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1.
Open Heart ; 7(2)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32938758

RESUMO

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.


Assuntos
Infecções por Coronavirus/terapia , Dieta com Restrição de Carboidratos , Suplementos Nutricionais , Hiperinsulinismo/terapia , Insulina/sangue , Magnésio/uso terapêutico , Pneumonia Viral/terapia , Trombose/terapia , Vitamina D/uso terapêutico , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Glicemia/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/epidemiologia , Cetonas/sangue , Magnésio/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Fatores de Risco , Trombose/sangue , Trombose/epidemiologia , Trombose/virologia , Vitamina D/sangue , Zinco/uso terapêutico
3.
Gan To Kagaku Ryoho ; 47(4): 605-608, 2020 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-32389961

RESUMO

The efficacy of magnesium oxide(MgO)when taken daily as a laxative for hypomagnesemia and renal dysfunction due to cisplatin(CDDP)administration is not clear. It is known that the efficacy of MgO is suppressed when used in combination with antacids, such as proton pump inhibitors. Therefore, we conducted a retrospective analysis of the effects of MgO and antacid administration on serum Mg levels and renal function(estimated glomerular filtration rate: eGFR)in CDDP-treated patients. In the analysis of up to 6 cycles of CDDP administration, the serum Mg levels and eGFR of CDDP-treated patients (n=614)were significantly reduced(p<0.001 and p=0.002, respectively, ANOVA). Patients who used MgO had higher serum Mg levels than patients who did not use MgO(p<0.001, ANOVA). However, no effect of MgO administration was observed on eGFR(p=0.832, ANOVA). There was no effect of antacid combination on serum Mg levels and eGFR in patients receiving MgO. MgO use may have contributed to a reduction in hypomagnesemia. However, it was considered that the decrease in eGFR could not be suppressed as the improvement in hypomagnesemia was slight. Intravenous Mg supplementation is required when CDDP is administered. Furthermore, it is expected that oral Mg supplementation will improve Mg absorption.


Assuntos
Magnésio/uso terapêutico , Administração Oral , Antiácidos , Cisplatino , Humanos , Óxido de Magnésio , Estudos Retrospectivos
4.
Artigo em Inglês | MEDLINE | ID: mdl-31861951

RESUMO

The aims of this study were to evaluate the efficacy of magnesium alginate in decreasing functional regurgitation symptoms in infants, and to assess the cost-benefit ratio of magnesium alginate compared to a thickened formula. A multicenter perspective cross-over study was conducted in formula-fed infants with persisting regurgitation, randomly assigned to receive two weeks of a magnesium-alginate-based formulation followed by two weeks of thickened formula, or vice-versa. Infants, exclusively breast-fed, were followed up for two weeks while receiving magnesium alginate. Symptoms of gastroesophageal reflux (GER) were evaluated through the Infant Gastroesophageal Reflux Questionnaire Revised (I-GERQ-R). Direct cost of treatments was also calculated. Seventy-two infants completed the study. We found a significant reduction of I-GERQ-R scores over time (F = 55.387; p < 0.001) in all groups with no difference between the sequences of administration (F = 0.268; p = 0.848) in formula-fed infants and between exclusively breast-fed and formula-fed infants receiving magnesium alginate (t = 1.55; p = 0.126). The mean cost savings per infant was € 4.60 (±11.2) in formula-fed infants treated with magnesium alginate compared to thickened formula (t = 2.91, p < 0.0005). Conclusions were that the magnesium-alginate formulation reduces GER symptoms both in formula-fed and breast-fed infants. In formula-fed infants, clinical efficacy is similar to thickened formulas with a slightly lower cost of treatment.


Assuntos
Alginatos/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Fórmulas Infantis , Magnésio/uso terapêutico , Alginatos/administração & dosagem , Estudos Cross-Over , Feminino , Humanos , Lactente , Recém-Nascido , Magnésio/administração & dosagem , Masculino
5.
Medicine (Baltimore) ; 98(45): e17774, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702629

RESUMO

The impact of magnesium on risk of knee osteoarthritis (KOE) is still under investigation. This meta-analysis evaluated the relationship between magnesium and risk of KOE.A comprehensive search was performed to identify retrospective cohort study or cross-sectional study of the association between magnesium and KOE from the Cochrane library, PubMed, and Embase. The search time limit was from the establishment of the database to December 2018. Two evaluators selected the literature, extracted the data, and evaluated the quality of the literature according to the inclusion and exclusion criteria, independently. Meta-analysis was performed using RevMan 5.3 software and publication bias was assessed using Begg and Egger test and funnel plot.Finally, 6 studies were included with a total of 15,715 participants. Although higher daily intake of magnesium was associated with a significantly reduced risk of fracture in patients with KOE (OR = 0.66, 95%CI: 0.56, 0.78; P < .00001), it was not significant for lowering the risk of KOE (OR = 0.80; 95% CI: 0.61, 1.04; P = .1). Meta-analysis also showed that population with higher serum magnesium levels had significantly lower risk of KOE (odds ratio (OR) = 0.84; 95% confidence interval (CI): 0.72, 0.98; P = .03). Further subgroup analysis showed that the relationship between serum magnesium level and KOE risk was significantly affected by serum magnesium level (P = .006 for quartiles 4 vs 1).Higher level of magnesium intake was not associated with lower risk of KOE. However, higher daily intake of magnesium may be inversely associated with risk of fracture in KOE patients.


Assuntos
Magnésio/uso terapêutico , Osteoartrite do Joelho/epidemiologia , Fraturas por Osteoporose/epidemiologia , Idoso , Estudos Transversais , Feminino , Humanos , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/complicações , Fraturas por Osteoporose/sangue , Estudos Retrospectivos
6.
Pain Res Manag ; 2019: 6320163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687058

RESUMO

None of the clinical trials on migraine conducted thus far have focused on the possibility to modulate the phenomenon of aura. Furthermore, whether proper management of aura results in a better control of the headache phase has been poorly investigated. In the setting of a single-center, pilot, clinical trial, we aimed at comparing the effects of Aurastop (a combination of tanacetum parthenium (150 mg extracted at 0.8% = 1.2 mg di of active parthenolide), griffonia simplicifoila (20 mg of 5-hydroxy tryptophan), and magnesium (185 mg of magnesium pidolatum)) with those of magnesium alone (2.25 grams/tablet, corresponding to 184 mg of Mg++) in the treatment of acute attacks of migraine with aura. Between June 2017 and June 2018, 50 consecutive patients (27/23 male/female; mean age, 31 [18-57] years) with at least 3 episodes of aura per year were included (t 0). Participants were instructed to keep track of the following 4 episodes of migraine with aura (t 1) and invited to assume (1) a tablet of Aurastop at the beginning of the following 2 episodes of aura and (2) a magnesium tablet alone at the occurrence of the third and fourth aura attacks. Forty-eight patients (96.0%) had >50% reduction in aura duration when treated with Aurastop vs. 7 patients (14.0%) when treated with magnesium alone (p < 0.001); 48 patients (96.0%) had >50% reduction of aura-related disability when receiving Aurastop vs. 5 patients (10.0%) when treated with magnesium alone (p < 0.001); however, patients receiving Aurastop did not need to take pain killers in 35% of aura attacks vs. 3% when assuming magnesium (p < 0.001). These results support the hypothesis that Aurastop might be effective in interfering with the phenomenon of aura and provide evidence that the clinical benefit attributable to this combination of molecules might be greater than that obtained with single compounds of proven effect on the biology of migraine.


Assuntos
Magnésio/uso terapêutico , Enxaqueca com Aura/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Triptofano/uso terapêutico , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tanacetum parthenium , Adulto Jovem
7.
Cochrane Database Syst Rev ; 9: CD011358, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498421

RESUMO

BACKGROUND: Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life. This is an updated version of the review. OBJECTIVES: To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease. SEARCH METHODS: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 03 February 2019.Date of last search of other resources (clinical trials registries): 04 April 2019. SELECTION CRITERIA: We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium. DATA COLLECTION AND ANALYSIS: Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies. MAIN RESULTS: We included five randomized placebo-controlled studies with a total of 386 participants (aged three to 53 years). Of these, two shorter parallel studies (n = 306) compared intravenous magnesium sulphate to placebo (normal saline) for admission to hospital due to a vaso-occlusive crisis, for which we were able to analyse data. The quality of evidence was moderate for studies in this comparison, mainly due to limitations due to risk of bias and imprecision. Two of the three longer-term studies comparing oral magnesium pidolate to placebo had a cross-over design. The third was a parallel factorial study which compared hydroxyurea and oral magnesium to each other and to placebo over a longer period of time; we only present the comparison of oral magnesium to placebo from this study. The quality of evidence was very low with uncertainty of the estimation.The eight-hourly dose levels in the two studies of intravenous magnesium were different; one used 100 mg/kg while the second used 40 mg/kg. Only one of these studies (n = 104) reported the mean daily pain score while hospitalised (a non-significant difference between groups, moderate quality evidence). The second study (n = 202) reported a number of child- and parent-reported quality of life scores. None of the scores showed any difference between treatment groups (low quality evidence). Data from one study (n = 106) showed no difference in length of stay in hospital between groups (low quality evidence). Both studies reported on adverse events, but not defined by severity as we had planned. One study showed significantly more participants receiving intravenous magnesium experienced warmth at infusion site compared to placebo; there were no differences between groups for other adverse events (low quality evidence).Three studies (n = 80) compared oral magnesium pidolate to placebo. None of them reported data which we were able to analyse. One study (n = 24) reported on the number of painful days and stated there was no difference between two groups (low quality evidence). None of the studies reported on quality of life or length of hospital stay. Two studies (n = 68) reported there were no differences in levels of magnesium in either plasma or red blood cells (moderate quality evidence). Two studies (n = 56) reported adverse events. One reported episodes of mild diarrhoea and headache, all of which resolved without stopping treatment. The second study reported adverse events as gastrointestinal disorders, headache or migraine, upper respiratory infections and rash; which were all evenly distributed across treatment groups (moderate quality evidence). AUTHORS' CONCLUSIONS: Moderate to low quality evidence showed neither intravenous magnesium and oral magnesium therapy has an effect on reducing painful crisis, length of hospital stay and changing quality of life in treating sickle cell disease. Therefore, no definitive conclusions can be made regarding its clinical benefit. Further randomized controlled studies, perhaps multicentre, are necessary to establish whether intravenous and oral magnesium therapies have any effect on improving the health of people with sickle cell disease.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Magnésio/uso terapêutico , Adolescente , Adulto , Anemia Falciforme/sangue , Criança , Pré-Escolar , Feminino , Humanos , Hidroxiureia/uso terapêutico , Magnésio/sangue , Sulfato de Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
8.
Psychiatr Danub ; 31(Suppl 3): 549-553, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488789

RESUMO

Depression affects over 121 million people annually worldwide. Relatively low remission rates among depressive patients enforce the search for new therapeutic solutions and an urgent need to develop faster-acting antidepressants with a different mechanism of action occurs. The pathomechanism of depression postulated by the monoamine hypothesis is limited. The results of abnormalities in glutamate and γ-aminobutyric acid (GABA) systems in the brains of people with mood disorders allowed to develop new theories regarding pathophysiology of these disorders. Glutamatergic transmission is influenced by magnesium and ketamine through glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonistic effects. Magnesium and ketamine have a common mechanism of action in the treatment of depression: an increase in GluN2B (NMDAR subunit) expression is related to the administration of both of the agents, as well as inhibition of phosphorylation of eEF2 (eukaryotic elongation factor 2) in cell culture and increase of the expression of BDNF in the hippocampus. Combination of ketamine and magnesium in a normal magnesium level presents a superadditive effect in depression treatment. Analysed substances affect the GABAergic system and have anti-inflammatory effects, which is correlated with their antidepressant effect. The synergistic interaction between the pharmacodynamic activity of magnesium and ketamine may be of particular importance for patients with mood disorders. Further research is needed to determine the relationship between magnesium levels and ketamine treatment response mainly in the attempt to establish if the magnesium supplementation can change ketamine treatment response time or present superadditive effect.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Ketamina/uso terapêutico , Magnésio/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Humanos , Fator 2 de Elongação de Peptídeos/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
9.
Muscle Nerve ; 60(6): 693-699, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31469909

RESUMO

INTRODUCTION: The etiology of acute exacerbations of myasthenia gravis (MG) is not well understood and further characterization can lead to improved preventative measures. This study aims to characterize factors contributing to MG exacerbations. METHODS: A total of 127 MG patient charts were reviewed retrospectively (2011-2016) to obtain demographics, immunizations, pharmaceutical records, contributing factors of each MG exacerbation, emergency department (ED) visits, hospitalizations, and duration. RESULTS: There were 212 exacerbations requiring 106 ED visits and 141 hospitalizations (average admission 6.5 days). Highest contributors were infections (30%) and medications that may worsen MG (19%), with 24% unattributed. Infection related exacerbations were associated with 44.3% of ED visits and 39.7% of hospitalizations. Patients prescribed beta-blockers were associated with more exacerbations (P < .01). Patients prescribed medications that may worsen MG had a higher exacerbation frequency shortly after administration. DISCUSSION: Infections and cautioned medications are frequently factors in acute MG exacerbations needing urgent medical attention and warrant caution.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antibacterianos/uso terapêutico , Glucocorticoides/uso terapêutico , Infecções/epidemiologia , Miastenia Gravis/fisiopatologia , Exacerbação dos Sintomas , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , Progressão da Doença , Serviço Hospitalar de Emergência , Feminino , Fluoroquinolonas/uso terapêutico , Gentamicinas/uso terapêutico , Hospitalização , Humanos , Magnésio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
10.
Expert Rev Med Devices ; 16(9): 757-769, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345074

RESUMO

Introduction: Bioresorbable scaffold technology provides transient vessel support with drug-delivery capability without the long-term limitations of the permanent metallic drug-eluting stents (DES). The technology has the potential to overcome many of the safety concerns associated with metallic DES, such as hypersensitivity reactions, late stent thrombosis and progression of atherosclerosis within the stented segment (i.e. neoatherosclerosis). Areas covered: The sirolimus-eluting resorbable magnesium scaffold Magmaris is the only metallic CE-marked resorbable scaffold currently available. This magnesium scaffold is designed for providing a short-term lumen support (up to 3 months) before being completely bioresorbed, eliminating the permanent caging typical of the metallic DES. This review will focus on the device development and characteristics, currently available clinical efficacy and safety data, and potential future perspectives. Expert opinion: The first clinical studies testing this device in a small number of patients have shown promising results with good clinical and safety outcomes up to 3 years' clinical follow-up, supporting the use of Magmaris in simple coronary artery disease.


Assuntos
Implantes Absorvíveis/efeitos adversos , Doença da Artéria Coronariana/terapia , Magnésio/uso terapêutico , Tecidos Suporte/efeitos adversos , Animais , Stents Farmacológicos , Humanos , Resultado do Tratamento
11.
Muscle Nerve ; 60(5): 598-603, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31350753

RESUMO

BACKGROUND: Recent investigations have questioned the role of hydration and electrolytes in cramp susceptibility and thus the efficacy of consuming electrolyte-rich carbohydrate beverages (EB) to control/prevent cramping. METHODS: Nine euhydrated, cramp-prone participants had their cramp susceptibility assessed by measuring the nerve stimulation threshold frequency at which cramping occurs (TF) before and after consumption of an EB (kCal: 120, Na: 840 mg, K: 320 mg, Mg: 5 mg) and placebo beverage (PB: kCal: 5, Na: 35 mg). Cramp intensity was assessed using a verbal pain scale and poststimulation electromyography (EMG). RESULTS: TF was greater in EB (14.86 ± 7.47 Hz) than PB (14.00 ± 5.03 Hz; P = .038) and reported pain was lower in EB (2.0 ± 0.6) than PB (2.7 ± 0.8; P = .025) while EMG was similar (P = .646). DISCUSSION: EB consumption decreased cramp susceptibility and pain but did not prevent cramping in any participants. These results suggest that electrolyte consumption independent of hydration can influence cramp susceptibility in young people.


Assuntos
Bebidas , Eletrólitos/uso terapêutico , Cãibra Muscular/prevenção & controle , Nervo Tibial , Adulto , Alanina/uso terapêutico , Sacarose na Dieta/uso terapêutico , Estimulação Elétrica/métodos , Eletromiografia , Feminino , Humanos , Magnésio/uso terapêutico , Masculino , Músculo Esquelético , Medição da Dor , Potássio/uso terapêutico , Sódio/uso terapêutico , Adulto Jovem
12.
Int J Mol Sci ; 20(12)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31207912

RESUMO

The 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome is an emerging disorder that encompasses four genes (NIPA1, NIPA2, CYFIP1, and TUBGCP5). When disturbed, these four genes can lead to cognitive impairment, language and/or motor delay, psychiatric/behavioral problems (attention-deficit hyperactivity, autism, dyslexia, schizophrenia/paranoid psychosis), ataxia, seizures, poor coordination, congenital anomalies, and abnormal brain imaging. This microdeletion was reported as the most common cytogenetic finding when using ultra-high- resolution chromosomal microarrays in patients presenting for genetic services due to autism with or without additional clinical features. Additionally, those individuals with Prader-Willi or Angelman syndromes having the larger typical 15q11-q13 type I deletion which includes the 15q11.2 BP1-BP2 region containing the four genes, show higher clinical severity than those having the smaller 15q11-q13 deletion where these four genes are intact. Two of the four genes (i.e., NIPA1 and NIPA2) are expressed in the brain and encode magnesium transporters. Magnesium is required in over 300 enzyme systems that are critical for multiple cellular functions, energy expenditure, protein synthesis, DNA transcription, and muscle and nerve function. Low levels of magnesium are found in those with seizures, depression, and acute or chronic brain diseases. Anecdotally, parents have administered magnesium supplements to their children with the 15q11.2 BP1-BP2 microdeletion and have observed improvement in behavior and clinical presentation. These observations require more attention from the medical community and should include controlled studies to determine if magnesium supplements could be a treatment option for this microdeletion syndrome and also for a subset of individuals with Prader-Willi and Angelman syndromes.


Assuntos
Deficiência Intelectual/tratamento farmacológico , Magnésio/uso terapêutico , Aberrações Cromossômicas , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 15/metabolismo , Suplementos Nutricionais , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/metabolismo , Magnésio/administração & dosagem
13.
ACS Appl Mater Interfaces ; 11(26): 23546-23557, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31252468

RESUMO

Poly(l-lactic acid) (PLLA) and magnesium (Mg) are widely concerned biodegradable materials, but during in vivo implantation, the former produces acidic degradation byproducts and can easily induce inflammation in surrounding tissues, whereas the latter is fast corroded and generates alkaline products. The purpose of this study is to develop Mg/PLLA composite microspheres as a novel delivery system, in which Mg particles are used to regulate the drug release profile and suppress PLLA-induced inflammatory response. Morphological observation shows that multiple Mg particles are dispersed both on the surface and in the interior of composite microspheres. In vitro release study indicates that by varying the Mg contents or its particle sizes, the internal connectivity of composite microspheres is changed during hydrolytic degradation, and drug delivery can be facilely manipulated with tunable release patterns. In vivo release study further confirms the feasibility of Mg/PLLA microspheres for tailoring drug release in a physiological environment. The animal experiment reveals that Mg particles can alleviate macrophage infiltration and inflammatory cytokine expression. These results demonstrate the availability of using biodegradable Mg particles to manipulate drug release as well as alleviate PLLA-induced inflammation. The present Mg/PLLA composite microspheres have potential applications in controlled delivery of various therapeutic agents, especially some growth factors, for bone regeneration.


Assuntos
Plásticos Biodegradáveis/química , Inflamação/prevenção & controle , Magnésio/química , Microesferas , Animais , Plásticos Biodegradáveis/efeitos adversos , Plásticos Biodegradáveis/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Quitosana/química , Sistemas de Liberação de Medicamentos , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Magnésio/efeitos adversos , Magnésio/uso terapêutico , Poliésteres/química , Poliésteres/uso terapêutico , Polímeros/química
14.
J Trauma Acute Care Surg ; 87(3): 606-613, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31162330

RESUMO

BACKGROUND: Noncompressible torso hemorrhage is a leading cause of traumatic death. Our aim was to examine survival time and the expression of key master genes of cellular metabolism after 3% NaCl adenosine, lidocaine, and Mg (ALM) bolus and 4 hours 0.9% NaCl/ALM "drip" in a rat model of uncontrolled hemorrhagic shock. METHODS: Male Sprague-Dawley rats (425 ± 8 g) were anesthetized and randomly assigned to saline controls (n = 10) or ALM therapy (n = 10). Hemorrhage was induced by liver resection (60% left lateral lobe). After 15 minutes, a single intravenous bolus of 3% NaCl ± ALM (0.7 mL/kg) was administered (Phase 1), and after 60 minutes, a 0.9% NaCl ± ALM stabilization "drip" (0.5 mL/kg per hour) was infused for 4 hours (Phase 2) with 72 hours monitoring. Mean arterial pressure and lactate were measured. After 72 hours (or high moribund score), tissues were freeze-clamped and stored at -80°C. Total RNA was extracted in heart, brain, and liver, and the relative expressions of amp-k, mtCO3, PGC-1α, and sirt-1 genes were determined. RESULTS: Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6 ± 4.5 hours, and ALM animals, 72 ± 0 hours (p < 0.05). Death in controls was accompanied by approximately sevenfold increase in lactate, while ALM animals maintained lactates similar to baseline over 72 hours. The relative expression of amp-k, PGC-1α, and sirt-1 in heart and brain was 1.5-fold and 2.7-fold higher in the ALM group compared with controls (p < 0.05), with the exception of mitochondrial encoded cytochrome C oxidase III pseudogene 1 in heart, which was 19-fold higher. In contrast, amp-k, sirt-1, and mtCO3 gene expression in liver was significantly 29-41% lower in the ALM group compared with controls, and PGC-1α was 75% lower. CONCLUSION: Small-volume ALM therapy led to 3.3-times longer survival time compared with saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of amp-k, PGC-1α, sirt-1, and mtCO3 to presumably "boost" mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.


Assuntos
Adenosina/uso terapêutico , Hidratação/métodos , Lidocaína/uso terapêutico , Magnésio/uso terapêutico , Choque Hemorrágico/terapia , Adenosina/administração & dosagem , Animais , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Lidocaína/administração & dosagem , Magnésio/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Choque Hemorrágico/mortalidade , Fatores de Tempo
15.
Mater Sci Eng C Mater Biol Appl ; 102: 150-163, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146986

RESUMO

Metal stents are used as base material for fabrication of medical devices to support and improve the quality of life of patients with cardiovascular diseases such as arterial stenoses. Permanently present implants may induce responses that resemble adverse wound healing that compromise tissue function. A similar process namely restenosis, frequently may occur after the use of this kind of implants. However, the use of non-permanent, resorbable stents are a promising option to avoid this problem. The advantage of these implants is that they can degraded upon vascular repair. The most common metal used for this application, is magnesium (Mg) which is an interesting material due its biological properties and because it is an essential element for human life. However, Mg-based resorbable biomaterial have some restrictions in clinical applications because its corrosion resistance, and mechanical properties. As solutions of this problem, the material can be modified in its composition (Mg-based alloys) or by surface treatments. This review shows and discusses recent challenges in the improvement of Mg-based biomaterials to be used to treat vascular disease and novel approaches at design-based biomaterials engineering of the same. Design-based methodologies are introduced and discussed in the context of balancing multi-functional properties against adaptation to the complex extreme in vivo environment. Traditional alloying approaches of Mg-based biomaterials are also discussed in the context of corrosion resistance controlled by surface modification strategies including conversion techniques: physicochemical or electrochemical transformation such as anodization, plasma and electrophoretic deposition.


Assuntos
Materiais Revestidos Biocompatíveis/uso terapêutico , Magnésio/uso terapêutico , Doenças Vasculares/terapia , Implantes Absorvíveis , Animais , Corrosão , Humanos , Stents
17.
J Trauma Acute Care Surg ; 87(1): 68-75, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30985476

RESUMO

BACKGROUND: Adenosine, lidocaine, and magnesium (ALM) is a cardioplegic agent shown to improve survival by improving cardiac function, tissue perfusion, and coagulopathy in animal models of shock. We hypothesized prehospital ALM treatment in hemorrhagic shock would improve survival compared to current Tactical Combat Casualty Care (TCCC) resuscitation beyond the golden hour. METHODS: Swine were randomized to: (1) TCCC, (2) 2 mL·kg vehicle control (VC), (3) 2 mL·kg ALM + drip, (4) 4 mL·kg ALM + drip, 5) 4 mL·kg ALM + delayed drip at 0.5 mL·kg·h, 6) 4 mL/kg VC, 7) 4 mL·kg ALM for 15 minutes + delayed drip at 3 mL·kg·h. Animals underwent pressure controlled hemorrhage to mean arterial pressure (MAP) of 30 mm Hg (S = 0). Treatment was administered at T = 0. After 120 minutes of simulated prehospital care (T = 120) blood product resuscitation commenced. Physiologic variables were recorded and laboratories were drawn at specified time points. RESULTS: Tactical Combat Casualty Care demonstrated superior survival to all other agents. The VC and ALM groups had lower MAPs and systolic blood pressures compared with TCCC. Except for the VC groups, lactate levels remained similar with correction of base deficit after prehospital resuscitation in all groups. Kidney function and liver function remained comparable across all groups. Compared with baseline values, TCCC demonstrated significant hypocoagulability. CONCLUSION: Adenosine, lidocaine, and magnesium, as administered in this study, are inferior to current Hextend-based resuscitation for survival from prolonged hemorrhagic shock in this model. In survivors, ALM groups had lower systolic blood pressures and MAPs, but provided a protective effect on coagulopathy as compared to TCCC. Adenosine, lidocaine, and magnesium do not appear to be a suitable low volume replacement to current TCCC resuscitation. The reduced coagulopathy compared to TCCC warrants future studies of ALM, perhaps as a therapeutic adjunct.


Assuntos
Adenosina/uso terapêutico , Soluções Cardioplégicas/uso terapêutico , Serviços Médicos de Emergência/métodos , Lidocaína/uso terapêutico , Magnésio/uso terapêutico , Medicina Militar/métodos , Ressuscitação/métodos , Choque Hemorrágico/terapia , Ferimentos e Lesões/terapia , Adenosina/administração & dosagem , Animais , Soluções Cardioplégicas/administração & dosagem , Modelos Animais de Doenças , Lidocaína/administração & dosagem , Magnésio/administração & dosagem , Masculino , Ressuscitação/mortalidade , Choque Hemorrágico/mortalidade , Suínos , Ferimentos e Lesões/mortalidade
18.
Agri ; 31(2): 86-92, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30995329

RESUMO

OBJECTIVES: The aim of this prospective, randomized study was to investigate the effect of magnesium added to midazolam on the hemodynamics, transition time to a T-piece, mechanical ventilation duration, additional sedative-analgesic requirement using bispectral index (BIS) monitorization and sedation scales. METHODS: Fifty critically ill patients receiving mechanical ventilation support in the intensive care unit were randomly assigned to 2 groups. Group I received a 0.03-0.3 mg/kg bolus loading dose+0.03-02 mg/kg/hour midazolam infusion; Group II received a 2 g bolus at 30 minutes, 16 mg/24-hour magnesium infusion+0.03-02 mg/kg/hour midazolam infusion. BIS levels and sedation levels were continuously monitored. RESULTS: The duration of mechanical ventilation in Group I was longer than that of Group II (31+-12 hours, 19+-11 hours, respectively; p<0.01). The length of time to start spontaneous breathing trials with a T-piece was greater in Group I than in Group II (27+-11 hours, 16+-11 hours, respectively; p<0.01). The 48-hour insulin requirement of Group I was greater than that of Group II (p<0.05). CONCLUSION: Adding intravenous magnesium to the traditional sedation protocols in the intensive care unit decreased midazolam use as well as the additional analgesic requirement and mechanical ventilatory support duration without any side effects.


Assuntos
Sedação Consciente , Estado Terminal , Hipnóticos e Sedativos/uso terapêutico , Magnésio/uso terapêutico , Midazolam/uso terapêutico , Respiração Artificial , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Unidades de Terapia Intensiva , Magnésio/administração & dosagem , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
19.
Adv Emerg Nurs J ; 41(2): 150-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31033663

RESUMO

Migraine headaches account for approximately 1.2 million emergency department (ED) visits annually. Despite the prevalence of this condition, there is little consensus on the best pharmacotherapeutic interventions to use in the ED setting. Guidelines published by the American Headache Society and the Canadian Headache Society offer some direction to ED providers but are not widely utilized. This article reviews the best evidence behind some of the medications frequently used to treat acute migraines in the ED setting, including dopamine receptor antagonists, serotonin receptor agonists, anti-inflammatory medications, opioids, magnesium, valproate, and propofol. The evaluation of patients presenting to the ED with an acute headache, the diagnostic criteria for migraines, and implications for advanced practice are also discussed.


Assuntos
Dor Aguda/diagnóstico , Dor Aguda/tratamento farmacológico , Serviço Hospitalar de Emergência , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Dor Aguda/enfermagem , Dor Aguda/fisiopatologia , Corticosteroides/uso terapêutico , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Antagonistas de Dopamina/uso terapêutico , Humanos , Magnésio/uso terapêutico , Transtornos de Enxaqueca/enfermagem , Transtornos de Enxaqueca/fisiopatologia , Medição da Dor , Propofol/uso terapêutico , Agonistas do Receptor de Serotonina/uso terapêutico , Ácido Valproico/uso terapêutico
20.
Clin Perinatol ; 46(2): 311-325, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010562

RESUMO

Neonatal brain injury (NBI) remains a major contributor to neonatal mortality and long-term neurodevelopmental morbidity. Although therapeutic hypothermia is the only proven treatment to minimize brain injury caused by neonatal encephalopathy in term neonates, it provides incomplete neuroprotection. There are no specific drugs yet proven to prevent NBI in preterm neonates. This review discusses the scientific and emerging clinical trial data for several neuroprotective drugs in development, examining potential efficacy and safety concerns. Drugs with the highest likelihood of success and closest to clinical application include erythropoietin for term and preterm neonates and antenatal magnesium for preterm neonates.


Assuntos
Hemorragia Cerebral Intraventricular/prevenção & controle , Hipóxia-Isquemia Encefálica/prevenção & controle , Leucomalácia Periventricular/prevenção & controle , Neuroproteção , Corticosteroides/uso terapêutico , Alopurinol/uso terapêutico , Anestésicos Inalatórios/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antioxidantes/uso terapêutico , Hemorragia Cerebral Intraventricular/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Darbepoetina alfa/uso terapêutico , Eritropoetina/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Hematínicos/uso terapêutico , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Indometacina/uso terapêutico , Recém-Nascido , Leucomalácia Periventricular/tratamento farmacológico , Magnésio/uso terapêutico , Melatonina/uso terapêutico , Cuidado Pré-Natal , Topiramato/uso terapêutico , Xenônio/uso terapêutico
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