Effects of administration of iron, iodine and simultaneous iron-plus-iodine on the thyroid hormone profile in iron-deficient adolescent Iranian girls

OBJECTIVE: To investigate whether iron supplementation can improve thyroid hormone function in iron-deficient adolescent girls. DESIGN: A double-blind randomized intervention study. SETTING: The study was performed from 2002 through 2003 in the Islamic Republic of Iran. SUBJECTS: 103 iron-deficient non-anaemic girls who fulfilled all inclusion criteria were included, and 94 subjects successfully completed the study. INTERVENTIONS: Patients were randomly assigned to one of four groups and treated with a single oral dose of 190 mg iodine plus 300 mg ferrous sulphate 5 times/week (n=24), 300 mg ferrous sulphate 5 times/week (n=23), a single oral dose of 190 mg iodine (n=25), or a placebo (n=22) for 12 weeks. RESULTS: All groups were comparable at baseline. After the intervention, there was a significant increase in ferritin and transferrin saturation in the iron+iodine group (17.6 vs 8.7 microg/dl, and 18.8 vs 7.2%, respectively, P<0.001 for both) and in the iron group (P<0.001 for both). Urinary iodine doubled in the iron+iodine group and in the iodine group (P<0.001 for both). Thyroid indices tT4, tT3 and T3RU increased and reverse RT3 decreased in the iron+iodine group (10 vs 8.9 microg/dl, P< 0.001; 143 vs 138 microg/dl, P<0.05; 32.3 vs 28.4%, P<0.001 and 24.8 vs 44.2 ng/dl, P<0.001, respectively) and in the iron group. These two groups did not differ for any of the four indices, but both differed significantly from the iodine and placebo groups. CONCLUSIONS: Our results indicate that improvement of iron status was accompanied by an improvement in some indices of thyroid hormones. SPONSORSHIP: This study was supported by the Dean of Research Affairs of the Tehran University of Medical Sciences.     

High-dose MDMA does not result in long-term changes in impulsivity in the rat

Rationale Evidence suggests that recreational users of (±)3,4-methylenedioxymethamphetamine HCl (MDMA, “ecstasy”) have cognitive and behavioral deficits and show increased impulsivity consistent with 5-hydroxytryptamine (5-HT) neurotoxicity. MDMA effects on impulsivity in users are difficult to establish being confounded by polydrug use and individual predisposition to impulsivity or behavioral inhibition.Objective We previously observed a long-term anxiolytic effect of a neurotoxic dose of MDMA on elevated plus maze behavior in Dark Agouti (DA) rats while other strains were reported to show anxiogenesis. We have now examined whether MDMA influences impulsivity producing disinhibited behavior interpretable as anxiolysis.Methods Impulsivity was measured using an operant visuospatial discrimination procedure. Male DA rats (n=24) were trained to lever press for food reward in response to a light-stimulus and subsequently required to withhold responding. Correct responses, premature responses, and response latencies were used as measures of accuracy and impulsivity. Trained rats were administered MDMA (5 mg/kg, i.p. at 3-h intervals to a total of three injections). Performance was measured at 3 h and 7, 27, 49, and 80 days posttreatment.Results There was a short-term effect of MDMA on the percentage of correct responses at 3 h and day 1 with recovery to control levels by days 7–8 and no significant long-term changes up to day 80. There was no effect of MDMA on premature responses on any of the days measured. MDMA reduced cortical 5-HT content (MDMA 363±14 ng/g and control 440±10 ng/g tissue).Conclusion These results suggest that impulsivity may not be directly altered by MDMA despite serotonergic neurotoxicity.     

Task analysis of the preincision period in a pediatric operating suite: an independent observer-based study of 656 cases

We designed this cross-sectional investigation to assess anesthesia release time (ART = patient-on-table until release for surgical preparation) and surgical preparation time (start of surgical preparation to incision) of children undergoing anesthesia and surgery (n = 656). Data collected by trained independent observers included variables such as age, ASA physical status, anesthetic technique, and placement of invasive monitoring. We found that mean ART was 11.0 +/- 9.7 min and the mean surgical preparation time was 11.1 +/- 10.0 min. Also, ART ranged from 7 +/- 7 min (for mask anesthesia) to 52 +/- 18 min (general anesthesia/endotracheal tube and invasive hemodynamic monitoring). The percentage of ART of the total case length was 15% +/- 7%, with a wide variability depending on the total case length. We also found that there is a significant variability in ART as a function of the surgical service involved (analysis of variance; P = 0.0001), ASA physical status (P = 0.0001), and age. For example, younger children had a significantly longer ART as compared with older children (P = 0.001). Room coverage ratio by the attending anesthesiologist and training level of the anesthesia resident did not impact ART (P = not significant). We conclude that ART in children undergoing surgery is highly variable and is a function of factors such as the surgical service involved, age of the child, and ASA physical status of the child. These factors should be considered when scheduling a surgical case.     

Chemoprevention by pyrimethamine

The goal of the current research was to investigate the chemopreventive potency of an antimalaria drug, pyrimethamine, in in vitro conditions. The fibrosarcoma (WEHI-164) cell line was used for evaluating cytotoxicity, matrix metalloproteinase 2 (MMP-2) activity, and apoptosis. Pyrimethamine and methotrexate were used at concentrations of 0-8 µg/ml in triplicate and 2-fold dilutions. MMP-2 activity was assessed using zymoanalysis method. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used. Cytotoxicity analysis of pyrimethamine showed a greater tolerability than methotrexate at concentrations of 1-8 µg/ml. The dose-dependent inhibitory effect of pyrimethamine on MMP-2 activity was significantly less than that of methotrexate at concentrations of 1-8 µg/ml. Moreover, the rate of apoptosis for pyrimethamine-treated cells at different doses (0.1, 1, and 10 µg/ml) was 3.30%, 9.42%, and 11.32%, respectively. Our data suggest that pyrimethamine enables suppression of MMP-2 activity and induces apoptosis that could be assumed for chemoprevention therapy.     

Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid arthritis: discovery of (E)-1-(4-((1R,2S,3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime (LX2931) and (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (LX2932)

Sphingosine 1-phosphate lyase (S1PL) has been characterized as a novel target for the treatment of autoimmune disorders using genetic and pharmacological methods. Medicinal chemistry efforts targeting S1PL by direct in vivo evaluation of synthetic analogues of 2-acetyl-4(5)-(1(R),2(S),3(R),4-tetrahydroxybutyl)-imidazole (THI, 1) led to the discovery of 2 (LX2931) and 4 (LX2932). The immunological phenotypes observed in S1PL deficient mice were recapitulated by oral administration of 2 or 4. Oral dosing of 2 or 4 yielded a dose-dependent decrease in circulating lymphocyte numbers in multiple species and showed a therapeutic effect in rodent models of rheumatoid arthritis (RA). Phase I clinical trials indicated that 2, the first clinically studied inhibitor of S1PL, produced a dose-dependent and reversible reduction of circulating lymphocytes and was well tolerated at dose levels of up to 180 mg daily. Phase II evaluation of 2 in patients with active rheumatoid arthritis is currently underway.     

Alteration of serum sex hormonal profile in male gasoline filling station workers in respect to their polymorphism of glutathione S-transferase M1

Alterations in offspring sex ratio at birth and level of serum testosterone in filling-station workers have been reported. To determine the association of glutathione S-transferase M1 (GSTM1) polymorphism with serum levels of total testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) of male filling-station workers, the present study was carried out on 114 gasoline workers and 100 age- and sex-matched controls with no occupational exposure to gasoline. We have found no significant difference between the workers and controls for levels of sex hormones in the presence of active GSTM1 genotype. Among subjects with the GSTM1 null genotype, there was significant difference between exposed and unexposed subjects for the concentration of testosterone (t = 4.37, df = 97, P < 0.001). To investigate whether one null genotype could be compensated by an active genotype for the other isoenzyme, the mean concentrations of sex hormones was compared between the exposed and control groups with respect to their combinations of the GSTM1 and GSTT1 genotypes. The exposed group having either “null GSTM1/positive GSTT1” (t = 2.76, df = 72, P = 0.007) or “null GSTM1/null GSTT1” (t = 4.91, df = 23, P < 0.001) combinations had a lower testosterone compared with the controls. It seems that GSTM1 polymorphism has more effect on serum testosterone compared to the GSTT1 polymorphism, in exposed workers.