Long-term treatment of familial male-limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole

Background Familial male-limited precocious puberty (FMPP) or testotoxicosis is a rare gonadotrophin-independent form of sexual precocity caused by constitutively activating mutations of the LH receptor. Several clinical therapeutic approaches have been reported for this disorder, but with a paucity of long-term outcome data. Objective To evaluate the long-term treatment of testotoxicosis with cyproterone acetate or ketoconazole. Design A multicentric retrospective clinical study. Patients Ten boys from eight unrelated Brazilian families who carried known LH-receptor activating mutations were treated with 70 mg/m(2) cyproterone acetate (n = 5) or 10 mg/kg ketoconazole (n = 5) for a mean period of 5 and 8 years, respectively. Measurements Chronological and bone ages, bone age/chronological age ratio, target height (TH) range, adult height, basal and GnRH-stimulated gonadotrophin levels and basal testosterone levels were assessed. Results Growth velocity decreased significantly during treatment with cyproterone acetate or ketoconazole when compared to pretreatment value in each group (P < 0.05). Bone age/chronological age ratio decreased significantly after cyproterone acetate or ketoconazole therapy. Basal testosterone levels were significantly lower in patients undergoing ketoconazole compared to cyproterone acetate treatment [0.6 +/- 0.3 nmol/l (42 +/- 21 ng/dl) vs. 5.6 +/- 4.0 nmol/l (392 +/- 280 ng/dl); P < 0.05], as expected. Secondary gonadotrophin-dependent precocious puberty occurred at a similar frequency (40%) in both groups. Five patients have attained adult height and two patients have already reached 90% of their adult height. Two of them achieved their TH range and one patient, for whom TH was not available, had an adult height of 0.3 SDS. Four boys (two in each group) did not attain their TH range. Conclusion Long-term treatment with cyproterone acetate or ketoconazole resulted in similar outcomes without important side-effects in boys with testotoxicosis. However, both therapies showed limited efficacy in attaining normal adult height.

Liver iron overloading in captive muriquis (Brachyteles spp.)

Background Iron accumulation was investigated qualitatively and quantitatively in the liver of 15 captive Brachyteles spp. Methods Hepatic hemosiderosis index (HHI) was determined as the area percentage of the liver parenchyma occupied by hemosiderin and ferritin deposits, through computerized histomorphometric analysis of Prussian blue-stained histologic sections. Results All studied animals presented liver hemosiderosis, and HHI ranged from 0.2% to 41.7%. There were no significant differences in HHI between muriqui species or genders, and no correlations were detected among HHI and age, time in captivity or body mass. Iron deposits were accompanied by other hepatic disorders. Conclusions This is the first study addressing the occurrence and consequences of iron overloading in the liver of muriquis. We propose that hemosiderosis may act as a contribute factor for the development of hepatic injuries. Further studies are advised to clarify the role of diet in the pathogenesis of hemosiderosis in these atelids.

Transplacental Transfer of Iron in the Water Buffalo (Bubalus bubalis): Uteroferrin and Erythrophagocytosis

The objectives of this investigation were to understand transplacental transport of iron by secreted uteroferrin (UF) and haemophagous areas of water buffalo placenta and clarify the role(s) of blood extravasation at the placental-maternal interface. Placentomes and interplacentomal region of 51 placentae at various stages of gestation were fixed, processed for light and transmission electron microscopy, histochemistry and immunohistochemistry. Haemophagous areas were present in placentomes collected between 4 and 10 months of pregnancy. Perl`s reaction for ferric iron was negative in placentomes, but positive in endometrial glands. Positive staining for UF indicated areas in which it was being taken up by phagocytosis and/or fluid phase pinocytosis in areolae of the interplacentomal mesenchyme, with little staining in endometrial stroma. Imunohistochemistry detected UF in trophectoderm of haemophagous regions of placentomes and in other parts of the foetal villous tree, but the strongest immunostaining was in the epithelial cells and lumen of uterine glands. Ultrastructural analyses indicated that erythrophagocytosis was occurring and that erythrocytes were present inside cells of the chorion that also contained endocytic vesicles and caveolae. Results of this study indicate that both the haemophagous areas of placentomes and the areolae at the interface between chorion and endometrial glands are important sites for iron transfer from mother to foetal-placental tissues in buffalo throughout pregnancy.

Effect of Iron on Matrix Metalloproteinase Inhibition and on the Prevention of Dentine Erosion

It is known that some metal salts can inhibit matrix metalloproteinase (MMP) activity, but the effect of iron has not been tested yet. On the other hand, it has recently been suggested that MMP inhibition might influence dentine erosion. Based on this, the aims of this study were: (1) to test in vitro the effect of FeSO(4) on MMP-2 and -9 activity, and (2) to evaluate in situ the effect of FeSO(4) gel on dentine erosion. MMP-2 and -9 activities were analysed zymographically in buffers containing FeSO(4) in concentrations ranging between 0.05 and 1.5 mmol/l or not. Volunteers (n = 10) wore devices containing bovine dentine blocks (n = 60) previously treated with the following gel treatments: FeSO(4) (1 mmol/l FeSO(4)), F (NaF 1.23%; positive control) and placebo (negative control). The gels were applied once and removed after 1 min. Erosion was performed extraorally with Coca-Cola 4 times per day for 5 min over 5 days. Dentine wear was evaluated by profilometry. The data were analysed by Kruskal-Wallis and Dunn`s tests (p < 0.05). FeSO(4) inhibited both MMP-2 (IC(50) = 0.75 mmol/l) and MMP-9 (IC(50) = 0.50 mmol/l) activities. In the in situ experiment, the mean wear (+/- SD) found for the F gel (0.79 8 +/- 0.08 mu m) was significantly reduced in more than 50% when compared to the placebo gel (1.77 +/- 0.33 mu m), but the FeSO(4) gel completely inhibited the wear (0.05 +/- 0.02 mu m). Since FeSO(4) was able to inhibit MMP in vitro, it is possible that the prevention of dentine wear by the FeSO(4) gel in situ might be due to MMP inhibition, which should be investigated in further studies. Copyright (C) 2010 S. Karger AG, Basel

Preventive effect of iron gel with or without fluoride on bovine enamel erosion in vitro

Background: The aim of this study was to evaluate the preventive effect in vitro of experimental gel containing iron and/or fluoride on the erosion of bovine enamel. Methods: To standardize the blocks (n = 80), specimens (4 x 4 mm) were previously selected to measure the initial microhardness. The blocks were randomly allocated into four groups of 20 samples each: C (control, placebo gel); F (fluoride gel, 1.23% NaF); Fe (iron gel, 10 mmol/L FeSO(4)) and F + Fe (fluoride + iron gel). The gels were applied and removed after 1 minute. The blocks were then submitted to six alternating remineralization and demineralization cycles. The beverage Coca-Cola (R) (10 minutes, 30 mL) was used for demineralization, and artificial saliva (1 hour) for remineralization. The effect of erosion was measured by wear analysis (profilometry). Data were analysed by ANOVA and the Tukey test for individual comparisons (p <0.05). Results: The mean wear (+/- SD, mu m) was C: 0.94 +/- 0.22; F: 0.55 +/- 0.12; Fe: 0.49 +/- 0.11 and F + Fe: 0.55 +/- 0.13. When the experimental gels were used, there was statistically significant reduction in enamel wear in comparison with the control (p <0.001). However, the experimental gels did not differ significantly among them. Conclusions: The gels containing iron with or without fluoride are capable of interfering with the dissolution dental enamel in the presence of erosive challenge.

Preventive effect of an iron varnish on bovine enamel erosion in vitro

Objective: The aim of this study was to evaluate, in vitro, the effect of an experimental varnish containing iron on the dissolution of bovine enamel by carbonated beverage. Methods: Eighty specimens were randomly allocated to four groups (n = 20 per group), according to the following treatments: Fe varnish (FeV, 10 mmoL/L Fe), F varnish (FV, 2.71% F), placebo varnish (PV) and control (not treated, NT). The varnishes were applied in a thin layer and removed after 6 h. Then, the samples were submitted to six cycles, alternating re- and demineralisation (only 1 day). Demineralisation was performed with the beverage Coca-Cola (R) (10 min, 30 mL/block) and remineralisation with artificial saliva for I h. In order to determine the amount of enamel dissolved, the wear was analysed by profilometry. Data were analysed by ANOVA and Tukey`s test (p < 0.05). Results: The mean wear (+/- S.E.) was significantly lesser for the FeV (0.451 +/- 0.018 mu m) when compared to the other treatments. The FV caused significantly less wear (0.554 +/- 0.022 mu m) when compared to PV (0.991 +/- 0.039 mu m) and NT (1.014 +/- 0.033), which did not significantly differ from each other. Conclusions: The results suggest that the iron varnish can interfere with the dissolution of dental enamel in the presence of acidic beverages. (C) 2008 Elsevier Ltd. All rights reserved.

Iron deficiency anaemia and blood lead concentrations in Brazilian children

This study investigated the relationship between iron deficiency/iron deficiency anaemia, assessed by several parameters, and blood lead concentration in children. This cross-sectional study involved 384 Brazilian children, aged 2-11 years, who lived near a lead-manipulating industry. Complete blood counts were obtained by an automated cell counter. Serum iron, total iron binding capacity (TIBC) and ferritin were determined respectively, by colorimetric, turbidimetric methods and chemiluminescence. Blood lead was measured by atomic absorption spectrophotometry. The impact of several parameters for assessment of iron status (haemoglobin, serum iron, TIBC, transferrin saturation, ferritin, red cell indices and red cell distribution width) and variables (gender, age, mother`s education, income, body mass index, iron intake, and distance from home to lead-manipulating industry) on blood lead concentration was determined by multiple linear regression. There were significant negative associations between blood lead and the distance from home to the lead-manipulating industry (P < 0.001), Hb (P = 0.019), and ferritin (P=0.023) (R(2)=0.14). Based on these results, further epidemiological studies are necessary to investigate the impact of interventions like iron supplementation or fortification, as an attempt to decrease blood lead in children. (C) 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Fortified food made by the extrusion of a mixture of chickpea, corn and bovine lung controls iron-deficiency anaemia in preschool children

A fortified food that was rich in protein, vitamins and iron made of chickpea, bovine lung and corn was developed with the aim of controlling iron-deficiency anaemia in children from poorer areas. It was tested in Teresina, State of Piaui, Northeastern Brazil, on a population with high anaemia prevalence. Two local daycare units with similar characteristics were selected and the children at one of them received a 30 g pack three times a week, representing a total iron daily intake of 6.96 mg. The other daycare unit was followed as a control. The capillary haemoglobin concentration was determined for the children at both daycare units, at the beginning of the study and after a two-month intervention period. The mean haemoglobin concentration in the test group at the beginning of the intervention was 11.8 g/dL, which increased to 13.1 g/dL at the end of the intervention. In the control group these figures remained practically constant (11.6-11.8 g/dL). These represented a dramatic and significant drop in anaemia prevalence, from 61.5% to 11.5% in the test group, and an insignificant reduction (63.1-57.7%) in the control group. The acceptance of the fortified snack was excellent and no undesirable effects were observed. (C) 2007 Published by Elsevier Ltd.

Iron Concentrations in Breast Milk and Selected Maternal Factors of Human Milk Bank Donors

The aim of this study was to evaluate the relationship between iron concentration in mature breast milk and characteristics of 136 donors of a Brazilian milk bank. Iron, vitamin A, zinc, and copper concentrations were assessed in human milk and maternal blood. Data were collected on maternal anthropometrics, obstetric, socioeconomic, demographic, and lifestyle factors. Iron, zinc, and copper in milk and zinc and copper in blood were detected by spectrophotometry. Vitamin A in milk and blood was determined by high-performance liquid chromatography. Hemoglobin was measured by electronic counting and serum iron and ferritin by colorimetry and chemoluminescence, respectively. Transferrin and ceruloplasmin were determined by nephelometry. According to multivariate linear regression analysis, iron in milk was positively associated with vitamin A in milk and with smoking but negatively associated with timing of breast milk donation (P < .001). These results indicate that iron concentration in milk of Brazilian donors may be influenced by nutritional factors and smoking. J Hum Lact. 26(2):175-179

PHYSICAL AND CHEMICAL CHARACTERISTICS OF FROZEN GROUND BEEF AND AGED BEEF MEAT FROM BOS INDICUS STEERS SUPPLEMENTED WITH alpha-TOCOPHEROL ACETATE

The objective of this study was to evaluate the effects of diet supplementation with vitamin E on the physical and chemical characteristics of ground, frozen and stored or aged Quadriceps femoris (QF) and Longissimus dorsi (LD) muscles from Nellore steers fed high concentrate diets. Muscles were obtained from 24 animals that were 30 months old with a mean live weight of 279 kg. Half of the animals received daily doses of 1,000 mg of alpha-tocopherol acetate (VIT E) per head per day that was added to 100 g of corn meal. The other half received 100 g of corn meal without the antioxidant. Twenty-four hours after slaughtering, QF samples from each animal were ground, frozen and stored for up to 6 months. In addition, 4 samples from the LD of each animal were vacuum packed individually and kept for 21 days. All samples were analyzed to determine the pH, color and water-holding-capacity. The VIT E supplementation improved only the water loss characteristics of frozen ground QF and did not have any positive effect on the physical-chemical characteristics of the aged LD.

Investigation of some dielectric properties of phosphate glasses doped with iron oxides, by a microwave technique

The effects of iron ions on dielectric properties of lithium sodium phosphate glasses were studied by non-usual, fast and non-destructive microwave techniques. The dielectric constant (epsilon`). insertion loss (L) and microwave absorption spectra (microwave response) of the selected glass system xFe(2)O(3)center dot(1 - x)(50P(2)O5 center dot 25Li(2)O center dot 25Na(2)O), being x = 0, 3, 6, ....,15 expressed in mol.%, were investigated. The dielectric constant of the samples was investigated at 9.00 GHz using the shorted-line method (SLM) giving the minimum value of epsilon` = 2.10 +/- 0.02 at room temperature, and increasing further with x, following a given law. It was observed a gradual increasing slope Of E in the temperature range of 25 <= t <= 330 degrees C, at the frequency of 9.00 GHz. Insertion loss (measured at 9.00 GHz) and measurements of microwave energy attenuation, at frequencies ranging from 8.00 to 12.00 GHz were also studied as a function of iron content in the glass samples. (C) 2009 Elsevier Ltd. All rights reserved.

Dielectric properties and physical features of phosphate glasses containing iron oxide

Microwave techniques were applied to the study of dielectric properties of phosphate glasses on the basis of contributions from permanent and induced dipolar polarization of local structural units interacting with the electrical component of the electromagnetic radiation. The dielectric constant of the selected glass system (100-x)(50P(2)O(5)center dot 25Li(2)O center dot 25Na(2)O)center dot xFe(2)O(3), where 0 <= x <= 21 is in mol%, was measured using a microwave setup assembled to measure the phase shift of the standing wave pattern produced by the insertion of the sample. It is shown that the Fe2+ ions contribute effectively to the dielectric constant, as expected from the interactions of the dipoles of the local charge compensation pairs with the microwave radiation. However, there is the possibility of occurrence of some ions Fe3+, in general, at low iron content, which reinforces the glass structure and, therefore, decreases the dielectric constant. There is a gradual conversion from Fe3+ to Fe2+ as the iron ions increases. This is possibly the reason of the anomaly in the dielectric constant values observed in the results. These assumptions can be checked by results of electronic paramagnetic resonance (EPR) and optical absorption (OA). The dielectric constant of the glasses studied in this work was found to increase with the temperature in the range of 25-330 degrees C. (C) 2007 Elsevier B.V. All rights reserved.

A mechanism for the formation of oxygen and iron bimodal radial distribution in the disc of our Galaxy

Recently, it has been proposed that there are two type Ia supernova progenitors: short-lived and long-lived. On the basis of this idea, we develop a theory of a unified mechanism for the formation of the bimodal radial distribution of iron and oxygen in the Galactic disc. The underlying cause for the formation of the fine structure of the radial abundance pattern is the influence of the spiral arms, specifically the combined effect of the corotation resonance and turbulent diffusion. From our modelling, we conclude that in order to explain the bimodal radial distributions simultaneously for oxygen and iron and to obtain approximately equal total iron output from different types of supernovae, the mean ejected iron mass per supernova event should be the same as quoted in the literature if the maximum mass of stars, which eject heavy elements, is 50 M(circle dot). For the upper mass limit of 70 M(circle dot), the production of iron by a type II supernova explosion should increase by about 1.5 times.

Lifetime Overproduction of Circulating Angiotensin-(1-7) Attenuates Deoxycorticosterone Acetate-Salt Hypertension-Induced Cardiac Dysfunction and Remodeling

We evaluated the development of arterial hypertension, cardiac function, and collagen deposition, as well as the level of components of the renin-angiotensin system in the heart of transgenic rats that overexpress an angiotensin (Ang)-(1-7)-producing fusion protein, TGR(A1-7)3292 (TG), which induces a lifetime increase in circulating levels of this peptide. After 30 days of the induction of the deoxycorticosterone acetate (DOCA)-salt hypertension model, DOCA-TG rats were hypertensive but presented a lower systolic arterial pressure in comparison with DOCA-Sprague-Dawley (SD) rats. In contrast to DOCA-SD rats that presented left ventricle (LV) hypertrophy and diastolic dysfunction, DOCA-TG rats did not develop cardiac hypertrophy or changes in ventricular function. In addition, DOCA-TG rats showed attenuation in mRNA expression for collagen type I and III compared with the increased levels of DOCA-SD rats. Ang II plasma and LV levels were reduced in SD and TG hypertensive rats in comparison with normotensive animals. DOCA-TG rats presented a reduction in plasma Ang-(1-7) levels; however, there was a great increase in Ang-(1-7) (approximate to 3-fold) accompanied by a decrease in mRNA expression of both angiotensin-converting enzyme and angiotensin-converting enzyme 2 in the LV. The mRNA expression of Mas and Ang II type 1 receptors in the LV was not significantly changed in DOCA-SD or DOCA-TG rats. This study showed that TG rats with increased circulating levels of Ang-(1-7) are protected against cardiac dysfunction and fibrosis and also present an attenuated increase in blood pressure after DOCA-salt hypertension. In addition, DOCA-TG rats showed an important local increase in Ang-(1-7) levels in the LV, which might have contributed to the attenuation of cardiac dysfunction and prefibrotic lesions. (Hypertension. 2010;55:889-896.)

Transepithelial transport of glucose and mRNA of glucose transporters in the small intestine of rats with iron-deficiency anemia

Objective: To evaluate the transepithelial transport of sodium, glucose, potassium, and water and the mRNA level of the sodium-glucose cotransporter (SGLT1) and the facilitated sugar transporter (GLUT2) in the small intestine of iron-deficient rats. Methods: After 6 wk of receiving diets with low or normal iron content, rats (Wistar-EPM) were subjected to two experiments: 1) evaluation of the transepithelial transport of sodium, glucose, potassium, and water by an ""in vivo"" experimental model of intestinal perfusion and 2) determination of relative SGLT1 and GLUT2 mRNA levels in the proximal, intermediate, and distal portions of the small intestine by the northern blotting technique. Results: Hemoglobin and hepatic iron levels were statistically lower in the anemic rats. The mean transepithelial transports of sodium (-33.0 mu Eq . min(-1) . cm(-1)), glucose (426.0 mu M . min(-1) . cm(-1)), and water (0.4 mu L . min(-1) . cm(-1)) in the small intestine of the anemic rats were significantly lower than in the control group (349.1 mu Eq . min(-1) cm(-1), 842.6 mu M . min(-1) . cm(-1), and 4.3 mu l . min(-1) cm(-1), respectively, P < 0.05). The transepithelial transport of potassium was similar for both groups. The relative SGLT1 mRNA levels of the anemic rats in the intermediate (1.796 +/- 0.659 AU) and distal (1.901 +/- 0.766 AU) segments were significantly higher than the values for the control rats (intermediate 1.262 +/- 0.450 AU, distal 1.244 +/- 0.407 AU). No significant difference was observed for the relative SLGT1 mRNA levels in the proximal segment or for the GLUT2 mRNA levels in all segments. Conclusion: Iron deficiency decreases the absorption of glucose, sodium, and water and increases SGLT1 mRNA in the intermediate and distal segments of the small intestine of rats. (C) 2011 Elsevier Inc. All rights reserved.