Publications by authors named "Rubén Lopez"

23 Publications

  • Page 1 of 1

Extension of Intravenous Tubing and Pumps Outside Rooms for Safety and Efficiency.

Crit Care Nurse 2021 Aug;41(4):84-88

Anita Catlin is the manager of nursing research, Kaiser Permanente Vallejo Medical Center.

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http://dx.doi.org/10.4037/ccn2021107DOI Listing
August 2021

Parametric Study of the Factors Influencing Liposome Physicochemical Characteristics in a Periodic Disturbance Mixer.

Langmuir 2021 07 7;37(28):8544-8556. Epub 2021 Jul 7.

Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame West, Montreal, Quebec H3C 1K3, Canada.

Liposomes encapsulate different substances ranging from drugs to genes. Control over the average size and size distribution of these nanoparticles is vital for biomedical applications since these characteristics determine to a high degree where liposomes will accumulate in the human body. Micromixers enable the continuous flow synthesis of liposomes, improving size control and reproducibility. Recently, Dean flow dynamics-based micromixers, such as the periodic disturbance mixer (PDM), have been shown to produce controlled-size liposomes in a scalable and reproducible way. However, contrary to micromixers based on molecular diffusion or chaotic advection, their production factors and their influence over liposome properties have not yet been addressed thoroughly. In this work, we present a comprehensive parametric study of the effects of flow conditions and molecular changing factors such as concentration, lipid type, and temperature on the physicochemical characteristics of liposomes. Numerical models and confocal images are used to quantitatively and qualitatively evaluate mixing performance under different liposome production conditions and their relationship with vesicle properties. The total flow rate (TFR) and, to a lesser extent, the flow rate ratio (FRR) control the liposome size and size distribution. Effects on liposome size are also observed by changing the molecular factors. Moreover, the liposome ζ potential is independent of the factors studied here. The micromixer presented in this work enables the production of liposomes as small as 24 nm, with monodispersed to low or close to low polydispersed liposome populations as well as a production rate as high as 41 mg/h.
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http://dx.doi.org/10.1021/acs.langmuir.1c01005DOI Listing
July 2021

The effect of different organic solvents in liposome properties produced in a periodic disturbance mixer: Transcutol®, a potential organic solvent replacement.

Colloids Surf B Biointerfaces 2021 Feb 4;198:111447. Epub 2020 Nov 4.

Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame-West, Montreal, QC H3C 1K3, Canada.

Liposomes are versatile particles used in the biomedical field as drug delivery systems (DDS). Liposome production using micromixers have shown to yield nanoparticles for DDS in a single step with a controllable size by changing flow conditions. Nonetheless, other factors such as the organic solvent, play a crucial role in the liposome formation process. Furthermore, drug solubility and toxicity are pivotal when deciding which organic solvent to choose. In this work, liposomes were produced in a periodic disturbance mixer (PDM). We investigated three conventional organic solvents: ethanol, methanol, and isopropanol as well as Transcutol®. We assessed the organic solvent influence on liposome characteristics (size, size distribution and zeta potential). Among the four organic solvents, Transcutol® yielded the smallest liposomes, which ranged from 80 nm to 160 nm. Moreover, a more in-depth investigation showed that Transcutol® produced smaller or similar-sized particles under different temperature and lipid concentration conditions, compared with ethanol. Furthermore, we proved that particles zeta potential was not influenced by the organic solvent, production temperature, or lipid concentration. This work results show that Transcutol® could replace the conventional alcohol-based solvents and can potentially avoid filtration steps due to its low toxicity. Therefore, the present approach is appealing for DDS development.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111447DOI Listing
February 2021

Characteristics and Outcomes in Patients with Ventilator-Associated Pneumonia Who Do or Do Not Develop Acute Respiratory Distress Syndrome. An Observational Study.

J Clin Med 2020 Oct 29;9(11). Epub 2020 Oct 29.

Department of Pneumology and Respiratory Intensive Care Unit, Institut Clinic de Respiratori, Hospital Clinic of Barcelona, 08036 Barcelona, Spain.

Ventilator-associated pneumonia (VAP) is a well-known complication of patients on invasive mechanical ventilation. The main cause of acute respiratory distress syndrome (ARDS) is pneumonia. ARDS can occur in patients with community-acquired or nosocomial pneumonia. Data regarding ARDS incidence, related pathogens, and specific outcomes in patients with VAP is limited. This is a cohort study in which patients with VAP were evaluated in an 800-bed tertiary teaching hospital between 2004 and 2016. Clinical outcomes, microbiological and epidemiological data were assessed among those who developed ARDS and those who did not. Forty-one (13.6%) out of 301 VAP patients developed ARDS. Patients who developed ARDS were younger and presented with higher prevalence of chronic liver disease. Pseudomonas aeruginosa was the most frequently isolated pathogen, but without any difference between groups. Appropriate empirical antibiotic treatment was prescribed to ARDS patients as frequently as to those without ARDS. Ninety-day mortality did not significantly vary among patients with or without ARDS. Additionally, patients with ARDS did not have significantly higher intensive care unit (ICU) and 28-day mortality, ICU, and hospital length of stay, ventilation-free days, and duration of mechanical ventilation. In summary, ARDS deriving from VAP occurs in 13.6% of patients. Although significant differences in clinical outcomes were not observed between both groups, further studies with a higher number of patients are needed due to the possibility of the study being underpowered.
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http://dx.doi.org/10.3390/jcm9113508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692126PMC
October 2020

Surface Response Based Modeling of Liposome Characteristics in a Periodic Disturbance Mixer.

Micromachines (Basel) 2020 Feb 25;11(3). Epub 2020 Feb 25.

Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame-West, Montreal, QC H3C 1K3, Canada.

Liposomes nanoparticles (LNPs) are vesicles that encapsulate drugs, genes, and imaging labels for advanced delivery applications. Control and tuning liposome physicochemical characteristics such as size, size distribution, and zeta potential are crucial for their functionality. Liposome production using micromixers has shown better control over liposome characteristics compared with classical approaches. In this work, we used our own designed and fabricated Periodic Disturbance Micromixer (PDM). We used Design of Experiments (DoE) and Response Surface Methodology (RSM) to statistically model the relationship between the Total Flow Rate (TFR) and Flow Rate Ratio (FRR) and the resulting liposomes physicochemical characteristics. TFR and FRR effectively control liposome size in the range from 52 nm to 200 nm. In contrast, no significant effect was observed for the TFR on the liposomes Polydispersity Index (PDI); conversely, FRR around 2.6 was found to be a threshold between highly monodisperse and low polydispersed populations. Moreover, it was shown that the zeta potential is independent of TFR and FRR. The developed model presented on the paper enables to pre-establish the experimental conditions under which LNPs would likely be produced within a specified size range. Hence, the model utility was demonstrated by showing that LNPs were produced under such conditions.
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http://dx.doi.org/10.3390/mi11030235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7143066PMC
February 2020

Tobacco smoking is an independent factor associated with retinal damage in systemic lupus erythematosus: a cross-sectional and retrospective study.

Rheumatol Int 2020 Mar 27;40(3):367-374. Epub 2019 Nov 27.

Rheumatology Service, Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas, GC, Spain.

To analyze the influence of tobacco smoking on systemic lupus erythematosus (SLE) clinical features and damage. Cross-sectional and retrospective, case-control study comparing SLE patients with and without tobacco exposure. Cumulative clinical data and comorbidities were collected, and severity (Katz index) and damage (SLICC/ACR damage index) (SDI) indices were calculated. Pack-years (PY) was used to estimate lifetime tobacco exposure. A logistic regression was carried out to explore the impact of tobacco use on retinal damage. 216 patients were included. The mean age was 49 years (± 12.7), 93% were females, and median disease duration was 17 years [interquartile range (IQR):9-25]. Fifty-three percent of patients were smokers at some point. The median PY was 13 (IQR: 6-20.5). Only 54.8% of active smokers recalled having been informed of the negative effects of smoking, versus 83.3% of never smokers (< 0.001). In a bivariant analysis, an association between tobacco use at any time and discoid lupus [OR: 3.5(95%CI 1.5-8.9); p = 0.002] photosensitivity [OR: 2.06(95%CI 1.16-3.7); p = 0.01] and peripheral arteriopathy (p = 0.007) was found. Considering SDI item by item, a significant association with retinal damage, adjusted for age [OR: 1.03(95%CI 1-1.07); p = 0.04], was found. Using PYs, an association was found with discoid lupus (p = 0.01), photosensitivity (p = 0.03) and peripheral arteriopathy (p = 0.01), global SDI > 0 (p = 0.002) and retinal damage (p = 0.02). In a multivariate analysis exploring factors associated with retinal damage, any previous smoking history and SDI remained associated with retinal damage. Tobacco smoking is associated with cutaneous manifestations and damage and is an independent predictor of retinal damage in SLE patients.
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http://dx.doi.org/10.1007/s00296-019-04473-8DOI Listing
March 2020

Pomolic acid reduces contractility and modulates excitation-contraction coupling in rat cardiomyocytes.

Eur J Pharmacol 2019 May 13;851:88-98. Epub 2019 Feb 13.

Laboratory of Cellular Physiology, Centre of Biophysics and Biochemistry, Venezuelan Institute for Scientific Research (IVIC), Caracas, Venezuela; Physiology and Biochemistry Research Group-PHYSIS, Department of Physiology and Biochemistry, Faculty of Medicine, University of Antioquia, Medellín, Colombia. Electronic address:

Pomolic acid (PA) isolated from Licania pittieri has hypotensive effects in rats, inhibits human platelet aggregation and elicits endothelium-dependent relaxation in rat aortic rings. The present study was designed to investigate the effects of PA on cardiomyocytes. Trabeculae and enzymatically isolated cardiomyocytes from rats were used to evaluate the concentration-dependent effects of PA on cardiac muscle tension and excitation-contraction coupling (ECC) by recording Ca transients reported with Fluo-3 and Fura-2, as well as L-type Ca currents (LTCC). PA reduced the contractile force in rat cardiac trabeculae with an EC = 14.3 ± 2.4 μM. PA also reduced the amplitude of Ca transients in a concentration-dependent manner, with an EC = 10.5 ± 1.3 μM, without reducing sarcoplasmic reticulum (SR) Ca loading. PA decreased the half width of the Ca transient by 31.7 ± 3.3% and increased the decay time and decay time constant (τ) by 7.6 ± 2.7% and 75.6 ± 3.7%, respectively, which was associated with increased phospholamban (PLN) phosphorylation. PA also reversibly reduced the macroscopic LTCC in the cardiomyocyte membrane, but did not demonstrate any effects on skeletal muscle ECC. In conclusion, PA reduces LTCC, Ca transients and cardiomyocyte force, which along with its vasorelaxant effects explain its hypotensive properties. Increased PLN phosphorylation protected the SR from Ca depletion. Considering the effects of PA on platelet aggregation and the cardiovascular system, we propose it as a new potential, multitarget cardiovascular agent with a demonstrated safety profile.
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http://dx.doi.org/10.1016/j.ejphar.2019.02.016DOI Listing
May 2019

Endovascular aortic sealing with Nellix reduces intraoperative radiation dose when compared to endovascular aortic repair.

J Vasc Surg 2018 04 9;67(4):1068-1073. Epub 2017 Oct 9.

Department of Vascular Surgery, Lucerne Cantonal Hospital, Lucerne, Switzerland.

Objective: To analyze radiation exposure during endovascular aortic sealing (EVAS) in comparison with standard endovascular aortic repair (EVAR) in clinical practice.

Methods: From December 2013 to October 2016 (35 months), 60 patients were analyzed for intraoperative radiation exposure during EVAR: 30 consecutive patients (mean age, 73.10 years; 28 male) received EVAS (Nellix Endologix); within the same time frame, 30 patients were treated with standard EVAR (mean age, 71.87 years; 30 male). An indirect dose analysis was performed for both groups of patients, including effective dose and cumulative air kerma. Furthermore, fluoroscopy time (FT), dose area product, and time of procedure were included in the study.

Results: The effective dose was significantly reduced in the EVAS group (3.72 mSv) compared with the group treated with standard EVAR (6.8 mSv; P ≤ .001). The cumulative air kerma was also lowered in EVAS (67.65 mGy vs 139 mGy in EVAR; P ≤ .001). FT for the entire group was 13 minutes and was shorter (P < .001) for EVAS (9 minutes) in comparison with EVAR (19 minutes). The dose area product for the entire cohort was 16.95 Gy.cm and was lower during EVAS (12.4 Gy.cm) than during EVAR (22.6 Gy.cm; P < .001). The median operating time for the entire group was 123.5 minutes and was significantly shorter (P < .01) for EVAS (119 minutes vs EVAR at 132 minutes). The FT shows a significant correlation with the patient's weight (P = .022), body mass index (P = .004), and time of procedure (P = .005).

Conclusions: EVAS is associated with a relevant decrease in indirect measured radiation dose and time of procedure compared with standard EVAR. A relevant reduction in dose during EVAS is highly likely to result in lower exposure to radiation for physicians and staff. Such a result would be highly advantageous and calls for further analysis.
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http://dx.doi.org/10.1016/j.jvs.2017.07.126DOI Listing
April 2018

Levator Palpebrae Superioris Muscle Direct Neurotization.

J Craniofac Surg 2017 Nov;28(8):e747-e748

*Plastic and Reconstructive Surgery Department, Hospital General "Dr. Manuel Gea González;" †Neurophysiology Department, Hospital Angeles Pedregal ‡Opthalmology Department, Hospital General "Dr. Manuel Gea González," Mexico City, Mexico.

Direct muscle neurotization has been proved to be a feasible technique for facial reanimation microsurgical procedures. Direct muscle neurotization is performed by implanting the interposition nerve graft directly into the substance of the muscle. The authors present the case of a 36-year-old male patient with upper eyelid dysfunction secondary to facial trauma. The levator palpebrae superioris muscle was macroscopically unaffected; however, neurophysiological test proved a selective denervation of the CN III motor branch to the levator palpebrae superioris muscle. Direct muscle neurotization was performed by means of 2 separate nerve procedures. The authors have made follow-up for 3 months after surgery. The authors have noted development of upper eyelid movement meaning adequate function of the neurotized muscle. The authors believe that this procedure could be integrated into the surgical options to treat selective nerve injuries should the right patient is encountered.
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http://dx.doi.org/10.1097/SCS.0000000000003924DOI Listing
November 2017

An RYR1 mutation associated with malignant hyperthermia is also associated with bleeding abnormalities.

Sci Signal 2016 07 5;9(435):ra68. Epub 2016 Jul 5.

Department of Paediatric Neurology, Neuromuscular Service, Evelina Children's Hospital, St Thomas' Hospital, London SE1 7EH, UK. Randall Division of Cell and Molecular Biophysics, Muscle Signalling Section, King's College, London SE1 1UL, UK. Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 9RX, UK.

Malignant hyperthermia is a potentially fatal hypermetabolic disorder triggered by halogenated anesthetics and the myorelaxant succinylcholine in genetically predisposed individuals. About 50% of susceptible individuals carry dominant, gain-of-function mutations in RYR1 [which encodes ryanodine receptor type 1 (RyR1)], though they have normal muscle function and no overt clinical symptoms. RyR1 is predominantly found in skeletal muscle but also at lower amounts in immune and smooth muscle cells, suggesting that RYR1 mutations may have a wider range of effects than previously suspected. Mild bleeding abnormalities have been described in patients with malignant hyperthermia carrying gain-of-function RYR1 mutations. We sought to determine the frequency and molecular basis for this symptom. We found that some patients with specific RYR1 mutations had abnormally high bleeding scores, whereas their healthy relatives did not. Knock-in mice with the malignant hyperthermia susceptibility RYR1 mutation Y522S (MHS RYR1Y522S) had longer bleeding times than their wild-type littermates. Primary vascular smooth muscle cells from RYR1Y522S knock-in mice exhibited a higher frequency of subplasmalemmal Ca(2+) sparks, leading to a more negative resting membrane potential. The bleeding defect of RYR1Y522S mice and of one patient was reversed by treatment with the RYR1 antagonist dantrolene, and Ca(2+) sparks in primary vascular smooth muscle cells from the MHS RYR1Y522S mice were blocked by ryanodine or dantrolene. Thus, RYR1 mutations may lead to prolonged bleeding by altering vascular smooth muscle cell function. The reversibility of the bleeding phenotype emphasizes the potential therapeutic value of dantrolene in the treatment of such bleeding disorders.
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http://dx.doi.org/10.1126/scisignal.aad9813DOI Listing
July 2016

Duloxetine for the treatment of painful diabetic peripheral neuropathy in Venezuela: economic evaluation.

Medwave 2015 Sep 25;15(8):e6265. Epub 2015 Sep 25.

Eli Lilly and Company, Buenos Aires, Argentina.

Introduction: Painful diabetic peripheral neuropathy affects 40-50% of patients with diabetic neuropathy, leading to impaired quality of life and substantial costs. Duloxetine and pregabalin have evidence-based support, and are formally approved for controlling painful diabetic peripheral neuropathy.

Methods: We used a 12-week decision model for examining painful diabetic peripheral neuropathy first-line therapy with daily doses of duloxetine 60mg or pregabalin 300mg, under the perspective of the Instituto Venezolano de los Seguros Sociales. We gathered model parameters from published literature and expert´s opinion, focusing on the magnitude of pain relief, the presence of adverse events, the possibility of withdrawal owing to intolerable adverse events or due to lack of efficacy, and the quality-adjusted life years expected in each strategy. We analyzed direct medical costs (which are expressed in Bolívares Fuertes, BsF) comprising drug acquisition besides additional care devoted to treatment of adverse events and poor pain relief. We conducted both deterministic and probabilistic sensitivity analyses.

Results: Total expected costs per 1000 patients were BsF 1 046 146 (26%) lower with duloxetine than with pregabalin. Most of these savings (91%) corresponds to the difference in the acquisition’s cost of each medication. duloxetine also provided 23 more patients achieving good pain relief and a gain of about two quality-adjusted life years per 1000 treated. Model was robust to plausible changes in main parameters. Duloxetine remained the preferred option in 93.9% of the second-order Monte Carlo simulations.

Conclusions: This study suggests duloxetine dominates (i.e., is more effective and lead to gains in quality-adjusted life years), remaining less costly than pregabalin for treatment of painful diabetic peripheral neuropathy.
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http://dx.doi.org/10.5867/medwave.2015.08.6265DOI Listing
September 2015

Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation-contraction coupling supramolecular complex.

Biochem J 2015 Feb;466(1):123-35

*Departments of Anesthesia and of Biomedicine, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland.

The protein mammalian target of rapamycin (mTOR) is a serine/threonine kinase regulating a number of biochemical pathways controlling cell growth. mTOR exists in two complexes termed mTORC1 and mTORC2. Regulatory associated protein of mTOR (raptor) is associated with mTORC1 and is essential for its function. Ablation of raptor in skeletal muscle results in several phenotypic changes including decreased life expectancy, increased glycogen deposits and alterations of the twitch kinetics of slow fibres. In the present paper, we show that in muscle-specific raptor knockout (RamKO), the bulk of glycogen phosphorylase (GP) is mainly associated in its cAMP-non-stimulated form with sarcoplasmic reticulum (SR) membranes. In addition, 3[H]-ryanodine and 3[H]-PN200-110 equilibrium binding show a ryanodine to dihydropyridine receptors (DHPRs) ratio of 0.79 and 1.35 for wild-type (WT) and raptor KO skeletal muscle membranes respectively. Peak amplitude and time to peak of the global calcium transients evoked by supramaximal field stimulation were not different between WT and raptor KO. However, the increase in the voltage sensor-uncoupled RyRs leads to an increase of both frequency and mass of elementary calcium release events (ECRE) induced by hyper-osmotic shock in flexor digitorum brevis (FDB) fibres from raptor KO. The present study shows that the protein composition and function of the molecular machinery involved in skeletal muscle excitation-contraction (E-C) coupling is affected by mTORC1 signalling.
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http://dx.doi.org/10.1042/BJ20140935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843809PMC
February 2015

Longitudinal practice patterns of prophylaxis of glucocorticoid-induced osteoporosis in patients with polymyalgia rheumatica.

Rheumatol Int 2014 Oct 12;34(10):1459-63. Epub 2014 Apr 12.

Department of Rheumatology, Hospital Universitario Gran Canaria Dr. Negrin, Universidad de Las Palmas de Gran Canaria, La Ballena s/n, 35010, Las Palmas, Spain,

The aim of this study was to analyze the longitudinal practice patterns of prophylaxis of glucocorticoid-induced osteoporosis in patients with polymyalgia rheumatica (PMR). Patients diagnosed with PMR were collected retrospectively in two rheumatology departments. In addition to demographic and diagnostic criteria, the chart review included the following information at baseline and at follow-up: doses of prednisone, prescription of calcium, vitamin D and bisphosphonates, bone mass measurement (BMD) and fragility fractures. We analyzed the percentage of patients undergoing BMD and were prescribed a bisphosphonate over the years. We evaluated 158 patients: 117 of them were women, mean age was 73 years, and they had an average follow-up of 4.8 years. 104 patients (66 %) received osteoporosis medication during the first visit, 44 of them were given bisphosphonate. During follow-up, another 30 treatments with bisphosphonate were added (46 % overall) while 37 cases (23 %) received no treatment with calcium or bisphosphonate. BMD was performed in 111 patients (69 %; 53 % of males and 76 % of females). Factors associated with the use of bisphosphonates were female sex (OR 4.4, 95 % CI 4.02-4.86), BMD (OR 2.4, 95 % CI 2.05-2.78) and commencement of treatment after the year 2005 (54 vs 37 %, OR 1.93, 95 % CI 1.60-2.26). No significant differences were found with age, initial doses of prednisone or the hospital. According to recent prevention guidelines, treatment with biphosphonate should have been administered in more than 90 % of patients. Although prophylaxis of glucocorticoid-induced osteoporosis in patients with PMR has increased in the recent years, many patients do not receive prophylaxis with bisphosphonate during the first visit.
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http://dx.doi.org/10.1007/s00296-014-3014-2DOI Listing
October 2014

Fabrication of VB2/air cells for electrochemical testing.

J Vis Exp 2013 Aug 5(78). Epub 2013 Aug 5.

Department of Chemistry, The George Washington University, USA.

A technique to investigate the properties and performance of new multi-electron metal/air battery systems is proposed and presented. A method for synthesizing nanoscopic VB2 is presented as well as step-by-step procedure for applying a zirconium oxide coating to the VB2 particles for stabilization upon discharge. The process for disassembling existing zinc/air cells is shown, in addition construction of the new working electrode to replace the conventional zinc/air cell anode with a the nanoscopic VB2 anode. Finally, discharge of the completed VB2/air battery is reported. We show that using the zinc/air cell as a test bed is useful to provide a consistent configuration to study the performance of the high-energy high capacity nanoscopic VB2 anode.
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http://dx.doi.org/10.3791/50593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846757PMC
August 2013

Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45/CASQ1 double knockout mice.

Nat Commun 2013 ;4:1541

Department of Experimental and Diagnostic Medicine, General Pathology section, University of Ferrara, Via Borsari 46, Ferrara 44121, Italy.

Muscle strength declines with age in part due to a decline of Ca(2+) release from sarcoplasmic reticulum calcium stores. Skeletal muscle dihydropyridine receptors (Ca(v)1.1) initiate muscle contraction by activating ryanodine receptors in the sarcoplasmic reticulum. Ca(v)1.1 channel activity is enhanced by a retrograde stimulatory signal delivered by the ryanodine receptor. JP45 is a membrane protein interacting with Ca(v)1.1 and the sarcoplasmic reticulum Ca(2+) storage protein calsequestrin (CASQ1). Here we show that JP45 and CASQ1 strengthen skeletal muscle contraction by modulating Ca(v)1.1 channel activity. Using muscle fibres from JP45 and CASQ1 double knockout mice, we demonstrate that Ca(2+) transients evoked by tetanic stimulation are the result of massive Ca(2+) influx due to enhanced Ca(v)1.1 channel activity, which restores muscle strength in JP45/CASQ1 double knockout mice. We envision that JP45 and CASQ1 may be candidate targets for the development of new therapeutic strategies against decay of skeletal muscle strength caused by a decrease in sarcoplasmic reticulum Ca(2+) content.
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http://dx.doi.org/10.1038/ncomms2496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856057PMC
June 2013

Effects of Mediterranean dehesa management on epiphytic lichens.

Sci Total Environ 2010 Dec;409(1):116-22

Biodiversity and Conservation Area, ESCET, University Rey Juan Carlos, c/ Tulipán s/n, 28933-Móstoles, Madrid, Spain.

Spanish holm oak (Quercus ilex subsp. ballota) open woodlands (dehesas) maintain a high diversity of plants and animals compared to other forested Mediterranean habits, but little is known about the responses of epiphytic lichens to different management regimes that are applied to this woodland type. The present study was carried out in central-southern Spain and included four management regimes: agriculture, grazing of sheep, grassland grazed by wild ungulates (deer), and abandoned dehesas covered by shrubs. Total species richness and cover exhibited considerable variation among management regimes. Both parameters tended to decrease with the intensity of management, abandoned dehesas maintaining a higher number of species than more intensively managed habitats. Lichen composition also significantly differed among the four regimes. Nitrophytic species were clearly associated with more intensive management regimes (farming or livestock management), whereas non-nitrophytic species favored abandoned dehesas.
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http://dx.doi.org/10.1016/j.scitotenv.2010.09.034DOI Listing
December 2010

Painful ophthalmoplegia of the left eye in a 19-year-old female, with an emphasis in Tolosa-Hunt syndrome: a case report.

Cases J 2009 Sep 17;2:8271. Epub 2009 Sep 17.

Department of Internal Medicine, Calzada de Tlalpan 4800, Colonia Sección XVI, Tlalpan, C.P. 14080. Distrito Federal, México.

Introduction: Painful ophthalmoplegia refers to periorbital or hemicraneal pain plus ipsilateral ocular motor nerve palsies with or without oculo-sympathetic paralysis, sensory loss in the distribution of V1 and V2 can co-occur. There are many etiologies of painful ophthalmoplegia. Tolosa-Hunt syndrome is a steroid-responsive painful ophthalmoplegia secondary to idiopatic granulomatous inflammation of the cavernous sinus or orbital apex. THS is a diagnosis of exclusion and treatment should be with high dose steroid.

Case Presentation: We describe the case of a 19-year-old female that was admitted to our hospital for painful ophthalmoplegia of the left eye. After the diagnostic work-up, we concluded that the patient had a benign form of Tolosa-Hunt syndrome. We initiated treatment with steroids and 72 hours later saw a response.

Conclusion: In conclusion, steroid treatment is the cornerstone in the management of THS. Even though there is no standardized dose specified in the literature, this type of treatment with steroids at a dose of 1 mg/kg/day tapered slowly over 3 to 4 months has been well received.
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http://dx.doi.org/10.4076/1757-1626-2-8271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769420PMC
September 2009

Importance of diffuse pollution control in the Patzcuaro Lake Basin in Mexico.

Water Sci Technol 2008 ;58(11):2179-86

Department of Hydrobiology and Environmental Assessment, Mexican Institute for Water Technology, Paseo Cuauhnáhuac 8532, Progreso, Jiutepec 62550, México.

In the catchment area of the Lake Patzcuaro in Central Mexico (933 km2) the apportionments of erosion, sediment, nutrients and pathogen coming from thirteen micro basins were estimated with the purpose of identifying critical areas in which best management practices need to be implemented in order to reduce their contribution to the lake pollution and eutrophication. The ArcView Generalized Watershed Loading Functions model (AV-GWLF) was applied to estimate the loads and sources of nutrients. The main results show that the total annual contribution of nitrogen from point sources were 491 tons and from diffuse pollution 2,065 tons, whereas phosphorus loads where 116 and 236 tons, respectively during a thirty year simulation period. Micro basins with predominant agricultural and animal farm land use (56% of the total area) accounts for a high percentage of nitrogen load 33% and phosphorus 52%. On the other hand, Patzcuaro and Quiroga micro basins which comprise approximately 10% of the total catchment area and are the most populated and visited towns by tourist 686,000 people every year, both contributes with 10.1% of the total nitrogen load and 3.2% of phosphorus. In terms of point sources of nitrogen and phosphorus the last towns contribute with 23.5% and 26.6% respectively. Under this situation the adoption of best management practices are an imperative task since the sedimentation and pollution in the lake has increased dramatically in the last twenty years.
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http://dx.doi.org/10.2166/wst.2008.820DOI Listing
March 2009

Searching for intermediates in the carbon skeleton rearrangement of 2-methyleneglutarate to (R)-3-methylitaconate catalyzed by coenzyme B12-dependent 2-methyleneglutarate mutase from Eubacterium barkeri.

Biochemistry 2005 Aug;44(31):10541-51

Laboratorium für Mikrobiologie, Fachbereich Biologie, Philipps-Universität, Marburg, Germany.

Coenzyme B(12)-dependent 2-methyleneglutarate mutase from the strict anaerobe Eubacterium barkeri catalyzes the equilibration of 2-methyleneglutarate with (R)-3-methylitaconate. Proteins with mutations in the highly conserved coenzyme binding-motif DXH(X)(2)G(X)(41)GG (D483N and H485Q) exhibited decreased substrate turnover by 2000-fold and >4000-fold, respectively. These findings are consistent with the notion of H485 hydrogen-bonded to D483 being the lower axial ligand of adenosylcobalamin in 2-methyleneglutarate mutase. (E)- and (Z)-2-methylpent-2-enedioate and all four stereoisomers of 1-methylcyclopropane-1,2-dicarboxylate were synthesized and tested, along with acrylate, with respect to their inhibitory potential. Acrylate and the 2-methylpent-2-enedioates were noninhibitory. Among the 1-methylcyclopropane-1,2-dicarboxylates only the (1R,2R)-isomer displayed weak inhibition (noncompetitive, K(i) = 13 mM). Short incubation (5 min) of 2-methyleneglutarate mutase with 2-methyleneglutarate under anaerobic conditions generated an electron paramagnetic resonance (EPR) signal (g(xy) approximately 2.1; g(z) approximately 2.0), which by analogy with the findings on glutamate mutase from Clostridium cochlearium [Biochemistry, 1998, 37, 4105-4113] was assigned to cob(II)alamin coupled to a carbon-centered radical. At longer incubation times (>1 h), inactivation of the mutase occurred concomitant with the formation of oxygen-insensitive cob(II)alamin (g(xy) approximately 2.25; g(z) approximately 2.0). In order to identify the carbon-centered radical, various (13)C- and one (2)H-labeled substrate/product molecules were synthesized. Broadening (0.5 mT) of the EPR signal around g = 2.1 was observed only when C2 and/or C4 of 2-methyleneglutarate was labeled. No effect on the EPR signals was seen when [5'-(13)C]adenosylcobalamin was used as coenzyme. The inhibition and EPR data are discussed in the context of the addition-elimination and fragmentation-recombination mechanisms proposed for 2-methyleneglutarate mutase.
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http://dx.doi.org/10.1021/bi050049nDOI Listing
August 2005

[Are granulomas necessary for the final diagnosis of Crohn disease?].

Rev Gastroenterol Peru 2004 Apr-Jun;24(2):171-4

A case of a 38 year-old male patient, from Lima, with a three-year period illness, characterized by abdominal pain, diarrhea, ponderal weight loss and fever is showed. He is examined by colonoscopy, with endoscopic diagnosis of colon cancer and undergoes surgery. The histopathological diagnosis was severe acute and chronic ulcerative ileocolitis, suggesting Crohn disease. A month later he again showed abdominal pain, diarrhea and fever, so a new colonoscopy is performed revealing multiple ileum ulcers and in the anastomotic area. The biopsy revealed an acute and chronic inflammatory process. The colon radiography showed a filling defect and irregularity in the cecum, and the upper endoscopy revealed esophageal ulcers. In addition, a number of analyses were carried out, such as: coproculture, HIV, and VK on sputum and feces, as well as CEA dosage, resulting all of them negative. The thorax radiography was also normal.He was diagnosed with Crohn's disease and was treated with mesalacin. Evolution was fast, showing weight gain, which allowed the discharge of the patient from the hospital seven (7) days later. The anatomical pathology never did confirm the final diagnosis, which brings us to the question:Are the granulomas always necessary for the final diagnosis of Crohn's disease?
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November 2004

Efficacy assessment of meloxicam, a preferential cyclooxygenase-2 inhibitor, in acute coronary syndromes without ST-segment elevation: the Nonsteroidal Anti-Inflammatory Drugs in Unstable Angina Treatment-2 (NUT-2) pilot study.

Circulation 2002 Jul;106(2):191-5

Centro de Trombosis de Buenos Aires, Catedra de Magister en Trombosis, Facultad de Medicina de Tucuman, Buenos Aires, Argentina.

Background: Despite the use of heparin, aspirin, and other antiplatelet agents, acute coronary syndrome patients without ST-segment elevation remain at risk of cardiovascular thrombotic events. Given the role of inflammation in the pathogenesis of arterial thrombosis, we tested the hypothesis that the combination of meloxicam, a preferential COX-2 inhibitor, and heparin and aspirin would be superior to heparin and aspirin alone.

Methods And Results: In an open-label, randomized, prospective, single-blind pilot study, patients with acute coronary syndromes without ST-segment elevation were randomized to aspirin and heparin treatment (n=60) or aspirin, heparin, and meloxicam (n=60) during coronary care unit stay. Patients then received aspirin or aspirin plus meloxicam for 30 days. During the coronary care unit stay, the primary outcomes variable of recurrent angina, myocardial infarction, or death was significantly lower in the patients receiving meloxicam (15.0% versus 38.3%, P=0.007). The second composite variable (coronary revascularization procedures, myocardial infarction, and death) was also significantly lower in meloxicam-treated patients (10.0% versus 26.7%, P=0.034). At 90 days, the primary end point remained significantly lower in the meloxicam group (21.7% versus 48.3%, P=0.004), as did the secondary end point (13.3% versus 33.3%, P=0.015) and the need for revascularization alone (11.7% versus 30.0%, P=0.025). No adverse complications associated with the meloxicam treatment were observed.

Conclusions: Meloxicam with heparin and aspirin was associated with significant reductions in adverse outcomes in acute coronary syndrome patients without ST-segment elevation. Additional larger trials are required to confirm the findings of this pilot study.
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July 2002
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