Changes in redox ratio and protein glycation in precataractous lens from fructose-fed rats: effects of exogenous L-carnitine.

1. Rats fed high dietary fructose are documented to form an acquired model of insulin resistance. The present study measured the effects of administration of L-carnitine (CA) on lens protein glycation, oxidative stress and redox homeostasis in rats fed a high-fructose diet. 2. Animals were divided into four groups: (i) an untreated control group (fed starch diet); (ii) an untreated fructose-group (fed a high-fructose diet); (iii) a CA-treated (300 mg/kg per day), fructose-fed group; and (iv) a CA-treated, starch-fed group. After 60 days treatment, lenses were dissected and multiple oxidative stress markers, glycation of proteins and the ratio of oxidized to reduced glutathione (GSSG/GSH) were determined. 3. A significant decline in enzyme and non-enzyme anti-oxidants and an increase in lipid peroxidation products, protein oxidation, protein glycation, GSSG/GSH ratio and aldehyde formation were observed in lens samples obtained from fructose-fed rats. Administration of CA to fructose-fed rats significantly attenuated oxidative damage and protein glycation and returned levels of anti-oxidants to near those seen in the control group. 4. The results of the present study indicate that dietary fructose disturbs lens integrity and exogenous CA may safeguard the lens by preventing glycation and oxidative stress.

Effects of L-carnitine on RBC membrane composition and function in hyperinsulinemic rats.

The purpose of the study was to investigate the effects of L-carnitine (CA) on the susceptibility of erythrocyte (RBC) to peroxide-induced lipid oxidation, RBC membrane composition, ATPases activity and oxidative stress in fructose-fed hyperinsulinemic rats. The rats were subjected to experimental hyperinsulinemia and hyperglycemia by feeding a high fructose diet (60 g/100 g) for 6 weeks. The rats showed significant alterations in the RBC membrane composition. The protein content was lower than control animals, while cholesterol, phospholipids and free fatty acids were higher in fructose-fed animals. Significant differences in the total carbohydrate and relative proportions of hexose, hexosamine, sialic acid and fucose of membranes were observed. In these rats, membrane-bound ATPases (total ATPase, Na+, K+ ATPase, Mg2+ and Ca2+ ATPases) were significantly lower while thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LHP) in RBC membrane were significantly higher than those of control rats. The red cells were more susceptible to peroxide-induced oxidative stress that correlated with reduced levels of vitamin E found RBC membrane. When fructose-diet fed rats were treated simultaneously with CA (300 mg/kg b.w/day, i.p.), such alterations in membrane composition and enzyme activities did not occur. Effects of fructose loading on lipid peroxidation was also alleviated by CA. These findings suggest that high levels of dietary fructose is detrimental to RBC membrane integrity and that CA may have membrane stabilizing effects in this diet-induced model of type 2-diabetes.

Biochemical assessment of cholelithiasis.

Bile and serum were analysed in 45 cases of cholelithiasis and 25 control subjects for cholesterol, phospholipids, bilirubin, alkaline phosphatase and LCAT activity. Serum phospholipids were found to be elevated in sixty percent of cases, whereas phospholipids in bile were found to be decreased. Serum alkaline phosphatase and alanine aminotransferase were normal. Serum and bile LCAT activity was found to be significantly depressed.

Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery.

The pharmacokinetic parameters of buprenorphine (BN) after a single bolus dose of 10 microg/kg i.v. was investigated in 6 male patients whose age averaged 59+/-9.8 years and body weight of 65.8+/-5.7 kg undergoing coronary artery bypass graft surgery (CABG). The unbound BN plasma concentrations were detected using ultrafiltration and high performance liquid chromatography/electro-chemical detection (HPLC/ECD) method. During cardiopulmonary bypass (CPB) there was a fall in BN plasma concentrations, observations similar to reports on fentanyl, sufentanil and alfentanil. This is probably due to haemodilution, hypothermia and hydrophobic sequestration of drug on to the CPB tubing. After CPB the concentrations rose to values higher than during CPB, though it did not attain pre CPB concentrations. These variations were not statistically significant indicating that plasma levels were adequately stable during CPB. The plasma concentration time curves were biexponential and the pharmacokinetic parameters obtained were : distribution half-life 37.24+/-6.57 min, elimination half-life 482.69+/-79 min, clearance 1221.97+/-209.42 ml/min, and volume of distribution 736.46+/-71.25 L. BN in the dose used follows the pharmacokinetic pattern of other commonly used narcotics during CABG. The mean +/- SEM plasma BN concentration during CPB was 0.51+/-0.03 ng/ml which was adequate for the maintenance of analgesia and anaesthesia, as none of our patients expressed the signs and symptoms of awareness during surgery. Further, unlike the other narcotics muscle rigidity was absent. Thus BN is a safe and good alternative to other narcotics for patients undergoing CABG.

Compliances of human rib cage and diaphragm-abdomen pathways in relaxed versus paralyzed states.

The respiratory magnetometer method of Konno and Mead was used to measure separately the rib cage and the diaphragm-abdomen components of the total respiratory system compliance in 11 subjects with normal respiratory systems. Measurements made in the awake, relaxed state by the method of Heaf and Prime were compared with similar measurements made in the anesthetized, paralyzed state by the supersyringe method. The rib cage component was greater in the paralyzed than the relaxed state in 9 of 11 subjects, but the diaphragm-abdomen component was greater in the relaxed than the paralyzed state in 8 of 11 subjects. We believe that these differences can be explained by respiratory muscle activity in the presumed relaxed state. The fraction of the tidal volume attributable to rib cage displacement compared to abdominal displacement was greater during mechanical ventilation in the paralyzed state than during awake, spontaneous breathing. This can be explained by the different distribution of inflating forces produced by diaphragmatic contraction compared to positive airway and alveolar pressure, in particular by the very different patterns of diaphragmatic displacement in the 2 states.

Effect of priming volume on serum catecholamines during cardiopulmonary bypass.

Several theories have been proposed to explain the transient hypotension which occurs upon the initiation of cardiopulmonary bypass. The present study investigated the possibility that addition of the lactated Ringer's solution pump priming volume to the circulation causes dilution of circulating catecholamines leading to the hypotension. Circulating epinephrine and norepinephrine levels were measured during cardiopulmonary bypass in patients anaesthetized with halothane. The results demonstrate dilution of circulating catecholamines at the start of bypass in conjunction with the observed hypotension. During the bypass period, mean blood pressure graudally recovered to normotensive levels even though circulating catecholamine levels remained significantly lowered, indicating a mechanism for the recovery of blood press which is not sympathoadrenal. The results obtained from this study demonstrate a temporal relationship between catecholamine dilution by the pump priming volume and the observed hypotension. Whether catecholamine dilution is the sole factor causing the hypotension remains to be determined.

Serum epinephrine and norepinephrine during valve replacement and aorta-coronary bypass.

A comparison of the levels of serum epinephrine, norepinephrine and blood pressure was made in 25 patients undergoing aorta-coronary bypass or valve replacement who were anaesthetized with a nitrous oxide-narcotic technique. Serum epinephrine and norepinephrine were measured in arterial samples drawn pre-induction, post-induction, before cardiopulmonary bypass, two and eight minutes after initiation of cardiopulmonary bypass, 20 minutes before termination and after termination of cardiopulmonary bypass. In both patient groups significant increases in epinephrine and norepinephrine occurred befored cardiopulmonary bypass, with accompanying increase of blood pressure in the valve replacement patients. During cardiopulmonary bypass an initial hypotensive response (p less than 0.001) was recorded, followed by a significant increase in blood pressure and epinephrine in both groups. After cardiopulmonary bypass, aorta-coronary bypass patients had epinephrine, norepinephrine and blood pressure equal to levels before cardiopulmonary bypass. In contrast, serum epinephrine continued to rise in the valve replacement patients, with a gradual recovery of blood pressure to pre-bypass levels. These findings demonstrate significant differences in blood pressure and catecholamine response in patients with valvular disease from patients with coronary artery disease.