Effect of dilauryl succinate on reproduction of the cock and hen and preventive effect of vitamin E

Fertility of White Leghorn cocks fed a diet containing 12% of dilauryl succinate (LS) for 16 weeks was significantly lower than that of cocks fed the control diet. Little difference in fertility and hatchability of fertile eggs was observed between White Leghorn hens fed the control or LS diets, but the percentage of chicks at hatch, which showed signs of encephalomalacia with lesions on the cerebellum, and the percentage of the hens and offspring having fragile erythrocytes were much higher when LS was fed. Total tocopherol in the plasma of the cocks and hens fed LS and in the eggs laid by the hens fed LS was lower than that in birds fed the control diet, though that of the hens was within the range of plasma tocopherol of normal hens. Offspring of the cocks and hens fed LS died from encephalomalacia earlier than those fed the control diet. These observations with LS feeding were all prevented by oral administration of dl-alpha-tocopheryl acetate. The responses of the cocks and hens to LS were compared with those to linoleic acid in the literature. The direct effect of LS, or more likely of monolauryl succinate, independent of peroxides from unsaturated fatty acids was discussed.     

Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats

There are three ways to approach and resect the caudate lobe of the liver, that is; and isolated caudate lobectomy, a combined resection of the liver overlying the caudate lobe, and a transhepatic anterior approach by splitting parenchyma of the liver. We had two patients with neoplasms originating in the caudate lobe who underwent a complete caudate lobectomy. Both patients have been doing well without liver dysfunction. Although after the transhepatic anterior approach we anticipated an adverse effect from splitting the parenchyma of the liver, the postoperative course was uneventful and similar to that of the right side approach.     

The effect of excessive dietary vitamin A on performance and vitamin E status in swine fed diets varying in dietary vitamin E

A study was conducted to evaluate the effects of high dietary vitamin A on vitamin E status and performance of growing-finishing pigs fed diets supplemented with varying levels of vitamin E. Treatments consisted of corn-soybean meal-based diets supplemented with retinyl acetate to provide 2,000 or 20,000 IU of vitamin A/kg of diet and with DL-alpha-tocopheryl acetate to provide 0, 15, or 150 IU of added vitamin E/kg in a 2 x 3 factorial arrangement. The trial involved 84 crossbred pigs (26 kg initial BW) allotted to pens of two pigs each (one gilt, one barrow). Serum was obtained from all pigs on d 0, 3, 7, 21, 35, 63, and 77 of the 83- or 90-d feeding period. Tissue samples (liver, leg, and neck muscle, backfat, and leaf fat) were collected from one pig (barrow) in each pen at the end of the feeding period. Average daily gain and gain:feed were .93 kg and .30, respectively, without treatment differences (P > .10). Serum alpha-tocopherol increased linearly (P < .01) by d 3 with increasing level of dietary vitamin E supplementation. High dietary vitamin A resulted in a small decrease (P < .01) in serum alpha-tocopherol on d 3, but serum alpha-tocopherol concentration was not affected (P > .10) on other days. Tissue alpha-tocopherol increased linearly (P < .001) as dietary vitamin E increased in all tissues examined. No consistent evidence was found to indicate that a high level of dietary vitamin A interfered with performance or with blood serum or tissue alpha-tocopherol concentrations in growing-finishing swine.     

Influence of vitamin E acetate on stratum corneum hydration

The influence of vitamin E (tocopherol, CAS 10191-41-0) on stratum corneum hydration was tested in O/W and W/O emulsions. Additionally, the O/W emulsion was used in an in vivo/in vitro method to gravimetrically obtain evidence concerning the water-binding capacity of the stratum corneum. In the W/O emulsion, 2.5%, 5%, and 7.5% vitamin E were compared. With both types of emulsions, vitamin E increased the stratum corneum hydration statistically significantly (p = 0.0002). In addition, we could provide evidence of an enhanced water-binding capacity after treatment with vitamin E (p = 0.05). For the hydrating effect of vitamin E. its concentration is of importance. The optimum concentration turned out to be 5%.     

Influence of poultry litter on the toxicity of cadmium to aquatic organisms

Gallium nitrate is active against lymphoma and bladder cancer; however, little is understood about tumor resistance to this drug. Transferrin, the iron transport protein, increases gallium uptake by cells, whereas pyridoxal isonicotinoyl hydrazone (PIH), an iron chelator, transports iron into cells. Therefore, we examined whether these metal transporters would increase the cytotoxicity of gallium in gallium nitrate-resistant CCRF-CEM cells. Transferrin, in increasing concentrations, enhanced the cytotoxicity of gallium nitrate. One mg/ml transferrin decreased the 50% inhibitory concentration of gallium nitrate from 1650 to 75 micrometer in gallium-resistant cells and from 190 to 150 micrometer in gallium-sensitive cells. Transferrin also enhanced the cytotoxicity of gallium even at drug concentrations that were not growth inhibitory. The gallium chelate Ga-PIH inhibited the growth of both gallium nitrate-resistant and -sensitive cells. Fifty micrometer Ga-PIH inhibited cellular proliferation by 50%, whereas similar concentrations of PIH or gallium nitrate were not growth inhibitory. However, because higher concentrations of PIH also inhibited cell growth, the cytotoxicity of Ga-PIH was greater than PIH only at concentrations of <100 micrometer. Cross-titration experiments demonstrated that the cytotoxicity of PIH was partially reversed by gallium nitrate, whereas the cytotoxicity of gallium nitrate was enhanced by PIH. Our studies suggest that Ga-PIH warrants further evaluation as a potential antineoplastic agent. Because transferrin increases the cytotoxicity of gallium nitrate in transferrin receptor-bearing, gallium nitrate-resistant cells, future clinical trials of this drug should incorporate the development of strategies to increase plasma transferrin levels.     

Influence of beta carotene, vitamin E, and vitamin C on endogenous antioxidant defenses in erythrocytes

OBJECTIVE: To evaluate the in vivo radical scavenger activity of vitamin E, vitamin C, and beta carotene on erythrocyte membranes. DESIGN: A prospective, open trial without placebo. SETTING: Department of Clinical Pharmacy. PATIENTS: Ten healthy volunteers being supplemented with beta carotene, vitamin E, and vitamin C. MEASUREMENTS: Erythrocytes were incubated in water bath with 2,2' azobis (2 amidinopropane) hydrochloride (AAPH). AAPH decomposes spontaneously at 37 degrees C to generate free radicals inducing membrane cellular damage and hemolysis. The absorbance was measured at 405 nm at 0, 30, and 60 min, and then every 20 minutes for four hours. The time for 50 percent of maximal hemolysis (T50%), which expresses the radical scavenger activity of erythrocytes, was determined. RESULTS: The physiologic T50% value determined in 52 healthy volunteers is 117 +/- 12 min. Patients receiving these supplements have a higher value of T50% (143.2 +/- 11.6 min at 30 d and 145.7 +/- 10.5 min at 60 d) than the physiologic value (p < 0.001). CONCLUSIONS: These data suggest that vitamin C, vitamin E, and beta carotene stimulate the radical scavenger activity of erythrocyte membranes after 30 days.     

维生素A和E抗辐射氧化损伤作用的研究

目的:探讨维生素A(vitamin A,VA)和维生素E(vitamin E,VE)抗辐射氧化损伤的相互作用.方法:实验分为VA、VE抗辐射氧化损伤实验和VA、VE联合应用抗辐射氧化损伤实验.前者设阴性对照组、阳性对照组、VA(30mg/kg)组、VE(30 mg/kg)组及VA+VE半量(均为15 mg/kg)联合用药组.各组大鼠每天用受试物灌胃1次,连续灌胃6d,第7天除阴性对照组外其它各组大鼠均以6Gy的60Co照射,再继续灌胃3 d后处死大鼠,取血、脑和肝组织,测定MDA、SOD、CAT等指标.VA、VE联合应用抗辐射氧化损伤实验设阴性对照组、阳性对照组、VE组(30 mg/kg)、VE(30 mg/kg)与4个不同VA剂量(分别为2.5、5、10、20 mg/kg)的联合应用组,共7组.各组大鼠的处理同前述.结果:与阳性对照相比,单独补充VA、VE均可以对辐射损伤产生一定的保护作用,血清、脑、肝脏的MDA含量均显著降低(P均<0.05),各种抗氧化酶活性均显著升高(P均<0.05).与阴性对照组比较,固定VE剂量(30mg/kg)与不同VA剂量联合应用时,大鼠血清、脑、肝脏的MDA含量均显著增加,CAT和SOD活性降低,脑、肝脏组织中VE含量显著减少(P均<0.05),并具有一定的剂量-效应关系.VA、VE联合应用时产生的抗氧化作用明显弱于VA、VE单独使用的效果.结论:维生素A和维生素E均具有抗辐射氧化损伤的作用,但在一定的剂量下,VA、VE联合应用可以产生拮抗作用.     

Interaction of vitamins E and K: effect of high dietary vitamin E on phylloquinone activity in chicks

Age-standardised mortality rates are often used in epidemiologic studies to describe the dimension of social inequalities in mortality. This, however, conceals any age-dependence of social inequality. In an ecologic study, all causes and cause-specific mortality of all citizens of Bochum, FRG, who died 1988-1990, were evaluated using 13.171 death certificates. Data was aggregated on census tract level. The social status of a census tract was determined using 6 variables from the census 1987 describing the socio-economic situation in each census tract. Census tracts were grouped into quintiles according to their social status. Age and sex-specific mortality rates as well as rate ratios, using the quintile with the highest social status as reference, were calculated. Results for men (n = 6.288) indicate that social inequality is age-dependent for total mortality. Social differentials are especially marked for the age groups 35-64 years. For age group < 35 years and > 84 years no social differentiation in mortality is visible. Similar patterns are found with mortality from cardiovascular diseases (ICD-9: 390-459) and cancer (ICD-9: 140-208). Mortality from diseases related to health behaviour such as lung cancer or diseases associated with high alcohol intake are characterised by social inequalities above average in the middle age groups. For total mortality in women (n = 6.883) large social differentials are found for age groups 25-34 years and 45-54 years. Efforts to reduce social inequality on community level should especially be aimed at adolescents and young adults living in underprivileged areas.     

Influence of age on the vitamin E requirement for resolution of necrotizing myopathy

Weanling rats were fed either a vitamin E-deficient diet or the deficient diet supplemented with vitamin E or the antioxidant ethoxyquin. Ethoxyquin was not effective in preventing the elevation in platelet number or percent aggregation. However, ethoxyquin was as effective as vitamin E in maintaining body weight, testes weight, pigmentation of the incisors and in preventing myopathy, observed either histologically or by an elevation in plasma glutamic oxalacetic transaminase (GOT) activity. Removal of ethoxyquin from the diet after 19 weeks of feeding resulted in a rapid onset of myopathy. These observations permitted us to study the requirement for vitamin E at various ages without the complication of any cumulative pathological effects of vitamin E deficiency. Ethoxyquin was deleted from the diet at 8, 20, 44 and 64 weeks of age. The requirement for vitamin E to reduce plasma GOT and pyruvate kinase (PK) activity was measured at 12, 24, 48 and 68 weeks of age. The requirement for vitamin E did not change significantly during this time period.     

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia

Study of the solubilization of commercial grades of soya phosphatidylcholine (SPC) with different purities by bile salts (BS) indicated that only highly pure grades of SPC are suitable for the preparation of clear solutions of BS/SPC-mixed micelles (BS/SPC-MM). The solubilizing capacity of different BS towards SPC increased in the following order; Sodium cholate (SC) < sodium deoxycholate (SDC) < sodium glycocholate (SGC). Moreover, egg phosphatidylcholine (EPC) was solubilized to a higher extent than SPC. Furthermore, the solubility study of different drugs in the prepared MM showed substantial enhancement of solubility, the extent of which is essentially affected by the chemical nature of the drug and the composition of MM. Benzodiazepine drugs such as clonazepam, tetrazepam, diazepam, and lorazepam displayed higher affinity for MM compared with BS alone, whereas steroidal drugs, such as estradiol, prednisolone and progesterone, compared with benzodiazepines, displayed relatively higher affinity for BS alone. The solubilizing capacity of MM for the different drugs was increased to different degrees by the addition of benzyl alcohol which was comparable to the solubility of the drug in pure benzyl alcohol. The interaction between benzyl alcohol and the drug in MM could be proved by NMR.     

High-dose vitamin E supplementation has no effect on ethanol-induced pathological liver injury

The effect of alpha-tocopherol (alpha-T) supplementation on ethanol-induced liver damage was studied. The intragastric feeding rat model was used in this study. Both normal and alpha-T supplemented animals (3125 IU/kg body weight) were fed liquid diet and ethanol for 1 mo. In pair-fed animals, ethanol was isocalorically replaced by dextrose. The blood ethanol level in the ethanol-fed groups was between 150 to 350 mg/dl. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substances (TBARS) and conjugated dienes. Liver damage was assessed by light microscopy. Overall, chronic ethanol treatment resulted in increase in TBARS and conjugated dienes in both normal (60% and 35%, P < .01, respectively) and alpha-T-supplemented groups (50% and 47%, P < .01, respectively). In animals receiving either dextrose or ethanol and regular diet, there was a significant inverse correlation between liver alpha-T and TBARS (r = 0.88, P < 0.01) and conjugated dienes (r = -0.75, P < .05). In contrast, in the vitamin E-supplemented rats, a significant positive correlation was observed between liver alpha-T, TBARS (r = 0.78, P < .01) and conjugated dienes (r = 0.87, P < .01). Of major significance is that alpha-T supplementation had no effect on ethanol-induced pathological changes in the liver. In conclusion, these results show that in the intragastric feeding model, alpha-T supplementation had no protective effect on ethanol-induced liver damage.     

The effect of vitamin A and beta-carotene on the vitamin E status, ejaculation parameters and health of boar used for insemination

In this study consequences of vitamin A-supplementation to the vitamin E-status was investigated in the boar. Three groups of boars, each with 9 animals were fed over a period of seven month with 30000 I.E. Vit. A/kg concentrate (group A), 90 mg b-carotene + 1000 I.E. Vit. A/kg (group B) and 1000 I.E. Vit. A/kg (group C). Every boar was given 100 mg Vit. E/kg plus 50 ml soybean oil/kg to induce oxidative stress. After four month group C showed a higher amount of tocopherol in serum (p < 0.05). The amount of tocopherol in serum of the group B were exactly between group A and C. The amount of retinol in serum of the group C began to decrease after three month due to the high reserve capacity of the liver (p < 0.01). The retinyl ester in serum reflected the state of supply. 90 mg b-carotene led to an efficiency of 15000 I.E. Vit. A. The vitamin antagonism between Vit. A and Vit. E is not based on an antagonism of the intestinal resorption. There was no influence on the daily sperm production caused by different supplementations. The sperm quality was lowered in group C; the number of defective sperm increased (p < 0.001). The supplementation of soybean oil lead to an increase of the saturated fatty acids in the fatty acid pattern of the sperm cells. The increase of saturated fatty acids was the lowest in group C that showed the highest amount of tocopherol in serum.     

Haloperidol-induced extrapyramidal reaction: lack of protective effect by vitamin E

Haloperidol treatment has been shown to produce oxidative stress in patients with acute psychosis. Oxidative stress has also been implicated in the extrapyramidal symptoms (EPS) produced by haloperidol. Supporting the oxidative stress hypothesis, vitamin E (antioxidant) has demonstrated therapeutic efficacy in idiopathic parkinsonism. The prophylactic efficacy of vitamin E (antioxidant) on haloperidol-induced EPS was examined in a randomized controlled trial. The sample consisted of 24 acute psychotic patients hospitalized for a 2-week trial. All patients received oral haloperidol 10 mg/day. The sample was equally randomized to receive either haloperidol alone or haloperidol + vitamin E (3200 IU/day). EPS was rated at recruitment, both live and with video records, and on days 3, 7, 10 and 14. Psychopathology was rated at recruitment and weekly thereafter. Vitamin E had no prophylactic effect on drug-induced EPS, though it did not interfere with the therapeutic efficacy of haloperidol.     

Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures

Dermatosparaxis is a recessive disorder of animals (including man) which is caused by mutations in the gene for the enzyme procollagen N-proteinase and is characterised by extreme skin fragility. Partial loss of enzyme activity results in accumulation of pNcollagen (collagen with N-propeptides) and abnormal collagen fibrils in the fragile skin. How the N-propeptides persist in the tissue and how abnormal fibril morphology results in fragile skin is poorly understood. Using biochemical and quantitative mass mapping electron microscopy we showed that the collagen fibrils in the skin of a dermatosparactic calf contained 57% type I pNcollagen and 43% type I collagen and the fibrils were irregularly arranged in bundles and hieroglyphic in cross-section. Image analysis of the fibril cross-sections suggested that the deviation from circularity of dermatosparactic fibrils was caused by N-propeptides of pNcollagen being located at the fibril surface. Comparison of experimental and theoretical axial mass distributions of the fibrils showed that the N-propeptides were located to the overlap zone of the fibril D-period (where D=67 nm, the characteristic axial periodicity of collagen fibrils). Treatment of the dermatosparactic fibrils with N-proteinase did not remove the N-propeptides from the fibrils, although the N-propeptides were efficiently removed by trypsin and chymotrypsin. However, the N-propeptides were efficiently cleaved by the N-proteinase when the pNcollagen molecules were extracted from the fibrils. These results are consistent with close packing of N-propeptides at the fibril surface which prevented cleavage by the N-proteinase. Long-range axial mass determination along the fibril length showed gross non-uniformity with multiple mass bulges. Of note is the skin fragility in dermatosparaxis, and also the appearance of mass bulges along the fibril long axis symptomatic of the fragile skin of mice which lack decorin. Western blot analysis showed that the dermatosparactic fibrils bound elevated levels of the proteoglycan, compared with normal skin fibrils. The results showed that N-propeptides can distort the morphology of fibrils, that they do not inhibit binding of gap-associated macromolecules (such as decorin) and that the normal mechanical properties of skin are strongly dependent on the close association of near-cylindrical fibrils, thereby enabling maximal fibril-fibril interactions.     

Effect of dietary linoleic to linolenic acid ratio and vitamin E supplementation on vitamin E status of poults

Two experiments were conducted to determine the effect of dietary linoleic to linolenic acid (LO:LN) ratio and dl-alpha-tocopheryl acetate (TA) supplementation on selected characteristics of the liver and cerebellum and on vitamin E status of turkey poults from hatch through 22 d of age. In Experiment 1, 1-d-old poults were fed diets containing no supplemental TA (0E) or 150 IU TA/kg diet (150E). Poults fed the 150E diet had greater (P < 0.001) concentrations of alpha-tocopherol (TOC) in the liver and plasma than those fed the 0E diet from 7 to 22 d of age. The 150E diet, however, did not completely overcome the decrease in liver and plasma TOC concentrations observed at these ages. The 150E diet had no effect on poult BW, feed efficiency, or on the weight, protein, lipid, or fatty acid concentrations of the liver. Thiobarbituric acid reactive substances assay of liver and hemolysis assay of red blood cells (RBC) showed that the 150E diet decreased the susceptibility of liver and RBC to in vitro peroxidation at 13 and 22 d of age. In Experiment 2, 1-d-old poults were fed the 0E and 150E diets in a complete factorial arrangement with decreasing ratios of LO:LN (10, 5, and 1). Dietary LO:LN ratio had no effect on RBC hemolysis or cerebellum TOC concentration. As the ratio of LO:LN decreased, the arachidonic acid content of liver and cerebellum lipids decreased. Ratios of n-6 to n-3 fatty acids in liver and cerebellum were directly related to dietary LO:LN at 13 and 22 d of age.     

The effect of altered selenium and vitamin E nutritional status on learning and memory of third-generation rats

It has been proposed that selenium (Se) and Vitamin E (Vit E) are involved synergistically in protection of cell membrane lipids from peroxidation. However, little is known about the effect of both deficiencies of Se and Vit E and toxic status of those antioxidants on the peroxidation potentiality of the brain. We aimed to study the effects of both Se and Vit E inadequate diet and Se rich diet on the learning and memory processes of third-generation young rats. Their ancestors were also fed by the same diets starting from their births. To test the learning and memory, the rats aged 60 days were trained by using automated two ways active avoidance shuttle box. The acquisition tests were terminated with training the rat from each group to be 25 trials per day during three days. Ten days after the last acquisition test, the retention test was performed and the acquisition of the conditioned avoidance responses (CAR) of the rats were evaluated. It is demonstrated that the CAR of all rats from three groups showed a significant increase in three consecutive days while the differences observed in CAR of same sessions was not significantly different among three groups. The memory process of these young rats also was not affected significantly by two types of diets. Under the light of our results one can suggest that, in the case of alterations in antioxidant defense status, the learning and the memory mechanisms seems to be not affected. Further researches are needed to be able to explain the possible role of oxidative stress on the mechanisms of learning and memory.     

The effect of vitamin E on antioxidant tissue activity in pregnant rats with streptozocin-induced diabetes]

When home enteral nutrition is needed, there is still, despite the undisputed increase in the quality of life that can be achieved with a Percutaneous Endoscopic Gastrostomy (PEG), a reservation in its use because this technique and its maintenance is considered to be very costly. We aim to assess the true cost of home enteral nutrition using the oral route, a nasogastric tube, and PEG. PATIENTS AND METHODS: The data of 65 patients who required home enteral nutrition during 1996, were analyzed retrospectively. The access route was a nasogastric tube in 20 cases, 18 patients had PEG, and 27 candidates used an oral route. The average age was 56 years. 50% were men and 50% were women. The most common diagnoses that led to the indication were oropharyngeal-maxillofacial neoplasms and neurological disorders. In all cases the material and formula used was assessed, as were the associated complications and the cost of the at home enteral nutrition. RESULTS: The average duration of the treatment was 175 +/- 128 days, and this was similar in all three groups. The average formula/day cost was slightly higher in the patients using the oral access route. The average total day cost and the average material/day cost was slightly higher in patients with a PEG. Patients with a PEG presented fewer complications than those with a nasogastric tube. The cost derived from possible complications must be higher in the nasogastric tube group, especially considering the repeated tube changes due to obstruction or loss. CONCLUSIONS: The cost of home enteral nutrition is slightly lower if one uses a nasogastric tube. The greater incidence of complications that were mild but required a tube change, in this case a nasogastric tube, suggests higher indirect costs. The oral route is associated with the need for special formulae that are more expensive.     

Effects of dithiocarbamates on toxicity of cadmium in rat primary hepatocyte cultures

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the toxicity of Cd in the rat primary hepatocyte cultures were studied. Cytotoxicity was assessed by measuring cell viability, extra cellular lactic dehydrogenase (LDH) activity, and intracellular lipid peroxidation and active oxygen species. Primary hepatocyte cultures were treated with 109CdCl2 (5, 10 or 50 microM Cd and 1.7 KBq of 109Cd/well) for 30 min or 4 h. BGD or HBGD was added to the culture medium to make the final concentration of 100 microM and incubated for 4.5 h in 30 min Cd exposure or 1 h in 4 h Cd exposure. Decreases in the hepatocyte viability caused by all Cd exposure concentrations were significantly prevented by treatment with BGD or HBGD. The treatment with the chelating agents for 4.5 h after Cd exposure for 30 min significantly prevented increases in extracellular LDH activity. Increases in the lipid peroxidation in hepatocytes exposed to Cd for 30 min or 4 h were prevented significantly by treatment with BGD or HBGD for 4.5 h or 1 h, respectively. Moreover, the increases in the level of active oxygen species caused by Cd exposure for 30 min were significantly prevented by treatment with the chelating agents for 1.5 h. These findings suggest that BGD and HBGD protect against the cytotoxicity of Cd in rat primary hepatocyte cultures and that the protective effects of chelating agents presumably result from a decrease in the Cd level, the effective sequestration of the reactive Cd ion, and the direct preventive effect on the active oxygen species in the hepatocytes.     

Inhibitory effect of vitamin E succinate on the proliferation of cultured bovine choroidal endothelial cells

We report the effect of vitamin E succinate (VE succinate) on the proliferation of cultured bovine choroidal endothelial cells (BCECs). BCECs were incubated with a medium containing vitamin E (VE) or one of the VE derivatives gamma-tocopherol, VE phosphate, VE succinate, VE nicotinate, VE acetate, or trolox, at a concentration of 10 microM. The proliferation of BCECs was assessed by 3H-thymidine uptake and cell counting. Especially in VE and VE succinate, the proliferation assay was performed on BCECs at two different stages, that is, the proliferating stage and the quiescent stage. The effect of protein kinase C (PKC) stimulator phorbol ester (PMA) on the VE succinate-induced inhibition of BCEC proliferation was also examined. VE succinate was found to significantly inhibit BCEC proliferation at a concentration of 10 microM or greater both by 3H-thymidine uptake assay and by cell counting. This inhibitory effect was not noted in other VE derivatives. The inhibitory effect was the most prominent in the proliferating BCECs and co culture of PMA. VE succinate inhibits the proliferation of cultured BCECs and PKC is involved in this action at least in part.