A finely tuned interplay between calcium binding, ionic strength and pH modulates conformational and oligomerization equilibria in the Respiratory Syncytial Virus Matrix (M) protein.

As in most enveloped RNA viruses, the Respiratory Syncytial Virus Matrix (RSV-M) protein plays key roles in viral assembly and uncoating. It also plays non-structural roles related to transcription modulation through nucleo-cytoplasmic shuttling and nucleic acid binding ability. We dissected the structural and conformational changes underlying the switch between multiple functionalities, identifying Ca2+ binding as a key factor. To this end, we tackled the analysis of M's conformational stability and equilibria. While in silico calculations predict two potential calcium binding sites per protomer, purified RSV-M dimer contains only one strongly bound calcium ion per protomer. Incubation of RSV-M in the presence of excess Ca2+ leads to an increase in the thermal stability, confirming additional Ca2+ binding sites. Moreover, mild denaturant concentrations trigger the formation of higher order oligomers which are otherwise prevented under Ca2+ saturation conditions, in line with the stabilizing effect of the additional low affinity binding site. On the other hand, Ca2+ removal by chelation at pH 7.0 causes a substantial decrease in the thermal stability leading to the formation of amorphous, spherical-like aggregates, as assessed by TEM. Even though the Ca2+ content modulates RSV-M oligomerization propensity, it does affect its weak RNA binding ability. RSV-M undergoes a substantial conformational change at pHs 4.0 to 5.0 that results in the exposure of hydrophobic surfaces, an increase beta sheet content but burial of tryptophan residues. While low ionic strength promotes dimer dissociation at pH 4.0, physiological concentrations of NaCl lead to the formation of soluble oligomers smaller than 400 kDa at pH 4.0 or insoluble aggregates with tubular morphology at pH 5.0, supporting a fine tuning by pH. Furthermore, the dissociation constants estimated for the low- and high affinity calcium binding sites are 13 µM and 58 nM, respectively, suggesting an intracellular calcium sensing mechanism of RSV-M upon infection. We uncover a finely tuned interplay between calcium binding, ionic strength, and pH changes compatible with the different cellular compartments where M plays key roles, revealing diverse conformational equilibria, oligomerization, and high order structures, required to stabilize the virion particle by a layer of molecules positioned between the membrane and the nucleocapsid.

A conformational switch balances viral RNA accessibility and protection in a nucleocapsid ring model.

Virus from the Mononegavirales order share common features ranging from virion structure arrangement to mechanisms of replication and transcription. One of them is the way the nucleoprotein (N) wraps and protects the RNA genome from degradation by forming a highly ordered helical nucleocapsid. However, crystal structures from numerous Mononegavirales reveal that binding to the nucleoprotein results in occluded nucleotides that hinder base pairing necessary for transcription and replication. This hints at the existence of alternative conformations of the N protein that would impact on the protein-RNA interface, allowing for transient exposure of the nucleotides without complete RNA release. Moreover, the regulation between the alternative conformations should be finely tuned. Recombinant expression of N from the respiratory syncytial virus form regular N/RNA common among all Mononegavirales, and these constitute an ideal minimal unit for investigating the mechanisms through which these structures protect RNA so efficiently while allowing for partial accessibility during transcription and replication. Neither pH nor high ionic strength could dissociate the RNA but led to irreversible aggregation of the nucleoprotein. Low concentrations of guanidine chloride dissociated the RNA moiety but leading to irreversible aggregation of the protein moiety. On the other hand, high concentrations of urea and long incubation periods were required to remove bound RNA. Both denaturants eventually led to unfolding but converged in the formation of an RNA-free ß-enriched intermediate species that remained decameric even at high denaturant concentrations. Although the N-RNA rings interact with the phosphoprotein P, the scaffold of the RNA polymerase complex, this interaction did not lead to RNA dissociation from the rings in vitro. Thus, we have uncovered complex equilibria involving changes in secondary structure of N and RNA loosening, processes that must take place in the context of RNA transcription and replication, whose detailed mechanisms and cellular and viral participants need to be established.

Microabrasion: a treatment option for white spots.

The aim of the present study was to describe a clinical protocol for the treatment of white spots with the use of an abrasive material. A four-year-old patient presented with a white spot on tooth 51 and a white spot associated with a carious lesion in the cervical region of tooth 52. Treatment was planned with microabrasion and restoration of the upper right lateral incisor. Prophylaxis was first performed, followed by protection with a dental dam and the application of the abrasive material (silicon carbide and hydrochloric acid 6%). Five applications were needed to remove the spots. The restoration of the upper right lateral incisor was then performed with a resin composite. A good esthetic outcome was achieved and both the patient and her guardians were satisfied with the results. Microabrasion is a conservative treatment option that achieves satisfactory results with regard to tooth color.

Continuous reporting of new cases in Spain supports the relationship between Herbalife® products and liver injury.

PURPOSE: Previous publications have linked Herbalife® products to hepatotoxicity. The identification of earlier cases in which the culprit agent could not be established raised the hypothesis of a possible contamination of some specific batches of Herbalife products. METHODS: We searched the Spanish Pharmacovigilance Centres' database of adverse reactions for reports of liver injury associated with the use of Herbalife products from 2003, when the first case was submitted, through September 2010. RESULTS: The search resulted in 20 reports of liver damage (mean age, 49 years; 16 women), with 12 patients (60%) requiring hospitalization. Hepatocellular damage predominated, and nine (53%) of the hepatocellular cases with bilirubin values were jaundiced, fulfilling the Hy's law criteria, which increases the risk for serious outcomes. Two patients experienced a positive rechallenge. One patient developed cirrhosis, whereas all the others recovered. Causality assessment by the Karch and Lasagna modified algorithm showed a category of definite in 1 case, probable in 14, and possible in 5. Analysis of the different Herbalife products that each patient had taken did not enable us to identify any commonly known hepatotoxic ingredient. CONCLUSIONS: Our results support the relationship between the consumption of Herbalife products and hepatotoxicity, underscore the concern regarding the liver-related safety of this dietary supplement, and emphasize the need to establish further regulatory measures.

Signs of an in situ inflammatory reaction in scars of human American tegumentary leishmaniasis.

Skin inflammation plays an important role during the healing of American tegumentary leishmaniasis (ATL), the distribution of cells in active lesions may vary according to disease outcome and parasite antigens in ATL scars have already been shown. We evaluated by immunohistochemistry, 18 patients with 1- or 3-year-old scars and the corresponding active lesions and compared them with healthy skin. Small cell clusters in scars organized as in the active lesions spreaded over the fibrotic tissue were detected, as well as close to vessels and cutaneous glands, despite a reduction in the inflammatory process. Analysis of 1-year-old scar tissue showed reduction of NOS2, E-selectin, Ki67, Bcl-2 and Fas expression. However, similar percentages of lymphocytes and macrophages were detected when compared to active lesions. Only 3-year-old scars showed reduction of CD3(+), CD4(+) and CD8(+)T cells, in addition to reduced expression of NOS2, E-selectin, Ki67 and BCl-2. These results suggest that the pattern of cellularity of the inflammatory reaction observed in active lesions changes slowly even after clinical healing. Analysis of 3-year-old scars showed reduction of the inflammatory reaction as demonstrated by decrease in inflammatory cells and in the expression of cell-activity markers, suggesting that the host-parasite balance was only established after that period.

Leishmania (Viannia) braziliensis genotypes identified in lesions of patients with atypical or typical manifestations of tegumentary leishmaniasis: evaluation by two molecular markers.

Analyses of MLEE, RAPD and LSSP-PCR were used to compare the panel of american tegumentary leishmaniasis (ATL) isolates obtained from lesions of patients with rare clinical manifestations of the disease and typical lesions. All of the 34 samples analyzed by MLEE demonstrated similar electromorphic profiles with Leishmania (Viannia) braziliensis reference strain. Through the RAPD analysis, nine genetic profiles (genotypes) were identified. LSSP-PCR corroborates the initial screening and phenetic analysis has grouped the isolates into two major clusters comprising the nine different genotypes. Prevalent genotype defined as LbmtDNAgen1 was detected in the largest number of isolates. There was no association between genotypes and clinical symptoms. However, two different genotypes could be identified in the initial (LbmtDNAGen9) and reactivated lesion (LbmtDNAGen3) of the same patient. Our results support the idea of a less pronounced genotypic diversity among L. (V.) braziliensis circulating in the State of Rio de Janeiro and demonstrate the useful application of these molecular markers in genetics variability studies.

The impact of social influence on adolescent intention to smoke: combining types and referents of influence.

OBJECTIVES: Theory and research suggest that the intention to smoke is the main determinant of smoking initiation and emphasizes the role of cognitive and social factors on the prediction of the intention to smoke. However, extended models such as the I-Change and results from published studies reveal inconsistencies regarding the impact of social influence on the intention to smoke. Possible explanations for this may be the definition and measurement of the constructs that have been used. DESIGN AND METHODS: The current study was designed with two main goals: (i) to test a measurement model for social influence, combining different types of social influence (subjective norms, perceived behaviour, and direct pressure) with various referents of influence (parents, siblings, peers, and teachers); (ii) to investigate the impact of social influence on adolescent intention to smoke, controlling for smoking behaviour. LISREL was used to test these models. The sample includes 3,064 Portuguese adolescents, with a mean age of 13.5 years, at the beginning of the seventh school grade. RESULTS: The hypothesized measurement model of social influence was supported by results and explained 29% of the variance of the intention to smoke. A more extended model, including attitude and self-efficacy, explained 55% of the variance of the intention to smoke. Perceived behaviour of peers, parental norms, and perceived behaviour of parents were the social influence factors with impact on adolescent intention to smoke. CONCLUSIONS: Results suggest that different referents exert their influence through distinct types of social influence and recommend further work on the definition and measurement of social influence.

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.

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.

Respiratory sleep disturbance in children and adolescents with cystic fibrosis.

UNLABELLED: Sleep disturbance has been described in cystic fibrosis (CF) patients as relevant to clinical and lung function predictive factors helping to improve the diagnosis and early intervention. Related paediatric studies are scarce. OBJECTIVE: To describe respiratory sleep disturbance (RSD) and its association with spirometric indices in a population of CF children. A second aim was to determine if spirometric indices and wake-time SpO2 are predictors of sleep disturbance. METHODS: A cross-sectional study involving 33CF paediatric patients. All participants underwent in-lab polysomnography (PSG), pulse oximetry and spirometry. A standardized sleep questionnaire was completed for each patient. Two subgroups were considered: I - Normal (FEV1>-1.64 z-score); II - Obstructed (FEV1≤-1.64 z-score). RESULTS: Participant's median age was 12 (6-18) years, 16 (48.5%) were male. Twenty-nine patients (87.9%) presented sleep complaints. Sleep efficiency was reduced; sleep latency and waking after sleep onset (WASO) increased. N1 increased, N2, N3, REM and awakenings were normal. The apnoea-hypopnoea index was 0.6/h (sd 0.9); respiratory disturbance index (RDI) was 6.6/h (sd 5.2). Mean awaking (97% (sd 1.1)) and sleep SpO2 (95% (sd 2.7)) were normal; mean nocturnal oximetry desaturation index was 2.36/h; minimal nocturnal SpO2 was 89% (sd 4.1). We found associations between mean nocturnal SPO2 and mean values of FEV1 (r=0.528; p=0.002) and FEF25-75 (r=0.426; p=0.013). There were significant differences in nocturnal SpO2 between normal and obstructed patients (p<0.000). PSG data correlated with the questionnaire answers for night awakenings and WASO (p=0.985) and difficult breathing during sleep and RDI (p=0.722). This study points to most CF children having sleep complaints, and highlights the correlation between subjective assessment of sleep and PSG and spirometric results. Awake-time SpO2 and spirometric values are possible risk predictors for nocturnal desaturation.

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.

Cholesterol: a useful parameter for distinguishing between pleural exudates and transudates.

Previously established criteria were used to classify 253 pleural effusions as transudates (65 cases), neoplastic exudates (67 cases), tuberculous exudates (65 cases), or miscellaneous exudate (56 cases). The parameters pleural LDH (PLDH), pleural LDH/serum LDH ratio (P/SLDH), and pleural protein/serum protein ratio (P/SPROT) were compared with pleural cholesterol (PCHOL) and the pleural cholesterol/serum cholesterol ratio (P/SCHOL) with regard to their usefulness for distinguishing between pleural exudates and transudates. The PCHOL values determined were 28.5 +/- 12.8 mg/dl for transudates, 88.1 +/- 30 mg/dl for neoplastic exudates, 96.5 +/- 28 mg/dl for tuberculous exudates, and 88 +/- 35.9 mg/dl for the miscellaneous group; the differences between the transudate group and the others are statistically significant (p less than 0.001). The sensitivity and specificity of P/SPROT for diagnosis of exudates were both 89 percent; the sensitivity of PLDH was 67 percent and its specificity was 95 percent; the sensitivity and specificity of P/SLDH were both 84.6 percent. Using Light's three criteria as a battery, the sensitivity was 94.6 percent and its specificity was 78.4 percent. All the transudates and 17 (9 percent) of the 188 exudates had PCHOL values below 55 mg/dl, so that with this threshold, PCHOL had a sensitivity of 91 percent and a specificity of 100 percent for diagnosis of exudates. With a threshold of 0.3, P/SCHOL had a sensitivity of 92.5 percent and a specificity of 87.6 percent. The number of misclassifications by PCHOL was less than with any other of the parameters, with statistically significant differences with respect to PLDH (p less than 0.001) and P/SLDH (p less than 0.01). We conclude that determination of PCHOL and P/SCHOL is of great value for distinguishing between pleural exudates and transudates, and should be included in routine laboratory analysis of pleural effusions.

Diagnosis of tuberculous pleurisy using the biologic parameters adenosine deaminase, lysozyme, and interferon gamma.

We compared the parameters pleural adenosine deaminase (PADA, determined in 405 patients), the PADA/serum ADA ratio (P/SADA; 276 cases), pleural lysozyme (PLYS, 276 cases), the PLYS/serum LYS ratio (P/SLYS; 276 cases), and pleural interferon gamma (IFN, 145 cases) regarding their ability to differentiate tuberculous pleural effusions from others. The 405 pleural effusions were classified by previously established criteria as tuberculous (91), neoplastic (110), parapneumonic (58), empyemas (10), transudates (88), or miscellaneous (48). The intermean differences between the tuberculous group and each of the others were statistically significant for all five parameters (p < 0.01 for PLYS and P/SLYS with respect to the empyema group; p < 0.001 otherwise), except for PADA and P/SADA with respect to the empyema group. All the tuberculous pleurisy cases had PADA values of 47 U/L or more, as compared to only 5 percent of the other cases (sensitivity, 100 percent; specificity, 95 percent). P/SADA was above 1.5 in 85.7 percent of tuberculous effusions and 11 percent of the others (sensitivity, 85.7 percent; specificity, 89 percent). PLYS, with a diagnostic threshold of 15 g/ml, had a sensitivity of 85.7 percent and a specificity of 61.6 percent; P/SLYS, with a threshold of 1.1, had a sensitivity of 67.3 percent and a specificity of 90.3 percent; and IFN, with a threshold of 140 pg/ml, had a sensitivity of 94.2 percent and a specificity of 91.8 percent. The lowest misclassification rate was achieved by PADA, with statistically significant differences (p < 0.001) with respect to P/SADA, PLYS, and P/SLYS, but not with respect to IFN. The only significant pairwise correlations among these parameters were between P/SLYS and PADA and between P/SLYS and P/SADA. We conclude that PADA and IFN are useful parameters for early diagnosis of tuberculous pleurisy, and that the other parameters considered have no advantages over PADA and IFN for this purpose (though the high specificity of P/SLYS may be noted).

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.

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.

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.

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.

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.

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.