Antimalarial evaluation of alkyl-linked bis-thiadiazine derivatives in murine model infected with two Plasmodium strains.

Background and Purpose: Plasmodium falciparum and P. vivax are responsible for most malaria cases in humans in the African Region and the Americas; these parasites have developed resistance to classic antimalarial drugs. On the other hand, previous investigations of the alkyl-linked bis tetrahydro-(2H)-1,3,5-thiadiazine-2-thione (bis-THTT) derivatives compounds show satisfactory results against protozoan parasites such as Trypanosoma cruzi, Trypanosoma vaginalis, Trypanosoma brucei rhodesiense and Leishmania donovani. Therefore, it is possible to see some effect of bis-THTT derivatives on other protozoan parasites, such as Plasmodium. Experimental Approach: This study aimed to perform an in vivo biological evaluation of bis-THTT (JH1 to JH6) derivatives compounds as possible anti-malaria drugs in BALB/c mice infected with Plasmodium berghei ANKA and Plasmodium yoelii 17XL strains. In this work, we evaluated the compounds as potential antimalarial drugs in BALB/c mice infected with Plasmodium strains. Key Results: For each compound, we assess the percentages of parasitemia by smears from tail blood and the humoral response by indirect ELISA test using each compound as an antigen. We also evaluated the B lymphocyte response and the cytotoxicity of the bis-THTT derivatives compounds with MTT cell proliferation assays. Conclusions: Our results show that the bis-THTT derivatives JH2 and JH4 presented effective parasitemia control in mice infected with P. berghei; JH5 and JH6 compounds have similar infection control results as chloroquine in mice infected P. yoelii strain. The evaluation of bis-THTT derivatives compounds in a model of BALB/c mice infected with P. berghei and P. yoelii allowed us to conclude that some of them have an antimalarial effect; however, none of the tested compounds exceeded the efficiency of chloroquine.

Isolation of local strains of the yeast Metschnikowia for biocontrol and lipid production purposes.

The bioprospection of indigenous microorganism strains with biotechnological potential represents a prominent trend. Metschnikowia yeasts exhibit diverse capabilities, such as ethanol reduction in winemaking, biocontrol potential, and lipid production. In this work, local Metschnikowia strains were isolated from different fruits by their ability to produce pulcherrimic acid, a molecule that has been linked to biocontrol activity and that binds iron giving colored colonies. Five strains were selected, each from one of five distinct sources. All of them were identified as M. pulcherrima. All five were able inhibit other yeasts and one M. pulcherrima, called M7, inhibited the growth of Aspergillus nidulans. The selected strains accumulated lipid bodies in stationary phase. Certain non-conventional yeasts like Hanseniaspora vineae are very sensitive to biomass drying, but cell extracts from M. pulcherrima added to the growth media as a source of antioxidant lipids increased their tolerance to drying. All strains isolated showed good stress tolerance (particularly to heat) and have nutrient requirements similar to a commercial M. pulcherrima strain. In addition, the M7 strain had a good growth in sugarcane and beet molasses and behaved like Saccharomyces cerevisiae in a growth medium derived from agricultural waste, a persimmon hydrolysate. Therefore, the isolation of local strains of Metschnikowia able to grow in a variety of substrates is a good source of biocontrol agents.

Cysteine-Based Perfluorinated Derivatives: A Theoretical and Experimental Study.

Cysteine-based perfluoroaromatic (hexafluorobenzene (HFB) and decafluorobiphenyl (DFBP)) were synthesized and established as a chemoselective and available core to construct molecular systems ranging from small molecules to biomolecules with interesting properties. The DFBP was found more effective than HFB for the monoalkylation of decorated thiol molecules. As proof of concept of the potential application of perfluorinated derivatives as non-cleavable linkers, some antibody-perfluorinated conjugates were prepared via thiol through two different strategies, i) using thiol from reduced cystamine coupling to carboxylic acids from mAb by amide bond, and ii) using thiols from reduction of mAb disulfide bond. Conjugates cell binding analysis demonstrated that the bioconjugation does not affect the macromolecular entity. Besides, some molecular properties of synthesized compounds are evaluated through spectroscopic characterization (FTIR and 19 F NMR chemical shifts) and theoretical calculations. The comparison of calculated and experimental 19 F NMR shifts and IR wavenumbers give excellent correlations, asserting as powerful tools in structurally identifying HFB and DFBP derivatives. Moreover, molecular docking was also developed to predict cysteine-based perfluorated derivatives' affinity against topoisomerase Il and cyclooxygenase 2 (COX-2). The results suggested that mainly cysteine-based DFBP derivatives could be potential topoisomerase II α and COX-2 binders, becoming potential anticancer agents and candidates for anti-inflammatory treatment.

Synthesis of [60]Fullerene Hybrids Endowed with Steroids and Monosaccharides: Theoretical Underpinning as Promising anti-SARS-CoV-2 Agents.

Cyclopropanation reactions between C60 and different malonates decorated with monosaccharides and steroids using the Bingel-Hirsch methodology have allowed the obtention of a new family of hybrid compounds in good yields. A complete set of instrumental techniques has allowed us to fully characterize the hybrid derivatives and to determine the chemical structure of monocycloadducts. Besides, the proposed structures were investigated by cyclic voltammetry, which evidenced the exclusive reductive pattern of fullerene Bingel-type monoadducts. Theoretical calculations at the DFT-D3(BJ)/PBE 6-311G(d,p) level of the synthesized conjugates predict the most stable conformation and determine the factors that control the hybrid molecules' geometry. Some parameters such as polarity, lipophilicity, polar surface area, hydrophilicity index, and solvent-accessible surface area were also estimated, predicting its potential permeability and capability as cell membrane penetrators. Additionally, a molecular docking simulation has been carried out using the main protease of SARS-CoV-2 (Mpro) as the receptor, thus paving the way to study the potential application of these hybrids in biomedicine.

3,4-Dihydro-2(1H)-Pyridones as Building Blocks of Synthetic Relevance.

3,4-Dihydro-2(1H)-pyridones (3,4-DHPo) and their derivatives are privileged structures, which has increased their relevance due to their biological activity in front of a broad range of targets, but especially for their importance as synthetic precursors of a variety of compounds with marked biological activity. Taking into account the large number of contributions published over the years regarding this kind of heterocycle, here, we presented a current view of 3,4-dihydro-2(1H)-pyridones (3,4-DHPo). The review includes general aspects such as those related to nomenclature, synthesis, and biological activity, but also highlights the importance of DHPos as building blocks of other relevant structures. Additional to the conventional multicomponent synthesis of the mentioned heterocycle, nonconventional procedures are revised, demonstrating the increasing efficiency and allowing reactions to be carried out in the absence of the solvent, becoming an important contribution to green chemistry. Biological activities of 3,4-DHPo, such as vasorelaxant, anti-HIV, antitumor, antibacterial, and antifungal, have demonstrated this heterocycle's potential in medicinal chemistry.

Chemical Conjugation in Drug Delivery Systems.

Cancer is one of the diseases with the highest mortality rate. Treatments to mitigate cancer are usually so intense and invasive that they weaken the patient to cure as dangerous as the own disease. From some time ago until today, to reduce resistance generated by the constant administration of the drug and improve its pharmacokinetics, scientists have been developing drug delivery system (DDS) technology. DDS platforms aim to maximize the drugs' effectiveness by directing them to reach the affected area by the disease and, therefore, reduce the potential side effects. Erythrocytes, antibodies, and nanoparticles have been used as carriers. Eleven antibody-drug conjugates (ADCs) involving covalent linkage has been commercialized as a promising cancer treatment in the last years. This review describes the general features and applications of DDS focused on the covalent conjugation system that binds the antibody carrier to the cytotoxic drug.

An Androsterone-H2 @C60 hybrid: Synthesis, Properties and Molecular Docking Simulations with SARS-Cov-2.

Invited for this month's cover are the collaborating groups of Dr. Margarita Suárez at Universidad de La Habana, Cuba, and Dr. Nazario Martín at Universidad Complutense de Madrid, Spain, together with groups at other institutions worldwide. The Front Cover shows a representation of the H2 @C60 hybrid molecule with a dehydroepiandrosterone moiety interacting with the active site of the SARS Cov-2. Read the full text of the article at 10.1002/cplu.202000770.

An Androsterone-H2 @C60 hybrid: Synthesis, Properties and Molecular Docking Simulations with SARS-Cov-2.

We report the synthesis and characterization of a fullerene-steroid hybrid that contains H2 @C60 and a dehydroepiandrosterone moiety synthesized by a cyclopropanation reaction with 76 % yield. Theoretical calculations at the DFT-D3(BJ)/PBE 6-311G(d,p) level predict the most stable conformation and that the saturation of a double bond is the main factor causing the upfield shielding of the signal appearing at -3.13 ppm, which corresponds to the H2 located inside the fullerene cage. Relevant stereoelectronic parameters were also investigated and reinforce the idea that electronic interactions must be considered to develop studies on chemical-biological interactions. A molecular docking simulation predicted that the binding energy values for the protease-hybrid complexes were -9.9 kcal/mol and -13.5 kcal/mol for PLpro and 3CLpro respectively, indicating the potential use of the synthesized steroid-H2 @C60 as anti-SARS-Cov-2 agent.

Diastereoselective Synthesis of Steroid-[60]Fullerene Hybrids and Theoretical Underpinning.

The reaction of C60 with pregnen-20-carboxaldehyde, a biologically active synthetic steroid, by using a 1,3-dipolar cycloaddition reaction (Prato's protocol) results in the formation of pyrrolidine rings bearing a new stereogenic center on the C2 of the five-membered ring. The formation of the fullerene-steroid hybrids proceeds with preference for the Re face of the 1,3-dipole, with formation of a diastereomeric mixture in 73:15 ratio. The investigation of the chiroptical properties of these conjugates allowed determining the absolute configuration of the new fulleropyrrolidines. In addition, a thorough spectroscopical study permitted to determine the structure of the two mono-cycloadducts. The electrochemical properties of the new hybrids were also evaluated by cyclic voltammetry, both systems exhibit three quasi-reversible reduction waves which are cathodically shifted in regard to the parent C60. Theoretical calculations help supporting the experimental data. A conformational study combining semiempirical methods and density functional theory has predicted the most stable diastereomer. On the basis of this agreement, a possible reaction mechanism is presented. Additionally, a molecular docking simulation has been carried out using the HIV-1 protease as receptor, thus paving the way to study the possible application of these stereoisomers in biomedicine.

Chloro-formyl steroids as precursors for hybrid heterosteroids: synthesis, spectroscopic characterization, and molecular and supramolecular structures.

Two new functionalized steroids containing both chloro and formyl substituents in ring A, and intended as precursors for the synthesis of hybrid systems, have been synthesized from ketosteroid precursors. 3-Chloro-2-formyl-17,17-dimethyl-18-nor-5α-androstane-2,13-diene, (I), and methyl 3-chloro-4-formyl-12-oxo-5ß-cholan-3-ene-24-oate, C26H37ClO4, (IV), have been synthesized using Vilsmeier reactions with 17ß-hydroxy-17α-methyl-5α-androstan-3-one and methyl 3,13-dioxo-5ß-cholan-24-oate, respectively. These products have been fully characterized using IR spectroscopy, 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry, and in the case of (IV), a single-crystal X-ray diffraction study. Crystal structures have also been determined for the known analogues 3-chloro-2-formyl-17-oxo-5α-androst-2-ene, C20H27ClO2, (II), 3-chloro-2-formyl-5α-cholest-2-ene, C28H45ClO, (III), and the absolute and relative configurations are assigned for all four compounds (I)-(IV): when the fusion between rings A and B is trans, 3-chloro-2-formyl products are formed, but when this ring fusion is cis, a 3-chloro-4-formyl product results. The formation of (I) involves not only chloroformylation at ring A, but also dehydration and the 1,2 migration of a methyl group at ring D. In each of (II), (III) and (IV), rings B and C adopt almost perfect chair conformations, while ring A adopts a half-chair conformation. Ring D adopts an envelope conformation in each of (II) and (III), albeit differently folded in the two compounds, while in (IV), it adopts a half-chair conformation. A single C-H...O hydrogen bond links the molecules of (II) into C(6) chains which are linked into sheets by means of carbonyl-carbonyl interactions. The molecules of (IV) are linked into simple C(7) chains, again by a single C-H...O hydrogen bond, but there are no direction-specific interactions in (III) that are structurally significant.

Laparoscopic Nephrectomy for the Management of Xanthogranulomatous Pyelonephritis: Still a Challenging Procedure.

OBJECTIVE: The aim of the study was to assess the feasibility of laparoscopic nephrectomy (LN) in the treatment of patients with xanthogranulomatous pyelonephritis (XGP). METHODS: Retrospective review of medical records of 17 patients (mean age 60.0 ± 13.3 years) who underwent LN by a single surgeon from 2010 to 2018. Sociodemographic and clinical data including diagnosis, presenting clinical features, surgical management, and postoperative course were analyzed. RESULTS: LN was successfully performed in 15 (88.2%) patients. Two (12.5%) patients with disseminated disease were electively converted to open nephrectomy (ON) due to failure to progress. Two (11.8%) patients experienced intraoperative complications (grades 3b and 4b). Among patients in whom LN was successfully performed (n = 15), the mean operative time was 198.0 ± 107.1 min and was shorter when no intraoperative complications occurred (169.0 ± 48.1 min). Three (20%) of these patients required transfusions and nine (60.0%) required postoperative pelvic drainage (PD). Six (40%) patients experienced postoperative complications: one grade 1, four grade 2, and one grade 5. Mean hospital stay was 4.4 ± 4.3 days, and 3.4 ± 2.2 for those experiencing manageable or no complications. Among patients without postoperative complications (n = 6), mean hospital stay was shorter when no PD was placed (1.6 vs 2.6 days). CONCLUSION: LN is a feasible surgical option in patients with XGP although given the nature of XGP, it is associated with complications-nearly all manageable-which makes it a challenging surgical procedure. Advanced laparoscopic skills and experiences are needed. Dissemination of the disease is associated with the occurrence of more severe complications and conversion to ON. PD placement seems associated with shorter hospital stay.

15-Hydroxygermacranolides as Sources of Structural Diversity: Synthesis of Sesquiterpene Lactones by Cyclization and Rearrangement Reactions. Experimental and DFT Study.

A study on the electrophile-induced rearrangement of two 15-hydroxygermacranolides, salonitenolide and artemisiifolin, was carried out. These compounds underwent electrophilic intramolecular cyclizations or acid-mediated rearrangements to give sesquiterpene lactones with different skeletons such as eudesmanolides, guaianolides, amorphanolides, or other germacranolides. The cyclization that gives guaianolides can be considered a biomimetic route to this type of sesquiterpene lactones. The use of acetone as a solvent changes the reactivity of the two starting germacranolides to the acid catalysts, with a 4,15-diol acetonide being the main product obtained. The δ-amorphenolide obtained by intramolecular cyclization of this acetonide is a valuable intermediate for accessing the antimalarials artemisinin and its derivatives. Mechanistic proposals for the transformations are raised, and to provide support them, quantum chemical calculations [DFT B3LYP/6-31+G(d,p) level] were undertaken.

[Laparoscopic uretero-ureterostomy for iatrogenic lesions of the distal uréter.] / Uretero­ureterostomía laparoscópica en las lesiones iatrogénicas del uréter distal.

OBJECTIVES: The most frequent ureteral lesions are iatrogenic, mainly due to gynecologic and urologic procedures. The resolution and repair of these lesions, when they require surgery, is often the performance of ureteroneocystostomy. We describe the technique for the repair of distal ureter lesions that preserves both anatomy and function of the urinary tract (1). The operation consists in dissection and extraction of the distal ureteral stump from its intramural tract to get at least 1 cm of free ureter, percutaneous insertion of a ureteral stent, checking the absence of tension between proximal ureter and distal dissected stump, end to end anastomosis and reinsertion of the distal ureter in the previously dissected bladder muscle layer. We present 4 cases of ureteral injury after laparoscopic simple total hysterectomy for uterine myomas with complete section of the distal ureter, that were operated 3-5 days after injury, performing laparoscopic repair surgery. We performed clinical and radiological control with intravenous urography demonstrating ureteral continuity normalization and good renal function. We believe that repair of the urinary tract with anatomical and physiological preservation must be the first option in the laparoscopic treatment of complete distal ureteral injuries, and intramural ureter dissection when needed avoids the performance of ureteroneocystostomy. It is necessary to keep progressing in the technique improvement, and to increase the number of cases and experience.

Uretero-ureterostomía laparoscópica en las lesiones iatrogénicas del uréter distal / Laparoscopic uretero-ureterostomy for iatrogenic lesions of the distal uréter

OBJETIVO: Las lesiones ureterales más frecuentes son las iatrógenas, fundamentalmente debidas a procedimientos ginecológicos y urológicos. Habitualmente la resolución y reparación de estas lesiones, cuando precisan cirugía, es la realización de una ureteroneocistostomía. Describimos una técnica para la reparación de lesiones de ureter distal que preserva tanto la anatomía como la función de la vía urinaria (1). La cirugía consiste en la disección y extracción del muñón ureteral distal de su trayecto intramural, para conseguir al menos 1 centímetro de uréter libre, colocación de stent ureteral por vía percutánea, comprobación de ausencia de tensión entre uréter proximal y muñón distal disecado, anastomosis término-terminal y reinserción de uréter distal en capa muscular vesical previamente disecada para la anastomosis. Presentamos 4 casos de lesión ureteral tras histerectomía total simple laparoscópica por miomas con sección completa de uréter distal, que se intervienen entre 3 y 5 días tras la lesión, realizando cirugía de reparación por vía laparoscópica. Se realiza control clínico y radiológico con urografía observando normalización de la continuidad ureteral y buen funcionalismo renal. Pensamos que la reparación con preservación anatómica y fisiológica de la vía urinaria, debe ser la primera opción en el tratamiento laparoscópico de las lesiones completas de uréter distal, y que la disección del uréter intramural en casos necesarios evita la realización de una ureteroneocistostomía. Es preciso seguir avanzando en el perfeccionamiento de la técnica y aumentar el número de casos y la experiencia

OBJECTIVES: The most frequent ureteral lesions are iatrogenic, mainly due to gynecologic and urologic procedures. The resolution and repair of these lesions, when they require surgery, is often the performance of ureteroneocystostomy. We describe the technique for the repair of distal ureter lesions that preserves both anatomy and function of the urinary tract (1). The operation consists in dissection and extraction of the distal ureteral stump from its intramural tract to get at least 1 cm of free ureter, percutaneous insertion of a ureteral stent, checking the absence of tension between proximal ureter and distal dissected stump, end to end anastomosis and reinsertion of the distal ureter in the previously dissected bladder muscle layer. We present 4 cases of ureteral injury after laparoscopic simple total hysterectomy for uterine myomas with complete section of the distal ureter, that were operated 3-5 days after injury, performing laparoscopic repair surgery. We performed clinical and radiological control with intravenous urography demonstrating ureteral continuity normalization and good renal function. We believe that repair of the urinary tract with anatomical and physiological preservation must be the first option in the laparoscopic treatment of complete distal ureteral injuries, and intramural ureter dissection when needed avoids the performance of ureteroneocystostomy. It is necessary to keep progressing in the technique improvement, and to increase the number of cases and experience

Catalytic Stereodivergent Synthesis of Steroid-Fulleropyrrolidine Hybrids.

The diastereoselective synthesis of cis and trans steroid-fulleropyrrolidines hybrids by reaction of N-metalated azomethine ylides [Cu(II) or Ag(I)] with the appropriate chiral ligand and C60 is described. The experimental findings reveal that the azomethine ylide stabilized by an allylic group cycloadds to [60]fullerene in an efficient manner and with a good diastereomeric excess. Furthermore, the new generated stereocenters are fully controlled by the catalytic systems used without being influenced by the chirality of the steroid. Interestingly, by this synthetic methodology the each one of the four possible stereoisomers have efficiently been obtained and characterized by CD spectra.

Theoretical Study on the Mechanism of the Thermal Retro-Cycloaddition of Isoxazolinofullerenes.

The retro-cycloaddition thermal reaction of isoxazolino[4,5:1,2][60]fullerenes to pristine fullerene seems to be guided by the electronic nature of the substituted nitrile oxide 1,3-dipole in the isoxazoline ring. Trapping experiments proved that the reaction mechanism occurs by thermal removal of the nitrile oxide 1,3-dipole in a process that is favored in the presence of a big excess of a highly efficient dipolarophile such as maleic anhydride. Theoretical gas phase calculations carried out at the B3LYP/6-31G(d) and M06-2X/6-31G(d) levels of theory underpin the experimental findings and predict that compound 1c, bearing the p-(CH3)2N-Ph substituent on the isoxazoline ring and with a remarkable experimental conversion efficiency in just 12 h, showed the lowest activation energy. Solvent calculations have predicted the same behavior in gas phase. Different approaches such as electrostatic natural population analysis and Houk's distortion/interaction model have been applied to understand how the electronic nature of these substituents affects the retro-cycloaddition reaction process. Analysis of the values of the condensed Fukui functions and dual descriptor shed light on the mechanism of the retro-cycloaddition reaction.

Competitive retro-cycloaddition reactions in heterocyclic fullerene bis-adducts ions: selective removal of the heterocyclic moieties.

RATIONALE: We have investigated the fragmentation reactions of ions from bis-adducts containing isoxazolino-, pyrrolidino- and methanofullerene moieties. METHODS: The fragmentation reactions induced by collision-induced dissociation (CID) of ions generated under electrospray ionization (ESI) in positive and negative modes of detection using an ion-trap spectrometer have been investigated. RESULTS: The competitive retro-cycloaddition process between isoxazoline and pyrrolidine rings fused to [60]fullerene reveals that it is strongly dependent on the experimental negative or positive ESI experimental conditions. Thus, whereas retro-cycloaddition reaction is favored in the pyrrolidine ring under negative conditions, the protonation occurring on the nitrogen atom of the pyrrolidine ring under positive conditions precludes its retro-cycloaddition and, therefore, only the isoxazoline ring undergoes the retro-cycloaddition process. The obtained experimental results are different from those reported when the reaction is carried out under thermal conditions. Competitive retro-cycloaddition reactions of isoxazolino- and methanofullerenes show that the heterocyclic ring undergoes cycloelimination, leaving the methanofullerene moiety unchanged. In this case, the same selectivity is observed under thermal and gas-phase conditions. CONCLUSIONS: The observed selectivity in the heterocyclic removal in these [60]fullerene derivatives is reversed from negative conditions (radical anions) to positive conditions (protonated molecules). Moreover, the retro-cycloaddition reaction behaves differently under spectrometric and thermal conditions.

Protocols of analgesia in immediate postoperative period in urological surgery. Evaluation of pain and satisfaction of the patient in their application.

OBJECTIVES: The objective of this work was to establish the analgesia protocols for different types of urological surgery and to analyze the impact on pain during the first 24 h after surgery. METHODS: The study included 186 patients undergoing urological surgery between 2011 and 2013. Seven analgesia protocols were established and applied according to the surgical procedure. At 24 h post-surgery, i.e., the initiation of analgesic treatment, patients` pain was evaluated by visual analog scale/numeric scale (VAS/NS), and their degree of satisfaction and nausea were assessed. RESULTS: The study sample comprised 137 males (73.7%) and 49 females (26.3%), with a mean age of 58.5 ± 14.7 yrs. Analgesia protocol 1 was applied in 5.9% of patients, protocol 2 in 17.8%, protocol 3 in 8.6%, protocol 4 in 38.9%, protocol 5 in 13.5%, protocol 6 in 14.6%, and protocol 7 in 0.5%. At 24 h post-surgery, the VAS/NS score was = 3 in 82.3% of patients; hence, only 17.7% required rescue analgesia; 71% of patients were highly satisfied with the treatment provided and 22.6% were satisfied. 6.4% were not satisfied. CONCLUSION: Establishing analgesia protocols according to the type of surgery is a valid and useful measure to control postoperative pain during the first 24 h and to provide appropriate treatment standardization and follow-up.

Aplicación de protocolos de analgesia en el postoperatorio inmediato en cirugía urológica. evaluación del dolor y satisfacción del paciente / Protocols of analgesia in immediate postoperative period in urological surgery. Evaluation of pain and satisfaction of the patient in their application

OBJETIVO: El objetivo de este estudio es establecer unos protocolos de analgesia distribuidos según tipos de cirugías urológicas y analizar el impacto sobre el dolor en las primeras 24 horas tras la cirugía. MÉTODOS: Estudio con 186 pacientes intervenidos de cirugía urológica entre 2011 y 2013 en los que se establecen 7 protocolos de analgesia según tipos de cirugía urológica. Analizamos a las 24 horas de la cirugía y de iniciar por tanto el tratamiento analgésico, el dolor mediante escala visual analógica/escala numérica y el grado de satisfacción del paciente y presencia de nauseas. RESULTADOS: La distribución de los pacientes según sexos fue de 137 hombres (73,7%) y 49 mujeres (26,3%), con una edad media de 58,5 ± 14,7 años. La distribución de los pacientes según el tipo de protocolo asignado fue la siguiente: 5,9% protocolo 1; 17,8% protocolo 2; 8,6% protocolo 3; 38,9% protocolo 4; 13,5% protocolo 5; 14,6% protocolo 6; 0,5% protocolo 7.Tras analizar a las 24 horas post-cirugía el nivel de dolor de los pacientes con la escala EVA/EN observamos que el 82,3% presentan un EVA/EN ≤ 3, por tanto sólo en el 17,7% de los pacientes fue preciso la utilización de analgesia de rescate. El 71% de los pacientes estaban muy satisfechos con el tratamiento pautado, y el 22,6% satisfechos. El 6,4 % no estaba satisfecho. CONCLUSIÓN: El establecimiento de protocolos de analgesia según tipos de cirugía es una medida válida, aceptable, que permite el control del dolor postoperatorio en las primeras 24 horas y que proporciona la estandarización del tratamiento y el control del mismo de forma adecuada

OBJECTIVES: The objective of this work was to establish the analgesia protocols for different types of urological surgery and to analyze the impact on pain during the first 24 h after surgery. METHODS: The study included 186 patients undergoing urological surgery between 2011 and 2013. Seven analgesia protocols were established and applied according to the surgical procedure. At 24 h post-surgery, i.e., the initiation of analgesic treatment, patients` pain was evaluated by visual analog scale/numeric scale (VAS/NS), and their degree of satisfaction and nausea were assessed. RESULTS: The study sample comprised 137 males (73.7%) and 49 females (26.3%), with a mean age of 58.5±14.7 yrs. Analgesia protocol 1 was applied in 5.9% of patients, protocol 2 in 17.8%, protocol 3 in 8.6%, protocol 4 in 38.9%, protocol 5 in 13.5%, protocol 6 in 14.6%, and protocol 7 in 0.5%.At 24 h post-surgery, the VAS/NS score was ≤ 3 in 82.3% of patients; hence, only 17.7% required rescue analgesia; 71% of patients were highly satisfied with the treatment provided and 22.6% were satisfied. 6.4% were not satisfied. CONCLUSION: Establishing analgesia protocols according to the type of surgery is a valid and useful measure to control postoperative pain during the first 24 h and to provide appropriate treatment standardization and follow-up

Resistance profile for pathogens causing urinary tract infection in a pediatric population, and antibiotic treatment response at a university hospital, 2010-2011.

INTRODUCTION: Urinary tract infection (UTI) is one of the most common bacterial infections in childhood and causes acute and chronic morbidity and long-term hypertension and chronic kidney disease. OBJECTIVES: To describe the demographic characteristics, infectious agents, patterns of antibiotic resistance, etiologic agent and profile of susceptibility and response to empirical treatment of UTI in a pediatric population. METHODS: This is a descriptive, retrospective study. RESULTS: Included in the study were 144 patients, 1:2.06 male to female ratio. The most common symptom was fever (79.9%) and 31.3% had a history of previous UTI. 72.0% of the patients had positive urine leukocyte count (>5 per field), urine gram was positive in 85.0% of samples and gram negative bacilli accounted for 77.8% for the total pathogens isolated. The most frequent uropathogens isolated were Escherichia coli and Klebsiella pneumoniae. Our E.coli isolates had a susceptibility rate higher than 90% to most of the antibiotics used, but a resistance rate of 42.6% to TMP SMX and 45.5% to ampicillin sulbactam. 6.3% of E. coli was extended-spectrum beta-lactamases producer strains. The most frequent empirical antibiotic used was amikacin, which was used in 66.0% of the patients. 17 of 90 patients who underwent voiding cistouretrography (VCUG) had vesicoureteral reflux. CONCLUSION: This study revealed that E. coli was the most frequent pathogen of community acquired UTI. We found that E. coli and other uropathogens had a high resistance rate against TMP SMX and ampicillin sulbactam. In order to ensure a successful empirical treatment, protocols should be based on local epidemiology and susceptibility rates.

ANTECEDENTES: La infección del tracto urinario (ITU) es una de las infecciones bacterianas más frecuentes en la infancia, se asocia con alta morbilidad aguda y de enfermedades a largo plazo como hipertensión arterial e insuficiencia renal crónica. OBJETIVO: Describir las características demográficas, agente etiológico, perfil de sensibilidad y respuesta al tratamiento empírico de una población pediátrica. MÉTODOS: Estudio descriptivo, retrospectivo realizado en el Hospital Pablo Tobón Uribe (HPTU), Medellín (Colombia), entre enero de 2010 y diciembre de 2011. RESULTADOS: Se incluyeron 144 pacientes, con una relación hombre: mujer de 1:2.06. El 79.9% consultó por fiebre objetiva y el 31.3% había tenido un episodio de ITU previa. El 72.0% presentó leucocituria y el gram de gota de orina sin centrifugar fue positivo en el 86.0% (77.8% de bacilos con tinción de gram negativos). Los uropatógenos más frecuentes fueron Escherichia coli y Klebsiella pneumoniae. Escherichia coli tuvo una sensibilidad mayor al 90% para la mayoría de antibióticos, excepto en el de trimetropín sulfametoxazol, con una resistencia del 42.6% y del 45.5% a la ampicilina sulbactam. Se usó la amikacina como tratamiento empírico en el 66.0%. En 17 de 90 pacientes se encontró algún grado de reflujo vesicoureteral (RVU). CONCLUSIÓN: La elección del tratamiento empírico precoz debe basarse en el conocimiento de la epidemiología y el perfil de sensibilidad y resistencia de cada institución. En este estudio se encontró elevado porcentaje de resistencia de la E. coli y otros uropatógenos a trimetropín sulfametoxazol y ampicilina sulbactam.