Sustainable application of surfactants in soil remediation: Selective pollutants adsorption and hydrogen peroxide-driven adsorbent regeneration.

The uncontrolled disposal of the liquid lindane wastes have led to the formation of dense non-aqueous phase liquids (DNAPL), consisting of 28 chlorinated organic compounds (COCs), contaminating soil and groundwater. Surfactant-enhanced aquifer remediation is proposed as technology to treat these sites. However, the polluted emulsion generated must be manged on-site. In this work a two-step process is applied to treat emulsion composed of E-Mulse® 3 (4 g·L-1) as surfactant and a DNAPL (2 gCOCs·L-1). In the first, the COCs were selectively adsorbed in a granular activated carbon (GAC) column with Fe (II) previously adsorbed (10-20mg·g-1) onto the carbon surface, recovering an aqueous phase with surfactant for their reuse. In the second step, the spent GAC was regenerated with a 40 g·L-1 solution of hydrogen peroxide fed to the column at 2 mL·min-1 to promote the oxidation of the COCs adsorbed in the GAC. The kinetic and adsorption model in a multisolute (surfactant and DNAPL) system has been proposed. Five successive cycles of regeneration/adsorption have been successfully applied in the column process. About 50 % of the COCs were retained from the emulsion, and more than 70 % of the surfactant was recovered. The consumption of unproductive oxidants decreased with the number of regeneration cycles. The water effluent obtained after regeneration of GAC did not present chlorinated compounds desorbed and nontoxic by-products generated, such as short-chain acids.

3-styrylcoumarin scaffold-based derivatives as a new approach for leishmaniasis intervention: biological and molecular modeling studies.

Seven 3-styrylcoumarins were tested for antileishmanial activity against Leishmania (Viannia) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. The 3-methoxy-4-hydroxy coumarin derivative 6 was the most active with an IC50 of 40.5 µM, and did not reveal any conspicuous toxicity toward mammalian U-937 cells. Therefore, it may have potential to be considered as candidate for antileishmanial drug development. Further, among several druggable Leishmania targets, molecular docking studies revealed that compound 6 had docking preference by the N-myristoyltransferase (Lp-NMT) of Leishmania panamensis, showing a higher docking score of - 10.1 kcal mol-1 than positive controls and making this protein as a presumably druggable target for this compound. On the other hand, molecular dynamics simulations affirm the docking hypothesis, showing a conformational stability of the 6/Lp-NMT complex throughout 100 ns simulation. Moreover, the molecular mechanics/Poisson-Boltzmann surface area method also support the docking findings, revealing a total free energy of binding of - 47.26 ± 0.08 kcal mol-1, and identifying through energy decomposition analysis that those key aminoacids are contributing strongly to ligand binding. Finally, an optimal pharmacokinetic profile was also estimated for 6. Altogether, coumarin 6 could be addressed as starting point for further pharmacological studies concerning the therapeutic leishmaniasis intervention.

Sustainable reuse of toxic spent granular activated carbon by heterogeneous fenton reaction intensified by temperature changes.

A common strategy for removing highly toxic organic compounds, such as chlorinated organic compounds, is their adsorption on granular activated carbon. Spent granular activated carbon results in a toxic residue to manage; therefore, the regeneration and reuse of granular activated carbon on the site would be advisable. This work studies the regeneration of a granular activated carbon saturated in 1,2,4-trichlorobenzene, chosen as the model chlorinated organic compounds, by heterogeneous Fenton, where iron was previously immobilised on the granular activated carbon surface. This methodology avoids the addition of iron to the aqueous phase at concentrations above the allowable limits and the need for acidification. Three successive cycles of adsorption-regeneration were carried out batchwise (5 gGAC·L-1) with a granular activated carbon saturated with 300 mg124-TCB·gGAC-1. The recovery of the adsorption capacity after regeneration was studied with H2O2 (166 mM, 1.5 the stoichiometric dosage), at different concentrations adsorbed with iron adsorbed concentrations (0-12 mgFe·gGAC-1) and temperatures (20-80 °C). Stable recovery of the adsorption capacity values of 65% were obtained at 180 min with 12 mgFe·gGAC-1 and 60 °C. The porosity and surface chemistry of the adsorbent remained very similar after different adsorption-regeneration cycles without iron leaching into the aqueous phase. The oxidant consumption was close to the stoichiometric value for the mineralization of 1,2,4-trichlorobenzene, with a low unproductive consumption of H2O2 with granular activated carbon. In addition, no aromatic or chlorinated by-products were detected in the aqueous solution obtained in the regeneration process. The negligible toxicity of the aqueous phase with the Microtox bioassay confirmed the absence of toxic oxidation by-products.

Use of complementary and alternative medicine by cancer patients in Colombia.

BACKGROUND: The use of complementary and alternative medicines (CAM) among cancer patients varies greatly. The available data suggest an increasing use of CAM over time and a higher prevalence in low- and middle-income countries. However, no reliable data are available from Latin America. Accordingly, we examined the prevalence of CAM use among cancer patients from six Colombian regions. METHODS: We conducted a survey on cancer patients attending comprehensive cancer centres in six capital cities from different regions. The survey was designed based on a literature review and information gathered through focus groups on CAM terminology in Colombia. Independent random samples of patients from two comprehensive cancer centres in every city were obtained. Patients 18 years and older with a histopathological diagnosis of cancer undergoing active treatment were eligible. The prevalence of CAM use is reported as a percentage with the corresponding confidence interval. CAM types are reported by region. The sociodemographic and clinical characteristics of CAM users and non-users were compared using Chi square and t tests. RESULTS: In total, 3117 patients were recruited. The average age 59.6 years old, and 62.8% were female. The prevalence of CAM use was 51.7%, and compared to non-users, CAM users were younger, more frequently women, affiliated with the health insurance plan for low-income populations and non-Catholic. We found no differences regarding the clinical stage or treatment modality, but CAM users reported more treatment-related side effects. The most frequent types of CAM were herbal products, specific foods and vitamins, and individually, soursop was the most frequently used product. Relevant variability between regions was observed regarding the prevalence and type of CAM used (range: 36.6% to 66.7%). The most frequent reason for using CAM was symptom management (30.5%), followed by curative purposes (19.5%). CONCLUSIONS: The prevalence of CAM use among cancer patients in Colombia is high in general, and variations between regions might be related to differences in cultural backgrounds and access to comprehensive cancer care. The most frequently used CAM products and practices have little scientific support, suggesting the need to enhance integrative oncology research in the country.

Description of the colonizing mycobiota of endotracheal tubes from patients admitted to two intensive care units in Bogotá, Colombia / Descripción de la micobiota de los tubos endotraqueales de pacientes de unidades de cuidados intensivos en Bogotá, Colombia

Introduction. Medical device colonization by pathogenic microorganisms is a risk factor for increasing infections associated with health care and, consequently, the morbidity and mortality of intubated patients. In Colombia, fungal colonization of endotracheal tubes has not been described, and this information could lead to new therapeutic options for the benefit of patients. Objective. To describe the colonizing fungi of the endotracheal tubes from patients in the intensive care unit, along with its antifungal sensitivity profile. Materials and methods. We conducted a descriptive, observational study in two health centers for 12 months. Endotracheal tubes were collected from patients in intensive care units. Samples were processed for culture, fungi identification, and antifungal sensitivity profile assessment. Results. A total of 121 endotracheal tubes, obtained from 113 patients, were analyzed: 41.32 % of the tubes were colonized by Candida albicans (64.62%), C. non­albicans (30.77%), Cryptococcus spp. (3.08%) or molds (1.54%). All fungi evaluated showed a high sensitivity to antifungals, with a mean of 91%. Conclusion. Fungal colonization was found in the endotracheal tubes of patients under invasive mechanical ventilation. The antifungal sensitivity profile in these patients was favorable. A clinical study is required to find possible correlations between the colonizing microorganisms and infectivity.

Introducción. La colonización por microorganismos patógenos de los dispositivos médicos usados en las unidades de cuidados intensivos es un factor de riesgo para el aumento de infecciones asociadas con la atención en salud y, por lo tanto, al de la morbilidad y la mortalidad de los pacientes intubados. En Colombia, no se ha descrito la colonización por hongos de los tubos endotraqueales, con lo cual se podrían considerar nuevas opciones terapéuticas para el beneficio de los pacientes. Objetivo. Describir los hongos que colonizan los tubos endotraqueales de los pacientes en unidades de cuidados intensivos, junto con su perfil de sensibilidad a los antifúngicos. Materiales y métodos. Se realizó un estudio observacional, descriptivo, en dos centros hospitalarios durante 12 meses. Se recolectaron tubos endotraqueales de pacientes de las unidades de cuidados intensivos. Estos fueron procesados para cultivar e identificar hongos, y para establecer su perfil de sensibilidad a los antifúngicos. Resultados. Se analizaron 121 tubos endotraqueales obtenidos de 113 pacientes. De estos, el 41,32 % se encontró colonizado por los hongos Candida albicans (64,61 %), C. no-albicans (30,77 %), Cryptococcus spp. (3,08 %) o mohos (1,54 %). Todos los hongos evaluados presentaron una gran sensibilidad a los antifúngicos, con un promedio del 91 %. Conclusión. Se encontró colonización fúngica en los tubos endotraqueales de pacientes con asistencia respiratoria mecánica. El perfil de sensibilidad en estos pacientes fue favorable. Se requiere un estudio clínico para correlacionar los microorganismos colonizadores y su capacidad de generar infección.

Clinical Outcomes and Prognostic Factors of Patients With Early Malignant Melanoma in One Latin American Country: Results of the Epidemiological Registry of Malignant Melanoma in Colombia Study.

To describe the population with early malignant melanoma, we performed a cohort study on the basis of the Epidemiological Registry of Malignant Melanoma in Colombia-Asociacion Colombiana de Hematologia y Oncologia. From January 2011 until December 2021, 759 patients were included; the average age was 66 years, 57% were women, acral lentiginous histology was found in 27.8% of patients, and the median follow-up was 36.5 months. The prognostic factors for overall survival in our population are Eastern Cooperative Oncology Group 3-4 (hazard ratio [HR], 13.8), stage III (HR, 5.07), received radiotherapy (HR, 3.38), ulceration on histology (HR, 2.68), chronic sun exposure (HR, 2.3), low income (HR, 2.04), previous local surgery (HR, 0.27), and have received adjuvant treatment (HR, 0.41).

Novel Multipotent Amantadine-M30D Hybrids with Highly Selective Butyrylcholinesterase Inhibition and Neuroprotective Effects as Effective Anti-Alzheimer's Agents.

As a contribution to the development of new dual/multifunctional drugs, a novel therapeutical scaffold merging key structural features from memantine and M30D was designed, synthesized, and explored for its AChE/BuChE inhibitory activity and neuroprotective effects. All synthetized hybrids were not able to inhibit AChE, but most of them exhibit inhibition with high selectivity toward butyrylcholinesterase (BuChE). Notably, among the tested compounds, amantadine/M30D hybrids with six, seven, nine, and twelve methylene groups in the spacer (5d, 5e, 5f, and 5g) not only highlighted having the best potency and selective butyrylcholinesterase inhibition greater than 83% but also, particularly 5e and 5d, elicited considerable neuroprotection when evaluated in pretreatment conditions, by reducing injury effects caused by glutamate with maximum protection reached about 47.82 ± 0.81% (5e) and 42 ± 2.20% (5d) in comparison with memantine (37.27 ± 2.69%). Likewise, we chose 5e as the hit compound, which in a glutamate excitotoxity coculture model prevented astroglia reactivity and neuronal death, as well as a 91% restoration of calcium levels and an increasing ATP level in both pre-/post-treatments of 61.48 ± 4.60 and 45.16 ± 10.55%, respectively. Regarding docking studies, a blockade of the NMDA channel pore by 5e would explain its neuroprotective response. Finally, the hit compound 5e exhibited in vitro blood-brain barrier (BBB) permeability and human plasma stability, as well as an optimal in silico neuropharmacokinetic profile. From a therapeutic perspective, merging key pharmacophoric features from memantine and M30D provides a new medicinal scaffold with dual-/multifunctional properties and human plasma stability for the future development of potential drugs for treating AD.

Regeneration of Granulated Spent Activated Carbon with 1,2,4-Trichlorobenzene Using Thermally Activated Persulfate.

Chlorinated organic compounds (COCs) are persistent organic pollutants often found in groundwater near industrial sites or in industrial wastewaters. Adsorption into activated carbon is a common strategy to remediate these waters, but spent activated carbon results in a toxic residue to manage. To avoid the transport of the chlorinated compounds out of the site, the in-situ regeneration of the spent activated carbon can be considered for reuse to implement a circular economy. In this work, the regeneration of a commercial granular activated carbon (GAC) has been carried out using thermally activated sodium persulfate (TAP). GAC was previously saturated in 1,2,4-trichlorobenzene (124-TCB) as the model compound. The initial adsorption value was 350 mg124-TCB·gGAC -1. First, the nonproductive consumption of sodium persulfate was studied at different temperatures using nonsaturated GAC. Then, the regeneration of the saturated GAC (5 g) was studied by an aqueous solution (166 mM) of TAP (1 L) at a temperature range from 20 to 80 °C. The possible recovery of the adsorption capacity was studied after 3 h of treatment in three successive adsorption-regeneration cycles at the selected temperature (60 °C). The physicochemical changes of the GAC were also investigated before and after the regeneration treatments. The results evidence the significant deposition of sulfate on the GAC after each treatment of regeneration, which avoids the recovery of the initial adsorption capacity. Therefore, each regeneration cycle was necessarily followed by a washing step at 60 °C to remove this sulfate. After that, the regeneration treatment achieved a stable and high recovery of the initial adsorption capacity of about 48.2%.

Proapoptotic Effect and Molecular Docking Analysis of Curcumin-Resveratrol Hybrids in Colorectal Cancer Chemoprevention.

Different hybrids based on curcumin and resveratrol were previously synthesized and characterized by spectroscopic techniques. The most active molecules (3a, 3e, 3i, and 3k) were evaluated in vitro as an approach to determine the possible mechanism of action of the hybrids. The results indicated that the evaluated curcumin/resveratrol hybrids induce mitochondrial instability in SW620 and SW480 cells. Moreover, these molecules caused a loss in membrane integrity, suggesting an apoptotic process mediated by caspases after the treatment with compounds 3i (SW480) and 3k (SW620). In addition, the results suggest that the mechanism of action of the hybrids could be independent of the p53 status. Furthermore, hybrids 3e and 3i caused G0/G1 phase arrest, which highlights the potential of these molecules not only as cytotoxic but also as cytostatic compounds. Hybrids 3e and 3i caused a negative modulation of the matrix metalloproteinase 7 (MMP7) on SW480 cells. These curcumin resveratrol hybrids could be potential candidates for further investigations in the search for potential chemopreventive agents, even in those cases with resistance to conventional chemotherapy because of the lack of p53 expression or function. Molecular docking simulations showed that compounds 3e, 3i, and 3k bind efficiently to proapoptotic human caspases 3/7 proteins, as well as human MMP-7 and p53, which, in turn, could explain at the molecular level the in vitro cytotoxic effect of these compounds in SW480 and SW620 colon cancer cell lines.

Endotracheal tube microbiome in hospitalized patients defined largely by hospital environment.

BACKGROUND: Studies of the respiratory tract microbiome primarily focus on airway and lung microbial diversity, but it is still unclear how these microbial communities may be affected by intubation and long periods in intensive care units (ICU), an aspect that today could aid in the understanding of COVID19 progression and disease severity. This study aimed to explore and characterize the endotracheal tube (ETT) microbiome by analyzing ETT-associated microbial communities. METHODS: This descriptive study was carried out on adult patients subjected to invasive mechanical ventilation from 2 to 21 days. ETT samples were obtained from 115 patients from ICU units in two hospitals. Bacteria isolated from endotracheal tubes belonging to the ESKAPE group were analyzed for biofilm formation using crystal violet quantification. Microbial profiles were obtained using Illumina sequencing of 16S rRNA gene. RESULTS: The ETT microbiome was mainly composed by the phyla Proteobacteria, Firmicutes and Bacteroidetes. Microbiome composition correlated with the ICU in which patients were hospitalized, while intubation time and diagnosis of ventilator-associated pneumonia (VAP) did not show any significant association. CONCLUSION: These results suggest that the ICU environment, or medical practices, could be a key to microbial colonization and have a direct influence on the ETT microbiomes of patients that require mechanical ventilation.

S-allylCysteine Ester/Caffeic Acid Amide Hybrids as Promising Antiprotozoal Candidates: Synthesis, Biological Evaluation and Molecular Modeling Studies

Abstract In order to overcome the challenges of discovering new antiprotozoal drugs, we synthesized a new class of hybrids based on S-allylCysteine Ester/Caffeic Acid Amide and evaluated four of them against Trypanosoma cruzi and Plasmodium falciparum. Hybrid 6 exhibited good activity on T. cruzi with an EC50 value of 5.45 µM, whereas hybrid 3 was active over P. falciparum with an EC50 of 18.08 µM. All hybrids displayed a good selectivity index on P. falciparum. Molecular docking computations indicated that several hybrids have good binding affinities towards the protozoa related enzymes (Cruzipain or Falcipain-2) when compared against current inhibitors. In silico studies showed that conjugates 1-3 and 6 fulfilled optimal ADME characteristics, suggesting them as safe alternatives for oral treatment of protozoal infections.

Promising Hybrids Derived from S-Allylcysteine and NSAIDs Fragments against Colorectal Cancer: Synthesis, In-vitro Evaluation, Drug-Likeness and In-silico ADME/tox Studies.

We synthesized twelve hybrids, S-allyl Cysteine methyl, ethyl and propyl ester-based non-steroidal anti-inflammatory drugs and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of all compounds was evaluated against SW480 human colon adenocarcinoma cells and the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 10b-c, 11b and 12b displayed the best anticancer activity with IC50 values between 0.131-0.183 mM and selectivity indices higher than 1 after 48 h of treatment. Selectivity indices were comparable to those reported for the reference drug, 5-fluorouracil (SI > 1). The SAR analysis showed that compounds with two carbon atom alkylic chains displayed the best activity (10b, 11b and 12b). Modeling studies including drug-likeness, bioactivity score and ADME/tox studies using online tools like molinspiration and Osiris suggested that these designed hybrids have a good pharmacological profile and can be considered as promising scaffolds for further studies in the search for new therapeutic alternatives to treat colorectal cancer.

Antileishmanial and cytotoxic activities of four Andean plant extracts from Colombia.

BACKGROUND AND AIM: Licania salicifolia (L.S) Cuatrec., Persea ferruginea (P.F) Kunth, Oreopanax floribundus (O.F), and Psychotria buchtienii (P.B) belong to the families Chrysobalanaceae, Lauraceae, Araliaceae, and Rubiaceae, respectively, which have been used as medicines by communities in the Andes. This study evaluated the leishmanicidal and cytotoxic activities of alcohol and non-alcohol extracts from four Andean plant extracts (L.S, O.F, P.F, and P.B). MATERIALS AND METHODS: Extracts were obtained by percolation with solvents of different polarities - hexane, dichloromethane, ethyl acetate, and ethanol. Phytochemical screening was conducted based on reported methods. All products were evaluated in vitro to determine the leishmanicidal activity against amastigotes of Leishmania panamensis and cytotoxicity against U937 cells. RESULTS: Flavonoids, triterpenes, and tannins were the main secondary metabolites found. From the results, dichloromethane extracts from O.F and P.B, ethanol extract from P.B, and ethyl acetate extracts of all plants were active, with EC50 <30 µg/mL. Ethyl acetate was the most active extract, which showed EC50 values of 9.8, 14.1, 23.7, and 25.5 µg/mL, for L.S, P.B, O.F, and P.F, respectively. Hexane extracts from P.B and O.F exhibited moderate activity with EC50 values of 84.8 and 87.4 µg/mL, respectively. Hexane and ethanol extracts from O.F, ethyl acetate, and ethanol extracts from L.S, and all extracts from P.F were not toxic. Alternatively, hexane and dichloromethane extracts from L.S and P.B as well as dichloromethane and ethyl acetate extracts from O.F displayed high toxicity. CONCLUSION: Based on the activity we observed, ethyl acetate extract can continue in its usage in the search for new antileishmanial drugs, mainly ethyl acetate extract from L.S showed activity comparable to meglumine antimoniate and was not cytotoxic.

Recomendaciones para el cuidado de pacientes con cáncer y neoplasias hematológicas en el estado de pandemia COVID-19 en Colombia / Care recommendations for patients with cancer and hematological neoplasms amid the COVID-19 pandemic in Colombia

Resumen Ante la pandemia COVID 19, declarada en marzo de 2020 por la Organización Mundial de la Salud (OMS), desde la Asociación Colombiana de Hematología y Oncología (ACHO) hemos venido emitiendo comunicaciones destinadas a orientar a los profesionales de la salud implicados en el tratamiento de pacientes hematológicos y oncológicos. Consideramos importante realizar una nueva actualización dada la fase de mitigación de la pandemia que actualmente estamos enfrentando y ante el planteamiento gubernamental de desdescalonamiento progresivo, de la cuarentena. Estas recomendaciones no pretenden imponer una conducta única pues entendemos que cada caso es particular y debe actuarse individualizando a cada situación específica. Están basadas en documentos emitidos por asociaciones científicas oncológicas y hematológicas reconocidas y son susceptibles de sufrir modificaciones a medida que se disponga de mayor información.

Abstract In response to the Covid-19 pandemic, declared in March 2020 by the World Health Organization (WHO), the Colombian Association of Hematology and Oncology (ACHO) has been issuing communications aimed at providing guidance to health professionals involved in the treatment of hematological and oncological patients. Considering the pandemic mitigation phase we are currently facing, and the government's approach to progressively tapering-off the quarantine, we deem it important to release a new update. These recommendations are not intended to impose a single conduct, since we understand that each case has particular characteristics and therefore it must be acted upon by individualizing each specific situation. The recommendations are based on documents issued by well-known cancer and hematological scientific associations, and are subject to change as more information becomes available.

Real-time ultrasound-guided thoracentesis in the intensive care unit: prevalence of mechanical complications.

BACKGROUND: The use of thoracic ultrasound during thoracentesis reduces complications. The aim of this study was to determine the prevalence of complications for real-time ultrasound-guided thoracentesis performed by intensivists. As a secondary objective, the change in oxygenation before and after the procedure was evaluated. PATIENTS AND METHODS: An observational prospective study was conducted. A total of 81 cases of real-time ultrasound-guided thoracentesis performed by intensivists in the intensive care unit (ICU) of Méderi Major University Hospital, Bogotá, Colombia, between August 2018 and August 2019 were analyzed. Thoracentesis performed by interventional radiologists and using techniques different from the focus of this study were excluded from the analysis. RESULTS: There was one pneumothorax, for a prevalence rate of mechanical complications in this population of 1.2%. The mean partial oxygen pressure to inspired oxygen fraction ratio (PaO2/FiO2) prior to the procedure was 198.1 (95% CI 184.75-211.45), with a PaO2/FiO2 after the procedure of 224.6 (95% CI 213.08-226.12) (p < 0.05). CONCLUSIONS: Real-time ultrasound-guided thoracentesis performed by intensivists is a safe procedure and leads to a significant improvement in oxygenation rates. Future studies are required to determine the impact of these results on other outcomes, such as mortality, ICU stay, and days of mechanical ventilation.

Response of Leptomeningeal Metastases in EGFR-Mutated Non-Small-Cell Lung Cancer to Afatinib in the Absence of Radiotherapy.

Palliative radiotherapy is currently the medical standard of care for non-small-cell lung cancer (NSCLC) patients with symptomatic CNS and leptomeningeal disease. We report the case of a 62-year-old male patient with EGFR mutation (del19+) NSLC with symptomatic lymph node, bone, CNS, and leptomeningeal metastases. Taking into account on one hand the response to tyrosine kinase inhibitors (TKIs) and on the other hand the short- to medium-term side effects of radiotherapy and the lack of timely availability in our healthcare system, the patient was treated with afatinib (40 mg daily) and exhibited a rapid response with improvement of neurological symptoms. The patient presented partial response of extracranial, CNS, and leptomeningeal lesions at 3, 6, and 12 months of treatment, currently completing 16 months of progression-free survival despite presenting mild dermatological and gastrointestinal toxicities. Afatinib is an effective and safe option in patients with NSLC EGFR mutation del19+ with CNS and leptomeningeal compromise avoiding or delaying radiotherapy and its side effects, especially in countries where there is a lack of access to this kind of therapy.

Hybrid Molecules: Promising Compounds for the Development of New Treatments Against Leishmaniasis and Chagas Disease.

Leishmaniasis and Chagas disease are endemic pathologies in tropical countries. These cause high morbidity and a public health problem. Current chemotherapies are based on conventional drugs with variable efficacy and toxicity related with the length of therapeutic schemes and high doses. When two pharmacological agents are combined into a single molecule, the result is the so-called hybrid molecule. In the search for new treatments against Chagas disease and leishmaniasis, several studies have shown that hybrid molecules display high antiprotozoal activity and this emerging strategy is quite promising in the field of new drug discovery and development. This review focuses on the antiprotozoal activity of different hybrids obtained from the hybridization of pharmacophores, showing that the most of the efforts have been concentrated in the molecular hybridization of quinoline, chalcone and hydrazone moieties.

Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015 / Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

Ensayo clínico cruzado y aleatorizado para comparar dos modelos farmacocinéticos de propofol usando índices de entropía / Randomized cross-over clinical trial comparing two pharmacokinetic models of propofol using entropy indices

Introduction: There are two different pharmacokinetic models (Marsh and Schnider) for the administration of total intravenous anesthesia with propofol, the parameter differences could have some impact over the depth of anesthesia. Objective: To determine if there is a significant difference in the variability of depth of anesthesia suggesting that one model is superior in achieving a more stable and predictable depth of anesthesia during surgery. Methods: A cross-over clinical trial was conducted on 16 healthy patients programmed for upper or lower limb ambulatory orthopedic surgery. Patients were randomly assigned to (i) effect site target controlled infusion of propofol with Marsh model at a target concentration of 2.5 μg/ml for 20 min, a 20 min washout, then propofol was administered with Schnider model at the same effect site target for the reminder of the surgery, or (ii) the reverse sequence. Differences in variability of depth of anesthesia, were assessed by comparing records of spectral entropy indices during surgery through an unpaired t-test. Results: There was no evidence of significant difference in the mean variances of either spectral entropy indices between the two models (p-value: 0.57 for State Entropy, p-value: 0.51 for Response Entropy). Conclusion: The study suggests that both pharmacokinetic models are equivalent in terms of stability of depth of anesthesia. It is important to keep testing determinants of the efficacy of the models in different types of population because their behavior according to individual characteristics of patients or variables such as cost-effectiveness could end up tilting the scale.

Introducción: Hay dos modelos farmacocinéticos diferentes para la administración de la anestesia total intravenosa con propofol (Marsh y Schnider), las diferencias entre los parámetros podrían tener algún impacto sobre la profundidad anestésica. Objetivo: Comparar la variabilidad de la profundidad anestésica durante administración de infusión de propofol con los modelos de Marsh y Schnider para determinar si hay diferencias significativas que sugieran que uno de los modelos es superior en lograr una profundidad anestésica más estable y predecible. Métodos: Estudio clínico cruzado, controlado y aleatorizado llevado a cabo en 16 pacientes programados para cirugía ambulatoria de ortopedia. Los pacientes fueron asignados aleatoriamente a i) infusión controlada por objetivo de propofol con el modelo de Marsh a una concentración objetivo en sitio de efecto de 2.5μg/ml durante 20 minutos, 20 minutos de periodo de lavado, seguido de infusión de propofol con modelo de Schnider a la misma concentración objetivo; o ii) la secuencia inversa. La diferencia en variabilidad de profundidad anestésica fue evaluada mediante la comparación de registros de índices de entropía con una prueba t no pareada. Resultados: No se encontró evidencia de diferencias significativas de la varianza media en los índices de entropía espectral asociada a los modelos (valor-p: 0.57 para entropía de estado, valor-p: 0.51 para entropía de respuesta). Conclusión: El estudio sugiere que ambos modelos son equivalentes en términos de estabilidad de profundidad anestésica. Es importante continuar estudiando la eficacia de los modelos en diferentes tipos de población, dado que su comportamiento según características individuales de los pacientes o variables cómo costo-efectividad podrían inclinar la balanza.