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1.
Neurosurg Rev ; 45(3): 2161-2173, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35022937

ABSTRACT

The objective of this study is to determine the role of multimodal intraoperative neurophysiologic monitoring (IONM) in the overall outcome of intracranial aneurysms surgery, and the risk factors associated with ischemic complications. We grouped 268 ruptured and unruptured intracranial aneurysms surgically treated at our institution into 2 cohorts, based on the use of IONM (180; 67.16%) or non-use of IONM (88; 32.84%). The IONM technique used was multimodal: electroencephalogram (EEG), somatosensory evoked potentials (SSEPs), transcranial (TES), and direct cortical (DCS) stimulation motor evoked potentials (MEPs). There was a significant difference, with a reduction in perioperative strokes (p = 0.011) and better motor surgery-related outcome in the IONM group (p = 0.016). Independent risk factors identified for surgery ischemic complications were temporary clipping time ≥ 6'05″ (odds ratio [OR]: 3.03; 95% CI: 1.068-8.601; p = 0.037), aneurysm size ≥ 7.5 mm (OR: 2.65; 95% CI: 1.127-6.235; p = 0.026), and non-use of IONM (OR: 2.79; 95% CI: 1.171-6.636; p = 0.021). Conversely, aneurysm rupture was not detected as an independent risk factor (OR: 2.5; 95% CI: 0.55-4.55; p = 0.4). Longer temporary clipping time, larger aneurysm size, and the non-use of IONM could be considered as risk factors for ischemic complications during microsurgical clipping. A standardized designed protocol including multimodal IONM with DCS provides continuous information about blood supply and allows reduction of treatment-related morbidity. Multimodal IONM is a valuable technique in intracranial aneurysm surgery.


Subject(s)
Intracranial Aneurysm , Intraoperative Neurophysiological Monitoring , Evoked Potentials, Motor/physiology , Evoked Potentials, Somatosensory/physiology , Humans , Intracranial Aneurysm/surgery , Intraoperative Neurophysiological Monitoring/methods , Retrospective Studies
2.
Article in English | MEDLINE | ID: mdl-32845096

ABSTRACT

Introduction: Ambient air pollution is associated with premature death caused by heart disease, stroke, chronic obstructive pulmonary disease (COPD), and lung cancer. Recent studies have suggested that ribonucleic acid (RNA) oxidation is a sensitive environment-related biomarker that is implicated in pathogenesis. Aims and Methods: We used a novel approach that integrated RNA-Seq analysis with detection by immunoprecipitation techniques of the prominent RNA oxidative modification 8-oxo-7,8-dihydroguanine (8-oxoG). Our goal was to uncover specific messenger RNA (mRNA) oxidation induced by mixtures of volatile organic compounds (VOCs) and ozone in healthy human epithelial lung cells. To this end, we exposed the BEAS-2B human epithelial lung cell line to the gas- and particle-phase products formed from reactions of 790 ppb acrolein (ACR) and 670 ppb methacrolein (MACR) with 4 ppm ozone. Results: Using this approach, we identified 222 potential direct targets of oxidation belonging to previously described pathways, as well as uncharacterized pathways, after air pollution exposures. We demonstrated the effect of our VOC-ozone mixtures on the morphology and actin cytoskeleton of lung cells, suggesting the influence of selective mRNA oxidation in members of pathways regulating physical components of the cells. In addition, we observed the influence of the VOC-ozone mixtures on metabolic cholesterol synthesis, likely implicated as a result of the incidence of mRNA oxidation and the deregulation of protein levels of squalene synthase (farnesyl-diphosphate farnesyltransferase 1 [FDFT1]), a key enzyme in endogenous cholesterol biosynthesis. Conclusions: Overall, our findings indicate that air pollution influences the accumulation of 8-oxoG in transcripts of epithelial lung cells that largely belong to stress-induced signaling and metabolic and structural pathways. A strength of the study was that it combined traditional transcriptome analysis with transcriptome-wide 8-oxoG mapping to facilitate the discovery of underlying processes not characterized by earlier approaches. Investigation of the processes mediated by air pollution oxidation of RNA molecules in primary cells and animal models needs to be explored in future studies. Our research has thus opened new avenues to further inform the relationship between atmospheric agents on the one hand and cellular responses on the other that are implicated in diseases.


Subject(s)
Air Pollutants/pharmacology , Epithelial Cells/drug effects , Lung/drug effects , Ozone/pharmacology , RNA/drug effects , Volatile Organic Compounds/pharmacology , Acrolein/analogs & derivatives , Acrolein/pharmacology , Down-Regulation , Humans , Oxidation-Reduction , Time Factors
3.
Environ Monit Assess ; 186(9): 5393-400, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24816591

ABSTRACT

The healthcare sector is an important contributor to mercury (Hg) pollution because of the potential presence of mercury in thermometers, blood pressure cuffs, amalgams, etc. There are also other potential sources of mercury in this sector which are used frequently and in high volumes where the presence of the metal is not obvious and which might be collectively contributing to pollution. For instance, some chemicals used for the clinical diagnosis of illness may contain mercury. The goal of this study was to investigate potential sources of mercury pollution, which originate from clinical laboratory discharges, using an exploratory approach. The focus was on the residue generated during automatic analysis of patients' bodily fluids at a medical center in Hermosillo, Sonora, Mexico. This study shows an overview of what might be happening in the region or the country related to non-obvious sources of mercury in the healthcare sector. The results showed measurable levels of mercury in the residues coming from urine sediment analysis. These amounts do not exceed the maximum allowed by Mexican environmental regulations; nevertheless, the frequency and cumulative volume of residues generated, combined with the potential for persistence and the bioaccumulation of mercury in the environment, warrant attention. The work carried out in this study is being taken as a model for future studies for pollution prevention in the healthcare sector with the goal of measuring mercury emissions to the environment from clinical laboratory wastewater, including identifying sources which--while not obvious--could be important given the frequency and volume of their use in the clinical diagnosis.


Subject(s)
Environmental Monitoring , Environmental Pollutants/analysis , Environmental Pollution/statistics & numerical data , Laboratories , Mercury/analysis , Environmental Pollution/analysis , Mexico
4.
Rehabilitacion (Madr) ; 58(2): 100828, 2024.
Article in Spanish | MEDLINE | ID: mdl-38141425

ABSTRACT

This study aimed to evaluate the effectiveness of early pelvic muscle training in reducing urinary incontinence symptoms, improving quality of life, sexual function, and increasing pelvic floor strength in post-radical prostatectomy patients. A search was carried out in 8 databases until October 26, 2022, the methodological quality and the risk of bias of 14 included studies (n=1236) were evaluated, moreover, the evidence and the meta-analysis were calculated. The intervention significantly reduced urinary incontinence symptoms compared to a control group (SMD=-2.80, 95% CI=-5.21 to -0.39, P=.02), with significant heterogeneity (I2=83%; P=<.0001) and moderate evidence. In addition, it presented moderate evidence to improve quality of life, and very low evidence to improve sexual function and pelvic floor strength. These results should be viewed with caution due to the significant heterogeneity of the studies analysed.


Subject(s)
Muscle Strength , Pelvic Floor , Prostatectomy , Quality of Life , Randomized Controlled Trials as Topic , Urinary Incontinence , Humans , Prostatectomy/adverse effects , Urinary Incontinence/etiology , Male , Muscle Strength/physiology , Exercise Therapy/methods , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Treatment Outcome
5.
Parasitology ; 140(2): 202-9, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23058125

ABSTRACT

Protein kinases (PKs) of parasitic protozoa are being evaluated as drug targets. A large number of protein kinases within the protein kinome of Entamoeba histolytica strongly suggest that protein phosphorylation is a key component of pathogenesis regulation by this parasite. PI3 K and Src are kinases previously described in this parasite, but their role is poorly understood. Here, the effect of Src-1-inhibitor and PI3 K inhibitor (Wortmannin) on the virulence factors of E. histolytica was evaluated. Results show that both inhibitors affect the actin cytoskeleton and the amoebic movement. Also, the proteolytic activity is diminished by Wortmannin, but not by Src-inhibitor-1; however, the phagocytic capacity is diminished by Wortmannin and Src-1-inhibitor. Finally, we found that the virulence in vivo of E. histolytica is affected by Wortmannin but not by Src-1-inhibitor. This study opens the way for the design of anti-amoebic drugs based on kinase inhibition.


Subject(s)
Entamoeba histolytica/drug effects , Entamoeba histolytica/enzymology , Protein Kinase Inhibitors/pharmacology , Virulence Factors/metabolism , Actin Cytoskeleton/drug effects , Androstadienes/pharmacology , Androstadienes/therapeutic use , Animals , Cells, Cultured , Cricetinae , Entamoeba histolytica/pathogenicity , Entamoebiasis/drug therapy , Entamoebiasis/pathology , Humans , Male , Phagocytosis/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Protein Kinase Inhibitors/therapeutic use , Proteolysis/drug effects , Wortmannin , src-Family Kinases/metabolism
6.
J Prev Alzheimers Dis ; 10(4): 810-820, 2023.
Article in English | MEDLINE | ID: mdl-37874103

ABSTRACT

INTRODUCTION: Lower blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) are correlated with worse cognitive functions, particularly among APOE ε4 carriers. Whether DHA supplementation in APOE ε4 carriers with limited DHA consumption and dementia risk factors can delay or slow down disease progression when started before the onset of clinical dementia is not known. METHODS: PreventE4 is a double-blind, single site, randomized, placebo-controlled trial in cognitively unimpaired individuals with limited omega-3 consumption and dementia risk factors (n=368). Its objectives are to determine (1) whether carrying the APOE ε4 allele is associated with lower delivery of DHA to the brain; and (2) whether high dose DHA supplementation affects brain imaging biomarkers of AD and cognitive function. RESULTS: 365 cognitively unimpaired individuals between 55 and 80 (mean age 66) were randomized to 2 grams of DHA per day or identically appearing placebo for a period of 2 years. Half the participants were asked to complete lumbar punctures at baseline and 6-month visits to obtain cerebrospinal fluid (CSF). The primary trial outcome measure is the change in CSF DHA to arachidonic acid ratio after 6 months of the intervention (n=181). Secondary trial outcomes include the change in functional and structural connectivity using resting state functional MRI at 24 months (n=365). Exploratory outcomes include the change in Repeatable Battery of the Assessment of Neuropsychological Status at 24 months (n=365). CONCLUSIONS: Findings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.


Subject(s)
Alzheimer Disease , Fatty Acids, Omega-3 , Humans , Alzheimer Disease/drug therapy , Apolipoprotein E4/genetics , Brain/diagnostic imaging , Docosahexaenoic Acids/therapeutic use , Fatty Acids, Omega-3/therapeutic use , Middle Aged , Aged , Aged, 80 and over
7.
Antimicrob Agents Chemother ; 56(5): 2612-8, 2012 May.
Article in English | MEDLINE | ID: mdl-22330920

ABSTRACT

The global control of tuberculosis (TB) is at risk by the spread of multidrug-resistant TB (MDR TB). Treatment of MDR TB is lengthy and involves injected drugs, such as capreomycin, that have severe side effects. It was previously reported that a single daily dose of inhaled capreomycin had a positive effect on the bacterial burden of TB-infected guinea pigs. The modest effect observed was possibly due to a dose that resulted in insufficient time of exposure to therapeutic systemic and local levels of the drug. In order to determine the length of time that systemic and local drug concentrations are above therapeutic levels during the treatment period, the present study investigated the disposition of capreomycin powders after sequential pulmonary administration of doses of 20 mg/kg of body weight. Capreomycin concentrations in bronchoalveolar lavage fluid and lung tissue of animals receiving a series of one, two, or three doses of capreomycin inhalable powder were significantly higher (50- to 100-fold) at all time points than plasma concentrations at the same time points or those observed in animals receiving capreomycin solution by intramuscular (i.m.) injection (10- to 100-fold higher). Notably, at the end of each dosing period, capreomycin concentrations in the lungs were approximately 100-fold higher than those in plasma and severalfold higher than the MIC, suggesting that sufficient capreomycin remains in the lung environment to kill Mycobacterium tuberculosis. No accumulation of capreomycin powder was detected in the lungs after 3 pulmonary doses. These results indicate that the systemic disposition of capreomycin after inhalation is the same as when injected i.m. with the advantage that higher drug concentrations are present at all times in the lungs, the primary site of infection.


Subject(s)
Antitubercular Agents/pharmacokinetics , Capreomycin/pharmacokinetics , Lung/drug effects , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/drug therapy , Administration, Inhalation , Animals , Antitubercular Agents/blood , Antitubercular Agents/therapeutic use , Bronchoalveolar Lavage Fluid/chemistry , Capreomycin/blood , Capreomycin/therapeutic use , Disease Models, Animal , Drug Administration Schedule , Guinea Pigs , Injections, Intramuscular , Lung/microbiology , Male , Mycobacterium tuberculosis/physiology , Particle Size , Powders , Tuberculosis, Multidrug-Resistant/blood , Tuberculosis, Multidrug-Resistant/microbiology
8.
ScientificWorldJournal ; 2012: 171292, 2012.
Article in English | MEDLINE | ID: mdl-22919292

ABSTRACT

Percolation theory has been applied in order to study the existence of critical points as well as the possibility to find a "combined percolation threshold" for ternary hydrophilic matrices prepared with HPMC, NaCMC, and theophylline. For this purpose, different batches of ternary as well as binary hydrophilic matrices have been prepared. Critical points have been found for binary hydrophilic matrices between 21.5 and 31.3% (v/v) of HPMC and between 39 and 54% (v/v) of NaCMC, respectively. In a previous work carried out with the same polymers but a much more soluble drug (KCl), it was demonstrated the existence of a partial collaboration between the polymers in order to establish the gel layer. In this work, it has been observed for the first time the need of a minimum concentration of one of the matrix-forming polymer (between 10 and 20% v/v, approximately) for establishing an effective collaboration.


Subject(s)
Carboxymethylcellulose Sodium/chemistry , Methylcellulose/analogs & derivatives , Polymers/chemistry , Theophylline/chemistry , Hydrophobic and Hydrophilic Interactions , Hypromellose Derivatives , Methylcellulose/chemistry , Microscopy, Electron, Scanning , Solubility
9.
Water Sci Technol ; 65(6): 1142-9, 2012.
Article in English | MEDLINE | ID: mdl-22378015

ABSTRACT

Agricultural solid residues are a potential renewable energy source. Rice harvesting and production in Sancti Spíritus province, Cuba, currently generates residues without an environmentally sustainable disposal route. Rice residues (rice straw, rice husk and rice residues from the drying process) are potentially an important carbon source for anaerobic digestion. For this paper, rice residues were placed for 36 days retention time in anaerobic batch reactor environments at both mesophilic (37 °C) and thermophilic (55 °C) conditions. Biogas and methane yield were determined as well as biogas composition. The results showed that rice straw as well as rice residues from the drying process had the highest biogas and methane yield. Temperature played an important role in determining both biogas yield and kinetics. In all cases, rice straw produced the highest yields; under mesophilic conditions the biogas yield was 0.43 m(3) kg(VS)(-1), under thermophilic conditions biogas yield reached 0.52 m(3) kg(VS)(-1). In the case of the rice husk, the biodegradability was very low. Methane content in all batches was kept above 55% vol. All digested material had a high carbon:nitrogen (C:N) ratio, even though significant biodegradation was recorded with the exception of rice husk. A first-order model can be used to describe the rice crop residues fermentation effectively.


Subject(s)
Biodegradation, Environmental , Methane/metabolism , Oryza , Plant Stems , Water , Refuse Disposal
10.
Acta Gastroenterol Belg ; 85(3): 509-517, 2022.
Article in English | MEDLINE | ID: mdl-35833906

ABSTRACT

Background and study aims: Small-bowel capsule endoscopy (SBCE) is a safe and efficient method for diagnosis of small-bowel diseases. Since its development, different models have appeared. The aim of this study was to analyze which of the different models of SBCE has the best diagnostic yield. Patients and methods: Extensive medical literature research was reviewed, using MESH terms, searching studies comparing different SBCE types. We analyzed the diagnostic yield of all the comparisons and when there were 2 or more studies that compared the same model of SBCEs, a meta-analysis was performed. Results: Ten eligible studies including 1065 SBCEs procedures were identified. The main indication was occult gastrointestinal bleeding in 9/10 studies. Two of them included anemia, chronic diarrhea and/or chronic abdominal pain. The indication in one article was celiac disease. In 9 studies, different types of SBCEs (MiroCam, Endocapsule, OMOM and CapsoCam) were compared with PillCam (SB, SB2 and SB3). Three studies compared MiroCam vs PillCam and CapsoCam vs PillCam, while two studies contrast Endocapsule vs PillCam. None of the SBCEs show superiority over PillCam [OR 0.78 (95%CI;0.60-1.01)]. One study compared SBCEs other than Pillcam (MiroCam vs Endocapsule). Nine studies did not find statistical differences between SBCEs, one showed better diagnostic yield of Mirocam compared with PillCam SB3 (p=0.02). The difference between these SBCE was not replayed in the metaanalysis [OR 0.77 (95%CI;0.49-1.21)]. Conclusions: Despite the appearance of new SBCE models, there are no differences in diagnostic yield; therefore, SBCE endoscopist's performance should be based on experience and availability.


Subject(s)
Capsule Endoscopy , Celiac Disease , Intestinal Diseases , Capsule Endoscopy/methods , Celiac Disease/diagnosis , Gastrointestinal Hemorrhage/diagnosis , Humans , Intestinal Diseases/diagnosis , Intestine, Small
11.
Eur J Pharm Sci ; 161: 105770, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-33610738

ABSTRACT

Although mechanistic numerical simulations can offer great insights into a process, they are limited with respect to resolved process time. While statistical models provide long-term predictability, determining the underlying probability distributions is often challenging. In this work, detailed CFD-DEM simulations of a pharmaceutical Wurster coating process for microspheres are used to evaluate the input parameters for a novel Monte-Carlo simulation approach. The combined strengths of both modeling approaches make it possible to predict the coating mass and thickness distributions over the entire process time. It was observed that smaller beads receive a thicker coating layer since they pass the spray zone closer to the nozzle. Moreover, it was established that, in contrast to the airflow rate, the spray rate has a great impact on the inter-particle coating variability. A stochastic model was developed to investigate the relative contribution of coating layer variability and fill weight variability to the product non-uniformity in a capsule filling process of Multiple Unit Pellet Systems (MUPS).


Subject(s)
Pharmaceutical Preparations , Computer Simulation , Drug Compounding , Monte Carlo Method , Particle Size , Technology, Pharmaceutical
12.
AJNR Am J Neuroradiol ; 42(7): 1276-1281, 2021 07.
Article in English | MEDLINE | ID: mdl-33926902

ABSTRACT

BACKGROUND AND PURPOSE: The Woven EndoBridge has proved to be a safe and effective treatment, especially for wide-neck intracranial aneurysms. The recent fifth-generation Woven EndoBridge came with smaller devices. The purpose of this study was to assess the safety and efficiency of Woven EndoBridge treatment of small and very small aneurysms. MATERIALS AND METHODS: Between September 2017 and March 2020, all consecutive patients treated with a 3- or 3.5 mm-width Woven EndoBridge device were included in this retrospective intention-to-treat study. Clinical and radiologic findings were evaluated at immediate and last-available follow-up. Angiographic outcome was assessed by an external expert reader. RESULTS: One hundred twenty-eight aneurysms were treated with a fifth-generation Woven EndoBridge device including 29 with a width of ≤3.5 mm. Ten aneurysms were ruptured (34%). In 3 cases (10%), Woven EndoBridge treatment could not be performed because the aneurysm was still too small for the smallest available Woven EndoBridge device and another endovascular strategy was chosen. The median follow-up time was 11.2 months. Complete and adequate occlusion was obtained in 71% and 90% of the treated aneurysms, respectively. Retreatment was needed in 2 cases (10%). Symptomatic ischemic complications leading to transient neurologic deficits occurred in 2 cases (7%) (1 procedure-related and 1 device-related) but with full spontaneous recovery at discharge. CONCLUSIONS: The fifth-generation Woven EndoBridge device seems to be a safe and technically feasible treatment for both ruptured and unruptured small and very small intracranial aneurysms, with satisfactory occlusion rates on midterm follow-up. However, further study is needed to evaluate longer-term efficiency.


Subject(s)
Intracranial Aneurysm , Blood Vessel Prosthesis , Embolization, Therapeutic , Endovascular Procedures , Female , Humans , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/surgery , Male , Middle Aged , Retrospective Studies , Treatment Outcome
13.
Sci Rep ; 11(1): 19451, 2021 09 30.
Article in English | MEDLINE | ID: mdl-34593916

ABSTRACT

Assessing the body condition of wild animals is necessary to monitor the health of the population and is critical to defining a framework for conservation actions. Body condition indices (BCIs) are a non-invasive and relatively simple means to assess the health of individual animals, useful for addressing a wide variety of ecological, behavioral, and management questions. The Antillean manatee (Trichechus manatus manatus) is an endangered subspecies of the West Indian manatee, facing a wide variety of threats from mostly human-related origins. Our objective was to define specific BCIs for the subspecies that, coupled with additional health, genetic and demographic information, can be valuable to guide management decisions. Biometric measurements of 380 wild Antillean manatees captured in seven different locations within their range of distribution were obtained. From this information, we developed three BCIs (BCI1 = UG/SL, BCI2 = W/SL3, BCI3 = W/(SL*UG2)). Linear models and two-way ANCOVA tests showed significant differences of the BCIs among sexes and locations. Although our three BCIs are suitable for Antillean manatees, BCI1 is more practical as it does not require information about weight, which can be a metric logistically difficult to collect under particular circumstances. BCI1 was significantly different among environments, revealing that the phenotypic plasticity of the subspecies have originated at least two ecotypes-coastal marine and riverine-of Antillean manatees.


Subject(s)
Body Size , Ecotype , Trichechus manatus/anatomy & histology , Animals , Biometry , Female , Male
14.
Rehabilitacion (Madr) ; 54(2): 116-127, 2020.
Article in Spanish | MEDLINE | ID: mdl-32370826

ABSTRACT

OBJECTIVE: To analyse the evidence on the effects of blood flow restriction training in people with cardiovascular disease. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, SPORTDiscus, CINAHL, LILACS, SCOPUS and Wiley databases. Experimental and non-experimental studies investigating the effects of blood flow restriction in participants with cardiovascular disease were included. RESULTS: Six clinical trials and three non-experimental studies met the inclusion criteria. The experimental studies were conducted in participants with hypertension and ischaemic heart disease. Non-experimental studies described hemodynamic adaptations and potential adverse effects of therapy. The risk of bias of the included clinical trials was moderate to high. Exercise-induced hemodynamic stress increased significantly during training with blood flow restriction compared with traditional training. The small number of available studies have focused mostly on acute effects, but chronic effects are unknown. CONCLUSION: There is currently no evidence to recommend the use of blood flow restriction in people with cardiovascular disease.


Subject(s)
Cardiac Rehabilitation/methods , Resistance Training/methods , Tourniquets , Bias , Cardiovascular Diseases/therapy , Clinical Trials as Topic , Coronary Artery Disease/rehabilitation , Exercise Therapy , Female , Humans , Hypertension/rehabilitation , Lower Extremity , Male , Manometry , Middle Aged , Oxygen Consumption , Pressure , Regional Blood Flow , Resistance Training/instrumentation
15.
Eur Rev Med Pharmacol Sci ; 24(13): 7412-7419, 2020 07.
Article in English | MEDLINE | ID: mdl-32706080

ABSTRACT

OBJECTIVE: Vorinostat is a drug used to treat cutaneous T cell lymphoma whose action mechanism is based on Histone Deacetylase inhibition. Histone Deacetylases are a family of enzymes that remove acetyl groups from histone and non-histone proteins that control many crucial processes, such as gene regulation, cell cycle progression, differentiation, and apoptosis. Histone Deacetylase homologues are also expressed in parasites of the genus Plasmodium, Leishmania, Cryptosporidium, Schistosoma, Entamoeba, and others. In this way, antiparasitic properties of Vorinostat have been explored. The aim of this review is to report the current state knowledge of Vorinostat as antiparasitic drug against Plasmodium, Leishmania, Cryptosporidium, Schistosoma and Entamoeba in order to support future investigation in this field. MATERIALS AND METHODS: The authors revised the recent and relevant literature concerning the topic and discussed advances and limitations of studies on Vorinostat as potential drug to treat human parasitic diseases. RESULTS: Vorinostat has been efficient in vitro and, in some cases, in vivo, against parasites that cause parasitic diseases, such as malaria, leishmaniasis, cryptosporidiosis, amoebiasis, and schistosomiasis. CONCLUSIONS: In vitro and in vivo models have demonstrated the antiparasitic activity of Vorinostat, however, the challenge is to assay its activity in animal models and to evaluate if Vorinostat is safe for humans as new alternative to treat human parasitic infections.


Subject(s)
Antiparasitic Agents/therapeutic use , Histone Deacetylase Inhibitors/therapeutic use , Histone Deacetylases , Parasites/drug effects , Parasitic Diseases/drug therapy , Protozoan Proteins/antagonists & inhibitors , Vorinostat/therapeutic use , Animals , Antiparasitic Agents/adverse effects , Drug Repositioning , Histone Deacetylase Inhibitors/adverse effects , Histone Deacetylases/metabolism , Host-Parasite Interactions , Humans , Parasites/enzymology , Parasites/pathogenicity , Parasitic Diseases/diagnosis , Parasitic Diseases/parasitology , Protozoan Proteins/metabolism , Vorinostat/adverse effects
16.
J Biomol Struct Dyn ; 38(2): 597-603, 2020 02.
Article in English | MEDLINE | ID: mdl-30744531

ABSTRACT

AbbreviationsSAHAsuberoylanilide hydroxamic acidEhHDACHistone Deacetylase from Entamoeba histolyticaRgRadius of gyrationRMSDroot-mean-square deviationRMSFroot-mean-square fluctuationMDSmolecular dynamics simulationVMDVisual Molecular DynamicsNAMDNanoscale Molecular DynamicsPBCperiodic boundary conditionsPMEParticle Mesh Ewald3Dthree-dimensionalCαalpha carbonFDAFood and Drug AdministrationnsnanosecondsGPU CUDAGraphics Processing Unit Compute Unified Device ArchitectureCommunicated by Ramaswamy H. Sarma.


Subject(s)
Amebiasis/drug therapy , Amebiasis/parasitology , Entamoeba histolytica/physiology , Metronidazole/therapeutic use , Vorinostat/therapeutic use , Entamoeba histolytica/drug effects , Entamoeba histolytica/enzymology , Histone Deacetylases/chemistry , Metronidazole/chemistry , Metronidazole/pharmacology , Molecular Docking Simulation , Molecular Dynamics Simulation , Phylogeny , Structural Homology, Protein , Trophozoites/drug effects , Trophozoites/physiology , Vorinostat/chemistry , Vorinostat/pharmacology
17.
Int J Clin Pharmacol Ther ; 47(10): 596-602, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19825322

ABSTRACT

OBJECTIVE: The aims of the present study were to assess the prevalence of fatal adverse drug reactions (FADRs) in a hospitalized population, identify the drugs involved and investigate reported risk factors for these events. METHODS: The study population of this retrospective, single-centre case study comprised 289 patients dying between 1 January 2004 and 31 December 2004 and registered in the Cause of Death Register of a teaching hospital. All compiled data were recorded by two observers especially trained to identify and report adverse drug reactions (ADRs). The degree of probability that the ADR led directly to death was determined by using WHO criteria and an adapted version of Naranjo's score. RESULTS: Among 289 deceased study subjects, 17 (5.9%) were suspected to have died from an ADR. The most common suspected FADRs were gastrointestinal hemorrhages (52.9%), central nervous system hemorrhages (17.6%), cardiac disorders (17.6%), drug-induced myelosuppression (6%) and antimicrobial-related enterocolitis (6%). The drugs most frequently implicated in a FADR were antithrombotic drugs (65%), nonsteroidal anti-inflammatory drugs (NSAIDs) (47%) and corticosteroids (29%). The only risk factors associated with FADRs in this population were multiple-drug therapy and the presence of platelet antiaggregants and NSAIDs, alone or associated. CONCLUSIONS: FADRs are an important cause of death in hospitalized patients. Hemorrhages were seen in a majority of the fatal reactions, and antithrombotic agents or NSAIDs were implicated in most of these events.


Subject(s)
Adverse Drug Reaction Reporting Systems/statistics & numerical data , Drug-Related Side Effects and Adverse Reactions , Hospital Mortality , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Cause of Death , Female , Fibrinolytic Agents/adverse effects , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Prevalence , Registries , Retrospective Studies , Risk Factors , Young Adult
19.
Eur Rev Med Pharmacol Sci ; 23(1): 397-401, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30657582

ABSTRACT

OBJECTIVE: Metronidazole is an antibiotic widely used in different medical conditions such as trichomoniasis, amoebiasis, and giardiasis among others. Its use has been associated with toxicity; however, it is not well characterized. In this review, we discuss the different therapeutic uses of metronidazole and its side effects in order to aid future investigation in this field. MATERIALS AND METHODS: Relevant information, original research articles, clinical trials, and reviews were collected from PubMed to know the state of the art of the different therapeutic uses of metronidazole and the reported side effects. RESULTS: Metronidazole was used by the first time in 1959, to treat an infection caused by Trichomonas vaginalis; subsequently, new therapeutic properties were discovered. Nowadays, Metronidazole is used to treat infections caused by Bacteroides, Fusobacteria and Clostridia, rosacea, oral and dental infections, bone and joint infections, gynecologic infections, endocarditis, septicemia, and respiratory tract infections. It also can be used to treat Crohn´s disease or even like prophylaxis, before surgical procedures. Metronidazole is well tolerated with mild to moderate side effects such as nausea, abdominal pain, and diarrhea. Nevertheless, serious neurotoxicity, optic neuropathy, peripheral neuropathy, and encephalopathy have been reported in rare cases. Their genotoxic effects observed in animal models are controversial in humans. CONCLUSIONS: The therapeutic use of metronidazole had increased worldwide. Even though it is widely used, metronidazole has been associated with neurotoxicity and genotoxicity; however, its side effects are not well established. Conversely, its veterinary use is restricted in some countries because of its tumor association. Subsequently, further studies are needed to discover the secure use of metronidazole and describe new usages for this drug.


Subject(s)
Antiprotozoal Agents/adverse effects , Metronidazole/adverse effects , Neurotoxicity Syndromes/etiology , Protozoan Infections, Animal/drug therapy , Protozoan Infections/drug therapy , Animals , Carcinogenesis/drug effects , DNA Damage/drug effects , Disease Models, Animal , Drug Utilization/statistics & numerical data , Humans , Legislation, Veterinary , Veterinary Drugs/adverse effects
20.
J Pharm Biomed Anal ; 46(4): 799-803, 2008 Mar 13.
Article in English | MEDLINE | ID: mdl-18182268

ABSTRACT

Poloxamers (PXMs) are amphiphilic non-ionic block polymers commonly used in the cosmetic and pharmaceutical industries. In spite of the wide use of PXMs, few studies have dealt with the analysis of these polymers in pharmaceutical preparations. In this work, high-performance thin-layer chromatography (HPTLC) has been used to quantify both PXM-188 and PXM-407 in pharmaceutical preparations. The separation of these compounds was carried out using reverse phase HPTLC plates with a chloroform-methanol mixture as the mobile phase. Detection was performed densitometrically using the Dragendorff's reagent for the visualization of PXMs. Quality parameters were established, and the detection limits ranged from 24 to 47ng/spot. A good precision (day to day and run to run), with relative standard deviations <11.18%, was obtained. The proposed method was satisfactorily applied to the analysis of laboratory-made and commercial pharmaceutical products.


Subject(s)
Chromatography, Thin Layer/methods , Poloxamer/analysis , Chemistry, Pharmaceutical
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