Biological effects of brachytherapy using a (32)P-patch on the skin of Sencar mice.

In recent years, specially designed patches containing beta emitters have been developed for contact brachytherapy of skin lesions. The aim of the present work was to evaluate the biological effects of the (32)P-patch on the skin of Sencar mice as a result of a brachytherapy treatment. For this purpose, a (32)P-patch was prepared with Chromic (32)P-phosphate and silicone and the classical model of two-stage skin carcinogenesis was reproduced in Sencar mice. Animals were divided in six groups. Four groups received the contact brachytherapy treatments using a scheme of a single session of 40 and 60Gy (SD40 and SD60) and a scheme of two sessions of 40 and 60Gy each (FD40 and FD60). The other two groups were used as controls of the single (CSD) and the fractionated (CFD) treatments. Radiation doses were estimated with equations derived from the MIRD DOSE scheme, and biologically effective doses (BED) were calculated according to equations derived from the linear-quadratic model. The endpoint to evaluate the treatments effects was tumor size after a follow-up period of 44 days. Finally, animals were sacrificed in order to get samples of all tumors for histological analysis and PCNA staining. Erythema, dermatitis and skin ulceration developed in almost all treated animals, but they gradually healed with regeneration of tissue during the follow-up period. Radiation effects on the skin of SD40, SD60, FD40 and FD60 showed a significant reduction of the tumor size with regard to controls, independently of the scheme and the radiation dose considered. PCNA staining scores of control groups were higher than for treated groups, independently of the scheme and the radiation dose considered. This radioactive (32)P-silicone-patch which is easy to prepare and use in the treatment of skin diseases, seems promising as a radioactive device for clinical use.

Stabilized-solubilized ferric pyrophosphate as a new iron source for food fortification. Bioavailability studies by means of the prophylactic-preventive method in rats.

The purpose of the present work was to evaluate the iron bioavailability of a new ferric pyrophosphate salt stabilized and solubilized with glycine. The prophylactic-preventive test in rats, using ferrous sulfate as the reference standard, was applied as the evaluating methodology both using water and yogurt as vehicles. Fifty female Sprague-Dawley rats weaned were randomized into five different groups (group 1: FeSO(4); group 2: pyr; group 3: FeSO(4) + yogurt; group 4: pyr + yogurt and group 5: control). The iron bioavailability (BioFe) of each compound was calculated using the formula proposed by Dutra-de-Oliveira et al. where BioFe % = (HbFef - HbFei) x 100/ToFeIn. Finally, the iron bioavailability results of each iron source were also given as relative biological value (RBV) using ferrous sulfate as the reference standard. The results showed that both BioFe % and RBV % of the new iron source tested is similar to that of the reference standard independently of the vehicle employed for the fortification procedure (FeSO(4) 49.46 +/- 12.0% and 100%; Pyr 52.66 +/- 15.02% and 106%; FeSO(4) + yogurth 54.39 +/- 13.92% and 110%; Pyr + yogurt 61.97 +/- 13.54% and 125%; Control 25.30 +/- 6.60, p < 0.05). Therefore, the stabilized and soluble ferric pyrophosphate may be considered as an optimal iron source for food fortification.

Design and bioevaluation of a 32P-patch for brachytherapy of skin diseases.

The purpose of this study was to design and evaluate a 32P patch for brachytherapy of skin diseases. We employed Phosphoric-32P-acid and Chromic 32P-phosphate in combination with natural rubber or silicone to produce the patches. Stability studies in vitro to evaluate the leakage of radioactivity, autoradiographic studies to evaluate homogeneity and shielding, as well as therapeutic efficacy in an animal model of skin cancer of the selected 32P patch were performed. The 32P-silicone-patch demonstrated its safety for external application. Tumor growth was arrest and complete regressions of tumors were seen in some other cases with 40 Gy applied in a single-dose scheme. In conclusion, the 32P-silicone-patch is easy to prepare and use in the treatment of skin diseases.

32P-patch contact brachyradiotherapy in the management of recalcitrant keloids and hypertrophic scars.

Keloids are the result of excessive fibroblast proliferation and then over-abundant collagen deposition. There is no method able to guarantee absolute success in the therapeutic approach to keloids. Our case report involves a female patient with six lesions treated with a 32P-patch brachyradiotherapy. Pre-treatment and adjuvant treatment of the lesions were performed with thiomucase, 5-fluoruracil, procaine and triamcinolone. Taking into account the activity contained in each of the patches and the total radiation dose to be administered according to clinical practice, dosimetric calculations were done for each lesion. Separate silicone patches with chromic [32P]phosphate were designed for each lesion based on these calculations. Total remission was achieved in three treated lesions. The other lesions did not achieve total remission yet, but their sizes are diminishing. The differences observed in treatment outcome may be related with lesion features, adjuvant treatments and/or treatment schedule.

Dietary zinc effects on zinc, calcium, and magnesium content in bones of growing rats.

The aim of the present study was to assess dietary zinc effects on femur weight and mineral content in growing rats. For this purpose, 70 weanling Sprague-Dawley rats were divided into four groups. Each group was subject to a diet containing 2 (BZ), 5 (DZ), 10 (MZ), and 30 (CZ) ppm zinc. The calcium and magnesium content in all diets was 5 g/kg and 507 mg/kg, respectively. The animals were kept on this regime for 28 d and then sacrificed and their femurs were removed for analysis using atomic absorption spectrophotometry. The weights of the BZ and DZ groups were significantly different from the MZ and CZ groups (38.5+/-10.5, 89.9+/-13.7, 118.6+/-13.6, and 134+/-19.9 g, p<0.01) respectively. There were no differences between the MZ and CZ groups. Femur weight also varied with dietary zinc, as it was significantly different among all groups (BZ, 265+/-49 mg; DZ, 380+/-40 mg; MZ, 452+/-54 mg; CZ, 735+/-66 mg; p<0.01). The femur zinc content varied with diets, following a different pattern than the above parameters. Femur zinc from the BZ group (51.5+/-5.4 ppm) was significantly different from the MZ and CZ groups (115.9+/-14.2 and 175.0+/-13.5 ppm, respectively), whereas the DZ group (62.5+/-11.3 ppm) did not differ from the other three groups. The femur content of calcium (BZ, 83.2+/-9.8 mg/g; DZ, 88.0+/-9.2 mg/g; MZ, 90.2+/-13.6 mg/g; CZ, 83.1+/-14.7 mg/g) and magnesium (BZ, 1.82+/-0.13 mg/g; DZ, 1.98+/-0.09 mg/g; MZ, 1.93+/-14 mg/g; CZ, 1.83+/-0.19 mg/g) were not significantly different among the groups, nor was the calcium-magnesium ratio. These results suggest that although dietary zinc deficiency retards growth and causes bone fragility, bone deposition of calcium and magnesium and its ratio are not affected.

Zinc deficiency and growth: current concepts in relationship to two important points: intellectual and sexual development.

Zinc deficiency remains a serious health problem worldwide affecting developed as well as developing countries. Despite the evidence proving that zinc deprivation during the periods of rapid growth negatively affects the cognitive brain as well as sexual development, there are few complete studies carried out in children. The present article proposes a revision of the evidence gathered until now on the relationship existing between zinc deficiency and intellectual and sexual development during the stages of childhood, preadolescence, and adolescence.

Zinc and diabetes mellitus: is there a need of zinc supplementation in diabetes mellitus patients?

Diabetes mellitus is a group of metabolic disorders, the incidence of which varies widely throughout the world. The treatment of diabetes mellitus includes insulin, oral antidiabetic agents, and dietary regimens. Although the emphasis is on macronutrients intakes, there is strong evidence that there is an abnormal metabolism of several micronutrients in diabetic individuals. Zinc is one of the essential micronutrients of which status and metabolism is altered in this condition. This work is a short review about the close relation among zinc, glucose metabolism, and insulin physiology, as well as about the few experimental data about zinc absorption and zinc supplementation in diabetes mellitus patients.

Bioavailability study of dried microencapsulated ferrous sulfate--SFE 171--by means of the prophylactic-preventive method.

Microencapsulated ferrous sulfate with soy lecithin (SFE-171) has been used as an iron source for the fortification of milk and dairy products. With the purpose to extend the use of this agent to other kind of foods or even to pharmaceutical preparations for oral administration, the SFE-171 was turned into a fluid powder (SFE-171-P) by means of vacuum drying. The iron bioavailability (BioFe) of SFE-171-P was evaluated in this work by means of the prophylactic-preventive method in rats, using ferrous sulfate as reference standard. Both iron sources were separately added to a basal diet of low iron content in a concentration of 10 mg iron/kg diet. Two groups of 10 weaned rats 25 days old received the fortified diets during 28 days, while a third group of the same size received the basal diet without iron additions. The weights and haemoglobin concentrations (HbC) of every animal were determined before and after the treatment, thus allowing the calculation of the mass of iron incorporated into haemoglobin (HbFe) during this period. The BioFe of the iron sources were obtained as the percentage ratio between the HbFe and the mass of iron consumed by each animal. The results were also given as Relative Biological Value (RBV), which relates the BioFe of the studied source with that of the reference standard. The liver iron concentration (LIC) of each animal was determined at the end of the experiment in order to evaLuate the influence of the studied iron sources on the liver iron stores. SFE-171-P presented BioFe, RBV and LIC values of (47 +/- 7)%, 109% and (46.6 +/- 3.4) mg/kg respectively, while the corresponding values for the reference standard were of (43 +/- 7)%, 100% and (45.0 +/- 4.7) mg/kg. These results show that the drying process used to produce the SFE-171-P does not affect its bioavailability, which is also adequate for the potential use of this product in food fortification or with pharmaceutical purposes.

Zinc status and immune system relationship: a review.

The essentiality of zinc for humans was first documented by Prasad in the 1960s. The main clinical manifestations associated with zinc deficiency are growth retardation, hypogonadism, diarrhea, and increased susceptibility to infectious diseases. Thus, in the past 25 yr, there was an increased interest of researchers in studying the role of zinc in human immunity. Although mechanistic research has been carried out using animal models, there are several studies in humans with similar results. This work is an attempt to review the information available in this field to understand the important role that zinc plays in the normal development and function of the immune system.

Bioavailability, biodistribution, and toxicity of BioZn-AAS(1): a new zinc source. comparative studies in rats.

Food fortification with a proper zinc compound is an economic and effective strategy to prevent zinc deficiency. BioZn-AAS, a zinc gluconate stabilized with glycine, was compared with zinc sulfate (reference standard), zinc hydroxide, and zinc gluconate, all of them labeled with (65)Zn. This preclinical study was performed on Sprague-Dawley rats of both sexes, and the administered dose was 85 microg/kg of zinc. Bioavailability studies showed that absorption of BioZn-AAS was not statistically different than absorption from other sources in female rats (25.65% +/- 2.20% for BioZn-AAS, 28.24% +/- 4. 60% for ZnSO(4), 24.91% +/- 4.02% for Zn[OH](2), and 25.51% +/- 2. 70% for Zn-gluconate). In the case of the male rats, absorption of BioZn-AAS (27.97% +/- 4.20%) was higher (P<0.05) than that from the other compounds (23.15% +/- 2.90% for ZnSO(4), 22.62% +/- 3.90% for Zn[OH](2), and 22.30% +/- 3.90% for Zn-gluconate). Biodistribution studies demonstrated that the zinc from BioZn-AAS followed the same metabolic pathway as zinc from the other sources. Toxicity studies were performed with 50 female and 50 male rats. The value of oral lethal dose 50 (LD(50)) was 2000 mg/kg for female rats and 1900 mg/kg for male rats. Therefore, we conclude that BioZn-AAS has adequate properties to be considered a proper zinc compound for food fortification or dietary supplementation.

Study of industrial microencapsulated ferrous sulfate by means of the prophylactic-preventive method to determine its bioavailability.

Radio-iron tests are frequently used to measure the bioavailability of different iron sources for food fortification. As the labeling procedures must be done under laboratory conditions, complementary studies should be carried out to evaluate the bioavailability of iron sources produced on an industrial scale. The iron bioavailability of SFE-171 (ferrous sulfate microencapsulated with phospholipids) was studied in previous reports using the compounds labeled with 59Fe and 55Fe; the results showed an iron bioavailability similar to that of ferrous sulfate. In the present work, the iron bioavailability of industrial SFE-171 was studied by the prophylactic-preventive method in rats using ferrous sulfate as the reference standard. Elemental iron powder was also studied by the same method for comparative purposes. The liver iron concentration of each animal was determined at the end of the experiment in order to evaluate the influence of each iron source on the liver iron stores. Relative biological values of 98 and 34% were found for SFE-171 and elemental iron powder, respectively, while the corresponding relative liver iron concentrations were 104 and 45%. The results provided by the prophylactic-preventive method show that the iron bioavailability of industrial SFE-171 is similar to that of ferrous sulfate; these results are also in agreement to those obtained with the radioactive compounds. We can conclude that the SFE-171 obtained by industrial procedures for massive use in iron food fortification has the same bioavailability as that of the SFE-171 produced and labeled under laboratory conditions.

99mTc-ENS: a new radiopharmaceutical for aerosol lung scintigraphy. Comparison between different freeze-dried formulations.

UNLABELLED: Exogenous natural surfactant (ENS) labeled with 99mTc(99mTc-ENS) is a new radiopharmaceutical for pulmonary aerosol scintigraphy. In this study, different freeze-dried formulations were evaluated to develop a suitable and long-storage method for the ENS, the nonradioactive precursor of this radiopharmaceutical. METHODS: Two freeze-dried formulations were evaluated: the sterile ENS suspension-stannous chloride altogether lyophilized (chlorlioENS) and the lyophilized sterile ENS suspension with the addition of stannous chloride as a solid drug (lioENS). These precursors were stored at room temperature for 3 mo and then labeled with 99mTc. For comparative purposes, the sterile ENS suspension with the addition of stannous chloride labeled with 99mTc(99mTc-chlorENS) was also studied. The quality controls for each radiopharmaceutical were performed by an ascending paper chromatography to determine the labeling yield percentages. The study was performed in 30 female Sprague Dawley rats, which inhaled each radiopharmaceutical by nebulization. Twenty-five minutes after the aerosol inhalation, the animals were killed to extract their organs and measure their activity in a gamma spectrometer. The data are given as the percentage of activity concentration (C%) for each organ. RESULTS: The physicochemical properties of lioENS were adequate for a freeze-dried product. The labeling yields for 99mTc-lioENS and for 99mTc-chlorENS were always greater than 95% even after nebulization. The results of the biologic distribution studies showed that the activity concentration found in lungs for these radiopharmaceuticals were 95.7% +/- 2.6% and 96.7% +/- 2.6% respectively, results that do not differ statistically. On the other hand, the activity concentration found in lungs for the 99mTc-chlorlioENS (31.3% +/- 11.1%) and its labeling yield percentages (<10%) are statistically different (P < 0.05) from the results obtained with the two radiopharmaceuticals mentioned above. CONCLUSION: Taking into account the lioENS physicochemical properties, its long shelf life and that 99mTc-lioENS shows the same radiochemical and radiopharmacological behavior of the 99mTc-chlorENS, it can be concluded that the 99mTc-lioENS can be used for aerosol lung scintigraphy.

Microencapsulated ferrous sulfate to fortify cow milk: absorption and distribution in mice.

To determine the absorption and biodistribution of iron from microencapsulated ferrous sulfate (SFE-171), used to fortify dairy products with iron, a comparative study in four groups of 30 mice each was carried out. In two of the groups, the absorption of iron from ferrous ascorbate in water (13.3 +/- 4.3%) and from ferrous sulfate in water (12.7 +/- 3.9%) was determined and taken as reference standards. In the third group the iron absorption from SFE-171 in milk was determined, giving a value of 12.1 +/- 4.2%, which statistically does not differ from the data obtained with either reference standard. In the fourth group, the absorption of iron from ferrous sulfate in milk showed a value of 7.7 +/- 3.4%, which statistically differs with a p < 0.01 from the data corresponding to the other three groups. The biodistribution studies showed that the iron from the SFE-171 follows the same metabolic pathway as the iron from the reference standards thus, giving a higher radioactivity percentage and radioactivity concentration in organs or systems, principally blood, that are closely related to iron metabolism. Our studies allow us to conclude that the iron from SFE-171 in milk follows the same behavior as the nonhemic iron, with a higher absorption than that of ferrous sulfate in milk.

Modification of the ferrozine technique to analyze iron contents in different foods: comparative study using an internal standard as reference methodology.

A methodology for the determination of iron in foods fortified with this element or in nutritional products is important and has to be sensitive and rapid. In developing countries, an inexpensive and reliable methodology is also required. For this purpose, the Gordon's Ferrozine technique was slightly modified and assayed with yogurt, dry powdered milk, and cereal mixtures, all of them fortified with iron, using an internal standard as the reference methodology. The obtained results demonstrate a close correlation between the standard curve interpolation method and the internal standard reference method (correlation coefficient r2 = 0.9950) in a wide range of concentrations. The slope (0.9998+/-0.0040) demonstrates that both procedures measure equal amounts of iron. The conclusion is that the proposed technique is a reliable, practical, and inexpensive methodology for iron determination in different foods fortified with iron.