Metabolism of a lipid nanoemulsion resembling low-density lipoprotein in patients with grade III obesity

Introduction: Obesity increases triglyceride levels and decreases high-density lipoprotein concentrations in plasma. Artificial emulsions resembling lipidic plasma lipoprotein structures have been used to evaluate low-density lipoprotein metabolism. In grade III obesity, low density lipoprotein metabolism is poorly understood. Objective: To evaluate the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of patients with grade III obesity by the fractional clearance rate. Methods: A low-density emulsion was labeled with [14C]-cholesterol ester and [³H]-triglycerides and injected intravenously into ten normolipidemic non-diabetic patients with grade III obesity [body mass index higher than 40 kg/m²] and into ten non-obese healthy controls. Blood samples were collected over 24 hours to determine the plasma decay curve and to calculate the fractional clearance rate. Results: There was no difference regarding plasma levels of total cholesterol or low-density lipoprotein cholesterol between the two groups. The fractional clearance rate of triglycerides was 0.086 ± 0.044 in the obese group and 0.122 ± 0.026 in the controls (p = 0.040), and the fractional clearance rate of cholesterol ester (h-1) was 0.052 ± 0.021 in the obese subjects and 0.058 ± 0.015 (p = 0.971) in the controls. Conclusion: Grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower.

Effect of a cholesterol-rich diet on the metabolism of the free and esterified cholesterol components of a nanoemulsion that resembles LDL in rabbits

We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1 percent cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with ³H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h-1) was considerably greater than CE-FCR (0.046 ± 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580 percent/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319 percent/g) was greater than CE uptake (0.0595 ± 0.0207 percent/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.

Isoflurano em emulsão lipídica por via venosa promove estabilidade cardiovascular respiratória em modelo experimental / Intravenous isoflurane in lipid emulsion promotes cardiovascular and respiratory stability. Experimental model

JUSTIFICATIVA E OBJETIVOS: A administração venosa de anestésico inalatório pode causar lesão pulmonar. Halotano em solução lipídica por via venosa promove anestesia com estabilidade hemodinâmica e respiratória. Esta pesquisa procurou estabelecer a dose de indução para emulsão lipídica de isoflurano a 10 por cento e observar as condições cardiovasculares e respiratórias, em anestesia experimental. MÉTODO: Sete porcos machos foram selecionados. Os animais receberam infusão de propofol para as preparações cirúrgicas invasivas: dissecção de artéria femoral e veia jugular, sensor de ecodopplercardiografia no esôfago. Foram registrados freqüência cardíaca (FC), eletrocardiograma (ECG), pressão arterial sistólica (PAS), diastólica (PAD), média (PAM), venosa central (PVC), índice cardíaco (IC), débito cardíaco (DC) e índice bispectral (BIS). As frações inspirada e expirada dos gases respiratórios foram analisadas continuamente. Iniciada infusão da emulsão lipídica de isoflurano até o índice bispectral atingir valor de 40 ± 5 (BIS40). Os animais foram mantidos anestesiados e submetidos a laparotomia exploradora para sutura gástrica. RESULTADOS: O volume total infundido para atingir BIS40 foi 25,6 ± 11,2 ml (2,56 ml de isoflurano). O tempo médio para atingir BIS40 foi 15,6 ± 6,9 minutos. Maior velocidade de infusão reduziu o tempo para os animais atingirem BIS40. Condições cardiovasculares e respiratórias mostraram-se estáveis durante a experimentação. A freqüência cardíaca aumentou com a elevação da fração expirada do isoflurano. CONCLUSÕES: A infusão venosa do isoflurano em solução emulsificada promoveu diminuição do índice bispectral, estabilidades hemodinâmica e respiratória e correlação direta com sua fração expirada. O uso do isoflurano em emulsão lipídica pode se constituir em modalidade segura de aplicação deste anestésico.

Cinética plasmática de uma emulsão lipídica que se liga aos receptores da lipoproteína de baixa densidade - em pacientes com doença arterial coronariana / Plasma kinetics of a lipidic emulsion that binds to low-density lipoprotein receptors in patients with coronary artery disease

A cinética plasmática de uma emulsão lipídica, que se liga aos receptores de LDL, foi estudada em 23 pacientes com Doença Arterial Coronariana (DAC) e em 16 indivíduos sadios (não apresentaram lesões obstrutivas, nem irregularidades, após serem submetidos à cineangiocoronariografia). Foram selecionados 39 participantes, sendo 30 do sexo masculino e 9 do sexo feminino, na faixa etária de 30 a 84 anos, com Índice de Massa Corpórea (IMC) entre 21 e 41 (Kg/m²), divididos em 2 grupos: DAC e Sadio. Após jejum de 12 horas, foram coletadas amostras de sangue total para determinação dos níveis séricos de lipídios e apolipoproteínas. A seguir foram injetadas, endovenosamente, emulsões com marcação radioativa, constituídas por lipídes puros (40 mg), trioleína (TG) 1 mg, oleato de colesterol (CE) 20 mg, colesterol (CL) 0,5 mg e os isótopos radioativos `ANTPOT. 14Cï-oleato de colesterol e ANTPOT. 3Hï-colesterol...

Clearance of a chylomicron-like emulsion from plasma is delayed in patients with coronary artery disease

To determine whether the metabolism of chylomicrons and their remmants is related to atherogenesis, a triglyceride-rich emulsion known to mimic chylomicron behavior in plasma and labeled with 1-14C-cholesteryl oleate was injected intravenously into 11 normolipidemic patients (triglycerides: 133 + or - 60 mg/dl; total cholesterol: 207 + or - 20 mg/dl; LDL: 143 + or - 20 mg/dl; VLDL: 27 + or - 13 mg/dl; and HDL cholesterol: 41 + or - 11 mg/dl; apo AI: 1.27 + or - 0.54 g/l and apo B: 1.42 + or - 0.31 gl) with atherosclerotic coronary artery disease and into 11 control subjects (triglycerides: 109 + or - 32 mg/dl; total cholesterol: 190 + or - 38 mg/dl; LDL: 125 + or - 29 mg/dl; VLDL: 22 + or - 6 mg/dl; and HDL cholesterol: 44 + or - 9 mg/dl; apo AI: 1.09 + or - 0.28 g/land apo B: 1.09 + or - 028 g/l) without the disease. The emulsion (69 percent triolein, 23 percent lecithin, 6 percent cholesteryl oleate and 2 percent cholesterol) was injected intravenously at approximately 9:00 a.m., after a 12-h fast. The clearance of the emulsion label from plasma, expressed as fractional clearance rate (FCR), was lower in coronary artery disease compared to controls (0.019 + or - 0.005/min vs 0.036 + or - 0.018/min, respectively, P<0.05). These results indicate that the rate of removal of chylomicron remmants is slower in patients with coronary artery disease

Increased plasma removal of microemulsions resembling the lipid phase of low-density lipoproteins (LDL) in patients with acute myeloid leukemia: a possible new strategy for the treatment of the disease

A microemulsion of lipid composition resembling low-density lipoprotein (LDL), but devoid of apolipoproteins and labeled with [14C]-cholesteryl oleate was injected into 16 healthy subjects and into 15 patients with acute myeloid leukemia (AML). Removal from plasma of the lipid label was higher in the leukemic group compared to healthy subjects in terms of fractional clearance rate (0.185 +/- 0.205 and 0.080 +/- 0.030 h-1, respectively, P < 0.03). When the emulsion was again injected into 10 of the AML patients after complete hematological remission, the fractional clearance rate of cholesteryl ester was reduced to one third of the value observed prior to treatment (0.061 +/- 0.038 h-1) and was not different from that obtained for the healthy subjects. Also, in untreated AML patients, serum LDL-cholesterol levels inversely correlated with the values of fractional clearance rate of the microemulsion. This correlation was no longer observed after treatment. These data suggest that the LDL-like microemulsion was selectively taken up by the neoplastic cells presumably by interaction with LDL receptors. Therefore, microemulsions may function as potential carriers for anticancer drugs that are targeted to tumor cells for patients with acute myeloid leukemia. Unlike native LDL, microemulsions are suitable for utilization in routine clinical practice

Factors affecting diazepam availability from intravenous admixture solutions

Foram estudadas as variaçöesaçöes de concentraçäo do diazepam diluído em diferentes solventes e frascos, para emprego endovenoso contínuo. Foram feitas soluçöes em soro fisiológico (NS) e soro glicosado a 5% (G5w), frascos de vidro ou de polietileno (PE), volume total de 500ml, concentraçäo inicial de dizepam de 200 ug/ml. Cada frasco foi conectado a equipo de polivinilcloreto (PVC) e as soluçöes foram infundidas a razäo de 30 ml/h. Amostras coletadas dos frascos e dos equipos até 12 horas de infusäo foram testadas em triplicata, por expectrofotometria ultravioleta. O maior decréscimo da concentraçiao de diazepam ocorreu em todos os frascos aos 30 minutos de infusäo, com concentraçöes 63,5% (G5W vidro), 55% (G5W PE), 60,5% (NS vidro) e 58% (NS PE) da concentraçäo inicial. As concentraçöes nos frascos de vidro e PE permaneceram constantes. A diminuiçäo das concentraçöes de diazepam deve-se a adsorçäo do diazepam aos equipos de PVC e essa perda deve ser levada em conta durante seu emprego em situaçöes clínicas graves como status epilepticus, tétano e eclâmpsia