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Mucocutaneous infections caused by Herpes simplex virus (HSV-1 and HSV-2) are characterized by the appearance of vesicles that cause pain and embarrassment to the carrier. The standard treatment is based on the use of antivirals in gels or ointments, however, relapses are common. Local anesthetics decrease the pain caused by the lesion, in addition to showing antiviral properties. Semi-solid form facilitates application and its transformation into a thin film favors the maintenance of the formulation in place, with a more discreet final aspect. The objective of this study was to develop and evaluate formulations containing anesthetics for the treatment of cold sores. For this purpose, two semi-solid film-forming formulations were developed and evaluated, containing HPMC K100, lidocaine (LIDO) and prilocaine (PRILO) combined with adjuvants, in the presence (F1T) or not (F1) of the absorption promoter Transcutol®. The mixture of PRILO and LIDO resulted in the formation of a eutectic mixture (EM), essential for penetration of drugs into the skin. The quantification of drugs was performed by HPLC (High Performance Liquid Chromatography), and Transcutol® did not influence the release of drugs from the formulation. The bioadhesiveness of the formulation was evaluate and the drugs did not impair the adhesive potential of the polymers used. The formulations were evaluated in vivo for skin irritation and did not show any negative sign on macroscopic examination. The in vivo efficacy test proved the anesthetics' ability to decrease the lesions caused by HSV-1. Thus, the proposed formulations proved to be good alternatives to the treatment of oral lesions caused by HSV-1.

Brosimum gaudichaudii Trecul, Moraceae, is a Brazilian plant species used in traditional medicine to treat vitiligo or as an additive in natural suntan lotions. Even though it is widely used in Brazil, its safety and efficacy have not been studied. In this study, the hydroalcoholic extract was standardized for its psoralen and 5-methoxypsoralen content, and its biological effects were studied in B16F10 cells. Melanin synthesis capacity of the extract was compared with synthetic psoralen and 5-methoxypsoralen in the same cell line. Safety assessment of the extract was performed by neutral red uptake, comet, and micronucleus cytome assays. The herbal extract was less cytotoxic to the B16F10 cells than pure active ingredients, psoralen, and 5-methoxypsoralen in equivalent doses. Melanin synthesis was enhanced by 300% with the extract compared with the 130% increase with psoralen and 5-methoxypsoralen. The extract prepared with the roots, as well as the synthetic compounds used as control standards, exhibited mutagenic activity on B16F10 cells. Consequently, caution has to be taken with the use of these roots for the treatment of vitiligo in popular herbal medicine.

Made available in DSpace on 2019-10-06T08:11:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Insulin (INS) is a protein that plays a crucial role in many cellular functions, including wound healing processes. However, its topical ocular administration is a challenge, mainly because of INS degradation and low retention time, which can significantly reduce its bioavailability. The objective of this work was to develop films based on silk fibroin (SF), a natural polymer with anti-inflammatory properties, containing INS aimed at the sustained release of a bioactive INS in the eye for the treatment of corneal wounds. SF films containing 100 IU/cm(2) INS and glycerin as plasticizer were prepared by casting. They were homogeneous, transparent, permeable to water vapor, with low swelling index and high mechanical resistance. Fourier transformed infrared spectroscopy and differential scanning calorimetry analyses suggested the beta-sheet/Silk II conformation of SF and the occurrence of non-covalent interactions between INS and SF. Scanning electron microscopy suggested that the INS was embedded inside the film in its native globular form. In fact, the INS released from the film maintained its native conformation, as observed by circular dichroism, in addition to conserving its biological activity in vivo, reducing the blood glycemia of Wistar rats. Sustained release, of approximately 1 IU/cm(2)/h(1/2) of INS per hour, following a burst release, suggests that the film could be effective in the recovery of injured corneal epithelium, avoiding the need for the various daily administrations. Therefore, SF films demonstrated potential to transport and release INS in a sustained manner, a promising strategy for the treatment of corneal wounds. Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Ribeirao Preto, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, Araraquara, SP, Brazil Sao Paulo State Univ, Sch Pharmaceut Sci, Araraquara, SP, Brazil FAPESP: 2014/19018-0 FAPESP: 2014/22451-7 CAPES: 2014/19018-0 CAPES: 2014/22451-7 CNPq: 162175/2014-0

The skin is the largest human organ and an important topical route. Even with some challenges, it is an important ally in medication administration, mainly because it is painless and easy-to-apply. Semisolid formulations are the most used dosage forms for drug administration via this delivery route and can be optimized when transformed into a film, favoring on-site maintenance, and promoting drug permeation. However, in situ film-forming systems are difficult to assess and characterize using Franz-type diffusion cells once this apparatus is ideal to formulations without transition phases. The present study proposed a different method to characterize these formulations and provide complementary data on drug and penetration enhancer behaviors, as close as possible to real application conditions. This characterization method allowed us to analyze drug concentration on three necessary occasions: remaining in the polymer film, stratum corneum using adhesive tape, and skin to check where drugs will have a desirable effect. As a proof-of-concept, the proposed ex vivo permeation method was used to evaluate a film-forming system containing lidocaine and prilocaine. We could also evaluate transition phases of drug compositions and quantify drugs at key times after application. Hence, the developed method may be used to provide complementary data to the Franz diffusion cell method, in terms of drug and penetration enhancer behaviors incorporated into film-forming delivery systems.

Infections caused by the herpes simplex virus 1 (HSV-1), commonly called herpes simplex labialis (HSL), are a public health problem, reaching around 40% of the world's population. Thus, the search for effective therapeutic alternatives in the control of the limitations caused by this virus during the stages of evolution of the disease, is necessary, since they have a direct impact on the quality of life of the patients. The aim of the present study was to evaluate the efficacy of the in situ film precursor semisolid composition in the treatment of herpes simplex lesions in human HSV-1. Ninety-eight (n = 98) patients with HSV-1 were used for this study. The initial exclusion criteria left 81 patients to be considered in the present study. Three applications were performed, the first at time zero (T0) and the other two at 8 and 16 hours, after initial application (T8 and T16). Photographs were taken in the first appointment and 24 and 72 hours after the last application. After the three periods, each patient received a total amount of 90 mg of anesthetic and the prognosis of the patients was followed for 6 months and 1 year after the application. Frequency analysis showed that 40.3% of patients had remission of symptoms 24 hours after the last application. For the present study, the film presented a positive therapeutic potential and an esthetic benefit that is absent in the current products (ointments and gels). The invent presents dosage convenience (only three applications in a 24-hour period) and a low production cost, with a much shorter healing time than that reported using topical antiretrovirals.

The treatment of vitiligo includes the combination of psoralens and ultraviolet type A exposure. Psoralens belong to a group of natural furanocoumarins that cause the skin to become sensitive temporarily to ultraviolet type A. The aim of this study was to develop a physiologically based pharmacokinetic model of 5-MOP from Brosimum gaudichaudii to support psoralen and ultraviolet type A therapy. A study of rats was used to establish and validate rat tissue distribution. The same chemical-specific parameters used in the rat model were also employed in the human model to project human pharmacokinetics. The highest exposures in the rats were in the brain and skin. Following a single dose of 1.2 mg/kg 5-MOP in humans, the model predicted a maximum concentration of 20 ng/mL and an area under the curve of 125 ng.h/mL, matching clinical results. The half-maximum melanogenesis concentrations in B16F10 cells were 29.5, 18.5, 11.5, and 6.5 ng/mL for synthetic 5-MOP, synthetic 5-MOP with ultraviolet type A, B. gaudichaudii alone, and B. gaudichaudii plus ultraviolet type A, respectively. Physiologically based pharmacokinetic model prediction in humans supported a once-every-two-day regimen for optimal melanin production. This type of framework can be applied to support strategies for dose selection and to investigate the impact of drugs on melanocyte recovery.

Objective To evaluate a pilocarpine spray as a treatment for xerostomia in patients treated with radiotherapy (RT) for head and neck cancer (HNC). Methods This was a placebo-controlled, double-blind, crossover clinical trial of patients complaining of dry mouth after RT for HNC. Forty patients were randomly assigned to either placebo or pilocarpine (1.54%) spray and instructed to use three times a day for 3 months. After 1-month washout period, patients were crossed over to receive placebo or pilocarpine. The assessments were salivary flow (Stimulated Whole Saliva Flow - SWSF), xerostomia (Xerostomia Inventory - XI), and quality of life (QoL/Oral Health Impact Profile - OHIP-14), assessed at baseline, 1 hr (only SWSF), and at 1, 2, and 3 months of treatment. Results Posttreatment SWFS was not statistically different between pilocarpine and placebo regardless of the treatment sequence (paired T test; p > .05), except for the SWFS rates at 2 months after therapy. When comparing pilocarpine with placebo in the time points, there was no significant difference (p > .05) for QoL or XI. Significant differences in improvement in QoL and xerostomia experience appeared along time for pilocarpine group. Conclusion The topical application of pilocarpine spray tested was similar to placebo on SWSF assessments in patients treated with RT for HNC.

The aim of this work was to develop a mucoadhesive iontophoretic patch for anesthetic delivery in the buccal epithelium. The patch was comprised of three different layers, namely i) drug release (0.64 cm2); ii) mucoadhesive (1.13 cm2); and iii) backing (1.13 cm2). Prilocaine and lidocaine hydrochlorides were used as model drugs (1:1 ratio, 12.5 mg per unit). An anode electrode (0.5 cm2 spiral silver wire) was placed in between the drug release and mucoadhesive/backing layers to enable iontophoresis. Surface microscopy; mechanical and in vitro mucoadhesive properties; drug release kinetics and mechanism; and drug permeation through the porcine esophageal epithelium were assessed. Topographic analysis evidenced differences in the physical structures for the several layers. All layers presented suitable handling properties i.e., flexibility, elasticity and resistance. Both the release and mucoadhesive layers presented features of a soft and tough material, while the backing layer matched the characteristics of a hard and brittle material. A synergy between the drug release and mucoadhesive layers on the mucoadhesive force and work of adhesion of the tri-layered patch was observed. Passive drug release of both drugs fitted to First-order, Hixson-Crowell and Weibull kinetic models; and the release mechanism was attributed to anomalous transport. Iontophoresis remarkably enhanced the permeation of both drugs, but mainly prilocaine through the mucosa as evidenced by the permeability coefficient parameter (3.0-fold). The amount of these amino amide salts retained in the mucosa were also equally enhanced (4.7-fold), while the application of a tiny constant electric current (1 mA·cm−2·h−1) significantly decreased the lag time for lidocaine permeation by about 45%. In view of possible in vitro / in vivo correlations, the buccal iontophoretic patch displays a promising strategy for needle-free and patient-friendly local anesthesia in dentistry.

The effect of a drug-delivery system containing antibacterial metronidazole (MDZ) prescribed for periodontitis on supragingival biofilm was evaluated, and possible interference by this biofilm in the drug release profile was investigated. Streptococcus mutans biofilms were grown and exposed to a controlled-release formulation of MDZ or the same formulation without MDZ (vehicle control). Untreated biofilms were used as a negative control (NC). Biofilms and culture medium (containing detached cells) were collected 24, 48, 72, and 96 h after first exposure to treatments. The biomass of the MDZ group was lower than that of the NC group at all times. Although MDZ yielded low drug-release rates in the presence of the biofilm, it was sufficient for reducing viability for 24 h and affecting bacterial metabolism for 48 h. These results suggest that MDZ appears to destabilize supragingival biofilm. This biofilm may interfere with MDZ release from the formulation.

(1) Background: For any antibacterial oral formulation to be successful, it must present effects in the presence of biofilms. Therefore, our aim is to analyze the drug release and the antibiofilm effects of a semi-solid formulation containing chlorhexidine (CHX) in the presence of pathogenic biofilms. (2) Methods: The biofilms of Streptococcus mutans (n = 6) or Porphyromonas gingivalis (n = 3) were formed for 6 and 4 days, respectively, being exposed to: 1) a CHX system or 2) vehicle control without CHX. A group without treatment was included as negative control. The acidogenicity, CHX quantification and bacterial viability were determined. A dissolution assay in a buffer and culture medium in the absence of bacteria was also performed. (3) Results: Although the CHX quantification in the culture medium of both biofilms was lower compared to the buffer (p &lt, 0.05) and the culture medium in the absence of bacteria, the CHX system was able to display antibiofilm effects until 96 h for the S. mutans biofilms (p &lt, 0.05) and 72 h for the P. gingivalis biofilms (p &lt, 0.05). (4) Conclusions: The experimental formulation is able to extend chlorhexidine effects, even in challenging conditions such as in the presence of bacteria, allowing the in vitro control of cariogenic biofilms for 4 days and periodontopathogenic biofilms for 3 days.

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, 110A) 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 Wiley & Sons, Ltd.

The methodologies used to calculate piled raft foundations are normally more complex than conventional foundations due to the large number of variables involved in the problem. In the conventional block, the interaction variables considered are only between the pile and the soil. In the piled raft, all the interaction effects must be considered, as follows: plate-soil, plate-piles and piles-soil, simultaneously. The Finite Element Method (FEM) has proven to be a useful tool in analyzing these types of problems. This study aims at assessing the behavior of piled rafts using the Cesar-LCPC numerical tool, version 4.0, which is based on the finite element method. Literature cases of rafts supported by 9, 15 and 16 piles were analyzed. The results obtained were compared with analysis methods presented in the bibliography. The following parameters were assessed: relative spacing (S/D), relative length (L/D), relative stiffness between piles and the soil (KPS), and settlement of piles and the raft. The spacing between piles has a significant influence on load distribution between piles and the raft. Very small spacing provides stiffness to the foundation, which then functions as a conventional pile foundation, in which only the piles absorb the load from the superstructure. The larger the L/D ratio, the lower the settlement and for a given modulus of elasticity of the pile, the increase in relative stiffness (KPS) causes an increase in settlement. In all analyses, the data obtained corroborated the results presented by other methods published in the literature.

This paper describes the method development for sulfadimethoxine (SDM) and ormetoprim (OMP) quantitation in fish feed and fish fillet employing LC-MS/MS. In order to assess the reliability of the analytical method, valuation was undertaken as recommended by guidelines proposed by the Brazilian Ministry of Agriculture. The calibration curve for the quantification of both drugs in feed showed adequate linearity (r > 0.99), precision (CV 0.99), precision (CV < 16%) and trueness around 100%, with CCα < 100.2 ng g–1 and CCβ < 100.4 ng g–1. With a goal of avoiding the risk of drug leaching from feed into the aquatic environment during fish medication via the oral route, different procedures for drug incorporation into feed were evaluated. Coating feed pellets with ethyl cellulose polymer containing the drug s...

This paper describes the development of analytical methods for the quantification of albendazole (ABZ) in fish feed and ABZ and its main known metabolites (albendazole sulfoxide, albendazole sulfone and albendazole aminosulfone) in fish fillet employing LC-MS/MS. In order to assess the reliability of the analytical methods, evaluation was undertaken as recommended by related guides proposed by the Brazilian Ministry of Agriculture for analytical method validation. The calibration curve for ABZ quantification in feed showed adequate linearity (r > 0.99), precision (CV 0.99) for all analytes, precision (CV

Beta-caryophyllene (BCP) is a phytocannabinoid whose neuroprotective activity has been mainly associated with selective activation of cannabinoid-type-2 (CB2) receptors, inhibition of microglial activation and decrease of inflammation. Here, we addressed the potential of BCP to induce neuritogenesis in PC12 cells, a model system for primary neuronal cells that express trkA receptors, respond to NGF and do not express CB2 receptors. We demonstrated that BCP increases the survival and activates the NGF-specific receptor trkA in NGF-deprived PC12 cells, without increasing the expression of NGF itself. The neuritogenic effect of BCP in PC12 cells was abolished by k252a, an inhibitor of the NGF-specific receptor trkA. Accordingly, BCP did not induce neuritogenesis in SH-SY5Y neuroblastoma cells, a neuronal model that does not express trkA receptors and do not respond to NGF. Additionally, we demonstrated that BCP increases the expression of axonal-plasticity-associated proteins (GAP-43, synapsin and synaptophysin) in PC12 cells. It is known that these proteins are up-regulated by NGF in neurons and neuron-like cells, such as PC12 cells. Altogether, these findings suggest that BCP activates trka receptors and induces neuritogenesis by a mechanism independent of NGF or cannabinoid receptors. This is the first study to show such effects of BCP and their beneficial role in neurodegenerative processes should be further investigated.

Due to the considerable increase in public expenditure with health issues, mainly regarding drugs, several countries, including Australia and England, have already implemented, or are in the process of discussing the adoption of measures to ensure the quality of health care provided to the population. One of the less harmful strategies, rarely used in Brazil, is the adoption of economic techniques applied to health, more specifically, pharmacoeconomic analysis. This paper aims to contribute to the dissemination of concepts and techniques of economic analysis with a view to incorporate these into policy decisions of expenditure rationalization and the search for clinical efficiency. It includes a literature review covering the types of costs and benefits in health issues, the methodologies of pharmacoeconomic analysis, cost-minimization, cost-benefits, cost-effectiveness and cost-utility analysis, as well as its main characteristics, advantages, disadvantages and applicability.Em razão do aumento considerável no gasto público com saúde, principalmente no que tange a medicamentos, vários países, como Austrália e Inglaterra, já implementaram ou estão em fase de discussão da adoção de medidas visando garantir a qualidade do atendimento prestado à população. Uma das estratégias menos danosas, mas ainda incipiente no Brasil, é a adoção de técnicas de análises econômicas, mais especificamente, a avaliação farmacoeconômica. Neste contexto, este trabalho visa contribuir com a disseminação dos conceitos e técnicas de análises econômicas com a perspectiva de que possam ser incorporadas nas decisões políticas de racionalização dos gastos e na busca da eficiência clínica. Para tanto, este artigo apresenta uma revisão bibliográfica contemplando os tipos de custos e benefícios em saúde, as metodologias de análise farmacoeconômicas, quais sejam: análise de minimização de custo, de custo-benefício, de custo-efetividade e de custo-utilidade, assim como suas principais características, vantagens, desvantagens e aplicabilidades.

Made available in DSpace on 2013-08-12T19:03:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-01 Made available in DSpace on 2013-09-30T18:06:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:24:52Z No. of bitstreams: 0 Made available in DSpace on 2014-05-20T13:24:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) A solubilidade de fármacos ainda é um dos principais desafios no desenvolvimento de formulações farmacêuticas. As dispersões sólidas (DS) apresentam grande potencial para melhorar a solubilidade de fármacos. O praziquantel é o fármaco de primeira escolha no tratamento da esquistossomose, contudo a baixa solubilidade em água restringe seu uso à administração pela via oral. Apesar da baixa solubilidade, o PZQ é bem absorvido através do trato gastrintestinal, mas doses orais elevadas são requeridas para garantir concentrações suficientes de fármaco para o tecido alvo. O objetivo deste estudo foi melhorar a solubilidade, a dissolução e avaliar a absorção do PZQ. As DS foram formuladas com óleo de castor hidrogenado - PEG 60 (CR-60), pelo uso dos métodos de fusão e evaporação do solvente. PZQ puro, mistura física (MF) e DS de CR-60-PZQ (1:2; 1:1; 2:1) foram comparados quanto à solubilidade, dissolução e absorção intestinal. Os resultados experimentais mostraram aumento na solubilidade, na taxa de dissolução e na absorção intestinal do PZQ nas DS. A solubilidade do PZQ foi maior em meio ácido, mostrando uma dependência do pH. O aumento na solubilidade do PZQ nas DS com CR-60 foi atribuída a fatores como aumento da molhabilidade, solubilização local, redução granulométrica e redução da cristalinidade ou, ainda, a ocorrência de uma solução sólida intersticial. The solubility behavior of drugs remains one of the most challenging aspects in formulation development. Solid Dispersion (SD) has tremendous potential for improving drug solubility. Although praziquantel (PZQ) is the first drug of choice in the treatment of schistosomiasis, its poor solubility has restricted its delivery oral route. In spite of its poor solubility, PZQ is well absorbed in the gastrointestinal tract, but large doses are required to achieve adequate concentration at the target sites. The aim of this study was to improve the solubility and dissolution rate of PZQ and to evaluate its intestinal absorption. SDs were formulated with PEG-60 castor oil hydrogenated (CR-60) using a fusion and evaporation method. Pure PZQ and physical mixtures (PM) and PZQ-CR-60 (2:1; 1:1; 1:2 ratios) were compared as regards their solubility, dissolution and intestinal absorption. The experimental results demonstrated the improvement in the solubility, dissolution rate and intestinal absorption. In addition, the solubility behavior showed pH dependency and that the solubility of PZQ was slower in acidic medium than in neutral and basic mediums. The increase in PZQ solubility of the SD with the CR-60 could be attributed to several factors such as improved wettability, local solubilization, drug particle size reduction and crystalline or, interstitial solid solution reduction. Univ Sorocaba, Curso Farm, Dept Pharmaceut Sci, BR-18023000 Sorocaba, SP, Brazil Univ Metodista Piracicaba, Fac Hlth Sci, Dept Pharm, Piracicaba, Brazil São Paulo State Univ Julio de Mesquita Filho, Fac Pharmaceut Sci Araraquara, Dept Drugs & Pharmaceut, São Paulo, Brazil Univ São Paulo, Dept Pharmaceut Sci Ribeirao Preto, BR-05508 São Paulo, Brazil São Paulo State Univ Julio de Mesquita Filho, Fac Pharmaceut Sci Araraquara, Dept Drugs & Pharmaceut, São Paulo, Brazil

Objective To evaluate the efficiency of pharmaceutical care on the control of clinical parameters, such as fasting glycaemia and glycosylated haemoglobin in patients with Type 2 Diabetes mellitus. Setting This study was conducted at the Training and Community Health Centre of the College of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil. Methods A prospective and experimental study was conducted with 71 participants divided in two groups: (i) pharmaceutical care group (n=40), and (ii) the control group (n=31). The distribution of patients within these groups was made casually, and the patients were monitored for 12 months. Main outcome measure: Values for fasting glycaemia and glycosylated haemoglobin were collected. Results Mean values of fasting glycaemia in the pharmaceutical care group were significantly reduced whilst a small reduction was detected in the control group at the same time. A significant reduction in the levels of glycosylated haemoglobin was detected in patients in the pharmaceutical care group, and an average increase was observed in the control group. Furthermore, the follow-up of the intervention group by a pharmacist contributed to the resolution of 62.7% of 142 drug therapy problems identified. Conclusion In Brazil, the information provided by a pharmacist to patients with Type 2 Diabetes mellitus increases compliance to treatment, solving or reducing the Drug Therapy Problem and, consequently, improving glycaemic control.

Phenylketonuria (PKU) is the most common of all aminoacidopathies and is caused by autosomal recessive deficiency of the hepatic phenylalanine hydroxylase system. The diagnosis of PKU should be multifactorial and based on a protein overload test that reveals increased plasma phenylalanine levels during the ingestion of a normal diet, a phenylalanine tolerance test, and in vitro and in vivo activity of the liver enzyme. An individualized diagnosis that characterizes the severity of the disease in each patient provides objective and effective criteria for the dietary treatment of each particular case.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:41:06Z No. of bitstreams: 1 S1516-93322006000100004.pdf: 210055 bytes, checksum: f630f3dfde6e34089b296c3321ae19a4 (MD5) Made available in DSpace on 2013-08-22T18:41:06Z (GMT). No. of bitstreams: 1 S1516-93322006000100004.pdf: 210055 bytes, checksum: f630f3dfde6e34089b296c3321ae19a4 (MD5) Previous issue date: 2006-03-01 Made available in DSpace on 2013-09-30T18:07:26Z (GMT). No. of bitstreams: 2 S1516-93322006000100004.pdf: 210055 bytes, checksum: f630f3dfde6e34089b296c3321ae19a4 (MD5) S1516-93322006000100004.pdf.txt: 81135 bytes, checksum: 9a30f268c9efc1928a23c537c13f5b1d (MD5) Previous issue date: 2006-03-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:25:17Z No. of bitstreams: 2 S1516-93322006000100004.pdf: 210055 bytes, checksum: f630f3dfde6e34089b296c3321ae19a4 (MD5) S1516-93322006000100004.pdf.txt: 81135 bytes, checksum: 9a30f268c9efc1928a23c537c13f5b1d (MD5) Made available in DSpace on 2014-05-20T13:25:17Z (GMT). No. of bitstreams: 2 S1516-93322006000100004.pdf: 210055 bytes, checksum: f630f3dfde6e34089b296c3321ae19a4 (MD5) S1516-93322006000100004.pdf.txt: 81135 bytes, checksum: 9a30f268c9efc1928a23c537c13f5b1d (MD5) Previous issue date: 2006-03-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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. Universidade de São Paulo Faculdade de Ciências Farmacêuticas de Ribeirão Preto Departamento de Ciências Farmacêuticas Universidade de São Paulo Departamento de Materiais Dentários e Prótese Faculdade de Odontologia de Ribeirão Preto Universidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Fármacos e Medicamentos Universidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Fármacos e Medicamentos

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

Ethanol consumption has a toxic effect on the epithelium of the small bowel, but enterocyte maturity is very difficult to measure under these circumstances. However, when ethanol intake is combined with enterectomy, enterocyte immaturity is greater, permitting an easier separation of these two effects. In a group of rats (13 male Wistar rats weighing approximately 220 g) fed a liquid diet containing 35% ethanol for 4 weeks after resection of the proximal jejunum, the residual small intestine brush border maltase, sucrase, and lactase activities were similar to those of a pair-fed control group (13 animals). However, alkaline phosphatase activity was decreased in the mucosa and in the enterocyte brush border, probably because of the lower activity of this enzyme in the jejunum-ileum remnant of the alcoholic group.

A gestação de alto risco apresenta maior probabilidade de evolução desfavorável e está relacionada a fatores socioeconômicos, demográficos e de ordem médica. A crescente necessidade de medicamentos por gestantes de alto risco e o potencial teratogênico destes tornam os estudos epidemiológicos indispensáveis para fornecer dados para subisidiar medidas que garantam o uso racional desses medicamentos, prevenindo efeitos indesejáveis. Este estudo pretende descrever o perfil farmacoepidemiológico das gestantes de alto risco no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP) e correlacionar a utilização dos medicamentos com suas características socioeconômicas, demográficas e clínicas. Uma amostra de 386 gestantes foi entrevistada entre maio de 2014 e outubro de 2015. Dados socioeconômicos e demográficos; de acesso a serviços de saúde; sobre a gravidez; hábitos relacionados à saúde e informações sobre medicamentos e correlatos foram coletados. A idade média foi 28,7 anos (DP 6,2) e a mediana da renda per capita foi R$ 600,00 (IQ 550,00). A maioria das mulheres era branca (47,7%), possuía mais de nove anos de estudo (69,7%), não exercia atividade remunerada (54,7%), era casada ou morava com companheiro (76,9%), não possuía plano de saúde privado (87,6%), não planejou a gestação (61,9%), não era primigesta (68,8%), tinha filhos (55,7%), não teve aborto prévio (70,7%), confirmou a gestação (88,6%) e iniciou o pré-natal (86,8%) no primeiro trimestre, não fazia acompanhamento com outro médico além do ginecologista (75,1%) ou com outro professional de saúde (75,6%), recebeu orientações sobre o risco do uso de medicamentos durante a gestação (58%) e não era aderente à farmacoterapia (63%). Os diagnósticos mais prevalentes entre as entrevistadas foram hipertensão arterial (20,5%), diabetes mellitus (19,7%), obesidade (14,8%) e infecção no trato urinário (9,6%). A minoria consumia álcool (6%), fumava (8,8%), tomava café (39,6%), consumia adoçantes (14,2%), utilizava tinturas/produtos químicos capilares (9,6%), plantas medicinais (26%), praticava exercícios físicos (9,3%) e automedicação (12,7%). O consumo de medicamentos foi relatado por 99,7% das entrevistadas, com uma média de 5,1 (DP 2,1) por mulher. Os medicamentos mais utilizados pelas gestantes foram antianêmicos (88,9%), analgésicos (63,2%), antibacterianos de uso sistêmico (26,7%), medicamentos para distúrbios gastrintestinais (20,2%), anti-histamínicos de uso sistêmico (19,7%), anti-hipertensivos (19,4%), medicamentos para desordens relacionadas à acidez (18,1%), antinfecciosos e antissépticos ginecológicos (17,4%) e vitaminas (16,8%). De acordo com as categorias de risco para uso na gestação da Food and Drug Administration (FDA), 2,5% dos medicamentos utilizados são da categoria A, 25% da B, 35% da C, 11,3% da D e 1,2% da X. Segundo a classificação de risco de Briggs; Freeman e Yaffe (2015), a maioria dos medicamentos são classificados nas categorias \"compatível\" (25,6%) e \"dados humanos sugerem baixo risco\" (10,6%). Na categoria \"contraindicado\", encontram-se 10% dos medicamentos. Não foram encontradas evidências de associação entre o número de medicamentos utilizados pelas gestantes e as demais características estudadas. Os dados obtidos neste estudo podem contribuir para o desenvolvimento de estratégias para melhorar o atendimento e o uso racional de medicamentos pelas gestantes de alto risco, aumentando a qualidade de vida desta população High risk pregnancy is more likely to be unfavorable and is related to socioeconomic, demographic and medical factors. The increasing need for medicines by high-risk pregnant women and its teratogenic potential make epidemiological studies indispensable to provide data to subsidize measures that guarantee the rational use of these drugs, preventing undesirable effects. This study aims to describe the pharmacoepidemiological profile of high-risk pregnant women at the Clinical Hospital of the Faculty of Medicine of Ribeirão Preto of the University of São Paulo (HCFMRP-USP) and to correlate the use of medicines with their socioeconomic, demographic and clinical characteristics. A sample of 386 high-risk pregnant women was interviewed between May 2014 and October 2015. Socioeconomic and demographic data; access to health services data; pregnancy data; health-related habits data and medicines and correlated data were collected. The mean age was 28.7 years (SD 6.2) and the median per capita income was R$ 600.00 (IQ 550.00). The majority of the women were white (47.7%), had more than nine years of study (69.7%), were not emplyed (54.7%), were married or lived with a partner (76.9%), did not have a private health plan (87.6%), did not plan the pregnancy (61.9%), were not primigravida (68.8%), had children (55.7%), had no previous abortion (70.7%), confirmed gestation (88.6%) and started prenatal care (86.8%) in the first trimester, did not follow up with another physician other than the gynecologist (75.1%) or another health professional (75.6%), received guidance on the risk of using medication during pregnancy (58%) and was not adherent to pharmacotherapy (63%). The most prevalent diagnoses among the interviewees were hypertension (20.5%), diabetes mellitus (19.7%), obesity (14.8%) and urinary tract infection (9.6%). The minority consumed alcohol (6%), smoked (8.8%), drank coffee (39.6%), consumed sweeteners (14.2%), used tinctures/chemical hair products (9.6%), medicinal plants (26%), practiced physical exercises (9.3%) and self-medication (12.7%). Consumption of medicines was reported by 99.7% of the interviewees, with an average of 5.1 (SD 2.1) per woman. The medicines most used by pregnant women were antianemics (88.9%), analgesics (63.2%), systemic antibacterials (26.7%), medications for gastrointestinal disorders (20.2%), antihistamines (19.7%), antihypertensives (19.4%), medications for acidity-related disorders (18.1%), gynecological anti-infectives and antiseptics (17.4%) and vitamins (16.8%). According to the Food and Drug Administration (FDA) pregnancy risk categories, 2.5% of the drugs used are of category A, 25% of B, 35% of C, 11,3% of D and 1.2% of X. According to Briggs, Freeman and Yaffe\'s risk classification (2015), most medicines are classified in the categories \"compatible\" (25.6%) and \"human data suggest low risk\" (10.6%). In the \"contraindicated\" category, there are 10% of the medicines used. No evidence of association was found between the number of medications used by pregnant women and the other characteristics studied. The data obtained in this study may contribute to the development of strategies to improve care and rational use of medications by high-risk pregnant women, increasing the quality of life of this population

Os medicamentos representam uma conquista revolucionária do homem para a prevenção de doenças crônicas e agudas. Os riscos superam os benefícios quando inadequadamente empregados. Utilização irracional e erros que podem causar eventos e reações adversas são responsáveis anualmente por mais de 100 mil mortes, de 4ª a 6ª causa de morte somente nos Estados Unidos. Com a implementação do sistema de dispensação de medicamentos por dose unitária em hospitais, a administração de doses erradas foi reduzida em mais de 80%. A inadequada adesão ao tratamento das doenças crônicas é um problema mundial de grande magnitude. Nos países desenvolvi¬dos a adesão média é de 50% e nos países em desenvolvimento, este percentual é ainda menor. O presente estudo teve como objetivo desenvolver um Sistema de Dispensação de Medicamentos com Controle de Uso (SDMCU) para pacientes do município de Luiz Antônio-SP que usam cinco ou mais medicamentos diferentes continuamente. Empregaram-se cartelas e sachês personalizados e individualizados visando a utilização racional dos medicamentos com efetiva adesão ao tratamento farmacológico. Esperou-se a prevenção e redução dos problemas relacionados aos medicamentos contribuindo para o aprimoramento da qualidade da assistência à saúde da população. Foram entrevistados e acompanhados 24 pacientes por um período de 4 meses. Neste período foram recolhidos as cartelas e os sachês usados. Foram também mensurados parâmetros clínicos antes e após a implantação do SDMCU como métodos de medida de aderência.. Os parâmetros clínicos mensurados foram pressão arterial, glicemia, hemoglobina glicosilada, colesterol e triglicérides. Teste de Morisky e Green foi usado antes e após o SDMCU para avaliar o grau de adesão ao tratamento farmacológico. Também foram aplicados instrumentos para avaliar o grau de satisfação dos usuários da farmácia municipal de Luiz Antônio SP e do SDMCU. Antes do SDMCU 100% dos pacientes foram considerados como não aderentes pelo Critério 2 do Teste de Morisky e Green. Após o SDMCU, do total de pacientes, 33,3% foram considerados como não aderentes e 66,7% foram considerados aderentes pelo Critério 2. Pelo Critério 1, os com menor adesão contaram 0% e os com maior adesão 100%. O grau de satisfação dos pacientes com a farmácia municipal foi baixo; numa escala de 0 a 8 pontos apenas 20,8% dos entrevistados tiveram a pontuação máxima de 5. Em relação ao SDMCU 87,5% (n=21) obtiveram pontuação máxima, ou seja, estavam muito satisfeitos com o novo método de dispensação de medicamentos. Antes da intervenção apenas 3 (12,5%) e 9 (37,5%) pacientes apresentavam pressão arterial sistólica e diastólica normal respectivamente; após o uso do SDMCU esses números passaram a 13 (54,2%) e 21 (87,5%) respectivamente. No total 10 (41,7%) pacientes obtiveram uma melhora na pressão arterial sistólica e 12 (50%) obtiveram uma melhora na pressão diastólica. A glicemia que estava normal (abaixo do limite) em 11 (45,8%) pacientes antes do SDMCU passou para 23 (95,8%) pacientes após a intervenção, ou seja, 12 (50%) obtiveram uma diminuição no nível glicêmico. Apenas 2 (15,4%) pacientes dos 9 (69,2%) apresentavam valores de hemoglobina glicosilada acima de 7% antes do SDMCU obtiveram um nível abaixo desse limite após o SDMCU, porém 5 (38,46%) pacientes dos 13 (100%) diabéticos tiveram uma redução de mais de 1% no valor da A1c. Dos 24 pacientes acompanhados apenas 4 (16,7%) tinham um valor de colesterol acima da referência; após a intervenção esse número passou a ser de 1 (4,17%) paciente. Os valores de triglicérides melhoraram em 10 (41,7%) pacientes; de 16 (66,7%) com valores acima da referência, antes do SDMCU, apenas 6 (25%) continuaram com os mesmos números após a intervenção. A simplificação da terapia com menos horários de tomadas ao dia ajudou os pacientes a lembrarem de tomar seus medicamentos e a serem menos descuidados quanto ao horário de tomá-los. O SDMCU mostrou-se eficaz na adesão ao tratamento farmacológico baixando os níveis dos parâmetros clínicos e satisfazendo as necessidades individuais dos pacientes. Medicines are a revolutionary conquest of man for the prevention of acute and chronic diseases. Risks outweigh benefits when used improperly. Irrational utilization and errors that can cause adverse reactions and/or events are responsible annually for more than 100 thousand deaths, been the 4th to 6th leading cause of death only in the United States. With the implementation of medication unit dosis dispensing systems in hospitals the administration of wrong dose was reduced by over 80%. The poor adherence to treatment of chronic diseases is a worldwide problem of great magnitude. In developed countries the mean average is around 50% and in developing countries, this percentage is even lower. This study aimed to develop a medication system for dispensing and controlling use (SDMCU) for patients that use five or more different drugs, continuously, in the municipality of Luiz Antônio-SP. Medications blisters and sachets personalized and individualized were prepared in order to accomplish rational use of medicines with an effective pharmacological treatment. It was expected prevention and reduction of drugs related problems (DRP) as a contribution to improve the population quality of healthcare. We have interviewed 24 patients with follow up for a 4-month period. At this time used blisters and sachets were collected. It was also measured clinical parameters before and after the implementation of SDMCU as a method to estimate adhesion. The clinical parameters determined were blood pressure, blood glucose, glycosylated hemoglobin, cholesterol and triglycerides. Morisky and Green Test was used before and after use of SDMCU to assess the grade of adherence to pharmacological treatment. Instruments were also used to assess the degree of satisfaction of SDMCU users and Luiz Antonio´s healthcare unit pharmacy. Before the SDMCU 100% of patients were considered as non-adherent by Criterion 2 of the Morisky and Green Test. After use of SDMCU, 33.3% out of total patients were considered as non-adherent and 66.7% were considered adherent by Criterion 2. By Criterion 1 patients with higher adherence accounted for 100%. The patients degree of satisfaction with local pharmacy was low, on a scale of 0 to 8 points, only 20.8% of respondents had scored the maximum of 5. On the SDMCU 87.5% (n = 21) have obtained maximum scores, ie were very pleased with the new system of medicines dispensing. Before the intervention only 3 (12.5%) and 9 (37.5%) had normal systolic and diastolic blood pressure respectively. After the use of SDMCU these numbers have reached 13 (54.2%) and 21 (87, 5%) respectively. Overall, 10 (41.7%) patients have achieved an improvement in systolic blood pressure and 12 (50%) have achieved an improvement in diastolic pressure. In 11 (45.8%) patients, before the use of SDMCU, the blood glucose was normal (below the limit). After the intervention, 23 (95.8%) patients had normal levels of glucose in the blood. It means that 12 (50%) have achieved a decrease in glucose level to the normal. Glycosylated hemoglobin in only 2 (15.4%) out of 9 patients (69.2%) had a value above 7% before the SDMCU had achieved a level below this limit after SDMCU. In 5 (38.46%) patients out of 13 (100%) had a reduction of more than 1% in the value of A1c. Only 4 (16.7%) out of 24 patients had a value of cholesterol above the reference at the beginning of the study. After the intervention it has rested only one (4.17%) patient with cholesterol above normal level. The values of triglycerides improved in 10 (41.7%) patients, 16 (66.7%) with values above the reference before the SDMCU, only 6 (25%) continued with the same numbers after the intervention. Simplification of medication use practice, with less frequency daily, for taken them, have helped patients to remember to take their medications and to be more careful about the time of taking them. The SDMCU was effective pharmacological treatment by normalizing the levels of clinical parameters and satisfying the needs of individual patients.

A farmacoterapia complexa com múltiplos medicamentos aumenta a probabilidade de interações medicamentosas (IM) e eventos adversos a medicamentos(EAM) em pacientes de unidade de terapia intensiva (UTI). Este estudo teve como objetivos: analisar e classificar as IM potenciais dos tipos fármaco-fármaco e fármaco-nutrição enteral e os EAM detectados, durante a internação de pacientes, na UTI de um hospital de ensino, identificar os EAM relacionados a IM e investigar os fatores associados com IM e EAM. O estudo transversal, correlacional, retrospectivo investigou 299 prontuários de pacientes internados por cinco ou mais dias na UTI. As IM potenciais foram identificadas e classificadas empregando o software Drug Reax. Investigou-se IM em prescrições de três momentos: 24 horas de internação, mediana da internação e alta. Os EAM foram identificados empregando o método de monitorização intensiva e também critérios de rastreabilidade de EAM. Os EAM foram classificados em relação à causalidade e à gravidade Os dados foram analisados empregando análise descritiva, univariada e regressão logística múltipla. A maioria da casuística era do sexo feminino (50,5%) e com mediana de idade de 57 anos. Em 24 horas a prevalência de pacientes com IM potenciais foi 68,6%. A maior frequência de pacientes com IM potenciais foi 73,9% na mediana da internação. Na alta detectou-se que 69,6% dos pacientes apresentaram IM potenciais. Cerca de 99% das interações era do tipo fármaco-fármaco. As interações fármaco-nutrição enteral foram mais frequentes em prescrições de pacientes em alta. Em relação a gravidade a maioria das IM eram graves e moderadas. O número de medicamentos administrados e o uso de medicamentos do sistema cardiovascular foram os fatores associados com a ocorrência de IM, de forma independente, nos três momentos da internação. Detectou-se que 34,1% dos pacientes apresentaram EAM. Os EAM mais frequentes foram reações adversas a medicamentos (RAM) do Tipo A, de causalidade possível e gravidade moderada. Os pacientes com EAM relacionados a IM corresponderam a 7% da casuística. O tempo de internação e a administração de medicamentos cardiovasculares apresentaram associação com a ocorrência de EAM na regressão logística . Os resultados desta investigação mostraram que apesar da frequência elevada de IM potenciais, o número de EAM relacionados a IM foi reduzido, entretanto envolveu RAM de significância clínica como nefrotoxicidade e sedação excessiva que podem comprometer a segurança do paciente. Complex pharmacotherapy with multiple medications increases the chances of drug interactions (DI) and adverse drug events (ADE) in patients at intensive care units (ICU). This study aimed to analyze and classify potential drug interactions of the following types: drug-drug and drug-enteral nutrition and also ADE detected during patients\' hospitalization in the ICU of a teaching hospital; to identify drug adverse events related to DI; and investigate factors associated with DI and ADE. This crosssectional, correlational and retrospective study investigated 299 medical records of patients hospitalized for five or more days in the ICU. Potential DI were identified and classified through the software Drug-Reax. Interactions in prescriptions were identified in three occasions: at 24 hours of hospitalization, at median of stay and at discharge of ICU stay . ADE were identified through the method of intensive monitoring and also adverse drug event trigger. ADE were classified regarding causality and severity.Data were analyzed through descriptive analysis, univariate and multiple logistic regression. The majority was female (50.5%) and median age was 57 years. The prevalence of patients with potential DI at 24h was 68.6%. The highest frequency of patients with potential DI was 73.9% in the median of hospitalization. We found that 69.6% of patients presented potential DI at discharge. About 99% were drug-drug interactions. The drug-enteral nutrition interactions were more frequent in patients\' prescriptions at discharge. Most IM were severe or moderate.The number of administered medication and the use of medication for the cardiovascular system were the factors independently associated with the occurrence of DI in the three occasions of hospitalization. The study also detected that 34.1% of patients presented ADE The most frequent ADE were adverse drug reactions (ADR) type A, of possible causality and moderate severity. Patients with ADE related to DI corresponded to 7% of the sample. The multiple logistic regression revealed that time of hospitalization and administration of cardiovascular medication were associated with the occurrence of ADE. This study\'s results revealed that despite the high frequency of potential DI, the number of ADE related to DI was small, however, these involved ADR of clinical significance such as nephrotoxicity and oversedation, which might compromise patient safety.