Mehdi Hedayati

Prevention of non-communicable disease in a population in nutrition transition: Tehran Lipid and Glucose Study phase II

BackgroundThe Tehran Lipid and Glucose Study (TLGS) is a long term integrated community-based program for prevention of non-communicable disorders (NCD) by development of a healthy lifestyle and reduction of NCD risk factors. The study begun in 1999, is ongoing, to be continued for at least 20 years. A primary survey was done to collect baseline data in 15005 individuals, over 3 years of age, selected from cohorts of three medical heath centers. A questionnaire for past medical history and data was completed during interviews; blood pressure, pulse rate, and anthropometrical measurements and a limited physical examination were performed and lipid profiles, fasting blood sugar and 2-hours-postload-glucose challenge were measured. A DNA bank was also collected. For those subjects aged over 30 years, Rose questionnaire was completed and an electrocardiogram was taken. Data collected were directly stored in computers as database software- computer assisted system. The aim of this study is to evaluate the feasibility and effectiveness of lifestyle modification in preventing or postponing the development of NCD risk factors and outcomes in the TLGS population.Design and methodsIn phase II of the TLGS, lifestyle interventions were implemented in 5630 people and 9375 individuals served as controls. Primary, secondary and tertiary interventions were designed based on specific target groups including schoolchildren, housewives, and high-risk persons. Officials of various sectors such as health, education, municipality, police, media, traders and community leaders were actively engaged as decision makers and collaborators. Interventional strategies were based on lifestyle modifications in diet, smoking and physical activity through face-to-face education, leaflets & brochures, school program alterations, training volunteers as health team and treating patients with NCD risk factors. Collection of demographic, clinical and laboratory data will be repeated every 3 years to assess the effects of different interventions in the intervention group as compared to control group.ConclusionThis controlled community intervention will test the possibility of preventing or delaying the onset of non-communicable risk factors and disorders in a population in nutrition transition.Trial registrationISRCTN52588395

Ischemic and non-ischemic acute kidney injury cause hepatic damage

Recent studies have documented that remote organs are affected by ischemic injury to the kidney. Here we studied whether the liver also suffers damage during induction of renal ischemia-reperfusion in rats and compared this to bilateral nephrectomy. Hepatic levels of tumor necrosis factor-alpha increased significantly after 6 and 24 h of renal ischemia or nephrectomy. Malondialdehyde, an index of lipid peroxidation, increased while total glutathione was decreased in the liver in both the renal ischemia and nephrectomy groups, suggesting activation of oxidative stress. Expression of liver spermine-spermidine acetyl transferase, an enzyme upregulated in early phases of hepatic injury was significantly increased 6 h after either kidney ischemia or nephrectomy. Apoptosis was increased in hepatocytes 24 h after nephrectomy. We also found histological evidence of hepatocyte injury following both ischemia and bilateral nephrectomy. Infusion of reduced glutathione, before the induction of renal ischemia, significantly improved liver architecture and was associated with a reduction in hepatic malondialdehyde and serum alanine transaminase levels. Our study shows that acute kidney ischemia or renal failure activates oxidative stress and promotes inflammation, apoptosis, and tissue damage in hepatocytes.

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 antithyroperoxide 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 μg/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 antithyroglobulin, 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.

Is polycystic ovary syndrome an exception for reproductive aging

BACKGROUND Anti-Mullerian hormone (AMH) is increased in women with polycystic ovary syndrome (PCOS), suggesting a delay in ovarian aging. We examined AMH levels in PCOS and normo-ovulatory women in a population-based cohort over a period of 10 years and used this information to estimate their menopausal age. METHODS Of a subset of 1002 non-menopausal women randomly selected from the Tehran Lipid and Glucose Study, 85 cases of PCOS were diagnosed. We frequency-matched our control subjects with PCOS cases based on age and BMI. AMH levels were assessed at the time of recruitment (T1) and twice after that (T2 and T3). AMH levels were then plotted against age of the individual at the time of the measurement and the most appropriate model was selected. Menopause was calculated based on AMH levels below 0.2 ng/ml. RESULTS AMH levels were significantly higher in PCOS cases compared with controls at the beginning of the study (5.58 +/- 3.64 versus 4.35 +/- 2.90 ng/ml, P = 0.03), but the difference diminished considerably in subsequent assessments. The rate of AMH decline in PCOS cases decreased in the second compared with the first interval; however, no apparent change in the rate of decline was observed in controls. Estimated ages at menopause were 51 [95% confidence interval (CI), 34-81] and 49 (95% CI, 38-63) years in PCOS cases and controls, respectively. CONCLUSIONS The reproductive lifespan of PCOS women extends on average 2 years beyond that of normo-ovulatory women.

Broccoli sprouts reduce oxidative stress in type 2 diabetes: a randomized double-blind clinical trial

Background/Objectives:In vitro and animal studies have reported that young broccoli sprouts improve oxidative stress status in diabetic condition. The objective of this double-blind, placebo-controlled, randomized clinical trial was to investigate the effects of broccoli sprouts powder (BSP) on some oxidative stress parameters in type 2 diabetes patients.Subjects/Methods:A total of 81 patients with type 2 diabetes were randomly assigned to one of three treatment groups for 4 weeks. The groups received either 10 g/d BSP (n=27), 5 g/d BSP (n=29) or placebo (n=25). Serum total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), malondialdehyde (MDA) and oxidized low density lipoprotein (LDL) cholesterol were measured at baseline and at 4 weeks after treatment.Results:In all, 63 patients in three groups were included in the analysis: 10 g/d BSP (n=21), 5 g/d (n=22) and placebo (n=20). After 4 weeks, consumption of BSP resulted in significant decrease in MDA (P=0.001 for treatment effect), oxidized low density lipoprotein cholesterol (P=0.03 for treatment effect), OSI (P=0.001 for treatment effect) and significant increase in TAC (P=0.001 for treatment effect). No effects were found on TOS.Conclusion:BSP had favorable effects on oxidative stress status in type 2 diabetes patients.

A High Prevalence of Consanguineous and Severe Congenital Hypothyroidism in an Iranian Population

To determine the incidence of permanent congenital hypothyroidism (CH) in Tehran and Damavand, cord blood spots were collected from February 1998-August 2002 and infants with TSH > or =20 mU/l were recalled. CH was confirmed in neonates (aged > or =7 days) with serum TSH >10 mU/l and T4 <84 nmol/l. Cases were followed up until September 2003. Dysgenesis was detected by thyroid imaging. In eutopic cases, serum TSH and T4 measurements following levothyroxine discontinuation (2-3 years of age) confirmed dyshormonogenesis and transient CH. Of 35,067 neonates, 373 (1.06%) were recalled and 25 (1:1,403 births) had permanent CH (six had transient CH and four remain unknown). Dysgenesis was detected in 18 (1:1,948 births) and dyshormonogenesis in seven (1:5,010 births) infants. Parental consanguinity was present in 10 (55.6%) dysgenetic, three (42.9%) dyshormonogenetic, and overall 6,648 (28.6%) of 23,227 screened infants. Odds ratio (95%CI(OR)) of consanguinity in permanent CH and dysgenesis was 2.75 (1.17-6.47) and 3.74 (1.33-10.52), respectively. The high prevalence of parental consanguinity in infants with permanent CH warrants genetic assessment.

Synthesis and biological evaluation of new 4-carboxyl quinoline derivatives as cyclooxygenase-2 inhibitors

A group of 4-carboxyl quinoline derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-2 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 structure-activity relationships were determined by varying the substituents on the C-7 and C-8 quinoline ring. Among the 4-carboxyl quinolines, 7,8,9,10-tetrahydro-2-(4-(methyl sulfonyl)phenyl)benzo[h]quinoline-4-carboxylic acid (9e) was identified as potent and high selective COX-2 inhibitor (COX-2 IC(50)=0.043microM; selectivity index>513) that was more potent than the reference drug celecoxib (COX-2 IC(50)=0.060microM; SI=405). A molecular modeling study where 9e was docked in the binding site of COX-2 showed that the p-MeSO(2) substituent on the C-2 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket (Arg513, Phe518 and Val523) and the carboxyl group can interact with Arg120. The structure activity data acquired indicate that the presence of lipophilic substituents on the C-7 and C-8 quinoline ring is important for COX-2 inhibitory activity.

Assessment of intertrimester and seasonal variations of urinary iodine concentration during pregnancy in an iodine-replete area

Objective  To assess intertrimester and seasonal variations in urinary iodine concentration (UIC) among pregnant women.

Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines

Boron possesses widespread properties in biochemistry and nutrition. Acute supplementation with 11.6 mg of boron resulted in a significant increase in plasma boron concentration. Given such a fast bioavailability, the objective was to determine whether acute (hourly or daily), and weekly supplementation could have any significant biological effects on the steroid hormones and further on some inflammatory biomarkers. Eight healthy male volunteers attended the laboratory on three occasions (days 0, 1 and 7). On the first day (day 0), a blood sample collection at 8.00 A.M was followed by ingestion of placebo with the breakfast. On the next day (supplementation-day 1), similar procedure was followed by ingestion of a capsule containing 10mg of boron. On both occasions blood was collected every 2h for the next 6h. Subjects were requested to consume a capsule of 10mg boron every day with their breakfast, and on the day 7, the blood collection was carried out at 8.00 A.M, again. Boron in plasma increased significantly following hours and weekly consumption. Six hours supplementation showed a significant decrease on sex hormone binding globulin (SHBG), high sensitive CRP (hsCRP) and TNF-α level. After one week (in samples taken at 8.00 A.M, only), the mean plasma free testosterone increased and the mean plasma estradiol decreased significantly. Dihydrotestosterone, cortisol and vitamin D was elevated. Also, concentrations of all three inflammatory biomarkers decreased after supplementation. Of note, despite decreased proinflammatory cytokines, based on recent clinical data, this must be the first human study report to show an increase level of free testosterone after boron consumption.

Design and synthesis of 3-alkyl-2-aryl-1,3-thiazinan-4-one derivatives as selective cyclooxygenase (COX-2) inhibitors

A new group of 3-alkyl-2-aryl-1,3-thiazinan-4-ones, possessing a methylsulfonyl pharmacophore, were synthesized and their biological activities were evaluated for cyclooxygenase-2 (COX-2) inhibitory activity. In vitro COX-1/COX-2 inhibition studies identified 3-benzyl-2-(4-methylsulfonylphenyl)-1,3-thiazinan-4-one (11a) as a potent (IC(50)=0.06 microM) and selective (selectivity index >285) COX-2 inhibitor.