Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran

BACKGROUND: The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS: Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS: Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 ± 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION: High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions

Development and validation of a simple reversed-phase high-performance liquid chromatography method for the determination of testosterone in serum of males

An isocratic high-performance liquid chromatographic method with detection at 234 nm was developed, optimized and validated for the determination of testosterone in human serum. Propylparaben was used as internal standard. A Hypersil BDS RP-C18 column (150 mm × 4.6 mm, 5 μm), was equilibrated with a mobile phase composed of acetonitrile and water (35:65, v/v) and having a flow rate of 1 ml/min. The elution time for testosterone and internal standard was approximately 11.6 and 9.9 min, respectively. Calibration curves of testosterone in serum were linear in the concentration range of 1-20 ng/ml. Limits of detection and quantification in serum were 0.4 and 1.1 ng/ml, respectively. Recovery was greater than 92%. Intra- and inter-day relative standard deviation for testosterone in serum was less than 2.1 and 3.9%, respectively. This method was applied to the determination of testosterone serum levels of 12 healthy males and data were correlated with data obtained using a radioimmunoassay method. © 2005 Elsevier B.V. All rights reserved

Effect of fast-food Mediterranean-type diet on human plasma oxidation

Oxidation of lipoproteins, particularly of low-density lipoprotein (LDL), is of prime importance in the initiation and progression of atherosclerosis. The Mediterranean diet has been associated with an unexpectedly low rate of cardiovascular events. Type 2 diabetic patients are at high risk of developing atherosclerosis. Functional alterations in the endothelium, which lead to atherosclerosis, are stimulated by oxidized lipoproteins, particularly oxidized LDL. The present study investigated the effect of Greek quick casual Mediterranean-type diet (fast food Mediterranean-type diet) consumption on the resistance to oxidation in plasma from type 2 diabetic patients and healthy human subjects. Lipids from fast food Mediterranean-type foodstuffs were extracted and tested in vitro for their ability to inhibit copper (Cu 2+)-induced LDL oxidation. Foodstuffs that exerted the most potent in vitro antioxidative activity were chosen for the diet of study groups. Eighteen type 2 diabetic patients (group A) and 10 healthy subjects (group B) were fed a 4-week diet contained the chosen foodstuffs, while 17 type 2 diabetic patients (group C) were kept on their regular diet that they were following before the study. Type 2 diabetic patients were treated with sulfonylureas or metformin and were under good glycemic control (hemoglobin A1C <7%). Serum lipoproteins, triglycerides, glucose, body mass index (BMI), and plasma resistance to Cu2+-induced oxidation before and after the 4-week diet were monitored. At the beginning of the study, no statistical difference was detected in plasma resistance to Cu2+-induced oxidation between type 2 diabetic patients (groups A and C) and healthy human subjects (group B), as this was detected at a time before the oxidation products become detectable, namely, lag time. After the 4-week period on the chosen diet the lag time in groups A and B significantly increased, while it was not changed in group C. In type 2 diabetic patients lag time was increased from 57.3 ± 13.3 minutes (mean ± SD) to 103.8 ± 21.8 minutes (mean ± SD) (P < .000), while in healthy human subjects there was an increase from 58.0 ± 8.5 minutes (mean ± SD) to 85.7 ± 21.8 minutes (mean ± SD) (P < .004). In all groups, total cholesterol, high-density lipoprotein-cholesterol, LDL-cholesterol, triglycerides, glucose, and BMI were not changed. Fast food Mediterranean foodstuffs exerted antioxidant activities both in vitro and in vivo after consumption in type 2 diabetic patients and healthy human subjects. Therefore consumption of a fast food Mediterranean-type diet should contribute to prevention against cardiovascular diseases. © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition

Human galanin secretion is increased upon normal exercise test in middle-age individuals

Galanin, a neuropeptide, is found in the central nervous system and in a number of nonbrain areas including adrenal sympathetic medullar tissue and pancreas. Several studies involve galanin in the regulation of GH, which responds to stressful stimuli. This study refers to the investigation of the effect of a 20-min exercise on plasma human galanin (hGAL) and GH in middle-aged healthy volunteer adults. Thirteen individuals, 5 males and 8 females aged 40-50 years (44.7 +/- 2.95) were selected on the basis of normal body mass index (22.5 +/- 2.3 kg/m(2)) and the absence of endocrine or any other abnormality. Basal concentrations of GH and hGAL were measured between 0800 and 0900h after an overnight fast. Post exercise levels were recorded after termination of the stressful test and 15 min thereafter. GH and hGAL were determined by an immunoradiometric and radioimmunoassay, respectively. The exercise-potentiated GH response in all subjects with post-exercise levels significantly higher (11.09+/-1.8 ng/ml vs 1.27+/-0.7 ng/ml, p<0.0001, F=32.44) with the peak in the hormone level detected 15 min after the end of exercise (12.09+/-1.96 ng/ml). Plasma hGAL levels were also substantially affected by the acute exercise test, in that post exercise peripheral blood concentration was significantly higher from the basal values (21.51+/-9.94 vs 13.46+/-7.2 pg/ml, p<0.02, F=5.50). Again the hGAL values peaked 15 min after the end of exercise (24.0+/-10.5 pg/ml, P<0.015, F = 4.68). However, the time-correlation of the increments of GH and hGAL did not reach a statistically significant level (20 min: r=0.41, p=0.161., 35 min: r=-0.095, P=0.758). These results clearly show an independence of the two hormones. The responsivity of hGAL of middle-aged individuals to the exercise stimulus might be due to the higher releasable pool of the hormone

Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study

Background: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. Methods: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. Findings: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture ( age ≥ 74 yr and femoral neck bone mineral density T score ≤-3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. Conclusion: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis

EFFECT OF AN ACUTE ORAL PROTEIN LOAD ON MICROALBUMINURIA IN UNINEPHRECTOMIZED PATIENTS IN RELATION TO THE TIME SINCE NEPHRECTOMY

To evaluate the effect of an acute oral protein lend (OPL) on urinary albumin excretion (UAE) in uninephrectomized subjects with a negative Albustix test, in relation to the time since nephrectomy. the UAE was determined by a double-antibody I-125 radioimmunoassay in 3-hour urine collections before and after 150 g OPL under conditions of moderate physical activity in 18 subjects who underwent unilateral nephrectomy more than 10 years (346.5+/-178.60 months) before evaluation and had a mean basal creatinine clearance (C-Cr) of 45.3+/-14 ml/min (group 1), in 21 subjects who under went unilateral nephrectomy less than 10 years (31.5+/-28 months) before evaluation and had a mean basal C-Cr of 76.0+/-22 ml/min (group 2), and in 16 normal volunteers (controls) with a mean basal C-Cr of 103.1+/-12 ml/min. The UAE was higher in group 1 as compared with either group 2 or controls at both basal state (90.8+/-65, 19.6+/-17, and 11.0+/-5 mu g/min/100 C-Cr for groups 1 and 2 and controls, respectively; p&lt;0.001) and after OPL (92.0+/-65, 43.6+/-24, and 12.0+/-5 mu/min/100 C-Cr for groups 1 and 2 and controls, respectively; p&lt;0.001). However, the increase in UAE following OPL was significant (p&lt;0.001) only in group 2 patients. In all patients, the basal UAE was negatively correlated with basal C-Cr (r=0.63; p&lt;0.001) and positively correlated with the time since nephrectomy (r=0.73; p&lt;0.001) and with both systolic (r=0.57; p&lt;0.001) and diastolic blood pressures (r=0.69; p&lt;0.001). Ca calculated using 3-hour urine collections increased more in controls (11.2+/-44.2%) than in patient groups 1 (1.6+/-0.89) and 3 (7.7+/-3.7%; p&lt;0.001). Basal C-Cr calculated using 24-hour urine collections the day before the test was negatively correlated with the time since nephrectomy in group 1 (r=-0.69; p&lt;0.001) and positively correlated with the time since nephrectomy in group 2 (r=0.89; p&lt;0.001). Multiple regression analysis revealed that the relationship between C-Cr and duration of uninephric state was independent of age or systolic and diastolic blood pressures in both patient groups. These results suggest that UAE increase significantly after an OPL in subjects who have been nephrectomized less than 10 years before the study and have basal C-Cr values higher than 50% of normal. They also suggest that the risk of developing renal insufficiency increases with time in subjects with a solitary kidney for more than 10 years; this increase in risk seems to follow a progressive compensatory increase in glomerular filtration rate of the remnant kidney during the early years following uninephrectomy

Effect of traditional Greek Mediterranean meals on platelet aggregation in normal subjects and in patients with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus have increased risk of cardiovascular disease. Epidemiological studies have shown a correlation between diet and incidence of coronary heart disease. The aim of the study is to determine the effect of a traditional Greek Mediterranean diet on platelet aggregation induced by ADP, arachidonic acid (AA), and especially platelet-activating factor (PAF) on patients with type 2 diabetes mellitus as well as on healthy volunteers. The patients were randomized into two subgroups, A and B. The lipid extracts from traditional Greek Mediterranean-type meals were tested in vitro for their ability to reduce PAF- or thrombin-induced platelet aggregation. The meals with the most potent anti-aggregating activity were chosen for the diet of both subgroup A and healthy subjects and consumed for a period of 28 days, whereas subgroup B kept to their regular diet that was followed before entering the study. Platelet-rich plasma was isolated before and after the diet, and the ability of platelets to aggregate under the aggregating factors was tested. One-month consumption of diet resulted in a significant reduction in PAF- and ADP-induced aggregation of platelets in both groups of healthy volunteers (PAF and ADP, P &lt; .05) and subgroup A (PAF, P &lt; .001; ADP, P &lt; .05), whereas the AA-induced aggregation was not affected. No effect was observed in subgroup B, which followed the standard diet. Thus the consumption of a traditional Greek Mediterranean diet even for a short period can reduce platelet activity in patients suffering from type 2 diabetes mellitus and in healthy subjects. © Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition

Association of hyperandrogenemic and metabolic phenotype with carotid intima-media thickness in young women with polycystic ovary syndrome

Polycystic ovary syndrome ( PCOS), a common endocrinopathy of women of reproductive age, is associated with the early appearance of multiple risk factors for cardiovascular disease, such as abdominal obesity, dyslipidemia, and diabetes mellitus. However, premature atherosclerosis of the carotid artery has not yet been demonstrated in young women with PCOS. Measurement of carotid intima-media thickness (IMT) is considered an easy and reliable index of subclinical atherosclerosis, which is predictive of subsequent myocardial infarction and stroke. To evaluate the cardiovascular risk of PCOS and the participation of the hyperandrogenemic and metabolic pattern, we measured carotid IMT by B-mode ultrasound as well as hormonal and several cardiovascular disease-associated parameters in 75 young women with PCOS and 55 healthy, age- and body mass index-matched women. The PCOS women had significantly increased carotid IMT (0.58 vs. 0.47 mm, P &lt; 0.001) and abdominal adiposity; higher levels of androgens, insulin, homeostasis model assessment score of insulin sensitivity, and total and low-density lipoprotein-cholesterol; and significantly lower levels of SHBG and high-density lipoprotein-cholesterol. In the studied population (n = 130), PCOS status, age, body mass index, and parental history of coronary heart disease were strong positive predictors of carotid IMT, whereas dehydroepiandrosterone sulfate was a strong negative predictor. In PCOS patients lower Delta(4)-androstenedione and high-density lipoprotein-cholesterol levels were additionally strong positive predictors of carotid IMT, whereas in control women only total cholesterol was the additional positive predictor of carotid IMT. In conclusion, young women with PCOS have an early increase of cardiovascular risk factors and greater carotid IMT, both of which may be responsible for subclinical atherosclerosis. The hyperandrogenemic phenotype of the syndrome may attenuate the consequences of the dysmetabolic phenotype on the vascular wall