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Key Words public health, public policy Abbreviations FDA--Food and Drug Administration NTD--neural tube defect NHANES--National Health and Nutrition Examination Survey RBC--red blood cell IOM--Institute of Medicine, IN THEIR RECENT report, Williams et al (1) examined data from 21 population-based birth defect surveillance systems for trends in prevalence of spina bifida and anencephaly for specific racial/ethnic groups […]

Mandatory fortification of enriched cereal-grain products became effective in the United States on January 1, 1998. This fortification was undertaken to assist women of child-bearing age in increasing their intake of folic acid to reduce their risk of having a pregnancy affected by a neural tube birth defect. The process by which the Food and Drug Administration modeled the level of fortification with folic acid illustrates the complex issues and general principles that emerge when fortification of a nation's food supply is evaluated as a means of addressing a public health concern. The effectiveness of fortification for a target population and safety for the much larger general population impose conflicting challenges that must be considered concurrently when making decisions regarding fortification. Recent data show improved folate status and apparent decreases in risk of neural tube birth defects in the U.S. Much about the long-term effects of the fortification program remains unknown and careful monitoring over time will be necessary to ensure that the program functions as intended. Key words: fortification, folic acid, post-fortification assessments, vitamin [B.sub.12]

In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998. An average increase in folic acid intake of 100 [micro]g/d was projected as a result of this fortification. The objective of the present study was to estimate the effect of this fortification on the intake of folic acid and total folate, and on the prevalence of individuals with inadequate folate intake and with high folic acid intake. We used data on food and nutrient intake from 1480 individuals who participated in the 5th and 6th examinations of the Framingham Offspring Cohort Study. Fortification was instituted during the 6th examination so that 931 participants were examined before its implementation (nonexposed) and 549 after implementation (exposed). Published data on total folate in enriched cereal-grain products were used to correct folate content in these foods to reflect fortification. Among nonsupplement users, folic acid intake increased by a mean of 190 [95% confidence interval (CI): 176, 204] [micro]g/d (P < 0.001) and total folate intake increased by a mean of 323 (95% Ch 296-350) [micro]g dietary folate equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases were seen among supplement users exposed to fortification. The prevalence of exposed individuals with total folate intake below the estimated average requirement (320 [micro]g DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before fortification to 7.0% (95% Ch 3.1-10.9%) after fortification in individuals who did not use folic acid supplements. This prevalence was ~1% or less for users of supplements both before and after fortification. Prevalence of individuals with folic acid intake above the upper tolerable intake level (1000 [micro]g folic acid/d) increased only among supplement users exposed to fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake were observed over time in the nonexposed participants. By these estimations, folic acid fortification resulted in a mean increase in folic acid intake that was approximately twice as large as previously projected. KEY WORDS: * folate * folic acid * fortification * folate intake * humans

Folic acid fortification of enriched cereal-grain products (which became mandatory in the U.S. on January 1, 1998) was intended to increase folate intake among childbearing-aged women to reduce their risk of neural tube birth defect (NTD)-affected pregnancies. Interest now focuses on assessing the effects of fortification on risk of NTDs and on folate intake relative to homocysteine (Hcy) concentrations and risk of vascular disease, although a causal relationship between the latter two has not been demonstrated. Increased serum folate levels were first reported in 1999. Data from the Framingham Offspring Study cohort showed increased mean serum folate in middle-aged and older adults; additionally, the prevalence of high Hcy concentrations had decreased by ~50% in subjects examined before (1995-1996) and after (1997-1998) fortification. Another analyses of samples collected between 1994 and 1999 identified a trend of increasing serum folate values from 1996 onward with values in 1998 160% of those measured in 1996. Comparisons between 1988-1994 National Health and Nutrition Examination Survey (NHANES) III data and 1999 NHANES showed increased serum and erythrocyte folate concentrations among childbearing-aged women. While recent data show improved folate status in a short period of time, much about long-term effects of the fortification program remains unknown. Interest in the effects of increased folate intakes on risk of NTDs or vascular disease needs to be balanced against concerns about masking the anemia of vitamin B-12 deficiency and the general lack of data about safety of continuous high intakes. Careful monitoring over time is necessary to determine that the program functions as intended. KEY WORDS: * folate * fortification * folate status * serum folate * homocysteine

The Food and Drug Administration has several options that will assist the Public Health Service in implementing its September 1992 recommendation that all women of childbearing age consume 0.4 mg of folic acid daily to reduce their risk of having a pregnancy affected with a neural tube defect. The FDA can authorize the use of a health claim on labels and in the labeling of foods that characterizes the relationship between a nutrient and a health-related condition. Fortification of cereal-grain products with folic acid is a second option that has the potential for reaching most women of childbearing age without requiring them to change their food selection patterns. Consideration of these options has been intertwined with rapid developments in the scientific database that is the foundation of the health claim, by conflicting opinions regarding the effectiveness for women in the target population of FDA's proposed level of cereal-grain fortification, by lack of systematic safety data regarding the impact of fortification on persons in the general population and by changes in the regulatory environment in which the agency acts. INDEXING KEY WORDS: * fortification * health claims * folic acid * neural tube defects * public policy

Objectives. This article uses folic acid as an example to illustrate some of the complex issues and general principles that emerge when evaluating fortification of the food supply as one possible means to address a public health recommendation. Methods. Distributions of current daily folate intakes from conventional foods and dietary supplements were estimated. Intakes that might result, from fortification of cereal-grain products and ready-to-eat cereals at various levels for eight age-gender groups were also estimated by using the US Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey. Results. The results illustrate that fortification of the US food supply tends to increase folate intakes of consumers at the high end of the intake distribution curves in the general population to a greater extent than it affects consumers at the low end of the intake distribution curves in the target population. Conclusions. The effectiveness of food fortification options for a target population and the safety for the general population impose conflicting challenges that must be considered concurrently when making decisions about fortifying the US food supply. (Am J Public Health. 1995;85:660-666), Fortification of the US food supply may increase nutrient intakes to a much greater extent in consumers with high intakes from food than in consumers with low intakes. Supplement use has little affect on the consumers who need it more. Increases in daily folic acid consumption with fortification of dry cereal products were measured among age and gender groups using the US Department of Agriculture's 1987-1988 Nationwide Food Consumption Survey. For the target population of childbearing age women, supplements only slightly increased folate intake. But in children aged 4 to 10 who were high consumers of folic acid from foods alone, the supplements resulted in a 70% increase. Nutrient intakes for target groups should be increased to recommended levels, but at the same time, safe levels must be managed for people with high nutrient intakes.

The latent and active forms of recombinant plasminogen activator inhibitor 1 (rPAI-1) were purified from a single preparation. In addition, the proteins were functioanlly and structurally characterized. High-resolution ion exchange chromatography or affinity chromatography using immobilized anhydrotrypsin were used to separate the two forms. The active and latent forms exhibited close resemblace with respect to the primary and secondary structures but not with their tertiary structures, as revealed by circular dichroism spectral analyses.

Background: Currently, biotherapeutic medicines are the most effective options for the treatment of many severe and chronic diseases. For faster market entry of biotherapeutic products and their cost reduction, the principles of "biosimilarity" have been developed. Development and licensing of biosimilars is allowed only after the end of patent exclusivity of the original preparation period.Purpose: Characteristics of the main safety parameters of biosimilar hormone preparations licensed by EMA.Methods: This paper analyzes the results demonstrating the similarities and differences between biosimilar and reference hormone products indicated in the EPAR (public assessment report) for the examination of materials presented for the licensing of biosimilar products.Results: During the development of biosimilar hormone medicines, differences in the glycosylation profile between biosimilar and reference preparations are revealed. As biotherapeutical preparations are produced by cells, the differences in glycosylation profile between biosimilar and referent preparation are predictable. While carrying out clinical studies, a high similarity of biosimilar and reference product effectiveness is shown, but some differences between them in the safety profile are revealed.Conclusions: The study of biosimilar product safety has shown the necessity of further improvement in safety and standard approaches for the assessment of the immunogenicity of biosimilar products. [ABSTRACT FROM AUTHOR]

Mycobacterium ulcerans is recognised as the third most common mycobacterial infection worldwide. It causes necrotising infections of skin and soft tissue and is classified as a neglected tropical disease by the World Health Organization (WHO). However, despite extensive research, the environmental reservoir of the organism and mode of transmission of the infection to humans remain unknown. This limits the ability to design and implement public health interventions to effectively and consistently prevent the spread and reduce the incidence of this disease. In recent years, the epidemiology of the disease has changed. In most endemic regions of the world, the number of cases reported to the WHO are reducing, with a 64% reduction in cases reported worldwide in the last 9 years. Conversely, in a smaller number of countries including Australia and Nigeria, reported cases are increasing at a rapid rate, new endemic areas continue to appear, and in Australia cases are becoming more severe. The reasons for this changing epidemiology are unknown. We review the epidemiology of M. ulcerans disease worldwide, and document recent changes. We also outline and discuss the current state of knowledge on the ecology of M. ulcerans, possible transmission mechanisms to humans and what may be enabling the spread of M. ulcerans into new endemic areas. [ABSTRACT FROM AUTHOR]

Secretory IgA in the saliva is essential for protection from mucosally transmitted pathogens and maintaining homeostasis at mucosal surfaces of the oral cavity. Expression of submandibular gland polymeric Ig receptor (pIgR) is essential for IgA secretion. In the present study, we investigated the influence of indigestible carbohydrates on IgA production in the salivary gland and saliva. Five-week-old rats were fed a fibre-free diet (control), or a diet with 5% (w/w) fructo-oligosaccharide (FOS) or a combination of 2·5% (w/w) polydextrose (PDX) and 2·5% (w/w) lactitol for 21-d. IgA concentrations in the caecal digesta, submandibular gland tissue, and saliva in the FOS and PDX þ lactitol diet groups were significantly higher than those in the control group (P<0·05). The increase in IgA in the submandibular gland tissue was confirmed using immunohistochemical analysis. However, the IgA concentrations of serum did not differ between the FOS or PDX þ lactitol groups and the control group (P= 0·5). In the FOS and PDX þ lactitol groups, the pIgR mRNA (pIgR/b-actin) expression level in the submandibular gland tissue was significantly higher than that in the control group (P<0·05). The present study suggests that indigestible carbohydrates play an important role in the increase in IgA concentrations in the submandibular gland tissue, saliva, and caecal digesta. [ABSTRACT FROM AUTHOR]

A rapid, selective and sensitive ultra-high-performance liquid chromatography–multistage fragmentation mass spectrometry (UHPLC-MS3) method was developed and evaluated for the determination of aristolochic acids I and II (AA I and II) in herbal dietary supplements. A hybrid triple quadrupole/linear ion-trap mass spectrometry was used to monitor MS3ion transitionsm/z359.2 > 298.1 > 268.0 andm/z329.2 > 268.2 > 238.0 to detect AA I and II, respectively. The extraction and clean-up of target analytes from dry powdered samples was performed using the quick, easy, cheap, effective, rugged and safe (QuEChERS) procedure. Herbal liquid extracts were analysed directly. Average recoveries ranged from 89% to 112%, with relative standard deviations (RSDs) ranging from 3% to 16%. Limits of quantification (LOQs) estimated for three selected matrices were as follows (AA I/II): 5/10 ng g−1(tablets); 25/50 ng g−1(capsules); and 2.5/5.0 ng ml−l(liquid herbal extract). The method was applied in a limited survey of 30 herbal products marketed in the United States via the Internet. AA I and II were detected in 20% and 7%, respectively, of tested samples. [ABSTRACT FROM AUTHOR]

abstract 1. Toxicity of pyrrolizidine alkaloids (PAs) largely depends on their metabolic activation by hepatic enzymes, including cytochrome P450s, to become chemically reactive pyrrolic derivatives. These then spontaneously release the esterifying acids to generate carbonium ions that form covalent adducts with cellular nucleophiles to exhibit toxicity. 2. In our investigation, metabolism-mediated toxicity of monocrotaline, retrorsine, lycopsamine, echimidine (retronecine-type PAs), heliotrine (a heliotridine-type PA) and senkirkine (an otonecine-type PA) was studied using an in vitro co-incubation assay. 3. Human hepatocarcinoma (HepG2/C3A) cells were incubated with PAs in the presence and absence of rat liver S9 fraction and the toxicity was assessed as lowered mitochondrial activity. 4. Bioactivation potential was measured by incubating PAs with rat liver S9 fraction, NADPH and GSH in a cell free system. Pyrrolic metabolites generated were entrapped as glutathione conjugates (7-GSH-DHP and 7,9-di-GSHDHP) which were quantified using LC-MS-MS analysis. 5. Our results indicated that PAs were metabolized by rat liver S9 fraction into reactive pyrrolic derivatives which were toxic to HepG2/C3A cells. This approach can be used to determine and compare bioactivation potential and metabolism-mediated toxicity of various PAs [ABSTRACT FROM AUTHOR]

The NIH sponsored a scientific workshop, "Soy Protein/Isoflavone Research: Challenges in Designing and Evaluating Intervention Studies," July 28-29, 2009. The workshop goal was to provide guidance for the next generation of soy protein/isoflavone human research. Session topics included population exposure to soy; the variability of the human response to soy; product composition; methods, tools, and resources available to estimate exposure and protocol adherence; and analytical methods to assess soy in foods and supplements and analytes in biologic fluids and other tissues. The intent of the workshop was to address the quality of soy studies, not the efficacy or safety of soy. Prior NIH workshops and an evidence-based review questioned the quality of data from human soy studies. If clinical studies are pursued, investigators need to ensure that the experimental designs are optimal and the studies properly executed. The workshop participants identified methodological issues that may confound study results and interpretation. Scientifically sound and useful options for dealing with these issues were discussed. The resulting guidance is presented in this document with a brief rationale. The guidance is specific to soy clinical research and does not address nonsoy-related factors that should also be considered in designing and reporting clinical studies. This guidance may be used by investigators, journal editors, study sponsors, and protocol reviewers for a variety of purposes, including designing and implementing trials, reporting results, and interpreting published epidemiological and clinical studies. [ABSTRACT FROM AUTHOR]

The market for botanical dietary supplements in the US has grown rapidly during the last 15 years. Use of newly introduced botanical ingredients has often outpaced an adequate scientific understanding of the ingredients themselves. This may lead to problems, including misidentification, mislabeling, adulteration, and toxicity related to the intended ingredient or one substituted for it. This article reviews recent work with several botanical ingredients ( Ephedra, Citrus species, Hoodia gordonii, Teucrium, isoflavones) that illustrates the complexity of the current situation and approaches that contribute to ensuring the quality of botanical ingredients. Recent work with contamination of botanical products by mycotoxins is also reviewed. The need for tools for botanical authentication and methods for reproducible extraction of bioactive constituents is critical. Such tools, and improved analytical techniques for identifying potentially bioactive constituents in fresh plant material and in concentrated extracts and for detection of hazardous contaminants, are expected to improve the overall quality and safety of botanical dietary supplement ingredients. [ABSTRACT FROM AUTHOR]