When a pure preparation of 9-cis β-carotene was administered to rats through a stomach tube, it was absorbed and easily isomerized to all trans β-carotene in vivo. On the other hand, when synthetic all trans β-carotene was administered, 9-cis β-carotene was not found, indicating that isomerization of the all trans form to the 9-cis form does not occur in vivo. 9-cis β-Carotene and all trans β-carotene accumulated in the liver, but the levels of both carotenes in the plasma increased only transiently. However, the amounts of total β-carotene in the plasma and liver were larger in rats administered 9-cis β-carotene than in those given all trans β-carotene.
The modulation of lipoprotein lipase (LPL) activity and mass was examined in rats with insulin resistance induced by a beef tallow diet. Male sprague-Dawley rats were meal-fed an isoenergetic diet based on either beef tallow or safflower oil for an 8-week period. Insulin resistance brought about by long-term feeding of a beef tallow diet was confirmed by an oral glucose tolerance test. Plasma glucose and insulin levels were higher at almost all times of day in the rats fed the beef tallow diet than in those fed the safflower oil one. LPL activities of the skeletal and cardiac muscles and brown adipose tissue before and after a meal were lower in the beef tallow diet group than in the safflower oil diet group, however those of the perirenal and subcutaneous adipose tissues were not different between the two dietary groups. The amounts of LPL proteins in the soleus muscle and perirenal adipose tissue corresponded to the enzyme activities in these tissues. These results suggest that the effect of dietary saturated fat on LPL activity and mass are different in muscles and adipose tissues and that generalized peripheral insulin resistance, induced by feeding rats a beef tallow diet for a sufficient duration, is not followed by an impairment of the modulation of LPL activities and protein amount.
The mode of cell death in transplanted human cancer tissue following photodynamic therapy (PDT) was investigated from the perspective of apoptosis. Human pancreatic carcinoma transplanted into nude mice was treated by PDT following sensitization with Photofrin. PDT treatment showed significant therapeutic effects at 7 days post treatment as compared with laser irradiation treatment only at each laser energy dose when the mean of each overall split surface of the necrotic area was measured. The characteristic DNA ladder formation indicative of apoptosis was demonstrated 2h after PDT treatment in every group of PDT treatment regardless of the laser energy such as 25, 50, or 100J/cm2. However, no evidence of DNA ladder formation was found in the groups of laser irradiation only. Intense TUNEL signals were demonstrated in nuclei of tumor cells 2h after PDT treatment. In tumor tissues 7 days after PDT treatment, TUNEL signals were also recognized in the peripheral tumor cells close to the necrotic area. On the other hand, tumor cells with TUNEL signals could not be found in the untreated control group or in groups given only laser irradiation either 2h or 7 days after the irradiation. The observation that solid tumors treated by PDT undergo apoptosis implies that cell death in response to PDT is not only a passive phenomenon resulting from massive membrane damage, but is also one that requires the participation of cell metabolism, suggesting new possibilities of modifying the cell death program by modulation with cytokines, growth factors, and certain genes that control apoptosis.
Ischemia-reperfusion of the small intestine associated with hemorrhage and other shock states is characterized by increased microvascular permeability and mucosal barrier dysfunction. Glycoproteins play an important role as a barrier to diffusion, and some of the functions of prostaglandin E1 (PGE1) are related to mucosal protein synthesis. The present experiment was conducted to clarify the effect of PGE1 on mucosal levels of glycoproteins and ATP following acute ischemia-reperfusion of the small intestine. The canine jejunum was isolated, and the blood flow was blocked for 30min with or without intravenous infusion of PGE1. Mucosal levels of ATP, Na+-K+ ATPase activity, glucosamine, galactosamine, and cAMP decreased, and plasma endotoxin levels in portal blood increased, after reperfusion in the PGE1-non-treated group. These changes were suppressed and mucosal levels of cAMP were increased by the administration of PGE1. These results suggest that mucosal permeability increased and mucin synthesis decreased markedly following acute ischemia-reperfusion and that the administration of PGE1 suppressed these changes by stimulation of ATP and cAMP synthesis. We also conclude that the administration of PGE1 is useful to protect against acute ischemia-reperfusion injury in the small intestine.
Oxidative stress is suggested to be involved in the induction of tissue microsomal heme oxygenase (HO). Phorone (diisopropylidene acetone) is a glutathione (GSH)-depleting agent as well as a potent inducer of HO. In this study, phorone and another GSH-depleting agent, buthionine sulfoximine (BSO), were compared in rats given a normal (7IU/100g diet) or high (100IU/100g diet) level of dietary vitamin E (VE) to determine whether HO induction is mediated through GSH depletion and/or lipid peroxidation. In Experiment 1, single (250mg/kg B.W.) and three consecutive doses (250mg/kg B.W./day) of phorone to animals given normal dietary VE comparably decreased the liver GSH contents, but the liver microsomal HO was induced in a dose-dependent manner. Liver chemiluminescence intensity also increased in response to the dose level of phorone, suggesting an enhanced liver lipid peroxidation stimulated by phorone administration. In Experiment 2, phorone (250mg/kg B.W./day) or BSO (1mmol/kg B.W./day) was administered intermittently 4 times to animals given a normal or high level of dietary VE. Administration of phorone and BSO significantly decreased the GSH contents both in the liver and kidney, but no effect of high dietary VE on the contents was observed. HO was induced significantly in both the liver and kidney following phorone treatment, but not by BSO. High dietary VE also did not affect the phorone-induced HO activity. Phorone administration significantly enhanced the liver chemiluminescence intensity, but it was suppressed to the control level by high dietary VE. BSO administration did not promote lipid peroxidation in the liver. In the kidney, neither phorone nor BSO stimulated lipid peroxidation. From these results, we presume that induction of HO by phorone in the liver and kidney is not mediated by GSH depletion and lipid peroxidation.
In order to investigate the relationship between the changes in glycosylation and the placental materno-fetal transport of Immunoglobulin G (IgG), glycosylation profiles of IgG from healthy pregnant women and their umbilical cords at delivery were compared by use of a recently established high-performance liquid chromatography (HPLC) method. From the results of neutral oligosaccharide analysis, the digalactosyl IgG glycoform (G2) was markedly increased in pregnant women as compared with that in age-matched controls. Furthermore, the quantity of the digalactosyl glycoform in the umbilical cord was found to be higher than that in the mother. These findings demonstrate the existence of a placental selective transport with a preference for a digalactosyl oligosaccharide-linked IgG molecule. Concerning IgG sialo-oligosaccharides, however, no selective transport was observed between mother and umbilical cord. The mechanism and clinical importance of greater galactosylation in IgG still remain unclear, but we suggest that the relationship between changes in IgG galactosylation and the placental selective transport deserves further attention.