Publications by authors named "Luis Trujillo"

14 Publications

  • Page 1 of 1

Prospective randomized trial of interventions for vincristine-related neuropathic pain.

Pediatr Blood Cancer 2020 09 2;67(9):e28539. Epub 2020 Jul 2.

Department of Oncology, St Jude Children's Research Hospital, Memphis, Tennessee.

Background: To evaluate the efficacy of gabapentin at 20 mg/kg per day in the treatment of vincristine-related neuropathic pain.

Procedure: Children aged 1-18 years who developed vincristine-induced neuropathy on a St Jude frontline acute lymphoblastic leukemia trial were prospectively enrolled on a randomized, double-blind, placebo-controlled, phase II trial with two treatment arms: gabapentin plus opioid versus placebo plus opioid. Daily evaluations of morphine dose (mg/kg per day) and pain scores were conducted for up to 21 days; the values of the two arms were compared to assess analgesic efficacy.

Results: Of 51 study participants, 49 were eligible for analyses. Twenty-five participants were treated with gabapentin, with a mean (SD) dose of 17.97 (2.76) mg/kg per day (median 18.26, range 6.82-21.37). The mean (SD) opioid doses taken, expressed as morphine equivalent daily (mg/kg per day), were 0.26 (0.43) in the gabapentin group (25 patients, 432 days) and 0.15 (0.22) in the placebo group (24 patients, 411 days; P = .15). Only the risk classification of acute lymphoblastic leukemia was significantly associated with the daily morphine dosage (P = .0178): patients in the lower risk arm received higher daily morphine dosages. Multivariate analyses revealed a significant difference between the groups' average daily scores for the previous 24 h and "right now."

Conclusion: In this population of children with vincristine-related neuropathic pain, opioid consumption and pain scores were higher in the gabapentin group than in the placebo group. Future randomized, double-blind, placebo-controlled studies should test gabapentin given longer or at a higher dose.
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http://dx.doi.org/10.1002/pbc.28539DOI Listing
September 2020

Flow, dynamic viscoelastic and creep properties of a biological polymer produced by Sphingomonas sp. as affected by concentration.

Int J Biol Macromol 2019 Mar 21;125:1242-1247. Epub 2018 Sep 21.

Departamento de Ingeniería Química, Facultad de Química, Universidad de Sevilla, C/ Profesor García González, s/n, 41012 Sevilla, Spain. Electronic address:

In this work, the influence of the concentration on the flow behaviour, dynamic viscoelastic and creep properties of diutan gum in aqueous solution was investigated. Diutan gum is a biopolymer which belongs to the sphingans group. To know its rheological properties and its microstructure as a function of the concentration is directly related to the current and future applications of this biological polymer. Mechanical spectra showed a crossover point between G' and G″ which changed as a function of diutan gum concentration. A master curve for the frequency dependence on the η* was obtained. The creep compliance results made it possible to deduce the yield stress value and they were fitted to Burgers model. A shear-thinning behaviour was exhibited by diutan gum aqueous solutions, which was fitted to the Carreau-Yasuda model. Higher G', G″, τ and η values and lower ω, J, γ̇ and n values were obtained by increasing the gum concentration, it is being possible to modulate the viscoelasticity, viscosity and shear resistance as a function of concentration. A more complex structure with stronger entanglements between macromolecules of diutan was obtained when the concentration of diutan increases.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.09.100DOI Listing
March 2019

Fructooligosaccharides production by Schedonorus arundinaceus sucrose:sucrose 1-fructosyltransferase constitutively expressed to high levels in Pichia pastoris.

J Biotechnol 2018 Jan 12;266:59-71. Epub 2017 Dec 12.

Grupo Tecnología de Enzimas, Dirección de Investigaciones Agropecuarias, Centro de Ingeniería Genética y Biotecnología (CIGB), Ave 31 entre 158 y 190, Apartado Postal 6162, Habana, 10600, Cuba.

The non-saccharolytic yeast Pichia pastoris was engineered to express constitutively the mature region of sucrose:sucrose 1-fructosyltransferase (1-SST, EC 2.4.1.99) from Tall fescue (Schedonorus arundinaceus). The increase of the transgene dosage from one to nine copies enhanced 7.9-fold the recombinant enzyme (Sa1-SSTrec) yield without causing cell toxicity. Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (38%) and extracellular release (62%) of Sa1-SSTrec to an overall activity of 102.1 U/ml when biomass reached (106 g/l, dry weight) in fed-batch fermentation using cane sugar for cell growth. The volumetric productivity of the nine-copy clone PGFT6x-308 at the end of fermentation (72 h) was 1422.2 U/l/h. Sa1-SSTrec purified from the culture supernatant was a monomeric glycoprotein optimally active at pH 5.0-6.0 and 45-50 °C. The removal of N-linked oligosaccharides by Endo Hf treatment decreased the enzyme stability but had no effect on the substrate and product specificities. Sa1-SSTrec converted sucrose (600 g/l) into 1-kestose (GF) and nystose (GF) in a ratio 9:1 with their sum representing 55-60% (w/w) of the total carbohydrates in the reaction mixture. Variations in the sucrose (100-800 g/l) or enzyme (1.5-15 units per gram of substrate) concentrations kept unaltered the product profile. Sa1-SSTrec is an attractive candidate enzyme for the industrial production of short-chain fructooligosaccharides, most particularly 1-kestose.
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http://dx.doi.org/10.1016/j.jbiotec.2017.12.008DOI Listing
January 2018

Methadone prolongs cardiac conduction in young patients with cancer-related pain.

J Opioid Manag 2016 May-Jun;12(2):131-8

Lead Senior Biostatistician, Department of Biostatistics, St Jude Children's Research Hospital, Memphis, Tennessee.

Objective: Methadone prolongs cardiac conduction, from mild corrected QT (QTc) prolongation to torsades de pointes and ventricular fibrillation, in adults. However, methadone use for pain and its effects on cardiac conduction have not been investigated in pediatric populations.

Methods: A retrospective review of QTc intervals in patients receiving methadone analgesia was conducted. Medical records from a 4-year period (September 2006 to October 2010) at a pediatric oncology institution were reviewed, and correlations were tested between cardiac conduction and methadone dosage and duration of therapy, electrolyte levels, renal and hepatic dysfunction, and concurrent medications.

Results: Of the 61 patients who received methadone, 37 met our inclusion criteria and underwent 137 electrocardiograms (ECGs). During methadone treatment, the mean QTc was longer than that at baseline (446.5 vs 437.55 ms). The mean methadone dose was 27.0±24.3 mg/d (range, 5-125 mg/d; median, 20 mg/d) or 0.47±0.45 mg/kg per day (range, 0.05-2.25 mg/kg per day; median, 0.37 mg/kg per day), and the mean duration of therapy was 49 days. The authors identified a correlation between automated and manual ECG readings by two cardiologists (Pearson r=0.649; p<0.0001), but the authors found no correlations between methadone dose or duration and concurrent QTc-prolonging medications, sex, age, electrolyte abnormalities, or renal or hepatic dysfunction.

Conclusion: At a clinically effective analgesic dose, methadone dosage and duration were not correlated with QTc prolongation, even in the presence of other risk factors, suggesting that methadone use may be safe in pediatric populations. The correlation between automated and manual ECG readings suggests that automated ECG readings are reliable for monitoring cardiac conductivity during the reported methadone-dosage regimens.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073866PMC
http://dx.doi.org/10.5055/jom.2016.0325DOI Listing
September 2016

Patient-controlled analgesia at the end of life at a pediatric oncology institution.

Pediatr Blood Cancer 2015 Jul 27;62(7):1237-44. Epub 2015 Mar 27.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Patient controlled anesthesia (PCA) is increasingly used to manage pain in pediatric cancer patients and is important in the treatment of escalating pain at the end of life. The description of the use of opioid PCA in this population has been limited.

Procedure: This retrospective chart review of the last 2 weeks of life addressed the following objectives: (1) to describe the patient population treated with opioid PCA; (2) to describe the morphine-equivalent doses (MED) (mg/kg/day); and (3) to describe the pain scores (PS).

Results: Twenty-eight percent of inpatients used opioid PCA for pain control during the last 2 weeks of life. The mean MED (mg/kg/day) (SD) at 2 weeks prior and the day of death were 10.7 (17.9) and 19 (25.8). The mean MED increased over the last 2 weeks of life for all patients and across age groups and cancer diagnoses (all P < 0.05). The mean MED was significantly higher in the younger age group (age <13 vs. age ≥ 13) on the day of death (P < 0.04). There was a significant change in mean PS over the last 2 weeks of life (P < 0.001), with the highest PS on the day before death. The most frequently used concurrent medications were benzodiazepines (91%).

Conclusions: Children and young adults with cancer experience high opioid requirements and significant dose increases during the last 2 weeks of life. Additionally, PS increase toward the end of life. Opioid rotation and addition of adjuvant medications merit consideration in the context of escalating opioid requirements.
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http://dx.doi.org/10.1002/pbc.25493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433603PMC
July 2015

Complete sucrose hydrolysis by heat-killed recombinant Pichia pastoris cells entrapped in calcium alginate.

Microb Cell Fact 2014 Jun 18;13:87. Epub 2014 Jun 18.

Plant-Microbe Interactions Laboratory, Center for Genetic Engineering and Biotechnology (CIGB), Ave 31 entre 158 y 190, Apartado Postal 6162, Habana 10600, Cuba.

Background: An ideal immobilized biocatalyst for the industrial-scale production of invert sugar should stably operate at elevated temperatures (60-70°C) and high sucrose concentrations (above 60%, w/v). Commercial invertase from the yeast Saccharomyces cerevisiae is thermolabile and suffers from substrate inhibition. Thermotoga maritima β-fructosidase (BfrA) is the most thermoactive and thermostable sucrose-hydrolysing enzyme so far identified and allows complete inversion of the substrate in highly concentrated solutions.

Results: In this study, heat-killed Pichia pastoris cells bearing N-glycosylated BfrA in the periplasmic space were entrapped in calcium alginate beads. The immobilized recombinant yeast showed maximal sucrose hydrolysis at pH 5-7 and 90°C. BfrA was 65% active at 60°C and had no activity loss after incubation without the substrate at this temperature for 15 h. Complete inversion of cane sugar (2.04 M) at 60°C was achieved in batchwise and continuous operation with respective productivities of 4.37 and 0.88 gram of substrate hydrolysed per gram of dry beads per hour. The half-life values of the biocatalyst were 14 and 20 days when operated at 60°C in the stirred tank and the fixed-bed column, respectively. The reaction with non-viable cells prevented the occurrence of sucrose fermentation and the formation of by-products. Six-month storage of the biocatalyst in 1.46 M sucrose (pH 5.5) at 4°C caused no reduction of the invertase activity.

Conclusions: The features of the novel thermostable biocatalyst developed in this study are more attractive than those of immobilized S. cerevisiae cells for application in the enzymatic manufacture of inverted sugar syrup in batch and fixed-bed reactors.
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http://dx.doi.org/10.1186/1475-2859-13-87DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4078364PMC
June 2014

Clinical and pathological characterization of Mesoamerican nephropathy: a new kidney disease in Central America.

Am J Kidney Dis 2013 Nov 10;62(5):908-18. Epub 2013 Jul 10.

Division of Renal Medicine, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Background: An endemic of chronic kidney disease (CKD) of unknown cause among rural inhabitants in Central America has been identified. Young and otherwise healthy men working in plantations are frequently affected. The name Mesoamerican nephropathy (MeN) has been suggested. Clinically, MeN presents with low-grade proteinuria and progressive kidney failure. The renal pathology of this disease has not yet been described.

Study Design: Case series.

Setting & Participants: 8 male patients with CKD of unknown cause and clinically suspected MeN were recruited from a nephrology unit in El Salvador. All recruited patients had been working on plantations. Kidney biopsies, blood, and urine samples were collected.

Outcomes & Measurements: Renal morphology examined with light microscopy, immunofluorescence, and electron microscopy; clinical and biochemical characteristics.

Results: A similar pattern was seen in all 8 biopsy specimens, with extensive glomerulosclerosis (29%-78%) and signs of chronic glomerular ischemia in combination with tubular atrophy and interstitial fibrosis, but only mild vascular lesions. Electron microscopy indicates podocytic injury. Biochemical workup showed reduced estimated glomerular filtration rate (27-79 mL/min/1.73 m(2) with the CKD Epidemiology Collaboration [CKD-EPI] creatinine equation), low-grade albuminuria, and increased levels of tubular injury biomarkers. Hypokalemia was found in 6 of 8 patients.

Limitations: Small number of patients from one country.

Conclusions: This study is the first report of the biochemical and morphologic findings in patients with MeN. Our findings indicate that MeN constitutes a previously unrecognized kidney disease with damage to both glomerular and tubulointerstitial compartments.
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http://dx.doi.org/10.1053/j.ajkd.2013.05.019DOI Listing
November 2013

Constitutive high-level expression of a codon-optimized β-fructosidase gene from the hyperthermophile Thermotoga maritima in Pichia pastoris.

Appl Microbiol Biotechnol 2013 Feb 21;97(3):1201-12. Epub 2012 Jul 21.

Plant-Microbe Interactions Laboratory, Center for Genetic Engineering and Biotechnology (CIGB), Ave 31 entre 158 y 190, Apartado Postal 6162, Havana, 10600, Cuba.

Enzymes for use in the sugar industry are preferred to be thermotolerant. In this study, a synthetic codon-optimized gene encoding a highly thermostable β-fructosidase (BfrA, EC 3.2.1.26) from the bacterium Thermotoga maritima was expressed in the yeast Pichia pastoris. The gradual increase of the transgene dosage from one to four copies under the control of the constitutive glyceraldehyde 3-phosphate dehydrogenase promoter had an additive effect on BfrA yield without causing cell toxicity. Maximal values of cell biomass (115 g/l, dry weight) and overall invertase activity (241 U/ml) were reached at 72 h in fed-batch fermentations using cane sugar as the main carbon source for growth. Secretion driven by the Saccharomyces cerevisiae α-factor signal peptide resulted in periplasmic retention (44 %) and extracellular release (56 %) of BfrA. The presence of N-linked oligosaccharides did not influence the optimal activity, thermal stability, kinetic properties, substrate specificity, and exo-type action mode of the yeast-secreted BfrA in comparison to the native unglycosylated enzyme. Complete inversion of cane sugar at initial concentration of 60 % (w/v) was achieved by periplasmic BfrA in undisrupted cells reacting at pH 5.5 and 70 °C, with average productivity of 4.4 g of substrate hydrolyzed per grams of biomass (wet weight) per hour. The high yield of fully active glycosylated BfrA here attained by recombinant P. pastoris in a low-cost fermentation process appears to be attractive for the large-scale production of this thermostable enzyme useful for the manufacture of inverted sugar syrup.
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http://dx.doi.org/10.1007/s00253-012-4270-2DOI Listing
February 2013

A randomized controlled trial comparing the AccuVein AV300 device to standard insertion technique for intravenous cannulation of anesthetized children.

Paediatr Anaesth 2012 Sep 14;22(9):884-9. Epub 2012 Jun 14.

Department of Anesthesiology, American University of Beirut, Beirut, Lebanon.

Objectives And Aims: To evaluate the efficacy of the AccuVein AV300 device in improving the first-time success rate of intravenous cannulation of anesthetized pediatric patients.

Background: The AccuVein AV300 device was developed to assist venepuncture and intravenous cannulation by enhancing the visibility of superficial veins. It uses infrared light to highlight hemoglobin so that blood vessels are darkly delineated against a red background.

Methods/materials: Patients were randomized to cannulation with the AccuVein AV300 device or standard insertion by experienced pediatric anesthesiologists. An observer recorded the number of skin punctures and cannulation attempts required, and the time between tourniquet application and successful cannulation or four skin punctures, whichever came first.

Results And Conclusions: There were 146 patients with a median age of 4.6 years (range, 0.18-17.1 years), 46.6% were male, 80.8% were light skin colored, and 15.7% were younger than 2 years. The first-attempt success rates were 75% (95% CI, 63.8-84.2%) using AV300 and 73% (95% CI, 61.9-81.9%) using the standard method (P = 0.85). Patients with dark or medium skin color were 0.38 times less likely to have a successful first attempt than patients with light skin color. The difference between the two treatment groups in number of skin punctures and the time to insertion was not significant. Although the AV300 was easy to use and improved visualization of the veins, we found no evidence that it was superior to the standard method of intravenous cannulation in unselected pediatric patients under anesthesia.
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http://dx.doi.org/10.1111/j.1460-9592.2012.03896.xDOI Listing
September 2012

High levan accumulation in transgenic tobacco plants expressing the Gluconacetobacter diazotrophicus levansucrase gene.

J Biotechnol 2011 Jun 22;154(1):93-8. Epub 2011 Apr 22.

Laboratorio Interacciones Planta-Microorganismo, Centro de Ingeniería Genética y Biotecnología (CIGB), Habana, Cuba.

Bacterial levansucrase (EC 2.4.1.10) converts sucrose into non-linear levan consisting of long β(2,6)-linked fructosyl chains with β(2,1) branches. Bacterial levan has wide food and non-food applications, but its production in industrial reactors is costly and low yielding. Here, we report the constitutive expression of Gluconacetobacter diazotrophicus levansucrase (LsdA) fused to the vacuolar targeting pre-pro-peptide of onion sucrose:sucrose 1-fructosyltransferase (1-SST) in tobacco, a crop that does not naturally produce fructans. In the transgenic plants, levan with degree of polymerization above 10(4) fructosyl units was detected in leaves, stem, root, and flowers, but not in seeds. High levan accumulation in leaves led to gradual phenotypic alterations that increased with plant age through the flowering stage. In the transgenic lines, the fructan content in mature leaves varied from 10 to 70% of total dry weight. No oligofructans were stored in the plant organs, although the in vitro reaction of transgenic LsdA with sucrose yielded β(2,1)-linked FOS and levan. Transgenic lines with levan representing up to 30mgg(-1) of fresh leaf weight produced viable seeds and the polymer accumulation remained stable in the tested T1 and T2 progenies. The lsdA-expressing tobacco represents an alternative source of highly polymerized levan.
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http://dx.doi.org/10.1016/j.jbiotec.2011.04.007DOI Listing
June 2011

NmDef02, a novel antimicrobial gene isolated from Nicotiana megalosiphon confers high-level pathogen resistance under greenhouse and field conditions.

Plant Biotechnol J 2010 Aug;8(6):678-90

Center for Genetic Engineering and Biotechnology, Havana, Cuba.

Plant defensins are small cysteine-rich peptides that inhibit the growth of a broad range of microbes. In this article, we describe NmDef02, a novel cDNA encoding a putative defensin isolated from Nicotiana megalosiphon upon inoculation with the tobacco blue mould pathogen Peronospora hyoscyami f.sp. tabacina. NmDef02 was heterologously expressed in the yeast Pichia pastoris, and the purified recombinant protein was found to display antimicrobial activity in vitro against important plant pathogens. Constitutive expression of NmDef02 gene in transgenic tobacco and potato plants enhanced resistance against various plant microbial pathogens, including the oomycete Phytophthora infestans, causal agent of the economically important potato late blight disease, under greenhouse and field conditions.
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http://dx.doi.org/10.1111/j.1467-7652.2010.00501.xDOI Listing
August 2010

A type II protein secretory pathway required for levansucrase secretion by Gluconacetobacter diazotrophicus.

J Bacteriol 2004 Aug;186(15):5031-9

Plant-Microbe Interactions Lab, Plant Division, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana 10600, Cuba.

The endophytic diazotroph Gluconacetobacter diazotrophicus secretes a constitutively expressed levansucrase (LsdA, EC 2.4.1.10) to utilize plant sucrose. LsdA, unlike other extracellular levansucrases from gram-negative bacteria, is transported to the periplasm by a signal-peptide-dependent pathway. We identified an unusually organized gene cluster encoding at least the components LsdG, -O, -E, -F, -H, -I, -J, -L, -M, -N, and -D of a type II secretory system required for LsdA translocation across the outer membrane. Another open reading frame, designated lsdX, is located between the operon promoter and lsdG, but it was not identified in BLASTX searches of the DDBJ/EMBL/GenBank databases. The lsdX, -G, and -O genes were isolated from a cosmid library of strain SRT4 by complementation of an ethyl methanesulfonate mutant unable to transport LsdA across the outer membrane. The downstream genes lsdE, -F, -H, -I, -J, -L, -M, -N, and -D were isolated through chromosomal walking. The high G+C content (64 to 74%) and the codon usage of the genes identified are consistent with the G+C content and codon usage of the standard G. diazotrophicus structural gene. Sequence analysis of the gene cluster indicated that a polycistronic transcript is synthesized. Targeted disruption of lsdG, lsdO, or lsdF blocked LsdA secretion, and the bacterium failed to grow on sucrose. Replacement of Cys(162) by Gly at the C terminus of the pseudopilin LsdG abolished the protein functionality, suggesting that there is a relationship with type IV pilins. Restriction fragment length polymorphism analysis revealed conservation of the type II secretion operon downstream of the levansucrase-levanase (lsdA-lsdB) locus in 14 G. diazotrophicus strains representing 11 genotypes recovered from four different host plants in diverse geographical regions. To our knowledge, this is the first report of a type II pathway for protein secretion in the Acetobacteraceae.
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http://dx.doi.org/10.1128/JB.186.15.5031-5039.2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC451657PMC
August 2004

[Gallstone ileus (author's transl)].

Rev Invest Clin 1978 Jul-Sep;30(3):297-301

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December 1978