Search

1. Diabetic chronic wounds, mainly foot ulcers, constitute one of the most common complications of poorly managed diabetes mellitus. The most typical reasons are insufficient glycemic management, latent neuropathy, peripheral vascular disease, and neglected foot care. In addition, it is a common cause of foot osteomyelitis and amputation of the lower extremities. Patients are admitted in larger numbers attributable to chronic wounds compared to any other diabetic disease. In the United States, diabetes is currently the most common cause of non-traumatic amputations. Approximately five percent of diabetics develop foot ulcers, and one percent require amputation. Therefore, it is necessary to identify sources of lead with wound-healing properties. Redox imbalance due to excessive oxidative stress is one of the causes for the development of diabetic wounds. Antioxidants have been shown to decrease the progression of diabetic neuropathy by scavenging ROS, regenerating endogenous and exogenous antioxidants, and reversing redox imbalance. Matrix metalloproteinases (MMPs) play vital roles in numerous phases of the wound healing process. Antioxidant and fibroblast cell migration activity of Marantodes pumilum (MP) crude extract has previously been reported. Through their antioxidant, epithelialization, collagen synthesis, and fibroblast migration activities, the authors hypothesise that naringin, eicosane and octacosane identified in the MP extract may have wound-healing properties. 2. The present study aims to identify the bioactive components present in the dichloromethane (DCM) extract of M. pumilum and evaluate their antioxidant and wound healing activity. Bioactive components were identified using LCMS, HPTLC and GCMS. Excision wound on STZ-induced diabetic rat model, human dermal fibroblast (HDF) cell line and colorimetric antioxidant assays were used to evaluate wound healing and antioxidant activities, respectively. Molecular docking and pkCMS software would be utilised to predict binding energy and affinity, as well as ADME parameters. 3. Naringin (NAR), eicosane (EIC), and octacosane (OCT) present in MP displayed antioxidant action and wound excision closure. Histological examination HDF cell line demonstrates epithelialization, collagen production, fibroblast migration, polymorphonuclear leukocyte migration (PNML), and fibroblast movement. The results of molecular docking indicate a substantial attraction and contact between MMPs. pkCMS prediction indicates inadequate blood-brain barrier permeability, low toxicity, and absence of hepatotoxicity. 4. Wound healing properties of (NEO) naringin, eicosane and octacosane may be the result of their antioxidant properties and possible interactions with MMP. [ABSTRACT FROM AUTHOR]

Chickpea (Cicer arietinum) is one of the most consumed pulses worldwide (over 2.3 million tons enter the world market annually). Some chickpea components have shown, in preclinical and clinical studies, several health benefits, including antioxidant capacity, and antifungal, antibacterial, analgesic, anticancer, antiinflammatory, and hypocholesterolemic properties, as well as angiotensin I‐converting enzyme inhibition. In the United States, chickpea is consumed mostly in the form of hummus. However, the development of new products with value‐added bioactivity is creating new opportunities for research and food applications. Information about bioactive compounds and functional properties of chickpea ingredients in the development of new products is needed. The objective of this review was to summarize available scientific information, from the last 15 years, on chickpea production, consumption trends, applications in the food industry in the elaboration of plant‐based snacks, and on its bioactive compounds related to type 2 diabetes (T2D). Areas of opportunity for future research and new applications of specific bioactive compounds as novel food ingredients are highlighted. Research is key to overcome the main processing obstacles and sensory challenges for the application of chickpea as ingredient in snack preparations. The use of chickpea bioactive compounds as ingredient in food products is also a promising area for accessibility of their health benefits, such as the management of T2D. [ABSTRACT FROM AUTHOR]

Summary: Bioactive compounds from Brazilian hop (Humulus lupulus L.) cultivars were extracted by ultrasound and their phenolic profile compared with commercial hop from the USA. The most effective extraction conditions (solution of ethanol 49%, at 52 °C and a solid/liquid ratio of 1 g per 34 mL) for the total phenolic compounds (TPC) were determined using a Central Composite Rotatable Design. The Brazilian hop showed higher content of TPC (33.93 ± 0.67 mg GAE g−1), total flavonoids (54.47 ± 0.10 mg QE g−1) and higher antioxidant activity (ABTS: EC50 21.29 ± 1.36 μL mL−1; DPPH: EC50 3.91 ± 0.17 μL mL−1) when compared with the USA hop. The main phenolic compounds present in the extracts were the flavonoids isoquercitrin and quercetin. The antioxidant properties of the Brazilian hop extract had not been reported yet in the literature for this raw material, thus showing potential to be incorporated in polymeric films used as active packaging. [ABSTRACT FROM AUTHOR]

It is known that soil streptomycetes are active producers of a wide range of biologically active substances, including antibiotics. Since the issue of the relationship between the antibiotics synthesis and the ways of other biologically active substances synthesis is not studied in full at present, the research subject is relevant. The question is not fully investigated. The goal of the work was to research the correlation dependence between the biosynthesis of antibiotic and other biologically active substances produced by soil streptomycetes. Methods. To determine the relationship between the synthesis of antibiotic compounds and other biologically active substances by soil streptomycetes was held factorial analysis with using the method of the main components; for identification the coefficients of regression and dispersion analysis were used the package Statistika v.10.0 (StatSoft. Inc., USA) and Mathlab v . 6.0; cluster analysis was held by using the Ward method with determination Euclidean distance as the degree of difference (in%) between the estimated variables. Results. Correlation relations between the antibiotic synthesis by strains Streptomyces violaceus IMV Ac-5027 and S. netropsis IMV Ac-5025 with biosynthetic pathways of other biologically active substances, but with different links are identificated. Synthesis of polyene and anthracycline antibiotics correlates with the synthesis of phytohormones (indole-3-carbinol, indole-3-carboxylic acid, isopentynyladenosine and gibberellins) and sterols (sitosterol). Production of these antibiotics also shows the dependence in the synthesis of triglycerides, sterols and their esters and fatty acids (isopalmitin, heptadecene, stearic fat acid, oleic fat acid, peanut fat acid). These antibiotics synthesis does not have a direct relationship with the content of amino acids. Conclusions. The relationships between biosynthesis of antibiotics, phytohormones and steroid compounds by soil streptomycetes S. netropsis IMV Ac-5025 and S. violaceus IMV Ac-5027 provides new tools for understanding the complex interconnections associated with the optimization of the synthesis of industrially important metabolites. Thus we can broad the knowledge about the conditions of their formation, the biosynthesis ways and functional significance for microbial cells. [ABSTRACT FROM AUTHOR]

Pyrazolone was prepared through the reaction of ethyl acetoacetate and hydrazine hydrate in EtOH at room temperature. Then, bispyrazole derivatives, as attractive biologically active compounds, were synthesized by reacting two equivalents of prepared pyrazolone and one equivalent of aldehyde in the presence of SBA-Pr-SO3H under solvent-free condition at 120 °C. The reaction time was short (3–6 min), while the products' yield was high (85–97%). Discovery Studio 2.5 (Accelrys Inc, San Diego, CA, USA) was employed to dock the compounds to protein. Molecular docking (GOLD method) studies suggested that pyrazoles bind efficiently to RET kinase. Next, biological activities of the bispyrazoles were tested against some Gram-positive and Gram-negative bacteria and for antifungal activity via the disc-diffusion method. All compounds showed no significant anti-bacterial activities, but two of them showed good activities against Candida albicans. [ABSTRACT FROM AUTHOR]

Objective: To describe the history, key features, recent enhancements, and common applications of the Dietary Supplement Label Database (DSLD).Background and History: Although many Americans use dietary supplements, databases of dietary supplements sold in the United States have not been widely available. The DSLD, an easily accessible public-use database was created in 2008 to provide information on dietary supplement composition for use by researchers and consumers.Rationale: Accessing current information easily and quickly is crucial for documenting exposures to dietary supplements because they contain nutrients and other bioactive ingredients that may have beneficial or adverse effects on human health. This manuscript details recent developments with the DSLD to achieve this goal and provides examples of how the DSLD has been used.Recent Developments: With periodic updates to track changes in product composition and capture new products entering the market, the DSLD currently contains more than 71,000 dietary supplement labels. Following usability testing with consumer and researcher user groups completed in 2016, improvements to the DSLD interface were made. As of 2017, both a desktop and mobile device version are now available. Since its inception in 2008, the use of the DSLD has included research, exposure monitoring, and other purposes by users in the public and private sectors.Future Directions: Further refinement of the user interface and search features to facilitate ease of use for stakeholders is planned.Conclusions: The DSLD can be used to track changes in product composition and capture new products entering the market. With over 71,000 DS labels it is a unique resource that policymakers, researchers, clinicians, and consumers may find valuable for multiple applications. [ABSTRACT FROM AUTHOR]

Distillers corn oil (DCO) is a coproduct of bioethanol production. In the dry-grind ethanol process, DCO is extracted post-fermentation by the centrifugal separation of oil from the aqueous thin-stillage or whole stillage, and is a valuable coproduct currently used in animal production as a feed additive or as a feedstock for renewable biodiesel production. This study analyzes the variability in the fatty acid profiles and the content and composition of bioactive components in DCO from thirty bioethanol plants in the United States. The fatty acid profiles of the DCO samples were similar to commercial corn oil with an average of 56.0 % linoleic acid (C18:2), 27.6 % oleic (C18:1), 11.9 % palmitic (C16:0), 1.5 % stearic (C18:0), and 1.2 % linolenic (C18:3). There was low variability in fatty acid composition among the samples, with all major fatty acids having ≤ 3.5 % coefficient of variation (CV). Average total tocopherols were 1023 mg/kg comprised of gamma-, delta-, and alpha-tocopherols, with CV's ranging from 20.8 % to 57.8 %. The mean tocotrienol contents were 348 mg/kg, with CV's ranging from 18.8 % to 71.7 %. Mean carotenoid content was 239 mg/kg, comprised of lutein, zeaxanthin, beta-cryptoxanthin, and alpha- and beta-carotenes, with CVs ranging from 19.7 % to 39.6 %. Mean total phytosterols were 19,360 mg/kg, while a class of phytosterols, ferulate phytosterol esters, were 4626 mg/kg. There was lower variation in phytosterol content, with CVs ranging from 9 % to 13 %. Methanol extracts from DCO contained 242 mg/kg gallic acid equivalents (GAE), with a 27.9 % CV. The antioxidant activity of methanol extracts, measured by diphenyl picrylhydrazyl radical scavenging activity, was 3.8 µmol/kg Trolox equivalents (CV = 19.9 %). The oils had an average oxidative stability index (OSI) at 110 °C of 11.8 h. The OSI values were significantly positively correlated with lutein, delta-tocopherol, and phytosterols including stigmasterol and campesterol. The results indicate that there was a higher amount of variation between plants in the content and composition of tocopherols, carotenoids, and total phenolics than for fatty acids composition and phytosterols. However, DCO from the dry grind ethanol process may be a sustainable feedstock for bioactive lipids for foods, dietary supplements, and industrial use. • Phytochemical variation in centrifugally extracted distillers corn oil is presented. • Variation was higher for tocopherols, tocotrienols, and carotenoids. • DCO is a rich source of phytosterols and ferulate phytosterol esters. • Oxidative stability was correlated with several lipophilic antioxidants. [ABSTRACT FROM AUTHOR]

Long chain (LC) polyunsaturated fatty acids (PUFA) are major components of cell membrane phospholipids (PL) and serve as precursors for numerous bioactive lipid derivatives. Fatty acids (FA) are routinely analyzed in biological samples to assess composition of tissues, cells, and lipid fractions. In human studies, serum or plasma is often used because of their easy procurement. However, the lipid pool in serum and plasma is a mixture of triacylglycerol (TG), PL, cholesterol and its esters, and other components. Herein, we report findings from a serum FA analysis after fractionation of polar and neutral lipids by solid phase extraction in a large cohort of 400 hemodialysis patients. LC PUFA were found concentrated in the polar fraction compared to the total or the neutral lipid fraction. When correlated with clinical markers of disease, a greater number of significant correlations were found for PUFA in polar compared to total or the neutral fraction. We also observed that polar lipids are a reliable reflection of LC PUFA status compared to the total or neutral fractions because the latter are diluted by non-essential FA. The relative amounts of LC PUFA in the total and neutral fractions reflect the contribution of TG in blood that varies with diet, age, and physiologic state. Our data indicate that LC PUFA in the polar fraction are superior indicators of bioactive FA-status than in the total or the neutral fraction and should be used to establish important links between PUFA status, their bioactive substrates in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Several ancient apple varieties and a wild apple variety grown in Croatia were analysed for the polyphenol content and compared to two varieties grown in USA. In the flesh, flavanols, dihydrochalcones and phenolic acids (24 to 137, 23 to 109, 3 to 238 mg kg −1 of fresh weight (FW), respectively) were found. Peel contained flavanols, dihydrochalcones, phenolic acids, flavonols and anthocyanins (65 to 690, 21 to 141, 0 to 107, 205 to 1223, 0 to 213 mg kg −1 FW, respectively). The wild apple was characterized by much higher flavanol and phenolic acid content in the flesh (301 and 734 mg kg −1 FW, respectively) while the peel was similar to other apples. The polyphenol profile was similar to apples from USA. The varieties Zimnjara, Lještarka and Adamova zvijezda could be highlighted as sources of polyphenols. Varieties are categorized by the content of dihydrochalcones and flavanols in the flesh (whether that content is high or low), and by the relative portion of phenolic acids and flavanols in the flesh (high phenolic acid proportion, lower flavanol proportion and vice versa). There was not observed to be as strong a pattern for categorizing differences in the peel. [ABSTRACT FROM AUTHOR]

Dry-cured hams can become infested with ham mites, red-legged beetles, cheese skippers, and larder beetles during the aging process. Though other methods may be used for beetles and cheese skippers, methyl bromide is the only available fumigant that is effective at controlling ham mites in dry-cured ham plants in the United States. However, methyl bromide will be phased out of all industries by approximately 2015. This paper will review and explore potential alternatives that have been investigated to determine their feasibility for replacing methyl bromide to control pest infestations in dry-cured ham plants in the United States. Potential alternatives include: 1) fumigants such as phosphine and sulfuryl fluoride; 2) physical control approaches through cold treatment, modified atmosphere, inert dusts, etc.; 3) pesticides and bioactive compounds; 4) food-grade processing aids. The most promising potential alternatives to date include the use of propylene glycol on the ham surface, the exploration of alternative fumigants, and implementation of an integrated pest management plan. [ABSTRACT FROM AUTHOR]

The North Atlantic receives the highest aerosol (dust) input of all the oceanic basins. Dust deposition provides essential bioactive elements, as well as pollution-derived elements, to the surface ocean. The arid regions of North Africa are the predominant source of dust to the North Atlantic Ocean. In this study, we describe the elemental composition (Li, Na, Mg, Al, P, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Cd, Sn, Sb, Cs, Ba, La, Ce, Nd, Pb, Th, U) of the bulk aerosol from samples collected during the US-GEOTRACES North Atlantic Zonal Transect (2010/11) in order to highlight the differences between a Saharan dust end-member and the reported elemental composition of the upper continental crust (UCC), and the implications this has for identifying trace element enrichment in aerosols across the North Atlantic basin. As aerosol titanium (Ti) is less soluble than aerosol aluminum (Al), it is a more conservative tracer for lithogenic aerosols and trace element-to-Ti ratios. However, the presence of Ti-rich fine aerosols can confound the interpretation of elemental enrichments, making Al a more robust tracer of aerosol lithogenic material in this region. [ABSTRACT FROM AUTHOR]

Sisal- Agave sisalana Perrine ex. Engelm-is a key economical and social crop in the semi-arid region of Brazil, especially in the Bahia state. Sisal is severely affected by Aspergillus niger Thieg, the causal agent of sisal red rot. Currently, existing control strategies are fruitless. Here, we tested different homeopathic drugs Carbo vegetabilis, Ferrum metallicum, Natrum muriaticum, phosphorus and sulphur at centesimal Hahnemannian (CH) dynamizations, of 3CH, 5CH, 7CH, 9CH and 12CH, on Aspergillus niger. We measured in vitro growth inhibition, sporulation and germination of Aspergillus niger during 12 days. We assessed in planta Aspergillus niger incidence and disease severity. Our results show that homeopathic drugs inhibited Aspergillus niger growth in vitro, in a dynamization-dependent way. Natrum muriaticum 5CH revealed the higher inhibition of 66 %, whereas sulphur 5CH yielded the lowest inhibition of 6.4 %. Spore production was stimulated using all homeopathic drugs at all dynamization levels, whereas spore germination was reduced. In planta assays revealed different results from in vitro assays, corroborating that in planta and in vitro effectiveness is different according to the homeopathic drugs applied. Here, disease incidence was not reduced significantly, but disease severity was lower in treated plants, of 27.8 % using Ferrum metallicum 9CH than in control trials, of 73.6 %. Overall, our findings suggest that homeopathic drugs could be a good strategy to control Aspergillus niger incidence in sisal plants. [ABSTRACT FROM AUTHOR]

Lung cancer is a major cause of cancer-related mortality in the United States and around the world. Due to the pre-existing or acquired chemo-resistance, the current standard chemotherapy regimens only show moderate activity against lung cancer. In the current study, we explored the potential anti-lung cancer activity of cinobufotalin in vivo and in vitro, and studied the underlying mechanisms. We demonstrated that cinobufotalin displayed considerable cytotoxicity against lung cancer cells (A549, H460 and HTB-58 lines) without inducing significant cell apoptosis. Our data suggest that mitochondrial protein cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates cinobufotalin-induced non-apoptotic death of lung cancer cells. The Cyp-D inhibitor cyclosporine A (CsA), the mPTP blocker sanglifehrin A (SfA), and Cyp-D shRNA-silencing significantly inhibited cinobufotalin-induced mitochondrial membrane potential (MMP) reduction and A549 cell death (but not apoptosis). Using a mice xenograft model, we found that cinobufotalin inhibited A549 lung cancer cell growth in vivo . Thus, cinobufotalin mainly induces Cyp-D-dependent non-apoptotic death in cultured lung cancer cells. The results of this study suggest that cinobufotalin might be further investigated as a novel anti-lung cancer agent. [ABSTRACT FROM AUTHOR]

Abstract: Marine organisms such as fish and shellfish are rich sources of structurally diverse bioactive nitrogenous components. Based on emerging evidence of potential health benefits, these components show significant promise as functional food ingredients. Activities including antihypertensive, antioxidant, anti-microbial, anti-coagulant, anti-diabetic, anti-cancer, immunostimulatory, calcium-binding, hypocholesteremic and appetite suppression have been reported. Fish and shellfish waste components contain significant levels of high quality protein (10–23% (w/w)) which represents a source for biofunctional peptide mining. This review summarises the protein-derived bioactive peptides identified in marine processing waste, molluscs and crustaceans. Moreover, it highlights the potential of proteins derived from these marine organisms as substrates for the generation of biofunctional peptides. It outlines current technologies used in the production, fractionation and purification of marine protein-derived peptides and lists some commercially available products containing marine derived bioactive protein hydrolysates and peptides. Finally, bioactive proteins, non-protein peptides and amino acids found in fish and shellfish are briefly discussed. [Copyright &y& Elsevier]

Abstract: For nutrients and related substances, the Tolerable Upper Intake Level (UL) has become the internationally accepted risk assessment method. The major limitation of the UL method as applied by authoritative groups thus far is that no UL has been set for nutrients without established adverse effects. In contrast to the limitations inherent in the UL method, an alternative approach is available; it identifies a risk assessment value termed the Highest Observed Intake (HOI). In the absence of a UL, the HOI is the highest intake with adequate data to show, with acceptable confidence, the absence of adverse effects up to that intake. With this concept defined and accepted in a report by the authoritative international organizations FAO and WHO, a complete risk assessment for the nutrients and related substances would have to identify UL values for those with known adverse effects and HOI values for those without known adverse effects. The need for the HOI concept and value is illustrated by the unjustified policy and regulatory actions taken in relation to vitamin B12. Regulatory utility is explained and tentative HOI values are identified for several vitamins and non-essential nutrients. Endorsement of the concept and development of HOI values by authoritative bodies is likely to be required for broad acceptance and use. [Copyright &y& Elsevier]

Summary: The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new pharmacophores. Hookworms are blood-feeding, intestinal nematode parasites that infect up to 600 million people worldwide. Vaccination with recombinant Ancylostoma ceylanicum macrophage migration inhibitory factor (rAceMIF) provided partial protection from disease, thus establishing a “proof-of-concept” for targeting AceMIF to prevent or treat infection. A high-throughput screen (HTS) against rAceMIF identified six AceMIF-specific inhibitors. A nonsteroidal anti-inflammatory drug (NSAID), sodium meclofenamate, could be tested in an animal model to assess the therapeutic efficacy in treating hookworm disease. Furosemide, an FDA-approved diuretic, exhibited submicromolar inhibition of rAceMIF tautomerase activity. Structure-activity relationships of a pharmacophore based on furosemide included one analog that binds similarly to the active site, yet does not inhibit the Na-K-Cl symporter (NKCC1) responsible for diuretic activity. [ABSTRACT FROM AUTHOR]

We have successfully implemented the concept of Distributed Drug Discovery (D3) in the search for CNS agents. Herein, we demonstrate, for the first time, student engagement from different sites around the globe in the development of new biologically active compounds. As an outcome we have synthesized a 24-membered library of arylpiperazine derivatives targeted to 5-HT1A and 5-HT2A receptors. The synthesis was simultaneously performed on BAL-MBHA-PS resin in Poland and the United States, and on BAL-PS-SynPhase Lanterns in France. The D3 project strategy opens the possibility of obtaining potent 5-HT1A/5-HT2A agents in a distributed fashion. While the biological testing is still centralized, this combination of distributed synthesis with screening will enable a D3 network of students world-wide to participate, as part of their education, in the synthesis and testing of this class of biologically active compounds. [ABSTRACT FROM AUTHOR]

Background: The Food and Drug Administration (FDA) approved drug labels contain a broad array of information, ranging from adverse drug reactions (ADRs) to drug efficacy, risk-benefit consideration, and more. However, the labeling language used to describe these information is free text often containing ambiguous semantic descriptions, which poses a great challenge in retrieving useful information from the labeling text in a consistent and accurate fashion for comparative analysis across drugs. Consequently, this task has largely relied on the manual reading of the full text by experts, which is time consuming and labor intensive. Method: In this study, a novel text mining method with unsupervised learning in nature, called topic modeling, was applied to the drug labeling with a goal of discovering "topics" that group drugs with similar safety concerns and/or therapeutic uses together. A total of 794 FDA-approved drug labels were used in this study. First, the three labeling sections (i.e., Boxed Warning, Warnings and Precautions, Adverse Reactions) of each drug label were processed by the Medical Dictionary for Regulatory Activities (MedDRA) to convert the free text of each label to the standard ADR terms. Next, the topic modeling approach with latent Dirichlet allocation (LDA) was applied to generate 100 topics, each associated with a set of drugs grouped together based on the probability analysis. Lastly, the efficacy of the topic modeling was evaluated based on known information about the therapeutic uses and safety data of drugs. Results: The results demonstrate that drugs grouped by topics are associated with the same safety concerns and/or therapeutic uses with statistical significance (P<0.05). The identified topics have distinct context that can be directly linked to specific adverse events (e.g., liver injury or kidney injury) or therapeutic application (e.g., antiinfectives for systemic use). We were also able to identify potential adverse events that might arise from specific medications via topics. Conclusions: The successful application of topic modeling on the FDA drug labeling demonstrates its potential utility as a hypothesis generation means to infer hidden relationships of concepts such as, in this study, drug safety and therapeutic use in the study of biomedical documents. [ABSTRACT FROM AUTHOR]

The article discusses the existence and contribution of soy foods in the dietary habits of the Americans in the U.S. It mentions that the current intake behavior based on the Food Guide Pyramid is studied to better understand the potential effect of increasing soy intake. It states that the increasing use of soy has been controversial because of its bioactive components. Furthermore, the use of soy milk has increased by individuals with lactose intolerance, leading to an improvement in dietary calcium and protein content.

PubChem is a public repository of small molecules and their biological properties. Currently, it contains more than 25 million unique chemical structures and 90 million bioactivity outcomes associated with several thousand macromolecular targets. To address the potential utility of this public resource for drug discovery, we systematically summarized the protein targets in PubChem by function, 3D structure and biological pathway. Moreover, we analyzed the potency, selectivity and promiscuity of the bioactive compounds identified for these biological targets, including the chemical probes generated by the NIH Molecular Libraries Program. As a public resource, PubChem lowers the barrier for researchers to advance the development of chemical tools for modulating biological processes and drug candidates for disease treatments. [ABSTRACT FROM AUTHOR]

Aim of the study: This study uses historical texts in order to obtain information on the natural products used in traditional medicines in European/Mediterranean therapeutics over the last two millennia. The information obtained may lead to new directions in the area of drug discovery, as recent research has demonstrated the continued promise of looking to natural products for bioactive compounds. Researchers have increasingly turned to traditional medicines to provide clues as to which natural products to investigate, but the oral traditions on which much of this medical knowledge rests are often unstable. Thus researchers have been prompted to use historical medical texts, as this study does, to find potential sources of new drugs. Materials and methods: This study uses twelve Mediterranean/European medical texts from the 5th century BC to the 19th century AD to compile a list of the most commonly used “simples” - or single action drugs substances - used in therapeutics in traditional European medicine. This list was then compared to present-day herbal pharmacopoeia as represented by the National Institutes of Health (NIH). Results: This study finds that traditional European materia medica was based on a Dioscoridean tradition that lasted through the 19th century with remarkably little variation, but is significantly different from the present-day herbal pharmacopoeia according to the NIH. Conclusions: The most prominent simples in the European/Mediterranean medical tradition can provide clues to futher bioactive compounds that have not as of yet been fully exploited for their potential, but were clearly of great use in the past. [Copyright &y& Elsevier]

Abstract: This paper presents Biomonitoring Equivalents (BEs) for inorganic arsenic. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline, and are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for arsenic based on recent evaluations from the United States Environmental Protection Agency (US EPA), US Agency for Toxic Substances and Disease Registry (ATSDR) and Health Canada (HC). BE values corresponding to the Reference Dose (RfD) or risk-specific doses for cancer endpoints from these agencies were derived based on kinetic data (urinary excretion) from controlled dosing studies in humans. The BE values presented here provide estimates of the sum of inorganic arsenic-derived urinary biomarkers (inorganic arsenic, monomethylated arsenic, and dimethylated arsenic). The BE associated with the United States Environmental Protection Agency’s Reference Dose and the Agency for Toxic Substances and Disease Registry’s Minimal Risk Level is 6.4μg arsenic/L urine. The BEs associated with the various cancer risk assessments are significantly lower. These BE values may be used as screening tools for evaluation of biomonitoring data for inorganic arsenic in a public health risk context. [ABSTRACT FROM AUTHOR]

Cranberries are healthy fruit that contribute color, flavor, nutritional value, and functionality. They are one of only three fruits native to America. Over the past decade, public interest for the North American cranberry (Vaccinium macrocarpon) has been rising with reports of their potential health benefits linked to the numerous phytochemicals present in the fruit—the anthocyanins, the flavonols, the flavan-3-ols, the proanthocyanidins, and the phenolic acid derivatives. The presence of these phytochemicals appears to be responsible for the cranberry property of preventing many diseases and infections, including cardiovascular diseases, various cancers, and infections involving the urinary tract, dental health, and Helicobacter pylori-induced stomach ulcers and cancers. Recent years have seen important breakthroughs in our understanding of the mechanisms through which these compounds exert their beneficial biological effects, yet these remain to be scientifically substantiated. In this paper these characteristics, as well as the antioxidant, radical scavenging, antibacterial, antimutagen, and anticarcinogen properties of cranberry major bioactive compounds are explained. [ABSTRACT FROM AUTHOR]

We have screened the Library of Pharmacologically Active Compounds (LOPAC) and the National Institutes of Health (NIH) Small Molecule Repository (SMR) libraries in a horseradish peroxidase–phenol red (HRP-PR) H2O2detection assay to identify redox cycling compounds (RCCs) capable of generating H2O2in buffers containing dithiothreitol (DTT). Two RCCs were identified in the LOPAC set, the ortho-naphthoquinone -lapachone and the para-naphthoquinone NSC 95397. Thirty-seven (0.02%) concentration-dependent RCCs were identified from 195,826 compounds in the NIH SMR library; 3 singleton structures, 9 ortho-quinones, 2 para-quinones, 4 pyrimidotriazinediones, 15 arylsulfonamides, 2 nitrothiophene-2-carboxylates, and 2 tolyl hydrazides. Sixty percent of the ortho-quinones and 80% of the pyrimidotriazinediones in the library were confirmed as RCCs. In contrast, only 3.9% of the para-quinones were confirmed as RCCs. Fifteen of the 251 arylsulfonamides in the library were confirmed as RCCs, and since we screened 17,868 compounds with a sulfonamide functional group we conclude that the redox cycling activity of the arylsulfonamide RCCs is due to peripheral reactive enone, aromatic, or heterocyclic functions. Cross-target queries of the University of Pittsburgh Drug Discovery Institute (UPDDI) and PubChem databases revealed that the RCCs exhibited promiscuous bioactivity profiles and have populated both screening databases with significantly higher numbers of active flags than non-RCCs. RCCs were promiscuously active against protein targets known to be susceptible to oxidation, but were also active in cell growth inhibition assays, and against other targets thought to be insensitive to oxidation. Profiling compound libraries or the hits from screening campaigns in the HRP-PR H2O2detection assay significantly reduce the timelines and resources required to identify and eliminate promiscuous nuisance RCCs from the candidates for lead optimization. [ABSTRACT FROM AUTHOR]

Abstract: The cosmeceutical category is an undefined, unclassified, and unregulated area of dermatology that is yet in its infancy. Traditional cosmeceuticals involve the topical application of biologically active ingredients that affect the skin barrier and overall skin health. The ability of these ingredients to enhance skin functioning depends on how they are formulated into products that can maintain the integrity of the active ingredient, deliver it in a biologically active form to the skin, reach the target site in sufficient quantity to exert an effect, and properly release from the carrier vehicle. In the United States, cosmeceuticals are sold as cosmetics, making marketing, packaging, and aesthetic appeal important considerations. Ideally, the cosmeceutical should be clinically tested for efficacy to ensure a proven skin benefit and also to substantiate marketing claims. Governmental limitations of efficacy claims restrict cosmeceutical development because products can only be assessed in terms of their ability to improve skin appearance but not function. Improving function would remove the cosmeceutical from the cosmetic category and place it in the drug category. Herein lies the challenge of defining the cosmeceutical category. [Copyright &y& Elsevier]

Abstract: Cosmeceuticals, or physiologically active cosmetics, are subject to many misconceptions. Most consumers mistakenly believe that cosmeceuticals are regulated and tested as drugs. They also believe that the ingredients and final products have been tested for safety and that the claims made in advertisements are valid. Although cosmeceuticals and pharmaceutical ingredients have never been closer together, their regulatory environments are vastly different due to the distinct Congressional mandates given the Food and Drug Administration. Physicians are in a good position to help patients and potential cosmeceutical users understand the benefits and realistic limitations of these products. [Copyright &y& Elsevier]

Abstract: The inverse association between the intake of soybean foods and cancer incidence and mortality rates supported by published literature has led to studies on identifying bioactive components. The cancer preventive properties of the soybean peptides lunasin and Bowman-Birk protease inhibitor (BBI) have been demonstrated by in vitro and in vivo assays. Since there is no comprehensive information on the concentrations of these two peptides, US commercially available soy foods, including soy milk, soy-based infant formula, tofu, bean curd, soybean cake, tempeh, natto, miso and su-jae samples, were analyzed for lunasin and BBI. Both peptides were present in most of the products, in varying concentrations, depending mainly on the soybean variety and the manufacturing process. Lunasin and BBI were absent in the fermentation products natto and miso, suggesting that fermentation destroys both peptides. To study the bioavailability of lunasin and BBI, three soy milk samples with different concentrations of these peptides were subjected to an enzymatic hydrolysis process simulating physiological digestion. The results confirm the important role BBI plays in the protection of lunasin from digestion by pepsin and pancreatin. [Copyright &y& Elsevier]

Of all the food additives for which the FDA has received adverse reaction reports, the ones that most closely resemble true allergens are sulfur-based preservatives. Sulfites are used primarily as antioxidants to prevent or reduce discoloration of light-colored fruits and vegetables, such as dried apples and potatoes, and to inhibit the growth of microorganisms in fermented foods such as wine. This work aims to prepare an electrochemical biosensor based on bay leaf tissue homogenate that contains polyphenol oxidase enzyme abundantly for sulfite detection in foods. The principle of the biosensor is based on the inhibition effect of sulfites on polyphenol oxidase in the bioactive layer. Optimum conditions for the biosensor, such as temperature and pH, were investigated. Some stability parameters of the biosensor were also identified. The biosensor showed a linear calibration graph in the range of 25-100 µM sulfite. The biosensor presents a very simple, economical, reliable, and feasible method for sulfite detection in foods. [ABSTRACT FROM AUTHOR]

The article discusses the goals of the Global Institute for Bioexploration (GIBEX) which was established by joint efforts of Rutgers University and the University of Illinois in the U.S. GIBEX aims to encourage the search for new natural biologically active substances, maintain biodiversity, and to monitor the natural resources conservation.

The article reports on the California Department of Toxic Substances Control's request of the Ninth Circuit for reassessment if the District Court for the Central District of California's grant of summary judgment to various corporate defendants in litigation stemming from a state-initiated cost recovery action under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). It discusses that California had sued for cleanup costs it incurred in remedial action at a former lead treating facility operated by Morris P. Kirk of Alco Pacific, Incorporated.

N-benzylpiperazine (BZP) is the active ingredient in recreational 'party' or 'p.e.p.' pills, which are used to provide a stimulant, euphoric effect akin to that of methylenedioxymethamphetamine (NDMA, 'ecstasy'). BZP predominantly affects dopamine neurotransmission in a similar fashion to known 'drugs of abuse', such as methamphetamine and cocaine, which strongly suggests BZP has abuse liability. BZP is illegal in many countries including the United States of America and Australia, yet it remains legal in the United Kingdom, Canada and New Zealand. There has been little research, to date, on the neurological consequences of high dose or chronic exposure of BZP. Here we provide a comprehensive review of the information currently available on BZP and suggest a need for further research into the mechanisms of action, long-term effects and potentially addictive properties of BZP. [ABSTRACT FROM AUTHOR]

Since the establishment of the World Trade Organization (WTO) in 1995 and implementation of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) as a result, the United States (US) sought to impose still higher levels of intellectual property rights on developing countries, a phenomenon that is commonly known today as TRIPS-Plus. The Jordan–US FTA, signed in 2001, contains several TRIPS-Plus rules that restrict the poor's access to medicines, and is today touted by US officials and the US Trade Representative (USTR) as a success, and providing a wide range of benefits. These benefits not only include a higher growth rate, but also more specific benefits to the pharmaceutical sector in particular, such as an improved ability to develop generic medicine and engage in new innovative research, as well as increasing the presence of and collaboration with multinational drug makers. This article analyzes in detail the TRIPS-Plus provisions of the Jordan–US FTA. It challenges the claims that the FTA brings general and specific benefits to developing countries, and provides fresh evidence which strongly suggests that benefits from the Jordan–US FTA have been largely exaggerated while the costs underestimated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In a study to identify exposures associated with 15 cases of childhood leukemia, we found levels of tungsten, arsenic, and dichlorodiphenyldichloroethylene in participants to be higher than mean values reported in the National Report on Human Exposure to Environmental Chemicals. Because case and comparison families had similar levels of these contaminants, we conducted genetic studies to identify gene polymorphisms that might have made case children more susceptible than comparison children to effects of the exposures. DESIGN: We compared case with comparison children to determine whether differences existed in the frequency of polymorphic genes, including genes that code for enzymes in the folate and purine pathways. We also included discovery of polymorphic forms of genes that code for enzymes that are inhibited by tungsten: xanthine dehydrogenase, sulfite oxidase (SUOX gene), and aldehyde oxidase. PARTICIPANTS: Eleven case children were age- and sex-matched with 42 community comparison children for genetic analyses. Twenty parents of case children also contributed to the analyses. RESULTS: One bilalleleic gene locus in SUOX was significantly associated with either case or comparison status, depending on which alleles the child carried (without adjusting for multiple comparisons). CONCLUSIONS: Although genetic studies did not provide evidence that a common agent or genetic susceptibility factor caused the leukemias, the association between a SUOX gene locus and disease status in the presence of high tungsten and arsenic levels warrants further investigation. RELEVANCE: Although analyses of community clusters of cancer have rarely identified causes, these findings have generated hypotheses to be tested in subsequent studies. [ABSTRACT FROM AUTHOR]

To show that tadalafil is efficacious in Black American and Hispanic men with erectile dysfunction (ED) and efficacy is noninferior to that in Caucasian men. Multiple observations in men with ED in national tadalafil study in the US, a multicenter, open-label study, assessed the efficacy of tadalafil 20 mg taken as needed (maximum one dose/day before sexual activity) for 12 weeks by patients with ED in various populations. This analysis focuses on three groups: Caucasian (Reference group), Black American, and Hispanic men. Primary measurement of efficacy was change from baseline in erectile function (EF) domain of the International Index of Erectile Function (IIEF) and the primary analysis was whether efficacy in Black American and Hispanic groups was noninferior to efficacy in the Caucasian group. Secondary efficacy measures included sexual encounter profile (SEP), IIEF intercourse satisfaction (IS) and overall satisfaction (OS) domains, Global Assessment Question (GAQ), and Psychological and Interpersonal Relationship Scale (PAIRS). Safety was assessed from adverse events (AEs) reported by all enrolled patients. The increase in IIEF EF domain score (9.5) from baseline for each group was statistically significant (P<0.001) and clinically relevant. Efficacy of tadalafil in Black American and Hispanic patients was noninferior to the Caucasian group. IS and OS domains of IIEF had a statistically significant increase from baseline (P<0.001). Change from baseline in positive responses to SEP questions for each group was significant (P<0.001). At least 77% of intercourse attempts were successful over various time intervals up to 36 h postdose. At least 88% of patients in the various groups had a positive response to GAQ1. Improvement from baseline in Sexual Self-Confidence and Spontaneity domains of PAIRS was statistically significant (P<0.001). A low number of AEs and a low AE-related discontinuation rate (2.3%) were reported in all groups. Tadalafil 20 mg was as efficacious in Black American and Hispanic men with ED as in Caucasian patients and was well tolerated.International Journal of Impotence Research (2007) 19, 76–83. doi:10.1038/sj.ijir.3901484; published online 18 May 2006 [ABSTRACT FROM AUTHOR]

The efficacy and safety of tadalafil, dosed once a day for the treatment of erectile dysfunction, was assessed in a randomized, double-blind, placebo-controlled, parallel-design study at 15 US centers. Following a 4-week treatment-free run-in period, patients (18 years of age) were randomly assigned to 24 weeks treatment with tadalafil 2.5 mg, tadalafil 5 mg or placebo. Primary efficacy endpoints were change at 24 weeks in International Index of Erectile Function Erectile Function (EF) Domain score and mean per-patient percentage ‘yes’ responses to Sexual Encounter Profile diary questions 2 and 3. Tadalafil significantly improved erectile function compared with placebo for all three co-primary efficacy endpoints. Few patients discontinued because of adverse events (2.1%, placebo; 6.3%, tadalafil 2.5 mg; 4.1%, tadalafil 5 mg). Common treatment-emergent adverse events (5%) were nasopharyngitis, influenza, viral gastroenteritis and back pain. Tadalafil 2.5 mg and 5 mg, dosed once a day for 24 weeks, was well tolerated and significantly improved erectile function.International Journal of Impotence Research (2007) 19, 95–103. doi:10.1038/sj.ijir.3901496; published online 27 July 2006 [ABSTRACT FROM AUTHOR]

The article provides information on the decision of Food and Drug Administration (FDA) in the U.S. to make Emergency Contraception (EC) an over the counter drug. The decision of FDA reflects the extent to which contraception has become a new focal point of conflict in the battle over abortion. In Michigan and Missouri, pro-life advocates have already introduced bills that would restrict the sale of EC to prescription-only. Both FDA and medical community consider EC to be a preventive. Jurisprudence protects both the decision to use contraceptives and to have an abortion.

Several charts are presented that list new drugs approved by the U.S. Food and Drug Administration (FDA), new dosage forms and indications approved by the FDA, and the agents pending FDA approval from May 20 to June 9, 2006.

The article focuses on the Toxics Release Inventory (TRI), a nearly 20-year-old public database of toxic chemical emissions from the U.S. Environmental Protection Agency (EPA). TRI is a powerful tool that will help recognize potential contamination hot spots, and was recently employed by firefighters and first responders after the floods of Hurricane Katrina. Given the extensive use of TRI, EPA proposed to contour the TRI regulations which draw controversy to the public. Implications of the proposed change are presented.

Abstract: Although the avocado is known as a rich source of monounsaturated fatty acids, there has been far less attention given to its content of other bioactive substances including carotenoids, which might contribute to cancer preventive properties similar to those attributed to other fruits and vegetables. The yellow-green color of the avocado prompted us to study the carotenoid content of this fruit using established methods in our laboratory. The California Hass avocado (Persea americana Mill.) was selected for study, because it is the most commonly consumed variety in the southwest United States. These avocados were found to contain the highest content of lutein among commonly eaten fruits as well as measurable amounts of related carotenoids (zeaxanthin, α-carotene, and β-carotene). Lutein accounted for 70% of the measured carotenoids, and the avocado also contained significant quantities of vitamin E. An acetone extract of avocado containing these carotenoids and tocopherols was shown to inhibit the growth of both androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines in vitro. Incubation of PC-3 cells with the avocado extract led to G2/M cell cycle arrest accompanied by an increase in p27 protein expression. Lutein alone did not reproduce the effects of the avocado extract on cancer cell proliferation. In common with other colorful fruits and vegetables, the avocado contains numerous bioactive carotenoids. Because the avocado also contains a significant amount of monounsaturated fat, these bioactive carotenoids are likely to be absorbed into the bloodstream, where in combination with other diet-derived phytochemicals they may contribute to the significant cancer risk reduction associated with a diet of fruits and vegetables. [Copyright &y& Elsevier]

As initiatives to legalize the importation of prescription drugs draw more attention, the concern over counterfeit drugs is growing. The possibility of receiving counterfeit drugs has created an emerging dilemma for health-care professionals. FDA is relying on pharmacists to help ensure the integrity of drug products before they reach health-care consumers. Pharmacy and therapeutics committees can play a key role in achieving this goal by reviewing policies for medication acquisition and ensuring that necessary controls are in place to help prevent the acquisition of counterfeit drugs. FDA is also taking steps to help alleviate counterfeiting by mandating bar codes on all hospital drug packaging and implementing electronic pedigree papers to track distribution. FDA leaders project that by 2007, all prescription drugs will be tracked electronically to help ensure their authenticity. Formulary decision-makers, pharmacy directors, and clinicians must continue to be educated about the problem to help prevent counterfeit drugs from polluting the drug supply. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence about the extent to which sensitivity analysis has been used in the cost-effectiveness literature. Sensitivity analyses for health-related QOL (HR-QOL), cost and discount rate economic parameters are of particular interest because they measure the effects of methodological and estimation uncertainties.Aim: To investigate the use of sensitivity analyses in the pharmaceutical cost-utility literature in order to test whether a change in economic parameters could result in a different conclusion regarding the cost effectiveness of the intervention analysed.Methods: Cost-utility analyses of pharmaceuticals identified in a prior comprehensive audit (70 articles) were reviewed and further audited. For each base case for which sensitivity analyses were reported (n = 122), up to two sensitivity analyses for HR-QOL (n = 133), cost (n = 99), and discount rate (n = 128) were examined. Article mentions of thresholds for acceptable cost-utility ratios were recorded (total 36). Cost-utility ratios were denominated in US dollars for the year reported in each of the original articles in order to determine whether a different conclusion would have been indicated at the time the article was published. Quality ratings from the original audit for articles where sensitivity analysis results crossed the cost-utility ratio threshold above the base-case result were compared with those that did not.Results: The most frequently mentioned cost-utility thresholds were $US20,000/QALY, $US50,000/QALY, and $US100,000/QALY. The proportions of sensitivity analyses reporting quantitative results that crossed the threshold above the base-case results (or where the sensitivity analysis result was dominated) were 31% for HR-QOL sensitivity analyses, 20% for cost-sensitivity analyses, and 15% for discount-rate sensitivity analyses. Almost half of the discount-rate sensitivity analyses did not report quantitative results. Articles that reported sensitivity analyses where results crossed the cost-utility threshold above the base-case results (n = 25) were of somewhat higher quality, and were more likely to justify their sensitivity analysis parameters, than those that did not (n = 45), but the overall quality rating was only moderate.Conclusions: Sensitivity analyses for economic parameters are widely reported and often identify whether choosing different assumptions leads to a different conclusion regarding cost effectiveness. Changes in HR-QOL and cost parameters should be used to test alternative guideline recommendations when there is uncertainty regarding these parameters. Changes in discount rates less frequently produce results that would change the conclusion about cost effectiveness. Improving the overall quality of published studies and describing the justifications for parameter ranges would allow more meaningful conclusions to be drawn from sensitivity analyses. [ABSTRACT FROM AUTHOR]

Psychiatric medication use for children has increased dramatically over the past three decades. Despite substantial media attention to the issue, little is known about how the lay public feels about the use of psychiatric medications for children. Drawing on theories of medicalization, we describe and analyze Americans' attitudes towards the use of psychiatric medications generally and Prozac specifically for children described as having three types of behavioral problems. Using data from the 1998 General Social Survey's Pressing Issues in Health and Medical Care Module, we find that more Americans (57%) are willing to use psychiatric medications for children who have expressed suicidal statements than for "oppositional" behaviors (34.2%) or for hyperactivity (29.5%). Across the board, respondents are less willing to give Prozac than the general class of psychiatric medications. While socio-demographics do little to identify Americans with differing positions, the strongest and most consistent correlates of willingness to give psychiatric medications to children are trust in personal physicians, general attitudes towards psychiatric medications, and the respondent's expressed willingness to take psychiatric medications herself or himself. [ABSTRACT FROM AUTHOR]

The article discusses the method for the simultaneous extraction and analysis of two current use pesticides, atrazine and lambda- cyhalothrin, in sediment and aquatic plants. It has been estimated that 375,000 tons of pesticides are used for agriculture annually in the Midwest area of the United States, where approximately 65% of this total is used for production of corn and soybean crops. Within the Mississippi River Basin, greater than 100,000 tons of herbicides are used annually. Triazine herbicides and synthetic pyrethroids insecticides are two classes of pesticides currently used in this agricultural area.

Glioblastoma multiforme is one of the most deadly malignant tumors, with more than 10,000 cases recorded annually in the United States. Various clinical analyses and studies show that certain chronic diseases, including cancer, interact between cell-reactive radicals rise and pathogenesis. Reactive oxygen and nitrogenous sources include endogenous (physiological processes), and exogenous sources contain reactive oxygen and nitrogen (xenobiotic interaction). The cellular oxidation/reduction shifts to oxidative stress when the regulation mechanisms of antioxidants are surpassed, and this raises the ability to damage cellular lipids, proteins, and nucleic acids. This review is focused on how phytochemicals play crucial role against glioblastoma multiforme and to combat these, bioactive molecules and their derivatives are either used alone, in combination with anticancer drugs or as nanomedicine formulations for better cancer theranostics over the conventional approach. Bioactive molecules found in seeds, vegetables, and fruits have antioxidant, anti-inflammatory, and anticancer properties that may help cancer survivors feel better throughout chemotherapy or treatment. However, incorporating them into the nanocarrier-based drug delivery for the treatment of GBMs, which could be a promising therapeutic strategy for this tumor entity, increasing targeting effectiveness, increasing bioavailability, and reducing side effects with this target-specificity, drug internalization into cells is significantly improved, and off-target organ aggregation is reduced. [Display omitted] • Bioactive molecules are the best approach in GBM. • Bioactive molecules effective against GBM. • Phytonanocarriers enhanced the bioavailability and reduced severe side effects. • Target-specificity and drug internalization into cells is significantly improved. [ABSTRACT FROM AUTHOR]

The use of copaiba oil has been reported since the 16th century in Amazon traditional medicine, especially as an anti-inflammatory ingredient and for wound healing. The use of copaiba oil continues today, and it is sold in various parts of the world, including the United States. Copaiba oil contains mainly sesquiterpenes, bioactive compounds that are popular for their positive effect on human health. As part of our ongoing research endeavors to identify the chemical constituents of broadly consumed herbal supplements or their adulterants, copaiba oil was investigated. In this regard, copaiba oil was subjected to repeated silica gel column chromatography to purify the compounds. As a result, one new and seven known sesquiterpenes/sesquiterpenoids were isolated and identified from the copaiba oil. The new compound was elucidated as (E)-2,6,10-trimethyldodec-8-en-2-ol. Structure elucidation was achieved by 1D- and 2D NMR and GC/Q-ToF mass spectral data analyses. The isolated chemical constituents in this study could be used as chemical markers to evaluate the safety or quality of copaiba oil. [ABSTRACT FROM AUTHOR]

This paper has presented the first estimates of the effect of regulation on new drug introductions in the 1970s. Results indicate that regulation has had a major direct impact on introductions as well as a significant indirect effect through a reduction in research spending. These estimates indicate that regulation has reduced introduction rates by roughly 60%. Approximately one-fifth of this reduction was the previously ignored effect of regulation on research spending. Several additional points should be noted regarding these estimates besides their large quantitative magnitude. First, they show that regulation is currently a very significant factor affecting the flow of new drugs. Further, by a large range of criteria-the estimated cost of a new drug, the stability of regulatory effects over a variety of specifications, the economic merit and sensibility of the lag structure-the results of the model are believable and stable. Results indicate a steep trade-off between greater certainty about drugs' effectiveness and the rate of drug introductions. However, this still leaves us several steps away from final policy conclusions. The steepness of the trade-offs faced belie the underlying difficulty and expense of objectively establishing a product's effectiveness.