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At least 109 records · Page 6Linked to original sources
PubMed2003

The effect of pegvisomant-induced serum IGF-I normalization on serum leptin levels in patients with acromegaly.

BACKGROUND: In humans, serum leptin correlates positively with fat mass. GH is lipolytic and patients with active acromegaly have lowered serum leptin compared to age, sex and body mass index (BMI)-matched controls, but a direct influence of GH on serum leptin remains unclear. In patients with acromegaly, total leptin increases following successful pituitary surgery and during somatostatin (SMS) analogue therapy (despite no change in BMI) but whether this represents changes in soluble leptin receptor, bound or free leptin is unclear. Pegvisomant, a GH receptor antagonist capable of normalizing serum IGF-I in over 97% of patients, represents a novel treatment strategy in acromegaly and its effect on leptin has not previously been reported. PATIENTS: Sixteen patients (nine male (M), seven female (F), median age 52 years, range 27-78 years) with active acromegaly (serum IGF-I at least 30% above the upper limit of an age-related reference range) were studied. Serum IGF-I was normalized in all subjects with pegvisomant [mean duration 7 months (range 3-11 months), median dose 20 mg/day (range 10-40 mg/day)]. A single batch measurement of leptin, bound leptin (BL), soluble leptin receptor (SLR), insulin and glucose were performed on samples from baseline and first occurrence of serum IGF-I normalization. RESULTS: As in normal subjects, females with acromegaly had higher baseline serum leptin [median M = 6.1 (range 1.6-58.7), F = 25.9 (range 3.19-54.1) ng/ml; P = 0.04], which correlated positively with BMI (R = 0.78, P = 0.0004). Forward step-wise regression analysis demonstrated that BMI and gender accounted for 90% of the variance in mean serum log10 leptin. Pegvisomant-induced serum IGF-I normalization was associated with a rise in serum leptin [8.9 (range 1.6-58.3) to 12.7 (range 2.3-90.8) ng/ml, P < 0.0001]. Although the absolute increase was not significantly different, mean percentage increase was greater in men (M = 66.6 +/- 51%, F = 11.8 +/- 16%, P = 0.017) despite similar serum IGF-I and BMI in male and female subjects at baseline. No change in BL or SLR accompanied serum IGF-I normalization [0.27 (range 0.15-1.26) to 0.27 (range 0.14-1.2) nmol/l, P = 0.27 and 3.2 (range 1.2-6.8) to 2.7 (range 1-7.4) nmol/l, P = 0.5, respectively]. After normalization of serum IGF-I, a correlation between BMI and leptin remained (R = 0.86, P < 0.0001) and together BMI and gender accounted for 87% of the variance in mean log10 serum leptin (P = 0.0002). CONCLUSION: Pegvisomant-induced serum IGF-I normalization in patients with active acromegaly is associated with a significant increase in total, and by implication, free leptin.

Acromegaly↗
PubMed2003

Association between second-trimester isolated high maternal serum maternal serum human chorionic gonadotropin levels and obstetric complications in singleton and twin pregnancies.

OBJECTIVE: The purpose of this study was to examine the clinical significance of high maternal serum human chorionic gonadotropin levels in the second trimester in singleton and twin pregnancies within the Ontario maternal serum screening program. STUDY DESIGN: The study group comprised 564 women with singleton pregnancies with total maternal serum human chorionic gonadotropin levels of > or =4.0 multiples of the median (MoM) and serum marker alpha-fetoprotein levels of <2.0 MoM. The cases were matched with 1692 control subjects who had both serum marker alpha-fetoprotein levels and maternal serum human chorionic gonadotropin levels of <2.0 MoM. The second part of the study comprised 93 twin pregnancies with maternal serum human chorionic gonadotropin levels of > or =5.0 MoM and serum marker alpha-fetoprotein levels of <4.0 MoM; the control group (n = 1496) had serum marker alpha-fetoprotein levels of <4.0 MoM and maternal serum human chorionic gonadotropin levels of <5.0 MoM. The final part of the study included 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM). RESULTS: Of the singleton pregnancies with maternal serum human chorionic gonadotropin levels of > or = 14;4.0 MoM, 22.5% had severe adverse obstetric outcomes, compared with only 10.9% of the matched control population (P =.001). Women with markedly elevated maternal serum human chorionic gonadotropin levels had significantly increased risks of having spontaneous miscarriage, small-for-gestational-age infants, pregnancy-associated hypertensive disorder, and preterm delivery. Of the women with twin pregnancies with high maternal serum human chorionic gonadotropin levels (> or =5.0 MoM), 71% had at least one complication (such as miscarriage and preterm delivery) compared with 55.3% in the control group. Finally, 23 of 25 women with extremely high maternal serum human chorionic gonadotropin levels (> or = 14;10 MoM) had serious adverse outcomes (such as fetal abnormalities, pregnancy-associated hypertensive disorder, premature separation of placenta, intrauterine growth restriction, neonatal respiratory distress syndrome, and neonatal jaundice). CONCLUSION: Pregnancies with an elevated maternal serum human chorionic gonadotropin level are associated with adverse obstetric outcomes. Increased maternal and fetal surveillance is warranted in these pregnancies.

Case-Control Studies↗
PubMed1995

Assessment of GH status in acromegaly using serum growth hormone, serum insulin-like growth factor-1 and urinary growth hormone excretion.

OBJECTIVE: It is still not clear what is the most suitable method for monitoring progress of acromegaly. The aim of this study was to assess the relative merits of serum GH, serum IGF-I and urinary GH (uGH) excretion in the follow-up of acromegalic subjects. SUBJECTS AND METHODS: Thirty-six acromegalic patients each had a GH day series performed consisting of five serum GH measurements, together with an estimate of serum IGF-I and uGH. The first sample taken for serum GH was fasting (basal) whilst the third (1430h) was arbitrarily chosen as a random value. uGH was measured from two overnight collections and the mean value used for subsequent data analysis. MEASUREMENTS: Serum GH and IGF-I were measured by radioimmunoassay whilst uGH was estimated by an immunoradiometric assay using commercially available reagents. RESULTS: There is a highly significant linear correlation between serum GH and IGF-I following log transformation of these two variables (r = 0.85; P < 0.0001). Analysis of the raw data shows that the relation is in fact curvilinear rendering IGF-I less useful as a surrogate for integrated GH secretion at high levels of serum GH. There is a strong linear correlation between both a singleton basal serum GH and uGH (r = 0.78; P < 0.001) and the mean of five measurements (day series) and uGH (r = 0.81; P < 0.0001). Both uGH and IGF-I are excellent predictors of those patients with persistent elevation of serum GH, identifying 95 and 96% respectively with serum GH > 5mU/l. We have identified a number of patients, however, with persistent elevation of IGF-I in the presence of serum GH < 5mU/l and normal uGH. Until the significance of these findings with respect to long-term outcome is known, serum GH should continue to be used in the follow-up of these patients. An alternative, which reflects integrated overnight GH secretion, is uGH which is convenient and easy to collect as an outpatient and correlates strongly with serum GH. CONCLUSION: Acromegalic patients can be conveniently followed on an outpatient basis using a combination of uGH and serum IGF-I. Measurements of serum GH can be reserved for those with discrepant results.

Acromegaly↗
PubMed1983

Different regulatory mechanisms for serum amyloid A and serum amyloid P synthesis by cultured mouse hepatocytes.

Regulation of the in vitro synthesis of the serum amyloid proteins A and P has been studied with hepatocyte cultures from CBA/J and C3H/HeJ mice. Liver cells were isolated by the collagenase perfusion technique and established for 48 h in the presence of fetal calf serum. Viable cells could then be maintained in the absence of serum for at least 72 h and in the presence of serum for up to 2 weeks. Serum amyloid A synthesis differed from serum amyloid P synthesis in three significant ways. 1) Serum amyloid A production was stimulated in the presence of fetal calf serum, whereas serum amyloid P was not; 2) serum amyloid A synthesis was increased 200% by monokine-rich macrophage supernatants while serum amyloid P was increased only 10 to 20%; 3) serum amyloid A synthesis was strikingly resistant to cycloheximide inhibition as compared with serum amyloid P and other liver proteins. It is concluded that the in vivo asynchrony of the acute phase serum amyloid A and serum amyloid P responses results at least in part from differences in regulatory mechanisms for their synthesis by hepatocytes.

Amyloid↗
PubMed1989

Efficacy of wheat germ lectin-precipitated alkaline phosphatase in serum as an estimator of bone mineralization rate: comparison to serum total alkaline phosphatase and serum bone Gla-protein.

Serum levels of total alkaline phosphatase activity (S-T-AP), wheat germ lectin-precipitated alkaline phosphatase activity (S-L-AP), and bone Gla-protein immunoreactivity (S-BGP) were measured in 26 patients (23 females and 3 males) aged 35-73 years (mean 59 years) with primary hyperparathyroidism (n = 7), hyperthyroidism (n = 9), and hypothyroidism (n = 10) in whom the bone mineralization rate (m) was determined by 47Ca-kinetics (continuously expanding calcium pool model). A weak positive correlation (r = 0.42, P less than 0.05) was found between S-T-AP and m, which in the range from 0-18 mmol Ca/day could be estimated with a standard error of 4.6 mmol/day. A closer correlation (r = 0.65, P less than 0.001) was found between S-L-AP and m which was estimated with an error of 3.9 mmol Ca/day. The AP activity in the supernatant showed no significant correlation to m (r = 0.11, P greater than 0.50). The highest correlation coefficient (r = 0.81, P less than 0.001) was found between S-BGP and m which could be predicted with an error of 3.4 mmol Ca/day. S-BGP showed a closer correlation to S-L-AP (r = 0.71, P less than 0.001) than to S-T-AP (r = 0.58, P less than 0.01). We concluded that S-L-AP predicts bone mineralization at organ level better than S-T-AP in selected metabolic bone disorders and that the supernatant activity shows no relation to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

When is a serum iron really a serum iron? The status of serum iron measurements.

Although serum iron determinations play an important role in the diagnostic process, the accuracy of routine methods is suspect. The poor performance of currently used methods is well documented in the quarterly College of American Pathologists survey reports. Compared with the 1990 method of the International Committee for Standardization in Haematology (ICSH), the 1978 ICSH Reference Method shows a +3.4% bias and the standard method of the National Committee for Clinical Laboratory Standards shows a -17.8% bias for iron results. All routine methods checked--DuPont aca, Abbott TDx, Kodak Ektachem (except one lot), BM/Hitachi 717, and Synermed--show a negative bias over the entire analytical range, a significant negative intercept, and extremely poor correlation with the 1990 ICSH method for iron values < 750 micrograms/L. Individual discrepancies of several hundred percent were observed. Imprecision of the methods is not the reason for these discrepancies. We question whether most routine methods measuring low iron concentrations provide results sufficiently reliable for confirmation of iron deficiency.

Autoanalysis↗
PubMed2006

Serum HDL-C levels, log (TG/HDL-C) values and serum total cholesterol/HDL-C ratios significantly correlate with radiological extent of disease in patients with community-acquired pneumonia.

BACKGROUND: In several studies, it was shown that there was a marked decrease in serum levels of HDL-C during infection and inflammation in general. In particular, a decrease in the level of serum HDL-C was also shown in pneumonia. Correlations between inflammatory markers such as acute phase proteins, cytokines and serum HDL-C levels were shown. However, there are no studies indicating a correlation between serum HDL-C levels and the radiological extent of the disease (RED) in community-acquired pneumonia (CAP). AIM: We hypothesized that there could be a relationship between serum HDL-C levels and RED in CAP. MATERIALS AND METHODS: A case-controlled study, including 97 patients with CAP and 45 healthy subjects, was performed. Chest X-rays of CAP patients were scored for RED, and correlations were investigated between RED scores, serum lipid parameters, the erythrocyte sedimentation rate (ESR) and serum albumin levels. RESULTS: The mean serum HDL-C level was lower in CAP patients than in controls. A significant and negative correlation between RED scores (REDS) and serum HDL-C levels was detected (r = -0.64, P = 0.0001). There were also significant correlations between REDS and other lipid parameters. Significant correlations between ESR and serum HDL-C levels and between ESR and other serum lipid parameters were also found. CONCLUSION: It appears that serum HDL-C levels are generally lower in CAP cases than in healthy controls. Serum HDL-C levels and serum albumin levels might decrease and serum total cholesterol/HDL-C ratios and log (TG/HDL-C) values might increase proportionally with RED in CAP patients. These results might have some significance for individuals having long-standing and/or recurrent pneumonia and other cardiovascular risk factors.

Adolescent↗
PubMed2006

Multivariate analysis of prognostic determinants for colorectal cancer patients with high preoperative serum CEA levels: prognostic value of postoperative serum CEA levels.

High preoperative serum carcinoembryonic antigen (CEA) levels have been well investigated and found to be associated with poor prognosis in patients with colorectal cancer (CRC). However, it has been observed that the outcome varies after curative resection, along with postoperative serum CEA levels; some patients continue to have high postoperative serum CEA levels while postoperative CEA levels return to normal in others. The purpose of this study was to determine the prognostic significance of postoperative serum CEA levels in CRC patients with high preoperative serum CEA levels. Between January 2002 and December 2004, 423 CRC patients underwent operation in our hospital; 181 (42.8%) had high preoperative serum CEA levels and were enrolled in this study. Among the 181 patients, 165 patients had curative resection; the remaining 16 had stage IV disease, so they underwent palliative surgery and were subsequently excluded from analysis. Pre- and postoperative serum CEA levels were measured and analyzed. All patients had curative resection and were divided into two groups according to postoperative serum CEA levels: one group comprised patients with postoperative serum CEA > or = 5 ng/mL (n = 80) and the other group comprised patients with postoperative serum CEA levels < 5 ng/mL (n = 85). Postoperative serum CEA levels were significantly related to location of primary tumors (p = 0.042), lymph node metastases (p = 0.009), TNM stage (p = 0.001), and postoperative relapse (p = 0.004). The results of multivariate analysis showed that both lymph node metastases and high postoperative serum CEA levels (> or = 5 ng/mL) were independent prognostic factors for CRC patients after curative resection. Postoperative serum CEA levels can be a single independent prognostic determinant in CRC patients with high preoperative serum CEA levels. Intensive follow-up and adjuvant therapy may be necessary in CRC patients who continue to have high postoperative serum CEA levels even after curative resection.

Adult↗
PubMed2005

Effects of locoweed on serum swainsonine and selected serum constituents in sheep during acute and subacute oral/intraruminal exposure.

A study was conducted to evaluate the effects of acute and subacute locoweed exposure on serum swainsonine concentrations and selected serum constituents in sheep. Thirteen mixed-breed wethers (BW = 47.5 +/- 9.3 kg) were assigned randomly to 0.2, 0.4, or 0.8 mg of swainsonine x kg BW(-1) x d(-1) treatments. During acute (24 h) and subacute (19 d) exposure, serum swainsonine was detected in all treatments and was greatest (P < 0.03) in the 0.8 mg treatment. Serum alkaline phosphate (ALK-P) activity was increased (P < 0.01) for the 0.8 mg treatment compared with baseline (0 h) by 7 h and continued to increase throughout the initial 22 h following acute exposure to locoweed. A linear increase (P < 0.01) in serum ALK-P activity was noted, with the rate being 3.00 +/- 0.56 U x L(-1) x h(-1). Serum ALK-P activity was increased (P < 0.05) across treatments on d 7 over d -19, -12, 0, 1, 21, and 26; on d 14 over d -19, -12, 0, and 26; and on d 19 over d -19, -12, 0, 1, 21, and 26. By d 20, approximately 48 h after last exposure to swainsonine, serum ALK-P activities were no longer different (P = 0.13) than baseline (d -19, -12, and 0), and by d 26 values had generally returned to baseline. No linear (P = 0.98), quadratic (P = 0.63), or cubic effects of swainsonine with time from exposure were noted for serum aspartate aminotransferase. Similar to serum ALK-P activities, serum aspartate aminotransferase activities were increased (P < 0.05) across treatment levels on d 7, 14, 19, 20, 21, and 26 over those on d -19, -12, 0, and 1. Total serum Fe was decreased (P < 0.05) within the initial 22 h following the swainsonine exposure. On d 21 (48 h after swainsonine feeding ended), serum Fe increased to 472 mg/L. Concentrations of ceruloplasmin were lower (P < 0.10) on d 14 and 19 following exposure to locoweed. Recovery of ceruloplasmin levels coincided with similar changes in serum Fe. There was a linear (slope = 0.33 mg x dL(-1) x d(-1); P < 0.01) effect with time of exposure to locoweed (i.e., swainsonine) on serum triglyceride concentrations. Rapid changes in serum ALK-P and Fe concentrations without parallel changes in other damage markers indicate that acute exposure to swainsonine induces metabolic changes that may impair animal production and health before events of cytotoxicity thought to induce clinical manifestation of locoism.

Administration, Oral↗
PubMed1999

Natural estrous cycle in normal and diabetic bitches. II). Serum nonesterified fatty acids and serum free glycerol levels during glucose and insulin tests.

Actions and interactions of spontaneous diabetes mellitus (DM) and natural estrous cycles (sex seasons) on the regulation of serum nonesterified fatty acids (NEFAs) and free glycerol (FG) levels in bitches in the fasting condition and during i.v. glucose (IVGTT) and insulin (ITT) tolerance tests, were studied. DM increased serum NEFAs concentration both in the basal condition and during IVGTT; it provoked a fall response to glucose load which is absent in normal controls. Estrous cycles did not modify these observations. Serum NEFAs levels during ITT were unresponsive in normal and diabetic bitches at every sex stage; flat, overlapped serum NEFAs profiles were then observed except for the diabetic group at A, which showed an early abrupt fall response of this variable from its high base line. DM increased also serum FG concentration in the fasting condition and during IVGTT. In the normal controls, serum FG base line was not affected by sex status; similarly shaped, increasing, overlapped curves during the test were observed. In the diabetic bitches "in season" (either phase), serum FG basal value was hardly above in respect to anestrous, but during IVGTT their flat profiles coincided. DM increased serum FG concentration in the basal condition and during ITT, and modified the profiles of this variable. In normal dogs in the basal condition, serum FG concentration remained unaffected by sex status; this variable hard, transiently increased during ITT, which was not influenced by "sex seasons"; therefore, similarly shaped, overlapped serum FG profiles were then observed. In the normal and diabetic bitches, serum-FG base line was not changed by "sex seasons". During ITT, serum FG mean profile in the diabetic bitches at EP was modestly above that observed in those at LP; differences for any other comparisons in normals or diabetic bitches were nonsignificant. As reported by us elsewhere, impaired glucose metabolism and absolute insulin deficiency induced ketose-prone, acidotic, insulin-dependent diabetic chryses in certain normal and diabetic beaches "in season" studied here. The unability of these animals for hydrolizing glyceride-glycerol via lipoproteinlipase (IVGTT) or via hormone sensitive fractions of lipase (ITT) and the abolished serum NEFAs suppressibility during modest hiperinsulinemia (ITT) appear to contribute to the production of such chryses. Results are discussed on the basis of interactions of serum NEFAs and FG with respective blood sugar and serum immunoreactive insulin levels as influenced by DM and estrous cycle.

Analysis of Variance↗
PubMed1991

Serum lysyl oxidase activity in chronic liver disease in comparison with serum levels of prolyl hydroxylase and laminin.

Lysyl oxidase was partially purified from serum by a diethylaminoethyl batch procedure in the presence of 6 mol/L urea and dialyzed against 3 mol/L KSCN. Using this method, we determined serum lysyl oxidase activity in 52 patients with liver disease and in 14 healthy controls, and we examined usefulness of serum lysyl oxidase in assessing liver fibrogenesis. For this purpose, serum lysyl oxidase activity in chronic liver disease was compared with serum levels of prolyl hydroxylase and laminin P1. As compared with controls, serum lysyl oxidase activity increased 1.6-fold in chronic persistent hepatitis, 4.4-fold in chronic active hepatitis and 11.8-fold in cirrhosis, indicating an increase in concert with the development of liver fibrosis. In hepatocellular carcinoma, the serum activity, although significantly increased, was lower than that in cirrhosis. Serum prolyl hydroxylase was significantly increased in chronic active hepatitis, in liver cirrhosis and in hepatocellular carcinoma. Serum laminin P1 was significantly increased in chronic active hepatitis, in cirrhosis and in hepatocellular carcinoma. Serum lysyl oxidase activity did not correlate significantly with serum levels of prolyl hydroxylase and laminin P1 in any subject or in any subgroup. The magnitude of the increase and the abnormal percentage of serum lysyl oxidase activity were larger than those for serum prolyl hydroxylase and laminin P1. These results suggest that serum lysyl oxidase activity is a more sensitive indicator of liver fibrosis than serum prolyl hydroxylase and laminin P1.

Adult↗
PubMed1976

Serum dependence of expression of the transformed phenotype: experiments with subline of mouse L fibroblasts adapted to growth in serum-free medium.

Characteristics of LSF cells grown in serum-containing and serum-free medium were compared. LSF is a subline of the L-strain of mouse transformed fibroblasts adapted to continuous growth is serum-free medium. Proliferation of LSF cells in monolayer on solid substratum was almost similar in serum-containing and in serum-free media. However, several other characters were found to be altered by the addition of serum to the serum-free medium: ability of cells to form colonies in semi-solid medium increased considerably; agglutinability of cells by Concanavalin A increased; uptake of 2-deoxy-D-glucose by the cells increased considerably; ability of cells to metabolize benzo (a) pyrene was inhibited; cell morphology was altered and, in particular, the cells became less spread on the substratum and density of microvilli on the cell surface increased. All these changes induced by serum were reversed by transfer of the cells back into serum-free medium. Thus, addition of serum increased the expression of a number of cellular traits characteristic of transformed phenotype, while in serum-free medium partial phenotypic reversion of transformation was observed. A possible role of serum in the expression of the transformed phenotype is discussed. It is pointed out that cell lines adapted to growth in serum-free medium provide an experimental system convenient for analysis of the effects of different serum components on the cell phenotype.

Animals↗
PubMed2002

Serum vascular endothelial growth factor and serum leptin in patients with cervical cancer.

OBJECTIVE: Serum levels of vascular endothelial growth factor (VEGF) can be seen as surrogate markers of angiogenesis. Recently, leptin, which is involved in the control of satiety and energy expenditure, was also shown to modulate angiogenesis. As angiogenesis plays an abundant role in cervical carcinogenesis, we evaluated serum VEGF and leptin in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: Serum VEGF and leptin were measured in 84 patients with cervical cancer, in 28 patients with CIN I-III, and in 35 healthy women, using a commercially available enzyme-linked immunosorbent assay and radioimmunoassay, respectively. RESULTS: Serum VEGF was significantly elevated in patients with cervical cancer and in patients with CIN I-III compared to healthy women. In patients with cervical cancer serum VEGF was significantly correlated with tumor stage, but not with lymph node involvement and histological grade. Univariate and multivariate analyses showed that elevated pretreatment serum VEGF was not associated with the duration of disease-free and overall survival. Serum leptin did not differ among patients with cervical cancer, patients with CIN I-III, and healthy women. Serum leptin was significantly correlated with body mass index (BMI). All further analyses were performed with absolute and serum leptin corrected by BMI. No differences in serum leptin could be ascertained between patients with cervical cancer and patients with CIN I-III. Serum leptin was not associated with any clinicopathological parameter and patients' survival. No correlation between serum VEGF and leptin was found. CONCLUSIONS: It can be speculated that serum VEGF might be used as a surrogate marker of angiogenesis in patients with cervical cancer. Our data support the concept that VEGF plays a role in malignant transformation and tumor growth, but not in the lymphatic spread of cervical cancer. This is the first report on leptin in a gynecological malignancy. Our results show that serum leptin falls short of being a useful marker in patients with cervical cancer.

Adult↗
PubMed1991

Effects of serum, its protein and lipid extracts, and commercial serum proteins and lipid on the isolated frog heart.

This study investigates the inotropic effects of serum, its protein and lipid extracts, and commercial serum proteins and lipid on the isolated, spontaneously-beating heart and superfused, hypodynamic ventricle of the frog. Serum taken from either man, horse, calf, frog, or rabbit evoked marked positive inotropic responses which were unaffected by cholinergic, serotonergic, and adrenergic receptor antagonists. Dialysed serum (dialisand) and void volume fractions from Sephadex G200-120 columns corresponding to large molecular weight constituents evoked marked positive inotropic responses. When serum was separated into fractions containing either proteins or lipids/lipoproteins by high-density ultracentrifugation or activated charcoal, both extracts evoked marked positive inotropic responses. Commercial serum globulins and serum containing a high proportion of immunoglobulins elicited large increases in contractile force, whereas serum albumin evoked a negative inotropic effect. Serum which was either boiled and/or treated with chymotrypsin to denature proteins also caused a marked increase in isometric twitch tension in the frog heart. Similar inotropic response was obtained with fractions of boiled serum eluted on columns of Sephadex G200-120. These fractions corresponded to molecular weight in the region of 60-70 kDa. However, the inotropic effect of boiled serum was abolished following pretreatment with lipase. Superfusion of frog hearts with commercial cardiolipin resulted in marked dose-dependent increases in contractile force. The results demonstrate the presence of at least two large molecular weight cardioactive principles in serum. These substances are comparable in size to constituents of serum proteins (e.g., globulins and immunoglobulins) and serum lipids/lipoproteins (e.g., cardiolipin) and may serve as physiological regulators of cardiac function.

Animals↗
PubMed1992

Effect of serum and serum lipoproteins on testosterone production by adult rat Leydig cells in vitro.

The effect of serum factors other than luteinizing hormone on Leydig cell testosterone secretion was examined using an in vitro bioassay system based on the stimulation of purified adult rat Leydig cells during a 20 h incubation in the presence of a maximal dose of human chorionic gonadotrophin (hCG). Charcoal-extracted serum and testicular interstitial fluid (IF) from normal adult male rats were separated into lipoprotein and lipoprotein-deficient fractions by density ultracentrifugation. Stimulatory bioactivity was found in the lipoprotein fraction of both serum and IF, although the levels of lipoprotein and corresponding bioactivity recovered from IF were significantly lower (25%) than those of serum. There was no difference between the effects of serum lipoproteins on Leydig cell testosterone production stimulated by either hCG or dibutyryl cAMP. In time-course studies, the serum lipoprotein fraction had no effect on hCG-stimulated testosterone production in vitro at 3.0 or 6.0 h, but partially prevented the normal decline in hCG-stimulated testosterone production after 6.0 h. In contrast, unfractionated serum was stimulatory at all time-points. In the absence of hCG, the lipoprotein fraction was stimulatory at both 6.0 and 20 h, although not at 3.0 h. The lipoprotein-deficient protein fraction of serum had no effect on hCG-stimulated testosterone production alone, but significantly enhanced the bioactivity of the lipoprotein fraction, and caused a dose-dependent stimulation of testosterone production in the presence of a constant concentration of serum lipoproteins. Both a stimulatory peak of activity (apparent MW 40-80 kDa), and a large MW (> 100 kDa) inhibitor of testosterone production were identified in serum after fractionation by gel filtration (Sephadex G-100). The data indicate that (i) the stimulatory effect of serum on short-term hCG-stimulated Leydig cell testosterone production in vitro is predominantly due to the serum lipoprotein fraction, possibly by providing additional precursors for testosterone synthesis, (ii) the biological activity of the lipoproteins is influenced by both stimulatory and inhibitory serum proteins in addition to luteinizing hormone, and (iii) that serum lipoproteins may be involved in supporting Leydig cell steroidogenesis in vivo.

Animals↗
PubMed2004

Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population.

Leptin plays an important role in the regulation of body weight and is known to circulate in both free and bound forms. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. Clinical studies have shown that soluble leptin receptor (sOB-R) levels are lower in obese individuals. In the present study, we measured the serum sOB-R level in 419 healthy Japanese subjects (198 men and 221 women, aged 30 to 65 years, body mass index [BMI] 21.7 +/- 2.6 [SD] kg/m2) and in 150 type 2 diabetic patients (96 men and 54 women, BMI 24.3 +/- 3.8 kg/m2). We investigated the relationships between serum sOB-R level and BMI, blood pressure, homeostasis model assessment-insulin resistance index (HOMA-IR), serum leptin and adiponectin levels, lipid profile, and leptin receptor (LEPR) gene Lys109Arg and Gln223Arg polymorphisms. Serum leptin and sOB-R levels were measured by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), respectively. The serum sOB-R level in men was significantly higher than that in women. The serum sOB-R level was negatively correlated with BMI, fasting insulin, HOMA-IR, and serum leptin level and positively correlated with high-density lipoprotein (HDL)-cholesterol and serum adiponectin levels. The correlations between serum sOB-R level and fasting insulin, HOMA-IR, serum leptin, adiponectin, and HDL-cholesterol levels were significant even after adjustment for age, sex, and BMI in healthy subjects. There was no association between serum sOB-R level and the LEPR polymorphisms examined. These findings suggest that the serum sOB-R level is negatively correlated with HOMA-IR and serum leptin level and positively correlated with HDL-cholesterol level and serum adiponectin level, independent of age, sex, and BMI, in the Japanese population.

Adiponectin↗
PubMed2001

Delipidated serum abolishes the inhibitory effect of serum on in vitro liposome-mediated transfection.

All the standard in vitro lipofection has been routinely performed in serum-free medium as the transfection activity of liposome/DNA complexes is sensitive to the presence of serum. In this study, we have demonstrated that lipid-rich serum lipoprotein included in the transfection medium strongly inhibited the transfection activity of DC-chol liposome/DNA complexes in five different cell types (CHO, 293, A2780CP, A431 and SKBR3). The levels of inhibition by serum lipoprotein were rather greater than those by serum and varied with cell types. However, this inhibition was completely abolished by delipidation of serum. Thus, delipidated serum can be included in the transfection medium. The complexes formed in the presence of serum (zeta=-18.2+/-1.07 mV), delipidated serum (zeta=-19.6+/-0.54 mV), IgG (zeta=-21.6+/-1.92 mV) or serum lipoprotein (zeta=-10.5+/-2.33 mV) were as much negatively charged as those in serum-free medium (zeta=-21.3+/-1.60 mV). The results suggest that the inhibition of liposome-mediated transfection by serum was not associated with charges of serum proteins but with lipids or lipid-associated proteins present in serum.

Animals↗
PubMed2001

Serum crosslaps in comparison to serum osteocalcin and urinary bone resorption markers.

In this study we evaluated the routine practice and clinical application of serum crosslaps to urinary-crosslaps, -N-telopeptide-related fraction of type 1 collagen, -deoxpyridinoline, -totalpyridinoline and serum osteocalcin. The utility of both the serum and urine immunoassays for bone formation and resorption marker were tested in a cohort of 593 female and male patients from our outpatient clinic for osteology and rheumatology and compared to important osteoporosis risk factors like age, gender, E2 deficiency, bone density and chronic renal failure. The biochemical maker of bone formation, serum osteocalcin exhibit significant correlations to all five tested serum and urinary markers of bone resorption (p < 0.0001) crosswise to all different groups of patients. The group of chronic renal failure patients showed no significant correlation between the tested bone turnover parameters and the serum creatinine level except a significant increase and correlation for serum crosslaps and for the ratio of serum and urinary crosslaps. Associations between the age of the patients and the markers of bone turnover were rather poor. We found a significant, negative association between serum and urinary bone turnover markers and bone density and were interested, whether in patients with bone density < 2.5 SD an enhanced bone turnover could be detected in the same way as for E2 deficiency. Applying a discriminant analysis it was possible to discriminate between the patient with BD < 2.5 SD and those with BD > 1.0 SD with a sensitivity of 70% and a specificity of 65% using serum crosslaps. In case of urinary crosslaps the discriminatory power was slightly lower (sensitivity: 65.6%, specificity: 67.5%) and for serum osteocalcin the discriminatory power was negligible higher (sensitivity: 79%, specificity: 56%). The highly significant correlation between the urinary and serum crosslinked peptides by ELISA and serum osteocalcin supports the concept that these respective indices of bone formation and resorption both in urine and serum reflect a coupled process in vivo with sensitivity and specificity to pathological bone density, estrogen deficiency and chronic renal failure.

Adult↗