Time Window for the Contribution of the δ-opioid Receptor to Cardioprotection by Ischemic Preconditioning in the Rat Heart

The present study aimed to examine (1) whether the role of the opioid receptor in ischemic preconditioning (PC) is consistent regardless of the duration of ischemic insult and (2) which opioid receptor subtype contributes to PC. In the first series of experiments, the effects of PC, a nonselective opioid receptor antagonist (naloxone), and their combination on the infarct size after various durations of ischemia were assessed. In anesthetized, open-chest rats, the coronary artery was occluded for 20, 30, or 40 minutes to induce infarction and was reperfused for 3 hours, PC was performed with two cycles of 5-minute ischemia followed by 5-minute reperfusion before the sustained ischemia. At 25 minutes before the ischemia, naloxone was injected alone or in combination with subsequent PC. Infarct size was determined by tetrazolium staining and was expressed as a percentage of the risk area size (%IS/RA). In the second series of experiments, the effects of a -receptor selective antagonist, naltrindole (NTI), and a -receptor selective antagonist, nor-binaltrophimine (nor-BNI), on PC before 30-minute coronary occlusion were assessed. In untreated controls, %IS/RA was 53.1 ± 3.2 after 20 minutes, 67.9 ± 3.9 after 30 minutes, and 87.8 ± 2.0 after 40 minutes of ischemia, respectively. PC significantly reduced %IS/RA after 20, 30, and 40 minutes of ischemia to 3.1 ± 0.8, 12.8 ± 1.1, and 42.1 ± 4.3, respectively (P < 0.05 vs. each control). Naloxone (6 mg/kg) partially attenuated the protection afforded by PC when the sustained ischemia was 30 minutes (%IS/RA = 27.4 ± 4.5; P < 0.05 vs. PC), but this inhibitory effect of naloxone was not detected when the duration of the ischemia was 20 or 40 minutes. NTI (10 mg/kg) also attenuated infarct size limitation by PC after 30 minutes of ischemia (%IS/RA = 25.6 ± 3.7), but nor-BNI (10 mg/kg) failed to modify infarct size limitation by PC (%IS/RA = 13.3 ± 3.2). The present results suggest that activation of the opioid -receptor partly contributes to preconditioning against infarction in the rat and that there may be a time window (at around 30 minutes after the onset of ischemia) for this opioid receptor–mediated protective mechanism.     

Hepatic steatosis and the elevated plasma insulin level in patients with endogenous hypertriglyceridemia

Among 31 nonobese or obese patients with endogenous hypertriglyceridemia, hepatic steatosis was found by histologic examination of the biopsied specimen in 17 patients, and it was severe in six patients. They had no history of excessive alcohol intake. Chemical analysis revealed that the lipid accumulated in the liver was triglyceride. The hypertriglyceridemic patients, with or without histologic steatosis, showed significantly increased responses of both plasma insulin and blood glucose to oral glucose load compared with control subjects. The responses were more exaggerated in the hypertriglyceridemic patients with steatosis than in the hypertriglyceridemic patients without steatosis. Analysis of correlations between five variables (liver triglyceride, plasma insulin, blood glucose, body weight index, and serum triglyceride) was done on 15 subjects whose liver triglyceride values were quantified, and highly significant correlations were found between liver triglyceride and plasma insulin, blood glucose, or body weight index. A stepwise multiple regression analysis performed on the five variables with liver triglyceride as the dependent variable revealed that the plasma insulin level was the most closely related variable, and the blood glucose level the next. The prediction equation for liver triglyceride as a function of plasma insulin and blood glucose levels (r = 0.91, p < 0.001) accounted for 84% of the total variance of liver triglyceride. It was shown that the decay of intravenously injected insulin in plasma was not delayed in the hypertriglyceridemic patients with steatosis, while the insulin sensitivity examined after intravenous insulin injection significantly decreased in the hypertriglyceridemic patients with or without steatosis, thus suggesting that the hyperinsulinemia in the hypertriglyceridemic patients was due to an increased insulin secretion associated with the decrease in the insulin sensitivity. Therefore, the elevated plasma insulin and blood glucose levels—or the insulin insensitivity by itself—might be the essential abnormalities in patients with endogenous hypertriglyceridemia, which, in extreme cases, might lead to massive triglyceride accumulation in the liver.     

Secretion of lipoproteins from the liver of normal and Watanabe heritable hyperlipidemic rabbits.

We compared the rate of accumulation of lipoproteins in perfusates of isolated livers from normal New Zealand White rabbits and Watanabe heritable hyperlipidemic (WHHL) rabbits, in which a gene mutation has produced a virtually complete deficiency of low density lipoprotein (LDL) receptors. The rate of accumulation of apolipoprotein B-100 did not differ in perfusates of livers from normal and mutant animals and little or no apolipoprotein B-48 was detected. In both groups, virtually all apolipoprotein B accumulated in very low density lipoprotein (VLDL). Experiments in which [3H]lysine was added to the perfusates showed that the apolipoprotein B that accumulated in VLDL was newly synthesized by the liver whereas the small amount of apolipoprotein B found in lipoproteins of higher density appeared to be washed out of extravascular spaces during perfusion. Perfusate VLDL from both groups contained more triglycerides and less cholesteryl esters than their counterparts from blood plasma. As compared with perfusate VLDL from normal livers, those from livers of WHHL rabbits were enriched in cholesteryl esters. Experiments in which Triton WR-1339 was injected into the blood of intact rabbits confirmed the observations with perfused livers. Previous studies have shown that the extent to which VLDL is converted to LDL is increased several-fold in WHHL rabbits. Taken together with our present results, which fail to provide evidence for increased secretion of apolipoprotein B or de novo secretion of lipoproteins other than VLDL that contain apolipoprotein B, it can be concluded that overproduction of LDL in rabbits lacking LDL receptors is solely the result of altered metabolism of VLDL.     

Serum isoamylases in patients with autoimmune rheumatic diseases

We studied sera of 107 patients with autoimmune rheumatic diseases (46 with classical rheumatoid arthritis (RA), 36 with systemic lupus erythematosus (SLE) and 25 with primary Sj?gren's syndrome (SS). None of these patients had abdominal pain or gastrointestinal symptoms at the time of blood collection. We used as controls 81 normal age and sex matched volunteers. The presence of hyperamylasemia i) of P-type in 6 of 46 patients (13%) with RA and ii) of P-type and S-type in 11 of 36 patients (30.5%) with SLE and 6 of the 25 patients (24%) with primary SS suggests that asymptomatic pancreatic damage in autoimmune rheumatic diseases may occur frequently especially in patients with SLE. We conclude that the hyperamylasemia in these patients probably reflects a slow, subclinical, inflammatory process of the exocrine glands.     

Mother-to-Child Transmission of Chagas Disease in El Salvador

To estimate the incidence (any mother to child) and rate (from seropositive mother to child) of mother-to-child transmission of Trypanosoma cruzi, a serological census was conducted, targeting pregnant women and infants born to seropositive mothers, in four municipalities of El Salvador. Of 943 pregnant women, 36 (3.8%) were seropositive for T. cruzi. Of 36, 32 proceeded to serological tests of their infants when they became 6–8 months of age. Six infants seropositive at the age of 6–8 months further proceeded to second-stage serological test at the age of 9–16 months. As the result, one infant was congenitally infected. Thus, serological tests at the age of 6–8 months produced five false positives. To ensure earlier effective medication only for true positives, identification of seropositive infants at the age of 9–16 months is crucial. Incidence and rate of mother-to-child transmission were 0.14 (per 100 person-years) and 4.0%, respectively. Estimated number of children infected through mother-to-child transmission in El Salvador (170 per year) was much higher than that of human immunodeficiency virus (HIV; seven per year). It is recommended that serological testing for T. cruzi be integrated into those for HIV and syphilis as part of antenatal care package.