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[Advances in the Brazilian norm for commercialization of infant foods].

OBJECTIVE: To assess the advances in the Brazilian norm for commercialization of infant foods from 1988 to 2002, comparing the different texts with each other and with the International Code of Marketing of Breast-Milk Substitutes. METHODS: This was a descriptive study based on data collected from documents, reports, ordinances and resolutions from the Brazilian Ministry of Health. The versions utilized in the comparison were from 1992 and 2002. RESULTS: Comparative analysis made it possible to identify important advances in the legislation. In 1992, liquid and powdered milk were included in the scope, along with teats and dummies (pacifiers), and also warning phrases in advertising and on product labeling. In 2002, regulations for products were published by the National Agency for Sanitary Surveillance, thereby strengthening supervisory actions and including regulations for baby foods, nutrient formulae for high-risk newborns, and nipple protectors. The phrases used in commercial advertising and on product labeling, including dummies, teats and bottles, became Ministry of Health warnings. The labeling was defined according to product types, on the basis of more restrictive rules. CONCLUSIONS: Significant modifications in the control over the marketing of products aimed at mothers during the lactation period. However, there are still some legislative questions that would make it possible to improve the Brazilian norm, in order to protect breastfeeding. There is also a need for the government to implement systematic monitoring routines to supervise this legislation.

Brazil↗

Labeled oxidation products from [1-14C], [U-14C] and [16-14C]-palmitate in hepatocytes and mitochondria.

When [1-14C], [U-14C], and [16-14C]palmitate were oxidized by isolated rat hepatocytes, there was a differential distribution of label as a percent of total oxidized products, such that 14CO2 from [1-14C] greater than [U-14C] greater than [16-14C]palmitate and acid-soluble radioactivity from [16-14C] greater than [U-14C] greater than [1-14C]palmitate. The oxidation of [2,3-14C]succinate to 14CO2 by isolated hepatocytes was only 9.1% of that from [1,4-14C]succinate, demonstrating that the differences in distribution of labeled products are in part due to less 14CO2 production from label in the even carbon positions entering the citric acid cycle. Apparent total ketone body production from [16-14C]palmitate was markedly higher than [1-14C] and [U-14C]palmitate. In addition, the 14C-acetone:14CO2 ratio derived from decarboxylation of labeled acetoacetate from [1-14C]palmitate was less than 1 and positively correlated to the rate of fatty acid oxidation in hepatocytes. These findings indicate that the known preferential incorporation of the omega-C2 unit of fatty acids into 14C-ketone bodies also contributed to the differential distribution of labeled products and that this contribution was greatest at the lower rates of fatty acid oxidation. In isolated mitochondria, the distribution of label to 14CO2 and acid-soluble radioactivity from [1-14C], [U-14C] and [16-14C]palmitate was qualitatively similar to that seen with hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗

A qualitative assessment of direct-labeled cDNA products prior to microarray analysis.

BACKGROUND: The success of the microarray process in determining differential gene expression of thousands of genes is dependent upon the quality and integrity of the starting RNA, this being particularly true of direct labeling via a reverse transcription procedure. Furthermore, an RNA of reasonable quality still may not yield reliable hybridization data if the labeling efficiency was poor. RESULTS: Here we present a novel assay for assessing the quality of directly labeled fluorescent cDNA prior to microarray hybridization utilizing the Agilent 2100 Bioanalyzer, which employs microfluidic technology for the analysis of nucleic acids and proteins. Using varying amounts of RNase to simulate RNA degradation, we show the strength of this un-advertised assay in determining the relative amounts of cDNA obtained from a direct labeling reaction. CONCLUSION: Utilization of this method in the lab will help to prevent the costly mistake of hybridizing poor quality direct labeled products to expensive arrays.

Computational Biology↗

Changes in reported awareness of product warning labels and messages in cohorts of California Hispanics and non-Hispanic whites.

A cohort of 777 Hispanics and 234 non-Hispanic Whites were interviewed in San Francisco, California, over the telephone in 1991 and again 1 year later. Overall, both Hispanics and non-Hispanic Whites showed an increase in awareness of a general product warning label for beer and wine containers but a decrease in awareness of a product warning label for cigarettes. High- and low-acculturated Hispanics' awareness of a general product warning label increased for alcoholic beverage containers, although highly acculturated Hispanics were more aware. Both Hispanics and non-Hispanic Whites showed an increase in awareness of specific warning messages. The highly acculturated Hispanics showed more increased awareness of specific message than the less acculturated Hispanics.

Adult↗

Study of the labeling of two novel RGD-peptidic derivatives with the precursor [99mTc(H2O)3(CO)3]+ and evaluation for early angiogenesis detection in cancer.

In the initial stages of tumor formation, overexpression of integrins identifying the RGD sequence (Arg-Gly-Asp) is observed. The aim of the present study was the synthesis and labeling of two novel RGD derivatives, via the precursor [99mTc(H2O)3(CO)3]+, as well as the radiochemical and radiopharmacological evaluation of the labeled products. The labeling led to the formation of a single product in each case (>98%), with noteworthy in vitro stability, fast blood clearance and elimination by the hepatobiliary and the urinary systems.

Animals↗

Labeling effects on the isoelectric point of green fluorescent protein.

We studied the effects of fluorescent labeling on the isoelectric points (pI values) of proteins using capillary isoelectric focusing with laser-induced fluorescence detection (cIEF-LIF). Specifically, we labeled green fluorescent protein (GFP) from the jellyfish Aequorea victoria with the fluorogenic dye 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ). cIEF-LIF was used to monitor the native fluorescence of GFP and showed pI changes in GFP's FQ-labeled products. Multiple labeling of GFP with FQ produced a series of products with pI values shifted towards a low pH. We verified cIEF-LIF results with traditional slab gel IEF. Our cIEF-LIF technique can routinely detect 10(-11) M of FQ-labeled protein, whereas traditional slab gel IEF with silver stain detection gives detection limits of 10(-7) M in the same samples.

Animals↗

Mechanistic positron emission tomography studies: demonstration of a deuterium isotope effect in the monoamine oxidase-catalyzed binding of [11C]L-deprenyl in living baboon brain.

The application of positron emission tomography (PET) to the study of biochemical transformations in the living human and animal body requires the development of highly selective radiotracers whose concentrations in tissue provide a record of a discrete metabolic process. L-N-[11C-methyl]Deprenyl ([11C]L-deprenyl), a suicide inactivator of monoamine oxidase (MAO) type B, has been developed as a radiotracer for mapping MAO B in the living human and animal brain. In this investigation, [11C]L-deprenyl (1) and [11C]L-deprenyl-alpha, alpha-2H2 (2) have been compared in three different baboons by PET measurement of carbon-11 uptake and retention in the brain and the measurement of the amount of unchanged tracer in the arterial plasma over a 90-min time interval. For one baboon, N-[11C-methyl-2H3]L-deprenyl (3) was also studied. Kinetic parameters calculated using a three-compartment model revealed a deuterium isotope effect of 3.8 +/- 1.1. Comparison of the two tracers (1 and 2) in mouse brain demonstrated that deuterium substitution significantly reduced the amount of radioactivity bound to protein. HPLC and GLC analysis of the soluble radioactivity in mouse brain after injection of [11C]L-deprenyl showed the presence of [11C]methamphetamine as a major product along with unidentified labeled products. Sodium dodecyl sulfate-polyacrylamide electrophoresis with carbon-14-labeled L-deprenyl showed that a protein of molecular weight 58,000 was labeled. These results establish that MAO-catalyzed cleavage of the alpha carbon-hydrogen bond on the propargyl group is the rate limiting (or a major rate contributing) step in the retention of carbon-11 in brain and that the in vivo detection of labeled products in brain after the injection of [11C]L-deprenyl provides a record of MAO activity.

Animals↗

Evidence for cooperativity between neurons and astroglia in the regulation of CO2 fixation in vitro.

Increases in the extracellular potassium concentration which correspond to the increased potassium concentration seen with both normal and abnormal neuronal stimulation produce marked increases in the rate of CO2 fixation in astroglial cells in primary culture. This increase in CO2 fixation is seen only in astroglial cells; the low rate of CO2 fixation seen in the neurons did not respond to the increased potassium concentration. Cultures of astroglia and mixed astroglia-neurons were labeled with NaH[14C]O3 for 20 h to obtain material for preliminary identification of the labeled products of CO2 fixation in the extracellular and intracellular compartments. While both cultures had similar intracellular levels of labeled products (mainly amino acids), astroglial cultures released 4-fold more labeled products into the extracellular fluid. While labeled glutamine is a prominent product of astroglia, the bulk of the released labeled products are nonamino acids. These are presumably the products available to be recycled back to surrounding neurons (which cannot fix CO2) to replenish intermediates of the TCA cycle lost due to release of the neurotransmitters glutamate, aspartate and GABA.

Animals↗

[14C]-lycopene and [14C]-labeled polar products are differentially distributed in tissues of F344 rats prefed lycopene.

Epidemiologic evidence suggests a possible role for lycopene-rich foods in the prevention of prostate cancer and cardiovascular disease. Despite active research in disease reduction, there is a paucity of information on the absorption, biodistribution and metabolism of lycopene. The aim of this study was to evaluate the biodistribution of 14C-lycopene (specific activity, 1.83 microCi/mg) and 14C-labeled products after an oral dose of 22 microCi of 14C-lycopene in male rats that had been prefed a lycopene-containing diet (0.25 g lycopene/ kg diet) for 30 d. The percentage of 14C excreted in feces and urine over the 168 h was 68%. Quantitatively, serum 14C levels were maintained between 3 and 24 h then decreased at 72 h (P < 0.05). At all time points the majority of tissue 14C was in the liver (approximately 72%), although total hepatic 14C decreased after 24 h. In a comparison of the extrahepatic tissue at 168 h, the 14C was greatest in adipose tissue followed by spleen and then adrenal; approximately 80% of the 14C in the liver was in the cis and all-trans configuration at all time points. At 3 h, the 14C in seminal vesicles was primarily in the all-trans plus 5-cis forms (70%), but by 168 h, 55% of 14C was present as 14C-polar products. Despite the presence of unlabeled lycopene in the prostate, the primary 14C form was in 14C-polar products (67-92%), even at 3 h. The percentage and amount of 14C-polar products in the dorsolateral prostate lobe increased from 3 to 24 h and then reached a plateau. The data suggest that lycopene may be metabolized differently among tissues in rats prefed lycopene.

Adrenal Glands↗

High-level iodination of monoclonal antibody fragments for radiotherapy.

Two different murine monoclonal antibody Fab fragments specific for p97, a melanoma-associated antigen, were labeled with I-131 at high activity levels without excessive chemical damage. Up to 20 mg of Fab were labeled with up to 300 mCi of I-131 using the chloramine-T method and large working volumes at room temperature. As much as 90% of the initial activity was recovered as labeled product. The labeled Fabs varied in their sensitivity to radioiodination damage, as measured by an in vitro cell-binding assay. Radioiodination was performed safely using a remote iodination apparatus. The final product was of radiopharmaceutical quality suitable for clinical diagnosis and experimental radiotherapy in humans.

Animals↗

Food and Drug Administration monitoring of adverse drug reactions.

Food and Drug Administration requirements for reporting adverse drug reactions (ADRs), processing of ADR reports, and actions in response to these reports are described. FDA requires that drug manufacturers report ADRs to the FDA Division of Epidemiology and Surveillance; 90% of the ADR reports received are from manufacturers. Of the remaining 10%, one third are from pharmacists. FDA regulations were revised in 1985 to specifically define reportable ADRs and procedures for reporting; manufacturers are required to report within 15 days reactions that are serious and unlabeled. For newly approved drugs, reports on ADRs must be submitted quarterly for three years; subsequently, annual reporting is required. Any increase in the frequency of serious, labeled reactions must be reported. Serious reactions not listed in the product labeling must be reported for products marketed before 1962 for which new drug applications or abbreviated new drug applications were not filed. ADR information received by FDA is coded into standard terms and entered in a computerized database for evaluation by reviewers. If an important reaction is suspected, the report is entered in a tracking system for further monitoring. ADR reports may result in requirements for changes in product labeling, "Dear Doctor" letters, requirement of further study by the manufacturer, or withdrawal of the product. Information about ADRs is communicated to health-care practitioners in product labeling and in the literature. Pharmacists are encouraged to report suspected serious and unlabeled reactions to FDA so that the medical community and the public can benefit from current information about drug safety.

Communication↗

Computer applications in hospital pharmacy practice. I. Computer expectations/applications.

Following vendor selection of a pharmacy computer system, attention must be directed toward which computerized functions to include. Although most features are uniform among the various systems, a discussion is presented listing those applications considered the minimum acceptable for any hospital pharmacy computer system. The descriptions focus on computerization of those labor-intensive activities necessary to support drug distribution services. Computerized support of an intravenous (I.V.) admixture and unit dose program centers around label production and charging/crediting functions. Label production is used to generate a manual backup profile and unit dose cart fill list. The scope of information to include on I.V. and unit dose labels is described. Charging/crediting functions via computer are also discussed, with mention of free-form capabilities. Other computer applications mentioned include: medication profiling, drug interaction flagging, data confidentiality, census support, and hard copy reports. Feature selection depends on the aspects and unique needs that benefit most from computerization.

Accounting↗

Assays of retinoid dehydrogenases by phase partition.

Two modifications of an extraction assay for retinoid dehydrogenases are described. The first method involves the transfer of tritium from carbon-15 of [15-3H]-retinol or [15-3H]retinaldehyde to NAD, whereas in the second method, tritium from [3H]NADPH is transferred to all-trans-retinaldehyde. Since both versions of the assay involve the interconversion of water-soluble and -insoluble tritium-labeled compounds, a simple phase partition is sufficient to separate labeled products from labeled reactants. The assays are shown to provide reliable estimations of the reaction progress for three retinoid dehydrogenases of the visual system when compared to HPLC analysis of retinoid products or gel filtration analysis of pyridine nucleotide. The assays will be useful in studying retinoid dehydrogenases from other tissues and in principle can be modified for other dehydrogenase reactions with water-insoluble substrates.

Alcohol Oxidoreductases↗

Rat liver preproalbumin: in vitro synthesis and partial amino acid sequence.

Rat liver poly(A)-containing RNA greatly stimulated incorporation of radioactive amino acids into protein when added to a wheat germ in vitro translation system. Approximately 7% of the labeled synthetic product was precipitated following indirect immunoprecipitation with antisera to rat serum albumin. Analysis of this material, and of the cyanogen bromide fragments derived from it, by sodium dodecyl sulfate/polyacrylamide gel electrophoresis revealed that it contained an NH2-terminal extension of about 2500 daltons when compared to rat serum albumin. Automated sequence determination of purified cell-free product labeled with various radioactive amino acids revealed the presence of 18 additional amino acids NH2-terminal to the sequence of rat proalbumin. The partial sequence of this extension was found to be: Met-X-X-X-X-Phe-Leu-Leu-Leu-Leu-Phe-X-X-X-X-X-Phe-X-proalbumin. On the basis of this evidence, the immunoprecipitable cell-free product was designated preproalbumin.

Amino Acid Sequence↗

Prescribing of antipsychotic medication in a medicaid population: use of polytherapy and off-label dosages.

OBJECTIVES: To describe the use of atypical antipsychotic medications in a Medicaid-enrolled population composed primarily of elderly and disabled patients. Our analyses focused upon the frequency of use of polytherapy with multiple antipsychotic medications and the prescribing of off-label dosages. METHODS: We conducted a cross-sectional retrospective analysis of oral antipsychotic medication use, as prescribed for this population in 2003. The unit of analysis was the patient. We determined the prevalence of use of each type of antipsychotic medication according to gender and age group and determined the extent of use of combination therapies with multiple oral antipsychotic medications. Using the dosage ranges described in the product labeling, we identified the percentage of patients prescribed in-range dosages, overall and for each atypical antipsychotic medication studied. Those identified as receiving out-of-range (off-label) dosages were further stratified by gender and age group. The statistical significance of differences between these proportions was assessed using the chi-square test. RESULTS: Of the 8,616 patients meeting our inclusion criteria, 7,748 (90%) received monotherapy with an oral antipsychotic medication and 868 patients (10%) received polytherapy with multiple oral antipsychotic medications. Approximately 2 of 3 patients receiving atypical antipsychotic medications were prescribed a dosage that was within the range recommended in the product labeling. Dosages lower than recommended in the product labeling were prescribed for 27% of patients receiving atypical antipsychotics, while 6% of patients received an above-range dosage. The frequency of patients receiving in-range dosages varied substantially among medications. Younger patients and male patients were more frequently prescribed above-range dosages while older patients and female patients were more frequently prescribed below-range dosages of these medications (P<0.001 for both findings). CONCLUSION: In this subpopulation of Medicaid enrollees who were prescribed antipsychotic medications, we found a 10% incidence of use of antipsychotic polytherapy and a 33% incidence of prescribing of dosages outside the range listed in the product labeling. These findings suggest that physicians commonly prescribe antipsychotic medications in a manner that differs from the recommendations described in the prescribing information. The off-label use of atypical antipsychotic medications raises important questions regarding the purpose and applicability of the product labeling and the role and ability of the pharmacist to provide information regarding the risks and benefits of therapy as commonly prescribed.

Administration, Oral↗

2-Methoxyethanol metabolism in pregnant CD-1 mice and embryos.

Upon oxidation to 2-methoxyacetic acid (2-MAA), 2-methoxyethanol (2-ME) causes malformations in all animal species that have been examined. Commonly, 2-MAA is thought to be the proximate toxicant. However, our previous studies with [1,2-14C]2-ME and the present data obtained with [1-14C]2-MAA, [2-14C]2-ME and [methoxy-14C]2-ME revealed that metabolism beyond 2-MAA occurs. Regardless of the 14C position, dams exhaled approximately 5% of the radioactivity administered as a single teratogenic oral dose (3.3 mmol/kg on Gestation Day [gd] 11) as 14CO2. With all isotopic variants urine contained 70-80% of the dose within 24 hr after administration and 13-18% in the next 24 hr. Three labeled products were resolved using HPLC: an unidentified Peak A (12-18% of dose), 2-MAA (approximately 50%), and the glycine conjugate of 2-MAA (approximately 25%). Short-term (4 hr) whole embryo culture on gd 11 with 3 mM 2-MAA and a tracer dose of [1-14C]2-MAA, [2-14C]2-MAA, or [methoxy-14C]2-MAA showed that 14CO2 evolved from the former two substrates, while there was none detectable from the latter. The data indicate that dams metabolized [methoxy-14]2-MAA to 14CO2, while embryos apparently did not. The production of labeled CO2 from [2-14C]2-ME suggests that 2-methoxyacetyl approximately CoA (the precursor for amino acid conjugation with glycine) entered into the tricarboxylic acid (TCA) cycle. This interpretation is supported by the inhibition of 14CO2 evolution elicited by fluoroacetate (0.1 or 1.0 mM) and sodium acetate (5 mM). It is not yet clear whether entry of 2-methoxyacetyl approximately CoA as a "false substrate" in the TCA cycle is of significance for the embryotoxic effects of 2-ME/2MAA.

Acetates↗

Knowledge of dietary supplement label information among female supplement users.

The use of dietary supplements is a popular form of health behavior, especially among women. Little research has been conducted to determine consumers' comprehension of supplement label information. Therefore, this research evaluated comprehension of supplement label information among women 25-45 years of age who consumed a dietary supplement > or =4 times per week. Participants (n=51) completed a written questionnaire about supplement practices, a 10-item knowledge test, and an individual interview about terms used on supplement labels. Participants answered 70% of the questions correctly on the knowledge test indicating adequate knowledge of dietary sources of nutrients. Knowledge of recommended dosages, dosing instructions, and instructions about inappropriate use of supplements for certain people also was adequate. However, misconceptions regarding the term "natural" on supplement labels, product claims, and testing for product safety existed among participants. Supplement users need additional education about supplement claims and testing for product safety and efficacy to make informed health care choices.

Adult↗

Solubilization and mineralization of lignin by white rot fungi.

The white rot fungi Lentinula edodes, Phanerochaete chrysosporium, Pleurotus sajor-caju, Flammulina velutipes, and Schizophyllum commune were grown in liquid media containing C-lignin-labelled wood, and the formation of water-soluble C-labelled products and CO(2), the growth of the fungi, and the activities of extracellular lignin peroxidase, manganese peroxidase, and laccase were measured. Conditions that affect the rate of lignin degradation were imposed, and both long-term (0- to 16-day) and short-term (0- to 72-h) effects on the production of the two types of product and on the activities of the enzymes were monitored. The production of CO(2)-labelled products from the aqueous ones was also investigated. The short-term studies showed that the different conditions had different effects on the production of the two products and on the activities of the enzymes. Nitrogen sources inhibited the production of both products by all species when differences in growth could be discounted. Medium pH and manganese affected lignin degradation by the different species differently. With P. chrysosporium, the results were consistent, with lignin peroxidase playing a role in lignin solubilization and manganese peroxidase being important in subsequent CO(2) production.

Journal Article↗