Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 559
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Am J Emerg Med ; 80: 226.e1-226.e3, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38702220

RESUMEN

A 53-year-old male patient presented to a regional hospital Emergency Department approximately 2 h post an intentional ingestion of Coopers Instant Wetting Powder Sheep Dip (66% arsenic trioxide, 23% sulphur and 0.42% rotenone), mixed in 600 mL water, as a suicide attempt. On arrival to the Emergency Department, the patient had nausea, vomiting and diarrhoea. Seven hours post ingestion, hypotension developed (BP 90/60 mmHg) and intravenous fluids were commenced. He later developed QTc prolongation. He was treated with 2,3-Dimercapto-1-propanesulfonic acid (DMPS) and N-acetylcysteine and improved without development of neurology. Further investigation of NAC efficacy in humans in the setting of acute arsenic poisoning is required and the optimal duration of treatment and dosing needs to be established. This case highlights an uncommon poisoning which presented to the Emergency Department, the acute symptoms of arsenic toxicity and considerations for management.


Asunto(s)
Acetilcisteína , Intoxicación por Arsénico , Arsenicales , Intento de Suicidio , Masculino , Humanos , Persona de Mediana Edad , Acetilcisteína/uso terapéutico , Trióxido de Arsénico/envenenamiento , Óxidos/envenenamiento , Antídotos/uso terapéutico , Unitiol/uso terapéutico
2.
Int J Mol Sci ; 23(3)2022 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-35163756

RESUMEN

The increasing antibiotic resistance is a clinical problem worldwide. Numerous Gram-negative bacteria have already become resistant to the most widely used class of antibacterial drugs, ß-lactams. One of the main mechanisms is inactivation of ß-lactam antibiotics by bacterial ß-lactamases. Appearance and spread of these enzymes represent a continuous challenge for the clinical treatment of infections and for the design of new antibiotics and inhibitors. Drug repurposing is a prospective approach for finding new targets for drugs already approved for use. We describe here the inhibitory potency of known detoxifying antidote 2,3-dimercaptopropane-1-sulfonate (unithiol) against metallo-ß-lactamases. Unithiol acts as a competitive inhibitor of meropenem hydrolysis by recombinant metallo-ß-lactamase NDM-1 with the KI of 16.7 µM. It is an order of magnitude lower than the KI for l-captopril, the inhibitor of angiotensin-converting enzyme approved as a drug for the treatment of hypertension. Phenotypic methods demonstrate that the unithiol inhibits natural metallo-ß-lactamases NDM-1 and VIM-2 produced by carbapenem-resistant K. pneumoniae and P. aeruginosa bacterial strains. The 3D full atom structures of unithiol complexes with NDM-1 and VIM-2 are obtained using QM/MM modeling. The thiol group is located between zinc cations of the active site occupying the same place as the catalytic hydroxide anion in the enzyme-substrate complex. The sulfate group forms both a coordination bond with a zinc cation and hydrogen bonds with the positively charged residue, lysine or arginine, responsible for proper orientation of antibiotics upon binding to the active site prior to hydrolysis. Thus, we demonstrate both experimentally and theoretically that the unithiol is a prospective competitive inhibitor of metallo-ß-lactamases and it can be utilized in complex therapy together with the known ß-lactam antibiotics.


Asunto(s)
Klebsiella pneumoniae/enzimología , Pseudomonas aeruginosa/enzimología , Unitiol/farmacología , Inhibidores de beta-Lactamasas/farmacología , beta-Lactamasas/metabolismo , Carbapenémicos/farmacología , Reposicionamiento de Medicamentos , Farmacorresistencia Bacteriana/efectos de los fármacos , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Klebsiella pneumoniae/efectos de los fármacos , Modelos Moleculares , Conformación Proteica , Pseudomonas aeruginosa/efectos de los fármacos , Relación Estructura-Actividad Cuantitativa , beta-Lactamasas/química
3.
Artículo en Zh | MEDLINE | ID: mdl-35545590

RESUMEN

Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.


Asunto(s)
Enfermedades Renales , Intoxicación por Mercurio , Mercurio , Animales , Encéfalo/efectos de los fármacos , Glutatión , Inflamación , Riñón/efectos de los fármacos , Enfermedades Renales/inducido químicamente , Masculino , Cloruro de Mercurio/farmacología , Cloruro de Mercurio/uso terapéutico , Mercurio/orina , Intoxicación por Mercurio/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley , Solución Salina/farmacología , Solución Salina/uso terapéutico , Unitiol/farmacología , Unitiol/uso terapéutico
4.
Langmuir ; 37(45): 13430-13443, 2021 11 16.
Artículo en Inglés | MEDLINE | ID: mdl-34732050

RESUMEN

Dopamine (DA), a naturally occurring neurotransmitter, plays a crucial role in the function of the mammalian nervous system. DA-lipid-membrane interaction is inevitable during the neurotransmission process. In this report, we have studied the interaction of DA with anionic 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine (DMPS), neutral (zwitterionic) 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and synaptic membrane-mimicking mixed DMPC/DMPS (3:1 molar ratio) model multilamellar vesicle (MLV) membranes. Differential scanning calorimetry (DSC) studies suggest a strong specific interaction of DA with the anionic DMPS membrane, a weak interaction with the zwitterionic DMPC membrane, and a moderate interaction with the mixed DMPC/DMPS (3:1) membrane. The intrinsic fluorescence of DA was used as a new approach to gain a molecular-level understanding of DA-lipid-membrane interaction. Toward this end, a detailed photophysical study of DA, including its steady-state fluorescence anisotropy and fluorescence lifetime, was undertaken for the first time. The partition coefficient, location, and distribution of DA in the DMPS and DMPC model membranes were studied by employing intrinsic fluorescence. The effect of DA on the phase transition of the model membranes was also examined using the intrinsic fluorescence of DA. Zeta potential studies suggest a strong electrostatic interaction of DA with the anionic DMPS membrane and a nonspecific, relatively weak interaction of DA with the zwitterionic DMPC membrane. In addition, we observed cholesterol-induced DA expulsion from both DMPS and DMPC membranes. We believe that this work will provide a more in-depth understanding of DA-membrane interaction at a molecular level.


Asunto(s)
Dimiristoilfosfatidilcolina , Membrana Dobles de Lípidos , Aniones , Dopamina , Unitiol
5.
BMC Neurol ; 20(1): 255, 2020 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-32593295

RESUMEN

BACKGROUND: Even though recent research has achieved significant advancement in the development of therapeutic approaches for Wilson's diseases (WD), the current treatment options available for WD are still limited, especially for WD patients with neurological symptoms. This study is intended to compare the therapeutic approaches for WD patients with neurological symptoms receiving either combined sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) and zinc treatment or D-penicillamine (DPA) monotherapy as first-line therapy, and identify the more effective therapeutic approach. METHODS: The case records of 158 patients diagnosed with neurological WD were retrospectively analyzed. These patients treated with intravenous DMPS + Zinc and in combination with oral zinc as a maintenance therapy (Group 1) or DPA alone (Group 2) for 1 year. During the period of treatment, the neurological symptoms of the patients were assessed using the Global Assessment Scale (GAS) and Barthel index. The key hematological and biochemical parameters of the patients (such as the levels of aminotransferase, serum ceruloplasmin, 24-h urine copper excretion), as well as adverse effects were recorded and analyzed. RESULTS: Ninety-three patients in Group 1, displayed decreased GAS scores and increased Barthel indexes consistently in comparison with the baseline (P < 0.01). Among them, 82 patients (88.2%) exhibited significant neurological improvement after 1 year, while 8 patients (8.6%) experienced neurological deterioration. Among the 65 patients in Group 2, 37 patients (58.5%) exhibited neurological improvements, while 17 patients (26.2%) experienced neurological deterioration after 1-year follow up. Six patients discontinued their treatment midway due to their exacerbating neurological symptoms. A comprehensive comparison of the effectiveness of the two courses of treatment revealed that patients in group 1 demonstrated a higher improvement ratio (P < 0.01) and lower worsening ratio of the neurological symptoms for the patients (P < 0.01) in comparison to the patients in group 2. Meanwhile, renal function, liver enzyme and blood cell counts remained stabilized in group1. CONCLUSIONS: This study indicates that the combined therapeutic approach of DPMS and zinc may be a preferred first-line therapy in treating the neurological symptoms of WD, in comparison to the treatment with DPA.


Asunto(s)
Quelantes/administración & dosificación , Degeneración Hepatolenticular/tratamiento farmacológico , Penicilamina/uso terapéutico , Unitiol/administración & dosificación , Zinc/administración & dosificación , Adulto , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
6.
BMC Nephrol ; 20(1): 374, 2019 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-31623560

RESUMEN

BACKGROUND: Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical practice in this area is rather scattered. CASE PRESENTATION: We present a case of symptomatic lead and arsenic poisoning from use of Ayurvedic medicine in a 28-year-old man with end-stage kidney disease on chronic hemodialysis. We describe his treatment course with chelating agents and extracorporeal blood purification, and review the relevant literature to provide general guidance. CONCLUSION: Cumulative clinical experience assists in identifying preferred chelators and modalities of extracorporeal blood purification when managing such patients. However, a larger body of real-world or clinical trial evidence is necessary to inform evidence-based guidelines for the management of heavy metal poisoning in anuric patients.


Asunto(s)
Anuria/complicaciones , Intoxicación por Arsénico/terapia , Quelantes/uso terapéutico , Terapia de Reemplazo Renal Continuo , Fallo Renal Crónico/complicaciones , Intoxicación por Plomo/terapia , Adulto , Animales , Intoxicación por Arsénico/complicaciones , Dimercaprol/uso terapéutico , Ácido Edético/uso terapéutico , Humanos , Fallo Renal Crónico/terapia , Intoxicación por Plomo/complicaciones , Masculino , Diálisis Renal , Succímero/uso terapéutico , Unitiol/uso terapéutico
7.
Pediatr Emerg Care ; 35(10): 696-699, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27977534

RESUMEN

OBJECTIVE: Elemental mercury is a toxic liquid element that is used widely in the home, medicine, agriculture, and industry. It is readily vaporized and inhaled at room temperature. Thereby, inhalation can cause acute or chronic poisoning. Mercury can be found in environmental naturally find but some dangers sources give rise to contaminations. It can be very dangerous to all living organisms, especially children. METHODS: This study presents the features of mercury poisoning in a group of pediatric cases. Data were obtained for 29 pediatric cases exposed to elemental mercury in a high school chemistry laboratory in Turkey. Patients with a blood mercury level exceeding 10 µg/L or a urine mercury level exceeding 15 µg/L were considered to have mercury poisoning. The patients were treated with 2,3-dimercaptopropane sulfonic acid or D-penicillamine. RESULTS: Twenty-nine children with mercury poisoning were admitted to the hospital. The median duration of exposure was 58 (range, 15-120) minutes. Ten (29%) children were asymptomatic. Physical and neurological examinations were normal in 19 (65.5%) children. The most common presenting complaint was headache. The most common neurological abnormality, partly dilated/dilated pupils, was present in 9 (31%) children. Mercury levels were measured in blood samples every 5 days, and the median blood mercury level was 51.98 (range, 24.9-86.4) µg/L. There was a positive correlation between the duration of exposure and maximum blood/urine mercury levels (P = 0.001). CONCLUSIONS: Elemental mercury exposure is potentially toxic; its symptomatology varies, especially in children. Secure storage of mercury and other toxic substances and provision of information about this subject to individuals who might be exposed to mercury and their families might help to prevent mercury poisoning.


Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Intoxicación por Mercurio/diagnóstico , Mercurio/sangre , Instituciones Académicas/estadística & datos numéricos , Enfermedad Aguda , Adolescente , Quelantes/uso terapéutico , Niño , Femenino , Humanos , Masculino , Mercurio/orina , Intoxicación por Mercurio/tratamiento farmacológico , Intoxicación por Mercurio/patología , Medicina de Urgencia Pediátrica , Penicilamina/uso terapéutico , Turquía/epidemiología , Unitiol/uso terapéutico
8.
Retina ; 38(9): 1688-1698, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28723845

RESUMEN

PURPOSE: Ophthalmologists serve an increasing volume of a growing elderly population undergoing increasingly complex outpatient medical care, including extensive diagnostic testing and treatment. The resulting prolonged patient visit times ("patient flow times") limit quality, patient and employee satisfaction, and represent waste. Lean Six Sigma process improvement was used in a vitreoretinal practice to decrease patient flow time, demonstrating that this approach can yield significant improvement in health care. METHODS: Process flow maps were created to determine the most common care pathways within clinic. Three months' visits from the electronic medical record system, which tracks patient task times at each process step in the office were collected. Care tasks and care pathways consuming the greatest time and variation were identified and modified. Follow-up analysis from 6 weeks' visits was conducted to assess improvement. RESULTS: Nearly all patients took one of five paths through the office. Patient flow was redesigned to reduce waiting room time by having staff members immediately start patients into one of those five paths; staffing was adjusted to address high demand tasks, and scheduling was optimized around derived predictors of patient flow times. Follow-up analysis revealed a statistically significant decline in mean patient flow time by 18% and inpatient flow time SD by 4.6%. Patient and employee satisfaction scores improved. CONCLUSION: Manufacturing industry techniques, such as Lean and Six Sigma, can be used to improve patient care, minimize waste, and enhance patient and staff satisfaction in outpatient clinics.


Asunto(s)
Instituciones de Atención Ambulatoria/normas , Eficiencia Organizacional , Oftalmopatías/terapia , Oftalmología , Satisfacción del Paciente , Gestión de la Calidad Total , Flujo de Trabajo , Humanos , Unitiol
9.
Proteins ; 85(7): 1336-1350, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28380689

RESUMEN

The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a "sandwich""-like structure. In the membrane context, the xα2-peptide interacts with the Fyn-SH3 domain via the proline-rich region and the ß-sheets of Fyn-SH3, with the latter wrapping around the proline-rich region in a form of a clip. Moreover, the simulations corroborate prior experimental evidence of the importance of upstream segments beyond the canonical SH3-ligand. This study thus provides a more-detailed glimpse into the context-dependent interaction dynamics and importance of the ß-sheets in Fyn-SH3 and proline-rich region of MBP. Proteins 2017; 85:1336-1350. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Membrana Dobles de Lípidos/química , Proteína Básica de Mielina/química , Proteínas Proto-Oncogénicas c-fyn/química , Agua/química , Dominios Homologos src , Secuencia de Aminoácidos , Animales , Sitios de Unión , Dimiristoilfosfatidilcolina/química , Humanos , Ratones , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Péptidos/química , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Prolina/química , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Estructura Terciaria de Proteína , Termodinámica , Unitiol/química
10.
J Pharmacol Sci ; 134(2): 108-115, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28648300

RESUMEN

Previously, we reported that specific lower dose of sodium 2,3-dimercapto-1-propanesulfonic acid (DMPS) which is an antidote to heavy metal intoxication, inversely enhanced cisplatin (CDDP)-induced antitumor activity to S-180 cell-bearing mouse. This activity was only weak with meso-2,3-dimercaptosuccinic acid (DMSA), however. This study investigated the effects of lower doses of DMPS or DMSA on the nephrotoxicity and kinetics of CDDP. Kidney and blood isolated from female mice which received CDDP with or without DMPS or DMSA once daily for 4 days were provided for measuring levels of blood urea nitrogen (BUN) and transporter proteins (OCT2: organic cation transporter; MATE1: multidrug and toxin extrusion) mRNA, and CDDP-originated platinum, and TUNEL staining of renal tubular cells. DMPS or DMSA reduced effectively CDDP-induced BUN, and caused a moderate reduction of platinum in kidney. Additionally, both dimercapto-compounds restored the CDDP-reduced mRNA levels of transporter proteins (OCT2 and MATE1), and apparently suppressed the CDDP-induced apoptosis. These results suggest that DMPS, as well as DMSA, at approximate 17-fold dose (µmol/kg) of CDDP, has an enough potential to reverse the CDDP nephrotoxicity, and concomitant use of DMPS considering both dose and timing for administration is potentially useful for preventing nephrotoxicity and enhancing antitumor activity during CDDP chemotherapy.


Asunto(s)
Antineoplásicos/toxicidad , Cisplatino/toxicidad , Enfermedades Renales/tratamiento farmacológico , Succímero/uso terapéutico , Unitiol/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Femenino , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Ratones , Proteínas de Transporte de Catión Orgánico/genética , Proteínas de Transporte de Catión Orgánico/metabolismo , Transportador 2 de Cátion Orgánico/genética , Transportador 2 de Cátion Orgánico/metabolismo , ARN Mensajero/metabolismo , Succímero/farmacología , Unitiol/farmacología
11.
Clin Nephrol ; 87 (2017)(4): 196-201, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28102816

RESUMEN

AIM: Membranous nephropathy and minimal change disease (MCD) have been involved in mercury-induced nephrotic syndrome. IgA nephropathy is not known to be a common pathological type. In the present article, we report a case of IgA nephropathy with MCD following exposure to mercury-containing skin lightening cream. MATERIAL AND METHODS: The patient was a 39-year-old woman who presented with nephrotic syndrome. She had a 6-month history of using as many as 8 kinds of skin-lightening creams, and urinary mercury excretion was high. Renal biopsy revealed IgA nephropathy with MCD. The use of cosmetics was stopped and chelation therapy was given. After 4 courses (1 month) of chelation therapy, there was a complete remission of proteinuria and hematuria, and urine tests remained normal during the 5-year follow-up period. RESULTS AND CONCLUSIONS: The unique clinical and pathological features of IgA nephropathy with MCD had raised the controversial question of whether MCD and IgA deposition are separate entities or a common pathophysiology. Repeated renal biopsy and similar cases were helpful and should be carried out as far as possible.
.


Asunto(s)
Glomerulonefritis por IGA/inducido químicamente , Intoxicación por Mercurio/complicaciones , Nefrosis Lipoidea/inducido químicamente , Preparaciones para Aclaramiento de la Piel/envenenamiento , Adulto , Quelantes/uso terapéutico , Femenino , Glomerulonefritis por IGA/patología , Glomerulonefritis por IGA/terapia , Hematuria/etiología , Humanos , Riñón/patología , Riñón/ultraestructura , Intoxicación por Mercurio/tratamiento farmacológico , Nefrosis Lipoidea/patología , Nefrosis Lipoidea/terapia , Síndrome Nefrótico/etiología , Síndrome Nefrótico/terapia , Proteinuria/etiología , Inducción de Remisión , Preparaciones para Aclaramiento de la Piel/química , Unitiol/uso terapéutico
12.
Arch Toxicol ; 91(12): 3787-3797, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29063135

RESUMEN

This article reviews the clinical use of the metal chelators sodium 2,3-dimercapto-1-propanesulfonate (DMPS), meso-2,3-dimercaptosuccinic acid (DMSA), and calcium disodium edetate (CaEDTA, calcium EDTA) in overexposure and poisonings with salts of lead (Pb), mercury (Hg), and arsenic (As). DMSA has considerably lower toxicity than the classic heavy metal antagonist BAL (2,3-dimercaptopropanol) and is also less toxic than DMPS. Because of its adverse effects, CaEDTA should be replaced by DMSA as the antidote of choice in treating moderate Pb poisoning. Combination therapy with BAL and CaEDTA was previously recommended in cases of severe acute Pb poisoning with encephalopathy. We suggest that BAL in such cases acted as a shuttling Pb transporter from the intra- to the extracellular space. The present paper discusses if a combination of the extracellularly distributed DMSA with the ionophore, Monensin may provide a less toxic combination for Pb mobilization by increasing both the efflux of intracellularly deposited Pb and the urinary Pb excretion. Anyhow, oral therapy with DMSA should be continued with several intermittent courses. DMPS and DMSA are also promising antidotes in Hg poisoning, whereas DMPS seems to be a more efficient agent against As poisoning. However, new insight indicates that a combination of low-dosed BAL plus DMPS could be a preferred antidotal therapy to obtain mobilization of the intracerebral deposits into the circulation for subsequent rapid urinary excretion.


Asunto(s)
Intoxicación por Arsénico/tratamiento farmacológico , Quelantes/uso terapéutico , Intoxicación del Sistema Nervioso por Plomo/tratamiento farmacológico , Intoxicación del Sistema Nervioso por Mercurio/tratamiento farmacológico , Ácido Edético/uso terapéutico , Humanos , Monensina/uso terapéutico , Succímero/uso terapéutico , Unitiol/uso terapéutico
13.
J Clin Pharm Ther ; 42(6): 783-785, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28635014

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Wilson's disease (WD) is an inherited disorder in which defective biliary excretion of copper leads to its accumulation. Sodium dimercaptosulphonate (DMPS) is used as the primary therapy in China. CASE DESCRIPTION: We report two cases, with WD and G6PD deficiency, who developed haemolysis on treatment with DMPS, without any other known risk. After withdrawal of DMPS and administration of dexamethasone and packed red blood cells, the patients recovered. WHAT IS NEW AND CONCLUSION: Clinicians should keep in mind haemolysis as a potentially life-threatening side effect of DMPS in patients with G6PD.


Asunto(s)
Deficiencia de Glucosafosfato Deshidrogenasa/tratamiento farmacológico , Hemólisis/efectos de los fármacos , Degeneración Hepatolenticular/tratamiento farmacológico , Unitiol/efectos adversos , Unitiol/uso terapéutico , Adulto , Humanos , Masculino , Adulto Joven
14.
J Clin Pharm Ther ; 42(4): 506-508, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28547870

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Massive acute arsenic poisoning is rare yet potentially life-threatening. 2,3-dimercaptopropane-1-sulphonate (DMPS) appears to have the appropriate chelating property. However, clinical experience on the use of DMPS in massive arsenic poisoning is limited. CASE DESCRIPTION: A 37-year-old woman attempted suicide by ingesting 37.5 g of arsenic trioxide. DMPS was promptly initiated based on history and clinical symptoms. The patient recovered completely, with no complications or side effects of the therapy. WHAT IS NEW AND CONCLUSION: TDMPS is useful for the treatment of massive acute arsenic poisoning.


Asunto(s)
Intoxicación por Arsénico/tratamiento farmacológico , Óxidos/envenenamiento , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Unitiol/uso terapéutico , Adulto , Trióxido de Arsénico , Arsenicales , Quelantes/uso terapéutico , Femenino , Humanos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Intento de Suicidio , Resultado del Tratamiento
15.
Soft Matter ; 12(1): 181-90, 2016 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-26451711

RESUMEN

Behavior of cationic tetra-p-guanidinoethylcalix[4]arene (CX1) and its building block, p-guanidinoethylphenol (mCX1) in model monolayer lipid membranes was investigated using all atom molecular dynamics simulations and surface pressure measurements. Members of two classes of lipids were taken into account: zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and anionic 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine sodium salt (DMPS) as models of eukaryotic and bacterial cell membranes, respectively. It was demonstrated that CX1 and mCX1 accumulate near the negatively charged DMPS monolayers. The adsorption to neutral monolayers was negligible. In contrast to mCX1, CX1 penetrated into the hydrophobic part of the monolayer. The latter effect, which is possible due to a flip-flop inversion of the CX1 orientation in the lipid layer compared to the aqueous phase, may be responsible for its antibacterial activity.


Asunto(s)
Calixarenos/química , Membrana Dobles de Lípidos/química , Simulación de Dinámica Molecular , Dimiristoilfosfatidilcolina/química , Interacciones Hidrofóbicas e Hidrofílicas , Unitiol/química
16.
Soft Matter ; 12(13): 3165-76, 2016 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-26934592

RESUMEN

One of the hallmarks of Alzheimer's disease is the formation of protein plaques in the brain, which mainly consist of amyloid-ß peptides of different lengths. While the role of these plaques in the pathology of the disease is not clear, the mechanism behind peptide aggregation is a topic of intense research and discussion. Because of their simplicity, synthetic membranes are promising model systems to identify the elementary processes involved. We prepared unsaturated zwitterionic/anionic lipid membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-phosphocholine (POPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine (DMPS) at concentrations of POPC/3 mol% DMPS containing 0 mol%, 3 mol%, 10 mol%, and 20 mol% amyloid-ß25-35 peptides. Membrane-embedded peptide clusters were observed at peptide concentrations of 10 and 20 mol% with a typical cluster size of ∼11 µm. Cluster density increased with peptide concentration from 59 (±3) clusters per mm(2) to 920 (±64) clusters per mm(2), respectively. While monomeric peptides take an α-helical state when embedded in lipid bilayers at low peptide concentrations, the peptides in peptide clusters were found to form cross-ß sheets and showed the characteristic pattern in X-ray experiments. The presence of the peptides was accompanied by an elastic distortion of the bilayers, which can induce a long range interaction between the peptides. The experimentally observed cluster patterns agree well with Monte Carlo simulations of long-range interacting peptides. This interaction may be the fundamental process behind cross-ß sheet formation in membranes and these sheets may serve as seeds for further growth into amyloid fibrils.


Asunto(s)
Péptidos beta-Amiloides/química , Membrana Dobles de Lípidos/química , Fragmentos de Péptidos/química , Péptidos beta-Amiloides/metabolismo , Aniones/química , Membrana Dobles de Lípidos/metabolismo , Microscopía , Método de Montecarlo , Fragmentos de Péptidos/metabolismo , Fosfatidilcolinas/química , Estructura Secundaria de Proteína , Unitiol/química , Difracción de Rayos X
17.
Soft Matter ; 12(5): 1444-51, 2016 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-26646730

RESUMEN

The peptide amyloid-ß (Aß) interacts with membranes of cells in the human brain and is associated with Alzheimer's disease (AD). The intercalation of Aß in membranes alters membrane properties, including the structure and lipid dynamics. Any change in the membrane lipid dynamics will affect essential membrane processes, such as energy conversion, signal transduction and amyloid precursor protein (APP) processing, and may result in the observed neurotoxicity associated with the disease. The influence of this peptide on membrane dynamics was studied with quasi-elastic neutron scattering, a technique which allows a wide range of observation times from picoseconds to nanoseconds, over nanometer length scales. The effect of the membrane integral neurotoxic peptide amyloid-ß, residues 22-40, on the in- and out-of-plane lipid dynamics was observed in an oriented DMPC/DMPS bilayer at 15 °C, in its gel phase, and at 30 °C, near the phase transition temperature of the lipids. Near the phase-transition temperature, a 1.5 mol% of peptide causes up to a twofold decrease in the lipid diffusion coefficients. In the gel-phase, this effect is reversed, with amyloid-ß(22-40) increasing the lipid diffusion coefficients. The observed changes in lipid diffusion are relevant to protein-protein interactions, which are strongly influenced by the diffusion of membrane components. The effect of the amyloid-ß peptide fragment on the diffusion of membrane lipids will provide insight into the membrane's role in AD.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Membrana Dobles de Lípidos/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/química , Difusión , Dimiristoilfosfatidilcolina/química , Humanos , Membrana Dobles de Lípidos/química , Dominios y Motivos de Interacción de Proteínas , Unitiol/química
18.
Health Prog ; 97(6): 80-3, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-30040358

RESUMEN

Finding ways that health care organizations can address the social determinants of health is a hot topic in health policy circles these days. It long has been known that social and economic factors have a significant impact on health, but addressing these factors traditionally has been the purview of government and philanthropic organizations, not health care providers. Why are policymakers now looking to health care to play a role?


Asunto(s)
Personal de Salud , Salud Poblacional , Rol Profesional , Determinantes Sociales de la Salud , Instituciones de Salud , Humanos , Unitiol
19.
Environ Sci Technol ; 49(2): 1165-72, 2015 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-25513720

RESUMEN

Silver nanoparticles (AgNP) are increasingly used as antimicrobials in consumer products. Subsequently released into aquatic environments, they are likely to come in contact with microbial communities like periphyton, which plays a key role as a primary producer in stream ecosystems. At present, however, very little is known about the effects of nanoparticles on processes mediated by periphyton communities. We assessed the effects of citrate-coated silver nanoparticles and silver ions (dosed as AgNO3) on five functional end points reflecting community and ecosystem-level processes in periphyton: photosynthetic yield, respiration potential, and the activity of three extracellular enzymes. After 2 h of exposure in experimental microcosms, AgNP and AgNO3 inhibited respiration and photosynthesis of periphyton and the activities of two of the three extracellular enzymes. Addition of a chelating ligand that complexes free silver ions indicated that, in most cases, toxicity of AgNP suspensions was caused by Ag(I) dissolved from the particles. However, these suspensions inhibited one of the extracellular enzymes (leucine aminopeptidase), pointing to a specific nanoparticle effect independent of the dissolved Ag(I). Thus, our results show that both silver nanoparticles and silver ions have potential to disrupt basic metabolic functions and enzymatic resource acquisition of stream periphyton.


Asunto(s)
Organismos Acuáticos/efectos de los fármacos , Nanopartículas del Metal/toxicidad , Fotosíntesis/efectos de los fármacos , Plata/toxicidad , Contaminantes del Agua/análisis , Quelantes/química , Ecosistema , Exposición a Riesgos Ambientales , Iones , Ligandos , Nanopartículas , Nanotecnología , Ríos , Nitrato de Plata/química , Nitrato de Plata/toxicidad , Unitiol/química
20.
Eksp Klin Farmakol ; 78(1): 30-3, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-25826872

RESUMEN

The results of experiments on noninbred albino rats showed that the acute intoxication with carbon tetrachloride (CT) at a dose of 1 LD50 reduced the parameters of cellular immune response and function of Th1 cells more significantly than the levels of humoral immune response and Th2-lymphocyte function, decreases the blood content of immunoregulatory cytokines IFN-g, IL-2, IL-4 and anti-inflammatory cytokine IL-13, while not changing the concentration of anti-inflammatory cytokine IL-10 and increasing the concentration of pro-inflammatory cytokine IL-6. The application of unithiol, tocopherol acetate, and combinations partially restores the parameters examined. The combined effects of drugs during intoxication with CT does not exceed their separate action.


Asunto(s)
Antiinflamatorios/farmacología , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Inmunidad Innata/efectos de los fármacos , Unitiol/farmacología , alfa-Tocoferol/farmacología , Animales , Animales no Consanguíneos , Intoxicación por Tetracloruro de Carbono/sangre , Intoxicación por Tetracloruro de Carbono/inmunología , Intoxicación por Tetracloruro de Carbono/patología , Quimioterapia Combinada , Femenino , Homeostasis/inmunología , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-13/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Interleucina-6/sangre , Masculino , Ratas , Células TH1/inmunología , Balance Th1 - Th2/efectos de los fármacos , Células Th2/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA