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Este artigo apresenta uma revisão e análise da assistência farmacêutica como parte integrante do sistema de atenção primária à saúde, no qual a qualidade do uso de medicamentos está diretamente relacionada à qualidade do serviço de saúde e aos elementos para a avaliação desta. As Unidades Básicas de Saúde constituem a principal porta de entrada do sistema de assistência à saúde estatal em nosso país. Entretanto, o vínculo do serviço farmacêutico está relacionado com o modelo curativo, centrado na consulta médica e pronto atendimento, com a farmácia apenas atendendo a essas demandas. A atividade de orientação aos usuários na farmácia das Unidades Básicas de Saúde torna-se praticamente impossível, pois na farmácia deságuam quase todas as mazelas do sistema de saúde, por estar no elo final do processo de atendimento. A solução do problema, no âmbito geral, não será simples, se mantida a forma como o serviço está estruturado, pois grande parte das pressões de demanda não depende do serviço de saúde em si, mas de políticas sociais inclusivas, as quais têm impacto direto nas condições de saúde da população. No âmbito específico, é fundamental que os gestores racionalizem a utilização dos medicamentos desde a prescrição até a utilização por parte do usuário.This paper presents a review and analysis of Pharmacist Care as an integrated part of the Primary Health Care System, in which quality use of medicines is directly related to quality health service and to elements for its evaluation. In our country the Basic Health Units represent the main entrance to the public health care system. The pharmaceutical services however are still linked to the care model centered in medical consultation and emergency care, with the pharmacy just satisfying their needs. Provide orientation to the users of a Basic Unit pharmacy is almost impossible because nearly all sore spots of the health system end up at the pharmacy as the final step in the care process. The solution of the problem will not be easy if the present structure of the service is maintained. Great part of the pressure resulting from the demand does not depend on the health service itself but on inclusive social policies with direct impact on the health conditions of the population. Rational use of medicines from the prescriber to the user is fundamental in this specific environment.

Introduction Almost 50% of the 17.5 million deaths worldwide from cardiovascular disease have been associated with systemic arterial hypertension (SAH). Into this scenario, Pharmaceutical Care (PC) has been inserted in order to improve the management of SAH and reduce its risks. Objective To evaluate the outcomes and healthcare assistance achieved after discharge of hypertension patients from the PC program. Methods This is a quasi-experimental study with historical controls. Retrospective data collection from 2006 to 2012 was begun in 2013 and included a PC program performed over one year. PC was performed in two basic units of the public health system in Ribeirão Preto-SP, Brazil, where the pharmacist followed up 104 hypertensive patients. The clinical indicators of systolic (SBP) and diastolic blood pressure (DBP), triglycerides, total-cholesterol, high and low density lipoprotein cholesterol were collected, as well as care indicators related to the number of consultations (basic, specialized and emergency care) and antihypertensive drugs used. The coronary risk of patients by the Framingham risk score was also calculated. For the analysis, the data were divided into three periods, 2006–2008 as pre-PC, 2009 as PC and 2010–2012 as post-PC. Results In the pre-PC period, 54.4%, 79.0% and 27.3% of patients presented satisfactory levels of SBP, DBP and total-cholesterol, respectively. In the post-PC period, the percentages were 93.0% for SBP and DBP [p

Expansive soils are characterized by volumetric changes caused by variations in moisture. They can cause several damages to civil constructions, especially to lightweight structures, including cracks and fissures. Chemical stabilization through addition of lime is one of the most effective techniques used to treat this type of soil. Due to cationic exchanges, lime can significantly reduce swell potential. This research studied a disturbed sample of expansive soil collected in Nossa Senhora do Socorro – Sergipe, Brazil, through the following laboratory tests: sieve and hydrometer tests, Atterberg Limits, compaction, free swell and swell pressure. All direct and indirect methods mentioned in this paper indicated that the natural soil presented high to very high degree of expansion, which reached approximately 20% of free swell and nearly 200 kPa of swell pressure. In order to evaluate the effect of lime, the same tests were conducted in soil-lime mixtures, using lime contents of 3%, 6% and 9%. The results confirmed the efficiency of lime stabilization. It was noted that, as lime content increased, there was reduction of clay fraction and increment of silt fraction; plasticity index decreased to nearly its half; compaction curve was displaced; and free swell and swell pressure reduced significantly.

Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by a pharmacist (intervention group) and 59 patients in the control group. Data collection was performed before and after this 4-month intervention and included an evaluation of asthma knowledge, lifestyle, inhaler techniques, adhesion to treatment, pulmonary function and quality of life. An economic viability analysis was also performed. The intervention group obtained an increase in asthma knowledge scores of 58.3-79.5% (P < 0.001). In this group, there was also an increase in the number of individuals who practiced physical exercise (36-43%), in the number of correct replies regarding the use of inhalers, in the percentage of adherent patients, and in quality of life scores for all domains. We concluded that this asthma self-management model was effective in improving the quality of life of asthma patients.

Microcapsules containing B. lactis and L. acidophilus were produced by complex coacervation and spouted bed dehydrated afterwards. The aim of this study was to evaluate the resistance of these microorganisms in face of the dehydration process, shelf life, and in vitro tolerance to acid pH besides microcapsules and particles morphology by optical microscopic and SEM. The processes of complex coacervation, drying, and formation of the casein/pectin complex were adjusted to microencapsulate L. acidophilus and B. lactis, but were not efficient in protecting these organisms at pH values similar to those of the human stomach. The microorganisms maintained greater viability at a storage temperature of 7°C.

Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus ( G ′), loss modulus ( G ″), and dynamic viscosity ( η ′), at 5°C, G ″ exceeded G ′. At 25 and 37°C, η ′ of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34–37°C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:2074–2089, 2007

Microcapsules containing Bifidobacterium lactis (BI 01) and Lactobacillus acidophilus (LAC 4) were produced by complex coacervation using a casein/pectin complex as the wall material, followed by spray drying. The aim of this study was to evaluate the resistance of these microorganisms when submitted to the spray drying process, a shelf-life of 120 days at 7-37 degrees C and the in vitro tolerance after being submitted to acid pH (pH 1.0 and 3.0) solutions besides morphology of microcapsules. Microencapsulated microorganisms were shown to be more resistant to acid conditions than free ones. Microencapsulated L. acidophilus maintained its viability for a longer storage period at both temperatures. The microcapsules presented a spherical shape with no fissures. The process used and the wall material were efficient in protecting the microorganisms under study against the spray drying process and simulated gastric juice; however, microencapsulated B. lactis lost its viability before the end of the storage time.

Iontophoresis is a strategy to increase the penetration of drugs through biological membranes; however, its use has been underexplored in mucosa. The aim of this work was to investigate the influence of iontophoresis in the mucosal penetration of prilocaine hydrochloride (PCL) and lidocaine hydrochloride (LCL), which are largely used in dentistry as local anesthetics, when combined in the same formulation. Semisolid hydrogels containing these drugs either alone or in combination were developed at two different pHs (7.0 and 5.8) and presented adequate mechanical and mucoadhesive properties for buccal administration. The distribution coefficients between the mucosa and the formulations (Dm/f) and the in vitro mucosa permeation and retention rates were evaluated for both PCL and LCL. At pH 7.0, the combination of the drugs decreased the Dm/f of PCL by approximately 3-fold but did not change the Dm/f of LCL; iontophoresis increased the permeation rate of PCL by 12-fold and did not significantly change LCL flux compared with the passive permeation rate of the combined drugs. Combining the drugs also resulted in an increase in both PCL (86-fold) and LCL (12-fold) accumulation in the mucosa after iontophoresis at pH 7.0 compared with iontophoresis of the isolated drugs. Therefore, applying iontophoresis to a semisolid formulation of this drug combination at pH 7.0 can serve as a needle-free strategy to speed the onset and prolong the duration of buccal anesthesia.

A simple, isocratic, high-resolution and prompt HPLC-PDA method was developed and validated for the simultaneous quantification of prilocaine (PCL) and lidocaine (LCL) hydrochlorides in in vitro buccal iontophoresis-driven permeation studies. A reversed-phase C18 column (250 mm x 4.6 mm, 3μm, 110Å) was used for the chromatographic separation. The mobile phase contained acetonitrile: 0.1M sodium phosphate buffer, pH 7.0 (1:1, v/v), plus 0.05% (v/v) diethylamine. The isocratic flow rate was set at 1 mL/min and the detection wavelength was 203 nm. PCL and LCL eluted in 8.9 min and 13 min, respectively, and the system suitability parameters varied within an acceptable range. The method was selective, sensitive, precise, accurate and robust, producing a linear plot at the concentration range of 0.25 to 10 µg/mL. The application of this method was demonstrated by a significant enhancement of the permeation of PCL and LCL with the application of iontophoresis (1 mA/cm(2) per 1 h) through isolated porcine esophageal epithelium. The amount of the drug retained in the epithelium also increased with the application of an electrical current. Copyright © 2015 John WileySons, Ltd.

Esta revisão apresenta e discute os problemas relacionados aos acidentes envolvendo medicamentos, da prescrição ao uso, as etapas críticas e estratégias para minimizá-los. Os medicamentos são reconhecidos, em sua maioria, como eficazes, minimizando sofrimentos e curando pessoas, porém, quando utilizados de maneira inadequada podem representar riscos à saúde. Portanto, os serviços de saúde devem priorizar a segurança do usuário, visando à redução dos acidentes previsíveis com os medicamentos. Acidentes com medicamentos são todos os incidentes, problemas ou insucessos, previsíveis ou não, produzidos ou não por erro, conseqüência ou não de imperícia, imprudência ou negligência, que ocorrem durante o processo de utilização dos medicamentos, causem estes eventos danos, ou não, ao paciente. Podem ser classificados como "reações adversas" e "erros de medicação". Considerando que maioria dos erros de medicação ocorre no estágio de prescrição do medicamento, a adoção de sistemas de prescrição eletrônica de medicamentos, com suporte à decisão clínica, pode reduzir significativamente os eventos adversos relacionados aos medicamentos, melhorando a qualidade e a eficiência do tratamento farmacológico, com redução de custos para o sistema de saúde.The readiness of the medicines for the prevention and combat to diseases makes the medicine therapy the main instrument of medical practice in the individuals' treatment for recovery of health. Although they are recognized as effective, minimizing suffering and curing people, they can also represent serious risks for health, especially when used in an inadequate way. Consequently, the user's safety in the process of using medicines, seeking the reduction of damages and predictable injuries, should be a priority in the health services. Considering that more than half of all of the medication mistakes happen in the apprenticeship of prescription of medicine, the adoption of mechanisms that alerts the doctor during the prescription can have a positive impact in the reduction of the total number of adverse events associated to medicines and in the expenses with the health service. The adoption of electronic systems in medicine prescription as a support to the clinical decision can significantly reduce the occurrence of adverse events related to medicines, improving the quality and efficiency of the pharmacological treatment.

No presente estudo foi feita avaliação da Assistência Farmacêutica em farmácias de Unidades de Saúde do município de Ribeirão Preto, no Estado de São Paulo, Brasil. Partindo-se do referencial de avaliação tecnológica em saúde e suas interfaces, foram realizadas entrevistas com os profissionais farmacêuticos, procurando-se conhecer as concepções desses atores sobre a assistência farmacêutica. Os resultados obtidos mostram um trabalho baseado na gestão burocrática dos medicamentos com objeto no controle de estoque do medicamento. Alguns elementos emergentes que poderão contribuir para a alteração deste quadro foram detectados: voluntarismo, busca pela valorização profissional, iniciativa de integração com a equipe de saúde, percepção do paciente como objeto de trabalho e formação profissional complementar.In the present study we evaluated the Pharmaceutical Assistance in pharmacies of Basic Health Care Units in Ribeirão Preto, State of São Paulo, Brazil. Considering the technological evaluation reference in health and its interfaces, pharmaceutical professionals were interviewed in a way to find out their conceptions about pharmaceutical assistance. The results showed a work based on the bureaucratic management of medicines specially the control of medicine supplies. Some emergent elements were thought to contribute to change this system: voluntarism, professional valorization, integration of the health team, perception of the patient as object of the work and complementary professional formation.

A doença periodontal é morbidade com alta prevalência na população mundial. É causada pelo acúmulo de componentes microbianos do biofilme dental no interior das áreas subgengivais do periodonto, desencadeando processo inflamatório que afeta as estruturas de suporte dental, resultando em formação de bolsa periodontal e perda dos dentes, se não tratada. O tratamento convencional consiste de raspagem e alisamento radicular, associado ou não ao uso de antimicrobianos de ação sistêmica, o que implica altas doses, porém com eficácia reduzida, efeitos adversos e dificuldades de adesão ao tratamento por parte do paciente. Nas últimas décadas, o tratamento tem sido otimizado pelo uso de sistemas de liberação de fármaco intrabolsa periodontal, com a vantagem de liberar o fármaco no local de ação, possibilitando prolongar e/ou controlar sua concentração. A presente revisão aborda os principais sistemas de liberação de fármaco intrabolsa periodontal, o potencial de utilização, assim como os protocolos disponíveis para a avaliação da efetividade dos mesmos na terapia periodontal.Periodontal disease is very common in the world population. It is caused by the accumulation of microbial components of the dental biofilm inside the subgingival areas, producing an inflammatory process that affects the supporting structures of tooth, periodontal pockets and loss of the teeth, if not treated. The conventional treatment consists of tooth surface mechanical cleaning and root planning, associated or not to the systemic use of high concentrations of antibiotics, but with reduced effectiveness, and adverse effects. The patient compliance to the therapeutic is committed too. In the last decades, the treatment has been optimized for the use of drug delivery systems to the periodontal pocket, with the advantage of delivering the drug in the specific site, sustaining and/or controlling the drug concentration. Recently, the use of new drug delivery systems has been receiving great interest. This review approaches the main delivery systems for the administration of drugs to the periodontal pocket, their usefulness, as well as the available protocols for the evaluation of these systems effectiveness in the periodontal therapy.

We describe the preparation of pancreatic enzymes hydrolysate of milk whey proteins containing low levels of aromatic amino acids. Pancreatin and trypsin/chymotrypsin (6.3% w/w protein) when used to hydrolyze whey proteins for 27 h at 37±2 ºC, released 74% of the Phe, 100% of the Tyr and 100% of the Trp as free amino acids. Most of the free aromatic amino acids present in 2 kg hydrolysate were separated from the remaining peptides and other amino acids by gel filtration on a 15 liter Sephadex G-25 column eluted with 5% acetic acid at 60 liters h-1 at 25ºC. The product, recovered in 37% yield, contained 0.70 mmol Phe, 0.41 mmol Tyr, and Foi descrita a preparação de um hidrolisado de proteínas do soro de leite bovino com enzimas pancreáticas, contendo baixos níveis de aminoácidos aromáticos. Quando utilizadas pancreatina e tripsina/quimotripsina, por 27h a 37±2ºC, foram liberados 74% de Phe, 100% de Tyr e 100% de Trp como aminoácidos livres. A maioria dos aminoácidos aromáticos livres, presentes em dois quilos de hidrolisado (15 litros), foi separada dos peptídeos e outros aminoácidos remanescentes por filtração em coluna de gel de Sephadex G-25C eluída com ácido acético 5%, fluxo de 60 litros por hora a 25ºC. O produto, recuperado com 37% de rendimento, continha 0,70 mmol de Phe, 0,41 mmol de Tyr e

In the present study, the effect of dietary fish oil, a highly unsaturated fat source, on the intestinal mucosa before and after proximal small bowel resection in rats was studied. Forty Wistar rats were fed defined diets containing fish oil (experimental group) or corn oil (control group). After 2 weeks, animals underwent a 50% proximal small bowel resection. Mucosal disaccharidases, alkaline phosphatase, aminopeptidase, protein, DNA, and TBARs levels were assessed in samples immediately before and 6 and 12 days after surgery. Disaccharidase activities were reduced in the ileal mucosa from rats in the fish oil-fed group compared to the control group before and 12 days after surgery. The other parameters showed no significant differences. The results indicate that fish oil (omega-3 fatty acids) alters the functional parameters of the normal intestinal mucosa and after intestinal resection compared to omega-6 polyunsaturated fatty acids, suggesting that caution should be taken to use omega-3 fatty acids as adjuvants in the adaptive process after resection.No presente estudo, foi avaliado o efeito da dieta com óleo de peixe, uma fonte de ácidos graxos altamente insaturados, sobre a mucosa intestinal antes e após resecção do intestino delgado proximal em ratos. Quarenta ratos Wistar foram alimentados com dieta definida contendo óleo de peixe (grupo experimental) ou óleo de milho (grupo controle). Após duas semanas, os animais foram submetidos à ressecção de 50% do intestino delgado proximal. Os níveis das dissacaridases, fosfatase alcalina, animopeptidade, proteína, DNA e TBARS foram avaliados, imediatamente antes e 6 e 12 dias após a cirurgia. As atividades das dissacaridases foram reduzidas na mucosa ileal no grupo de ratos alimentados com óleo de peixe, comparado com grupo controle antes e 12 dias após a cirurgia. Os outros parâmetros não mostraram diferenças significativas. Este resultado indica que o óleo de peixe (ácidos graxos ômega-3) altera parâmetros funcionais na mucosa intestinal normal e após resecção, comparado ao ácido graxo ômega-6, sugerindo cautela no uso de ácidos graxos ômega-3 como adjuvante no processo adaptativo após resecção.

The oral mucosal cavity is a feasible, safe, and very attractive site for drug delivery with good acceptance by users. The mucosa is relatively permeable and robust, shows short recovery times after stress or damage, is tolerant to potential allergens, and has a rich blood supply. Moreover, oral mucosal drug delivery bypasses the first-pass effect and avoids presystemic elimination in the gastrointestinal tract. Bioadhesive systems provide intimate contact between a dosage form and the absorbing tissue, which may result in high concentration in a local area and hence high drug flux through the absorbing tissue. The efficacy of oral bioadhesive drug delivery systems is affected by the biological environment and the properties of the polymer and the drug. In the present paper, we review systematically some relevant citations regarding the environment, strategies for oral drug delivery and evaluation, and utilization of the main polymers.

Bioresorbable polymeric films were prepared by solvent casting using a tyrosine-derived polycarbonate and metronidazole (MDZ) as the model drug at 2.5%, 5% and 10% (w/w). Drug loading did not affect the water uptake, drug release, polymer degradation or erosion profiles. All devices released approximately 85% (w/w) of the drug within a 1.5 h period. This may be attributed to the rapid water uptake of the polymer. An increase in the water uptake correlated with a linear rate increase of the polymer degradation (0.968 ≤ R2 ≤ 0.999). Moreover, MDZ presented a remarkable plasticizing effect for the polymer and drug loading exerted a significant impact on the mechanical properties of the obtained films. The results obtained can be used to further the development of novel biocompatible and biodegradable polymeric platforms for the delivery of metronidazole and other drugs in a broad range of pharmaceutical applications.

The properties of an Fe(3+)-peptide complex containing 5.6% Fe, obtained by the reaction of ferric chloride with an enzymatic hydrolysate of casein, are described. The major site of iron binding corresponds primarily to the carboxylate groups and to a lesser extent to the peptide bonds. The Fe(3+)-peptide complex is insoluble at acid pH and completely soluble at neutral to alkaline pH. When soluble, the Fe(3+) is tightly bound to the complex peptide mixture but can be displaced and complexed by a low molecular weight ligand such as cysteine. Its efficacy in relation to iron sulfate was compared in rats. Both iron sources were administrated in Milli-Q water by gastric gavage to male Wistar rats (180-200 g) after an 18 h fast with water ad libitum. Fe(3+) from the Fe(3+)-peptide complex was transferred to the blood in a dose-dependent manner (1-8 mg of Fe/kg), and the serum iron levels were significantly higher (p0.001) than in a similar group of rats treated with iron sulfate. In the comparative kinetics experiments, the rats received 4 mg of Fe/kg. Both iron sources presented maximum absorption, as indicated by the elevation of serum iron levels, 30 min after administration, and the AUC(0)(--2h) of the Fe(3+)-peptide complex was significantly higher (p0.05) than that observed with iron sulfate. The simultaneous administration of free peptides (0-192 mg) with the Fe(3+)-peptide complex or iron sulfate did not modify the extent of absorption of iron from both sources, suggesting that the absorption is due to the complex formed and probably not to exchange reactions in the gastrointestinal tract. In the hemoglobin repletion experiments carried out on newly weaned rats with anemia induced by a low-iron diet, supplementation of the diet with the the Fe(3+)-peptide complex was as efficient as supplementation with iron sulfate in the conversion from diet to hemoglobin iron. These results, taken together, suggest that the Fe(3+)-peptide complex is a potential compound for use as an iron source in biological situations.

The use of biopolymers in sustained release systems has been studied by many research groups because of the bioavailability and biodegradability of these compounds. Casein is a natural biopolymer whose degradation results in biologically utilisable compounds. The objective of the present study was to assess the potential of casein microcapsules (CAS/MC) as sustained release systems using acetaminophen as a model drug. CAS/MC were prepared by aqueous coacervation in lactate buffer containing gelatin, hydroxypropyl cellulose (HPC) and lecithin. After preparation, the microcapsules were treated, or not, with glutaraldehyde as a cross-linking agent. CAS/MC were loaded using two distinct procedures, either by dissolving 50% of the drug (w/w), relative to casein, in the polymer dispersion or by dissolving the drug in the coacervating solution. The drug present in CAS/MC was quantified by HPLC after an enzymatic degradation assay, and the CAS/MC were analysed by scanning electron microscopy and thermal analysis (differential scanning calorimetry and thermogravimetrical analysis). Loading of the drug was approximately 8% (w/w), with high resistance to enzymatic attack. The absence of an acetaminophen melting peak indicated that there was no drug present on the surface of the cross-linked systems. In addition, loading was accompanied by a reduction of the specific heat capacity of the systems, which suggests a decrease in stability. The outer morphology of the encapsulating polymer was affected by the process of microencapsulation. The data suggest that the microencapsulation process of aqueous coacervation and cross-linking is appropriate for the preparation of microencapsulated systems for sustained drug delivery.

O uso racional de medicamentos e uma aspiracao que nao deve ser atribuida somente ao encontro entre profissional de saude e usuario, pois ultrapassa os limites da mera interacao entre prescricao e uso que se da na relacao medico-paciente. Essa pretensa racionalidade no uso do medicamento clamaria por um dificil alinhamento entre racionalidades distintas dos […]

Gastric acidity is an important luminal factor for non-heme iron absorption. The effect of iron supplementation (1 mg Fe/kg body weight) was studied in rats submitted to hypochlorhydria by daily oral administration of omeprazole (40 μmol/kg). Forty (40) rats received omeprazole (experimental group) and 20 rats received vehicle (control group) for 4 weeks. At the end of this period, 10 animals from each group were sacrificed. The remaining rats in the control group continued receiving vehicle alone for 2 additional weeks. The experimental group was divided into three subgroups of 10 rats each. One subgroup received omeprazole alone, and the other subgroups received omeprazole plus iron supplementation with iron sulphate (Fe +2 ) or iron-peptide complex (Fe +3 ) for 2 additional weeks. After 4 weeks of treatment, the group that received omeprazole presented an increase of serum transferrin and a decrease of hepatic iron levels. However, only after 6 weeks did a decrease of haemoglobin occur in this subgroup. Supplementation started during the 5th week prevented the decrease of haemoglobin, improved the transferrin levels but did not cause hepatic iron to return to control levels. These results suggest that iron deficiency due to hypochlorhydria could be prevented by iron supplementation and that the two iron sources were equally efficient in this respect.

Casein microparticles (CAS/MP) have a potential clinical use for targeting drugs. However, the use of organic solvents in their preparation is undesirable. This study was designed to investigate the influence of preparation procedures in aqueous media on the formulation and physicochemical properties of CAS/MP. The first stage involved the influence of the coacervating agents (lactic acid, succinic anhydride, succinic acid and tartaric acid). The second stage studied was the influence of the ionic strength and the third, the influence of adding a thickener, hydroxypropyl cellulose or hydroxypropyl methycellulose (HPC or HPMC), and a plasticizing agent (gelatin). Some physicochemical properties of CAS/MP were evaluated. While the infrared and the thermal analysis showed that all coacervating agents were appropriate for coacervation, the scanning electron microscopy studies showed that the external morphology of the particles was more homogeneous when lactic acid was used. Utilizing lactic acid as the coacervating agent, there was a trend effect of adding NaCl implying that the increasing of the ionic strength resulted in better stability. Finally, the addition of 0.1% HPC plus either 0.25 or 0.5% gelatin resulted in homogeneous formulations. In conclusion, the use of lactic acid plus 0.1% HPC and 0.25% gelatin results in biodegradable and homogeneous CAS/MP, presenting a potentially useful drug delivery system.

Background : The standardized liquid extract of Brosimum gaudichaudii Trecul is an alternative for the treatment of vitiligo. There is a shortage of solid oral dosage forms developed from standardized extracts of this plant specie. Objective: This study is aimed to obtain pellets with a standardized liquid extract of B. gaudichaudii. Results: The standardized liquid extract of B. gaudichaudii was obtained through maceration and percolation with a 55% ethanol-water solution (v/v). Pellets were obtained through a mixture of extract of 500 g of B. gaudichaudii standardized extract, 500 g of microcrystalline cellulose PH101 and 10 g of hydroxypropyl methylcellulose K100. The pellets obtained presented a homogeneity yield of 92%, aspect ratio of 1.16 ± 0.65, shape fator eR of 0.35 ± 0.09 and Feret diammeter of 0.87 ± 0.27. These pellets were coated with a suspension composed of titanium dioxide, aluminum red lacquer, ethyl cellulose, talc and magnesium stearate. Before the photostability test, the uncoated pellets showed psoralen content equal to 0.13 ± 0.01% and to the 5-MOP was 1.40 ± 0.27%. After exposure to one level (3 J.cm -2 ) of UVB irradiation the uncoated pellets presented a degradation of 2.16% of psoralen and 8.1% of 5-MOP. After exposure to three levels (10, 20 and 30 J.cm -2 ) of UVA irradiation the uncoated pellets exhibited photodegradation of 9.78, 17.64, 24.21% of psoralen and 18.95, 23.68, 28.48% for 5-MOP. The coated pellets where unaffected after photostability test. Conclusion: Pellets were obtained with the standardized liquid extract of B. gaudichaudii and coating is a technological alternative to ensure the stability of the formula.

Pectin is a heteropolysaccharide which has been investigated for the development of colon-specific drug delivery systems. Polymers have been associated with pectin to reduce its aqueous solubility and improve the performance of drug delivery systems. Pectin–casein interaction is widely known in food research, but it has not been fully considered by pharmaceutical scientists. Thus, this study investigated the potential of casein–pectin microparticles as a drug delivery system and clarified the impact of cross-linking and drying methods on the in vitro release of indomethacin (IND) or acetaminophen (PCT) from microparticles. Microparticles were prepared by coacervation and dried by spray or spouted bed methods. Drug recovery, in vitro drug release, size, morphology, and the thermal and diffractometric properties of dried microparticles were determined. Spray-dried non-cross-linked microparticles were able to prolong IND release, and pectin was still degraded by pectinolytic enzymes. On the other hand, glutaraldehyde cross-linking prevented the enzymatic breakdown of pectin without improving IND release. Spouted bed drying reduced IND recovery from all microparticles when compared with spray drying, thus the successful spouted bed drying of microparticles depends on the chemical characteristics of both the drug and the polymer. Release data from PCT microparticles suggested that the microparticle formulation should be improved to bring about a more efficient delivery of water-soluble drugs. In conclusion, casein–pectin microparticles show great potential as a drug delivery system because casein reduces the water solubility of pectin. The drying method and cross-linking process had significant effects on the in vitro performance of these microparticles.

The scope of this paper was to analyze the profile of medical consultations and drugs used for the treatment of comorbidities in patients with diabetes attended in the Brazilian Unified Health System. This was a pharmaco-epidemiological cross-sectional study conducted between March 2006 and February 2007 All patients with diabetes attended in the western sanitary district of Ribeirao Preto in the state of São Paulo were included in the study. The types of medical attendance (primary, secondary and emergency care) and the drugs prescribed for the treatment of comorbidities were analyzed. The drugs were classified according to the Anatomical Therapeutic Chemical Classification System and 3,198 patients were identified. The mean age was 60.4 years and more than 55% of the patients were 60 years or older. The cardiovascular drugs most used were captopril or enalapril (60%). About 40.6% of the patients used acetylsalicylic acid in platelet antiaggregant doses. The patients had an average of 5.1 medical consultations per year (primary care, secondary care and emergency care). The utilization of statins and acetylsalicylic acid was less than that reported in the literature and the data indicate a high prevalence of admission to emergency care. Analisar o perfil de consultas médicas e de medicamentos para o tratamento de comorbidades em pacientes com diabetes atendidos no Sistema Único de Saúde. Estudo farmacoepidemiológico e transversal realizado de mar/2006 a fev/2007. Foram incluídos no estudo portadores de diabetes atendidos no Distrito Sanitário Oeste de Ribeirão Preto (SP), sendo analisadas as consultas médicas realizadas na atenção primária, secundária e emergência, além dos medicamentos prescritos para tratamento de comorbidades associadas ao diabetes. Foram identificados 3.198 pacientes, com idade média de 60,4 anos e aproximadamente 55,0% idosos. Os medicamentos do sistema cardiovascular foram os mais prescritos, sendo que 60,0% dos pacientes utilizavam captopril ou enalapril. Além disso, 40,6% dos pacientes faziam uso de ácido acetilsalicílico em dose antiagregante plaquetário. Em relação às consultas médicas, os pacientes apresentaram média de 5,1 visitas ao ano, na atenção primária, na atenção secundária e no atendimento de emergência. A utilização de ácido acetilsalicílico e estatina foram menores do que a relatada na literatura e os dados indicam uma alta prevalência de admissão no atendimento de emergência.

Objective: This study was analyzed adult individuals rehabilitated with different types of dentures, with the purpose of verifying the effect that different types of denture rehabilitation have on maximal bite force and masticatory efficiency. The aim of this study is to facilitate diagnosis and prognosis, bringing contributions to the quality and stability of treatments Materials and Methods: Fifty individuals were divided into five groups: one control group with ten dentate individuals and another four groups formed according to the type of rehabilitation treatment. Maximal bite force was recorded on the first molar regions, and masticatory efficiency rates were recorded on the right, left and habitual sides. Results: Data related to the maximal bite force recordings were statistically significant across the analyzed groups [ANOVA for p ≤ 0.01]. The data related to masticatory efficiency rates also showed statistical significance across all groups [ANOVA for p ≤ 0.05] in the three tested conditions [mastication on the right, left and habitual sides]. Conclusion: The group of individuals rehabilitated with implants and single crowns showed greater bite force values and masticatory efficiency rates compared to the other groups, and the treatment with implantsupported mandibular overdenture improved the function compared to conventional complete dentures, thus evincing that the stomatognathic system has different functional behaviors depending on the type of oral rehabilitation.

This paper presents a review and analysis of Pharmacist Care as an integrated part of the Primary Health Care System, in which quality use of medicines is directly related to quality health service and to elements for its evaluation. In our country the Basic Health Units represent the main entrance to the public health care system. The pharmaceutical services however are still linked to the care model centered in medical consultation and emergency care, with the pharmacy just satisfying their needs. Provide orientation to the users of a Basic Unit pharmacy is almost impossible because nearly all sore spots of the health system end up at the pharmacy as the final step in the care process. The solution of the problem will not be easy if the present structure of the service is maintained. Great part of the pressure resulting from the demand does not depend on the health service itself but on inclusive social policies with direct impact on the health conditions of the population. Rational use of medicines from the prescriber to the user is fundamental in this specific environment.

OBJECTIVE: To analyze the costs related to visits and drug prescription in outpatients with type 2 diabetes mellitus assisted by a pharmaceutical care service. SUBJECTS AND METHODS: A prospective and experimental study was carried out. Seventy one patients were divided into two groups: control and pharmaceutical care. Patients in the pharmaceutical care group were followed up monthly by a single clinical pharmacist. RESULTS: The pharmaceutical care group had a statistically significant reduction in costs of metformin and emergency department visits, and increased costs with their family physicians. On the other hand, the control group had a statistically significant increase of 21.3% in the general costs of treatment and visits. CONCLUSION: The pharmaceutical care group maintained the same costs related to drugs and visits, while the control group showed a significant increase in general costs. OBJETIVO: Analisar os custos relacionados a medicamentos e consultas em pacientes portadores de diabetes melito tipo 2 acompanhados por um programa de atenção farmacêutica. SUJEITOS E MÉTODOS: Estudo prospectivo e experimental foi realizado em 71 pacientes, os quais foram divididos em dois grupos: atenção farmacêutica e controle. Os pacientes do grupo atenção farmacêutica foram acompanhados mensalmente por um farmacêutico clínico. RESULTADOS: O grupo atenção farmacêutica apresentou redução estatisticamente significativa no custo da metformina e nas visitas de pronto atendimento e aumento no custo das consultas de atenção primária. Por outro lado, o grupo controle apresentou elevação estatisticamente significativa nos custos gerais de tratamento farmacológico e nas consultas em geral na ordem de 21,3%. CONCLUSÃO: O grupo atenção farmacêutica apresentou manutenção dos custos relacionados a consultas e medicamentos, enquanto o grupo controle apresentou aumento destes.

OBJECTIVE: To analyze drug prescriptions for insulin and oral antidiabetic drugs in type 1 and type 2 diabetes mellitus patients seen in the Brazilian Public Healthcare System (Unified Health System - SUS) in Ribeirao Preto, SP, Brazil. SUBJECTS AND METHODS: All the patients with diabetes seen in the SUS in the western district of Ribeirao Preto, SP, Brazil between March/2006 and February/2007 were included in the study. RESULTS: A total of 3,982 patients were identified. Mean age of the patients was 60.6 years, and 61.0% were females. Sixty percent of the patients were treated with monotherapy. Doses of oral antidiabetic drugs were lower in monotherapy than in polytherapy. Ten patients received doses of glibenclamide or metformin above the recommended maximum doses, and in elderly patients there was no reduction in drug doses. CONCLUSION: Monotherapy with oral antidiabetic drugs was the predominant procedure, and the doses were not individualized according to age. OBJETIVO: Analisar as prescrições medicamentosas dos antidiabéticos orais e insulina em pacientes portadores de diabetes melito tipo 1 e tipo 2 atendidos pelo Sistema Único de Saúde (SUS) em Ribeirão Preto, SP, Brasil. SUJEITOS E MÉTODOS: Todos os pacientes com diabetes atendidos no distrito sanitário oeste de Ribeirão Preto, SP, do SUS, entre março/2006 e fevereiro/2007, foram incluídos no estudo. RESULTADOS: Foram identificados 3.982 pacientes com diabetes. Idade média dos pacientes foi de 60,6 anos e 61,0% do gênero feminino. Sessenta por cento foram tratados com monoterapia. A dose dos antidiabéticos foi menor em monoterapia quando comparada à politerapia. Dez pacientes receberam doses de glibenclamida e metformina acima da dose máxima recomendada. Além disso, em pacientes idosos, não houve redução da dose. CONCLUSÃO: A monoterapia com antidiabéticos orais foi prevalente e não houve individualização da dose de acordo com a faixa etária.

Fungal keratitis is a serious disease that can lead to loss of vision. Unfortunately, current therapeutic options often result in poor bioavailability of antifungal agents due to protective mechanisms of the eye. The aim of this work was to evaluate the potential of a chitosan solution as well as an in situ gel-forming system comprised of poloxamer/chitosan as vehicles for enhanced corneal permeation and sustained release of fluconazole (FLU). For this, in vitro release and ex vivo corneal permeation experiments were carried out as a function of chitosan concentration from formulation containing the chitosan alone and combined with the thermosensitive polymer, poloxamer. Microdialysis was employed in a rabbit model to evaluate the in vivo performance of the formulations. The in vitro release studies showed the sustained release of FLU from the poloxamer/chitosan formulation. Ex vivo permeation studies across porcine cornea demonstrated that the formulations studied have a permeation-enhancing effect that is independent of chitosan concentration in the range from 0.5 to 1.5% w/w. The chitosan solutions alone showed the greatest ex vivo drug permeation; however, the poloxamer/chitosan formulation presented similar in vivo performance than the chitosan solution at 1.0%; both formulations showed sustained release and about 3.5-fold greater total amount of FLU permeated when compared to simple aqueous solutions of the drug. In conclusion, it was demonstrated that both the in situ gelling formulation evaluated and the chitosan solution are viable alternatives to enhance ocular bioavailability in the treatment of fungal keratitis.

A method is described for the comprehensive characterization of protein hydrolysates for enteral nutrition. It includes (1) gel filtration on a 0.9×250 cm column of Sephadex G-25F eluted with 5% acetic acid, to prepare pools; (2) amino acid analysis with and without acid hydrolysis to determine the amounts of peptide bound and free amino acids; (3) reaction with TNBS to determine the amount of NH 2 -terminal groups; and (4) calculation of number-average peptide size of pools from TNBS and amino acid data. The preparation of three hydrolysates of casein with pancreatic enzymes on the industrial scale (5000 L) is described

Baru (Dipteryx alata Vog.) is a fruit distributed throughout the Brazilian savanna and contains a seed with a high protein content, whose properties have been rarely explored. The purpose of this study was to characterize this protein, especially by isolation and quantifying its fractions and measuring some of its molecular properties.Baru seeds contain 244 g kg(-1) protein on a dry weight basis. Solubility profiles showed a preponderance of globulins. This fraction dominated the seed composition, with 61.7 wt% of the total soluble proteins. Albumins and glutelins accounted for 14 and 3.3 wt%, respectively. SDS-PAGE resolution of albumin and globulin showed main bands with molecular weights of 84 kDa and 64, 66 and 73 kDa, respectively. The total protein of the flour and the globulin showed values of in vitro digestibility of 85.59% and 90.54%, relative to casein. Total globulin produced only one chromatographic peak, both on Sepharose CL-6B gel filtration and on DEAE-cellulose ion-exchange columns, eluted at a concentration of 0.12 mol L(-1) NaCl.The baru seed had high protein content with large quantities of storage proteins. The chromatographic and solubility profiles indicate the predominance of a fraction with characteristics of a legumin-type protein.

PURPOSE: to discuss the contribution of psoralen and bergapten metabolites on psoralens toxicity. METHODS: Computational chemistry prediction of metabolic reactions and toxicophoric groups based on the expert systems Derek and Meteor. RESULTS: a total of 15 metabolites were suggested for both psoralen and bergapten based on phase 1 and 2 biotransformations until the 3rd generation. Five toxicophoric substructures were shared among psoralen, bergapten and their corresponding metabolites; one toxicophoric marker (resorcinol) was only identified in bergapten and its biotransformation products. CONCLUSION: Although the toxic effects of psoralens are well known and documented, there is little information concerning the role of their metabolites in this process. We believe this work add to the knowledge of which molecular substructures are relevant to the process of metabolism and toxicity induction, thus guiding the search and development of more effective and less toxic drugs to treat vitiligo.

To identify clinically significant drug interactions and potentially related adverse drug events associated with the use of midazolam.Retrospective data analysis was performed at a single tertiary Brazilian Teaching Hospital from an electronic database derived from the Hospital's computerized physician order entry system over 1 year. Records from patients who received injectable midazolam within a period of 24 hours before flumazenil use were selected. Patients' orders were checked for the presence of clinically significant drug interactions and for the inclusion and discontinuation of potential trigger medications for adverse drug events related to midazolam.A total of 7431 patients were exposed to midazolam, representing 28% of all patients admitted to the hospital. Twenty-six (0.35%) patients received flumazenil within 24 hours after midazolam, corresponding to more than one third of the orders for flumazenil. Clinically significant drug interactions were observed in prescriptions of drugs preceding the use of flumazenil for 23 (88%) of these patients. The most prevalent group of drug interactions were related to the prescription of central nervous system depressants (22 cases), mainly opiate agonists. Analysis of inclusion and discontinuation of drugs demonstrated that the first order for opiates preceded the use of flumazenil in 31% of the cases and, except for tramadol, all opiates were discontinued after its administration, highlighting the potential of these drugs to act as triggers for adverse drug events.Midazolam-related drug interactions are not infrequent and may conduce to serious adverse drug events, including hypotension, respiratory depression, and arrest. Efforts directed toward monitoring interactions and preventing injuries from midazolam use are expected to have a substantial impact on patient safety concerning the use of midazolam.

RESUMO: O objetivo deste trabalho foi avaliar físico-química e nutricionalmente os grãos secos de labe-labe (Lablab purpureus (L.) Sweet). Os resultados obtidos permitiram concluir que a leguminosa estudada presta-se ao processamento tradicional, possui bom nível de lisina (5,86%) com alta disponibilidade (83%), é deficiente em aminoácidos sulfurados, contém substâncias antinutricionais e não suporta o crescimento animal. PALAVRAS-CHAVE: Labe-labe; avaliação físico-química; avaliação nutricional.

RESUMO: O objetivo do presente trabalho foi verificar as possibilidades de uso na alimentação humana e/ou animal de grãos de feijão-guandu (Cajanus cajan (L) Mill sp). Mediante os resultados obtidos, observou-se que a leguminosa estudada tem possibilidades de compor a dieta alimentar do homem e/ou animais, pois, presta-se ao processamento tradicional para consumo, apresenta composição centesimal adequada, possui elevado teor de lisina com alta disponibilidade (86%) e suporta satisfatoriamente o crescimento animal (PER = 1,650). Todavia, este aproveitamento exige que se observem algumas limitações, tais como, o conteúdo insuficiente e a baixa disponibilidade de metionina e a presença de antitrípticos, lectinas e taninos. PALAVRAS-CHAVE: Faijão-guandu; avaliação físico-química e nutricional.

O sistema de saúde nacional, impulsionado por contextos econômicos restritivos, passou por uma reestruturação organizacional na década de 1990, voltada à atenção primária. Apesar das reformas, a incidência de diabetes mellitus ainda atinge elevadas proporções. Devido à alta morbi-mortalidade, a prevenção dessa morbidade tem-se tornado foco atual, fazendo-se necessário o desenvolvimento de programas eficazes e viáveis ao Sistema Único de Saúde, tais como ênfase na prevenção primária, controle da incidência e complicações da doença. Para que isso ocorra, o modelo da atenção atual prestada ao paciente deve ser modificado, priorizando a atenção primária, com a substituição do modelo médico-hegemônico por uma equipe interdisciplinar, onde o farmacêutico, como membro da equipe, possa prover seus serviços, minimizando assim impactos sociais, humanísticos e econômicos que a doença acarreta para a sociedade. O objetivo da presente revisão foi abordar a temática do diabetes mellitus e as dificuldades do controle associado à ineficácia da logística adotada, principalmente no Sistema Único de Saúde.The Brazilian Health Care System stimulated for restrictive economic contexts had passed for reorganization in the decade of 1990, directed mainly to the primary attention. Although the reforms, the incidence of diabetes mellitus still reaches epidemic levels. The diabetes prevention has become actual preoccupation due the high morbimortality that accompanies this disease, becoming necessary the development of efficient and viable programs for Brazilian Public Health system such as emphasis in the primary prevention, control of the diseases incidence and complications. To obtain this goal, the current model of attention given to the patient must be modified, prioritizing the primary attention and a replacement of the hegemonic medical model for another one, formed by an interdisciplinary team, where the pharmacist as a member could offer his/her services should occur, thus minimizing social, humanistic and economic impacts that the diabetes causes for the society. The aim of this present revision is to approach the diabetes mellitus, the difficulties for its control associated with the adopted ineffective system, mainly in the Brazilian Public Health System.

CONTEXT: The association of primary carcinoma of the ureter and lithiasis is extremely rare. We report a rare case of a primary carcinoma of the ureter with corariform calculus. CASE REPORT: 60-year-old phaeodermal female, reported a history of right-side nephritic colic, hyperthermia and pyuria during the past 20 years and had received treatment for urinary infections a number of times. The first clinical presentation was related to lithiasis and the tumor had not been shown up by excretory urography, cystoscopy or ultrasonography. Two months after the calculus had been eliminated, the patient began to have serious symptoms and a grade III transitional cell carcinoma of the ureter was discovered. Total nephroureterectomy and M.V.A.C. (Metotrexate + Vinblastina + Doxo Rubicina + Cisplatina) chemotherapy were tried unsuccessfully. In this report we emphasize the diagnostic difficulty caused by the concomitant presence of the two pathologies. In our opinion, the rapid evolution in this case is directly related to the high grade of the tumor.

Este artigo apresenta uma revisão e análise da assistência farmacêutica como parte integrante do sistema de atenção primária à saúde, no qual a qualidade do uso de medicamentos está diretamente relacionada à qualidade do serviço de saúde e aos elementos para a avaliação desta. As Unidades Básicas de Saúde constituem a principal porta de entrada do sistema de assistência à saúde estatal em nosso país. Entretanto, o vínculo do serviço farmacêutico está relacionado com o modelo curativo, centrado na consulta médica e pronto atendimento, com a farmácia apenas atendendo a essas demandas. A atividade de orientação aos usuários na farmácia das Unidades Básicas de Saúde torna-se praticamente impossível, pois na farmácia deságuam quase todas as mazelas do sistema de saúde, por estar no elo final do processo de atendimento. A solução do problema, no âmbito geral, não será simples, se mantida a forma como o serviço está estruturado, pois grande parte das pressões de demanda não depende do serviço de saúde em si, mas de políticas sociais inclusivas, as quais têm impacto direto nas condições de saúde da população. No âmbito específico, é fundamental que os gestores racionalizem a utilização dos medicamentos desde a prescrição até a utilização por parte do usuário. This paper presents a review and analysis of Pharmacist Care as an integrated part of the Primary Health Care System, in which quality use of medicines is directly related to quality health service and to elements for its evaluation. In our country the Basic Health Units represent the main entrance to the public health care system. The pharmaceutical services however are still linked to the care model centered in medical consultation and emergency care, with the pharmacy just satisfying their needs. Provide orientation to the users of a Basic Unit pharmacy is almost impossible because nearly all sore spots of the health system end up at the pharmacy as the final step in the care process. The solution of the problem will not be easy if the present structure of the service is maintained. Great part of the pressure resulting from the demand does not depend on the health service itself but on inclusive social policies with direct impact on the health conditions of the population. Rational use of medicines from the prescriber to the user is fundamental in this specific environment.

Precursor systems of liquid crystalline phase were prepared using the surfactant PPG-5-Ceteth-20, isopropyl myristate, and water; gelatin microparticles containing propolis were then added into these systems. Homogeneity of dispersion, the in-system microparticle morphology, and sedimentation behavior of each formulation were evaluated. The rheological and mechanical properties (hardness, compressibility, and adhesiveness), the work of syringing, and the propolis release profile were also evaluated. All the formulations exhibited pseudoplastic flow and thixotropy, and they displayed storage modulus, loss modulus, dynamic viscosity, and loss tangent that depended on temperature, frequency, and composition. Mechanical properties varied significantly among the formulations being affected by changes in the composition and temperature. Raising the concentration of surfactant and adding propolis microparticles significantly decreased the work of syringing. The drug release was non-Fickian (anomalous) and there was no significant difference between the tested systems in the times required for 10%, 30%, and 50% release of the initial drug loading.

The instability of polysaccharide/protein mixtures occurs because of either thermodynamic incompatibility or complexation. We studied which instability mechanism dominated given the external conditions. Therefore the effect of temperature, pH, and biopolymer concentration on the phase separation of pectin/caseinate mixtures was investigated. At pH > 6, thermodynamic incompatibility with spinodal decomposition was observed in pectin/caseinate mixtures resulting in the formation of water-in-water emulsions in intermediate stages of the phase separation process. The demixing rate of these emulsions and appearance of two macroscopic phases (lower phase enriched with caseinate and upper phase with pectin) was retarded when the pectin concentration increased or when the storage temperature decreased due to a higher viscosity of the mixtures at those conditions. As the pH of the mixture was lowered below 6, pectin accumulated in the caseinate-rich phase. Complexation of pectin and caseinate led to the formation of microparticles (approximately 3 microm), whose shape depends on the biopolymer concentration ratio and rate of acidification. These pectin/caseinate particles do not coalesce and are insensitive to salt addition. ispartof: Biomacromolecules vol:8 issue:11 pages:3345-3354 ispartof: location:United States status: published