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Influence of garlic on serum cholesterol, serum triglycerides, serum total lipids and serum glucose in human subjects.

Human subjects were used for a garlic experiment. The subjects were given a fat-rich diet for 7 days and on the 8th day the fasting blood was analyzed for serum cholesterol, serum triglycerides, serum total lipids and serum glucose. The human subjects were then given a fat-rich diet with 40 g of garlic for 7 days and on the 15th day the fasting blood was analyzed for the above investigations. On a fat-rich diet the serum cholesterol, serum triglycerides and serum total lipids were significantly increased as compared to normally fed diet. When 40 g of garlic was substituted in fat-rich diet for 7 days, the garlic significantly reduced the serum cholesterol and serum triglycerides.

Adult↗

Human tumor cells grown in fetal calf serum and human serum: influences on the tests for lymphocyte cytotoxicity, serum blocking and serum arming effects.

Peripheral blood lymphoid cells (PBL) from cancer patients and normal donors were tested against three melanoma cell lines grown in either 10% fetal calf serum (FCS) or 2.5-5% human AB serum in order to determine if the heterologous membrane (HM) antigen or other FCS antigens acquired from the bovine serum supplement could influence lymphoid cell-mediated cytotoxicity in vitro. FCS-grown melanoma cells were more susceptible than the AB serum-grown subline to lymphocyte cytotoxic effects. Arming effects by autologous sera on normal donor lymphocytes and to a lesser extent on lymphocytes of cancer patients were more pronounced on the FCS-grown M12 melanoma cells. This effect was abrogated when the cells were grown in human AB serum for at least 8 weeks. The non-HM tumor-associated antigen remained at the same original low level. Blocking effects were more evident on the AB-grown M14 melanoma line. These data suggest that the FCS antigens on the cell surface may have been responsible for the augmented PBL cytotoxicity. The anti-FCS antibody present in normal and cancer patients' blood induced an antibody-dependent cellular cytotoxicity (ADCC). Elimination of arming activity against HM or other FCS antigens from AB-grown cells may have made the serum blocking factors more apparent. However, cytotoxicity against tumor cells by PBL from normal donors was still apparent even on the human serum-grown cells, suggesting that a different antigen-antibody system was also responsible for this "non-specific" activity.

Animals↗

Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. I. Course of transplanted cancers of various kinds in mice and rats given guinea pig serum, horse serum, or rabbit serum.

In the experiments here described transplanted lymphomas of two kinds regularly regressed following repeated injections of normal guinea pig serum intraperitoneally into mice carrying them, the animals meanwhile remaining lively and devoid of signs of illness or wasting. The lymphomas of untreated control mice, by contrast, usually grew progressively and killed their hosts within 20 to 30 days, and the same was true of the growth of other mice given repeated injections of horse serum or rabbit serum. In similar experiments, the cells of a transplanted lymphosarcoma of rats were temporarily kept from proliferating by repeated intraperitoneal injections of guinea pig serum, though the cells of two transplanted mammary carcinomas of mice, and those of fibrosarcoma, grew unimpeded in hosts likewise treated. Additional experiments related to the phenomenon here described, and a discussion of the findings as a whole, are given in an associated paper.

Animals↗

Relation of serum ascorbic acid to serum vitamin B12, serum ferritin, and kidney stones in US adults.

BACKGROUND: Concern has been raised that high levels of ascorbic acid consumption may lead to potential adverse effects, such as vitamin B12 deficiency, iron overload, and kidney stones. OBJECTIVE: To examine the relation of serum ascorbic acid level, which reflects intake, to serum vitamin B12 level, serum ferritin level, and kidney stones. METHODS: We analyzed data collected on a random sample of the US population enrolled in the Second National Health and Nutrition Examination Survey, 1976-1980. We analyzed data using linear and logistic regression models. Serum ascorbic acid, serum vitamin B12, hemoglobin, red blood cell mean corpuscular volume (MCV), and serum ferritin levels were measured using standardized protocols. History of kidney stones was determined by self-report. RESULTS: After multivariate adjustment, serum ascorbic acid level was associated with higher serum vitamin B12 levels among women in regression models that assumed a linear relationship; each 57-pmol/L (1.0-mg/dL) increase in serum ascorbic acid level (range, 6-153 micromol/L [0.1 to 2.7 mg/dL]) was independently associated with a serum vitamin B12 level increase of 60 pmol/L (81 pg/ mL) (P<.001). Among men, serum ascorbic acid level was marginally associated with higher serum vitamin B12 levels: each 57-micromol/L (1.0-mg/dL) increase in serum ascorbic acid level was associated with a serum vitamin B12 level increase of 27 pmol/L (36 pg/mL) (P = .10). In addition, serum ascorbic acid level was not associated with correlates of vitamin B12 deficiency, such as higher MCV levels, macrocytosis (MCV >100), or lower hemoglobin concentrations. Serum ascorbic acid level was not independently associated with serum ferritin levels. However, among women only, serum ascorbic acid levels were associated in a nonlinear fashion with prevalence of elevated serum ferritin levels (P = .02). We found no association between serum ascorbic acid level and prevalence of kidney stones in women or men (both P>.05). CONCLUSIONS: Serum ascorbic acid levels were not associated with decreased serum vitamin B12 levels (or indicators of vitamin B12 deficiency), prevalence of kidney stones, serum ferritin levels, or-among men-prevalence of elevated serum ferritin levels. Serum ascorbic acid levels were associated with prevalence of elevated serum ferritin levels among women. Although the clinical relevance of these findings is uncertain, it seems prudent to suggest that women with a genetic susceptibility to iron overload should consider moderating their intake of ascorbic acid.

Adult↗

Flavonoid administration immediately displaces thyroxine (T4) from serum transthyretin, increases serum free T4, and decreases serum thyrotropin in the rat.

Naturally occurring and synthetic plant flavonoids, such as EMD 21388, are potent inhibitors of thyroid hormone 5'-deiodinase (5'-D) in vitro, but not when given in vivo, since they are tightly bound by serum transthyretin (TTR). EMD 21388 also inhibits the binding of T4 to human, dog, and rat serum TTR in vitro and when administered to rats in vivo. In the present studies the administration of EMD 21388 inhibited the binding of T4 to TTR within 3 min, resulting in a decrease in the serum T4 concentration, an increase in the percentage of serum free T4 assessed by equilibrium dialysis, and an increase in the serum total free T4 concentration. Depending upon the dose of EMD 21388 employed, the serum total free T4 concentration was either elevated for at least 60 min or transiently elevated, returning to normal values by 60 min. Although the total serum T3 concentration was decreased and the percent free T3 increased, these changes were modest, and the serum free T3 concentrations remained normal after EMD 21388 administration. The transient elevations of serum free T4 concentrations 10 and 20 min after the administration of 0.3 mumol EMD 21388/100 g BW resulted in a significant decrease in the serum TSH concentration at 60 min. These observations strongly suggest that the serum free T4 concentration and not T4 bound to serum TTR is biologically available to the pituitary to regulate TSH secretion and/or synthesis. The administration of EMD 21388, which rapidly increases the serum free T4, but not the serum free T3, concentration, will now permit studies of the effect(s) of endogenously elevated serum free T4 concentrations, rather than those after the administration of pharmacological quantities of T3 and T4, on various aspects of the biosynthesis and release of pituitary TSH.

Animals↗

Effect of serum on the intracellular pH of BALB/c-3T3 cells: serum deprivation causes changes in sensitivity of cells to serum.

One of the earliest responses of quiescent mammalian cells to the addition of serum is an increase in intracellular pH (pHin). This pHin change is generally believed to be due to an increased activity of Na+/H+ exchange. A number of investigators have observed steady-state differences in pHin between cells in the presence and absence of serum. However, no one has examined differences in pHin regulation that may exist between cells chronically exposed to, or deprived of serum. In this study, we investigated the effects of serum deprivation to identify those components of pHin regulation that were associated with quiescence. To do this, we examined pHin in cells growing chronically in 10% serum as well as in cells that were either acutely (1.5-2 hr) or chronically (48 hr) deprived of serum. Intracellular pH was monitored using the fluorescence of intracellularly loaded pyranine dye. Our results indicate that the resting pHin values of chronically or acutely serum-deprived cells were not significantly different from each other yet, in both cases, were lower than those observed in cells exposed to 10% serum. Furthermore, we observed significant increases in pHin of both acutely or chronically serum-deprived cells in response to the addition of serum at various concentrations, in the presence of 24 mM bicarbonate. Chronically serum-deprived cells had slightly smaller responses and were more sensitive to lower concentrations of serum than were acutely deprived cells. Therefore, our data suggest that long-term serum deprivation affects the magnitude and sensitivity of pHin to serum stimulation and causes the loss of some form of pHin regulatory mechanism(s).

Animals↗

Inhibition of the morning cortisol peak abolishes the expected morning decrease in serum osteocalcin in normal males: evidence of a controlling effect of serum cortisol on the circadian rhythm in serum osteocalcin.

Osteocalcin (OC) in serum varies in a remarkably constant circadian rhythm with zenith at night and nadir in the morning. The factors controlling this rhythm are unknown, but several studies indicate that serum cortisol could be of major importance. We tested this hypothesis in a double-blind, placebo-controlled, cross-over study comprising 10 normal male volunteers (aged 23-31 yr) by measuring the response in serum OC and cortisol rhythms to a single dose of metyrapone (30 mg/kg body weight) administered at midnight. During placebo, serum cortisol consistently peaked early in the morning before 0730 h. Ingestion of metyrapone at 2400 h significantly postponed and flattened this peak (P less than 0.01). On both occasions, serum OC increased towards peak levels around 0300 h (P less than 0.01) with no overall differences in the OC profiles. However, when the serum OC time series were synchronized according to the individual cortisol nadirs, we found a significant (P less than 0.01) decrease in serum OC on the placebo day approximately 4 h after the cortisol nadir, whereas no significant changes (P greater than 0.50) were seen on the metyrapone day. Moreover, the mean serum OC level tended to be higher (P less than 0.10 in the interval 0-12 h, and P = 0.06 in the interval 4-8 h) on the metyrapone day compared with the placebo day. On the placebo day, the mean level of serum cortisol during the interval 0-4 h correlated inversely with the mean level of serum OC in the interval 4-8 h (r = 0.77, P less than 0.05). This relation was not found on the metyrapone day. In conclusion, administration of metyrapone, which reduced and postponed the early morning cortisol peak, abolished the normal morning decrease in serum OC. This strongly supports that changes in endogenous serum cortisol are of major importance for the circadian rhythm in serum OC.

Adult↗

Serum leptin correlates with serum uric acid but not serum testosterone in non-obese male adolescents.

To identify the serum factors that affect circulating leptin levels, we measured the serum concentrations of leptin, testosterone (T), estradiol (E), serum alanine aminotransferase, total cholesterol and uric acid (UA) in healthy male adolescents (age, 18.3 +/- 0.1 years, n=96). We also measured body mass index (BMI), percent body fat and thickness of skin fold to assess the effect of body constitution on serum leptin level. Since serum concentration of leptin significantly correlated with BMI (r=0.820, p<0.001), we analyzed the relation-ship between leptin/BMI ratio (L/BMI) and serum parameters. Analysis of data of subjects with normal serum T level showed a significant inverse correlation between L/BMI and serum T levels (n=96, r=-0.294, p<0.005), but no such correlation was present among non-obese subjects (n=70) with BMI of +/-20% of normal (22 kg/m2). There was no correlation between L/BMI and serum E level. Serum UA level significantly correlated with L/BMI in both the test group (n=96, r=0.520, p<0.001) and non-obese subjects (r=0.369, p<0.005). Stepwise multiple regression analysis showed that UA independently and significantly influenced serum leptin levels in both the test and control groups. Our results demonstrate that T weakly influences serum leptin concentration, and that UA concentrations strongly influences serum leptin in healthy male adolescents independent of their obesity level.

Adolescent↗

Serum transferrin and serum prealbumin are early predictors of serum albumin in chronic hemodialysis patients.

Protein-calorie malnutrition is a known risk factor for increased morbidity and mortality in maintenance hemodialysis patients (MHD). Serum albumin is the most commonly measured nutritional index in MHD patients because of its easy routine availability and association with outcomes of interest. However, its long half-life of approximately 20 days makes it a late index of nutritional status, and its exclusive use may delay implementation of appropriate nutritional interventions. Serum prealbumin and transferrin have been proposed as earlier nutritional markers. However, the temporal associations among these indices and serum albumin have not been well documented. To assess the ability of serum prealbumin and serum transferrin to predict changes in serum albumin over time, we prospectively analyzed these parameters in 105 MHD patients every month for 6 consecutive months. The mixed model analysis showed that early changes in either serum transferrin or prealbumin predicted and were significantly associated with changes in serum albumin (P<.0001). Using a prototype equation, a change of 0.12 g/dL in serum albumin concentration can be predicted by a 10% change in the same direction of serum transferrin and prealbumin. We conclude that clinically significant changes in albumin can be reliably predicted by earlier changes in serum transferrin and prealbumin.

Adult↗

Serum bone Gla-protein as a marker of bone growth in children and adolescents: correlation with age, height, serum insulin-like growth factor I, and serum testosterone.

Serum bone Gla-protein (BGP) was determined by RIA in 450 normal children (229 girls and 221 boys, aged 6-19 yr). Serum BGP concentrations changed in relation to age and sex with a pattern that resembles the height velocity curves for children. The increase in serum BGP occurred at the expected age of the growth spurt in both sexes, and the peak values occurred at the age of 12 yr in girls [mean, 49.2 +/- 5.6 (+/- SE) micrograms/L] and 14 yr in boys (64.0 +/- 6.3 micrograms/L). In the boys aged 10-14 yr and in the girls aged 9-12 yr, serum BGP correlated significantly with serum insulin-like growth factor I (IGF-I), serum testosterone, age and height. When the interrelationship was analyzed by means of partial correlation, with age held constant, serum BGP still correlated significantly with the other parameters, but when height was fixed there was only a correlation with serum IGF-I. In children with untreated central precocious puberty, the mean serum BGP concentration was significantly higher than in age-matched normal children [mean, 61.4 +/- 31.7 (+/- SD) vs. 29.0 +/- 10.3 micrograms/L; P less than 0.001]. Serum BGP values decreased significantly in these patients during 1 yr of treatment with a LHRH analog (buserelin) and cyproterone acetate. We conclude that serum BGP is a sensitive marker of bone growth in normal children and in children with increased growth velocity. Repeated measurements may provide useful information in the diagnosis and treatment of children with disturbances in bone turnover.

Adolescent↗

Correlation of serum, tumor, and liver serum glycoprotein: N-acetylneuraminic acid transferase activity with growth of the R3230AC mammary tumor in rats and relationship of the serum activity to tumor burden.

The observation that the activity of sialyltransferase (EC 2.4.99.1; serum glycoprotein:N-acetylneuraminic acid transferase) is often elevated in the serum of cancer patients necessitates an elucidation of the interrelationships of this serum enzyme with host tissues. Accordingly, the activity of this enzyme in serum, tumor, and liver was determined at various times after implantation of the R3230AC mammary carcinoma into Fischer rats. Results from samples obtained at numerous, sequential time points demonstrated that significant elevations in serum sialyltransferase enzyme activity occurred only in animals bearing large tumor burdens, i.e., greater than 20 g, or in animals with tumors present for longer than 21 days. In these tumor-bearing rats, the activity of sialyltransferase increased in liver tissue at 21 to 25 days concurrently with the increase in serum enzyme activity, suggesting that the liver may be a potential source of the serum enzyme. Sialyltransferase activity in tumor tissue was quite variable; the activity increased one week after tumor implantation and remained at the same level thereafter. When tumors were excised, the activity of the serum enzyme returned to control values within four days after surgery, suggesting that the half-life of serum sialyltransferase was two days. Serum enzyme levels were again elevated upon regrowth of the tumor. These results show that the serum sialyltransferase alters its activity in conjunction with changes in tumor burden.

Adenocarcinoma↗

Differential growth requirements of serum factors (bovine serum albumin and low density lipoprotein) for normal and transformed human cells in a serum-free culture.

Serum-free culture is a useful method for identifying the growth requirements of normal cells of human origin and comparing them to the requirements of transformed human cells. We examined differential growth requirements of serum factors (bovine serum albumin (BSA) and low density lipoprotein (LDL) on normal (HEL), Co-60 gamma ray-transformed (CT-1) and 4-nitroquinoline 1-oxide-transformed (SUSM-1) human fibroblast cells in the absence of serum. A decreased requirement for serum was closely related to a decreased requirement for BSA in both types of transformed cells. The growth rate and saturation density of HEL and CT-1 cells grown in serum-free medium supplemented with the optimal concentrations of BSA were almost equal to the rates of cells grown in serum-supplemented medium. When BSA alone was added to the serum-free medium it did not support the continuous growth of SUSM-1 cells because of cellular detachment. An addition of LDL to serum-free cultures not only promoted the moderate growth of HEL cells, it promoted the continuous growth of SUSM-1 cells as well. In contrast, LDL was not required for the optimal growth of CT-1 cells. Transformed human cells specifically had reduced quantitative and qualitative growth requirements for one or more serum factors.

Blood↗

The capacity of chondrocytes to respond to serum is enhanced by organ culture in the absence of serum, stimulated by serum, and modified by ascorbate.

Cartilage slices maintained in organ culture have been shown to develop an enhanced capacity to respond to serum. The response was measured at the initiation of culture and after 3 and 7 days of culture in medium containing an inhibitor of DNA synthesis and 0, 1, or 16% serum. At these times, cartilage slices were washed to remove serum and inhibitor, and then exposed to various concentrations of serum for evaluation of DNA and proteoglycan synthesis. The range of the derived dose-response curves and the indicated sensitivity to low serum concentrations were the parameters used to evaluate the response capacity. Response capacity increased gradually, reaching a maximum after 8 days of culture. Considerable enhancement was obtained after maintenance in the absence of serum using both DNA and proteoglycan synthesis as markers. Additional, graded enhancement of response capacity was obtained when the cartilage slices were maintained in 1 or 16% serum. The effects of maintenance in serum were much greater when DNA synthesis rather than proteoglycan synthesis was used to measure the response. However, this serum-dependent enhancement was only prominent when ascorbate was present during the dose-response assay. Ascorbate caused a similar but less-marked increase in sensitivity to serum when proteoglycan synthesis was measured. The possibility that ascorbate may function as a cofactor during the progression phase of cell proliferation is discussed.

Animals↗

Control of DNA synthesis in cultured vascular endothelial and smooth muscle cells--response to serum, platelet-deficient serum, lipid-free serum, insulin and oestrogens.

Endothelial and smooth muscle cell proliferation has an important role in the pathogenesis of atherosclerosis. To study the effect of serum and some of its putative growth factors on DNA synthesis, the incorporation of thymidine into DNA was studied in cultured human umbilical endothelial and rat aortic smooth muscle cells. DNA synthesis in endothelial cells was progressively stimulated by increasing concentrations of human serum, maximum stimulation occurring with 20% serum. Foetal calf serum had a much lesser effect on DNA synthesis in endothelial cells. Smooth muscle cells responded equally to human and foetal calf serum. Exposure to serum prepared to exclude the platelet-derived growth factor resulted in reduced DNA synthesis in smooth muscle cells. However, endothelial cells increased DNA synthesis in platelet-poor serum. Serum from which lipid had been extracted stimulated DNA synthesis less well than whole serum in both endothelial and smooth muscle cells. Insulin stimulated DNA synthesis in smooth muscle cells but not in endothelial cells, while ethinylestradiol, estrone and estriol had no effect on DNA synthesis in either type of cell. Thus cultured endothelial and smooth muscle cells differ in their requirements for human serum and in their response to platelet factor and to insulin.

Animals↗

Comparison of fortified calf serum, serum substitutes and fetal calf serum with or without extenders for propagation of cell cultures for virus plaque assays.

Two studies comparing sewage-isolated and laboratory stock viruses were conducted to determine if alternative forms of serum or serum extenders could be used in place of fetal bovine serum without a significant loss of viral titer. In the first study, BGM cells were grown in standard MEM-L15 medium which was supplemented with Nuserum, Sigma serum replacement (CPSR-1), HyClone defined iron supplemented calf bovine serum, fetal bovine serum (FBS) or FBS supplemented with either SerXtend or Mito serum extenders. Comparison of virus titers showed that CPSR-1 gave the best overall results and was comparable to FBS. Of the serum extenders, only SerXtend improved virus recovery from sewage samples. In the second study, all sera were tested with and without SerXtend. In these experiments, SerXtend enhanced virus sensitivity of the BGM cell line grown in the HyClone serum but reduced the sensitivity of those cultured in Sigma serum. In both series, the growth of BGM cells was monitored for 12 weeks and all test products were shown to support long-term cell growth.

Analysis of Variance↗

Distinct proteolytic mechanisms in serum-sufficient and serum-restricted fibroblasts. Transformed 3T3 cells fail to regulate proteolysis in relation to culture density only during serum-sufficiency.

Thymidine incorporation (reflecting cell division), degradation of long-half-life proteins and protein synthesis were compared in normal Swiss mouse 3T3 fibroblasts and their counterparts transformed by simian virus 40 at both high and low culture densities (no. of cells/cm2). Normal cells maintained faster proteolysis at high culture density than at low. Degradation was in all conditions enhanced by serum deprivation (1% serum). In serum-sufficient (10%) conditions, there was an inverse correlation between degradation and cell division, but in serum-restricted conditions proteolysis increased substantially as culture density was increased, without change in cell division. Protein synthesis generally changed in a converse sense to protein degradation. In serum-sufficient conditions, transformed 3T3 cells failed to regulate proteolysis in response to culture density. However, in serum-restricted conditions they can regulate proteolysis as do normal cells. Transformed 3T3 cells regulate protein synthesis and thymidine incorporation very poorly in response to culture density in both conditions studied. The failure of regulation of both protein synthesis and degradation may contribute to the exaggerated growth of transformed cells in serum-sufficient conditions. The retention by such cells of regulation of proteolysis during serum restriction may also aid their survival. Studies with several lysosomotropic agents indicated that lysosomes contribute to proteolysis in all conditions studied, but also that its regulation in serum restriction is distinct from that in serum sufficiency, and may involve primarily a non-lysosomal mechanism.

Animals↗

Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin concentrations in anaemic subjects.

Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin were determined on 2 successive days in 48 patients with anaemia. The correlation coefficients between the paired determinations were 0.86, 0.89, 0.95 and 0.95, and the day-to-day coefficients of variation (in per cent) were 33, 11, 12 and 13 for serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin, respectively. Thus, in patients with anaemia, day-to-day variations in serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin are at least as high as in healthy controls. The results indicate important limitations in the use, particularly, of serum iron in the clinical investigation of anaemia.

Adolescent↗

Serum thyrotropin concentrations are more highly correlated with serum triiodothyronine concentrations than with serum thyroxine concentrations in thyroid hormone-infused thyroidectomized rats.

To assess the relative role of circulating T4 and T3 in the regulation of serum TSH, we have measured serum T4, T3, and TSH concentrations in normal and thyroidectomized rats, some of which were chronically infused with T3 or T4. Serum T3, T4, and TSH concentrations were measured 7 and 14 days after surgery. Some groups of infused rats were mildly hypothyroid, as judged by elevated serum TSH concentrations. At both 7 and 14 days, there was a significant inverse correlation between serum T3 and serum TSH concentrations (day 7, r = 0.65, P less than 0.01; day 14, r = 0.71, P less than 0.01). The coefficients for the inverse correlations between serum T4 and TSH concentrations were 0.37 on day 7 (P less than 0.05) and 0.37 (P less than 0.05) on day 14. Linear regression analysis was performed using TSH as the dependent variable for outcome and serum T3 and T4 concentrations as the independent predictor variables. This analysis revealed that after controlling for T3, TSH and T4 were no longer significantly correlated (P = 0.14). The correlation between T3 and TSH remained highly significant. These results suggest that in the euthyroid and mildly hypothyroid rat, serum T3 has a greater inhibitory effect on TSH secretion than does serum T4.

Animals↗