignocaine and the effects on nerve block duration by inclusion of dexamethasone into the system. METHODS: In vitro release of lignocaine from the lipid formulation was studied in a US Pharmacopoeia rotating apparatus. Sciatic nerve blocks were induced in rats by 0.1 ml of test formulations containing lignocaine HCl 20 mg. ml-1 in aqueous solution, lignocaine base 20, 100 or 200 mg. ml-1 in lipid formulation or the last formulation with dexamethasone 0.05, 0.5 or 5 mg. ml-1. The durations of sensory and motor block and the arterial blood concentrations of lignocaine were investigated. RESULTS: In vitro there was a sustained release of lignocaine from the lipid formulation, with 50% release at around 48 h. In vivo lignocaine base 20 mg. ml-1 in lipid formulation produced sciatic nerve blocks of significantly shorter duration than lignocaine HCl 20 mg. ml-1 in aqueous solution, while lignocaine base 100 and 200 mg. ml-1 in lipid formulation produced blocks lasting two and three times longer, respectively, than the lignocaine HCl solution. Addition of dexamethasone did not affect the duration of nerve block. Following administration of lignocaine base 200 mg. ml-1 in lipid formulation, as compared to lignocaine HCl 20 mg. ml-1 in aqueous solution, the maximal blood concentration of lignocaine was only three times higher in spite of the ten-fold difference in dose, and the mean terminal half-life was three times longer, reflecting the slow release from the formulation. CONCLUSIONS: Our findings indicate that lignocaine base in polar lipids acts as a slow-release preparation of local anaesthetic both in vitro and in vivo.     

糖基化终产物对培养大鼠主动脉平滑肌细胞二酰基甘油的影响

目的:研究糖基化终产物(AGEP)对主动脉平滑肌细胞信号转导环节之一二酰基甘油(Dia)的影响和维生素E、氨基胍对Dia水平的干预作用.方法:采用放射酶标记、薄层层析、放射自显影技术测定细胞中Dia含量.结果:AGEP-BSA孵育的平滑肌细胞Dia水平在15 s和10min出现两个峰值,对照组和AGEP-BSA 50,11,200 mg·L~(-1)作用SMC的Dia水平分别为(220 ±15)pmol~(-1),(328±15)pmol·L~(-1),(662±33)pmol·L~(-1)和(940±43)pmol·L~(-1). Dia水平也随AGEP-BSA糖基化的程度和修饰BSA的糖浓度增加而增高.维生素E和氨基胍可明显减弱AGEP刺激平滑肌细胞Dia水平升高的效应.结论:AGEP-BSA能升高培养的大鼠血管平滑肌细胞中的Dia水平,维生素E和氨基胍能明显抑制这一效应.     

Digestion and absorption

Carbohydrates are digested by salivary and pancreatic amylases to di-, tri- and oligosaccharides, and then to monosaccharides by enzymes on the wall of the small intestine to allow them to be absorbed. Proteins are absorbed as amino acids and small peptides that are broken down to amino acids within the cells. Monosaccharides and amino acids pass into the liver via the portal vein. Fats are digested and absorbed as free fatty acids and glycerides that are then mostly reconstituted as triglycerides in the mucosal cells of the small intestine. They combine with phospholipids and a protein to form chylomicrons, which pass via the lymphatics and the thoracic duct into the systemic circulation. Fatty acids are re-esterified and stored as triglycerides in adipose tissue or oxidized for energy. Water is passively absorbed due to the osmotic gradient that results mainly due to the active absorption of sodium ions.     

Concentrations of iron,copper and zinc in human milk and powdered infant formula

Concentrations of iron, copper and zinc were determined in 56 samples of mature human milk from Canarian women and 5 samples of powdered infant formula. According to the literature our data fall within the normal limits in each kind of milk. The mean concentration of Fe, Cu and Zn of powdered infant formula was significantly higher than those concentrations found in the human milks. Significant differences among the concentrations of the studied metals for the milks of considered mothers were observed. The Fe, Cu and Zn intakes of infants fed with human milk are lower than the requirements recommended by the Food and Nutrition Board (1989). However, the infants fed with powdered infant formula had consumed an adequate intake of Fe and Cu. A progressive decrease of the metal concentrations with the lactation stage was observed. The human milk obtained in spring presented Fe and Zn concentrations lower than in autumn, which could be due to changes in nutritional habits of the mothers. Age of mother and number of previous children seem to influence the Zn and Cu concentrations of human milk.     

Advanced glycosylation end products increase diacylglycerol levels in cultured human umbilical vein endothelial cells

Ｍｅｔｈｏｄｓ　ＴｈｅｅｆｆｅｃｔｓｏｆＡＧＥＰｏｎＤｉａｌｅｖｅｌｓｉｎｃｕｌｔｕｒｅｄＨＵＶＥＣｗｅｒｅｓｔｕｄｉｅｄｗｉｔｈｒａｄｉｏ ｅｎｚｙｍａｔｉｃａｓｓａｙ Ｑｕａｎｔｉｔａｔｉｖｅｍｅａｓｕｒｅｍｅｎｔｓｏｆ32 Ｐｐｈｏｓｐｈａｔｉｄｉｃａｃｉｄｗｅｒｅａｃｈｉｅｖｅｄｂｙｔｈｉｎ ｌａｙｅｒｃｈｒｏｍａｔｏｇｒａｐｈｙａｎｄａｕｔｏｒａｄｉｏｇｒａｐｈｙ Ｒｅｓｕｌｔｓ　ＴｈｅＤｉａｌｅｖｅｌｓｉｎＨＵＶＥＣｓｗｅｒｅｉｎｃｒｅａｓｅｄｂｙＡＧＥＰｍｏｄｉｆｉｅｄｂｏｖｉｎｅｓｅｒ…     

Estimating relative diglyceride to triglyceride content with localized MRS at 3 T

It has been previously shown that the MRS sequence stimulated echo acquisition mode (STEAM; mixing time, TM = 20 ms) with an echo time (TE) of 100 ms resolves triglyceride glycerol resonances from that of water at 3 T. The purpose of this work is to determine if STEAM with a TE of 100 ms facilitates relative quantification of diglyceride/triglyceride levels at 3 T. Spectra were obtained from tricaprylin (triglyceride) and dicaprylin (diglyceride) with a range of STEAM TE values (TM = 20 ms). TE values that resulted in two resolved glycerol resonances for triglycerides (rendering them suitable for distinguishing triglyceride contributions from those of diglycerides) were selected. One resonance resides in the 3.85–4.2 ppm spectral range (overlapping the 1,3-diglyceride resonance) and the other in the 4.2–4.6 ppm spectral range (overlapping one of the 1,2-diglyceride resonances). STEAM with TE values of 40 ms and 100 ms (TM = 20 ms) yielded two resolvable triglyceride resonances (tricaprylin phantom), at about 4 ppm and 4.4 ppm. Direct integration of the resonances showed that the former peak has 0.86 and 0.17 times the area of the latter for TE = 40 ms and 100 ms, respectively. Spectra obtained from the phantoms containing mixtures of diglyceride (1,3-dicaprylin) and triglyceride (tricaprylin) were acquired. The triglyceride contribution to the 4 ppm glycerol resonance, a mixture of signal from 1,3-diglyceride and triglyceride, can be approximated from the area of the 4.4 ppm peak, resulting in an estimate of the 1,3-diglyceride contribution. Analysis was performed for STEAM TE = 40 ms and TE = 100 ms spectra acquired from phantoms with 1,3-dicaprylin/tricaprylin weight/weight contents of 2.5%/97.5%, 5%/95%, 10%/90% and 20%/80%. Concentration ratios of 1,3-dicaprylin/tricaprylin estimated with both STEAM TE values resulted in linear correlations with expected concentration ratios (R² > 0.99).     

Lipid composition of metacestodes of Taenia taeniaeformis and lipid changes during growth

A lipid analysis was performed on developing metacestodes of Taenia taeniaeformis removed from the livers of rats at times varying from 3 to 35 weeks post infection. Lipid accounted for 7–21% of the dry weight of the parasites. The highest proportions were found at the earlier stages. The distribution was as follows; neutral lipid 27–45%; glycolipid 5–11%; and phospholipid 50–61%. The major neutral lipid was cholesterol, and minor neutral lipids were sterol esters, triglycerides, diglycerides and monoglycerides. Hydrocarbons were present throughout development, but in the highest amounts at the earlier stages. Five different glycolipids were found, all of which were identified as glycosphingolipids. An increase in the proportion of more complex glycolipids was noted as parasites grew older. Ten different phospholipids were identified, with the major components being phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Other phospholipids were: lysophosphatides, phosphatidylinositol, phosphatidic acid, diphosphatidylglycerol, sphingomyelin, and an unknown phospholipid component. Changes in the relative amounts of the two major phospholipids were found when the early and late stages were compared. Two lipids found throughout development were identified as glycosylated dolichol phosphates, and they comprised between 1 and 3% of the total phospholipid fraction. Nineteen fatty acids were detected, and the fatty acid distribution for each lipid class at each stage was determined. Seven major fatty acids were common to each. These were: hexadecanoic, octadecanoic, oleic, linoleic, arachidonic, docosanoic, and docosahexaenoic.     

The mechanism and regulation of fat mobilization from adipose tissue: desnutrin, a newly discovered lipolytic enzyme

A new member of a family of proteins functioning in the regulation of lipolysis in adipose tissue has been discovered and named "desnutrin." Desnutrin is transiently induced by fasting and decreased by re-feeding. A close homolog, termed adiponutrin, has the opposite expression pattern, being induced by feeding and disappearing upon fasting. Desnutrin functions by acting as the first enzyme in lipolysis, hydrolyzing triglycerides to diglycerides, whereas the well-known hormone-sensitive lipase takes the diglycerides to monoglycerides and on to free fatty acids.     

Neutral lipids of frog and rat rod outer segments

Neutral lipids of rod outer segments (ROS) from frog and rat comprise roughly 10 mol% of the total lipids and consist of free sterol, free fatty acids, and 1,2-diglycerides, but contain no detectable sterol esters or triglycerides. Expressed as nmol per mg ROS protein, the levels of both free fatty acids and free sterol are higher in the rat than in the frog, whereas the diglycerides in frogs are about four times higher than in rats. The level of 22:6 omega 3 in the free fatty acids fraction of the frog is twice that of the rat, although the level of 22:6 omega 3 in both the frog and rat free fatty acids is lower than in any of the glycerolipids. The diglyceride fraction from both animals consists almost entirely of two molecular species: in the frog, the C-38 and C-40 type predominate in a molar distribution of 52 and 42% respectively, whereas in the rat, the C-36 and C-38 types are most abundant in a molar distribution of 28 and 60%, respectively. Comparison of the diglyceride fatty acid and molecular species compositions with those of phosphatidylinositol and phosphatidic acid led to the suggestion that ROS diglycerides are derived from phosphatidylinositol.