Sialyl Lewis X modification of the epidermal growth factor receptor regulates receptor function during airway epithelial wound repair.

BACKGROUND: Epidermal growth factor receptor (EGFR) is a major regulator of airway epithelial cell (AEC) functions such as migration, proliferation and differentiation, which play an essential role in epithelial repair. EGFR is a glycoprotein with 12 potential N-glycosylation sites in its extracellular domain. Glycosylation of EGFR has been shown to modulate its function. Previously, our laboratory demonstrated an important role of the carbohydrate structure sialyl Lewis x (sLe(x)) in airway epithelial repair. OBJECTIVE: To examine whether an sLe(x) decoration of EGFR can modulate receptor function during AEC repair. METHODS: Primary normal human bronchial epithelial (NHBE) cells were cultured in vitro. Co-localization of sLe(x) and EGFR was examined using confocal microscopy. Expressions of RNA and protein were analysed using RT-PCR and Western blotting. The final step in the synthesis of sLe(x) was catalysed by a specific alpha-1,3-fucosyltransferase (FucT-IV). To evaluate the role of sLe(x) in EGFR activation, a knockdown of the FucT-IV gene with small interfering RNA (siRNA) and an inhibitory anti-sLe(x) antibody (KM-93) was used. RESULTS: We demonstrated a co-localization of sLe(x) with EGFR on NHBE cells using confocal microscopy. Using a blocking antibody for sLe(x) after a mechanical injury, we observed a reduction in EGFR phosphorylation and epithelial repair following injury. FucT-IV demonstrates a temporal expression coordinate with epithelial repair. Down-regulation of FucT-IV expression in NHBE by specific siRNA suppressed sLe(x) expression. The use of FucT-IV siRNA significantly reduced phosphorylation of EGFR and prevented epithelial repair. An immunohistochemical analysis of human normal and asthmatic airways showed a significant reduction in sLe(x) and tyrosine-phosphorylated EGFR (pY(845)-EGFR) in the epithelium of asthmatic subjects compared with that of normal subjects. CONCLUSION: The present data demonstrate that sLe(x), in association with EGFR, in NHBE is coordinate with repair. This glycosylation is important in modulating EGFR activity to affect the repair of normal primary AEC.

Carbohydrates and epithelial repair - more than just post-translational modification.

Epithelia are the layers of cells that form barriers between external milieu and underlying tissues and thus, are important components of most organs of the body. Epithelial layers of organs, such as the lung, are exposed to various challenges resulting in frequent injury. Epithelial wound healing represents an important process by which repair restores the physical barrier lost as a result of cell damage and apoptosis. The repair of epithelial layers consists of a series of ordered events including epithelial cell spreading, migration proliferation and, differentiation. Carbohydrates attached to cell surface proteins and lipids can modulate the function of structures that they are conjugated to and therefore, can affect cell behavior. Although the basic mechanisms of epithelial repair are not entirely understood, many studies suggest glycoconjugates attached to proteins on the cell surface of epithelial cells play important roles in many of these cellular processes. In the present review, the role of carbohydrates in epithelial repair of different organs, including the sources of epithelial injury and current models of epithelial repair will be discussed with a focus on our understanding of the airway epithelium. With a better understanding of carbohydrates and their role in epithelial repair, new therapeutic targets for diseases involving damage to the epithelium can be identified.

Reappraisal of the risk of iodine-induced hyperthyroidism: an epidemiological population survey.

The occurrence of iodine-induced hyperthyroidism (IIH) has been reported after iodine supplementation from clinics and hospitals, but not following an epidemiologic survey. We studied the prevalence of thyroid derangement in a population following iodine supplementation. One yr after more than 75% of the population had been consuming 40 ppm iodized salt; information regarding history of endemic goiter and iodized salt production, distribution, consumption and monitoring were collected in four cities of the Islamic Republic of Iran. A total of 6048 subjects were randomly selected. All subjects were assessed for size of goiter, and urinary iodine and serum T4, T3, TSH, anti-thyroglobulin and anti-thyroperoxide were measured. Before iodine supplementation, all four cities were areas of endemic goiter. The rate of household consumption of iodized salt was 50, 75 and 90% in 1994, 1995 and 1996, respectively. Ninety-one percent of the salt samples contained 15-55 ppm iodide. Total goiter rate was 57, 62 and 68%; median urinary iodine was 188, 197 and 190 microg/l in the age groups of 6-18, 19-40 and >40 yr, respectively. Prevalence of clinical and subclinical hyperthyroidism was 0.34 and 0.41 and those of clinical and subclinical hypothyroidism were 0.51 and 1.07%, respectively. Nine point eight and 18% in the 19-40 yr age group and 17.6 and 25.6% in >40 yr old subjects had positive anti-thyroperoxidase and anti-thyroglobulin, respectively. This systemic epidemiologic study in an iodine deficient population showed that, following a well-executed iodine supplementation program, the occurrence of IIH is rare.

Cardiovascular risk factors in males with hypertriglycemic waist (Tehran Lipid and Glucose Study).

BACKGROUND: Many studies performed on nontraditional risk factors have proposed a metabolic triad including increased serum level of apolipoprotein B, hyperinsulinemia and high small, dense LDL-C as a risk factor of cardiovascular diseases. Hypertriglycemic waist (increased waist circumference as well as high fasting triglyceride level) can be used as a simple criterion to predict the metabolic triad. The aim of this study was to investigate the prevalence of hypertriglycemic waist and the frequency of cardiovascular risk factors in the affected population. MATERIALS AND METHODS: The study was performed on 4169, 18-70 y-old male subjects of the population of Tehran Lipid and Glucose Study (TLGS). The subjects fell into four groups with respect to serum level of fasting triglycerides (Tg) and waist circumference (WC). Subjects of group 1 had serum Tg > or =1.8 mmol/l as well as WC > or =95 cm, while those of group 2 had Tg > or =1.8 mmol/l and WC <95 cm. The triglycerides level was less than 1.8 mmol/l in groups 3 and 4, whereas WC was > or =95 cm and lower than 95 cm, respectively. Cardiovascular risk factors, anthropometric and laboratory variables were compared between the groups. RESULTS: In total, 784 subjects had high serum levels of Tg as well as increased WC. The mean age of subjects was significantly higher in groups 1 and 3 compared to others (37+/-15, 48+/-14, 41+13 and 46+/-13 y of age in groups 4, 3, 2 and 1, respectively, P<0.001). The prevalence of cardiovascular risk factors was significantly higher in group 1 as compared with others. Systolic and diastolic blood pressure, body mass index and WC were significantly higher in group 1 than in the others. Serum total cholesterol, Tg and LDL-C were significantly higher in group 1 compared to others, whereas HDL-C was significantly lower in this group. The prevalence of subjects who had at least four risk factors was 75 and 8% in groups 1 and 4, respectively. CONCLUSION: Hypertriglycemic waist can be used as a simple criterion to predict cardiovascular risk factors.

Gender differences in dietary intakes, anthropometrical measurements and biochemical indices in an urban adult population: the Tehran Lipid and Glucose Study.

BACKGROUND AND AIM: In order to investigate gender differences in health indices, dietary intakes and obesity in urban Iranian adults, we considered a sub-sample of the adult population of the Tehran Lipid and Glucose Study. METHODS AND RESULTS: The randomly selected sub-sample consisted of 483 subjects aged 25-50 years (229 men and 254 women) and 153 aged more than 50 years (81 men and 72 women). Their anthropometrical variables were recorded, and their body mass index (BMI) and waist/hip ratio were calculated. Dietary intake was assessed by means of two-day dietary recall and the completion of dietary habit questionnaires during face-to-face interviews. Underreporting was defined as a ratio of energy intake (EI)/basal metabolic rate (BMR) < 1.27. The mean BMI of the women in both age groups was significantly higher than that of the men (p < 0.05). Central obesity was more frequent in the women and among older subjects. The women had higher plasma concentrations of high-density lipoprotein cholesterol, but lower levels of total and low-density lipoprotein cholesterol. Underreporting of EI was more frequent in the women than the men: 34.0% vs 15.4% in the younger group, and 40.3% vs 17.3% in the older group (p < 0.01). There were major gender differences in the mean daily intakes of energy, protein, carbohydrate, fat, fibre, cholesterol, iron, calcium and phosphorus. A higher proportion of women met the cholesterol intake guidelines. Data from the dietary habit questionnaires showed that more men than women usually sprinkle salt on their food. CONCLUSIONS: The results of this study partially support the hypothesis of gender differences in dietary intakes, and the prevalence of obesity and some health-related indices, and suggest the need for gender-specific, targeted nutrition messages and behavioural interventions in developing prevention strategies for cardiovascular risk factors.

Cardiovascular risk factors in an Iranian urban population: Tehran lipid and glucose study (phase 1).

OBJECTIVES: Coronary artery disease is becoming more prevalent in developing countries, particularly in urban areas. This study was conducted to determine the prevalence of cardiovascular risk factors among Tehran urban population. METHODS: The prevalence and distribution of high blood pressure, cigarette smoking, dyslipoproteinemia, diabetes mellitus, and obesity was determined in 15,005 subjects, aged three years and over, selected by cluster random sampling in Tehran urban district-13 between February 1999 to August 2001. Total energy intake, percent of energy derived from protein, carbohydrate, and fat were assessed in a subsidiary of 1,474 persons by means of two 24-hour dietary recalls. RESULTS: In adults, 78% of men and 80% of women presented at least one CVD risk factor. The percentage of adult women with two or more risk factors was significantly greater than the one for men. Prevalence of DM, hypertension, obesity, high TC, low HDL, high TGs, and smoking was 9.8, 20.4, 14.4, 19.3, 32, 5.3, and 22.3%, respectively. In children and adolescents, two or more CVD risk factors were found in 9% of boys and 7% of girls. Prevalence of hypertension, obesity, high TC, low HDL, and high TGs, was 12.7, 5.2, 5.1, 10.2, and 5%, respectively. The mean percentage values of energy intake derived from carbohydrate, protein, and fat were 57.8 +/- 6.9, 11.1 +/- 1.8, and 30.9 +/- 7.2, respectively. CONCLUSION: The prevalence of cardiovascular risk factors among Tehran urban population is high; particularly of high total cholesterol, low HDL cholesterol levels, and high waist to hip ratio. An effective strategy for life style modification is a cornerstone of a population approach to the cardiovascular risk factors. Moreover, these results will serve as a baseline for assessment of future trends in the risk factors studied.

Serum lipid levels in an Iranian population of children and adolescents: Tehran lipid and glucose study.

Data from 3148 participants aged 3-19 years (1447 males and 1701 females) in the cross-sectional phase of Tehran lipid and glucose study (February 1999-May 2000) were used to determine serum lipid levels [total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] after 12-14 hours overnight fast. The values were analyzed by sex and age. Mean serum TC concentration was 170 mg/dl. TC was significantly greater in females than males (173 vs. 167 mg/dl, p < 0.05). The 90th and 95th percentiles for serum TC were 211 and 227 mg/dl, respectively. There was a significant decrease in mean TC in males during puberty. Thirty-one percent of population had TC values between 170 and 199 mg/dl and 16% had values of 200 mg/dl or greater. The mean TGs values were 103 for males and 108 mg/dl for females [non-significant (NS)]. The prevalence of high-risk values of TGs increased with age in males, reaching a peak at 17-19 years. The mean HDL-C level was 45 mg/dl. Mean HDL-C was highest at 7-10 years of age and decreased thereafter. The mean LDL-C was 102 in males and 107 mg/dl in females (NS). Twenty-two percent had LDL-C values between 110 and 129 mg/dl and 17% had values 130 mg/dl or greater. The results showed higher levels of TC, LDL-C and TGs and lower HDL-C in Tehranian children and adolescents than other studies. To design comprehensive public health programs to reduce serum lipid levels among Iranian children and adolescents, underlying factors for the high prevalence of dyslipoproteinemia should be sought.

Dietary factors and body mass index in a group of Iranian adolescents: Tehran lipid and glucose study--2.

OBJECTIVE: To study the prevalence of overweight and obesity in an adolescent population in Tehran and to determine possible association with energy and nutrient intake and distribution of energy over the day. METHOD: A cross-sectional study on 177 boys and 244 girls between 10-19 years old was performed. Overweight and obesity were defined by using recommended body mass index (BMI) cut-off values for adolescents. Total energy intake, percent of energy derived from protein, carbohydrate and fat and percent of energy supplied by each meal and snack were assessed by means of two 24-hour dietary recalls. RESULTS: Prevalence of overweight and obesity was 10.7 and 5.1 in boys and 18.4 and 2.8 in girls, respectively. The composition of diet was not different between overweight/obese and normal weight subjects. BMI was related with breakfast energy percentage in girls (r = -0.18, p < 0.01), with total energy intake in boys (r = 0.23, p < 0.01), and with lunch energy percentage in both sexes. In boys (r = 0.16, p < 0.05) and in girls (r = 0.22, p < 0.01). CONCLUSION: High prevalence of overweight and obesity among adolescents was seen. In boys some relationship between total energy intake, distribution of energy over the day and BMI was seen. In girls BMI was only related with distribution of energy over the day.

Effects of salted food consumption on urinary iodine and thyroid function tests in two provinces in the Islamic Republic of Iran.

We evaluated sources of difference in urinary iodine between two neighbouring Iranian provinces, Gilan and Mazandaran. In the cities of Rasht (Gilan) and Sari (Mazandaran), 340 and 343 participants respectively were selected by cluster sampling. Urinary iodine in Rasht was significantly higher than in Sari (31 microg/dL versus 21 microg/dL). Sodium and potassium urine levels in Rasht were also higher than Sari. Mean daily intake of iodized salt and thyroid function tests were not significantly different. Average annual consumption of some salted foods was significantly higher in Rasht than Sari. We conclude that higher consumption of salted foods in Rasht is responsible for an increase in urinary iodine.

Effects of salted food consumption on urinary iodine and thyroid function tests in two provinces in the Islamic Republic of Iran

We evaluated sources of difference in urinary iodine between two neighbouring Iranian provinces, Gilan and Mazandaran. In the cities of Rasht [Gilan] and Sari [Mazandaran], 340 and 343 participants respectively were selected by cluster sampling. Urinary iodine in Rasht was significantly higher than in Sari [31 micro g/dL versus 21 micro g/dL]. Sodium and potassium urine levels in Rasht were also higher than Sari. Mean daily intake of iodized salt and thyroid function tests were not significantly different. Average annual consumption of some salted foods was significantly higher in Rasht than Sari. We conclude that higher consumption of salted foods in Rasht is responsible for an increase in urinary iodine