[The long and winding road of the clinical pharmacy in Chile]. / El largo y sinuoso camino de la farmacia clinica en Chile.

Clinical pharmacy is a health discipline in which pharmacists provide patient care that optimizes rational medication use and promotes health, wellness and disease prevention. The beginnings of clinical pharmacy in Chile were inspired by the origin in the School of Pharmacy of the University of California, San Francisco (UCSF), in the mid-1960s. However, the historical development in our country, both in teaching and in the professional field, was accompanied by difficulties and success, which became a long and winding road. This article shares the events that gave rise to its beginnings in Chile, first through teaching, then in pharmacovigilance and clinical pharmacokinetics, to later describe its professional expansion and recognition as a specialty of pharmacy. This article briefly recounts the history of the Chilean clinical pharmacy to this day. Some names of people or institutions were not mentioned. Therefore the authors apologize in advance to pharmacists and organizations whose contribution cannot be recognized in this way. However, we know that this specialty has not been forged only by the names that appear, but by all those who love and respect the work of the clinical pharmacy.

El largo y sinuoso camino de la farmacia clinica en Chile / The long and winding road of the clinical pharmacy in Chile

Clinical pharmacy is a health discipline in which pharmacists provide patient care that optimizes rational medication use and promotes health, wellness and disease prevention. The beginnings of clinical pharmacy in Chile were inspired by the origin in the School of Pharmacy of the University of California, San Francisco (UCSF), in the mid-1960s. However, the historical development in our country, both in teaching and in the professional field, was accompanied by difficulties and success, which became a long and winding road. This article shares the events that gave rise to its beginnings in Chile, first through teaching, then in pharmacovigilance and clinical pharmacokinetics, to later describe its professional expansion and recognition as a specialty of pharmacy. This article briefly recounts the history of the Chilean clinical pharmacy to this day. Some names of people or institutions were not mentioned. Therefore the authors apologize in advance to pharmacists and organizations whose contribution cannot be recognized in this way. However, we know that this specialty has not been forged only by the names that appear, but by all those who love and respect the work of the clinical pharmacy.

The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway.

(+)-Aeroplysinin-1 (Apl-1) is a brominated compound isolated from the marine sponge Aplysina aerophoba that exhibits pleiotropic bioactive effects, impairing cell growth in cancer cells, inhibiting angiogenesis in vitro and in vivo and modulating the redox status of different cell types, among other reported activities. In addition to the aforementioned effects, the anti-inflammatory potential of this natural compound was explored in previous work of our laboratory, but the mechanism of action underlying this effect was not described. In this work, we delve into the anti-inflammatory effect of Apl-1 in the context of vascular endothelial cells in vitro, providing new data regarding the molecular mechanism underlying this activity. The characterization of the mechanism of action points to an inhibitory effect of Apl-1 on the NF-κB pathway, one of the main axes involved in endothelial response during inflammatory events. Our results show that Apl-1 can inhibit the expression of pro-inflammatory genes in tumor necrosis factor alpha (TNF-α)- and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), targeting the nuclear factor kappa B subunit (NF-κB) pathway through a mechanism of action involving the inhibition of I kappa B kinase (IKK) complex phosphorylation and RelA/p65 nuclear import. In addition, Apl-1 prevented the phosphorylation of Akt induced by TNF-α in HUVECs, probably supporting the inhibitory effect of this compound in the NF-κB pathway. Experimental evidence reported in this work opens the door to the potential pharmacological use of this compound as an anti-inflammatory agent in diseases that course with a pathological endothelial response to inflammation, such as atherosclerosis.

From Food to Genes: Transcriptional Regulation of Metabolism by Lipids and Carbohydrates.

Lipids and carbohydrates regulate gene expression by means of molecules that sense these macronutrients and act as transcription factors. The peroxisome proliferator-activated receptor (PPAR), activated by some fatty acids or their derivatives, and the carbohydrate response element binding protein (ChREBP), activated by glucose-derived metabolites, play a key role in metabolic homeostasis, especially in glucose and lipid metabolism. Furthermore, the action of both factors in obesity, diabetes and fatty liver, as well as the pharmacological development in the treatment of these pathologies are indeed of high relevance. In this review we present an overview of the discovery, mechanism of activation and metabolic functions of these nutrient-dependent transcription factors in different tissues contexts, from the nutritional genomics perspective. The possibility of targeting these factors in pharmacological approaches is also discussed. Lipid and carbohydrate-dependent transcription factors are key players in the complex metabolic homeostasis, but these factors also drive an adaptive response to non-physiological situations, such as overeating. Possibly the decisive role of ChREBP and PPAR in metabolic regulation points to them as ideal therapeutic targets, but their pleiotropic functions in different tissues makes it difficult to "hit the mark".

Feeding behavior, life history, and virus transmission ability of Bemisia tabaci Mediterranean species (Hemiptera: Aleyrodidae) under elevated CO2.

The continuous rise of CO2 concentrations in the atmosphere is reducing plant nutritional quality for herbivores and indirectly affects their performance. The whitefly (Bemisia tabaci, Gennadius) is a major worldwide pest of agricultural crops causing significant yield losses. This study investigated the plant-mediated indirect effects of elevated CO2 on the feeding behavior and life history of B. tabaci Mediterranean species. Eggplants were grown under elevated and ambient CO2 concentrations for 3 weeks after which plants were either used to monitor the feeding behavior of whiteflies using the Electrical Penetration Graph technique or to examine fecundity and fertility of whiteflies. Plant leaf carbon, nitrogen, phenols and protein contents were also analyzed for each treatment. Bemisia tabaci feeding on plants exposed to elevated CO2 showed a longer phloem ingestion and greater fertility compared to those exposed to ambient CO2 suggesting that B. tabaci is capable of compensating for the plant nutritional deficit. Additionally, this study looked at the transmission of the virus Tomato yellow leaf curl virus (Begomovirus) by B. tabaci exposing source and receptor tomato plants to ambient or elevated CO2 levels before or after virus transmission tests. Results indicate that B. tabaci transmitted the virus at the same rate independent of the CO2 levels and plant treatment. Therefore, we conclude that B. tabaci Mediterranean species prevails over the difficulties that changes in CO2 concentrations may cause and it is predicted that under future climate change conditions, B. tabaci would continue to be considered a serious threat for agriculture worldwide.

Two Salix Genotypes Differ in Productivity and Nitrogen Economy When Grown in Monoculture and Mixture.

Individual plant species or genotypes often differ in their demand for nutrients; to compete in a community they must be able to acquire more nutrients (i.e., uptake efficiency) and/or use them more efficiently for biomass production than their competitors. These two mechanisms are often complementary, as there are inherent trade-offs between them. In a mixed-stand, species with contrasting nutrient use patterns interact and may use their resources to increase productivity in different ways. Under contrasting nutrient availabilities, the competitive advantages conferred by either strategy may also shift, so that the interaction between resource use strategy and resource availability ultimately determines the performance of individual genotypes in mixtures. The aim was to investigate growth and nitrogen (N) use efficiency of two willow (Salix) genotypes grown in monoculture and mixture in a fertilizer contrast. We explored the hypotheses that (1) the biomass production of at least one of the involved genotypes should be greater when grown in mixture as compared to the corresponding monoculture when nutrients are the most growth-limiting factor; and (2) the N economy of individual genotypes differs when grown in mixture compared to the corresponding monoculture. The genotypes 'Tora' (Salix schwerinii ×S. viminalis) and 'Loden' (S. dasyclados), with contrasting phenology and functional traits, were grown from cuttings in a growth container experiment under two nutrient fertilization treatments (high and low) in mono- and mixed-culture for 17 weeks. Under low nutrient level, 'Tora' showed a higher biomass production (aboveground biomass, leaf area productivity) and N uptake efficiency in mixture than in monoculture, whereas 'Loden' showed the opposite pattern. In addition, 'Loden' showed higher leaf N productivity but lower N uptake efficiency than 'Tora.' The results demonstrated that the specific functional trait combinations of individual genotypes affect their response to mixture as compared to monoculture. Plants grown in mixture as opposed to monoculture may thus increase biomass and vary in their response of N use efficiency traits. However, young plants were investigated here, and as we cannot predict mixture response in mature stands, our results need to be validated at field scale.

Elymus repens biomass allocation and acquisition as affected by light and nutrient supply and companion crop competition.

BACKGROUND AND AIMS: Competitive crops are a central component of resource-efficient weed control, especially for problematic perennial weeds such as Elymus repens Competition not only reduces total weed biomass, but denial of resources can also change the allocation pattern - potentially away from the underground storage organs that make perennial weeds difficult to control. Thus, the competition mode of crops may be an important component in the design of resource-efficient cropping systems. Our aim was to determine how competition from companion crops with different modes of competition affect E. repens biomass acquisition and allocation and discuss that in relation to how E. repens responds to different levels of light and nutrient supply. METHODS: Greenhouse experiments were conducted with E. repens growing in interspecific competition with increasing density of perennial ryegrass or red clover, or growing at three levels of both light and nutrient supply. KEY RESULTS: Elymus repens total biomass decreased with increasing biomass of the companion crop and the rate of decrease was higher with red clover than with perennial ryegrass, particularly for E. repens rhizome biomass. A reduced nutrient supply shifted E. repens allocation towards below-ground biomass while a reduced light supply shifted it towards shoot biomass. Red clover caused no change in E. repens allocation pattern, while ryegrass mostly shifted the allocation towards below-ground biomass, but the change was not correlated with ryegrass biomass. CONCLUSIONS: The companion crop mode of competition influences both the suppression rate of E. repens biomass acquisition and the likelihood of shifts in E. repens biomass allocation.

[Monitoring medication errors in an internal medicine service]. / Errores de medicación en el Servicio de Medicina de un hospital de alta complejidad.

BACKGROUND: Patients admitted to internal medicine services receive multiple drugs and thus are at risk of medication errors. AIM: To determine the frequency of medication errors (ME) among patients admitted to an internal medicine service of a high complexity hospital. MATERIAL AND METHODS: A prospective observational study conducted in 225 patients admitted to an internal medicine service. Each stage of drug utilization system (prescription, transcription, dispensing, preparation and administration) was directly observed by trained pharmacists not related to hospital staff during three months. ME were described and categorized according to the National Coordinating Council for Medication Error Reporting and Prevention. In each stage of medication use, the frequency of ME and their characteristics were determined. RESULTS: A total of 454 drugs were prescribed to the studied patients. In 138 (30,4%) indications, at least one ME occurred, involving 67 (29,8%) patients. Twenty four percent of detected ME occurred during administration, mainly due to wrong time schedules. Anticoagulants were the therapeutic group with the highest occurrence of ME. CONCLUSIONS: At least one ME occurred in approximately one third of patients studied, especially during the administration stage. These errors could affect the medication safety and avoid achieving therapeutic goals. Strategies to improve the quality and safe use of medications can be implemented using this information.

Constituents of Hondurian propolis with inhibitory effects on Saccharomyces cerevisiae multidrug resistance protein Pdr5p.

Chemical investigation of a propolis sample collected in Honduras has led to the isolation of the new (E,Z)-cinnamyl cinnamate (2) together with 14 known compounds: 6 cinnamic ester derivatives, 2 flavanones, 1 chalcone, 2 triterpenes, and 3 aromatic acids. Structural determination was accomplished by spectroscopic analysis, particularly two-dimensional (2D) nuclear magnetic resonance (NMR) and electrospray ionization-tandem mass spectrometry (ESI-MS/MS) techniques. Futhermore, we checked the ability of the propolis extract and the most representative compounds of each class (1, 5, 8, and 10) to inhibit the activity of Pdr5p, a protein responsible for a multidrug resistance phenotype in yeast. The present study appears to be the first report on Honduras propolis. Isolated cinnamic ester derivatives indicated the possible relation between Honduras propolis and the genus Liquidambar .

Phenolic derivatives from the leaves of Martinella obovata (Bignoniaceae).

A new phenolic derivative, 4-methoxyphenol 1-O-beta-D-apiofuranosyl-(1 --> 6)-O-beta-D-glucopyranoside (1), has been identified together with uncommon 3,4-dimethoxyphenol 1-O-beta-D-apiofuranosyl-(1 --> 6)-O-beta-D-glucopyranoside (2) and 3-hydroxy, 4-methoxyphenol 1-O-beta-D-apiofuranosyl-(1 --> 6)-O-beta-D-glucopyranoside (3) from the leaves of Martinella obovata (Kunth) Bureau & K. Schum., an Honduran species used in folk medicine for the treatment of eyes diseases. Verbascoside, isoverbascoside, leucoceptoside A, vitexin, isovitexin, luteolin 8-C-beta-D-glucopiranoside and spireoside were also found. All structures were elucidated on the basis of mass spectrometry and 2D NMR techniques.

Magnoflorine and phenolic derivatives from the leaves of Croton xalapensis L. (Euphorbiaceae).

The alkaloid magnoflorine 1, has been isolated for the first time from Croton xalapensis (Euphorbiaceae), in addition two phenylpropenols derivates, 3,4-dimethoxy-(E)-cinnamyl alcohol 2 and 3,4-dimethoxy-5-hydroxy-(E)-cinnamyl alcohol 3, 3,4,5-trimethoxycinnamic acid 4, gallic acid 5, methyl gallate 6 and 3,4-dihydroxybenzoic acid 7 have been also found; these compounds were identified by spectroscopic analysis particularly, 2D NMR and ESI-MS/MS techniques. The high concentration of magnoflorine, calculated with quantitative HPLC, of the aqueous extract, probably contributes to the remarkable medicinal properties of this plant. In addition this is the first phytochemical study on Croton xalapensis to be reported.

[Consumption of antidepressants in Chile from 1992 to 2004]. / Consumo de antidepresivos en Chile entre 1992 y 2004.

BACKGROUND: Data from the Ministry of Health show that in Chile in 2004, 17% of the population had some form of depression, and mood disorders are the tenth cause of disability-adjusted life years (DALY) loss. AIM: To determine consumption of antidepressants (ADs) in Chile from 1992 to 2004. MATERIAL AND METHODS: National sales data were obtained from the company IMS Health Chile and converted into defined daily doses (DDDs) per 1,000 inhabitants per day. Available ADs were classified in four pharmacological groups (i.e., serotonin-norepinephrine reuptake inhibitors, SNRLs; selective-serotonin reuptake inhibitors, SSRLs; tricyclic antidepressants, TCAs; and others). Total economic burden of ADs utilization and cost per DDDs were also calculated. Trends over time were analyzed using Pearson-R2. RESULTS: Total ADs consumption in Chile measured by DDDs per 1,000 inhabitants per day (DHD) increased linearly (y =0.901x + 1.9129; R2 =0.9296; p <0.001) from 2.5 in 1992 to 11.7 in 2004 (total growth of 470.2%). SSRLs were the drug class with higher consumption, and fluoxetine the most commonly consumed antidepressant. SSRLs were the drugs that dominated the market representing 79% of the total drug consumption throughout the years. Total economic burden of ADs in Chile (total cost of DDDs consumed) increased from US$65.4 million in 2001 to US$74.6 million in 2004 (14% increase). Average cost per DDD of all AD increased linearly, however not significantly from US$ 0.94 in 2001 to US$ 1.04 in 2004 (y =0.0362x + 0.8784; R2 =0.7382; p =0,262). CONCLUSIONS: DDDs per 1,000 inhabitants per day increased linearly over 470% from 1992-2004. SSRLs were the most commonly consumed drugs in Chile. Future research should evaluate the cost-effectiveness of antidepressants in Chile, comparing the results with drug utilization, and determining if unnecessary expenditures have been paid out.

Consumo de antidepresivos en Chile entre 1992 y 2004 / Consumption of antidepressants in Chile from 1992 to 2004

Background: Data from the Ministry of Health show that in Chile in 2004, 17 percent of the population had some form of depression and mood disorders are the tenth cause of disability-adjusted Ufe years (DALY) loss. Aim: To determine consumption of antidepressants (ADs) in Chile from 1992 to 2004. Material and methods: National sales data were obtained from the company IMS Health Chile and converted into defined daily doses (DDDs) per 1,000 inhabitants per day Available ADs were classified in four pharmacological groups (i.e., serotonin-norepinephrine reuptake inhibitors, SNRIs; selective-serotonin reuptake inhibitors, SSRIs; tricyclic antidepressants, TCAs; and others). Total economic burden of ADs utilization and cost per DDDs were also calculated. Trends over time were analyzed using Pearson-R2. Results: Total ADs consumption in Chile measured by DDDs per 1,000 inhabitants per day (DHD) increased linearly (y =0.901x+1.9129; R2 =0.9296; p <0.001) from 2.5 in 1992 to 11.7 in 2004 (total growth of 470.2 percent). SSRIs were the drug class with higher consumption, and fluoxetine the most commonly consumed antidepressant. SSRIs were the drugs that dominated the market representing 79 percent of the total drug consumption throughout the years. Total economic burden of ADs in Chile (total cost of DDDs consumed) increased from US$65.4 million in 2001 to US$74.6 million in 2004 (14 percent increase). Average cost per DDD of all AD increased linearly, however not significantly from US$ 0.94 in 2001 to US$ 1.04 in 2004 (y =0.0362x+0.8784; R2 =0.7382; p =0,262). Conclusions: DDDs per 1,000 inhabitants per day increased linearly over 470 percent from 1992-2004. SSRIs were the most commonly consumed drugs in Chile. Future research should evaluate the cost-effectiveness of antidepressants in Chile, comparing the results with drug utilization, and determining if unnecessary expenditures have been paid out.

The economic impact of introducing serotonin-noradrenaline reuptake inhibitors into the Brazilian national drug formulary: cost-effectiveness and budget-impact analyses.

OBJECTIVE: To determine the cost effectiveness, from the Brazilian Ministry of Health viewpoint, of three antidepressant classes for major depressive disorder (MDD), and the budget impact of introducing serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) into the current Brazilian national drug formulary, assuming a 6-month treatment duration. METHODS: An existing decision-tree model was adapted to Brazil, based on local guidelines. Clinical data were obtained from published meta-analyses. Patients included adults aged > or =18 years with MDD, diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, third and fourth editions (DSM-III/IV), with moderate-to-severe disease (Hamilton Depression Rating Scale [HAMD] > or =15 or Montgomery-Asberg Depression Rating Scale [MADRS] > or =18), without co-morbidities or co-medications, receiving > or =6 weeks of treatment with SNRIs, selective serotonin reuptake inhibitors (SSRIs) and/or tricyclic antidepressants (TCAs). Clinical outcome was remission (HAMD < or =7 or MADRS < or =12). Direct costs (drugs, physician visits, hospitalisations) were included. Drug costs were obtained from the 2006 Brazilian National Drug Price List, and hospitalisation and physician costs from the 2006 Healthcare System database. Costs were valued in Brazilian Reais ($Brz), year 2006 values ($Brz1 = $US0.47). Univariate and Monte Carlo sensitivity analyses tested model robustness. RESULTS: Expected costs per patient treated were SNRIs $Brz4848; SSRIs $Brz5466; and TCAs $Brz5046, and overall success rates (primary plus secondary treatment across all decision tree branches) were SNRIs 78.1%; SSRIs 74.0%; and TCAs 76.4%. Average costs/success were SNRIs $Brz6209; SSRIs $Brz7385; and TCAs $Brz6602. SNRIs dominated in incremental cost-effectiveness analyses. Monte Carlo analysis confirmed drug classes' relative positions; however, there was considerable uncertainty. Introducing SNRIs into the formulary could generate average savings of 1% of the total budget, with a 52% probability of savings. CONCLUSIONS: SNRIs appear to be cost effective against SSRIs and TCAs when prescribed to patients with MDD in Brazil. However, their inclusion into the national drug list would generate minor savings compared with the current formulary of SSRIs and TCAs. Thus, we considered such inclusion as 'cost-neutral', since no major probability of savings or increased expenditures were observed.

Remission, dropouts, and adverse drug reaction rates in major depressive disorder: a meta-analysis of head-to-head trials.

OBJECTIVE: To summarize remission rates and dropouts due to adverse drug reactions (ADRs) or lack of efficacy (LoE) of serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin-reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs) in treating major depressive disorder. METHODS: We searched MEDLINE, EMBASE, IPA, and the Cochrane International Library from 1980-2005. Meta-analysis summarized outcomes from head-to-head randomized clinical trials comparing >or= 2 drugs from three antidepressants classes (SNRIs, and/or SSRIs, and/or TCAs) followed by >or= 6 weeks of treatment. Remission was a final Hamilton Depression Rating Scale (HAMD) score 0.05 for SNRIs versus TCAs; p < 0.001 for TCAs versus SSRIs and SNRIs versus SSRIs). When categorized as inpatients (n = 582) and outpatients (n = 1613), SNRIs had the highest remission rates (52.0% for 144 inpatients and 49.3% for 559 outpatients). SNRIs had lowest overall dropouts (26.1%), followed by SSRIs (28.4%), and TCAs (35.7%). Dropouts due to ADRs and LoE were 10.3% and 6.2% for SNRIs, 8.3% and 7.2% for SSRIs, and 19.8% and 9.9% for TCAs, respectively (p > 0.05 for ADR dropouts only). One limitation was the inclusion of only venlafaxine-XR; results may not be the same for immediate release forms. In addition, few studies reported remission rates. CONCLUSIONS: SNRIs had the highest efficacy remission rates (statistically significant for inpatients and outpatients), and the lowest overall dropout rates, suggesting clinical superiority in treating major depression.