Changes in circulating levels of immunoreactive follicle stimulating hormone, luteinizing hormone, and testosterone during sexual development in the rhesus monkey, Macaca mulatta

Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH.     

The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women

The aim of our study was to determine whether adipocyte-derived hormones leptin, adiponectin and resistin contribute to the improvement of insulin sensitivity after very-low calorie diet (VLCD). Therefore, serum levels of these hormones were measured in fourteen obese females before and after three weeks VLCD and in seventeen age- and sex-matched healthy controls. Body mass index, HOMA index, serum insulin and leptin levels in obese women before VLCD were significantly higher than in control group (BMI 48.01+/-2.02 vs. 21.38+/-0.42 kg/m(2), HOMA 10.72+/-2.03 vs. 4.69+/-0.42, insulin 38.63+/-5.10 vs. 18.76+/-1.90 microIU/ml, leptin 77.87+/-8.98 vs. 8.82+/-1.52 ng/ml). In contrast, serum adiponectin and soluble leptin receptors levels were significantly lower in obese women before VLCD than in the control group. No differences were found in serum glucose and resistin levels between the obese group before VLCD and the control group. VLCD significantly decreased BMI, HOMA index, serum glucose, insulin and leptin levels and increased soluble leptin receptor levels. The changes in serum adiponectin and resistin levels in obese women after VLCD did not reach statistical significance. We conclude that leptin and soluble leptin receptor levels were affected by VLCD while adiponectin and resistin concentrations were not. Therefore, other mechanisms rather than changes in the endocrine function of the adipose tissue are probably involved in the VLCD-induced improvement of insulin sensitivity.     

Effects of PPARgamma and PPARalpha agonists on serum leptin levels in diet-induced obese rats.

Leptin and peroxisome proliferator-activated receptors are two important adipose tissue factors involved in energy metabolism regulation. It has been shown that PPARgamma agonists decrease leptin levels. However, the effects of PPARalpha agonists on leptin have not been investigated much. The aim of this study was to compare the effects of a PPARgamma agonist rosiglitazone (RSG) and PPARalpha agonist gemfibrozil (G) on body weight and serum insulin and leptin levels in diet-induced obese rats. Male Wistar rats were divided into six groups according to diet and drug therapy. After four weeks, serum glucose, triglyceride, insulin and leptin levels were significantly decreased in the high-fat-fed and RSG-treated groups compared to the group fed a high-fat diet only (162 +/- 19 vs. 207 +/- 34 mg/dl, 58 +/- 20 vs. 112 +/- 23 mg/dl, 3.1 +/- 1.0 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.5 vs. 3.6 +/- 1.6 ng/ml, respectively). However, these parameters were not statistically different in RSG animals treated with a standard diet compared to the standard diet group. The high fat+RSG group gained much more weight compared to high-fat and high-fat+G groups (p > 0.05). Additionally, serum glucose, insulin and leptin levels were significantly decreased in the high-fat-fed and G-treated group compared to high-fat group (149 +/- 19 vs. 207 +/- 34 mg/dl, 57 +/- 16 vs. 112 +/- 23 mg/dl, 4.3 +/- 2.1 vs. 15.2 +/- 4.0 ng/ml, 1.6 +/- 0.4 vs. 3.6 +/- 1.6 ng/ml, respectively). These results suggest that PPARalpha agonists may decrease serum glucose, insulin and leptin levels as PPARgamma agonists do in diet-induced obese rats.     

Changes in circulating inhibin levels during pregnancy and early lactation in the Japanese monkey

Changes in immunoreactive (ir-) inhibin concentrations in serum throughout pregnancy and early lactation up to one month after parturition were characterized in 6 Japanese monkeys (Macaca fuscata fuscata) by a heterologous radioimmunoassay (RIA) based on a bovine RIA. Serum levels of FSH, LH/monkey chorionic gonadotropin (mCG), estradiol-17 beta, and progesterone were also monitored for the entire period. Ir-inhibin levels in the serum were low (under 0.5 ng/ml) before conception. Three marked increases in serum ir-inhibin levels were found during pregnancy. The first increase was noted during early pregnancy, with a peak (2.2 +/- 0.2 ng/ml) at Day 22 of pregnancy (Day 0 = day of LH surge). The second increase was noted after Day 38 until Day 72 of pregnancy, when a peak value was noted (19.0 +/- 1.4 pg/ml). Plateau levels were maintained until late pregnancy, and a final rise was evident near the term with a peak (36.7 +/- 3.8 ng/ml) at Day 158 of pregnancy, 5 days before parturition. After parturition, ir-inhibin levels in the serum plummeted to nonpregnant levels within one day, and were maintained during early lactation. The first rise in serum inhibin during pregnancy was parallel to the rise of mCG and estradiol-17 beta, and the second and third rise were well correlated with serum estradiol-17 beta. Serum FSH was maintained at low levels throughout pregnancy, followed by a slight increase after parturition when serum inhibin decreased abruptly. Both bioactivity and immunoreactivity of inhibin were detected in the placental homogenates obtained at 120 days of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leptin levels in obese children: effects of gender,weight reduction and androgens

Obesity in children is accompanied by increased circulating leptin concentrations. Girls have higher leptin concentrations than boys. The aim of our study was to compare serum leptin levels before and after a five-week weight reduction program and to study the relationship of leptin levels, serum total cholesterol, and androgens (testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulphate) in 33 obese boys (age: 12.7+/-1.97 years, BMI: 30.46+/-4.54) and 66 obese girls (age: 12.7+/-2.51 years, BMI: 29.31+/-4.62). We found that serum leptin concentrations in obese children were significantly decreased after a weight reduction program (before 20.79+/-9.61 ng/ml, after 13.50+/-8.65 ng/ml in girls; before 12.25+/-10.09 ng/ml and after 5.18+/-3.56 ng/ml in boys, p<0.0001 in both genders). Leptin levels correlated positively with the body mass index before and after weight reduction. There was a positive association in obese boys and a negative one in obese girls between leptin levels and the WHR (waist to hip circumference ratio). Serum leptin also shows a strong relationship to fat distribution (p=0.02 in boys, p<0.0001 in girls). No significant correlation was found between leptin concentrations and total cholesterol or androgens. We confirmed that leptin is a sensitive parameter of body composition and weight reduction in obese children.     

The relationship between androgens concentrations (testosterone and dehydroepiandrosterone sulfate) and metabolic syndrome in non-obese elderly men

INTRODUCTION: The metabolic syndrome characterized by central obesity, insulin and lipid dysregulation, and hypertension, is a precursor state for atherosclerotic process and, in consequence, cardiovascular disease. Decline of both testicular and adrenal function with aging causes a decrease in androgen concentration in men. It has been postulated that low levels of total testosterone and dehydroepiandrosterone sulfate (DHEA-S) are associated with unfavorable levels of several strong cardiovascular disease risk factors, such as lipids and blood pleasure, which are components of the metabolic syndrome, and insulin levels. Both testosterone and DHEA-S deficiency are risk factors of obesity and insulin resistance, but it is not clear, whether this possible influence is independent. The aim of this study was to determined whether lower androgens (testosterone and DHEA-S) levels are associated with the development of metabolic syndrome in non-obese elderly men as well as analysis, whether these sex hormones influents on measured parameters separately. MATERIAL AND METHODS: Together 85 men age from 60 to 70 years (mean 66.3 +/- 1.5 years; mean +/- SEM) were analyzed. Testosterone levels < 4 ng/ml or DHEA levels < 2000 ng/ml and BMI < 30 kg/m(2) were including criteria. Patients were divided into three groups: 52 with testosterone deficiency (L-T), 32 with DHEA deficiency (L-DHEA-S) and 67 with deficiency of both sex hormones (L-T/DHEA-S). The influence of sex hormones deficiency in these groups on blood pressure, lipids, visceral obesity and fasting glucose were measured (according to metabolic syndrome definition NCEP III/IDF). RESULTS: Testosterone levels in L-T, L-DHEA and L-T/DHEA-S groups were respectively 3.19 +/- 0.23 ng/ml, 4.89 +/- 0.45 ng/ml and 3.25 +/- 0.34 g/ml (p < 0.002). While DHEA-S levels were respectively 2498 +/- 98 ng/ml, 1435 +/- 1010 ng/ml and 1501 +/- +/- 89 ng/ml). BMI values do not differ between groups. Waist circumference was significantly higher in L-T/DHEA-S group than in L-T i L-DHEA-S groups (respectively: 99.9 +/- 6,1 cm, 97.1 +/- 7.1 cm i 96.2 +/- 6.4 cm; mean +/- SD, p < 0.05 vs. L-T and L-DHEA-S groups). Mean triglycerides concentration in L-T/DHEA-S group was significantly higher than in L-T and L-DHEA-S groups (respectively: 188.2 +/- 13.3 mg/dl, 161.7 +/- 14.7 mg/dl and 152.2 +/- 12.8 mg/dl (mean +/- SD; p < 0.02 vs. L-T and L-DHEA-S groups). Analysis of prevalence of risk factors showed, that in L-T/DHEA-S group they were more frequent than in other groups. The most significant percentage difference was observed for triglycerides: concentration > or = 150 mg/dl was measured in 31% men in L-T group, 28% men in L-DHEA-S group and 42% men in L-T/DHEA-S group. According metabolic syndrome definition NCEP III/IDF prevalence of this syndrome was: 71% patients in L-T/DHEA-S group, 67% patients in L-T group and 64% patients in L-DHEA-S group. CONCLUSIONS: The DHEA-S and testosterone deficiency was a significant and independent risk factor of the metabolic syndrome in non-obese elderly men. It seems, that triglycerides concentration and waist circumference are more sensitive then others parameters to reflect the influence of sex hormones deficiency on risk of the metabolic syndrome in elderly men.     

Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma.

The aim of this study was to verify whether treatment with slow-release lanreotide (SRL) before surgery is useful in the management of patients with GH-secreting pituitary macroadenoma. Twenty untreated acromegalics were enrolled randomly in two groups. Ten patients (group 1: 2 males and 8 females aged 44.5 +/- 4.3 years) underwent surgery via transsphenoidal access. Only one of them was cured by surgery, whereas the other nine were treated with SRL. In the other ten patients (group 2: 3 males and 7 females aged 43.2 +/- 12.3 years), transsphenoidal surgery followed SRL treatment. Surgery induced the normalization of GH and IGF-1 levels in four group 2 patients - three of them had shown an evident shrinkage of the tumor after SRL treatment. After surgery, group 1 showed a significant decrease of mean IGF-1 (580 +/- 63 vs. 789 +/- 64 ng/ml, p < 0.02), but not of GH values (26.1 +/- 9.8 vs. 44.8 +/- 19.3 ng/ml, NS); the cured patient was excluded from the following evaluations. Group 2 showed an evident, but not significant, decrease of both GH and IGF-1 values compared to values measured at the end of medical treatment (GH: 22.4 +/- 9.7 vs. 7.7 +/- 4.7 ng/ml, NS. IGF-1: 570 +/- 69 vs. 402 +/- 58 ng/ml, NS). Gonadal, thyroid and adrenal impairment was evident in six, four and no patients in group 1 and in three, two and one patients in group 2, respectively. SRL 30 mg was administered every 14 days for three months and then every 10 days until the 6th month. Before SRL treatment, mean GH and IGF-1 levels did not differ significantly in group 1 vs. group 2 (GH: 29.3 +/- 10.5 vs. 43.4 +/- 22.0 ng/ml; IGF-1: 633 +/- 38 vs. 778 +/- 83 ng/ml). In group 1, a significant decrease of serum GH, but not of IGF-1 levels, was achieved at the end of 1st trimester of SRL (GH: 17.6 +/- 5.4 ng/ml, p < 0.05. IGF-1: 540 +/- 48 ng/ml, NS), whereas a significant decrease in both GH and IGF-1 values was evident during the 2nd trimester (GH: 6.1 +/- 3.0 ng/ml, p < 0.05. IGF-1: 433 +/- 74 ng/ml, p < 0.02). Serum GH levels, measured during the 2nd trimester of SRL therapy, were also significantly lower than levels measured at the end of the 1st trimester (p < 0.05). Group 2 serum GH and IGF-1 levels were not significantly decreased at the end of the 1st trimester (GH: 27.2 +/- 12.1 ng/ml, NS. IGF-1: 698 +/- 74 ng/ml, NS), whereas only serum IGF-1 (570 +/- 69 ng/ml, p < 0.05) was significantly reduced during the 2nd trimester of SRL (GH: 22.4 +/- 9.7 ng/ml, NS). Serum GH and IGF-I fell in the normal range in 4 patients in group 1 and one in group 2 at the end of the second trimester of SRL therapy. Independently of the trial applied, the mean clinical score level ameliorated significantly in both groups (group 1: p < 0.0005; group 2: p < 0.0001). In both groups, the proportion of patients complaining of headache and tissue swelling and the score level of headache, tissue swelling and excessive sweating decreased significantly. In group 1 the score level of fatigue and arthralgia also decreased significantly. In conclusion, this study proves that in patients with GH-secreting pituitary macroadenoma: (i) surgery followed by SRL induces a better clinical and biochemical status than SRL alone; (ii) SRL treatment before surgery ameliorates the clinical and biochemical outcome and reduces the prevalence of hypopituitarism due to surgery.     

Preclinical pharmacokinetic characterization of an adipose tissue-targeting monoclonal antibody in obese and non-obese animals

Target receptor levels can influence pharmacokinetics (PK) or pharmacodynamics (PD) of monoclonal antibodies (mAbs), and can affect drug development of this class of molecules. We generated an effector-less humanized bispecific antibody that selectively activates fibroblast growth factor receptor (FGFR)1 and βKlotho receptor, a FGF21 receptor complex highly expressed in both white and brown adipocytes. The molecule shows cross-species binding with comparable equilibrium binding affinity (Kd) for human, cynomolgus monkey, and mouse FGFR1/βKlotho. To understand the PK/PD relationship in non-obese and obese animals, we evaluated the adipose tissue distribution of the antibody, serum exposures, and an associated PD marker (high-molecular-weight adiponectin), in both non-obese and obese mice and monkeys. Antibody uptake into fat tissue was found to be higher on a per gram basis in non-obese animals compared to obese animals. Since obesity has been reported to be associated with reduced expression of FGFR1 and βKlotho receptor in white adipose tissues in mice, our results suggest that the distribution in adipose tissues was influenced by target expression levels. Even so, the overall dose-normalized serum exposures were comparable between non-obese and obese mice and monkeys, suggesting that adipose tissue uptake plays a limited role in overall systemic PK determination. It remains to be determined if and how obesity and receptor expression in humans influence the PK and PD profile of this novel therapeutic candidate.     

Radioimmunoassay of 5-androstene-3 beta,17 beta-diol in plasma and in breast cyst fluid

A simple and reliable radioimmunoassay for the determination of 5-androstene-3 beta, 17 beta-diol in peripheral plasma and in breast cyst fluid, after a chromatography on Celite microcolumn has been described and evaluated. The antiserum used was raised in rabbits injected with dehydroepiandrosterone-15 alpha-(O-carboxymethyl)-bovine serum albumin. In men below 40 years of age the levels ranged from 0.85 to 2.80 ng/ml (mean +/- SEM: 1.52 +/- 0.11; n = 24) and from 0.50 to 2.20 ng/ml (mean +/- SEM: 0.93 +/- 0.09; n = 20) in men aged between 41 and 62 years. The mean level was significantly different (P less than 0.001) between the 2 groups. A significant correlation (r = -0.56; P less than 0.01) was demonstrated between age and all male levels. In females the mean plasma level was in the follicular phase: 0.81 +/- 0.07 ng/ml (range: 0.40-1.50; n = 17; age: 19-41 years) and in the luteal phase: 0.83 +/- 0.05 ng/ml (range: 0.40-1.30; n = 29; age: 18-43 years). No cyclical change and no correlation with age could be evidenced. A significant difference (P less than 0.001) was shown between females and the young male group. In breast cyst fluid the levels ranged from 0.05 to 13.70 ng/ml (mean +/- SEM: 2.36 +/- 0.86; n = 20) whereas the sulfate concentrations ranged from 75 to 7500 ng/ml (mean +/- SEM: 1891 +/- 565; n = 15), thus demonstrating very wide inter-individual variations.     

Measurment of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins.

A sensitive and specific double antibody radio-immunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The anti-serum was raised to LDL (d 1.030-1.040 g/ml) and the LDL(2) (d 1.020-1.050 g/ml) was labeled with (125)I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02-0.5 micro g of LDL(2), had an inter-assay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an "average American diet," a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet. The control monkeys (n = 13) had a serum cholesterol of 146 +/- 28 mg/dl and an apoB of 50 +/- 18 mg/dl. In the monkeys maintained on the atherogenic diets the serum apoB was elevated: 103 +/- 28 mg/dl (American), 102 +/- 35 mg/dl (peanut oil), and 312 +/- 88 mg/dl (coconut oil). The values for serum total cholesterol were 333 +/- 65 mg/dl (American), 606 +/- 212 mg/dl (peanut oil), and 864 +/- 233 mg/dl (coconut oil) and were elevated relative to controls (P < 0.001). For each of the diets, total serum cholesterol correlated with serum apoB (P < 0.001). The slopes of the regression lines of serum apoB vs. cholesterol for the monkeys on the PMC, American, and coconut oil diets were similar (m = 0.531, 0.401, and 0.359, respectively), but differed from that of monkeys on the peanut oil diet (m = 0.121). The immunoreactivities of rhesus and human LDL were compared using specific antisera raised against these antigens. In homologous assay systems, monkey and human LDL exhibited unique immunological determinants. The same results were obtained with the delipidated preparations of the two LDLs using antisera raised against either monkey or human apoB. Crossover studies using a heterologous tracer with each anti-serum resulted in the selection of a specific population of antibodies directed against antigenic sites shared by these two LDL species.     

Proinflammatory cytokines and leptin are increased in serum of prepubertal obese children

It has not yet been shown in prepubertal children how cytokines, leptin, and body mass, as well as parameters of obesity are interrelated. The aim of this study was to explore the relation between circulating levels of some cytokines with leptin and body mass index. A case control study was carried out in obese children of both sexes. An obese group was carried out with 63 school prepubertal children and a control group comprised the same number of nonobese children paired by age and by sex. Mean serum leptin concentration was significantly higher in the obese children at 19.9 +/- 7.4 ng/mL, than the control group (7.9 +/- 5.1 ng/mL). Serum IL-1beta, IL-6, and TNF-alpha levels were also significantly higher in the obese group than controls (33.0 +/- 8.9, 45.2 +/- 11.8, and 9.2 +/- 2.3 pg/mL, versus 3.6 +/- 1.0, 13.1 +/- 3.9, and 3.9 +/- 1.0 pg/mL, resp). In controversy, serum IL-2 level was diminished in the obese group as 0.4 +/- 0.1 versus 0.9 +/- 0.1 U/L. Obesity may be a low-grade systemic inflammatory disease. Obese prepubertal children have elevated serum levels of IL-1beta , IL-6, and TNF-alpha which are known as markers of inflammation.     

Elevated serum leptin levels in patients with acute myocardial infarction; correlation with coronary angiographic and echocardiographic findings

ABSTRACT: BACKGROUND: To assess the relationship between serial serum leptin levels in patients with acute myocardial infarction (AMI) who received thrombolysis and the degree of coronary atherosclerosis, coronary reperfusion, echocardiographic findings, and clinical outcome. 51 consecutive patients presenting with AMI were studied. Clinical characteristics including age, sex, body mass index (BMI) and cardiovascular risk factors were recorded. Serial serum leptin levels at the time of admission and subsequently at 0, 6, 12, 24, 36, 60 hours afterwards were obtained. Coronary angiography was performed in 34 patients; the relation between serum leptin levels and evidence of coronary reperfusion as well as the extent of coronary atherosclerosis according to the coronary artery surgery study classification (CASS) were evaluated. Echocardiographic evaluation was performed in all patients. 36 matched patients were enrolled as control group who had serum leptin level 9.4 +/- 6.5 ng/ml. RESULTS: The patients mean age was 50.5 +/- 10.6 years. There were 47 males and 3 females. 37.1% were diabetics, 23.5% were hypertensive, 21.6% were dyslipidemic and 22.7% were obese (BMI [greater than or equal to] 30). Leptin concentrations (ng/ml) increased and peaked at the 4th sample (36 hrs) after admission (mean +/- SD) sample (1) =9.55 +/- 7.4, sample (2) =12.9 +/- 8.4, sample (3) =13.8 +/- 10.4, sample (4) =18.9 +/- 18.1, sample (5) =11.4 +/- 6.5, sample (6) =10.8 +/- 8.9 ng/ml. There was a significant correlation between serum leptin and BMI (r = 0.342; p =0.03). Leptin levels correlated significantly to creatine kinase level on the second day (r = 0.43, p [less than or equal to] 0.01). Significant correlation of mean serum leptin with the ejection fraction (P < 0.05) was found. No difference in timing of peak serum leptin between patients who achieved coronary reperfusion vs. those who did not (p= 0.8). There was a trend for an increase in the mean serum leptin levels with increasing number of diseased vessels. There was no correlation between serum leptin levels and outcome neither during the hospitalization nor at 9 months follow up. CONCLUSION: Serum leptin levels increase after myocardial infarction. Serum leptin level may be a predictor of the left ventricular ejection fraction and the degree of atherosclerosis but not of coronary reperfusion.     

Endothelial t-PA release is impaired in overweight and obese adults but can be improved with regular aerobic exercise

Endothelial release of tissue-type plasminogen activator (t-PA) regulates fibrinolysis and is considered to be a primary endogenous defense mechanism against thrombosis. Adiposity is associated with an increased risk of atherothrombotic events. We determined the influence of overweight and obesity on the capacity of the vascular endothelium to release t-PA and the effects of regular aerobic exercise on endothelial t-PA release in previously sedentary overweight and obese adults. First, we studied 66 sedentary adults: 28 normal-weight (BMI < 25 kg/m2); 22 overweight (BMI > or = 25 and < 30 kg/m2); and 16 obese (BMI > or = 30 kg/m2). Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin (BK) and sodium nitroprusside. Second, we studied 17 overweight and obese adults who completed a 3-mo aerobic exercise intervention. Net release of t-PA in response to BK was approximately 45% lower (P < 0.01) in overweight (from 0.1 +/- 0.4 to 41.7 +/- 4.9 ng x 100 ml tissue(-1) x min(-1)) and obese (-0.1 +/- 0.6 to 47.7 +/- 5.2 ng x 100 ml tissue(-1) x min(-1)) compared with normal-weight (0.1 +/- 0.8 to 77.5 +/- 6.7 ng x 100 ml tissue(-1) x min(-1)) adults. There was no difference in t-PA release between the overweight and obese groups. Exercise training significantly increased t-PA release capacity in overweight and obese adults (from -0.3 +/- 0.5 to 37.1 +/- 4.9 ng x 100 ml tissue(-1) x min(-1) before training vs. 1.0 +/- 0.9 to 65.4 +/- 6.3 ng x 100 ml tissue(-1) x min(-1) after training) to levels comparable with those of their normal-weight peers. These results indicate that overweight and obesity are associated with profound endothelial fibrinolytic dysfunction. Importantly, however, regular aerobic exercise can increase the capacity of the endothelium to release t-PA in this at-risk population.     

Circulating blood volume of the Japanese monkey (Macaca fuscata) by means of the dye T-1824

The circulating blood volume has been measured in 65 healthy Japanese monkeys (Macaca fuscata) with the dye T-1824 (Evans blue). The values obtained were 83 ± 13 ml/kg in females, and 85 ± 12 ml/kg in females, almost the same as the figures reported in man.Sex difference of blood volume has been reported to be present in man, but from the data obtained here no significant difference was found in the Japanese monkey.In young monkeys aged from 1 to 5.5 years, the blood volume was 77 ± 5 ml/kg in males, and 78 ± 4 ml/kg in females. The blood volume of the monkey was found to increase with age; a significant difference was demonstrated between adult males and young males.     

Response of thyrotropin, prolactin and free thyroid hormones to graded exercise in normal male subjects

Serum levels of thyrotrophin (TSH), prolactin (PRL), free thyroxine (FT4) and free triiodothyronine (FT3) were determined before and after physical exercise in 21 normal male subjects. The subjects were divided into 3 groups as follows: group I--light exercise (exercise on the Mijnhardt bicycle ergometer at 100 Watts for 15 min); group II--moderate exercise (a 5 km marathon); group III--heavy exercise (a 10 km marathon). In group I, TSH level rose from 1.96 +/- 0.42 mu u/ml (mean +/- SEM) to 2.52 +/- 0.30 mu u/ml (p less than 0.01), and PRL levels rose from 11.0 +/- 2.0 ng/ml to 19.0 +/- 5.2 ng/ml (p less than 0.01). In group II, TSH rose from 2.11 +/- 0.51 mu u/ml to 2.62 +/- 0.56 mu u/ml (p less than 0.05), and PRL rose from 11.2 +/- 1.6 ng/ml to 24.0 +/- 5.2 ng/ml (p less than 0.01). In group III, TSH rose from 2.01 +/- 0.41 mu u/ml to 2.36 +/- 0.45 mu u/ml (p less than 0.02), and PRL rose from 12.1 +/- 2.0 ng/ml to 47.7 +/- 9.3 ng/ml (p less than 0.01). The serum levels of FT4 showed different results among the three groups: Group I showed an increased response from 1.60 +/- 0.12 ng/dl to 1.72 +/- 0.12 ng/dl (p less than 0.01); Group II showed no significant difference; and group III demonstrated a diminished response from 1.61 +/- 0.14 ng/dl to 1.45 +/- 0.16 ng/dl (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Establishment of an ELISA system for the determination of Japanese monkey calreticulin and its application to plasma samples in macaques

BACKGROUND: Calreticulin (Crt) is a molecular chaperone in endoplasmic reticulum, assisting a correct folding of glycoproteins. Establishment of its assay method might be advantageous to determine the Crt level in cell or other biosystems. METHODS: An enzyme-linked immunosorbent assay (ELISA) system for the determination of Crt of Japanese monkey, Macaca fuscata, was developed in this study. Japanese monkey Crt protein expressed in Escherichia coli was used as a standard protein. RESULTS AND DISCUSSION: The assay was sensitive even to <10 ng/ml of Crt. Since the amino acid sequence of Crt is quite similar (99%, similarity) between the Japanese and rhesus monkeys, the ELISA was applied to the determination of plasma Crt in these two species in association with various diseases. The Crt level increased significantly in monkeys suffering from pneumonia and diarrhea, suggesting that the ELISA might be applicable for preliminary diagnosis of inflammatory disease.     

Cortisol metabolism in the Bolivian squirrel monkey (Saimiri boliviensis boliviensis)

New World squirrel monkeys (Saimiri spp.) have high circulating cortisol levels but normal electrolytes and blood pressures. The goal of the present study was to gain insight into adaptive mechanisms used by Bolivian squirrel monkeys to minimize the effects of high cortisol on mineralocorticoid receptor (MR) activity and electrolyte and water balance. Aldosterone levels in serum from 10 squirrel monkeys were 17.7 +/- 3.4 ng/dl (normal range in humans, 4 to 31 ng/dl), suggesting that squirrel monkeys do not exhibit a compensatory increase in aldosterone. The squirrel monkey MR was cloned and expressed in COS-7 cells and found to have similar responsiveness to cortisol and aldosterone as human MR, suggesting that squirrel monkey MR is not inherently less responsive to cortisol. To determine whether altered metabolism of cortisol might contribute to MR protection in squirrel monkeys, serum and urinary cortisol and cortisone were measured, and a comprehensive urinary corticosteroid metabolite profile was performed in samples from anesthetized and awake squirrel monkeys. The levels of cortisone exceeded those of cortisol in serum and urine, suggesting increased peripheral 11beta-hydroxysteroid dehydrogenase 2 activity in squirrel monkeys. In addition, a significant fraction (approximately 20%) of total corticosteroids excreted in the urine of squirrel monkeys appeared as 6beta-hydroxycortisol, compared with that in man (1%). Therefore, changes in cortisol metabolism likely contribute to adaptive mechanisms used by Bolivian squirrel monkeys to minimize effects of high cortisol.     

Plasma soluble intercellular adhesion molecule 1 levels are increased in type 2 diabetic patients with nephropathy

BACKGROUND/AIM: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic complications is still a matter of debate. This study was performed to investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in patients with type 2 diabetes mellitus. METHODS: Ninety-three patients (24 males and 69 females) with type 2 diabetes mellitus were included into the study. Fifty patients had nephropathy, and 43 were free from nephropathy. Fifty healthy subjects (14 males and 36 females) served as the control group (group 1). Twenty-five of the diabetic patients had microalbuminuria (group 2), 25 had macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group 4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting. RESULTS: The mean plasma sICAM-1 levels were not different in the 93 diabetic patients as compared with the healthy controls (392.7 +/- 119.5 vs. 350.1 +/- 90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the diabetic patients with nephropathy than in those without nephropathy (430.3 +/- 78.2 vs. 368.2 +/- 122.5 ng/ml, p = 0.03) and in the controls (430.3 +/- 78.2 vs. 350.1 +/- 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups 2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 +/- 129.2 vs. 427.2 +/- 113.7 ng/ml and 368.2 +/- 122.5 vs. 350.1 +/- 90.2 ng/ml, respectively). CONCLUSIONS: The plasma sICAM-1 levels in patients with type 2 diabetes mellitus are not significantly different from those in nondiabetic subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the development of nephropathy in patients with type 2 diabetes mellitus.     

Opioid action on luteinizing hormone secretion in newborn pigs: paradoxical effect of naloxone

German Landrace piglets, 6-7 days of age, received either saline (9 males, 8 females), 0.5 mg naloxone/kg body weight (7 males, 7 females), 2.0 mg naloxone/kg (7 males, 8 females) or 0.5 mg DADLE (potent leu-enkephalin analog)/kg (7 males, 7 females) through a catheter inserted into the jugular vein 2-4 days previously. Male or female piglets were allocated randomly, within litter, to the different experimental groups. Blood samples were withdrawn for a period of 240 min at 10-min intervals for the first 60 min following injection and at 20-min intervals for the rest of the test period. Piglets were separated from their mother via a detachable wall and were allowed to suckle every 50 min. DADLE failed to alter plasma levels of LH in both males and females. Naloxone induced a significant (P less than 0.01) decrease in LH concentrations in females 10 to 60 min after injection (saline: 2.3 +/- 0.2 ng/ml plasma (SEM); 0.5 mg naloxone/kg: 1.0 +/- 0.2 ng/ml plasma and 2 mg naloxone/kg 1.2 +/- 0.4 ng/ml plasma). In males low doses of naloxone reduced plasma LH levels 10 to 40 min after injection (saline: 2.0 +/- 0.3 ng/ml plasma and 0.5 ng naloxone/kg: 1.1 +/- 0.3 ng/ml), whereas a decrease in plasma LH levels occurred 80 to 140 min after injection of high doses of naloxone (saline: 2.1 +/- 0.2 ng/ml and 2 mg naloxone/kg: 1.0 +/- 0.2 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of estrogen on serum leptin levels and leptin mRNA expression in adipose tissue in rats

OBJECTIVE: In this study, we examined changes in serum leptin levels during the estrus cycle and the role of estrogen in these changes. METHODS: We measured serum leptin levels during normal estrus cycles in intact rats and estradiol-17beta (E2)-induced artificial estrus cycles in ovariectomized rats. RESULTS: Serum leptin levels increased 1.6-fold from 4.2 +/- 0.2 ng/ml during diestrus stage 2 to 6.7 +/- 0.9 ng/ml during proestrus stage during the 4-day estrus cycle. During the E2-induced estrus cycle, serum leptin levels increased 2.3-fold from 2.3 +/- 0.1 ng/ml at estrus to 5.4 +/- 1.2 ng/ml at proestrus. E2 also increased serum leptin concentrations and leptin mRNA expression in adipose tissue of immature rats. DISCUSSION: These findings suggest that increased serum leptin induced by estrogen during proestrus may trigger the preovulatory release of luteinizing hormone. Furthermore, our findings indicate that estrogen has a positive effect on leptin production in adipose tissue.