Lack of effect of experimental ascorbic acid deficiency on bile acid metabolism, sterol balance, and biliary lipid composition in man

Extensive studies in animal models indicate that subclinical ascorbic acid deficiency impairs the conversion of cholesterol to bile acid, elevates plasma cholesterol levels, and predisposes to development of cholesterol cholelithiasis. The present study was designed to see if this is also true in man. Five normal volunteers were hospitalized in a metabolic ward and placed on a controlled diet containing 3-4 mg of ascorbic acid each day. Ascorbic acid supplementation was given as follows: control period I (days 1-33), 75 mg/day; deficient period (days 34-96), 0 mg/day; and repletion period (days 97-101), 1000 mg/day. In addition, three of the subjects were studied during a second control period (days 102-139) during which they were given 75 mg/day of ascorbic acid. Ascorbate levels at the end of both control periods were 0.87-1.34 mg/dl in plasma and 19.4-29.5 micrograms/10(8) cells in leukocytes. At the end of the deficient period these levels were 0.09-0.15 mg/dl in plasma and 6.2-10.0 micrograms/10(8) cells in leukocytes, levels approaching those seen in scurvy. There was no effect of ascorbic acid deficiency on plasma cholesterol and triglycerides; plasma cholesterol in high, very low, and low density lipoprotein fractions; biliary lipid composition and saturation index of gallbladder bile; synthesis, fractional turnover, or pool size of either cholic or chenodeoxycholic acids; output of fecal acid or neutral sterols; and fecal sterol balance. Total bile acid pool size calculated by the one-sample technique was reduced 11% in the deficient period compared to control period I (P less than 0.005), and increased to 98.7% of the baseline levels in control period II. However, total bile acid pool calculated by the Lindstedt method did not change during deficiency. These data demonstrate that short-term subclinical ascorbic acid deficiency near the scorbutic range has no significant effect on bile acid and cholesterol metabolism in man.     

Lipoprotein metabolism of pregnant women is associated with both their genetic polymorphisms and those of their newborn children

To explore whether the placenta contributes to the lipoprotein metabolism of pregnant women, we took advantage of the fact that placental proteins are encoded from the fetal genome and examined the associations between lipids of 525 pregnant women and the presence, in their newborns, of genetic polymorphisms of LPL and apolipoprotein E (APOE), two genes expressed in placenta. After adjustment for maternal polymorphisms, newborn LPL*S447X was associated with lower triglycerides (-21 +/- 9 mg/dl), lower LDL-cholesterol (LDL-C; -12 +/- 5 mg/dl), lower apoB (-14 +/- 4 mg/dl), higher HDL-C (5 +/- 2 mg/dl), and higher apoA-I (9 +/- 4 mg/dl) in their mothers; newborn LPL*N291S was associated with higher maternal triglycerides (114 +/- 31 mg/dl); and newborn APOE*E2 (compared to E3E3) was associated with higher maternal LDL-C (14 +/- 6 mg/dl) and higher maternal apoB (14 +/- 5 mg/dl). These associations (all P < 0.05) were independent of polymorphisms carried by the mothers and of lipid concentrations in newborns and were similar in amplitude to the associations between maternal polymorphisms and maternal lipids. Such findings support the active role of placental LPL and APOE in the metabolism of maternal lipoproteins and suggest that fetal genes may modulate the risk for problems related to maternal dyslipidemia (preeclampsia, pancreatitis, and future cardiovascular disease).     

Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival

The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen. We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref. 4). Cultured embryonic fibroblasts from homozygous Slc23a1(-/-) mice had less than 5% of normal ascorbic-acid uptake. Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1(-/-) mice. Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1(-/-) fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport. Slc23a1(-/-) mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1(-/-) mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content. We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta. Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period.     

Hydrogenation alternatives: effects of trans fatty acids and stearic acid versus linoleic acid on serum lipids and lipoproteins in humans.

The objective of this study was to compare the effects of linoleic acid (cis,cis-C18:2(n-6)) and its hydrogenation products elaidic (trans-C18:1(n-9)) and stearic acid (C18:0) on serum lipoprotein levels in humans. Twenty-six men and 30 women, all normolipemic and apparently healthy, completed the trial. Three experimental diets were supplied to every subject for 3 weeks each, in random order (multiple cross-over). The Linoleate-diet provided 12.0% of total energy intake as linoleic acid, 2.8% as stearic acid, and 0.1% as trans fatty acids. The Stearate-diet supplied 3.9 energy % as linoleic acid, 11.8% stearic acid, and 0.3% trans fatty acids. The Trans-diet provided 3.8 energy % as linoleic acid, 3.0% stearic acid, and 7.7% as monounsaturated trans fatty acids, largely elaidic acid (trans-C18:1(n-9)). Other nutrients were constant. Fasting blood was sampled at the end of each dietary period. Mean (+/- SD) serum LDL cholesterol was 109 +/- 24 mg/dl (2.83 +/- 0.63 mmol/l) on the Linoleate-diet. It rose to 116 +/- 27 mg/dl (3.00 +/- 0.71 mmol/l) on the Stearate-diet (change, 7 mg/dl or 0.17 mmol/l, P = 0.0008) and to 119 +/- 25 mg/dl (3.07 +/- 0.65 mmol/l) on the Trans-diet (change, 9 mg/dl or 0.24 mmol/l, P less than 0.0001). High density lipoprotein (HDL) cholesterol decreased by 2 mg/dl (0.06 mmol/l, P less than 0.0001) on the Stearate-diet and by 4 mg/dl (0.10 mmol/l, P less than 0.0001) on the Trans-diet, both relative to linoleic acid. Our findings show that 7.7% of energy (mean, 24 g/day) of trans fatty acids in the diet significantly lowered HDL cholesterol and raised LDL cholesterol relative to linoleic acid. Combination with earlier results (Mensink, R. P., and M. B. Katan. 1990. N. Engl. J. Med. 323: 439-445) suggests a linear dose-response relation. Replacement of linoleic acid by stearic acid also caused somewhat lower HDL cholesterol and higher LDL cholesterol levels. Hydrogenation of linoleic acid to either stearic or trans fatty acids produces fatty acids that may increase LDL and decrease HDL cholesterol relative to linoleic acid itself.     

Plasma lipoprotein lipid and Lp[a] changes with substitution of elaidic acid for oleic acid in the diet.

The effect of additional dietary trans fatty acids (7% energy) on plasma lipids was assessed in a double-blind comparison of four separate diets: 1, enriched with butter fat (lauric-myristic-palmitic); 2, oleic acid-rich; 3, elaidic acid-rich; 4, palmitic acid-rich. The total dietary period was 11 weeks and comprised normal foods plus specific fat supplements. In 27 mildly hypercholesterolemic men, total and LDL cholesterol were significantly lower during the 3-week oleic acid-rich diet, and were similar during the other three diets. For the four diets LDL cholesterol levels were in mg/dl: 1, 163; 2, 151; 3, 165; 4, 161. HDL cholesterol was significantly higher with the palmitic acid-rich diet, 42 mg/dl, compared with elaidic acid, 38 mg/dl, which in turn was not lower than with oleic acid, 38 mg/dl. Plasma elaidic acid concentration rose seven-fold with the trans fatty acid diet but did not increase the vulnerability of LDL to oxidative change. The elaidic acid-rich diet led to significant elevations in the level of Lp[a] compared to all the other test diets. The Lp[a] level increased to 296 +/- 220 U/l in the elaidic acid-rich period from 235 +/- 182 (mean +/- SD) in the first ("butter") period (P less than 0.001) compared with 249 +/- 204 in the palmitic acid period (P less than 0.001) and 236 +/- 201 in the oleic acid period (NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood Lead Levels During Different Trimesters of Pregnancy and the Possible Influencing Factors in Chengdu, China

Lead is a toxic element. It can damage multiple human organs and systems. In present study, we detected the blood lead levels (BLLs) during the whole pregnancy period and 6-12th weeks after delivery and analyzed their influencing factors by healthy pregnant women. We recruited 128 healthy pregnant women absent of pregnancy or obstetric complications or abnormal pregnancy outcomes as the gravida group. The control group consisted of 120 healthy non-pregnant women. The lead concentrations of all the three pregnancy trimesters and postpartum were: 5.95?±?2.27, 5.51?±?1.93, 5.57?±?1.85, and 6.88?±?1.90?μg/dl; and the mean lead concentration of control group was 6.87?±?2.29?μg/dl. We found that the BLLs of the gravida group were lower than that of control group during all three trimesters and occupations, supplement nutrition elements, and time of house painted could affect blood lead levels of pregnant women. Lead-related occupations, using cosmetics, and living in a house painted <1?year are risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors. These may help people especially pregnant women to reduce lead exposure via supplement of calcium, iron, zinc, and milk or avoiding contacting above risk factors.     

Leucocyte Ascorbic Acid Levels and Vitamin C Intake in Older People

Leucocyte ascorbic acid (L.A.A.) levels and vitamin C intake were measured in a random sample of men and women aged 62-94 years. L.A.A. distributions are positively skewed but log normal. L.A.A. mean values show no age difference in men but are significantly lower in older women. The mean value for all women (23·88μg/10⁸ cells) is significantly higher than that for all men (18·11 μg/10⁸ cells). L.A.A. values are significantly higher in both sexes in the six months July to December. Vitamin C intake distributions are positively skewed but not improved by log transformation. No significant age or sex differences were found except that a significantly greater proportion of men over than of those under 70 years have intakes less than 30 mg daily. Mean intake is significantly higher in men but not in women in the six months April to September, though in both sexes a significantly greater proportion have intakes less than 30 mg daily in October to March compared with April to September. Fifty per cent. of men and 58% of women have intakes less than 30 mg daily, 23·6% of men and 28·1% of women have intakes less than 20 mg daily, and 4·7% of men and 3% of women have intakes less than 10 mg daily. These percentages increase during the winter. A moderate correlation is present between vitamin C intake and L.A.A. level. L.A.A. levels increase in parallel with but lag behind seasonal increases in vitamin C intake.     

Blood vitamin values of common marmosets (Callithrix jacchus)

The blood vitamin analyses of the common marmoset (Callithrix jacchus) were determined to provide baseline reference values for the normal animal. Ascorbic acid, riboflavin (erythrocyte glutathione reductase) [ECR], measurement, thiamin (erythrocyte transketolase) measurement and vitamin A (retinol) were determined for Texas A&M colony-born animals and those obtained from the wild. The analyses were completed on the animals, three times each, for a total of 93 analyses, which included 51 colony-born and 60 wild-born marmosets. A mean value of 0.98 mg/dl for ascorbic acid was found for the colony with a range from 0.06 to 4.1 mg/dl. The normal range for the marmosets appeared to be 0.5 to 1.5 mg/dl. The mean activity coefficient (AC) for the marmosets was 1.0 indicating that the animals had adequate riboflavin in the diet. The mean transketolase activities were (ribose remaining ?30.1 IU/L) and (sedoheptulose appearance ?7.9 IU/L). The mean and range for serum vitamin A (retinol) were 20.4 mg/dl and 6.96–57.44 mg/dl, respectively. None of the animals (colony-born or wild-born) exhibited any clinical signs of vitamin deficiencies as a result of being maintained in an indoor-outdoor environment over a three-year period.     

Data-Derived Uncertainty Factors: Boric Acid (BA) as a Case Study

There is growing support for the use of data-derived uncertainty factors. In recent years, risk assessments of boric acid have been performed by several well-respected organizations, including IEHR, ECETOC, IPCS, and WHO. For each, the pivotal study was a developmental toxicity study in rats with a no-observed-adverse-effect level (NOAEL) of 55 mg BA/kg/day. These risk assessments employed reduced uncertainty factors in the range of 25 to 60 for boric acid, because available pharmacokinetic data for boric acid reduced uncertainty in evaluating the overall data base with this compound. However, a limitation of previous risk assessments was the absence of specific data on the renal clearance of boric acid in pregnant rats and pregnant women. New data has demonstrated that when renal clearance was normalized to body weight (ml/min/kg), pregnant rats cleared boric acid at a rate roughly three times greater than pregnant women. In addition, the boric acid specific allometric relationship was determined from the log-log plot of clearance vs. body weight. Based on the new renal clearance data, it was estimated that pregnant women and rats would have the same AUC when pregnant women are given 30% of the boric acid dose given to pregnant rats. In addition, the renal clearance of boric acid among pregnant women varied by a factor of about 2. Therefore, boric acid-specific data on renal clearance in pregnant women and rats supports reduced interspecies and intraspecies pharmacokinetic uncertainty factors of approximately 3 and 2, respectively. Further, growing evidence of the essentiality in animals, combined with consistency of effects among species in toxicity studies, suggests a reduced pharmacodynamic uncertainty factor is appropriate for boric acid. Total uncertainty factors in the range of 22 to 44 are scientifically justified for this compound. An acceptable daily intake of 1.25 to 2.5 mg BA/kg/day is estimated by applying an uncertainty factor of 22 to 44 to the NOAEL of 55 mg BA/kg/day. Data-derived uncertainty factors should be used whenever possible, and they should be determined and applied in a consistent manner. Ultimately, estimates based on target tissue dose-adjusted relationships should offer a better approach to risk assessment.     

Nutrient intake and meal patterns of Micmac indian and Caucasian women in Shubenacadie,NS.

North American Indians have a higher morbidity from gallbladder disease, diabetes mellitus and obesity than other North Americans; this may result from their food intake. Nutrient intake and meal patterns were compared in 120 Micmac Indian and 115 Caucasian women in Shubenacadie, NS. Findings were compared with the Canadian Dietary Standard (CDS) and the Nutrition Canada national and Indian survey reports. The diet of Indian women had higher carbohydrate, lower protein and lower fibre content than that of Caucasian women, who derived a higher percentage of energy from protein and had a higher intake of vitamin A, niacin and ascorbic acid. Overnight fast was longer among Indian women. A high percentage of all women studied reported diets that did not reach the CDS for total energy intake in kilocalories or for calcium, iron, vitamin A, thiamin or riboflavin.     

Correlation between apolipoprotein A-IV and triglyceride concentrations in human sera

Apolipoprotein A-IV concentration was measured by a newly developed competitive enzyme immunoassay in sera from fasted human subjects (n = 105) whose triglyceride concentrations ranged from 20 to 474 mg/dl (total cholesterol below 260 mg/dl) and in which chylomicrons could not be detected. Mean (+/- SD) apolipoprotein A-IV concentration was 13.0 +/- 2.6 mg/dl in sera with triglyceride levels ranging from 20 to 100 mg/dl, 16.9 +/- 3.7 mg/dl in sera with triglyceride levels ranging from 101 to 250 mg/dl, and 22.7 +/- 6.7 mg/dl in sera with triglyceride levels ranging from 251 to 474 mg/dl. The differences among the three groups were highly significant (P less than 0.001). Moreover, variations of apolipoprotein A-IV concentrations according to the triglyceride levels were noted within the normo-triglyceridemic population. Apolipoprotein A-IV concentration was 12.8 +/- 2.1 mg/dl for triglyceride levels ranging from 20 to 75 mg/dl and 16.4 +/- 3.8 mg/dl for triglyceride levels ranging from 76 to 150 mg/dl (P less than 0.01). In the entire population that was studied there was a significant linear correlation (r = 0.61, P less than 0.001) between the concentrations of serum apolipoprotein A-IV and triglyceride. Although the hypothesis of an unknown factor independently influencing both very low density lipoproteins and apolipoprotein A-IV cannot be ruled out, and although no apolipoprotein A-IV was found in the triglyceride-rich lipoprotein fraction after separation by gel filtration, these data suggest that, in fasting subjects, the secretion of very low density lipoproteins could contribute to the plasma apolipoprotein A-IV level.     

Dietary Adequacy of Vitamin D and Calcium among Inuit and Inuvialuit Women of Child-Bearing Age in Arctic Canada: A Growing Concern

Background

Arctic populations are at an increased risk of vitamin D inadequacy due to geographic latitude and a nutrition transition. This study aimed to assess the adequacy of dietary vitamin D and calcium among women of child-bearing age in Arctic Canada.

Methods

This study collected data from 203 randomly selected women of child-bearing age (19-44 years) in Nunavut and the Northwest Territories of Arctic Canada. Cross-sectional surveys using a validated quantitative food frequency questionnaire were analysed to determine the dietary adequacy of vitamin D and calcium and summarize the top foods contributing to vitamin D and calcium intake among traditional food eaters (TFE) and non-traditional food eaters (NTFE).

Results

The response rate was between 69-93% depending on the community sampled. Mean BMIs for both TFE and NTFE were above the normal range. Traditional food eaters had a significantly higher median vitamin D intake compared with non-traditional eaters (TFE = 5.13±5.34 µg/day; NTFE = 3.5±3.22 µg/day, p = 0·004). The majority of women (87%) were below the Estimated Average Requirements (EAR) for vitamin D. Despite adequate median daily calcium intake in both TFE (1299±798 mg/day) and NTFE (992±704 mg/day; p = 0.0005), 27% of the study population fell below the EAR for calcium. Dairy products contributed the most to intake of vitamin D (TFE = 30.7%; NTFE = 39.1%) and calcium (TFE = 25.5%; NTFE = 34.5%).

Conclusions

Inadequate dietary vitamin D intake is evident among Inuit and Inuvialuit women of child-bearing age in Arctic Canada. Promotion of nutrient-rich sources of traditional foods, supplementation protocols and/or expanded food fortification should be considered to address this nutrition concern.     

Effects of psyllium hydrophilic mucilloid on LDL-cholesterol and bile acid synthesis in hypercholesterolemic men.

The goal of the current study was to determine the mechanism of the hypocholesterolemic effect of psyllium using a randomized, double-blind, crossover design. Twenty males (age 44 +/- 4 yr, weight 79 +/- 10 kg) with moderate hypercholesterolemia (total 265 +/- 17 mg/dl, low density lipoprotein (LDL) 184 +/- 15 mg/dl) were studied at baseline (B) and after randomization to receive a 40-day course of 15 g/day of either psyllium (Ps) or placebo (Pl) (cellulose). After a washout period (11 +/- 2 days), subjects were crossed over to the other fiber treatment for an additional 40 days and restudied. Intestinal cholesterol absorption, cholesterol synthesis in isolated peripheral blood mononuclear cells, bile acid kinetics, gallbladder motility, and intestinal transit were measured at each study period. Psyllium lowered LDL cholesterol (x:184 (B), 169 (Ps), and 179 (Pl) mg/dl; Ps vs. B,Pl: P less than 0.004, P less than 0.02), decreased relative cholesterol absorption (x:51 (B), 45 (Ps), and 49 (Pl) %; Ps vs. B,Pl: P less than 0.03, P less than 0.03), did not alter absolute cholesterol absorption, and increased the fractional turnover of both chenodeoxycholic acid (x:0.176 (B), 0.203 (Ps), and 0.170 (Pl) day-1; Ps vs. B,Pl: P less than 0.0001, P less than 0.01) and cholic acid (x:0.303 (B), 0.411 (Ps), and 0.301 (Pl) d-1; Ps vs. B, Pl: P less than 0.006, P less than 0.002). Bile acid synthesis increased in subjects whose LDL cholesterol was lowered by more than 10% (Ps vs. B: 1304 +/- 489 vs 992 +/- 307 mumol/day, P less than 0.006; Ps vs. PI: 1304 +/- 489 vs. 914 +/- 321 mumol/day, P less than 0.0002). We conclude that psyllium lowers LDL cholesterol primarily via stimulation of bile acid synthesis.     

Effect of Environmental Perchlorate on Thyroid Function in Pregnant Women from Córdoba,Argentina, and Los Angeles,California

ObjectiveTo determine whether environmental perchlorate exposure adversely affects thyroid function in women in the first trimester of pregnancy.MethodsFirst-trimester pregnant women were recruited from prenatal clinics in the Los Angeles County Hospital, Los Angeles, California, and in the Hospital Universitario de Maternidad dependent Universidad Nacional de Córdoba, Córdoba, Argentina, between 2004 and 2007. Spot urine and blood specimens were obtained during the clinic visit. Urinary perchlorate, iodine, and creatinine were measured, and thyroid function tests were performed.ResultsThe study included 134 pregnant women from Los Angeles, California (mean gestational age ± SD = 9.1 ± 2.2 weeks), and 107 pregnant women from Córdoba, Argentina (mean gestational age = 10.0 ± 2.0 weeks). Median urinary iodine values were 144 mg/L in California and 130 mg/L in Argentina. Urinary perchlorate levels were detectable in all women (California: median, 7.8 mg/L [range, 0.4-284 mg/L] and Argentina: median, 13.5 mg/L [range, 1.1-676 mg/L]). Serum thyroperoxidase antibodies were detectable in 21 women from California (16%) and in 17 women from Argentina (16%). Using Spearman rank correlation analyses, there was no association between urinary perchlorate concentrations and serum thyrotropin, free thyroxine index, or total triiodothyronine values, including within the subset of women with urinary iodine values less than 100 mg/L. In multivariate analyses using the combined Argentina and California data sets and adjusting for urinary iodine concentrations, urinary creatinine, gestational age, and thyroperoxidase antibody status, urinary perchlorate was not a significant predictor of thyroid function.ConclusionsLow-level perchlorate exposure is ubiquitous, but is not associated with altered thyroid function among women in the first trimester of pregnancy. (Endocr Pract. 2011;17:412-417)     

Conjunctival papillomas in norther Canadian natives.

Cases of conjunctival papilloma evaluated at a hospital that acts as a referral centre for native people (Indian and Inuit) from northern Alberta and the Northwest Territories were compared with those from other hospitals in the same region whose referral base is primarily non-native. When the data were standardized for population unitsof 100,000 the tumours appeared to be occurring with a greater frequency among lnuit of the Western Arctic. These findings are supported statistically, although it is possible that bias may have been introduced by the small number of cases and other related factors.     

Indispensable and replaceable amino acids in the blood serum and their relationship with macro- and microelements in the newborns of Fe-deficient anemic mothers (in conditions of an industrial city)

Anemia of the newborn is undoubtedly an actual problem in pediatrics. The imbalance between amino acids and biologically active macro- and microelements participating in hematopoiesis and Fe metabolism play an important role in its pathogenesis. Therefore knowledge of amino acid metabolism in the newborn helps to gain insight into pathogenetic mechanisms and to choose the right therapy. A complex inspection of 169 newborns of 18–34-year-old women was done. The control group consisted of 42 newborns of women with normal pregnancy and parturition. The case group consisted of 127 newborns of women with Fe-deficit anemia. Unquestionably one of the factors of Fe-deficit anemia of women aggravates the gestation period, delivery and after-birth period, and has an injurious effect on the newborn. Changes in the trace element and free amino acid metabolism were interconnected in the “mother–newborn” system as evidenced from correlations between the levels of some amino acids, trace element metabolism and erythropoiesis. The pathogenetic importance of the disturbance of the trace element and amino acid metabolism dictates the choice of the correct therapy of Fe-deficit anemia of pregnant women. The experience and results of our investigations support the necessity of preventive estimation of the content of macro- and microelements and amino acids in the blood serum of newborn to correct metabolic disturbances.     

Serum cholesterol and triglyceride measurements in Canadian physicians.

In a study of serum cholesterol and triglyceride concentrations in male physicians, blood was drawn after fasting from 2071 registrants at 17 Canadian medical meetings from 1968 to 1973. Eight regional medical laboratories participated in the study. About two thirds of the samples were analysed in one of two laboratories to diminish method variations. When chylomicronemia, hyperglycemia or extremely high triglyceride values were detected, suggesting nonfasting, the data were discarded. The mean serum cholesterol value for the total study population was 233.9 plus or minus 1.22 mg/dl and the mean serum triglyceride value, 150.5 plus or minus 2.48 mg/dl. The mean values and the prevalence of elevated values (cholesterol larger than or equal to 250 mg/dl; triglyceride larger than or equal to 150 mg/dl) were related to age. Of the total study population 34.7% had elevated cholesterol values and 36.2% had elevated triglyceride values; only the cholesterol value was elevated in 17.5%, only the triglyceride value in 19.6% and both values were elevated in 16.8%. Although this was not a random sampling of Canadian physicians or of Canadian men, our findings of elevated serum lipid values were similar to those in French Canadian civic workers, American executives and Scandinavians, and somewhat higher than those in the Albany, New York and Framingham populations, but distinctly higher than those reported by a recent Nutrition Canada survey.     

Glycosidically bound sialic acid levels as a predictive marker of postoperative adjuvant therapy in gastric cancer

Summary A group of 293 gastric cancer patients were examined to see if the preoperative value of glycosidically bound sialic acid is a predictor of prognosis and effectiveness of postoperative adjuvant therapy. All patients had gastrectomies and were histologically confirmed to have primary adenocarcinoma of the stomach. Some patients then received either postoperative adjuvant chemotherapy or immunochemotherapy. Patients with sialic acid levels less than 74.5 mg/dl survived significantly longer than those with sialic acid levels of 74.5 mg/dl or of 85.3 mg/dl and over. No significant differences in survival were found among patients treated by gastrectomy alone, gastrectomy plus chemotherapy and gastrectomy plus immunochemotherapy. However, patients with abnormally elevated levels of sialic acid survived significantly longer when they were treated with immunochemotherapy after gastrectomy than those treated by gastrectomy alone or with chemotherapy after gastrectomy. By using Cox's multivariate regression model, pTNM stages, postoperative adjuvant therapy (chemotherapy and immunochemotherapy) and preoperative serum levels of sialic acid were examined as prognostic variables. Postoperative therapy was a significant prognostic variable in patients with abnormally elevated levels of sialic acid. The preoperative serum level of sialic acid is a promising predictive marker of the response to postoperative adjuvant immunochemotherapy.     

Oxidative damage to proteins and decrease of antioxidant capacity in patients with varicocele

To examine oxidative damage to blood proteins in the spermatic vein and seminal plasma antioxidant capacity of patients with varicocele, 30 young male patients with varicocele (group 1), 25 young male patients with subclinical varicocele (group 2), and 15 normal young males without varicocele (group 3) were recruited in this study. Varicocele and subclinical varicocele were confirmed by physical examination and Doppler ultrasonography. Blood samples were drawn from peripheral and spermatic veins before varicocelectomy. Plasma protein carbonyls were measured by a spectrophotometric assay after reacting with 2,4-dinitrophenylhydrazine. Protein thiols and ascorbic acid of seminal plasma were measured by spectrophotometric methods. We found that plasma protein carbonyls in the spermatic veins were significantly higher than those of corresponding peripheral veins in all 30 patients in group 1 and 12 patients in group 2 receiving varicocelectomy. Protein carbonyls in the spermatic veins of patients with varicocele (3.72 +/- 0.56 nmole/mg protein) and patients with subclinical varicocele (3.50 +/- 0.30 nmole/mg protein) were found to be higher than those of the control (2.35 +/- 0.33 nmole/mg protein). Protein thiols were 0.97 +/- 0.96, 1.50 +/- 0.89, and 3.49 +/- 0.81 nmole/ml, and ascorbic acid levels were 1.87 +/- 0.42, 2.13 +/- 0.24, and 2.38 +/- 0.07 mg/dl, in seminal plasma of the patients in groups 1, 2, and 3, respectively. Seminal plasma protein thiols and ascorbic acid levels in group 1 were significantly lower than those in groups 2 and 3, respectively. These results indicate that oxidative stress in the patients with varicocele and subclinical varicocele was higher than that of the control. We suggest that plasma protein carbonyls, and protein thiols and ascorbic acid of seminal plasma are useful markers for the assessment of oxidative stress in patients with varicocele and subclinical varicocele.